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As the "empty pelvis syndrome" continues to pose challenges in patients undergoing radical pelvic exenteration, there remains an ongoing need to consider solutions to mitigate or avoid its associated morbidity. As such, this study aims to review the long-term outcomes of a proposed strategy of pelvic reconstruction with BioA mesh.We conducted a retrospective observational cohort study, reviewing cases of pelvic exenteration and/or pelvic bone resection involving BioA mesh pelvic reconstruction between 2017 and 2021 at our quaternary institution, identified from a prospectively collected database. The primary outcome was pelvic complications including perineal fistula, wound breakdown and pelvic collections.Over a 4-year period, there were a total of 36 patients who had pelvic exenteration and/or pelvic bone resection with BioA mesh pelvic reconstruction. The overall pelvic complication rate was 36% (n = 13), including 11 symptomatic pelvic collections, two enteroperineal fistulas, and no cases of perineal hernia. Reoperation was required in two patients. There was no perioperative mortality.Given that pelvic complications post BioA mesh reconstruction are of an acceptable rate and can be considered minor, using this technique is a safe and practical strategy in patients undergoing major pelvic surgery with or without pelvic bone resection.

The need to identify and effectively treat COVID-19 cases at highest risk for severe disease remains critical. We identified five common genetic loci (two novel) that modulate both COVID-19 susceptibility and severity, implicating TMPRSS2, IFNAR2, CCHCR1, TCF19 and SLC6A20 as potential targets. A high genetic burden was strongly associated with increased risk of hospitalization and severe disease among COVID-19 cases, especially among individuals with few known clinical risk factors.

BACKGROUND Inguinal hernias are a common pathology that often requires surgical management. The use of groin ultrasound (GU) to investigate inguinal hernias is a growing area of concern as an inefficient use of healthcare resources. Our aim was to assess changes in the rates of GU and the impact on surgical practice. METHODS Medicare Item Reports and the Australian Institute of Health and Welfare Database were used to estimate annual GU and inguinal hernia repair (IHR) rates per 100 000 population for the period 2000/2001-2017/2018. Pearson's correlation coefficients and linear regression analyses were performed to assess associations between these variables. RESULTS Over the 18-year period, GU rates increased 13-fold from 88 to 1174 per 100 000 population. Overall, total IHR rates decreased from 217 to 192 per 100 000. Overall, unilateral IHR rates have decreased (182-146 per 100 000), bilateral IHRs have increased (35-46 per 100 000), laparoscopic IHR has increased (30-86 per 100 000) and open surgery has declined (187-106 per 100 000). The increase in GU rates were strongly associated with the decrease in unilateral (r = -0.936, P =

Insulin supplements, predominantly as a constant basal fish insulin infusion, were given to patients with mild diabetes to reduce the overnight fasting glucose level to normal. The basal plasma human insulin levels were reduced to subnormal levels by the infusion, and the insulin response to intravenous glucose was enhanced. The beta-cell in diabetes seems to be in a vicious circle in which an impaired insulin response to glucose produces hyperglycaemia, which stresses beta-cell function, making it more inefficient. A constant basal insulin supplement to induce basal normoglycaemia may benefit beta-cell function in diabetes.

The prevalence of diabetic autonomic neuropathy and its relationship with other diabetic complications were studied in a geographically defined population. Heart rate variability was measured by a computerized technique at rest and in response to both a single deep breath and a Valsalva manoeuvre. Among 43 Type 1 (insulin-dependent) and 202 Type 2 (non-insulin-dependent) patients results below the 2.5 centile for age-related normal ranges occurred in 9 Type 1 and 32 Type 2 patients (16.7, 95% Cl 12.6 to 21.9, %). Symptomatic autonomic neuropathy was uncommon but was significantly more frequent in Type 1 than Type 2 patients (5 Type 1, 1 Type 2, p less than 0.001 Fisher's exact test). In Type 1 diabetes, cardiovascular autonomic dysfunction was significantly associated with impaired vibration perception and a higher logarithmic urinary albumin concentration and, in Type 2 diabetes, it was associated with a significantly higher body mass index, systolic blood pressure, and logarithm of the urinary albumin and fasting insulin concentrations. The aggregation of these factors with cardiovascular autonomic dysfunction suggests that mortality might be increased in Type 2 patients with asymptomatic autonomic neuropathy.

The effect of insulin-induced hypoglycaemia on cerebral blood flow was examined using the intravenous xenon-clearance technique in 9 patients with Type 1 (insulin-dependent) diabetes (aged 20 to 43 years) and 9 age-matched control subjects before, during and after hypoglycaemia. Cerebral blood flow rose in both groups. The mean basal cerebral flood flow values were not significantly different and during hypoglycaemia mean cerebral blood flow increased by 17% (p = 0.008) in the diabetic patients and by 21% (p = 0.0003) in the control subjects. The results suggest that in young diabetic patients without autonomic neuropathy or microangiopathy cerebral vessels dilate normally in response to hypoglycaemia. The physiological importance of an increase in cerebral blood flow during hypoglycaemia is uncertain; but glucose availability is increased.

