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Biomedical subjects

M David

Publications and source records attributed to M David.

At least 127 records · Page 7Linked to original sources

Screening patch tests for pigmented contact dermatitis in Israel.

Pigmented contact dermatitis has been found to be caused by fragrances, cosmetics, washing powders, azo dyes in textiles, and rubber products in selected groups of patients. The aim of this study was to run screening patch tests in an unselected group of patients with pigmented contact dermatitis (n=29) encountered in our center over a 2-year period. The test series included the European standard, cosmetics, fragrance, Scandinavian photo, and personal products. 21 patients had a positive reaction in at least 1 of the series (total, 29 reactions): 16 - standard, 3 - cosmetics, 1 fragrance, 9 photo, and 1 - personal products; 16 (55%) had relevant results. We conclude that the highest yield for screening for pigmented contact dermatitis is achieved with the standard and photo series.

Adolescent↗

Atopic dermatitis and HTLV-1-associated myelopathy: associated or coincidental disorders?

Reports from Jamaica have indicated that some patients with infective dermatitis or atopic dermatitis (AD) are seropositive for antibodies to human T-lymphotropic virus type 1 (HTLV-1). We describe a 32-year-old Israeli woman with long-term AD and paresthesia in the distal parts of the extremities. Neurological examination revealed a positive Babinski's sign. HLA typing demonstrated that this patient has the common HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis haplotype for DRB1* DQB1*. The presence of HTLV-1 was demonstrated with polymerase chain reaction; HTLV-1-antibodies were detected by the Western blot method and by inoculation of the patient's peripheral blood mononuclear cells into F344 rats. This study confirms the presence of HTLV-1 antibodies and proviral genome in a patient with AD which later evolved into HAM/TSP. We cannot yet conclude whether these two diseases are associated or coincidental disorders.

Adult↗

Evaluation of gonadal function in 107 intersex patients by means of serum antimüllerian hormone measurement.

Fetal male sexual differentiation is driven by two testicular hormones: testosterone (synthesized by interstitial Leydig cells) and antimüllerian hormone (AMH; produced by Sertoli cells present in the seminiferous tubules). Intersex states result either from gonadal dysgenesis, in which both Leydig and Sertoli cell populations are affected, or from impaired secretion or action of either testosterone or AMH. Until now, only Leydig cell function has been assessed in children with ambiguous genitalia, by means of testosterone assay. To determine whether serum AMH would help in the diagnosis of intersex conditions, we assayed serum AMH levels in 107 patients with ambiguous genitalia of various etiologies. In XY patients, AMH was low when the intersex condition was caused by abnormal testicular determination (including pure and partial gonadal dysgenesis) but was normal or elevated in patients with impaired testosterone secretion, whereas serum testosterone was low in both groups. AMH was also elevated during the first year of life and at puberty in intersex states caused by androgen insensitivity. In 46,XX patients with a normal male phenotype or ambiguous genitalia, in whom the diagnosis of female pseudohermaphroditism had been excluded, serum AMH levels higher than 75 pmol/L were indicative of the presence of testicular tissue and correlated with the mass of functional testicular parenchyma. In conclusion, serum AMH determination is a powerful tool to assess Sertoli cell function in children with intersex states, and it helps to distinguish between defects of male sexual differentiation caused by abnormal testicular determination and those resulting from isolated impairment of testosterone secretion or action.

Adult↗

Role of the STAT1-SH2 domain and STAT2 in the activation and nuclear translocation of STAT1.

Interferon (IFN) induction of immediate-early response genes is mediated through the signal transducers and activators of transcription (STATs). Activation of STAT1 by IFNalpha or IFNgamma through its tyrosine phosphorylation involves members of the Jak tyrosine kinases. In addition, STAT2 is activated by IFNalpha, and, together with STAT1 and p48/ISGF3gamma, forms the transcription factor complex ISGF3. Previous findings suggested that the STAT1-SH2 domain, which is required for the homo- or heterodimerization of STAT1, also participates in the recruitment of STAT1 to the IFN-receptors, because mutations in the SH2-domain abolished STAT1 activation by IFNgamma. Furthermore, STAT2 was reported to be required for the activation of STAT1 by IFNalpha. We were able to induce STAT1 tyrosine phosphorylation by IFNalpha/beta in the absence of STAT2 or a functional STAT1-SH2 domain. In contrast, IFNgamma was unable to cause tyrosine phosphorylation of STAT1-(SH2:Arg --> Gln). Interestingly, although STAT1 was found in the nucleus in STAT2-deficient cells, the nuclear accumulation of the tyrosine phosphorylated SH2-mutant STAT1 was impaired. In summary, our results indicate that the SH2 domain of STAT1 is not required for its ligand-dependent activation by IFNalpha/beta. Moreover, tyrosine phosphorylation is not sufficient to target STAT1 to the nucleus; rather, dimerization appears to play a critical role in the subcellular distribution of STAT1.

