[Use of a rhomboid flap to repair temporal and frontotemporal cutaneous defects: 11 cases]. / Réparation de pertes de substance temporales et frontotemporales par un lambeau de transposition de type rhomboïdal : 11 observations.

BACKGROUND: Temporal and frontotemporal skin defects can be repaired using various reconstruction procedures: temporojugal rotation-advancement flaps, frontotemporal advancement flaps, skin grafts, etc. We propose an alternative method using a rhomboid transposition flap, thus extending the possibilities for repair in this region. MATERIALS AND METHODS: This is a retrospective, non-comparative study of patients in whom a rhomboid transposition flap of the temporal or frontotemporal region was created between February 2008 and March 2010. Sex, age, hospitalization, histological type of the excised lesion, type of anaesthesia, defect size, possible occurrence of complications and outcome were compiled from the medical records. RESULTS: Eleven patients (five women and six men) of average age 76 years were included. The lesions were due in all cases to basal cell carcinoma. Five patients were ambulatory and seven were hospitalized. All patients underwent surgery under local anaesthesia in a single session. Hospitalized patients had more extensive cutaneous defects, were older and had more comorbidities. One patient presented incomplete lateral resection. The most frequent complication was bruising on the lower eyelid (5/11), and two more severe complications occurred: distal flap necrosis and haematoma. The aesthetic result was good for all patients after a mean 20months of follow-up. CONCLUSION: Rhomboid transposition flaps appear to be a reconstruction option that warrants consideration in cutaneous defects in the temporal or frontotemporal region.

Perceptions of heat-health impacts and the effects of knowledge and preventive actions by outdoor workers in Hanoi, Vietnam.

Extreme heat is an increasing climate threat, most pronounced in urban areas where poor populations are at particular risk. We analyzed heat impacts and vulnerabilities of 1027 outdoor workers who participated in a KAP survey in Hanoi, Vietnam in 2018, and the influence of their mitigation actions, their knowledge of heat-risks, and access to early warnings. We grouped respondents by their main income (vendors, builders, shippers, others, multiple jobs, and non-working) and analyzed their reported heat-health impacts, taking into consideration socioeconomics, knowledge of heat impacts and preventive measures, actions taken, access to air-conditioning, drinking amounts and use of weather forecasts. We applied linear and logistic regression analyses using R. Construction workers were younger and had less knowledge of heat-health impacts, but also reported fewer symptoms. Older females were more likely to report symptoms and visit a doctor. Access to air-conditioning in the bedroom depended on age and house ownership, but did not influence heat impacts as cooling was too expensive. Respondents who knew more heat exhaustion symptoms were more likely to report impacts (p < 0.01) or consult a doctor (p < 0.05). Similarly, those who checked weather updates were more likely to report heat impacts (p < 0.01) and experienced about 0.6 more symptoms (p < 0.01). Even though occupation type did not explain heat illness, builders knew considerably less (40%; p < 0.05) about heat than other groups but were twice as likely to consult a doctor than street vendors (p < 0.01). Knowledge of preventive actions and taking these actions both correlated positively with reporting of heat-health symptoms, while drinking water did not reduce these symptoms (p < 0.01). Child carers and homeowners experienced income losses in heatwaves (p < 0.01). The differences support directed actions, such as dissemination of educational materials and weather forecasts for construction workers. The Red Cross assisted all groups with cooling tents, provision of drinks and health advice.

Quantification of taurodontism: interests in the early diagnosis of hypohidrotic ectodermal dysplasia.

OBJECTIVE: The aim of this study was to provide a quantification of taurodontism in Hypohidrotic Ectodermal Dysplasia (HED) and to report its occurrence in a cohort of HED patients to assess phenotypic-genotypic correlations. PATIENTS AND METHODS: Of 68 HED patients retrospectively reviewed, 16 patients aged 7-51 years were selected and compared with a control sample (n = 351). The pulp surface index of the first lower permanent molar was calculated from the panoramic radiograph of each individual, and statistical comparisons between the HED patients and the control sample were performed. RESULTS: Whatever the genetic disorder, 81.25% of the HED patients exhibited a relative enlargement (>or=1 s.d.) of the pulp. Major deviations (>5 s.d.) were respectively related to men affected by large deletion of the EDA gene or missense mutation. The autosomal recessive form was linked to a relative moderate pulp enlargement (3.44 s.d.). In NEMO forms, the increase of pulp size in men appeared to be less marked than in EDA mutations. CONCLUSION: This study provides for the first time an objective assessment of pulp enlargement in HED patients, and the various degrees of taurodontism depicted could be interesting dental phenotypic markers of HED forms.