Increasingly, interventional procedures require accessing the left atrium from the inside of the heart as well as from the pericardial space. The right phrenic nerve running along the fibrous pericardium is close to the atrial insertion of the right superior pulmonary vein while the left phrenic nerve passes over the left atrial appendage. Posteriorly, the esophagus descends adjacent to the fibrous pericardium covering the posterior and postero-inferior walls of the left atrium. The component parts of the left atrium are reviewed with emphasis on the structure of the atrial septum, the left atrial ridge, the mitral isthmus, and the left atrial walls. Although the atrial walls are mainly smooth, pits and crevices are common in the region of the mitral isthmus and the vicinity of the os of the atrial appendage. The muscular rim around the valve of the oval fossa delimits the extent of the true atrial septum. Interatrial muscular connections exist at the septum, along Bachmann's bundle and also at the muscular sleeves of the coronary sinus and pulmonary veins. Anatomical features relevant to interventional electrophysiologists are highlighted.

Function preserving management of a dominant thumb metacarpal chondrosarcoma is reported, with a literature review for this uncommon neoplasm. Wide local excision of the metacarpal followed by temporary silicone block interposition and definitive iliac crest bone grafting was performed. A persistent wound defect was managed by a radial artery forearm flap. The functional result was acceptable. In the literature, there were seven cases of thumb metacarpal chondrosarcoma reported; two were treated by ray amputation, and the other five were treated by excision of the metacarpal. Three of those five had bone graft and the other two had simple resection. Of these seven cases, three had local recurrence and one a distant metastasis.

The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study. Control Clin Trials 1999;20:573–600

A series of new enantiomerically pure acylnitroso compounds have been prepared and tested as dienophiles for the asymmetric oxyamination of dienes. Very high selectivities were obtained with acylnitroso compounds derived from diphenylmethoxymethyl pyrrolidine 2c, the C-2-symmetric pyrrolidines 2d-e and camphorsultam 2f. (C) 1998 Elsevier Science Ltd. All rights reserved.

The Th1-derived cytokine IFN-gamma inhibits the proliferation of Th2 lymphocytes, but the mechanism of inhibition is not known. Under certain disease conditions, an established Th2-mediated immune response is undesirable and a Th1-mediated response is beneficial. However, established Th2 cells appear to be phenotypically stable. Thus, learning more about cytokine-mediated regulation of established Th2 cells is important if deleterious immune responses are to be altered. We studied the effects of IFN-gamma on a panel of recently derived Th2 lines and clones, as well as a previously established Th2 clone, 13.26. Inhibition by IFN-gamma was observed only when there was a concomitant response to IL-1, a known costimulator of Th2. Clone 13.26 was particularly sensitive to both IL-1 and IFN-gamma, so it was studied in greater detail. We examined cytokine responses using stimulation by anti-TCR mAb-coated plates, or Ag presented by APC populations that do or do not produce IL-1. All IL-1-mediated proliferative responses of 13.26 were inhibited by IFN-gamma, whereas IL-1-independent (IL-4-associated) responses were unaffected. Our data suggest that IFN-gamma inhibits Th2 proliferation through an IL-1-dependent mechanism, and furthermore, that the costimulatory pathways used by APCs may be critical for subsequent Th cell responses to cytokines.

A 36-year-old man was treated with dapsone, rifampicin and clofazimine for borderline lepromatous leprosy. After 9 months, his leprosy plaques became progressively more red and after 23 months, the clofazimine was stopped and he was given minocycline instead. Six weeks later, he developed blue-black pigmentation in his leprosy lesions. The histology was consistent with minocycline-induced hyperpigmentation. This is the first report of minocycline-induced pigmentation in leprosy. We suggest it is important to consider this side-effect before the administration of minocycline in leprosy, particularly if it is prescribed in place of clofazimine.