Animals↗

Antiproliferative effects of SR31747A in animal cell lines are mediated by inhibition of cholesterol biosynthesis at the sterol isomerase step.

SR31747A is a new sigma ligand exhibiting immunosuppressive properties and antiproliferative activity on lymphocyte cells. Only two subtypes of sigma receptor, namely the sigma1 receptor and emopamil-binding protein, have been characterised molecularly. Only the sigma1 receptor has been shown to bind (Z)N-cyclohexyl-N-ethyl-3-(3-chloro4-cyclohexylphenyl)pro pen-2-ylamine hydrochloride (SR31747A) with high affinity. It was demonstrated that the SR31747A effect on the inhibition of T-cell proliferation was consistent with a sigma1 receptor-mediated event. In this report, binding experiments and sterol isomerase assays, using recombinant yeast strains, indicate that the recently cloned emopamil-binding protein is a new SR31747A-binding protein whose activity is inhibited by SR31747A. Sterol analyses reveal the accumulation of a delta8-cholesterol isomer at the expense of cholesterol in SR31747A-treated cells, suggesting that cholesterol biosynthesis is inhibited by SR31747A at the delta8-delta7 sterol isomerase step in animal cells. This observation is consistent with a sterol isomerase role of the emopamil-binding protein in the cholesterol biosynthetic pathway in animal cells. In contrast, there is no evidence for such a role of the sigma1 receptor, in spite of the structural similarity shared by this protein and yeast sterol isomerase. We have found that SR31747A also exerts anti-proliferative effects at nanomolar concentrations on various established cell lines. The antiproliferative activity of SR31747A is reversed by cholesterol. Sterol-isomerase overproduction enhances resistance of CHO cells. This last observation strongly suggests that sterol isomerase is implicated in the antiproliferative effect of the drug in established cell lines.

Animals↗

Interferon gamma activation of Raf-1 is Jak1-dependent and p21ras-independent.

Signal transduction through the interferongamma (IFNgamma) receptor involves the formation of a ligand-dependent multimolecular association of receptor chains (alpha and beta), Janus tyrosine kinases (Jak1 and Jak2), and the transcription factor (signal transducers and activators of transcription 1alpha (STAT1alpha)) in addition to activation of mitogen-activated protein kinases (MAPK). Interactions between components of the Jak/STAT cascade and the p21(ras)/Raf-1/MAPK cascade are unexplored. Treatment of HeLa cells with IFNgamma resulted in the rapid and transient activation of Raf-1 and MAPK. Parallel activation of cells resulted in essentially no enhancement of p21(ras) activation despite marked enhancement after treatment with epidermal growth factor. In HeLa (E1C3) and fibrosarcoma (U4A) cell lines, both of which are deficient in Jak1 kinase, Raf-1 activation by IFNgamma was absent. Reconstitution of Raf-1 activity was observed only with kinase active Jak1 in both cell lines. In COS cells, transient expression of wild type or kinase-inactive Jak1 coimmunoprecipitated with Raf-1, but activation of Raf-1 activity was only observed in cells expressing kinase-active Jak1. These observations suggest that a kinase-active Jak1 is required for IFNgamma activation of Raf-1 that is p21(ras)-independent.

Calcium-Calmodulin-Dependent Protein Kinases↗

Hemoglobins in Togolese newborns: Hb S, Hb C, Hb Bart's, and alpha-globin gene status.