Selective protection of methionine enkephalin released from brain slices by enkephalinase inhibition.

Methionine enkephalin release was evoked by depolarization of slices from rat striatum with potassium. In the presence of 0.1 microM thiorphan [(N(R,S)-3-mercapto-2-benzylpropionyl)glycine], a potent inhibitor of enkephalin dipeptidyl carboxypeptidase (enkephalinase), the recovery of the pentapeptide in the incubation medium was increased by about 100 percent. A similar effect was observed with the dipeptide phenylalanylalanine, a selective although less potent enkephalinase inhibitor. Inhibition of other known enkephalin-hydrolyzing enzymes--aminopeptidase by 0.1 mM puromycin or angiotensin-converting enzyme by 1 microM captopril--did not significantly enhance the recovery of released methionine enkephalin. These data indicate that enkephalinase is critically involved in the inactivation of the endogenous opioid peptide released from striatal neurons.

Convolutional Neural Network-Based Automated Segmentation of the Spinal Cord and Contusion Injury: Deep Learning Biomarker Correlates of Motor Impairment in Acute Spinal Cord Injury.

BACKGROUND AND PURPOSE: Our aim was to use 2D convolutional neural networks for automatic segmentation of the spinal cord and traumatic contusion injury from axial T2-weighted MR imaging in a cohort of patients with acute spinal cord injury. MATERIALS AND METHODS: Forty-seven patients who underwent 3T MR imaging within 24 hours of spinal cord injury were included. We developed an image-analysis pipeline integrating 2D convolutional neural networks for whole spinal cord and intramedullary spinal cord lesion segmentation. Linear mixed modeling was used to compare test segmentation results between our spinal cord injury convolutional neural network (Brain and Spinal Cord Injury Center segmentation) and current state-of-the-art methods. Volumes of segmented lesions were then used in a linear regression analysis to determine associations with motor scores. RESULTS: Compared with manual labeling, the average test set Dice coefficient for the Brain and Spinal Cord Injury Center segmentation model was 0.93 for spinal cord segmentation versus 0.80 for PropSeg and 0.90 for DeepSeg (both components of the Spinal Cord Toolbox). Linear mixed modeling showed a significant difference between Brain and Spinal Cord Injury Center segmentation compared with PropSeg (P < .001) and DeepSeg (P < .05). Brain and Spinal Cord Injury Center segmentation showed significantly better adaptability to damaged areas compared with PropSeg (P < .001) and DeepSeg (P < .02). The contusion injury volumes based on automated segmentation were significantly associated with motor scores at admission (P = .002) and discharge (P = .009). CONCLUSIONS: Brain and Spinal Cord Injury Center segmentation of the spinal cord compares favorably with available segmentation tools in a population with acute spinal cord injury. Volumes of injury derived from automated lesion segmentation with Brain and Spinal Cord Injury Center segmentation correlate with measures of motor impairment in the acute phase. Targeted convolutional neural network training in acute spinal cord injury enhances algorithm performance for this patient population and provides clinically relevant metrics of cord injury.

[Leflunomide-induced skin necrosis]. / Nécroses cutanées induites par le léflunomide.

