[GrS Montreal: A private hospital specializing in gender-affirming surgery in Canada]. / GrS Montréal : un hôpital privé spécialisé en chirurgie d'affirmation de genre au Canada.

Gender dysphoria refers to the suffering an individual experiences when his or her sex at birth does not correspond to the expression of his or her gender. Gender-affirmation surgery is a procedure that can alleviate this suffering. For 20 years, GrS Montreal has been Canada's only center dedicated exclusively to this type of surgery. Thanks to its expertise, quality of care, state-of-the-art infrastructure and convalescent home, GrS Montreal receives patients from all over the world. This article describes the particularities of this center and puts into perspective the evolution of this type of surgery.

Spontaneous resolution of a giant keratoacanthoma penetrating through the nose.

Although keratoacanthomas are common and spontaneous resolution well recognized, case reports with photographic documentation of resolution are few. The subtype of giant keratoacanthoma (GKA) can give rise to severe cosmetic destruction because of their size and their predilection for cosmetically sensitive areas (nose and eyelids). Spontaneous resolution of GKAs has not been widely reported. We present an impressive series of clinical photographs documenting the spontaneous resolution of a GKS on the nose of a 56-year-old patient.

Distinct cell proliferation events during abstinence after alcohol dependence: microglia proliferation precedes neurogenesis.

Excessive alcohol intake characteristic of Alcohol Use Disorders (AUDs) produces neurodegeneration that may recover with abstinence. The mechanism of regeneration is unclear, however neurogenesis from neural stem/progenitor cells is a feasible mechanism of structural plasticity. Therefore, a timecourse of cell proliferation was examined in a rat model of an AUD and showed a striking burst in cell proliferation at 2 days of abstinence preceding the previously reported neurogenic proliferation at 7 days. New cells at 2 days, assessed by bromo-deoxy-uridine incorporation and endogenous markers, were observed throughout hippocampus and cortex. Although the majority of these new cells did not become neurons, neurogenesis was not altered at this specific time point. These new cells expressed a microglia-specific marker, Iba-1, and survived at least 2 months. This first report of microglia proliferation in a model of an AUD suggests that microgliosis could contribute to volume recovery in non-neurogenic regions during abstinence.

Analysis of sphingosine 1-phosphate receptors involved in constriction of isolated cerebral arteries with receptor null mice and pharmacological tools.

BACKGROUND AND PURPOSE: Sphingosine 1-phosphate (S1P) selectively and potently constricts isolated cerebral arteries, but this response has not been pharmacologically characterized. EXPERIMENTAL APPROACH: The receptor subtype(s) involved in S1P-induced cerebrovascular constriction were characterized using genetic (S1P(2) and S1P(3) receptor null mice) and pharmacological tools (phospho-FTY720, a S1P(1/3/4/5) receptor agonist; SEW2871, a S1P(1) receptor agonist, JTE-013, a S1P(2) receptor antagonist, VPC23019, a S1P(1/3) receptor antagonist). Isolated basilar or peripheral (femoral, mesenteric resistance) arteries, from either rat or mouse, were studied in a wire myograph. KEY RESULTS: S1P concentration-dependently constricted basilar artery in rat, wild-type (WT) and S1P(2) null mice, but barely affected vascular tone in S1P(3) null mice. Vasoconstriction to U46619 (a thromboxane analogue) or to endothelin-1 did not differ between WT, S1P(2) and S1P(3) null mice. JTE-013 inhibited not only S1P-induced vasoconstriction, but also KCl-, U46619- and endothelin-1-induced constriction. This effect was observed in WT as well as in S1P(2) null mice. VPC23019 increased the concentration-dependent vasoconstriction to S1P in both rat and mouse basilar arteries with intact endothelium, but not in rat basilar artery without endothelium. Phospho-FTY720 concentration-dependently constricted rat basilar arteries, but not femoral or mesenteric resistance arteries, while SEW2871 did not induce any response in the same arteries. CONCLUSIONS AND IMPLICATIONS: S1P constricts cerebral arteries through S1P(3) receptors. The purported S1P(2) receptor antagonist JTE-013 does not appear to be selective, at least in rodents. Enhancement of S1P-induced contraction by VPC23019 might be related to blockade of S1P(1) receptors and NO generation.

Rho-kinase inhibition acutely augments blood flow in focal cerebral ischemia via endothelial mechanisms.