To elucidate signal transduction pathways leading to neuronal differentiation, we have investigated a conditionally immortalized cell line from rat hippocampal neurons (H19-7) that express a temperature sensitive simian virus 40 large T antigen. Treatment of H19-7 cells with the differentiating agent basic fibroblast growth factor at 39 degrees C, the nonpermissive temperature for T function, resulted in the activation of c-Raf-1, MEK, and mitogen-activated protein (MAP) kinases (ERK1 and -2). To evaluate the role of Raf-1 in neuronal cell differentiation, we stably transfected H19-7 cells with v-raf or an oncogenic human Raf-1-estrogen receptor fusion gene (deltaRaf-1:ER). deltaRaf-1:ER transfectants in the presence of estradiol for 1 to 2 days expressed a differentiation phenotype only at the nonpermissive temperature. However, extended exposure of the deltaRaf-1:ER transfectants to estradiol or stable expression of the v-raf construct yielded cells that extended processes at the permissive as well as the nonpermissive temperature, suggesting that cells expressing the large T antigen are capable of responding to the Raf differentiation signal. deltaRaf-1:ER, MEK, and MAP kinase activities in the deltaRaf-1:ER cells were elevated constitutively for up to 36 h of estradiol treatment at the permissive temperature. At the nonpermissive temperature, MEK and ERKs were activated to a significantly lesser extent, suggesting that prolonged MAP kinase activation may not be sufficient for differentiation. To test this possibility, H19-7 cells were transfected or microinjected with constitutively activated MEK. The results indicate that prolonged activation of MEK or MAP kinases (ERK1 and -2) is not sufficient for differentiation of H19-7 neuronal cells and raise the possibility that an alternative signaling pathway is required for differentiation of H19-7 cells by Raf.

Response characteristics of a microhole potentiostatic oxygen sensor and a Beckman membrane oxygen sensor were measured in a laboratory over temperatures ranging from 1° to 21°C. The response term τ of the microhole sensor changed 1.7-fold over this temperature range, and τ of the membrane sensor changed 1.6-fold. For the microhole sensor, the effect of temperature on τ can be modeled as lnτ+−6.5 + 1618T−1. For the membrane sensor the temperature effect on τ can be modeled as lnτ = −5.8 + 2116T−1, where T is temperature in kelvins.

In 1991 and 1992, toxigenic Vibrio cholerae O1, serotype Inaba, biotype El Tor, was recovered from nonpotable (ballast, bilge, and sewage) water from five cargo ships docked in ports of the U.S. Gulf of Mexico. Four of these ships had taken on ballast water in cholera-infected countries; the fifth took on ballast in a noninfected country. Isolates examined by pulsed-field gel electrophoresis were indistinguishable from the Latin American epidemic strain, C6707; however, they differed significantly from the endemic Gulf Coast strain (VRL 1984), the sixth-pandemic strain (569-B), and a V. cholerae non-O1 strain isolated from a ship arriving from a foreign port. On the basis of our findings, the Food and Drug Administration recommended that the U.S. Coast Guard issue an advisory to shipping agents and captains requesting that ballast waters be exchanged on the high seas before entry of ships into U.S. ports.

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.

The effect of transfection of the type 2 activin receptor, ACTR2, on binding of 125I-activin-A to the surface of bovine aortic endothelial cells (BAEC) was investigated. BAEC transfected either with full-length ACTR2 or with a truncated form of ACTR2 lacking the intracellular kinase domain (ACTR2T) displayed two classes of 125I-activin-A binding sites, one of high affinity (Kd = 250-254 pM) and one of low affinity (Kd = 6.5-16 nM). Affinity labeling of ACTR2-transfected BAEC with 125I-activin-A revealed labeled species of 55, 95, 100, and 160 kDa, all four of which were immunoprecipitated by an anti-ACTR2 monoclonal antibody. Only the 95- and 100-kDa species, however, were immunoprecipitated following denaturation of the affinity-labeled cell lysate with SDS. BAEC transfected with an epitope-tagged form of ACTR2T (ACTR2TMyc) displayed intense 55- and 70-kDa affinity-labeled forms of the truncated receptor, together with a 160-kDa species. As with the full-length receptor, the 160-kDa species associated non-covalently with ACTR2TMyc. These data indicate that, in vascular endothelial cells, ACTR2 forms a high affinity heterotrimeric receptor complex with activin-binding proteins characteristic of type 1 and type 3 activin receptors, and that formation of the complex does not require the kinase domain of ACTR2.

The demonstration of type 2 activin receptor expression in human umbilical vein endothelial cells prompted an investigation of the effects of the activin/inhibin family of hormones on vascular endothelial cell growth. Recombinant activin-A inhibited [3H]methylthymidine uptake and growth of a panel of endothelial cell types; recombinant inhibin-A was without effect. Affinity cross-linking studies demonstrated the presence of type 1 and type 2 activin receptors on the surface of bovine aortic endothelial cells, while detailed analysis of type 2 activin receptor expression revealed both type 2 and type 2B activin receptor mRNA in all endothelial cell types analyzed. In addition, capillary endothelial cells were found to express activin-beta A subunit mRNA and protein, the levels of which were increased in response to transforming growth factor (TGF)-beta. Furthermore, activin-A and TGF-beta caused additive inhibition of capillary endothelial cell [3H]methylthymidine uptake. These findings implicate the activins in the regulation of endothelial cell function, and suggest that TGF-beta and activin may interact to inhibit capillary endothelial cell growth.