BACKGROUND: Leflunomide is prescribed in inflammatory rheumatisms. Cutaneous side effects have rarely been described. We report the case of a patient presenting skin necrosis attributed to this drug. PATIENTS AND METHODS: A 73-year-old woman had been taking leflunomide for psoriatic arthritis for one year and subsequently, developed three abdominal ulcerations and necrosis of one hallux. No immunological, vascular or neoplastic aetiology was found. Corticotherapy was started, based on a hypothesis of vasculitis, but lesions progressed, leading to amputation of the hallux. Leflunomide was stopped and the ulcerations healed completely within 12 weeks, whereas prolonged local treatment had failed to yield any improvement. DISCUSSION: Skin necrosis due to leflunomide is rare; we found seven cases in the literature. Ulcerations may occur anywhere. Potentially life-threatening glomerulonephritis with mesangial deposits may be associated. Discontinuation of leflunomide followed by wash-out with cholestyramine allows healing. Corticosteroids or cyclophosphamide are sometimes necessary. The ulcerations appear to be result from excessive immunomodulation in the skin or from an inhibiting role of leflunomide on the epidermal growth factor receptor. CONCLUSION: In the absence of any demonstrated aetiology in patients presenting ulcerations or skin necrosis, a contributory role of leflunomide must be considered, even in cases of prolonged use.

Conservative management of an atypical intra-sinusal ossifying fibroma associated to an aneurysmal bone cyst.

Ossifying fibroma (OF) is a benign fibro-osseous lesion mainly occurring in young adults and seems to originate from the periodontal ligament. Aneurysmal bone cyst (ABC) is a benign intraosseous lesion characterized by blood-filled spaces of various sizes. These two lesions can specifically affect the jaws and are commonly described in the literature. However, few cases describing an association of OF and ABC have been reported in the literature, especially in the maxillary sinus. We report the case of a 40-year-old male patient affected with an asymptomatic lesion with a dual component of OF and ABC laying in the maxillary sinus. Our aim is to discuss its clinical and morphological features as well as treatment results.

Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis.

BACKGROUND AND PURPOSE: There is an emerging need for biomarkers to better categorize clinical phenotypes and predict progression in amyotrophic lateral sclerosis. This study aimed to quantify cervical spinal gray matter atrophy in amyotrophic lateral sclerosis and investigate its association with clinical disability at baseline and after 1 year. MATERIALS AND METHODS: Twenty-nine patients with amyotrophic lateral sclerosis and 22 healthy controls were scanned with 3T MR imaging. Standard functional scale was recorded at the time of MR imaging and after 1 year. MR imaging data were processed automatically to measure the spinal cord, gray matter, and white matter cross-sectional areas. A statistical analysis assessed the difference in cross-sectional areas between patients with amyotrophic lateral sclerosis and controls, correlations between spinal cord and gray matter atrophy to clinical disability at baseline and at 1 year, and prediction of clinical disability at 1 year. RESULTS: Gray matter atrophy was more sensitive to discriminate patients with amyotrophic lateral sclerosis from controls (P = .004) compared with spinal cord atrophy (P = .02). Gray matter and spinal cord cross-sectional areas showed good correlations with clinical scores at baseline (R = 0.56 for gray matter and R = 0.55 for spinal cord; P < .01). Prediction at 1 year with clinical scores (R2 = 0.54) was improved when including a combination of gray matter and white matter cross-sectional areas (R2 = 0.74). CONCLUSIONS: Although improvements over spinal cord cross-sectional areas were modest, this study suggests the potential use of gray matter cross-sectional areas as an MR imaging structural biomarker to monitor the evolution of amyotrophic lateral sclerosis.

Dopamine D3 receptors expressed by all mesencephalic dopamine neurons.

A polyclonal antibody was generated using synthetic peptides designed in a specific sequence of the rat D(3) receptor (D(3)R). Using transfected cells expressing recombinant D(3)R, but not D(2) receptor, this antibody labeled 45-80 kDa species in Western blot analysis, immunoprecipitated a soluble fraction of [(125)I]iodosulpride binding, and generated immunofluorescence, mainly in the cytoplasmic perinuclear region of the cells. In rat brain, the distribution of immunoreactivity matched that of D(3)R binding, revealed using [(125)I]R(+)trans-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)amino] tetralin ([(125)I]7-trans-OH-PIPAT), with dense signals in the islands of Calleja and mammillary bodies, and moderate to low signals in the shell of nucleus accumbens (AccSh), frontoparietal cortex, substantia nigra (SN), ventral tegmental area (VTA) and lobules 9 and 10 of the cerebellum. Very low or no signals could be detected in other rat brain regions, including dorsal striatum, or in D(3)R-deficient mouse brain. Labeling of perikarya of AccSh and SN/VTA appeared with a characteristic punctuate distribution, mostly at the plasma membrane where it was not associated with synaptic boutons, as revealed by synaptophysin immunoreactivity. In SN/VTA, D(3)R immunoreactivity was found on afferent terminals, arising from AccSh, in which destruction of intrinsic neurons by kainate infusions produced a loss of D(3)R binding in both AccSh and SN/VTA. D(3)R-immunoreactivity was also found in all tyrosine hydroxylase (TH)-positive neurons observed in SN, VTA and A8 retrorubral fields, where it could represent D(3) autoreceptors controlling dopamine neuron activities, in agreement with the elevated dopamine extracellular levels in projection areas of these neurons found in D(3)R-deficient mice.

