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Flow diverters (FD) have poor radiopacity, challenging visualization of deployment and vessel wall apposition with conventional neuroimaging modalities. We evaluated a novel cone beam computed tomography (CT) imaging technique that allows virtual dilution (VD) of contrast media to facilitate workflow and ensure accurate assessment of FD wall apposition. We retrospectively evaluated all patients treated for intracranial aneurysms with FD at our institution between November 2018 and November 2019. Undiluted injected dual cone beam CT acquisitions performed post-stenting were displayed with VD software (GE Healthcare). The resulting images were compared with conventional two-dimensional (2D) digital subtraction angiography (DSA) images. Two neurointerventionalists (Reader 1 and Reader 2, (R1, R2)) independently assessed FD deployment and wall apposition. Confidence in the diagnosis, inter-reader agreement, and X-ray exposure were assessed. A total of 27 cases were reviewed. FD deployment and wall apposition scores were 4.2 ± 1.0 (R1) and 4.0 ± 1.1 (R2) for DSA and 3.7 ± 1.2 (R1) and 4.1 ± 1.0 (R2) for VD. Confidence in the diagnosis was improved with VD, with scores of 3.7 ± 0.7 (R1) and 4.0 ± 0.7 (R2) using DSA and 4.9 ± 0.2 (R1) and 4.9 ± 0.2 (R2) using VD (P

Intraoperative rupture of an intracranial aneurysm is a life-threatening situation that carries a high risk of morbidity and mortality. Since 2000, adenosine has been used successfully to induce transient hypotension and/or asystole to control bleeding and facilitate surgical clipping of aneurysms that rupture intraoperatively. Given the paucity of reports describing this method in a limited number of patients, we performed a systematic review of the literature detailing the use and outcomes of this technique.The authors performed a systematic review and identified all studies in which adenosine was used in the setting of an intracranial aneurysm that ruptured intraoperatively. We then determined overall morbidity and mortality rates, adding an additional six of our own patients.Data was analyzed for a total of 29 patients, including 23 previously reported patients from the literature and 6 additional cases from our own experience (mean age 54.8 years, 58.6% female). Most patients (82.8%, 24/29) presented with subarachnoid hemorrhage (SAH). Overall mean dose of adenosine was 51.8 mg. Successful clipping was achieved in 100% of patients. Transient or permanent morbidity was reported in 5/29 (17.2%) and the overall mortality rate was 31% (9/29), which occurred primarily due to an initial severe SAH and its resultant complications.Adenosine-induced circulatory arrest appears to safely control intraoperative bleeding and facilitate the clipping of ruptured intracranial aneurysms based on the limited published literature available. Further studies comparing patient outcomes using this technique to traditional approaches are required to validate the safety and efficacy of adenosine in this high-risk setting.

The visualization of intracranial epidermoid tumors is often limited by difficulties associated with distinguishing the tumor from the surrounding cerebrospinal fluid using traditional computed tomography (CT) or magnetic resonance imaging (MRI) modalities. This report describes our experience using CT cisternography to visualize intracranial epidermoid tumors in three illustrative cases. CT cisternography of the epidermoid tumor provides more clarity and precision compared to traditional neuroimaging modalities. We demonstrate the feasibility of using CT cisternography to produce high-resolution images with well-defined tumor margins that can be used effectively for precise SRS treatment planning.

International audience; Congenital central hypoventilation syndrome (CCHS) represents a rare genetic disorder usually caused by mutations in the homeodomain transcription factor PHOX2B. Some CCHS patients suffer mainly from deficiencies in CO 2 and/or O 2 respiratory chemoreflex, whereas other patients present with full apnea shortly after birth. Our goal was to identify the neuropathological mechanisms of apneic presentations in CCHS. In the developing murine neuroepithelium, Phox2b is expressed in three discrete progenitor domains across the dorsal-ventral axis, with different domains responsible for producing unique autonomic or visceral motor neurons. Restricting the expression of mutant Phox2b to the ventral visceral motor neuron domain induces marked newborn apnea together with a significant loss of visceral motor neurons, RTN ablation, and preBötzinger complex dysfunction. This finding suggests that the observed apnea develops through non-cell autonomous developmental mechanisms. Mutant Phox2b expression in dorsal rhombencephalic neurons did not generate significant respiratory dysfunction, but did result in subtle metabolic thermoregulatory deficiencies. We confirm the expression of a novel murine Phox2b splice variant which shares exons 1 and 2 with the more widely studied Phox2b splice variant, but which differs in exon 3 where most CCHS mutations occur. We also show that mutant Phox2b expression in the visceral motor neuron progenitor domain increases cell proliferation at the expense of visceral motor neuron development. We propose that visceral motor neurons may function as organizers of brainstem respiratory neuron development, and that disruptions in their development result in secondary/ non-cell autonomous maldevelopment of key brainstem respiratory neurons.