Rho-kinase is a serine threonine kinase that increases vasomotor tone via its effects on both endothelium and smooth muscle. Rho-kinase inhibition reduces cerebral infarct size in wild type, but not endothelial nitric oxide synthase deficient (eNOS-/-) mice. The mechanism may be related to Rho-kinase activation under hypoxic/ischemic conditions and impaired vasodilation because of downregulation of eNOS activity. To further implicate Rho-kinase in impaired vascular relaxation during hypoxia/ischemia, we exposed isolated vessels from rat and mouse to 60 mins of hypoxia, and showed that hypoxia reversibly abolished acetylcholine-induced eNOS-dependent relaxation, and that Rho-kinase inhibitor hydroxyfasudil partially preserved this relaxation during hypoxia. We, therefore, hypothesized that if hypoxia-induced Rho-kinase activation acutely impairs vasodilation in ischemic cortex, in vivo, then Rho-kinase inhibitors would acutely augment cerebral blood flow (CBF) as a mechanism by which they reduce infarct size. To test this, we studied the acute cerebral hemodynamic effects of Rho-kinase inhibitors in ischemic core and penumbra during distal middle cerebral artery occlusion (dMCAO) in wild-type and eNOS-/- mice using laser speckle flowmetry. When administered 60 mins before or immediately after dMCAO, Rho-kinase inhibitors hydroxyfasudil and Y-27632 reduced the area of severely ischemic cortex. However, hydroxyfasudil did not reduce the area of CBF deficit in eNOS-/- mice, suggesting that its effect on CBF within the ischemic cortex is primarily endothelium-dependent, and not mediated by its direct vasodilator effect on vascular smooth muscle. Our results suggest that Rho-kinase negatively regulates eNOS activity in acutely ischemic brain, thereby worsening the CBF deficit. Therefore, rapid nontranscriptional upregulation of eNOS activity by small molecule inhibitors of Rho-kinase may be a viable therapeutic approach in acute stroke.

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

Inward rectifier K(+) channel Kir2.3 (IRK3) in reactive astrocytes from adult rat brain.

Astrocytic inward rectifying K(+) channels that participate in K(+) spatial buffering in the central nervous system have been extensively investigated, but specific gene products have not been fully identified. We studied primary cultured reactive astrocytes of stellate and polygonal morphology from adult rat brains, as well as stellate astrocytes from neonatal rat brains. Single-channel recordings of cell-attached patches revealed that polygonal reactive astrocytes expressed only one hyperpolarization-activated single-channel conductance of 11-15 pS whose open probability was independent of voltage, whereas stellate reactive and stellate neonatal astrocytes exhibited two conductances, 11-15 pS and 24-27 pS. All three subtypes of astrocytes exhibited a hyperpolarization-activated macroscopic inward K(+) current that was strongly rectifying and was abrogated by 1 mM intracellular Mg(2+) introduced during conventional but not perforated patch whole-cell recording. This Mg(2+)-sensitive current comprised the total inward rectifier current in polygonal reactive astrocytes, but only a fraction of the inward rectifier current in stellate reactive and stellate neonatal astrocytes. Because a strongly rectifying, inward rectifier K(+) channel with a single-channel conductance of 11-15 pS that is voltage independent is consistent with features of Kir2.3 (IRK3), we performed immunofluorescence experiments with anti-Kir2.3 and anti-glial fibrillary acidic protein antibodies. Both antibodies co-localized to all three subtypes of astrocytes in primary culture and to reactive astrocytes in situ within brain and gelatin sponge implants. Our data indicate that astrocytes of both polygonal and stellate morphology, from both adult and neonatal rat brain, express Kir2.3 both in vivo and in vitro. Constitutive expression of Kir2.3 regardless of cell morphology or age of origin of the source tissue suggests an important functional role for this channel in astrocytes.

Morphometric X-ray absorptiometry and morphometric radiography of the spine: a comparison of analysis precision in normal and osteoporotic subjects.

Morphometric techniques, which use conventional lateral spine radiographs to quantify vertebral body shape (morphometric radiography, MRX), have proved a useful tool in the identification and evaluation of osteoporotic vertebral deformities. Recently a new method of acquiring the images required for vertebral morphometry using dual-energy X-ray absorptiometry scanners (morphometric X-ray absorptiometry, MXA) has been developed. In this study we compare repeat analysis precision of vertebral height measurement using MXA and MRX. Twenty-four postmenopausal women were recruited (mean age 67 +/- 5.8 years): 12 normal subjects and 12 with osteoporosis and vertebral deformities. Each subject had a MXA scan and lateral thoracic and lumbar radiographs at a single appointment, which were each analyzed quantitatively in a masked fashion, using a standard 6-point method, twice by one observer and once by a second observer. Anterior (Ha), mid (Hm) and posterior (Hp) vertebral heights were measured and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios calculated for each vertebral body. Intra- and interobserver precision were consistently poorer in MXA compared with MRX in both normal subjects and those with vertebral deformities, with MXA CV% generally at least 50% higher than corresponding values for MRX. For both MXA and MRX interobserver precision was clearly poorer than intraobserver precision, a problem associated with any morphometric technique. MXA intra- and interobserver precision were significantly poorer for subjects with vertebral deformities compared with those without, with a CV% for deformity subjects up to twice that of normal subjects. Conversely, MRX showed little or no obvious worsening of intra- or interobserver precision for deformity subjects. Comparison of MXA precision in the normal and deformed vertebrae of the deformity subjects demonstrated that the poorer precision in these subjects compared with normal subjects was the result of increased variability in point placement on the deformed vertebrae themselves. However, the precision for normal vertebrae in these subjects was also somewhat poorer than the precision in normal subjects. We conclude that MXA precision is generally poorer than that of MRX and that the presence of vertebral deformities has a more pronounced effect on MXA precision than on MRX precision.