Physicochemical evidence for the existence of two pyridoxal 5'-phosphate binding sites on glutamate dehydrogenase and characterization of their functional role.

Kinetic studies of pyridoxal 5'-phosphate binding to glutamate dehydrogenase (EC 1.4.1.3) has provided evidence for two specific binding sites, chemically identified as Lys 126 and Lys 333. Use of protecting ligands permitted the selective modification of only one of these lysines, and showed that (1) Lys 333 modification results in depolymerisation of the enzyme into active hexamers; (2) Lys 126-modified enzyme was 92% inactivated. The residual activity was desensitized to GTP. The inactivation process was cooperative, maximum inactivation occurring as soon as half of the Lys 126 were modified.

Sensitivity of Na+-coupled D-glucose uptake, Mg2+-ATPase and sucrase to perturbations of the fluidity of brush-border membrane vesicles induced by n-aliphatic alcohols.

The aim of our work is to show the importance of the role of hydrophobic bonds in maintaining Mg2+-ATPase or sucrase activity and Na+-coupled D-glucose uptake normal for the brush border of rat enterocytes. The activity of the two enzymes and the D-glucose uptake were therefore measured under the action of n-aliphatic alcohols and related to the fluidity determined by ESR. Three concentrations were used for the first eight alcohols, those of octanol being about 1500-times lower than those of methanol. For each alcohol the D-glucose uptake and the fluidity were linear functions of the logarithm of the concentration, the linear regressions being practically parallel and equidistant. The concentrations (C) of the eight alcohols inhibiting the D-glucose uptake by 80% were similar to those increasing the membrane fluidity by 3%. The linear relationship which existed in both cases between log 1/C and log P, P being octanol/water partition coefficients of the alcohols, was evidence of great sensitivity to the hydrophobic effect of the alcohols. Only the first alcohols, however, produced any notable inhibition of Mg2+-ATPase and sucrase. Hydrophobic bonds are thus shown to have little influence in maintaining the activity of Mg2+-ATPase and sucrase, but they modulate the Na+-coupled D-glucose uptake.

The digital pen and paper. Evaluation and acceptance of a new data acquisition device in clinical settings.

OBJECTIVES: To evaluate the efficiency and acceptance of digital pen and paper technology for real-time clinical data acquisition. METHODS: A prospective interventional unblinded study involving consecutive patients in two clinical settings during a defined time-frame was proposed. The first trial was designed as a stress test to evaluate acceptance in a workload-intensive environment. Acceptance was assessed using observations and a satisfaction questionnaire. The second trial was intended to determine the reliability of data acquisition in a controlled environment. Reliability was assessed by comparing the performance of the digital pen against scanner analysis and a double human blinded acquisition. RESULTS: Overall, users were satisfied with the use of the digital pen (median 3 on a Likert-scale (-5, 5)). Without any specific user training, successful data acquisition was greater than 80%. Use of this technology required less adaptation than standard computer devices, and was easy to learn and use. Ergonomic problems shaded the perception of the technology by inducing an increased cognitive load. Digitalized data was missing either because of a bug or due to lack of data validation. The reliability obtained with the digital pen was significantly lower to that obtained with the scanner. CONCLUSIONS: Natural technology such as the digital pen proved to be a good tool in stressful clinical environments without interfering with the normal workload or increasing the time for data acquisition. However, in order to improve quality of data acquisition, designing acquisition forms specifically for the use of digital pens is of paramount importance.