The behavior of the keratinocyte during the initial stages of cutaneous wound repair has been the subject of intense investigation. Most of these studies have focused on the lateral edges of wounds as the source of activated keratinocytes. Less attention has been directed towards elucidating the role of the appendageal structures as sources of keratinocytes for re-epithelialization, particularly the sweat apparatus. Surgical wounds of specific depths were created in pig skin, above and below hair follicles, and wound healing was allowed to take place in a setting in which lateral ingrowth of keratinocytes by migration was prevented. In this manner, all re-epithelialization occurred from residual appendageal structures. In those wounds where only sweat gland elements remained, an epithelium formed that had clinical, morphologic, and protein electrophoretic features closer to palmar/plantar or mucosal-like epithelia. In contrast, wounds that retained elements of the hair follicle healed faster and the resultant epithelium clinically, morphologically, and biochemically resembled the surrounding nonwounded epidermis. These findings establish that the sweat apparatus is capable of re-epithelializing the skin surface after a major cutaneous wound, but may not be capable of mimicking the epidermis.

The 12-month clinical outcomes of nursing home patients who underwent videofluoroscopic swallowing evaluation was determined. A retrospective review of 40 patients in a teaching nursing home who had videofluoroscopic swallowing studies from 1987 through 1989 was performed. Clinical outcomes measured included feeding tube placement, rehospitalization within 1 year, prolonged nursing home stay (>6 months), pneumonia, and pneumonia death. It was determined if outcomes were associated with the presence of aspiration on videofluoroscopy and subsequent feeding tube placement. In the 12-month follow-up period, 17 of 40 patients (43%) who underwent videofluoroscopic swallowing evaluation developed pneumonia and 18 of 40 (45%) died. Twenty-two patients demonstrated aspiration on videofluoroscopy. Increased rehospitalization was the only outcome measure that was associated with the presence of aspiration on videofluoroscopy (p≤0.05). Of 22 patients with aspiration, 15 had feeding tubes placed. This group had a higher rate of pneumonia (p≤0.05) and pneumonia death (p≤0.05) compared with the 7 patients with aspiration who did not receive feeding tubes. Patients with nasogastric tubes had a higher death rate (7/9) than patients with gastrostomy tubes (2/8; p≤0.05), but similar rates of rehospitalization and pneumonia. Nursing home patients who underwent videofluoroscopic swallowing evaluation had poor clinical outcomes at 12 months, regardless of their test results. Though limited by its small size and retrospective nature, this pilot study questions whether videofluoroscopic swallowing studies accurately identify patients at risk for developing aspiration pneumonia and whether feeding tubes prevent aspiration or improve clinical outcomes. A larger, prospective study is needed to address these issues.

Primary human dermal fibroblasts isolated from the medial aspect of the proximal forearm of young and old donors were compared for the expression of interstitial collagenase, 72 kDa type IV collagenase, the tissue inhibitor of metalloproteinase type 1, and pro-α2 (I) collagen mRNA at basal levels and after stimulation with the tumor promotor 12- O -tetradecanoyl-phorbol-13-acetate. Higher basal and induced steady-state mRNA levels of interstitial collagenase were found in the cells from older donors. Ratios of basal and induced steady-state mRNA levels of interstitial collagenase to pro-α2 (I) collagen, and interstitial collagenase to the tissue inhibitor of metalloproteinases type 1 were also higher in the cells from older donors. Seventy-two kiloDalton type IV collagenase and pro-α2 (I) collagen mRNA showed similar levels of expression in the cells from young and old donors and were not altered by treatment with 12- O -tetradecanoyl-phorbol-13-acetate. Transient transfection assays with the interstitial collagenase promoter linked to a reporter gene showed increased activity of the reporter in cell strains with high interstitial collagenase mRNA levels. Mobility shift assays demonstrated increased binding activity to the specific 12- O -tetradecanoyl-phorbol-13-acetate response element in nuclear extracts from the cell strains with higher induced collagenase mRNA levels and higher reporter gene activity. These findings are consistent with the observed phenotype of interstitial collagenase and its specific tissue inhibitor in the senescent fibroblast aging model.

