Dyke Award. The search for human telencephalic ventriculofugal arteries

Our study traced the vascular development of the fetal telencephalon in the last two trimesters of gestation and the first 15 years of life in 60 fetal and childhood brains. We filled the macro- and microvascular beds with Microfil and made stereoscopic observations of cleared 0.5- to 1.0-cm-thick sections. Separately, we identified developing vascular structures histologically. In our youngest specimen (16-weeks gestation), transcerebral channels with walls consisting of a single layer of endothelium and varying in diameter from 10 to 50 microns originated from leptomeningeal arteries and veins at right angles to the surface and passed through the cortical plate (future cortex). They branched at varying depths within the mantle and germinal matrix surrounding the lateral ventricles. At deeper levels the channels freely anastomosed with each other. A cortical microvascular network did not appear until 22 to 24 weeks. The new endothelial channels were derived from leptomeningeal vessels and from larger transcerebral channels. Most regions of isocortex developed a microvascular plexus simultaneously, regardless of degree of maturation. Striatal channels matured earlier than extrastriatal channels, having developed a muscularis to within 100 microns of the ganglionic eminence by 22- to 24-weeks gestation. Maturation of the vascular walls of extrastriatal channels into proper arteries and veins occurred during the first postnatal year. Anastomotic channels were present throughout the leptomeningeal, striatal, and extrastriatal regions in all of our specimens from 16 weeks gestation to 15 years old. Our study does not support the existence of ventriculofugal arteries and deep white matter arterial border zones in the human fetus and neonate, which have been postulated to be the basis of "periventricular" leukomalacia.     

Primary cutaneous mucoepidermoid carcinoma: report of a case

Primary mucoepidermoid carcinomas of the skin are extremely rare tumors. We describe a primary cutaneous mucoepidermoid carcinoma arising in the right ear (posterior mid helix) of a 66-year-old white man. The tumor was 0.6 cm in diameter, ulcerated and nonencapsulated. No other tumors were found in the patient. Histologically the tumor showed the characteristics of a "low grade" mucoepidermoid carcinoma, consisting of lobules of polygonal cells with vesicular nuclei. In the center of the lobules were large vacuolated cells (goblet cells). Transitions between the two cell populations were present throughout the tumor. An epidermal attachment of the tumor, as well as epidermal dysplasia, predominantly at the acrosyringium was present, consistent with the theory of sweat duct histogenesis of these tumors. Immunoperoxidase staining showed positivity for epithelial membrane antigen, keratin and carcinoembryonic antigen. The latter was predominantly positive in the goblet cells. Cutaneous metastasis of mucoepidermoid carcinomas with epidermal attachment has been reported. Our case showed only ear involvement and follow-up at 8 months has revealed no evidence of recurrence. These findings are consistent with the diagnosis of primary cutaneous mucoepidermoid carcinoma.     

Scorpion alpha and alpha-like toxins differentially interact with sodium channels in mammalian CNS and periphery

Scorpion alpha-toxins from Leiurus quinquestriatus hebraeus, LqhII and LqhIII, are similarly toxic to mice when administered by a subcutaneous route, but in mouse brain LqhII is 25-fold more toxic. Examination of the two toxins effects in central nervous system (CNS), peripheral preparations and expressed sodium channels revealed the basis for their differential toxicity. In rat brain synaptosomes, LqhII binds with high affinity, whereas LqhIII competes only at high concentration for LqhII-binding sites in a voltage-dependent manner. LqhII strongly inhibits sodium current inactivation of brain rBII subtype expressed in HEK293 cells, whereas LqhIII is weakly active at 2 microM, suggesting that LqhIII affects sodium channel subtypes other than rBII in the brain. In the periphery, both toxins inhibit tetrodotoxin-sensitive sodium current inactivation in dorsal root ganglion neurons, and are strongly active directly on the muscle and on expressed muI channels. Only LqhII, however, induced repetitive end-plate potentials in mouse phrenic nerve-hemidiaphragm muscle preparation by direct effect on the motor nerve. Thus, rBII and sodium channel subtypes expressed in peripheral nervous system (PNS) serve as the main targets for LqhII but are mostly not sensitive to LqhIII. Toxicity of both toxins in periphery may be attributed to the direct effect on muscle. Our data elucidate, for the first time, how different toxins affect mammalian central and peripheral excitable cells, and reveal unexpected subtype specificity of toxins that interact with receptor site 3.     

Domestic violence in Australia: definition, prevalence and nature of presentation in clinical practice

Domestic violence is a complex pattern of behaviours that may include, in addition to physical acts of violence, sexual abuse and emotional abuse. Women experience domestic violence at far greater rates than men do, and women and children often live in fear as a result of the abuse that is used by men to maintain control over their partners. Domestic violence is a major public health problem and is very common in women attending clinical practice. Women present most commonly with a range of chronic symptoms to unsuspecting general practitioners, emergency department doctors or medical specialists. Women who have experienced partner abuse want to be asked about it and are more likely to disclose if asked in an empathic, non-judgemental way. Doctors can make a difference.     