We report a study of the change in lattice constant when single‐crystal silicon is substitutionally doped with boron. The measurements were made using 10‐μm‐thick epilayers with boron concentrations (NB) in the range 1.7×1019–1.2×1020 cm−3. The influence of elastic strain in the epilayers and their substrates was eliminated by including Bragg reflections from planes that were inclined to the (100) surface. We obtained a value for the lattice contraction coefficient β=(5.19±0.09)×10−24 cm3, where the range is ± one standard error. Specimens with NB≊2×1019 cm−3 were strained to give coherent interfaces with their substrates. Evidence for relaxation (presumably by misfit dislocations at the interface) was observed with NB≊5×1019 cm−3 (corresponding to a lattice mismatch of approximately 2.5×10−4), but this occurred in a patchy fashion and remained incomplete while NB was increased to 1.2×1020 cm−3 (corresponding to a mismatch of 6.5×10−4). This partial relaxation occurred at somewhat smaller mismatches than ...

A series of new enantiomerically pure acylnitroso compounds have been prepared and tested as dienophiles for the asymmetric oxyamination of dienes. Very high selectivities were obtained with acylnitroso compounds derived from diphenylmethoxymethyl pyrrolidine 2c, the C-2-symmetric pyrrolidines 2d-e and camphorsultam 2f. (C) 1998 Elsevier Science Ltd. All rights reserved.

Totally integrated design facilitates electrical cleanliness and light weight, which are necessary in subsonic parachute-borne payloads for electrodynamics investigations. 'Blunt' probes measure ion conductivity, as do Gerdien condensers. Recent finite-element computer analyses combining flow and electrodynamics have resolved problems in determining ion densities and mobilities from Gerdien data. Three-axis electric fields are measured with deployable boom-mounted electrodes from dc through VLF. Splitting the cylindrical payload with an insulator and measuring the current between halves has provided a vertical Maxwell current detector mechanically rigid enough to measure, at ELF, energy related to coupling. A nose tip 'Smith' probe turbulence measurement is usually performed on ascent. Other instrumentation, such as photo-ionization sources and X-ray detectors, can also be included. These electrodynamic measurement payloads are about one meter in length and have a mass of about 9 kg. They can be launched with an Orion-class or smaller vehicle.

Responses of bovine adrenal capillary endothelial cells (BACE) on treatment with transforming growth factor beta 1 (TGF-beta 1) have been characterized and tested for sensitivity to inactivation of pertussis toxin-sensitive G-proteins. TGF-beta 1 elicited growth inhibition, monolayer remodeling, elevation of steady state mRNA levels for collagen type 1 (alpha 1(1) and alpha 2(1)) and TGF-beta 1, and inhibition of p34cdc2 histone H1 kinase activity in BACE cells. Pertussis toxin treatment enhanced both inhibition of BACE cell [3H]methylthymidine uptake and remodeling of BACE monolayers by TGF-beta 1. These findings contrast with studies of mink lung epithelial cells, in which TGF-beta 1 growth inhibition has been shown to be pertussis-sensitive. Further investigation revealed that pertussis toxin treatment of BACE cells had no effect on TGF-beta 1-stimulated elevation of steady state mRNA levels for collagen type 1 (alpha 1(1) or alpha 2(1)) or for TGF-beta 1. Analysis of p34cdc2 activity in BACE cells revealed potent inhibition of p34cdc2 histone H1 kinase activity by TGF-beta 1. Pertussis toxin treatment also abolished the increase in p34cdc2 activity, however, precluding the determination of the pertussis toxin sensitivity of this response to TGF-beta 1. Consistent with suppression of p34cdc2 activation, pertussis toxin also caused substantial inhibition of mitogen-stimulated BACE cell [3H]methylthymidine uptake. It is concluded that TGF-beta 1 signal transduction in this cell type does not involve G-proteins of the pertussis toxin-sensitive class and that, in view of its potent effects on DNA synthesis and p34cdc2 activation, the use of pertussis toxin to determine G-protein involvement in cytokine signalling pathways should be approached with caution.

The build-operate-transfer (BOT) concept represents a step forward in meeting the needs of developing countries for more capital investments in infrastructure and industrial construction. However, for a private-sector consortium bidding for a BOT concession, the road to winning a major BOT contract is not easy. The consortium must be willing to take calculated risks and at the same time be adaptable to changing demands and circumstances in the host country. This paper describes the importance and characteristics of six critical success factors (CSF) that are vital for project sponsors in their endeavors to win lucrative BOT contracts. These factors are: entrepreneurship, picking the right project, a strong team of stakeholders, an imaginative technical solution, a competitive financial proposal, and the inclusion of special features in the bid.

