Search

The gender bias in adrenal diseases has been noticed for a long time. Mouse studies have shown that the adrenal gland is sexually dimorphic at different levels, such as transcriptome, histology, and cell renewal. However, the mechanism behind this sexual dimorphism is not fully understood. Here, we used RNA-seq to demonstrate how male and female adrenals respond differently to the same external cue, the thyroid hormone (T3) treatment, which directly elicits its function on the adrenal inner cortex by changing the cell fate of this population. Through the comparison of the adrenal gland transcriptomes from males and females with T3 or saline treatment, we found that more genes in female adrenals were responsive to the T3 treatment, whereas the fold change of the gene expressions was greater in male adrenals. Statistical analysis identified 104 sexually dimorphic T3-responsive genes. Immunostaining results showed that many of these genes were expressed in the adrenal gland inner cortex, which contains a unique cell population called X-zone (20-alpha-HSD positive). Previous studies showed that T3 treatment leads to the expansion of the 20αHSD-positive zone both in males and in females. Here we found that the top sexually dimorphic T3-responsive gene was expressed in the adrenal inner cortex partially colocalized with X-zone. Under T3 treatment, this unique cell population that surrounds the 20-alpha-HSD positive X-zone became obvious only in females but not in males. Our findings not only identified several novel marker genes for the adrenal inner cortex but also highlighted the sex-specific response of thyroid hormone action in the mouse adrenal gland.

It is well known that thyroid hormone plays a key role in amphibian metamorphosis and mammalian tissue remodeling. We and others have reported that treatment with thyroid hormone will prevent or postpone the regression of the adrenal inner cortex (X-zone) and leads to X-zone hypertrophy in mice. The expression of thyroid hormone receptor beta 1 (TRβ1) in the adrenal inner cortex indicates that thyroid hormone could elicit its function directly on this cell population. To support this idea, we examined the expression and the function of major thyroid hormone transporters Mct8, Mct10, and Oatp1c1 in mouse adrenal glands. RNA-seq data showed that the expression levels of Mct10 and Oatp1c1 are relatively low in the adrenal gland (with RPKM less than 5 and 1, respectively) whereas Mct8 is the most abundant transporter (with RPKM around 20). Quantitative RT-PCR showed that Mct8 in the adrenal gland has an expression profile similar to X-zone marker genes and TRβ1 throughout developmental stages. LacZ staining showed similarities between Mct8 and TRβ1 expression, with both specifically expressed in the most inner cortex of the adrenal gland next to the medulla. However, by using thyroid hormone (T3) treatment, we found that the T3-mediated effect in the adrenal gland was not fully blocked in Mct8 knock-out mice. The expression of thyroid hormone transporter Mct8 in the adrenal inner cortex supports our claim that transporters mediate the direct action of thyroid hormone in the adrenal inner cortex. The blunted response to thyroid hormone in Mct8 knockout mice suggests that Mct8 is responsible for the thyroid hormone action in the adrenal gland. However, the deletion of Mct8 does not completely block thyroid hormones effect in the adrenal gland. Our finding suggests other thyroid hormone transporter(s) in the adrenal gland are also responsible for thyroid hormone signaling in the adrenal gland.

In the present paper, the modulation of the basolateral membrane (BLM) Na + -ATPase activity of inner cortex from pig kidney by angiotensin II (Ang II) and angiotensin-(1–7) (Ang-(1–7)) was evaluated. Ang II and Ang-(1–7) inhibit the Na + -ATPase activity in a dose-dependent manner (from 10 −11 to 10 −5 M), with maximal effect obtained at 10 −7 M for both peptides. Pharmacological evidences demonstrate that the inhibitory effects of Ang II and Ang-(1–7) are mediated by AT 2 receptor: The effect of both polypeptides is completely reversed by 10 −8 M PD 123319, a selective AT 2 receptor antagonist, but is not affected by either (10 −12 –10 −5 M) losartan or (10 −10 –10 −7 M) A779, selective antagonists for AT 1 and AT (1–7) receptors, respectively. The following results suggest that a PTX-insensitive, cholera toxin (CTX)-sensitive G protein/adenosine 3′,5′-cyclic monophosphate (cAMP)/PKA pathway is involved in this process: (1) the inhibitory effect of both peptides is completely reversed by 10 −9 M guanosine 5′- O -(2-thiodiphosphate) (GDPβS; an inhibitor of the G protein activity), and mimicked by 10 −10 M guanosine 5′- O -(3-thiotriphosphate) (GTPγS; an activator of the G protein activity); (2) the effects of both peptides are mimicked by CTX but are not affected by PTX; (3) Western blot analysis reveals the presence of the G s protein in the isolated basolateral membrane fraction; (4) (10 −10 –10 −6 M) cAMP has a similar and non-additive effect to Ang II and Ang-(1–7); (5) PKA inhibitory peptide abolishes the effects of Ang II and Ang-(1–7); and (6) both angiotensins stimulate PKA activity.

The morphological change of the cell surface in the inner zone of the adrenal cortex was studied in intact, hypophysectomized, and ACTH-treated hypophysectomized rats, using freeze-fracture replicas. In both intact and hypophysectomized ACTH-treated animals, the P fracture face of the plasma membranes of the cortical cells facing capillaries shows groups of characteristic finger-shaped microvilli, which arise horizontally from the edges of a small cavity on the cell surface to form various configurations ranging from incompletely organized, flower budlike to complicated, arboraceous ones. In the non-treated hypophysectomized animals, however, the microvilli in such groups decrease in number and shorten in length but increase in width, looking like a blade of a prickly-pear cactus or an irregular-shaped plate. On the other hand, presumptive exocytotic and endocytotic specializations of intra-membranous particles were observed on the lateral plasma membrane, but they appeared only rarely and in both normal and experimental animals.

Summary Regional distribution of angiotensin converting enzyme(ACE) in the rat kidney was studied. The ACE activities in the inner cortex and outer medulla were about 10 and 5 times those in the outer cortex, respectively. The activity in the inner medulla or papilla was much the same as that in the outer cortex. Immunofluorescence was greatest in the proximal tubules in the inner cortex, while the outer medulla and the inner medulla or papilla showed a weak fluorescence. The brush border membranes isolated from the inner cortex also possessed about 10 times the ACE activity seen in the outer cortex. The results indicate that the major source of renal ACE is not the proximal convoluted tubules in the outer cortex, but rather the brush border membranes of proximal tubules in the inner cortex. The contribution of ACE in the inner cortex would therefore be predominant.

The rat kidney was separated into the outer cortex, inner cortex, outer medulla and inner medulla or papilla, and the distribution of angiotensin-converting enzyme (ACE) in response to consecutive administrations of captopril was studied. In normal animals, the ACE activity in the inner cortex and outer medulla was about 10 and 3 times higher than in the outer cortex, respectively, and the activity in the inner medulla was much the same as that in the outer cortex. Captopril was given in doses of 30 and 100 mg/kg/day for 7 days, and the renal ACE activity on the 8th day was examined. Since it was assumed that the ACE activity might be lower than the full activity when the tissue contained captopril, diamide, a sulfhydryl oxidant, was used to eliminate the effect of any captopril remaining in the tissue extracts. However, this compound at concentrations over 1 mM enhanced the activity of ACE itself to about twice the value when assayed without diamide. Thus, oxidation with sufficient concentrations of diamide resulted in an enhancement of a maximal activity of ACE. When all samples were pretreated with 10 mM diamide and the ACE activity determined, captopril caused a dose-related increase in the ACE activity, but only in the inner cortex. We conclude that ACE locates predominantly in the inner cortex of the rat kidney and it is this area which has an altered ACE activity in response to captopril.

This paper describes the morphological responses of adult male guinea pig adrenals to dexamethasone (DEX) and adrenocorticotrophic hormone (ACTH), in both qualitative and quantitative terms. Most organelles and inclusions are affected, but their responses often vary in the different cell types examined: zona fasciculata externa and interna, and zona reticularis. Following DEX the volume of lipid droplets increases in cells of zona fasciculata externa but decreases in zona reticularis; smooth endoplasmic reticulum decreases in fasciculata externa but increases in reticularis. Following ACTH, exactly the opposite occurs. This strongly suggests differing functions for these subcellular entities in each cell type, particularly for the smooth reticulum, as well as for the cells themselves. The volume of the Golgi complex markedly decreases following DEX in all cells but increases only in zona fasciculata interna and zona reticularis following ACTH. These deeper cortical cells are known to secrete at least one sulfated steroid, dehydroepiandrosterone sulfate, and these changes in the Golgi complex strengthen the suggestion that the Golgi plays a role in sulfation of steroids. Mitochondrial volume and number decrease in all cells following DEX, supporting their role in steroidogenesis. Further decreases in their volume, accompanied by increases in their number following ACTH, may be related to a proliferation of mitochondria in response to ACTH. Changes in peroxisome volume and number, following DEX and ACTH, suggest a possible role for these organelles in steroid cell metabolism. Lysosomes decrease in volume in all cells following ACTH. This does not support the recently suggested concept that they play a role in steroid secretion.