The opossum kidney (OK) cell was used as a model to test the hypothesis that estrogen directly affects proximal renal tubular epithelial cells. To demonstrate the expression of estrogen receptor in OK cells, we developed an approach using reverse transcription and the polymerase chain reaction. Analysis of the DNA amplified with nested primers revealed the predicted size fragment and restriction enzyme digestion products. To demonstrate the functional effects of estrogen, OK cells at confluence were preincubated in serum-free medium for 7-10 days with or without 17 beta-estradiol. Bovine PTH(1-34) (bPTH(1-34)) then stimulated a dose-dependent intracellular accumulation of cAMP that was maximal after 1 min and then gradually declined. Cyclic AMP in the medium slowly increased over 60 min. Preincubation with 17 beta-estradiol did not affect cell proliferation as measured by total protein content but caused an inhibition of bPTH(1-34)-stimulated intracellular cAMP accumulation that was maximal at 10(-11) M 17 beta-estradiol (71 +/- 3% control, p less than .001). bPTH(1-34) also increased cAMP release into the medium, an effect maximal using 10(-10) M 17 beta-estradiol (118 +/- 3% control, p less than .001). Preincubation with the inactive isomer 17 alpha-estradiol caused no changes in cAMP accumulation or release. Coincubation with the antiestrogen tamoxifen blocked the effects of 17 beta-estradiol. Sodium-dependent phosphate transport was: (1) inhibited by 2-h incubations with 10(-8) or 10(-10) M bPTH(1-34) and not affected by preincubation with 17 beta-estradiol, and (2) not inhibited by a 20-min incubation with 10(-8) M bPTH(1-34) unless cells were preincubated with 10(-8) M 17 beta-estradiol, suggesting that any possible effects of estrogen on phosphate transport are not directly mediated by changes in cAMP. These studies demonstrate the presence of estrogen receptor mRNA in OK cells as well as direct and specific effects of physiologic concentrations of estrogen on cAMP accumulation in these cells. This system may be a good model for further study of estrogen and PTH effects on the kidney.

Senescent human fibroblasts produce larger fibronectin molecules with altered binding properties. To determine if this change could involve alternative splicing of fibronectin precursor mRNA, we developed an approach using reverse transcription and the polymerase chain reaction to study fibronectin mRNA splicing at each of the three alternatively spliced regions. Two of the three regions showed changes with in vitro passage; incorporation of the ED-A region increased 8 fold.

REPORT OF A CASE A 5-year-old white boy was referred for evaluation of a solitary patch of hair loss, which had begun 8 weeks earlier. Initially, he had presented to his primary care physician with an inflamed plaque of alopecia involving the left frontal area. He was treated with oral antibiotics, with minimal response. Owing to persistence of the lesion, the patient was referred for further evaluation and treatment. On examination, a 3×3-cm, erythematous, crusted, scaling patch with broken hairs was present on the front part of the scalp (Figure 1). Purulent drainage and follicular pustules were absent. The social history was significant for 2 healthy cats and 1 dog at home. Wood light fluorescence was absent. A potassium hydroxide preparation of scrapings from the involved scalp and hairs was nondiagnostic. A fungal culture of broken hairs and scale showed some growth in 5 days. A mature colony plated on

REPORT OF A CASE A 40-year-old white woman presented with a 3-month history of painful, nonhealing ulcers on her lower extremities. Her medical history was remarkable for hepatitis C virus (HCV) infection. Her physical examination revealed multiple 1- to 5-cm discrete ulcers with surrounding hyperpigmented macules on the lower extremities ( Figure 1 ). The pulses in the lower extremities were full, symmetrical, and without bruits. Trace edema of the lower extremities was present without cyanosis. Diagnostic workup and laboratory tests revealed the following: HCV antigen (Ag) was detected in the serum sample by polymerase chain reaction; serum transaminase and alkaline phosphatase levels were moderately elevated; findings of a liver biopsy were consistent with active hepatitis; the antinuclear antibody (Ab) titer was 1:40; serologic tests were negative for hepatitis B Ab and Ag and anticardiolipin antibody and positive for HCV Ab; and the serum ceruloplasmin and α 1 -antitrypsin activity were

REPORT OF A CASE A 71-year-old man was hospitalized because of a transient ischemic attack. The dermatology department was consulted to evaluate an eruption on the left side of the trunk that was thought to be herpes zoster. The rash had appeared abruptly 6 months earlier and had failed to respond to topical steroid treatment. There was no history of previous skin disease or other illness. The patient's only medication was aspirin. Physical examination revealed grouped 2- to 4-mm red-brown, scaly papules in a linear array overlying the left flank (Figure 1). There were no abnormalities of the nails or oral mucosa. A punch biopsy was performed (Figure 2). What is your diagnosis?