Two new point mutations have been detected in the low density lipoprotein (LDL) receptor gene of a patient with a clinical diagnosis of homozygous familial hypercholesterolemia (FH). The patient is a compound heterozygote, in whom the mutant allele inherited from his English father has a single base substitution of A for G in exon 3, changing the codon for residue 80 in the mature protein from glutamic acid to lysine. The mutant allele inherited from his mother, who is of Irish origin, has a single base pair deletion in the codon for residue 743 in exon 15 that causes a frameshift and introduces a new stop codon in the adjacent position. The glu80 to lys mutation results in a transport-defective phenotype and a mature protein that migrates abnormally slowly on nonreduced SDS-PAGE, but normally under reducing conditions; this was confirmed by site-directed mutagenesis and expression in vitro. The deletion in exon 15 results in a null phenotype in which the putative truncated receptor protein cannot be detected in cultured skin fibroblasts and the amount of mRNA derived from the allele is reduced. The glu80 to lys mutation was found in a further five unrelated individuals in a sample of 200 FH patients from the London area and in 11 from a sample of 77 FH patients from Manchester. Haplotype analysis suggested that all the patients had inherited this allele from a common ancestor. The deletion in exon 15 was not found in the London sample, nor in any unrelated individuals in the Manchester sample.

Morris DG, Waters SM, McCarthy SD, Patton J, Earley B, Fitzpatrick R, Murphy JJ, Diskin MG, Kenny DA, Brass A, Wathes DC. Pleiotropic effects of negative energy balance in the postpartum dairy cow on splenic gene expression: repercussions for innate and adaptive immunity. Physiol Genomics 39: 28-37, 2009. First published June 30, 2009; doi: 10.1152/physiolgenomics.90394.2008.-Increased energy demands to support lactation, coupled with lowered feed intake capacity results in negative energy balance (NEB) and is typically characterized by extensive mobilization of body energy reserves in the early postpartum dairy cow. The catabolism of stored lipid leads to an increase in the systemic concentrations of nonesterified fatty acids (NEFA) and beta-hydroxy butyrate (BHB). Oxidation of NEFA in the liver result in the increased production of reactive oxygen species and the onset of oxidative stress and can lead to disruption of normal metabolism and physiology. The immune system is depressed in the peripartum period and early lactation and dairy cows are therefore more vulnerable to bacterial infections causing mastitis and or endometritis at this time. A bovine Affymetrix oligonucleotide array was used to determine global gene expression in the spleen of dairy cows in the early postpartum period. Spleen tissue was removed post mortem from five severe NEB (SNEB) and five medium NEB (MNEB) cows 15 days postpartum. SNEB increased systemic concentrations of NEFA and BHB, and white blood cell and lymphocyte numbers were decreased in SNEB animals. A total of 545 genes were altered by SNEB. Network analysis using Ingenuity Pathway Analysis revealed that SNEB was associated with NRF2-mediated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, natural killer cell signaling, p53 signaling, down-regulation of IL-15, BCL-2, and IFN-gamma; upregulation of BAX and CHOP and increased apoptosis with a potential negative impact on innate and adaptive immunity.

Build-operate-transfer (BOT) projects have become of increasing interest over the last few years. The BOT model entails a concession company providing the finance, design, construction, operation and maintenance of an asset for a fixed period, at the end of which the asset is transferred free of charge to the client. The paper outlines the nature of BOT projects, and examines aspects of the financial and contractual arrangements associated with BOT methods. The financial aspects include the raising of finance, the assistance needed from the host government, the use of existing facilities, the retention of title and construction-cost overrun. The methods of forming the concession and the construction and operation agreements, and the role of the maitre d'oeuvre, are also discussed.

Although the synoptic format is being increasingly used for primary cutaneous melanoma pathology reporting, no study assessing its value has yet been reported in the literature. The aim was to determine whether the use of synoptic reports increases the frequency with which pathological features that may influence prognosis and guide management are documented.Melanoma pathology reports (n = 1692) were evaluated; 904 were in a synoptic format [671 Sydney Melanoma Unit (SMU) reports and 233 non-SMU reports] and 788 were non-synoptic (184 SMU reports and 604 non-SMU reports). Reports (n = 1354) from 677 patients who had both a SMU report and a non-SMU report were compared. Almost all features were reported more frequently in synoptic than in non-synoptic reports (P0.001). No significant differences were found in the frequency of reporting the main pathological features between SMU and non-SMU synoptic reports. Synoptic reports were more frequently used by SMU (78%) than by non-SMU pathologists (28%).This is the first study to provide objective evidence that synoptic pathology reports for melanoma are more complete than non-synoptic reports (regardless of whether the reports are generated within or outside a specialist melanoma centre). All synoptic reports should include the facility for free text, be tailored to individual institutional requirements and be updated regularly to be of maximal value.