Effect of long-term therapy with fasidotril, a mixed inhibitor of neprilysin and angiotensin-converting enzyme (ACE), on survival of rats after myocardial infarction.

OBJECTIVE: Two hormonal systems with opposite effects are activated in congestive heart failure: the renin-angiotensin system that promotes vasoconstriction, cardiac hypertrophy and salt retention, and the atrial natriuretic factor (ANF), which has vasorelaxant and natriuretic effects. It could be of therapeutic interest to associate prevention of angiotensin II formation, by inhibition of angiotensin I-converting enzyme (ACE), with potentiation of the ANF effects, by inhibition of neprilysin (NEP). METHODS: The effects of long-term therapy with fasidotril, a mixed NEP/ACE inhibitor, were assessed in rats submitted to coronary artery ligation. Twenty-four hours after ligation, 172 rats were assigned to either placebo or fasidotril therapy (180 mg/kg/day, orally) for 40 weeks. The date of spontaneous death was recorded, myocardial infarct size was determined and rats were classified as having small, moderate or large infarcts. RESULTS: In rats with moderate infarcts, fasidotril prolonged survival, 50% of the control rats dying during the 40-week observation period compared with 30% of treated rats (P = 0.04, log-rank test)). In rats with large infarcts, mortality was significantly reduced during the initial 25 weeks of therapy, during which 23.5% of animals died compared to 53.8% in untreated rats (P = 0.015). Cardiac hypertrophy was significantly attenuated by fasidotril for the three infarct sizes. Plasma renin activity was not increased by therapy, which presumably reflected the inhibition of renal renin secretion by endogenous ANF. Fasidotril therapy had no significant effects on arterial blood pressure and heart rate. CONCLUSION: In addition to its beneficial effects on survival and cardiac hypertrophy, the lack of hypotensive effect of fasidotril is of interest by reducing the risk of renal hypoperfusion and differentiates the mixed inhibitor from selective ACE inhibitors.

Effect of sinorphan, an enkephalinase inhibitor, on plasma atrial natriuretic factor and sodium urinary excretion in cirrhotic patients with ascites.

We examined the acute effects of sinorphan, an inhibitor of enkephalinase, on plasma atrial natriuretic factor (ANF) and urinary sodium excretion in cirrhotic patients with ascites. A single oral dose of sinorphan (100 or 30 mg in 11 and 5 patients, respectively) was administered against placebo according to a double blind cross-over protocol. Basal plasma ANF levels varied over a large range between 2.6-79 pmol/L. Sinorphan, at a dose of 100 mg, inhibited 70% of plasma enkephalinase activity 60 min after ingestion and elicited simultaneously an increase in plasma ANF and cGMP levels 1.8 and 1.5 times basal values, respectively. There was a transient increase in sodium urinary output without a change in creatinine clearance over the initial 2-h period following drug administration. An increase in urinary cGMP was also observed on a longer period of 6 h. Plasma aldosterone decreased significantly, but the lowest concentration was reached 1 h later than the peak of plasma ANF. Mean blood pressure and PRA were unmodified. The effects of 30 mg sinorphan on plasma ANF, cGMP, and aldosterone were also significant, but less marked than those of the higher dose. Therefore, enkephalinase inhibition transiently increases sodium urinary excretion in cirrhotic patients with ascites via a mechanism that is likely to imply reduction of ANF catabolism. These results suggest that ANF could play a role in the control of sodium homeostasis in liver cirrhosis with ascites.

Detection of the tripeptide Tyr-Gly-Gly, a putative enkephalin metabolite in brain, using a sensitive radioimmunoassay.

A sensitive and specific radioimmunoassay has been developed for YGG. The tripeptide was previously derivatised with p-benzoquinone to prepare the immunogen and the 125I tracer as well as in samples submitted to the RIA. The sensitivity is about 1 nM as compared with 8000 nM for underivatised YGG. Measurable amounts of endogenous YGG immunoreactivity, co-eluting in HPLC with authentic YGG, were detected in mouse striatal extracts.

