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Biomedical subjects

M David

Publications and source records attributed to M David.

At least 163 records · Page 9Linked to original sources
PubMed1999

Follicular cutaneous T-cell lymphoma: a clinicopathological study of nine cases.

Nine patients with follicular cutaneous T-cell lymphoma (CTCL), a recently described variant of lymphoma, are presented. On the basis of clinical manifestations and disease course, three groups of patients were distinguished: (i) two patients with follicular CTCL not associated with conventional lesions of mycosis fungoides (MF) and showing no evolution towards MF in follow-up periods of 3 and 6 years; (ii) one patient with follicular CTCL that evolved into conventional MF within 3 years; (iii) six patients showing conventional MF lesions either before or concurrently with the follicular lesions and thus representing follicular CTCL of the true MF type. The follicular lesions included hair-devoid patches or plaques with spiky hyperkeratotic papules (four patients), keratosis pilaris-like lesions (four), comedo-like lesions (four), follicular papules with alopecia (three) and milia-like lesions (three). Histopathological examination showed perifollicular and intrafollicular lymphocytes, without mucin deposition and with minimal or no involvement of the overlying epidermis. Significant syringotropism was also observed in three cases. Immunohistochemical analysis showed the predominance of CD4 + T cells, deletion of CD7 in some cases, Ki-67 + lymphocytes confined mainly to the follicular epithelium, and expression of keratinocyte intercellular adhesion molecule-1 exclusively in the hair follicle. T-cell receptor gamma gene rearrangement was positive in the one case studied from each group. Different treatment modalities were employed, the most commonly used as monotherapy being phototherapy: psoralen ultraviolet A in four patients, two of whom showed a complete clinical and histopathological remission, and ultraviolet B in one patient, who showed a complete remission (both clinical and histopathological). This study indicates that follicular CTCL is more common than reflected in the literature, has heterogeneous clinical manifestations, and is either an expression of or closely related to MF. The influence of the follicular involvement on the therapeutic response remains to be clarified. However, our therapeutic experience clearly suggests that some patients with follicular CTCL can benefit from phototherapy.

Adult↗
PubMed1999

Perivalvular abscesses associated with endocarditis; clinical features and prognostic factors of overall survival in a series of 233 cases. Perivalvular Abscesses French Multicentre Study.

AIMS: The purposes of this study were to determine the clinical features and to identify prognostic factors of abscesses associated with infective endocarditis. METHODS AND RESULTS: During a 5-year period from January 1989, 233 patients with perivalvular abscesses associated with infective endocarditis were enrolled in a retrospective multicentre study. Of the patients, 213 received medical surgical therapy and 20 medical therapy alone. No causative microorganism could be identified in 31% of cases. Sensitivity for the detection of abscesses was 36 and 80%, respectively using transthoracic and transoesophageal echocardiography. Surgical treatment consisted of primary suture of the abscess (38%), insertion of a felt aortic or mitral ring using Teflon or pericardium (42%), or debridment of the abscess cavity (20%). The 1 month operative mortality was 16%. Actuarial rates for overall survival at 3 and 27 months in operated patients were 75 +/- 10% and 59 +/- 11%, respectively. Increasing patient age, staphylococcal infection, and fistulization of the abscess were found to be independent risk factors in both 1 month and overall operative mortality. Renal failure was a risk factor predictive of operative mortality at 1 month, whereas uncontrolled infection and circumferential abscess were regarded as risk factors predictive of overall operative mortality. CONCLUSION: The data determined prognostic factors of abscesses associated with infective endocarditis.

Abscess↗
PubMed1999

Differential expression of p53 and Ki-67 proteins in classic and iatrogenic Kaposi's sarcoma.

In many neoplasms, the finding p53 immunoreactivity correlates with striking cytologic atypia, a high tumor cell proliferation rate, and poor prognosis. The literature regarding p53 and Ki-67 (a nuclear proliferation-associated antigen) immunoreactivity in Kaposi's sarcoma is limited. We aimed to: (1) evaluate the role of p53 in the development of Kaposi's sarcoma; (2) determine whether there is a correlation between p53 and Ki-67 protein expression; and (3) determine possible differences between classical Kaposi's sarcoma, known usually to have a benign course, and iatrogenic Kaposi's sarcoma, the course of which is unpredictable, by studying the differential expression of p53 and Ki-67. Among 26 cases of classic KS and 19 of iatrogenic KS, 12 were classified histopathologically as early type and 33 as mixed or spindle-cell type. P53 and Ki-67 immunoreactivity correlated significantly with the histopathologic stage of KS (r=0.63, p=0.0001; r=0.42, p=0.0084, respectively). P53 was not detected in any of the cases in an early histopathologic stage but was present in 55% of the cases in a more advanced stage. The spindle cells increased in proportion with the histopathologic progression and were more often positive (p=0.019) and displayed more extensive staining than the endothelial cells (p=0.0001). There was a strong positive correlation between p53 and Ki-67 protein expression (r=0.43, p=0.0087). There was no correlation between the expression of either p53 or Ki-67 and the extent of the eruption. The expression of p53 and Ki-67 was significantly lower in iatrogenic cases than in the classic cases (p=0.009, p=0.0014, respectively), although no statistical difference was found between the histopathologic stages in the two clinical forms of KS. P53 immunoreactivity was detected in 79% of the cases of classic Kaposi's sarcoma in the mixed or spindle cell stage but in only 21.5% of the iatrogenic cases showing the same histopathologic stage (p=0.001), and the percentage of spindle cells as well as the endothelial cells expressing p53 was higher in the classic cases than in the iatrogenic cases (p=0.0032, p=0.0142, respectively). We conclude that p53 immunoexpression is a marker of tumor progression in classic Kaposi's sarcoma but not in most cases of iatrogenic Kaposi's sarcoma. The proliferative activity of the tumor cells in classic Kaposi's sarcoma is much higher than in iatrogenic Kaposi's sarcoma. Our work implies that the molecular steps involved in classic and iatrogenic Kaposi's sarcoma differ.

Aged↗
PubMed1999

Intrapulmonary artery and intrabronchial migration and extraction of a fragment of J-shaped atrial pacing catheter.

A fragment of a fractured Telectronics Atrial Accufix 330-801 lead asymptomatically perforated the adjacent bronchus and was detected on routine chest X-ray. The metallic fragment was located by chest CT scan and bronchial fluoroscopy to lie between the right lobar bronchus and the pulmonary artery, confirming bronchial perforation. The foreign body was removed without complication by direct visualisation with rigid bronchoscopy.

Bronchi↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