When first reported, EBM/11 reacted with mononuclear phagocyte system cells only in fresh frozen sections, but it has been shown to have similar cellular specificity in routine formalin fixed, paraffin wax embedded tissue. This was achieved by limited proteolysis with protease XIV before immunocytochemical staining. In archival biopsy specimens EBM/11 produced granular cytoplasmic staining of alveolar macrophages, Kupffer cells, tingible body macrophages and sinus histiocytes, cells of splenic cords, cortical and medullary macrophages of thymus; blood monocytes, peritoneal and mesothelial macrophages; bone marrow mononuclear cells, megakaryocytes and osteoclasts; lamina propria macrophages in the gastrointestinal tract, and connective tissue cells (presumptive macrophages) of thyroid, gall bladder, skin, pancreas, ovary, myometrium, endometrium, cervix, kidney, prostate, placenta, myocardium and breast. Unlike other anti-macrophage antibodies, EBM/11 did not react with granulocytes, lymphocytes, plasma cells, platelets, endothelial and epithelial cells in paraffin wax sections. It did not label skin Langerhans' cells, microglial cells, and interdigitating reticulum cells (as in frozen sections). This study opens a new area for the specific identification by EBM/11 of mononuclear phagocyte system cells in archival biopsy specimens. It also raises the possibility that some monoclonal antibodies, believed to be reactive only in frozen sections, may react in archival tissue after limited proteolysis with an appropriate enzyme.

The study examined the influence of the Pond Report on the teaching of medical ethics in the London medical schools. A questionnaire was given to both medical students and college officers. All medical colleges reported that ethics was included in the curriculum. However, from students' replies, it seems that attendance of optional courses is low and that not all current final year medical students have had any formal teaching in medical ethics. Stronger guidelines are necessary to ensure appropriate ethical training in London medical schools.

A description is given of the methodology, and problems encountered, for the use of a new fluorescent Ca2(+)-indicator dye, fluo-3, in neutrophils and platelets. The higher Kd and longer excitation wavelength of fluo-3 can have significant advantages over fura-2. Although neutrophils and platelets are used as examples, these observations will be applicable to other cell types. The Kd of fluo-3 for binding Ca2+ at 37 degrees C was measured and found to be 864 nM; the previously published value was 400 nM at 22 degrees C. The Kd of fluo-3, like that of fura-2, is therefore very temperature-dependent. Protocols for loading cells, and preventing leakage of fluo-3, are described; probenecid, known to inhibit fura-2 leakage from cells, was found to be essential to get good fluo-3 signals from platelets. Calibration of fluo-3 fluorescence signals to [Ca2+] and methods for obtaining maximum and minimum fluorescence signals are described; these methods differ from those used with fura-2. Agonist-stimulated responses of fluo-3-loaded neutrophils and platelets are shown, and the calculated cytosolic [Ca2+] is comparable with that previously obtained with fura-2. Responses of cells in the presence of plasma are also shown; such measurements, unobtainable with quin2, fura-2 or indo-1, are possible with fluo-3, owing to its longer excitation wavelengths. Co-loading of cells with bis-(o-aminophenoxy)ethane-NNN′N′-tetra-acetic acid and fluo-3 is included as an example of how cytosolic [Ca2+] can be buffered and manipulated. Many of these observations will be of value when using fluo-3 (or other Ca2(+)-indicator dyes) in most cell types.

We treated 50 patients with bony malignancy by en-bloc resection, extracorporeal irradiation with 50 Gy and re-implantation of the bone segment. The mean survivor follow-up was 38 months (12 to 92) when 42 patients were alive and without disease. There were four recurrences. The functional results were good according to the Mankin score (17 excellent, 13 good, nine fair, three failures), the Musculoskeletal Tumour Society score (mean 77) and the Toronto Extremity Salvage score (mean 81). There was solid union, but bone resorption was seen in some cases. The dose of radiation was lethal to all cells and produced a dead autograft of perfect fit. Extracorporeal irradiation is a useful technique for limb salvage when there is reasonable residual bone stock. It allows effective re-attachment of tendons and produces a lasting biological reconstruction. There should be no risk of local recurrence or of radiotherapy-induced malignancy in the replanted bone.