Antegrade nailing of proximal femur fractures is a widely accepted treatment that relies on lateral radiographs to assess distal nail positioning. However, the distal femur is trapezoidal in cross section, consequently standard lateral radiographs may be insufficient. This study aimed to utilise 3D modelling to virtually assess the accuracy of lateral radiographs in defining the position of a femoral nail in the distal femur, specifically considering distal cortical encroachment. Three-dimensional models of a commonly used nail, were positioned in 3D models of 63 femora, generated from CT scans. Lateral projections, representative of lateral radiographs, were generated and measurements of the closest point distance between the distal nail and anterior inner cortex were recorded. Axial slices through the model at the same distal position were produced for any nails located in the canal’s anterior 1/5th and used to quantify the shortest nail to anterior cortex distance. A significant (p = 0.000) difference exists between the positions of the nail in the lateral projection (− 1.7 ± 1.24 mm) compared with axial position (− 0.23 ± 1.41 mm) with reference to the inner cortical surface. In the lateral projection, 30 nails were located in the canal’s anterior 1/5th, of these, 14 nails were identified in the axial position as perforating the inner cortex, with four also perforating the outer cortex surface. Femoral nails are often anteriorly located in the distal femur and reviewed using lateral radiographs. However, this research demonstrates that owing to the geometry of the distal femur, a lateral radiograph may be inadequate for determining the true position of a femoral nail within the distal femur. Accurately assessing the position of femoral nails may help to address and prevent thigh pain, and iatrogenic fracture or perforation which have been associated with anterior positioning.

To evaluate thyroid, arytenoid, and cricoid cartilage invasion on computed tomography (CT) imaging in patients undergoing total laryngectomy for both primary and recurrent laryngeal carcinoma. Secondary endpoint was to compare laryngeal cartilage invasion between primary and recurrent tumours. Pre-treatment CT of 40 patients who had undergone total laryngectomy was retrospectively evaluated and compared with histology. Focal erosions of thyroid cartilage were accounted for neoplastic invasion of the inner cortex. Full-thickness thyroid cartilage invasion was defined as a tumour-like tissue replacing thyroid cartilage or extended in extra-laryngeal soft tissues. Sclerosis and erosion of arytenoid and cricoid cartilages were assessed as signs of neoplastic invasion. CT erosion showed perfect agreement for thyroid inner cortex and cricoid cartilage invasion and almost perfect agreement (87%) for arytenoid cartilage invasion. For tumours in contact with thyroid cartilages, the absence of CT erosion underestimated inner cortex infiltration. CT showed perfect agreement in predicting full-thickness thyroid cartilage invasion only in the case of extra-laryngeal neoplastic extension. Arytenoid sclerosis showed poor correlation with neoplastic invasion. For primary tumours, CT demonstrated good (inner cortex 75%; full-thickness 85%), substantial (67.5%), and perfect (100%) accuracy in thyroid, arytenoid, and cricoid cartilage invasion, respectively. No CT differences were observed between primary and recurrent laryngeal tumours. Tumour-like tissue extension in the extra-laryngeal soft tissues was accurate in predicting thyroid cartilage full-thickness invasion. Erosions of arytenoid, cricoid, and thyroid cartilages’ inner cortex on CT were highly indicative of neoplastic infiltration. No CT difference in cartilage infiltration between primary and recurrent tumours was observed.

The sex-specific prevalence of adrenal diseases has been known for a long time. However, the reason for the high prevalence of these diseases in females is not completely understood. Mouse studies have shown that the adult adrenal gland is sexually dimorphic at different levels such as transcriptome, histology, and cell renewal. Here we used RNA-seq to show that in prepubertal mice, male and female adrenal glands were not only sexually dimorphic but also responded differently to the same external stimulus. We previously reported that thyroid hormone receptor β1 (TRβ1) in the adrenal gland is mainly expressed in the inner cortex and the fate of this TRβ1-expressing cell population can be changed by thyroid hormone (triiodothyronine; T3) treatment. In the present study, we found that adrenal glands in prepubertal mice were sexually dimorphic at the level of the transcriptome. Under T3 treatment, prepubertal females had 1162 genes differentially expressed between the saline and T3 groups, whereas in males of the same age, only 512 genes were T3-responsive. Immunostaining demonstrated that several top sexually dimorphic T3-responsive genes, including Cyp2f2 and Dhcr24, were specifically expressed in the adrenal inner cortex, precisely in an area partially overlapping with the X-zone. Under T3 treatment, a unique cortical layer that surrounds the adrenal X-zone expanded significantly, forming a distinct layer peculiar to females. Our findings identified novel marker genes for the inner adrenal cortex, indicating there are different sub-zones in the zona fasciculata. The results also highlight the sex-specific response to thyroid hormone in the mouse adrenal gland.

OBJECTIVEThe authors describe a novel “in-out-in” technique as an alternative option for posterior C2 screw fixation in cases that involve narrow C2 isthmus. Here, they report the preliminary radiological and clinical outcomes in 12 patients who had a minimum 12-month follow-up period.METHODSTwelve patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation. All patients had unilateral hypoplasia of the C2 isthmus that prohibited insertion of pedicle screws. A new method, the C2 medial pedicle screw (C2MPS) fixation, was used as an alternative. In this technique, the inner cortex of the narrow C2 isthmus was drilled to obtain space for screw insertion, such that the lateral cortex could be well preserved and the risk of vertebral artery injury could be largely reduced. The C2MPS traveled along the drilled inner cortex into the anterior vertebral body, achieving a 3-column fixation of the axis with multicortical purchase.RESULTSSatisfactory C2MPS placement and reduction were achieved in all 12 patients. No instance of C2MPS related vertebral artery injury or dural laceration was observed. There were no cases of implant failure, and solid fusion was demonstrated in all patients.CONCLUSIONSThis novel in-out-in technique can provide 3-column rigid fixation of the axis with multicortical purchase. Excellent clinical outcomes with low complication rates were achieved with this technique. When placement of a C2 pedicle screw is not possible due to anatomical constraints, the C2MPS can be considered as an efficient alternative.

Background Implantation of Kerboull acetabular reinforcement cross-plates (Kerboull plate) carries a risk for injury to vascular structures and pelvic organs. To our knowledge, there is no study assessing anatomical assessment related to this risk with this specific design. Therefore, we performed a prospective study to answer the following four questions: 1) What is the minimum distance and angle between the plate and iliac vessels? 2) What is the distance between the plate and the inner cortex of the ilium? 3) What is the ratio of views with muscle tissue present on the inner surface of the ilium? 4) What are the boundaries of the safe zone for transacetabular screw fixation for a Kerboull plate? Hypothesis A safe zone for fixation screws would be defined by a narrow range of insertion angles. Materials and methods This is a CT-based 3D templating prospective study. Simulations were performed for 18 patients fitted with a Kerboull plate. An original Kerboull plate (Stryker, Mahwah, NJ, USA) was placed at a 45° abduction angle relative to the X-axis (alignment A) and the palette was placed vertically to the X-axis (alignment B). We measured the distance from the centre of the plate to the inner surface of the cortex of the ilium, the shortest distance to vessels and the angle of existing vessels, and the ratio of muscles on the inner surface of the ilium. Results The shortest distance to the vascular structures increased with increasing angle of insertion of the fixation screws, 85.8 ± 12.1 mm for A and 111.4 ± 12.0 mm for B at 45°. The distance to the inner cortex was further increased for screws inserted in posterior direction. At insertion angles ≥ 40°, the screws passed through muscle before invading the pelvis in most cases. However, at anterior-posterior angle (AP angles) ≤ −10°, the risk of direct insertion of screws into the sacroiliac joint increased. Discussion The safe zone for transacetabular screws would be insertion at an angle ≥ 40°, with an AP angle between 0° and −10° (slight posterior direction). Level of evidence Level IV prospective diagnostic study.

Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease.