The gene frequency of the most important hemoglobin (Hb) abnormalities is reported in a population of 171 Togolese newborns. Hb phenotypes, hematological parameters, and the more frequently described alpha-gene deletions were analyzed. Structural abnormalities of beta-globin were observed in 35.7% of the children with a gene frequency of 0.105 for beta(S) and 0.091 for beta(C). The frequency of the different alpha-globin genotypes was alpha alpha/ = 0.71, -alpha/ = 0.28, and alpha alpha alpha/ = 0.01. All of the individuals homozygous for the -alpha genotypes, and most of the heterozygous individuals, carried Hb Bart's. Within the alpha alpha/alpha alpha and the -alpha/alpha alpha groups, several individuals with or without Hb Bart's were found; they did not differ from the others by their red blood cell (RBC) parameters but by their levels of fetal hemoglobin (Hb F). The African alpha2 polymorphism marker, characterized by the replacement of G by TCGGCCC at position 7238 (EMBL HSHBA4, 1993) and of T 7174 by G, was found in 21 newborns. The mean value of Hb F was calculated for each genotype, the mean (G)gamma percentage was 69.4 +/- 4.0%, and the gene frequency of the AgammaT marker was 0.10; this marker was linked to the normal beta-globin cluster.

Blood Cell Count↗

Osteogenesis imperfecta with joint contractures: bruck syndrome.

We describe an Egyptian boy with osteogenesis imperfecta who was born with thumb contractures and bilateral antecubital pterygia. He was seen at 16 months of age with femur and tibial fractures, thoracic vertebral compression fractures, scoliosis and Wormian bones. The findings are consistent with a diagnosis of Bruck syndrome.

Abnormalities, Multiple↗

Incidence and risk factors of catheter-related deep vein thrombosis in a pediatric intensive care unit: a prospective study.

OBJECTIVE: To estimate the incidence and to characterize risk factors for central venous catheter (CVC)-related deep vein thrombosis (DVT) in a pediatric intensive care unit. STUDY DESIGN: Consecutive children admitted to a pediatric intensive care unit who required a CVC for more than 48 hours were examined by Doppler ultrasonography of the catheterized vein at days 2, 4, 6, or 7 after insertion and weekly thereafter until CVC removal. RESULTS: The incidence of CVC-related DVT was 18.3% (17 of 93) (95% confidence interval = 10.2% to 25.8%). Thromboses were diagnosed within the first 4 days of catheter placement for 15 of 17 CVC-related thromboses. Multivariate analysis showed that risk factors most predictive of CVC-related DVT were presence of a cancer (odds ratio = 17.23, 95% confidence interval = 1.5 to 194) and young age (odds ratio for age = 0.72, 95% confidence interval = 0.54 to 0.96). CONCLUSION: The frequency of CVC-related DVT is substantial in pediatric intensive care units. Risk is highest during the 4 days after insertion and decreases thereafter. The clinical impact, optimal prevention, and therapy of these thromboses remain to be determined.

Catheterization, Central Venous↗

Nitroglycerin to facilitate fetal extraction during cesarean delivery.

OBJECTIVE: To determine the efficacy of nitroglycerin in easing fetal extraction in elective cesarean deliveries in comparison with placebo and to collect maternal and fetal pharmacologic data after administration of nitroglycerin. METHODS: This randomized, double-blind clinical and descriptive pharmacokinetic study was carried out at the gynecology departments at Virchow Hospital and Charité Hospital (both university hospitals of Humboldt University, Berlin, Germany) between June 1994 and July 1996 in patients scheduled for elective cesarean delivery under general anesthesia. At the time of the uterine puncture incision, either 0.25 mg or 0.5 mg of nitroglycerin or a physiologic saline solution was administered as an intravenous bolus. Intraoperatively, maternal and neonatal pulse rates and blood pressure were monitored closely. The surgeons estimated reduction in uterine tone and the ease of fetal extraction by means of defined scales. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and from umbilical blood. RESULTS: Ninety-seven patients were included in the statistical evaluation of the study; 32 received 0.25 mg of nitroglycerin, 34 received 0.5 mg of nitroglycerin, and 31 received placebo. The evaluation of the surgeons' estimation revealed no significant difference in ease of fetal extraction (statistical power 0.7) and no significant reduction in uterine tone under treatment with both nitroglycerin dosages in comparison with placebo. Only substance-specific maternal side effects were noted. The neonates' conditions were not affected by administration of nitroglycerin. The median fetal-maternal ratio of venous nitroglycerin plasma levels was approximately 1:400 in the 0.25-mg nitroglycerin group and 1:160 in the 0.5-mg nitroglycerin group. Approximately 11-12 times more nitroglycerin was detected in the venous umbilical branch than in the arterial branch. CONCLUSION: Administration of nitroglycerin leads to no clinically relevant easing of fetal extraction, at least not in elective cesarean deliveries after the 34th week of gestation. With regard to pharmacokinetics, the measured median fetal-maternal venous nitroglycerin concentration was 1:400 in the 0.25-mg group and 1:160 in the 0.5-mg group.