As 115 cardinals began voting for a new pope on Monday, some Catholic organisations and priests working in AIDS ravaged areas called for the church to change its stance on condoms. Sophie Arie reports

The pathologist often has a difficult task in evaluating melanocytic lesions. For lesions involving the face the consequences of misdiagnosis are compounded for both cosmetic and therapeutic reasons. In this article, the pathological features of common and uncommon benign and malignant melanocytic lesions are reviewed and pitfalls in their diagnosis are highlighted. Benign lesions resembling melanomas include regenerating naevus, "irritated" naevus, combined naevus, "ancient naevus", Spitz naevus, dysplastic naevus, halo naevus, variants of blue naevi, balloon and clear cell naevi, neurotised naevus and desmoplastic naevus. Melanomas that can easily be missed on presentation include desmoplastic, naevoid, regressed, myxoid and metastatic types as well as so-called malignant blue naevi. Pathological clues to benign lesions include good symmetry, V-shaped silhouette, absent epidermal invasion, uniform cellularity, deep maturation, absent or rare dermal mitoses and clustered Kamino bodies. Features more commonly present in melanomas include asymmetry, peripheral epidermal invasion, heavy or "dusty" pigmentation, deep and abnormal dermal mitoses, HMB45 positivity in deep dermal melanocytes, vascular invasion, neurotropism and satellites. Familiarity with the spectrum of melanocytic lesions and knowledge of the important distinguishing features should assist in interpretation. Occasionally, the use of ancillary studies may also provide additional useful information. Application of standard criteria for diagnosing such lesions should enable the correct diagnosis to be established in most cases.

PCL/PEO copolymers with different compositions were obtained from ring opening polymerization of epsilon-caprolactone in the presence of ethylene oxide and characterized by various analytical techniques. Data collected from DSC and X-ray diffractometry suggested that the copolymer chains possess a blocky structure, leading to both PCL and PEO-type crystalline structures. Hydrolytic degradation of these copolymers was carried out in a pH=10.6 carbonate buffer solution at 37 degrees C. Comparison was made with a PCL homopolymer and a PCL/PEG blend which had the same gross composition as one of the copolymers. The results showed that the presence of PEO sequences considerably enhanced the hydrophilicity of the copolymers as compared with PCL homopolymer. Nevertheless, the degradability of PCL chains was not enhanced due to the phase separation between the two components. These materials should be of great interest for biomedical uses such as matrices for sustained drug delivery because of the presence of both hydrophilic and hydrophobic microdomains.

Taking a sexual history and discussing sexual health issues with patients form an important part of a medical consultation. These specific communication skills can be acquired through various teaching methods.This paper describes the communication skill workshops conducted for undergraduate medical students on how to talk to patients about sex.198 medical students participated in a series of workshops conducted in the University of Malaya in 2001-2002. Pre- and post-workshop evaluations of the programme were carried out to find out the students' difficulties and to assess the usefulness of the workshop. The workshop consisted of a short lecture, role-plays and discussion.Only 34% of the participants had received some informal training during their clinical years. The main barriers encountered were gender and age differences, language and choice of words, patients and doctors feeling shy, and cultural differences. The workshop was felt to be useful (mean score 4.38, maximum 5.0), most students felt comfortable during the workshop (mean score 4.10, maximum 5.0) and there was significant improvement in the "comfort level" when talking to patients about sex after attending the workshop (P0.001).Gender, language and cultural differences were the main barriers in taking a sexual history and discussing sexual health issues among the medical students. Communication workshop was felt to be a useful and comfortable method of learning these specific.

The paper documents progress to date on a research project, the goal of which is wartime event prediction. It describes the operational concept, the data mining environment, and data mining techniques that use Bayesian networks for classification. Key steps in the research plan are as follows: (1) implement machine learning; (2) test the trained networks; and (3) use the technique to support a battlefield commander by predicting enemy attacks. Data for training and testing the technique can be extracted from the object oriented database that supports the Integrated Marine Multi-Agent Command and Control System (IMMACCS). These data were derived from message traffic generated during US Marine Corps exercises. The class structure in the IMMACCS data model is especially well suited to support attack classification.

Two cases of pleomorphic angiomyolipoma (AML) composed of bizarre epithelioid smooth muscle cells located in the gastrointestinal tract are reported. One involved the appendix of a 6-year-old girl, and the second the cecum of a 22-year-old woman. In both instances the tumor cells were immunoreactive for HMB-45 and A103. To the best of our knowledge, this peculiar variant of an AML has not previously been recognized in this location. Int J Surg Pathol 8(1):67-72, 2000

Previously, we showed that NO induces thymocyte apoptosis via a caspase-1-dependent mechanism [(1) ]. In the present study, we investigated the role of heme oxygenase, catalase, bax, and p53 in this process. The NO donor, S-nitroso-N-acetyl penicillamine (SNAP), induced DNA fragmentation in thymocytes in a time- and concentration-dependent way. SNAP (100 microM) induced 50--60% apoptosis; higher doses did not increase the rate of apoptosis significantly. SNAP decreased catalase and heme iron (Fe) levels without affecting superoxide dismutase, glutathione, or total Fe stores in thymocytes. SNAP significantly increased the expression of heme oxygenase 1 (HSP-32), p53, and bax but not bcl-2. Treatment with the heme oxygenase inhibitor, tin protoporphyrin IX inhibited SNAP-induced thymocyte apoptosis. Furthermore, thymocytes from p53 null mice were resistant to NO-induced apoptosis. Our data suggest that NO may induce its cytotoxic effects on thymocytes by modulating heme oxygenase and catalase activity as well as up-regulating pro-apoptotic proteins p53 and bax.