Background Vascular endothelial growth factor (VEGF) induces angiogenesis and osteogenesis in bone allotransplants. We aim to determine whether bone remodeling in VEGF-treated bone allotransplants results from repopulation with circulation-derived autogenous cells or survival of allogenic transplant-derived cells. Methods Vascularized femoral bone transplants were transplanted from female Dark Agouti rats (DA;RT1a) to male Piebald Viral Glaxo (PVG;RT1c). Arteriovenous bundle implantation and short-term immunosuppression were used to maintain cellular viability. VEGF was encapsulated in biodegradable microspheres and delivered intramedullary in the experimental group (n = 22). In the control group (n = 22), no VEGF was delivered. Rats were sacrificed at 4 or 18 weeks. Laser capture microdissection of bone remodeling areas was performed at the inner and outer cortex. Sex-mismatched genes were quantified with reverse transcription-polymerase chain reaction to determine the amount of male cells to total cells, defined as the relative expression ratio (rER). Results At 4 weeks, rER was significantly higher at the inner cortex in VEGF-treated transplants as compared to untreated transplants (0.622 ± 0.225 vs. 0.362 ± 0.081, P = 0.043). At 4 weeks, the outer cortex in the control group had a significantly higher rER (P = 0.038), whereas in the VEGF group, the inner cortex had a higher rER (P = 0.015). Over time, in the outer cortex the rER significantly increased to 0.634 ± 0.106 at 18 weeks in VEGF-treated rats (P = 0.049). At 18 weeks, the rER was >0.5 at all cortical areas in both groups. Conclusions These in vivo findings suggest a chemotactic effect of intramedullary applied VEGF on recipient-derived bone and could imply that more rapid angiogenesis of vascularized allotransplants can be established with microencapsulated VEGF. © 2014 Wiley Periodicals, Inc. Microsurgery 35:45–51, 2015.

Although it is known that long cortical bone structurally alter their area moment of inertia with age related bone loss maintaining their bending strength, the incidence of fragility fractures associated with cortical thinning still prevails. We hypothesize that cortical thinning with aging increases the local buckling susceptibility under abnormal or eccentric loads, and initiates fracture. The paper presents a series of 3D geometrical model derived from CT scans of a human femoral neck used to simulate age-related bone loss. The purpose of the model is to predict the susceptibility of local buckling at the femoral neck in falls by elderly folks. Geometric three-dimensional models of femoral neck cortices were developed from 7 human cadaver femurs (4 female, 3 male, 52-68 years). Three age related femoral neck models were simulated by either reducing (young age-related model) or increasing (old age-related model) the outer cortical surfaces in the radial-direction, by 1-mm. The control model was the middle-age related model. The inner cortex diameter was also adjusted to equilibrate the compressive stresses, based on the load-profile of a single-legged stance. Based on the old age related model, two additional "fragile" models were simulated by reducing the compressive load profile by 10 and 20% changing the inner cortex diameter, respectively. Using these models for each specimen, the consequence of a fall on the greater trochanter was evaluated. The Finite Strip Method (FSM) was used to investigate the association between local buckling at the femoral neck and the load to failure. Under constant loading, buckling progressively reduced the load to failure with aging, as seen in 2/7 of the middle age (by 9-15%) and 5/7 of the old age (by 7-32%) related models. In the fragile models, a 51% reduction in the load to failure was noted. Structural adaptation to age-related bone loss might preserves the bending strength under physiologic loads, but cortical thinning effects the buckling ratio reaching a critical threshold that would make the bone susceptible to local buckling at the femoral neck increasing the risk of fracture in a fall.

The development of the adrenal cortex involves the formation and then subsequent regression of immature or fetal inner cell layers as the mature steroidogenic outer layers expand. However, controls over this remodeling, especially in the immature inner layer, are incompletely understood. Here we identify an inner cortical cell population that expresses thyroid hormone receptor-β1 (TRβ1), one of two receptor isoforms encoded by the Thrb gene. Using mice with a Thrbb1 reporter allele that expresses lacZ instead of TRβ1, β-galactosidase was detected in the inner cortex from early stages. Expression peaked at juvenile ages in an inner zone that included cells expressing 20-α-hydroxysteroid dehydrogenase, a marker of the transient, so-called X-zone in mice. The β-galactosidase-positive zone displayed sexually dimorphic regression in males after approximately 4 weeks of age but persisted in females into adulthood in either nulliparous or parous states. T3 treatment promoted hypertrophy of inner cortical cells, induced some markers of mature cortical cells, and, in males, delayed the regression of the TRβ1-positive zone, suggesting that TRβ1 could partly divert the differentiation fate and counteract male-specific regression of inner zone cells. TRβ1-deficient mice were resistant to these actions of T3, supporting a functional role for TRβ1 in the inner cortex.

Background: Cortical reaming and intramedullary nail insertion injure the medullary vascular system. Little attention has been directed toward quantitative assessment of bone injury and repair after locked intramedullary nailing of long-bone fractures with and without reaming. The effects of reamed versus unreamed locked intramedullary nailing on cortical porosity and new bone formation were compared in a sheep fractured tibia model. Methods: After creation of a standardized spiral fracture by three-point bending with torsion, each tibia was stabilized by insertion of a locked intramedullary nail. Ten sheep were randomized into two groups, one that had reaming before nail insertion and one that did not. Fluorochromes were given 2 weeks (xylenol orange), 6 weeks (calcein green), and 12 weeks (tetracycline) postoperatively. All animals were killed at 12 weeks postoperatively. Cortical porosity and new bone formation were determined for the proximal diaphysis, fracture site, and distal diaphysis. Results: Overall cortical porosity was greater with reamed nails than with unreamed nails (p = 0.02). Porosity in the inner cortex (18.3% (reamed) vs. 14.3% (unreamed); p = 0.09) and outer cortex (16.8% (reamed) vs. 12.2% (unreamed) ; p = 0.04) was greater in the reamed group. With reamed nails only, there was less new bone formation at 2 (p = 0.04) and 12 (p = 0.05) weeks in the inner cortex compared with the central cortex and outer cortex. Overall, there was no difference between reamed and unreamed nails in the amount of new bone formation at 2, 6, or 12 weeks. Conclusions: This study demonstrates that greater injury or overall cortical porosity is associated with reamed nail insertion. There is no difference, however, between the amount of new bone formation after reamed and unreamed nail insertion. Nail insertion without reaming may be initially advantageous when tibial cortical vascularity is compromised, by limiting further injury to cortical bone. This may be important with open tibial fractures in which there is a significant risk of infection after injury. Between 2 and 12 weeks after injury, neither reamed nor unreamed nail insertion seems to have a significant advantage with respect to the amount of new bone formation that occurs.

The effects of angiotensin II type 1 receptor antagonist (losartan), angiotensin I-converting enzyme (ACE) inhibitor (enalapril), and calcium channel blocker (nifedipine) on autoregulation of total and zonal glomerular filtration rate (GFR) were studied in spontaneously hypertensive rats (SHRs), 10 and 40 weeks of age, and 10-week-old Wistar-Kyoto (WKY) rats. Untreated animals in each group served as controls. Renal blood flow (RBF) was measured by a transit-time flow probe (Transonic) on the left renal artery. Total and zonal GFR (outer, middle, and inner cortex) were estimated from tubular uptake of 125 iodine-labeled aprotinin ( 125 I Ap ) injected i.v. at control renal arterial pressure (RAP), and 131 I Ap injected at a RAP reduced to the lower limit of RBF autoregulation. Autoregulation of RBF was reset to higher pressure levels in untreated hypertensive rats. Enalapril normalized this resetting in 10-week-old SHRs, but not in aged SHRs 40 weeks. Losartan did not completely normalize this resetting in either 10- or 40-week-old SHRs, whereas nifedipine impaired RBF autoregulation in both WKYs and SHRs. A decreased autoregulatory compensation of GFR after pressure reduction was observed in losartan-treated 10-week-old SHRs and after all drug regimens in 40-week SHRs. GFR autoregulation in outer, middle, and inner cortex was impaired in losartan-treated 10- and 40-week-old SHRs. With all treatments, the autoregulation in 10- and 40-week-old SHRs was better preserved in the inner than in the outer cortex. The impaired autoregulation may indicate that a part of the dilatory capacity of preglomerular vessels has already been taken out by hypotensive treatment. Renal vascular abnormalities may have an additional effect.

Autoregulation of total and zonal glomerular filtration rate (GFR) in outer, middle and inner cortex was estimated in spontaneously hypertensive rats (SHR), from the tubular uptake of 125I-labeled aprotinin (125I-Ap), injected at control renal arterial pressure (RAP), and 131I-Ap, injected at reduced RAP in left kidney. Normotensive Wistar-Kyoto (WKY) rats were used as controls. Renal blood flow (RBF) autoregulation was reset to higher pressure levels in SHR. When RAP was lowered close to the lower pressure limit of RBF autoregulation, total GFR was reduced to 89.5 +/- 3.1 and 88.1 +/- 3.3% of control in 10- and 40-wk WKY and to 87.7 +/- 2.3 and 88.0 +/- 2.2% in 10- and 40-wk SHR. In WKY, the fall of GFR in the three cortical layers was not different during RAP reduction. In 10- and 40-wk-old SHR, however, GFR fell significantly less in inner than in middle and outer cortex (P < 0.05). We conclude that autoregulation of GFR is most efficient in the inner cortex of SHR. In all animals, GFR was less well autoregulated than RBF.

