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Biomedical subjects

M David

Publications and source records attributed to M David.

At least 109 records · Page 6Linked to original sources
PubMed2001

A questionnaire for the assessment of pruritus: validation in uremic patients.

A questionnaire was constructed for the evaluation and measurement of pruritus. The questionnaire, based on the short form of the McGill Pain Questionnaire, was tested in 145 patients suffering from uremic pruritus and currently undergoing hemodialysis treatment in 3 centers. The newly developed questionnaire proved to be reliable and provided valid data on the sensory, affective and overall intensity of uremic pruritus. The data suggest that uremic pruritus tends to be prolonged, frequently intense and a major source of distress to the patient. Dialysis was not found to influence the pruritus. The questionnaire may also be useful in pruritus secondary to other causes.

Adult↗
PubMed2001

A familial case of congenital hypothyroidism caused by a homozygous mutation of the thyrotropin receptor gene.

Most of the time congenital hypothyroidism appears as a sporadic disease. In addition to the rare defects in hormonosynthesis associated with goiters, the causes of congenital hypothyroidism include agenesis and ectopy of the thyroid gland. The study of some familial cases has allowed the identification of a few genes responsible for congenital hypothyroidism. We report here a familial case of congenital hypothyroidism, transmitted as a recessive trait, and caused by a homozygous mutation in the thyrotropin receptor (TSH-R). The initial diagnosis of thyroid agenesis, based on the absence of tracer uptake on scintiscan, was incorrect, because ultrasound examination identified severely hypoplastic thyroid tissue in the cervical region.

Congenital Hypothyroidism↗
PubMed2001

Synthesis of diverse 4,5-dihydro-3(2H)-pyridazinones on Wang resin.

An efficient solid-phase synthesis of structurally diverse 4,5-dihydro-3(2H)-pyridazinones is described using readily available substituted 4-oxo-butanoic acids. Polymer-supported gamma-keto-esters prepared from Wang resin reacted with several hydrazines to afford the corresponding hydrazones. A protocol developed in mild conditions without isolating the intermediate hydrazone led to pyridazinones in good yields after a cyclization cleavage approach. This successful strategy represents an attractive method for a rapid synthesis of heterocyclic libraries for biological evaluation.

Butyrates↗
PubMed2001

Fracture embolization of a Tekna mitral prosthesis: case report.

The modified Duromedics-Tekna bileaflet pyrolitic carbon mechanical prosthesis was reintroduced by Baxter in 1990. This report details the first case of sudden leaflet fracture of a Tekna mitral valve five years after implantation, which was managed successfully by replacement with a St. Jude Medical mechanical prosthesis. The fracture had occurred transversely, with the fragments embolizing to the terminal aortic bifurcation and the left common femoral artery. These were localized by computed tomography and removed two days after valve replacement.

Aorta↗
PubMed2001

[Cardiogenic shock complicating extensive infarction with ventricular septal defect. Circulatory assistance and heart transplantation].

A 47 year old man had a massive anterior myocardial infarction with cardiogenic shock with a left parasternal murmur. Coronary angiography showed occlusion of the left anterior descending artery for which angioplasty resulted in failure. There was antero-lateral-apical akinesia and a ventricular septal defect (VSD) with a left-right shunt (Qp/Qs = 1.54). Persistence and aggravation of haemodynamic instability led to intra-aortic balloon pumping with inotropic pharmacological support followed by biventricular assistance with a MEDOS device. Under transoesophageal echocardiographic monitoring, the outcome was marked over 7 days by the progressive increase in the shunt volume of the VSD, a decrease of drainage and injection flow, progressive increase in spontaneous contrast echos followed by the presence of fibrin in the cardiac chambers and canulae, the presence of thrombus in the external ventricles, blockage of the right external valve which only opened after increasing the degree of anticoagulation, and, finally, cardiac tamponade which required drainage before the patient's state improved. On the 8th day, the patient being stable with a normal neurological status, the availability of a donor heart led to the decision to transplant, which was carried out without complications. This case poses the problem of cardiac assist devices and their daily monitoring, and then that of cardiac transplantation in this indication.

Assisted Circulation↗
PubMed2001

Cyclic GMP-dependent protein kinase activation and induction by exisulind and CP461 in colon tumor cells.