Morphometric X-ray absorptiometry: reference data for vertebral dimensions.

Vertebral fractures are a common and important consequence of osteoporosis and are often identified via morphometric analysis of conventional lateral spine radiographs (morphometric radiography or MRX). A new method of performing vertebral morphometry using images acquired on dual-energy X-ray absorptiometry (DXA) scanners (morphometric X-ray absorptiometry or MXA) has recently been developed. In this study, we derive reference data for vertebral heights and height ratios using MXA scans as the data source and compare the results with previously published MRX studies. One thousand and nineteen Caucasian women (mean age 63 years, range 33-86) were recruited. An MXA scan, covering 13 vertebrae from L4 to T4, was acquired for each subject on one of four DXA systems located at three centers in the U.K. Analysis of variance found statistically significant but relatively small differences among centers, machines, and scan modes, and therefore data were pooled for reference range calculations. Three vertebral heights (anterior, mid, and posterior) were measured and four ratios (wedge, mid-wedge, and two crush) calculated. These data sets were trimmed using an iterative algorithm to remove extreme values assumed to represent deformed vertebrae, then mean and SD values were calculated using the remaining data. When the data were split by age, a small but statistically significant decrease in vertebral height between the sixth and eighth decades was found, but this was not replicated for the vertebral height ratios. Marked differences were observed between MXA data and MRX, but were comparable to those between different MRX studies. These may result from differences in image quality and point placement protocols, population differences, differences in radiographic technique, and differences in the derivation of a group of "normal" vertebrae. This study suggests that reference data of vertebral dimensions should be specific to the technique which uses those data as a reference, i.e., MXA.

Heavy metal effects on Proteus mirabilis superoxide dismutase production.

Proteus mirabilis expressed three superoxide dismutase activities, which depended on the level of soluble iron and dioxygen in the culture medium. Cadmium and lead decreased production of super oxide dismutase in liquid culture and on solid medium. A fourth super oxide dismutase activity appeared in extracts from cells grown in the presence of cadmium. These results support the idea of an interaction between toxic metal ions and putative iron- and redox-dependent regulatory systems.

Diurnal and longitudinal variations in human milk sodium and potassium: implication for nutrition and physiology.

Human milk sodium ([Nal]) and potassium ([K)] concentrations were measured every 4 h for 24 h in 28 subjects 3.5 to 32 wk postpartum. A diurnal variation in milk Na was seen, which was reciprocal to K. Significant negative correlations between Na and K were seen in these periods: 3.5 to 6; 8 to 18, 20 to 32 wk postpartum (p less than 0.01 for each). The mean 24 h milk sodium concentrations (x(Na)) decreased between 3.5 and 18 wk postpartum (p less than 0.005 by paired t test). Changes in mean potassium (-XK) were not statistically significant. Diet apparently does not affect milk Na. Administration of a low Na diet: 10.8 +/- .9 (SD) mEq Na/day and 60 to 100 mEq K/day for 2 days did not change x(Na). But urinary Na decreased 7-fold as aldosterone increased 5-fold. No significant correlation was seen between 24 h Na excretion in urine and x(Na) in milk (n = 51). A significant positive correlation was seen between urinary K and -XK in milk (r = 0.36), p less than 0.001).

Lichen planus: a distinct entity from lupus erythematosus.

Thirty-five patients with classical lichen planus (LP) were extensively investigated with special reference to immunohistological changes and histocompatibility (HLA) typing. There was no evidence of lupus erythematosus (LE) in any patient, although one patient with LP and eczema had an elevated titre of antinuclear factor. There was no increased incidence of any HLA type--in particular HLA-B7 and HLA-B8--known to be associated with LE. The results suggest that LE and LP are separate disorders.

Modular Formula: an approach to management of infants with specific or complex food intolerances.

Modular Formula is a dietary preparation for use in treating infants with complex malabsorptive disorders and for weaning infants from total parenteral nutrition. With this formula the physician can alter the quality of the various nutrients normally fed to infants as well as concentrations of those nutrients. Infants who cannot tolerate existing proprietary formulas will often thrive with the judicious use of this flexible formula. Modular Formula provides the clinician with a useful aid in the diagnosis and treatment of chronic diarrhea of infancy.