During total hip arthroplasty (THA), the external iliac, femoral, and obturator vessels are at risk of vascular injury when penetrating the inner cortex of the pelvis. The purpose of this study was to clarify the location of these vessels using three-dimensional computed tomographic angiography (3DCT-A).We enrolled 100 subjects (200 hips) without hip disease and performed examinations on the following. (1) External iliac-femoral vessels: we measured the shortest distance from these vessels to the pelvis on axial CT images and investigated the factors affecting distance. The anatomical course of the iliac artery was classified as straight, curved, or tortuous, and the correlation between course and age was established. (2) Obturator vessels: we measured the shortest distance from the obturator vessels to the quadrilateral surface on axial CT images. (3) Visualization of pelvic vessels was through the pelvis by dual-phase 3DCT-A.(1) The external iliac vein was located significantly closer to the pelvis than the artery, especially on the left side and in aged and female subjects. The single-curved and tortuous double-curved vessel types were found in aged subjects, and external iliac vessels of these types were closer to the pelvis than vessels of the straight type. In 36 subjects, the external iliac veins lay directly on the osseous surface of the pelvis (right 16, left 36). Of these 36 subjects, only one had straight-type vessels. (2) Obturator vessels were located just behind the acetabulum near the obturator foramen. (3) Reconstructed 3DCT images enabled us to visualize the pelvic vessels and demonstrated the danger area for penetrating the inner cortex of the pelvis.Understanding the anatomical orientation of the pelvic vessels around the acetabulum using 3DCT-A could be helpful for preventing vascular injury during THA.

The relation between the arteriolar diameters and hypertensive glomerulosclerosis was studied by using microvascular casts and histological evaluation. Spontaneously hypertensive rats 4 weeks of age were divided into three groups: nontreated, captopril (40 mg/kg/day)-treated, and trichlormethiazide (1 mg/kg/day) with hydralazine (20 mg/kg/day)-treated. Wistar-Kyoto rats served as controls. At 6 weeks old, the captopril-treated rats showed a lower blood pressure and a larger afferent arteriolar diameter compared with the control rats. At 20 weeks old, the nontreated group exhibited hypertension and a lower arteriolar diameter ratio (afferent to efferent, 0.89 versus 1.22 in control group) because of afferent constriction and efferent dilatation, seen equally in the outer and inner cortexes. Glomerulosclerosis was accentuated only in the inner cortex of the nontreated group (score, 63 versus 29 in control group). In the two treated rat groups, the blood pressure was reduced and arteriolar diameter ratios were similar to those in the control group (1.18 and 1.26). The sclerosis score in the trichlormethiazide with hydralazine-treated rats (score, 26) was lower than in the nontreated rats but not the captopril-treated rats (score, 36). These results indicated that 1) in the hypertensive rats, despite a reduced diameter ratio, glomerulosclerosis was more severe in the inner cortex; 2) two therapies reduced blood pressure and reversed the arteriolar changes, but a decrease in glomerulosclerosis was seen only in the trichlormethiazide with hydralazine-treated rats; and 3) for development of glomerulosclerosis, factors other than hemodynamics may be important in addition to intraglomerular pressure.

While it is known that angiotensin-converting enzyme (ACE) in the kidney is concentrated at the brush borders of the proximal tubule, the role of tubular ACE in renal physiology is not well understood. The active site of tubular ACE is exposed on the luminal surface of the brush borders and may hydrolyze peptides in the glomerular filtrate. However, a positive correlation between blood pressure and renal ACE activity was observed in spontaneously hypertensive rats, as well as in cases of ACE inhibition. Determination of ACE activity in different renal zones and immunohistochemistry demonstrated that ACE predominates in the inner cortex and that the proximal tubule in the outer cortex contains less ACE. Perhaps the inner cortex is the area responsible for alteration of renal ACE activity, since only ACE activity in the inner cortex increased following administration of the ACE inhibitor captopril. This would suggest that the induction of ACE occurs in the inner cortex. Renal ACE activity is also affected by oxidation. Thus, the activity increased when diamide, an oxidizing agent, was added to the crude extract of renal cortex and when oxygen was introduced into the extract. Therefore, tissue oxidation may be one factor affecting renal ACE activity.

BACKGROUND In hypertensive nephropathy the morphological changes and albuminuria seem to start in the inner cortex but the mechanism of proteinuria is unknown. We tested the hypothesis of reduced glomerular charge selectivity in the juxtamedullary cortex of old spontaneously hypertensive rats (SHR) as a cause of proteinuria in rats with hypertensive nephropathy. METHODS The glomerular charge barrier was evaluated in 80-week-old SHR and age-matched normotensive Wistar-Kyoto rats (WKY) by measuring the glomerular clearance of radiolabelled cationic and anionic chymotrypsinogen (Chym and aChym, MW 25,000) accumulated by the proximal tubular cells in the outer, middle and inner cortex following intravenous injection. The glomerular filtration rates (GFR) in the cortical zones were obtained by aprotinin (MW 6500) and the sieving coefficient (theta) of the protein tracers calculated as their glomerular clearance/GFR. RESULTS The theta aChym was similar in SHR and WKY except in the inner cortex where it was 35% higher in SHR (0.65+/-0.05) than in WKY (0.48+/-0.03) (P = 0.01). The ratio of theta aChym to theta Chym was increased from 0.55+/-0.06 to 0.77+/-0.05 (P

The major problems in dealing with established mandibular loss are severe soft-tissue contracture and a limited number of recipient vessels. The skin portion of the iliac osteocutaneous flap often necrotizes in cases without perforators of the deep circumflex iliac vessel. To overcome these problems, eight patients with established mandibular loss and no skin perforators of the deep circumflex iliac vessel were treated with a sequential vascularized iliac bone graft and a superficial circumflex iliac perforator flap with a single recipient vessel. Regarding the recipient vessels, the ipsilateral cervical vessels were used for four patients, and the contralateral facial and ipsilateral superficial temporal vessels were used for two cases each. The superficial circumflex iliac perforator flaps were 7 to 28 cm in length and 3 to 15 cm in width. The iliac bone grafts ranged from 7 to 13 cm in length, and three cases were repaired with the inner cortex of the iliac bone. There were no serious complications, such as flap necrosis or bone infection and resulting absorption. The advantages of this method are that both pedicles are very close to each other and of suitable diameter for anastomosis. Simultaneous flap elevation and preparation for the recipient site is possible. The skin flap and vascularized bone graft can be obtained from the same donor site. A single source vessel can nourish both the large skin area and bone sequentially. Longer dissection of the superficial circumflex iliac system to the proximal femoral division is unnecessary. A large flap can survive with a short segment of the superficial circumflex iliac system. Only the vascularized inner cortex of the iliac bone needs to be used, and the outer iliac cortex can be preserved, which results in less morbidity at the donor site.

Cisplatin (CDDP) is a potent nephrotoxin, and nephrotoxicity is its most important dose-limiting toxicity. In this study, we aimed to investigate the role of recombinant human erythropoietin (rhEPO) in the protection of cisplatin-induced nephrotoxicity and compare its efficacy with the cell-protective agent amifostine. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to four groups, each including six rats. Group A received only CDDP, group B received CDDP plus rhEPO, group C received CDDP plus amifostine, and group D received only rhEPO. At the end of 7 wk, hemoglobin (Hgb), hematocrite (Htc), blood urea nitrogen (BUN), and creatinine (Cr) levels were determined and kidneys of the rats were removed. The weights of the kidneys were measured and sent for histopathological examination. Proximal tubules from four areas of the kidney (outer cortex, inner cortex, the medullary ray, and outer stripe of outer medulla [OSOM]) were evaluated. There were statistically significant differences among the groups in terms of tubular scores, including overall renal tubular score, cortex, inner cortex, OSOM, and medullary ray tubular scores, and Htc levels. Group A rats had the worse tubular scores in all categories when compared to group D rats. When the results of groups B and C were compared, there were no differences in terms of BUN, Cr levels, and tubular scores, but the Htc level was significantly higher in group B. Group B rats had better overall and OSOM tubular scores when compared to group A. Group C also had better overall and OSOM tubular scores compared to group A. The present study showed for the first time that rhEPO plays an important role in the prevention of cisplatin-induced nephrotoxicity and it is as effective as amifostine.

Pro-opiomelanocortin (POMC)-derived peptide [adrenocorticotropic hormone (ACTH), beta-endorphin, alpha-melanocyte-stimulating hormone (MSH)]- and cytokine (IL-1 alpha, IL-1 beta, IL-2, IL-6, TNF-alpha)-like molecules were demonstrated in PAS positive epithelial cells of the thymus of the anuran amphibian Rana esculenta by an immunocytochemical procedure. Three groups of PAS positive epithelial cells were identified in subcapsular cortex, inner cortex and medulla, respectively. The cells containing ACTH-, alpha-MSH- and cytokine-like molecules were distributed in the cortex and those containing beta-endorphin-like molecules in the medulla and inner cortex. Thymic lymphocytes were always negative for POMC-derived peptides and cytokines. These results suggest that the neuroendocrine function of the thymus can be traced back to lower vertebrates.