The WR21 Intercooled and Recuperated (ICR) gas turbine has been developed to meet the future military needs for a fuel efficient, low cost of ownership, high power marine gas turbine. The engine is rated at 25.6MW (ISO) and has an outstanding pedigree derived from its two parent engines, the Rolls-Royce aero RB211 and Trent. Having completed development in February 2000, a 3000 hour endurance test is now underway and a shock test is planned to qualify the engine for entry into service in the Royal Navy, United States Navy and French Navy. The 3000 hour endurance test commenced at DCN Indret, France in January 2001 and is planned to complete April 2002. Shock testing, conducted on the unrefurbished endurance engine, will complete in late 2002. The three Navies have invested considerable time and effort in developing comprehensive running profiles that will thoroughly test the engine to the satisfaction of all parties. The first 1500 - 2000 hours will be conducted with the engine operating in the mechanical drive configuration, with the remaining running simulating the engine driving a conventional constant speed alternator.

Many companies are beginning to focus on value in their health care purchasing decisions, and some are going beyond value-based purchasing to value-based partnering. Value-based partnering recognizes the interdependencies among stakeholder groups in the health care system and creates a strategic reason for them to exchange information and create long-term strategic alliances. This article discusses the principles of value-based partnering, impediments to practicing it and its future role in the health care system.

Value-based partnering is designed to move the healthcare system beyond cost-based competition. It recognizes that the healthcare "product" is not a commodity and that much of the value in the system comes from relationships between and among four stakeholders: consumers, providers, health plans, and employers. Given the difficulty of measuring such benefits as quality of care, improved health status, and increased employee productivity, stakeholders within the system traditionally have focused on easily measurable financial considerations such as premium rates. This focus has led to a system that defines relationships in purely financial terms. In contrast, the value-based partnering model presented in this article recognizes the range of factors that stakeholders consider in their relationships with each other. This approach has the potential to change the nature of competition and presents opportunities for those organizations that can effectively partner with other stakeholders and demonstrate value, rather than just lower cost. Moreover, by recognizing the interdependencies among stakeholder groups, the approach creates a strategic reason for employers, health plans, providers, and consumers to exchange information and create long-term alliances.

Under a shadow-pricing approach to physician compensation, physicians who deliver healthcare services to a mix of fee-for-service (FFS) and capitated patients are compensated for services via a payment schedule that treats all patients as if they were capitated. By encouraging physicians to adopt the same care-management approach for all patients, shadow pricing helps a group practice prepare for a larger share of revenues to be derived from capitation, thereby making the organization more attractive to many managed care payers. An apparent drawback of shadow pricing is that it gives physicians an incentive to reduce FFS utilization, resulting in a loss of potential revenue to the healthcare organization. This loss can be strategically justified, however, as an investment in the organization's ability to remain viable under capitation and to retain patients for whom payment may shift from FFS to capitation. In developing a shadow-pricing compensation approach, healthcare organizations can include incentives that encourage physicians to meet specific utilization targets, establish review procedures to identify physicians who deviate from the targets, and account for differences in acuity levels among different physicians' patient panels.

To investigate the effect of melanin bleach on Feulgen-DNA microdensitometry in pigmented melanocytic lesions.Twenty banal compound nevi with various grades of pigmentation were bleached by 0.5% and 1% KMnO4 for 0 to 20 minutes and by 10% H2O2 for 24 hours prior to Feulgen staining. DNA microdensitometry was performed by video image analysis to measure the integrated optical density (IOD) in nuclei from nevomelanocytes, lymphocytes and spinous keratinocytes. The DNA index of nevomelanocytes was calculated using spinous keratinocytes as the diploid controls.There were significant decreases in IOD (P.05) in the nuclei of nevomelanocytes, lymphocytes and spinous keratinocytes after treatment with 1% KMnO4 for 5 and 10 minutes, but no significant changes were detected after treatment with 0.5% KMnO4 for 5 and 10 minutes. Severe tissue damage was observed in the Feulgen-stained slides treated with 1% KMnO4 for 15 and 20 minutes and with 10% H2O2 for 24 hours. There was no significant change in DNA index in any bleached sets measured.KMnO4 can affect Feulgen-DNA content if used in high concentrations or for long periods of incubation. The DNA index, which is derived from internal controls, is not affected by the bleach procedure.