Na+-coupled D-glucose uptake and membrane order of enterocyte brush border membrane vesicles, under the effect of a series of N-phenylcarbamates.

The importance of the hydrophobic effect of exogenous substances and of modifications of membrane order on D-glucose uptake are still poorly defined. Our results show that the concentrative Na+ -coupled D-glucose uptake of rat enterocyte brush border membrane vesicles is inhibited by N-phenylcarbamates increase the membrane order. However, since the concentrations required for membrane order increase are much greater than those active on D-glucose uptake, the effects on lipid order cannot be responsible for the inhibition of D-glucose uptake. Measurements of D-glucose uptake under conditions of Na+ equilibrium show that these carbamates do not act directly on the carrier but indirectly by favouring the dissipation of the Na+ gradient.

Characterisation of enkephalinase (EC 3.4.24.11) activity on various leukemic cells expressing the common acute lymphocytic leukemia antigen (CALLA).

The deduced amino acid sequences of CALLA, a cell surface marker of human acute lymphocytic leukemia, and human enkephalinase (neutral endopeptidase, EC 3.4.24.11) were recently reported to be almost identical. We show that membranes of CALLA+ cells of the REH lymphoblastic cell line as well as blast cells derived from the blood or bone marrow of patients with acute lymphocytic leukemia display high enkephalinase activity. This activity was abrogated by several enkephalinase inhibitors at concentrations closely similar to those required to inhibit pure human enkephalinase. However, these compounds did not significantly modify the rate of REH cell proliferation in vitro. Hence, the functional role, if any, of the high peptidase activity in lymphoblastic cells remains to be established.

Major localization of aminopeptidase M in rat brain microvessels.

The localization of two enkephalin-hydrolysing aminopeptidases i.e. aminopeptidase M (aminopeptidase N, EC 3.4.11.2) relatively insensitive to puromycin (Ki = 78 microM), and a puromycin-sensitive aminopeptidase (Ki = 1 microM) was studied in rat brain. The two aminopeptidases were differentially identified and/or localized using polyclonal anti-aminopeptidase M antibodies displaying anticatalytic activity and the inhibitors puromycin, bestatin and amastatin. Microvessels represent a major localization of cerebral aminopeptidase M as shown by the intense immunostaining of their walls in sections from various regions as well as in a fraction isolated from cerebral cortex homogenates by a sieving procedure. As compared to the starting homogenate, aminopeptidase M activity was enriched about twenty fold in this microvascular fraction. Aminopeptidase M was identified in this fraction by comparing the inhibitory potencies of antibodies and peptidase inhibitors towards the hydrolysis of [tyrosyl-3,5-3H, Met5]enkephalin to those found for the purified enzyme. A rather high aminopeptidase M activity was also localized in choroid plexuses. Following differential and gradient centrifugation analysis of cerebral cortex homogenates, aminopeptidase M activity was also enriched (by five to six fold) in fractions containing synaptic membranes. No significant soluble aminopeptidase M activity could be detected. These data suggest a dual localization of cerebral aminopeptidase M in microvessels and synaptic membranes consistent with its roles in preventing the access of circulating peptides to brain as well as in inactivating neuropeptides released from cerebral neurones. In comparison, puromycin-sensitive aminopeptidase activity, which is about 100 fold higher than aminopeptidase M activity in brain, was relatively low in microvessels and non-detectable in fractions enriched in synaptic membranes, being almost entirely restricted to soluble fractions.

Inhibition of Ca2+ sequestration in foetal liver microsomes by carbon tetrachloride and bromotrichloromethane.

The purpose of the present work is to establish to what extent the calcium uptake of foetal liver microsomes can be modified, as in the adult, by classical hepatotoxins. The administration of liver toxins (BrCCl3, CCl4) to the pregnant rat or their addition to foetal and maternal liver microsome preparations causes a decrease in the level of cytochrome P-450 and a drop in the calcium storage capacity of microsomes. Lipid peroxidation of membrane phospholipids is observed in the mother but not in the foetus. On the 20th day of gestation, the foetal liver shows cytochrome P-450 dependent metabolic activity and constitutes a good model illustrating the hypothesis of calcium pump inhibition by .CCl3 radicals without lipoperoxidation.