Ontogeny of aromatic L-amino acid decarboxylase-containing tubule cells in rat kidney. Dopamine plays an important role in regulation of renal sodium transport. Proximal tubule cells produce dopamine after decarboxylation of L-DOPA via the enzyme aromatic L-amino acid decarboxylase (AADC). The presence and cellular localization of AADC-like immunoreactivity (-LI) and AADC mRNA were examined during pre- and postnatal development in rat kidney by indirect immunofluorescence and in situ hybridization histochemistry. Few scattered condensations of AADC-immunoreactive (-IR) tubule cells forming a lumen were detected on gestational day 18. From gestational day 21, many AADC-IR tubule cells were observed in the inner cortex, whereas the outer cortex lacked AADC-LI. Within 24 hours of birth, AADC-IR cells in the inner cortex could be identified as proximal tubule cells. During day 3 and 5 there was an increase in number of AADC-IR proximal tubule cells in the inner cortex, leaving less amount of AADC-negative cells in the outer cortex. Starting from day 8, AADC-IR cells could be seen in the outer cortex. An apparent decrease in AADC-immunofluorescence intensity was observed at 40 days, and at 80 days virtually no AADC-LI could be demonstrated. Intrarenal levels of dopamine showed a tendency to increase between 3 and 20 days, and showed significant decreases between 20 to 40 days and between 40 to 80 days. AADC mRNA was not detected in the kidney at 18 hours after birth, but could be observed in the inner cortex at 6 days. At 12, 19 and 40 days AADC mRNA was seen in the entire cortex. The results indicate that dopamine can be formed prenatally in the proximal tubules of the rat kidney and that the levels of dopamine increase postnatally to reach a peak at one month.

The potential of magnetic resonance (MR) imaging enhanced with albumin-(gadolinium diethylenetri-aminepentaacetic acid [DTPA])35, a macromolecular blood pool marker, for detection of focal changes in renal perfusion was studied in a myoglobinuric acute renal failure (ARF) model in the rat. T1-weighted spin-echo postcontrast images of injured kidneys at 3 hours after glycerol injection showed three distinct zones: a strongly enhanced outer cortex, a low-intensity inner cortex, and a strongly enhanced medulla. The distinct band of low intensity in the inner cortex indicated zonal decreased blood volume, corresponding to published microsphere data showing zonal low perfusion in the inner cortex. Contrast differences between parenchymal zones were significant for at least 30 minutes. No focal ischemic changes could be delineated on nonenhanced images. Enhanced and nonenhanced images of injured kidneys obtained at 24 hours after glycerol injection revealed no zonal differentiation. Contrast-enhanced MR imaging data in this ARF model correlated well with pathologic data and microsphere perfusion results. Contrast-enhanced characterization of the ischemic phase of renal injury with MR imaging may improve specificity for the diagnosis of ARF and may serve as a marker for therapeutic intervention.

To clarify the possible role of intrarenal renin-angiotensin system (RAS) in the evolution of renal hemodynamic alteration in diabetes, we investigated the change of tissue angiotensin-converting enzyme (ACE) activity, a key enzyme of RAS, in the kidneys obtained from streptozotocin-induced diabetic rats. Tissue ACE activity was significantly reduced in both outer cortex (0.29 ± 0.04, mean ± SEM, n = 6) and inner cortex with outer medulla (2.43 ± 0.28, n = 6) of the kidneys from diabetic rats 2 weeks after induction of diabetes compared with those from control rats (0.47 ± 0.05, n = 7, in outer cortex; 3.68 ± 0.32, n = 7, in inner cortex with outer medulla). ACE activities in the lung and aorta of diabetic rats were not different from those of control rats. ACE activities in the serum and urine were significantly elevated in diabetic rats. Treatment of diabetic rats with insulin to achieve near euglycemia completely prevented these alterations in ACE activity, except that, in the urine, the elevation of ACE was partially corrected with insulin. In contrast to ACE activity, activity of N-acetyl-β-D-glucosaminidase (a lysosomal enzyme of the tubule) and r-glutamyl transpeptidase (a brush border enzyme) in the kidney were not reduced in diabetic rats, whereas in the urine both enzyme activities were significantly elevated in diabetic rats. It is likely, therefore, that the reduction of ACE activity in the kidneys of diabetic rats may reflect the impairment of vascular endothelial cells in the kidney, rather than tubular damage. These results suggested that the reduction of tissue ACE activity in the kidneys of diabetic rats might play an important role for the alteration of renal microcirculation and contribute to the development of diabetic nephropathy.

Changes in adrenal medullary and total cortical blood flow after hemorrhage have been described using radioactive microspheres. To assess changes in adrenal capsular and in intracortical adrenal blood flow, a method was used based on microscopic detection of non-radioactive microspheres. Injection of microspheres labelled with fluorescent dyes permitted multiple determinations of blood flow. Pentobarbital anesthetized dogs ( n = 6) were prepared acutely with left ventricular and aortic catheters for injection and collection of microspheres, respectively. Adrenal denervation was done unilaterally by cutting the thoracic splanchnic nerve. Injections of 16-μm spheres were made prior to and immediately after 18 ml/kg hemorrhage done over 6 min. Dogs were killed with KCI and adrenals were removed, fixed and sectioned at 80 μm. Using fluorescence microscopy, microspheres were counted in the adrenal capsule, zona glomerulosa, inner cortex (zona facsiculata and reticularis), and the medulla. The majority (95%) of microspheres in the adrenal cortex were trapped in the zona glomerulosa, precluding an independent estimate of blood flow to the inner cortex. Thus, total cortical blood flow was determined by summing the number of 16-μm microspheres in the zona glomerulosa and inner cortex. Prior to hemorrhage, blood flow was greater in the capsule (5.4 ± 1.6 ml/min/g) compared to the cortex (1.8 ± 0.9 ml/min/g) and the medulla (2.9 ± 1.8 ml/min/g). Splanchnicotomy did not change blood flow in the resting state. Following hemorrhage, in innervated glands, medullary blood flow increased to 8.6 ± 3.1 ml/min/g, whereas blood flow to other zones was unchanged. Since the mean arterial pressure observed after hemorrhage varied among dogs, the relationship between blood flow in each adrenal zone and the mean arterial pressure in individual dogs was assessed by regression analysis. After hemorrhage, blood flow and vascular conductance in each adrenal zone were inversely proportional to mean arterial pressure. In the medulla, splanchnicotomy abolished sensitivity of blood flow to mean arterial pressure, whereas in capsule and cortex splanchnicotomy did not affect sensitivity of blood flow to mean arterial pressure. These findings support earlier work showing that the distribution of adrenal blood flow changes after hemorrhage and is influenced by splanchnic innervation. In addition, these findings suggest that blood flow to the adrenal capsule and cortex may be maintained during hypotension independently of thoracic splanchnic innervation.

This study aimed to summarize the current progress in the field of robot-assisted laminectomy in spinal surgery. A systematic search of the Institute of Electrical and Electronics Engineers (IEEE) Xplore, PubMed, Embase, Web of science, The Cochrane Library, Wanfang Data, China National Knowledge Infrastructure (CNKI), and Chinese Biomedicine Literature Database (CBM-SinoMed) was performed for papers related to robotic-assisted laminectomy. A total of 27 articles were selected for inclusion in our study. Among the articles, 10 robotic system, 2 bone cutting strategies, 6 state recognition strategies were founded. The most commonly adopted type of robot system was the Nathoo A type (6/10). Bone cutting strategies were mainly formulated based on force information and medical image information, and state recognition was based on a variety of factors, including force, sound, vibration, medical images, current or a combination of parameters. Early research on robot-assisted laminectomy did not reflect good continuity, and the studies mainly focused on the type of robotic system. In recent years, more researchers have chosen the Nathoo A as the robot system type, and the focus of research has gradually shifted to laminectomy path planning and safety control strategies, such as state recognition. Although these studies have been able to perform laminectomy without penetrating the inner cortex of the lamina, most experiments have been performed in vitro, and clinical application is still untested.

The present study evaluated the outcomes of internal fixation with a joint line plate in the treatment of tibial plateau fractures caused by hyperextension of the varus. The study included 25 cases (13 males and 12 females; age, 19-71 years) of tibial plateau fracture caused by hyperextension of the varus, which were treated at Puai Hospital, Tongji Medical College (Wuhan, China) between January 2015 and June 2017. Fractures were treated with internal fixations of the inner cortex with a self-clipped joint line plate made of steel. After the surgery, patients were examined immediately and at 3, 6 and 12 months. Healing was evaluated by X-ray examination. All cases were cured during follow-up. After surgery, one patient developed partial necrosis of the skin margin of the incision and recovered after a dressing change. Furthermore, one patient with a concomitant peroneal nerve injury and hypoesthesia recovered after treatment with neurotrophic drugs. No screw loosening, fractures or failure of the internal fixations occurred. According to the X-ray results, there were significant differences in the tibial plateau angle (TPA) and medial posterior slope angle (m-PSA) between the pre-operative stage and 12 months post-operatively (P0.05). In conclusion, internal fixation with a joint line plate is an appropriate treatment for tibial plateau fractures involving the anteromedial margin with good clinical efficacy.