These studies report on the activation and induction of cGMP-dependent protein kinase (PKG) by exisulind and analogs and test the hypothesis that PKG is involved in the induction of apoptosis in colon tumor cells. Exisulind and analogs are proapoptotic drugs developed as inhibitors of cGMP phosphodiesterase gene families 5 and 2 that have been shown to sustain increased cGMP in SW480 and HT29 cells. At concentrations that induced apoptosis, both exisulind and CP461 increased PKG activity in SW480 cell supernatants. PKG activation was dose-dependent and sustained. Activation of PKG by exisulind and analogs was also seen in the colon tumor cell lines HT29, T84, and HCT116. The guanylyl cyclase activators YC-1 and guanylin increased PKG activity secondary to increased cellular cGMP and induced apoptosis in colon tumor cells. Exisulind and CP461 had no direct effect on purified PKG activity or on basal and stimulated PKG activity from cell supernatants. An additional effect of exisulind after 8 h of drug treatment was a dose-dependent increase of PKG Ibeta protein expression. beta-Catenin, a potential new substrate for PKG, whose regulation influences apoptosis, was phosphorylated by PKG in vitro. 32P-labeled cells treated with exisulind showed increased phosphorylation of beta-catenin. These data indicate that exisulind and analogs activate and induce PKG, resulting in increased phosphorylation of beta-catenin and enhanced apoptosis to promote colon tumor cell death.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

The glucocorticoid receptor and STAT6 physically and functionally interact in T-lymphocytes.

In lymphocytes, glucocorticoids (GC)- and interleukin-4-signaling pathways are known to interact, as evidenced by inhibition of IL-4-mediated proliferation by dexamethasone or suppression of GC-induced apoptosis by IL-4. In this study, we characterized the molecular basis for this reciprocal interference. We report that, in murine CTLL-2 cells, IL-4 inhibits GC-induced MMTV (mouse mammary tumor virus) promoter transactivation, and that GC suppress IL-4-induced transactivation of a STAT6 (signal transducers and activators of transcription 6)-responsive promoter without affecting IL-4-stimulated STAT6 DNA-binding. Moreover, we evidenced a physical association between GC receptor and STAT6, which proved to be functionally relevant, since STAT6 overexpression increased the IL-4 inhibitory effect on GC-induced MMTV transactivation.

Animals↗
PubMed2000

Hydrophobic amino acid residues are critical for the immunodominant epitope of the Goodpasture autoantigen. A molecular basis for the cryptic nature of the epitope.

Goodpasture (GP) autoimmune disease is caused by autoantibodies to type IV collagen that bind to the glomerular basement membrane, causing rapidly progressing glomerulonephritis. The immunodominant GP(A) autoepitope is encompassed by residues 17-31 (the E(A) region) within the noncollagenous (NC1) domain of the alpha 3(IV) chain. The GP epitope is cryptic in the NC1 hexamer complex that occurs in the type IV collagen network found in tissues and inaccessible to autoantibodies unless the hexamer dissociates. In contrast, the epitope for the Mab3 monoclonal antibody is also located within the E(A) region, but is fully accessible in the hexamer complex. In this study, the identity of residues that compose the GP(A) autoepitope was determined, and the molecular basis of its cryptic nature was explored. This was achieved using site-directed mutagenesis to exchange the alpha3(IV) residues in the E(A) region with the corresponding residues of the homologous but non-immunoreactive alpha1(IV) NC1 domain and then comparing the reactivity of the mutated chimeras with GP(A) and Mab3 antibodies. It was shown that three hydrophobic residues (Ala(18), Ile(19), and Val(27)) and Pro(28) are critical for the GP(A) autoepitope, whereas two hydrophilic residues (Ser(21) and Ser(31)) along with Pro(28) are critical for the Mab3 epitope. These results suggest that the cryptic nature of the GP(A) autoepitope is the result of quaternary interactions of the alpha 3, alpha 4, and alpha 5 NC1 domains of the hexamer complex that bury the one or more hydrophobic residues. These findings provide critical information for understanding the etiology and pathogenesis of the disease as well as for designing drugs that would mimic the epitope and thus block the binding of GP autoantibodies to autoantigen.

Amino Acid Sequence↗
PubMed2000

Porphyrin analogues as novel antagonists of fibroblast growth factor and vascular endothelial growth factor receptor binding that inhibit endothelial cell proliferation, tumor progression, and metastasis.