Adult↗

Low-dose low-molecular-weight heparin (enoxaparin) is beneficial in lichen planus: a preliminary report.

BACKGROUND: Low-dose heparin devoid of anticoagulant activity inhibits T-lymphocyte heparanase activity, which is crucial in T-cell migration to target tissues. OBJECTIVE: The purpose of this study was to assess the efficacy of low-dose enoxaparin (Clexane), a low-molecular-weight heparin, as monotherapy in lichen planus. METHODS: Included in the study were 10 patients with widespread histopathologically proven lichen planus (LP) associated with intense pruritus of several months' duration. Patients were given 3 mg enoxaparin, subcutaneously once weekly; three patients received four injections, and seven patients received six injections. RESULTS: In nine patients the itch disappeared within 2 weeks. Within 4 to 10 weeks in eight of these patients, there was complete regression of the eruption with residual postinflammatory hyperpigmentation; in one patient, there was marked improvement. In one patient, no effect was observed. Of the four patients who also had oral LP, only one showed improvement. No side effects were observed in any of the patients. CONCLUSION: These findings indicate that enoxaparin may be a simple, effective treatment for cutaneous LP.

Adult↗

Detection of human herpesvirus-8 DNA in Kaposi's sarcomas from iatrogenically immunosuppressed patients.

BACKGROUND: Kaposi's sarcoma (KS) accounts for more than 5% of malignancies in immunosuppressed organ transplant patients (OKS). A new herpesvirus (HHV-8) was identified with high prevalence in biopsy specimens of AIDS-KS, endemic KS, and classic KS and in OKS. KS has also been associated with other underlying diseases in patients treated with corticosteroids, but this subset of KS has been reported to contain HHV-8 in only a few case reports. OBJECTIVE: In this larger study, we determined the prevalence of HHV-8 in seven patients of Jewish origin in whom KS developed during immunosuppressive therapy for different primary diseases (ISKS). METHODS: The study included HHV-8 DNA detection by polymerase chain reaction (PCR) coupled with Southern blot and sequence analysis as well as by in situ hybridization. RESULTS: HHV-8 sequences were detected by PCR with confirmation by Southern blot and sequence analysis in 100% of the ISKS samples. Direct sequencing revealed several previously unknown base changes within the 208 bp region from open reading frame 26 (ORF26[208]) of HHV-8 in ISKS. CONCLUSION: Ours is the largest known study describing the presence of HHV-8 in iatrogenic KS from immunosuppressed nontransplant patients and provides data of previously unknown sequence variations within the ORF26 of HHV-8 DNA.

Aged↗

-A new role for the pediatrician: the prevention of social violence-.

Social violence is a kind of violence which is applied by one individual to another. It is a stake in the field of public health because of an increasing number of children with such behaviors. In addition to environmental factors, the occurrence of abnormal social behavior before 9 years of age seems to precede social violence for the subsequent 20 years of life. One must therefore identify an inadequate attitude towards the parents and/or the teachers, or a poor child's self-esteem and self-respect. These phenomena are based on parental authority, on the ethical development of the child, on his verbalization capacity, on his socialization and his affective development. It is therefore important to stimulate ethical capacities and feelings in the child not only to provide autonomy but also to allow reflexive distinction of language, behavior and judgment, which enable him to understand, consider and respect other individuals.

Affect↗

A 5-year follow-up study of suicide attempts among French adolescents.