Background. Wiktor Dega originally described the surgical technique of transiliac osteotomy in 1969 in the Polish Orthopaedics and Trauma Surgery Journal. Its worldwide popularity spread just after it was presented in English by Grudziak and Ward in 2001 [1]. This paper aims to describe the development of the technique by Wiktor Dega’s team. Material and methods. An analysis of original papers published by Dega between 1929-1974 was performed to clarify the chronology of development of the technique. Results. Dega’s interest in developmental dysplasia of the hip (DDH) had begun as early as 1929, when he presented in Vilnius a paper about the aetiology and pathogenesis of the disease. The concept of transiliac osteotomy had been initially based on König’s idea of shelf procedure. Dega called this procedure plastic surgery of the acetabular roof and performed it between 1927 and 1930. In 1964, Dega published a paper that described the basic concept of DDH treatment with a pelvic osteotomy termed supraacetabular semi-circular osteotomy. This procedure differed from transiliac osteotomy because it did not involve cutting the inner cortex of the ilium. In 1968 the first ‘technically proper’ transiliac osteotomy was performed and then described in 1969. In 1974, Dega emphasized that both the outer and inner iliac walls should be osteotomized in the transiliac osteotomy. Conclusion. The political situation of the 1950s and the 1960s made it difficult to freely exchange views and clinical experiences between the Western and Eastern political camps. Despite this, Wiktor Dega became a precursor of effective surgical treatment in DDH worldwide.

Objectives: Laryngeal squamous cell carcinoma (LSCC) can involve different anatomic subunits with peculiar surgical and prognostic implications. Despite conflicting outcomes for the same stage of disease, the current staging system considers different lesions in a single cluster. The aim of this study was to critically discuss clinical and pathologic staging of primary and recurrent advanced LSCC in order to define current staging pitfalls that impede a precise and tailored treatment strategy. Methods: Thirty patients who underwent total laryngectomy in the past 3 years for primary and recurrent advanced squamous cell LSCC were analyzed, comparing endoscopic, imaging, and pathologic findings. Involvement of the different laryngeal subunits, vocal-fold motility, and spreading pattern of the tumor were blindly analyzed. The diagnostic accuracy and differences between clinicoradiologic and pathologic findings were studied with standard statistical analysis. Results: Discordant staging was performed in 10% of patients, and thyroid and arytenoid cartilage were the major diagnostic pitfalls. Microscopic arytenoid involvement was significantly more present in case of vocal-fold fixation ( P = .028). Upstaging was influenced by paraglottic and pre-epiglottic space cancer involvement, posterior commissure, subglottic region, arytenoid cartilage, and penetration of thyroid cartilage; on the contrary, involvement of the inner cortex or extralaryngeal spread tended to be down-staged. Radiation-failed tumors less frequently involved the posterior third of the paraglottic space ( P = .022) and showed a significantly worse pattern of invasion ( P < .001). Conclusions: Even with the most recent technologies, 1 in 10 patients with advanced LSCC in this case series was differently staged on clinical examination, with cartilage involvement representing the main diagnostic pitfall.

Laryngeal cancer represents 4,5% of all malignancies and 28% of cancers of the upper aerodigestive tract. Pretreatment staging of laryngeal carcinoma should involve evaluation of thyroid cartilage invasion. Cartilage invasion which determines T stage in laryngeal cancer can be detected in 26-75% of the patients and if not detected preoperatively, may cause errors in staging in 40-50% of the patients.1 In recent TNM classification inner cortex involvement is classified as T3 and outer cortex invasion is T4a.2 This article is protected by copyright. All rights reserved.

Category: Trauma Introduction/Purpose: The current gold-standard for unstable distal fibula fractures is plate and screw fixation; however, intramedullary distal fibular fixation is becoming more commonplace. Although surgeons may consider this technique only for patients requiring extra soft tissue protection, recent studies are showing that it is a safe and effective technique for maintaining adequate reduction and promoting proper fracture healing in a wide-variety of ankle fractures. As newer techniques and equipment are developed, it is important to continue with analyzation of patient outcomes. Our study evaluates a intramedullary device that contains a unique proximal locking mechanism that deploys fins against the inner cortex to help maintain fracture length and control rotation. To our knowledge, no other study in the literature has evaluated this technique for distal fibula fractures. Methods: A retrospective case-series was conducted on all patients >18-years old with unstable ankle fractures treated with the same intramedullary distal fibular fixation, that contained the unique proximal locking system. Surgeries were performed at a single institution by a single surgeon between September 2015 and June 2018. Patient imaging was carefully assessed for quality of reduction using previously established guidelines classifying reductions as “good”, ”fair”, or “poor”. Patient charts were also assessed for comorbidities, initial fracture classification, postoperative complications, and need for additional surgery. Results: Forty-one patients were included in the study. Twenty-five patients were female and 16 patients were male. Average age was 52. Average follow-up was 10.0 months. Eleven fractures were bimalleolar (27%), eight were isolated distal fibula fractures (20%), eight were bimalleolar-equivalent fractures (20%), nine were trimalleolar fractures (22%), and five were pilon fractures (12%). Seventy-one percent were Weber B and 29% were Weber C. Based on the classification system, 37 fracture reductions (90%) were classified as ”good”, four were “fair” (10%), and no reductions were ”poor”. There were no instances of hardware failure, loss of reduction, or nonunion. One patient had a superficial wound infection, one patient had a deep wound infection, five patients require painful hardware removal, and one patient had a delayed union. Conclusion: This large case-series is the first study, to our knowledge, in the Foot and Ankle literature to evaluate this specific intramedullary distal fibular fixation system that contains a unique-proximal fixation mechanism within the canal itself. This technique was used for a variety of unstable ankle fractures and was shown to be both safe and effective, and will help guide future prospective studies comparing outcomes with the gold-standard plate and screw fixation.

ObjectiveTo evaluate the ability of four objectively defined, cortical maturation features—surface area, gyrification index, sulcal depth and curvature—from structural MRI at term-equivalent age (TEA) to independently predict cognitive and language development at 2 years corrected age in very preterm (VPT) infants.DesignPopulation-based, prospective cohort study. Structural brain MRI was performed at term, between 40 and 44 weeks postmenstrual age and processed using the developing Human Connectome Project pipeline.SettingMulticentre study comprising four regional level III neonatal intensive care units in the Columbus, Ohio region.Patients110 VPT infants (gestational age (GA) ≤ 31 weeks).Main outcome measuresCognitive and language scores at 2 years corrected age on the Bayley Scales of Infant and Toddler Development, Third Edition.ResultsOf the 94 VPT infants with high-quality T2-weighted MRI scans, 75 infants (80%) returned for Bayley-III testing. Cortical surface area was positively correlated with cognitive and language scores in nearly every brain region. Curvature of the inner cortex was negatively correlated with Bayley scores in the frontal, parietal and temporal lobes. In multivariable regression models, adjusting for GA, sex, socioeconomic status, and injury score on MRI, regional measures of surface area and curvature independently explained more than one-third of the variance in cognitive and language scores at 2 years corrected age in our cohort.ConclusionsWe identified increased cortical curvature at TEA as a new prognostic biomarker of adverse neurodevelopment in very premature infants. When combined with cortical surface area, it enhanced prediction of cognitive and language development. Larger studies are needed to externally validate our findings.