Posterior Laryngeal Clefts: Preliminary Report of a New Surgical Procedure Using Tibial Periosteum As an Interposition Graft

Objective: To present the preliminary results of a new surgical procedure for posterior laryngeal cleft repair. Design: Retrospective study in an academic tertiary care center. Method: The study included three male patients (age at surgery, 2, 13, and 14 mo). One presented with severe aspiration and cyanotic attacks, the two others with aspiration and recurrent chest infections. The types of laryngeal clefts included complete cleft of the cricoid with varying degrees of tracheal involvement but not further than the first six tracheal rings. Associated malformations included one VATER syndrome, one esophageal atresia, and one tracheoesophageal fistula. Surgery was performed under general anesthesia with nasotracheaI intubation. A vertical anterior laryngofissure was performed. The mucosal margins of the clefts were incised and then repaired in two layers with polyglactin sutures. The original feature of this procedure was the interposition of a small piece of tibial periosteum between the two layers. This fascia graft is known to be strong and resistant in cleft palate surgery. Main Outcome Measure: Clinical and endoscopic follow-up was used for evaluation of results. Results: The three patients had successful laryngeal repair at a mean follow-up of 6 months (range, 4-14 mo). Conclusion: The anterior laryngofissure provides a good surgical access to the cleft. The interposition of tibial periosteum allows durability of the cleft repair. A longer follow-up is needed to confirm these preliminary results. A computed tomography scan study and a study on the rabbit are planned in order to evaluate the outcome of these periosteal grafts.     

The MDR1 (P-glycoprotein) and MRP (P-190) transporters do not play a major role in the intrinsic multiple drug resistance of Jurkat T lymphocytes

The response of T cells in relation to the cell cycle has not been extensively studied. We have attempted to address this question using Jurkat T cells treated with cytostatic drugs known to arrest cells at various transition points of their cycle. We tested several concentrations of drugs that act at G1/S (hydroxyurea, lovastatin, thymidine), early S (aphidicolin, cyclosporin A, rapamycin) or G2+M (colchicine, nocodazole) in 24 h cultures. Cytofluorimetric analyses showed that cycling Jurkat cells were equally distributed between the G1 (44.9 ± 6.5%) and S (42.3 ± 8.0%) phases. Cell distribution in G2+M was 12.7 ± 2.8%. Hydroxyurea but not lovastatin increased the percentage of cells in S phase to ≈60–70% and both drugs decreased it to ≈30% in G1. Thymidine had no effects. Aphidicolin increased the distribution in S phase to ≈70% with a decrease in G1 to ≈30%. Cyclosporin A and rapamycin increased the percentage of the cells in G1 to ≈70% and decreased it to ≈25% in S phase. Nocodazole increased cell distribution in G2+M to ≈60% and induced a decrease in G1 to ≈10%. The effects of the drugs were not related to their toxicity and their limited efficiency raised the possibility that Jurkat cells possessed an intrinsic resistance to these xenobiotics. Time-course analysis showed (scanning electron microscopy) that the early morphological changes induced by colchicine were reversible. Drug efflux experiments (vinblastine) suggested that an ATP-dependent process could be involved. However, Northern blot analyses showed a weak signal for MDR1 (P-glycoprotein). In contrast, a probe for MRP (P-190) showed a strong signal in Jurkat and peripheral lymphocytes. The presence of drugs (cyclosporin A, nocodazole, thymidine) (24 h) did not upregulate its message and cell treatment with -butathione (S,R)-sulfoximine only moderately affected the efficiency of the glutathione S-conjugate MRP transporter. Our data suggest that the intrinsic multidrug resistance of leukemic Jurkat T cells does not appear to involve the MDR1 and MRP members of the ABC family of reverse drug transporters and these observations raise the possibility of the involvement of multifaceted mechanisms.     

Prevalence and Predictors of Liver Fibrosis in People Living with Hepatitis B in Senegal

Hepatitis B virus (HBV) infection is the first cause of liver cirrhosis and cancer in West Africa. Although the exposure to additional environmental and infectious risk factors may lead to the faster progression of liver disease, few large-scale studies have evaluated the determinants of HBV-related liver fibrosis in the region. We used transient elastography to evaluate the prevalence of liver fibrosis and assessed the association between HBV markers and significant liver fibrosis in a cohort of people living with HBV in Dakar, Senegal. The prevalence of significant liver fibrosis was 12.5% (95% confidence interval [CI] 9.6%–15.9%) among 471 people with HBV mono-infection (pwHBV) and 6.4% (95% CI 2.6%–12.7%) in 110 people with HIV/HBV co-infection (pwHIV/HBV) on tenofovir-containing antiretroviral therapy (p = 0.07). An HBV viral load > 2000 IU/mL was found in 133 (28.3%) pwHBV and 5 (4.7%) pwHIV/HBV, and was associated with significant liver fibrosis (adjusted odds ratio (aOR) 1.95, 95% CI 1.04–3.66). Male participants (aOR 4.32, 95% CI 2.01–8.96) and those with elevated ALT (aOR 4.32, 95% CI 2.01–8.96) were especially at risk of having significant liver fibrosis. Our study shows that people with an HBV viral load above 2000 IU/mL have a two-fold increase in the risk of liver fibrosis and may have to be considered for antiviral therapy, independent of other disease parameters.     

Percutaneous blade and balloon atrioseptostomy as a supplement to extracorporeal membrane oxygenation as a bridge to heart transplantation

In patients with severe ventricular dysfunction, the extracorporeal membrane oxygenation (ECMO) could be insufficient to discharge the left ventricle. The percutaneous blade and balloon atrioseptostomy that requires transeptal catheter-based experience could be an advisable technique to supplement assistance as a bridge to partial recovery or to heart transplantation. We present a case of a young male who presented for cardiogenic shock with a huge thrombus in the left main coronary artery in whom blade and balloon atrioseptostomy in addition to the ECMO was helpful to bail out and to perform heart transplantation.