Fibroblast growth factors (FGFs) and vascular endothelial growth factor (VEGF) play a pivotal role in the multistep pathway of tumor progression, metastasis, and angiogenesis. We have identified a porphyrin analogue, 5,10,15,20-tetrakis(methyl-4-pyridyl)-21H,23H-porphine-tetra -p-tosylate salt (TMPP), as a potent inhibitor of FGF2 and VEGF receptor binding and activation. TMPP demonstrated potent inhibition of binding of soluble FGF receptor 1 (FGFR1) to FGF2 immobilized on heparin at submicromolar concentrations. TMPP inhibits binding of radiolabeled FGF2 to FGFR in a cell-free system as well as to cells genetically engineered to express FGFR1. Furthermore, TMPP also inhibits the binding of VEGF to its tyrosine kinase receptor in a dose-dependent manner. In an in vitro angiogenic assay measuring the extent of endothelial cell growth, tube formation, and sprouting, TMPP dramatically reduced the extent of the FGF2-induced endothelial cell outgrowth and differentiation. In a Lewis lung carcinoma model, mice receiving TMPP showed a marked inhibition of both primary tumor progression and lung metastases development, with nearly total inhibition of the metastatic phenotype upon alternate daily injections of TMPP at 25 microg/g of body mass. Finally, novel meso-pyridylium-substituted, nonsymmetric porphyrins, as well as a novel corrole-based derivative, with >50-fold increase in activity in vitro, had a significantly improved efficacy in blocking tumor progression and metastasis in vivo.

Animals↗
PubMed2000

Distinct mechanisms of STAT phosphorylation via the interferon-alpha/beta receptor. Selective inhibition of STAT3 and STAT5 by piceatannol.

Interferon-alpha (IFNalpha) can activate several members of the signal transducers and activator of transcription (STAT) transcription factor family, a process that requires the tyrosine kinases Jak1 and Tyk2. Here we provide evidence that IFNalpha-mediated activation of various STAT proteins is regulated by distinct mechanisms. Piceatannol, previously reported as a Syk/ZAP70-specific kinase inhibitor, selectively inhibits the tyrosine phosphorylation of STAT3 and STAT5, but not of STAT1 and STAT2. This inhibition is paralleled by the loss of Jak1 and IFNAR1 tyrosine phosphorylation in response to IFNalpha, whereas Tyk2 and IFNAR2 tyrosine phosphorylation is unaffected. Last, the IFNalpha-induced serine phosphorylation of STAT1 and STAT3 is not inhibited by piceatannol but is sensitive to the Src kinase-specific inhibitor PP2. Thus, our results not only demonstrate that the IFNalpha/beta receptor utilizes distinct mechanisms to trigger the tyrosine phosphorylation of specific STAT proteins, but they also indicate a diverging pathway that leads to the serine phosphorylation of STAT1 and STAT3.

Cell Line↗
PubMed2000

Stroke in children: the coexistence of multiple risk factors predicts poor outcome.

OBJECTIVE: To characterize the risk factors for stroke in children and their relationship to outcomes. METHODS: We reviewed charts of children with ischemic and hemorrhagic stroke seen at Hopital Sainte-Justine, Montreal between 1991 and 1997. RESULTS: We found 51 ischemic strokes: 46 arterial and 5 sinovenous thromboses. Risk factors were variable and multiple in 12 (24%) of the 51 ischemic strokes. Ischemic stroke recurred in 3 (8%) patients with a single or no identified risk factor and in 5 (42%) of 12 patients with multiple risk factors (p = 0.01). We also found 21 hemorrhagic strokes, 14 (67%) of which were caused by vascular abnormalities. No patient with hemorrhagic stroke had multiple risk factors. Hemorrhagic stroke recurred in two patients (10%). Outcome in all 72 stroke patients was as follows: asymptomatic, 36%; symptomatic epilepsy or persistent neurologic deficit, 45%; and death, 20%. Death occurred more frequently in patients with recurrent stroke (40%) than in those with nonrecurrent stroke (16%). CONCLUSIONS: Multiple risk factors are found in many ischemic strokes and may predict stroke recurrence. Recurrent stroke tends to increase rate of mortality. Because of the high prevalence and importance of multiple risk factors, a complete investigation, including hematologic and metabolic studies and angiography, should be considered in every child with ischemic stroke, even when a cause is known.

Adolescent↗
PubMed2000

Improvement of disseminated lymphangiomatosis with recombinant interferon therapy.

Disseminated lymphangiomatosis is a rare disorder with a poor prognosis. We present a case involving a 3-year-old boy who presented with pulmonary infiltrates, multiple lytic lesions of the ribcage, and small cystic lesions in the spleen. Open-lung and bone biopsies revealed disseminated lymphangiomatosis. Significant clinical and radiologic improvement were observed and persisted after 28 months of treatment with recombinant interferon alpha-2b (IFN alpha-2b). No significant toxicity has been observed.