Osteoid osteoma is a benign primary bone tumor of unknown etiology that occurs most commonly in males during adolescence and early adulthood. Osteoid osteoma affects the spine in 20% of cases, and may cause spinal deformity, stiffness, and pain that may sometimes be worst at night. We present a novel description of a partial laminectomy with cement augmentation after resection of an osteoid osteoma. A 22-year-old male with a past medical history of Hodgkin's lymphoma status post chemotherapy and radiation to the mediastinum, and right hip osteoblastoma treated with surgery and radiofrequency ablation presented with low back pain for five years with a recent onset of severe radicular symptoms. The pain was described as shooting and radiating laterally down the right leg to the mid-calf without bowel or bladder incontinence. He has a known right L5 laminar sclerotic lesion measuring 11 x 10 mm causing neuroforaminal narrowing and it kept increasing in size despite previous treatment with stereotactic radiosurgery and radiofrequency ablation. This lesion was metabolically active on positron emission tomography-computed tomography (PET-CT) imaging. His pain was worsening and was refractory to physical therapy, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and radiation therapy. A right L5 partial laminectomy was performed to resect the abnormality in an en-bloc fashion. The lesion did not involve the inner cortex of the bone. Lamina reconstruction was achieved with bone cement augmentation for the preservation of vertebral column strength. Pathology was consistent with osteoid osteoma with marrow edema. Microscopic findings include bony trabeculae associated with prominent rimming and hypercellular fibroblastic stroma. No nuclear atypia, necrosis or appreciable mitotic activity was observed. The patient remains neurologically intact with significantly improved radicular symptoms and low back pain. Osteoid osteoma of the lamina may be resected using a partial laminectomy and cement augmentation done to preserve the integrity of the posterior ligamentous complex, prevent potential fracture of the pars interarticularis, and avoid the need for lumbar fusion in younger patients in whom this pathology is commonly found.

we toke 32 laboratory female rats (Rattus norvegicus) sexually mature 16 weeks age and 200±50 gm in weight, were used, divided to four groups control, low dose, intermediate dose and high dose, later administration by oral gavage tamoxifen citrate for three months 50mg/kg low dose,100mg/kg intermediate dose and 200mg/kg high dose. after that the animals killed, tissue were taken fixed in 10% formalin, section prepares and stained with hematoxilin and eosin in addition special stains for connective tissue by Mallory was done. Histopathological result shoed as the kidney with moderate vacuolated subcapsular cortical tubules,dilated tubules in inner cortex and positive Mallory blue stain collagine fibers around congested blood vessels were seen. Finally it appears that subcabsuler cortical tubules (proximal convulated tubules)as the target toxic effect of tamoxifen citrate in the kidney. Keywords: histopathology, toxicity, tamoxifen, in rats I Introduction Tamoxifen is a drug that has been in worldwide use for the treatment of anti estrogen receptor (ER)- positive breast cancer for over 30 years; it has been used in both the metastatic and adjuvant setting (Matteo et al.,2012). At present, tamoxifen is the only proven oral agent for the adjuvant hormonal treatment of hormone receptor positive breast cancer in premenopausal women (Colleoni et al., 2006), and it can be used in both pre- and postmenopausal women who are at increased risk of breast cancer (Fisher et al.,2005). The concentrations of TAM was detected 2-9-Fold higher in kidneys, than the serum levels. Similar results have been reported following long term TAM administration both in human and animals, Tissue accumulation of TAM may be related to the presence of the anti estrogenic binding- sites (AEBS) in the tissue (Fronson et al .,1973). in the Tamoxifen treated the kidney was extensively degenerated with severe vasocongestion and edema in the renal parenchyma and also wide dilation in the Bowman's capsule. In most areas the Bowman's capsule lost its normal morphology(Sanjeev et al.,2014). The tamoxifen increased incidence of hypernephromas in DEN- initiated rats (Wolf and Jordan, 1992).

Brain abscess remains a life-threatening condition. Here, we are reporting a case of brain abscess due to Bacteroides thetaiotaomicron in a previously known case of recurrent otitis media. A 15 years old boy with a history of recurrent otitis media presented with the complaints of right otalgia, headache and fever. Computed Tomography (CT) brain and neck revealed fluid filled right middle ear cavity with bony destruction along the inner cortex of right temporal bone. The abscess was drained and culture showed growth of Bacteroides thetaiotaomicron. This report illustrates the importance of MALDI-TOF MS in the species level identification of anaerobes thereby facilitating the selection of appropriate and prompt adjuvant antibiotic therapy. This timely identification thus led to a favourable outcome in an era of increasing antimicrobial resistance.

Objective The purpose of this study was to analyze the risk factors for hinge fracture (HF) and non-union during cervical open-door laminoplasty (CODL). Methods We included 25 patients who underwent CODL with available serial computed tomography scans acquired at 2 days and 1 year postoperatively. Patients' medical records and radiographic data were reviewed. Risk factors related to the surgical procedures were evaluated including the lamina angle, spinous angle, difference in the lamina angle, outer cortex location (OCL), and inner cortex location. Results There were a total of 76 hinges. Of these, 44 laminae were classified as deformed hinges, and 32 were classified as fragmented hinges. Additionally, 66 laminae were healed completely, and 10 laminae were not healed by 12 months postoperatively. The OCL (odds ratio, 70.45; 95% confidence interval, 7.73-641.76) was identified as a predictor of HFs immediately following CODL. However, none of the factors we evaluated was related to hinge non-union. Conclusion A medially located hinge gutter ( >1.9 mm from the pedicle on the outer cortex) seems to be an important risk factor for HFs following CODL. However, the hinge healing status was not related to the surgical technique.

The radioactive microsphere method was used to study the distribution of cortical blood flow in anesthetized dogs during water diuresis and during antidiuresis. Infusion of antidiuretic hormone (ADH) at rates ranging from 0.33 to 0.5 mU/kg-min into dogs previously volume expanded with 3% dextrose resulted in an increase in urinary osmolality and a significant increase in fractional flow in the inner cortex. Mean arterial pressure, glomerular filtration rate, and renal plasma flow were unaltered by the infusion of ADH at these doses, suggesting that absolute, as well as fractional, blood flow to the inner cortex increased in response to ADH. In three additional experiments, termination of an infusion of ADH in hydropenic dogs and subsequent induction of water diuresis was accompanied by a shift in fractional cortical blood flow away from the inner cortex. The redistribution of cortical blood flow in response to ADH at a time when the kidney is producing a more concentrated urine supports the hypothesis that this vascular effect of ADH may have functional significance in the urinary concentration ability of the kidney.

1. 1. To determine whether a correlation between aldosterone activated sodium transport and renal protein synthesis exists, the incorporation of [3H]leucine into proteins from different regions of the rat kidney was compared between adrenalectomized and aldosterone substituted adrenalectomized rats. 2. 2. Aldosterone (5 μg-100 g body weight−1) or diluent was administered s.c. 1, 2 or 3 hr and [3H]leucine (350 μCi per rat) was injected i.v. 0.5, 1 or 2 hr prior to kidney removal. The kidneys from 10 rats (5 diluent and 5 aldosterone treated) were dissected into 3 zones (outer and inner cortex and medulla) and luminal plasma membranes (brush borders) were prepared. From these l mg protein of outer and inner cortex and 200 μg of medulla protein were subjected to polyacrylamide gel electrophoresis. The protein bands were identified under u.v.-light, cut into slices and [3H]leucine incorporation measured. 3. 3. The total membrane fractions were solubilized in SDS-mercaptoethanol and electrophoretically separated into 18 consistently reproduceable protein peaks. Molecular weights of the relevant proteins were estimated at 19,000 to 221,000 by comparing them to reference proteins subjected to the same procedure. 4. 4. The amount of label incorporated into proteins was dependent on the exposure time to [3H]leucine and aldosterone. Maximum labelling occurred one hour after injection of [3H]leucine. The maximum effect of aldosterone on label incorporation was found 2 hr after aldosterone substitution. Two hours after aldosterone substitution the isotope ratios of aldosterone/diluent in the total membrane fraction were: outer cortex—1.24 (P 5. 5. These results are the first evidence of in vivo effects of aldosterone on proteins in kidney membranes participating in sodium transport and correlate with the data showing a maximum labelling of lipids matching the minimum Na+:K+ ratio in the urine of adrenalectomized rats after aldosterone replacement (Kirsten et al., 1977, 1978).

In order to determine if the kidney is the critical organ affected by acute administration, 10 (50 and 53) rats were injected intramuscularly with a single dose of 192 (97*) mg/kg of gold sodium thiomalate. Five (39 and 23) controls were injected with physiologic saline solution. The intent was to examine 2 treated and 1 control rat each day for the subsequent 5 days. The concentration of blood urea nitrogen (BUN) was determined on plasma samples collected immediately before the rats were killed for autopsy. Two treated rats (19 and 13) and one control were killed on day 1. The BUN for the treated female was 137 mg%, for the treated male 189 mg% and for the control 23 mg% (normal range is 20 to 48 mg%). The cortex of the kidneys of the treated rats was pale at autopsy. Histologically, the inner cortex contained coagulative necrosis of tubular epithelium, while the outer cortex was spared (Figs. 1, 2). Four (19 and 3d) of the remaining 8 rats were dead on the morning of day 2. They were not examined histologically. Two (19 and 18) of the 4 remaining treated rats and 1 control were killed on day 2. The BUN for the treated female was 257 mg% and for the male was 315 mg% whereas that for the control was 17 mg%. The renal cortex was pale in treated rats. Coagulative necrosis of the tubular epithelium was more widespread than in the rats killed on day I, but was still located predominantly in the inner cortex. A treated and a control female rat were killed on day 3. The BUN of the treated rat was 249 mg% while that of the control was 17 mg%. The renal cortex of the treated rat was pale and had minute white spots. Histologically, the extent of necrosis in the inner cortex was about the same as in the rats killed on day 2. However, regeneration of the tubular epithelium, as evidenced by irregular basophilia and a few mitotic figures had begun. A few enlarged nuclei (karyomegaly) were seen. The remaining treated rat, a female, and 2 control males were killed on day 4. The BUN of the treated rat was 160 mg% whereas those of the 2 controls were 82 or 37 mg%. The renal cortex was pale. Histologically, the inner cortex had a minimal number of necrotic tubules with lumens filled with eosinophilic debris (Figs. 3-6). * The figure in parentheses indicates the gold content.