PURPOSE: The social, medical, and psychological outcomes of 552 adolescents hospitalized subsequent to an attempted suicide were assessed after an average 5-year follow-up period. METHODS: Evaluation took place by means of mailed questionnaires completed by the adolescents, their parents, and the general practitioner. Using regression analysis, responses were compared with those of a comparison group (n = 273). RESULTS: In the suicidal group, the mean annual mortality rate was seven-fold greater than in the general population of the same age. Education level was lower, and the consumption of alcohol, psychiatric hospitalizations, and contacts with the criminal justice system were more frequent than in the control group. No other variables explored were significantly different between the two groups. CONCLUSIONS: The results of this study carried out on a large sample of French suicidal adolescents tend to confirm results of previous studies performed in other countries. They show that the prognosis for the suicidal adolescent group is less favorable than that of the comparison group.

Adolescent↗

Use of the gel agglutination technique for determination of fetomaternal hemorrhage.

BACKGROUND: Adequate administration of Rh immune globulin requires an accurate determination of the number of D-positive cells in the circulation of D-negative women. Although several tests have been described for the detection of fetomaternal hemorrhage, there is still a need for a rapid, simple, and clinically relevant screening test. STUDY DESIGN AND METHODS: Serial dilutions of a monoclonal anti-D were incubated with stock solutions (0.2 mL) of adult D-negative red cells in the absence or presence of various amounts of fetal D-positive cells (0.1, 0.2, 0.3, 0.4, and 0.5%). After incubation, the supernatants were tested against D-positive red cells by using the new, gel agglutination technique (GAT). After the GAT was adapted to detect D-positive cells at concentrations of > or = 0.2 percent, unselected postpartum samples from D-negative women (n = 420) who delivered D-positive infants were analyzed by both the new test and the Kleihauer-Betke test (KBT). RESULTS: Three of a total of 420 postpartum samples were positive (> or = 0.4% fetal cells), and 406 were negative in both tests. One had 0.5-percent fetal cells in the KBT and gave negative results in the GAT. The latter test was, however, performed after administration of Rh immune globulin. The KBT gave false-positive results in two cases, because of hereditary persistence of hemoglobin F, and the GAT gave a false-positive reaction in one case because of a maternal weak D variant. In the remaining seven cases, the KBT results were only weakly positive (0.2%) and could not be attributed solely to D positive red cells. CONCLUSION: The GAT is suited for routine screening. It provides rapid and specific detection of D-positive red cells at clinically relevant concentrations. The test may (rarely) yield false-negative results due to insufficient administration of Rh immune globulin before testing.

Adult↗

The interest of surgical closure of patent foramen ovale after stroke: a preliminary open study of 8 cases.

The risk of stroke and the risk of recurrent strokes in patients with patent foramen ovale (PFO) need a prevention that still remains a therapeutic problem. There are 4 preventive treatments: anti-agregants, anti-coagulants, transcatheter closure, and surgical closure of PFO. The aim of this study was to demonstrate that surgical closure of PFO is safe and useful for prevention of strokes. Eight patients with stroke and PFO diagnosed by transesophageal echography (TEE) were prospectively selected for surgical closure. It was necessary to be younger than 70 years, not to have another cause of stroke, and to have either recurrent strokes or several ischemic lesions on MRI, isolated for PFO associated with an atrial septal aneurysm, and to have a Valsalva maneuver or cough inducing the stroke. For these reasons, these patients were considered to be an homogenous group with a strong relationship between the PFO and the stroke, and with a high risk of recurrence of stroke. The 8 patients had a direct suture of the PFO with a cardiopulmonary bypass. All patients were followed-up with clinical, MRI and TEE examinations during 12 months after surgery. No surgical complications were observed. After one year, without any anticoagulant treatment, no recurrent stroke or transient ischemic attack, no new ischemic lesions on MRI, nor neuropsychological disturbance were noted. No post-surgical inter-atrial right-to-left shunting was observed. In the absence of controlled studies to guide therapeutic options, our data suggest that surgical closure of PFO in patients with stroke, is safe and efficacious to prevent recurrent stroke without any anticoagulants in the first year of follow-up. Further studies are needed to evaluate the long-term role of surgical closure of PFO as an alternative to prolonged anti-thrombotic treatment.

Adult↗