Procoagulant activity in kidneys of normal and bacterial lipopolysaccharide–treated rabbits. Fibrin formation in the kidney is frequently associated with clinically–significant renal dysfunction. We therefore measured and characterized the procoagulant activity (PCA) which is present in normal kidneys and in kidneys of rabbits with the Shwartzman phenomenon induced by two injections of bacterial lipopolysaccharide (LPS; E. coli LPS 055:B5,25 µg/kg and 50 µg/kg administered 24 hrs apart with rabbits sacrificed 12 hrs after the second injection). PCA was measured in sonicated tissue by one–stage coagulation assay. In normal kidneys the amounts of PCA in the inner medulla, outer medulla and inner cortex were 18.2 ± 3.2, 44.1 ± 3.8 and 78.5 ± 5.7 percent, respectively, of that in the outer cortex (N = 31). Glomeruli (purified by the iron oxide magnetic method to greater than 95 percent homogeneity) contained 21.6 ± 8.8 arbitrary units/µg protein compared with tubular fragments which contained 13.9 ± 2.6 U/µg protein (N = 9). In LPS-treated rabbits PCA (in units/µg) increased in outer cortex from 33.7 ± 3.9 (control) to 73.4 ± 10.4 (LPS, P < 0.01), in inner cortex from 26.7 ± 2.9 (control) to 83.3 ± 17 (LPS, P < 0.02), in outer medulla from 12.9 ± 2.4 (control) to 54.5 ± 16.5 (LPS, P < 0.05), and in inner medulla from 12.2 ± 2.4 (control) to 32.1 ± 4.9 (LPS, P < 0.01). Glomerular PCA increased from 21.6 ± 8.8 (control) to 88.8 ± 20.7 (LPS) units/µg (P = 0.01), while tubular fragment preparation PCA increased from 13.9 ± 2.6 (control) to 44.6 ± 12.7 (LPS) U/µg (P = 0.02) (N = 9 per group). PCA was thromboplastin-like as judged by clotting assay using human deficient plasmas. Fibrin and monocytes were present within capillaries of glomeruli of LPS-treated rabbits. In contrast, isolated glomeruli incubated with LPS for six or 21 hours showed no increase in PCA. We conclude that most of the PCA in normal kidneys is in the cortex. The normal renal medulla contains only small amounts of PCA. PCA is distributed to both glomeruli and tubules. Following LPS injection PCA increased in all structures examined, particularly in the glomeruli where extensive fibrin formation had occurred. This increase in glomerular PCA may have been related to the influx of mononuclear cells.

In the rat, administration of 7,12-dimethylbenz(a)anthracene (DMBA) causes necrosis of the inner layers of the adrenal cortex and provokes rising levels of plasma cortisol. Histological and ultrastructural study of the thymus demonstrates a profound depletion of small thymocytes, especially in the inner cortex where they normally represent the greater part of the cell population. The thymic weight, and the cortico-medullary ratio as measured by histometry, decrease significantly. These findings are similar to those observed following steroid administration. However, whereas after steroid treatment restitution of the normal complement of thymocytes occurs within 7–10 days, in the present model the thymic weight and corticomedullary ratio remain at the low levels observed on days 1 and 3 until after day 24 following DMBA administration. A block in the regenerative process is confirmed by the results of morphometrical analysis of the thymocyte nuclear area in the cortex. On day 1 and 3 after DMBA the mean thymocyte nuclear area is reduced in the outer cortex and increased in the inner cortex, because of the selective destruction of small thymocytes and the migration of the corticoresistant blast thymocytes towards the medulla. Subsequently, until after day 24 the mean nuclear area of the thymocytes is significantly higher in the outer and in the inner cortex of treated rats than in the corresponding parts of the cortex of control rats. This aspect of the cortex is characteristic of the early phase of the regenerative process, i.e. of day 2 or 3 after steroids administration. It can be assumed that in this experimental model the thymic changes are due not only to the raised cortisol level but also to a direct effect of DMBA on the thymus, which is probably an inhibition of DNA synthesis in cells in the S phase of the mitotic cycle, i.e. in the replication of DNA. It also seems possible that a causal relationship exists between inhibition of DNA synthesis in proliferating organs like the thymus, and the carcinogenic activity of DMBA.

The effect of indomethacin (10 mg/kg) on the distribution of cortical blood flow during postocclusive reactive hyperemia was evaluated in denervated kidneys of anesthetized rabbits by the radioactive microsphere technique. Renal denervation caused a slight but not significant increase in renal blood flow with no remarkable alteration in the distribution of cortical blood flow. After release of 1-min occlusion of the renal artery, hyperemic responses developed with a fractional flow redistribution toward the inner cortex. The absolute perfusion rate increased in the inner cortex but did not significantly change in the outer cortex. Indomethacin produced a decrease in renal blood flow despite elevated blood pressure. Even in the indomethacin-treated animals, postocclusive reactive hyperemia appeared concomitantly with the fractional flow redistribution to the inner cortex. The percentage repayment by reactive hyperemia of ischemia during the artery clamping was not significantly different before and after indomethacin administration. The findings indicate that indomethacin did not significantly affect the postocclusive vascular response in denervated kidneys of rabbits, thereby giving evidence against the role of prostaglandins as mediators of reactive hyperemia.

In isolated blood-perfused canine kidneys, progressive increases in renal blood flow and its fractional distribution to the inner cortex were correlated with increases in perfusate concentrations of a prostaglandin E-like (PGE-like) substance. The ratio of blood flow to the outer and inner halves of the renal cortex measured by the radioactive-microsphere method changed from 77:23 to 68:32 ( P < 0.001) after 90 minutes of perfusion; simultaneously, the concentration of the PGE-like substance increased from 0.04 ng/ml to 0.59 ng/ml ( P < 0.02). Thus, the greatest rate of increase in the concentration of the PGE-like substance occurred coincidently with the largest increase in inner cortical blood flow, i.e., from 30 ml/min to 69 ml/min ( P < 0.001). During the two subsequent 90-minute perfusion periods, the ratio of outer cortical blood flow to inner cortical blood flow fell to 61:39, and the concentration of the PGE-like substance increased further. When indomethacin was added to the perfusate, the concentration of the PGE-like substance decreased from 1.00 ng/ml to 0.24 ng/ml ( P < 0.05), and renal blood flow decreased, especially in the inner cortex where the decline was from 34% to 19% of total renal blood flow ( P < 0.05). Thus, renal blood flow was redistributed after indomethacin was administered. PGE 2 was infused to determine whether substitution for the loss of circulating PGE-like substance could prevent the effects of indomethacin on the distribution of renal blood flow. Despite administration of exogenous PGE 2 , renal blood flow redistributed after administration of indomethacin, and the ratio of outer cortical blood flow to inner cortical blood flow increased from 68:32 to 80:20 ( P < 0.05). These results suggest that the intrarenal site of synthesis and release of PGE 2 determines its action as a local hormone affecting deep cortical blood flow.

The present study was designed to determine if the addition of albumin or mannitol to the priming solution of the pump oxygenator would diminish edema in organs, without diminishing some of the beneficial effects of hemodilution on blood flow and renal function. Tissue blood flow (15 mu spheres), water content, and renal clearances were determined in 8 animals during cardiopulmonary bypass. A 2(2) factorial, completely fixed experimental design was used. All animals were placed on cardiopulmonary bypass with hemodilution (hematocrit 25 +/- 2%) and hypothermia (25 degrees +/- 1 degree C). Albumin decreased flow to the midmyocardium of the left ventricle and to the spleen, and increased flow to the inner cortex of the kidney. Albumin caused decreased urine flow and decreased urine sodium, and also diminished renal osmolar, sodium, and free-water clearances. both mannitol and albumin decreased lung water. Mannitol decreased water content of the outer renal cortex, and decreased flow to the inner cortex and medulla of the kidney and to the spleen. Mannitol had no significant effect on urine flow, renal plasma flow, or renal clearances. Neither albumin nor mannitol had any effect on water content of the intestine, stomach, liver, or myocardium where the greatest accumulation of water occurs with hemodilution. The effect of albumin on renal function is potentially deleterious during cardiopulmonary bypass because it decreases urine flow, and osmolar and free-water clearance.