Angiogenesis Inhibitors↗
PubMed2000

Quantitative comparison of cytokine mRNA and inflammatory responses in cutaneous late phase allergic reactions.

UNLABELLED: The aim of this study was to quantitatively compare expression of mRNA for IL-5 and IFN-gamma with the frequency of mRNA-positive cells, total and activated eosinophils, neutrophils, lymphocytes, and vessels expressing adhesion molecules. Replicate biopsies of skin LPR to pollen antigens (Ag) and control injection sites (B) at 6 and 24 h were assessed for: (1) mRNA for IL-5 and IFN-gamma by quantitative RT-PCR (QC-RT/PCR); (2) frequency of cells expressing mRNA for IL-5 and IFN-gamma by in situ hybridization (ISH); (3) inflammatory cells and adhesion molecule expression. More mRNA for IL-5 was found in Ag- than in B-injected sites at 6 and 24 h by both QC-RT/PCR and ISH. Small amounts of mRNA for IFN-gamma were detected in Ag sites by QC-RT/PCR at 6 and 24 h, but were not significantly different than at B sites. The frequency of IFN-gamma mRNA(+)cells was higher in Ag than in B sites at 6 h. There was no correlation between the amount if IL-5 detected by QC-RT/PCR and frequency of IL-5 mRNA(+)cells by ISH. These findings also did not correlate with the degree of inflammatory responses. IN CONCLUSION: (1) greater IL-5 than IFN-gamma deposition in Ag sites suggests Th(2)predominance in LPR; (2) lack of correlation between QC-RT/PCR and ISH findings may reflect varying mRNA content of inflammatory cells.

Adult↗
PubMed2000

Preoperative intraarterial thrombolysis before surgical revascularization for popliteal artery aneurysm with acute ischemia.

Because a popliteal artery aneurysm (PAA) generates emboli that progressively deteriorate the distal arterial network, they can constitute limb-threatening lesions. In 20 to 40% of cases, discovery of PAA coincides with sudden occlusion and resulting acute ischemia. In 40 to 60% of these patients, surgical revascularization fails and amputation is required. The objective of this prospective study was to assess the value of intraarterial thrombolysis to restore distal runoff before surgical revascularization. Between January 1, 1992 and December 31, 1996, we treated 15 PAA causing acute ischemia in 15 male patients with a mean age of 66.7 years (range, 44 to 87 years). Diagnosis was documented by clinical examination and ultrasound imaging. Intraarterial thrombolysis was performed under arteriographic control through a multiperforated catheter inserted by the anterograde femoral route to the thrombus. After an initial bolus of 100,000 U of urokinase, 600,000 to 1,600,000 U was continuously infused over a period of 6 to 18 hr. Heparin sodium was administered throughout thrombolysis. Surgical revascularization was performed within 1 to 4 days (mean, 2 days) after thrombolysis by exclusion and bypass in 14 cases and percutaneous transluminal angioplasty with stenting in 1 case. The ensuing results showed that, if performed carefully, intraarterial thrombolysis can safely prepare patients presenting with occluded PAA with acute ischemia for surgical revascularization to restore distal runoff. We use this combined technique routinely in our department. Morbidity is low in comparison with the risks of amputation.

Acute Disease↗
PubMed2000

Nitroglycerin application during cesarean delivery: plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns.

OBJECTIVE: We sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery. STUDY DESIGN: At the time of the uterine puncture incision, either 0. 25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1, 5, and 10 minutes after birth. RESULTS: Sixty-two patients were included in the pharmacokinetic study. Median maternal plasma levels 1 and 5 minutes after injection of 0.5 mg nitroglycerin were 80 and 3.2 ng/mL, respectively; median maternal plasma levels 1 and 5 minutes after injection of 0.25 mg nitroglycerin were 38 and 1.2 ng/mL, respectively. In the umbilical vein 1 minute after application of 0. 5 mg or 0.25 mg nitroglycerin, the plasma levels were 0.41 and 0.09 ng/mL, respectively, and in the umbilical artery they were 0.03 and 0.008 ng/mL, respectively. Circulatory parameters and Apgar scores in the neonates did not differ significantly from those found in the placebo group. CONCLUSION: The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates.

Adolescent↗
PubMed2000

Surgical outcome of traumatic rupture of the thoracic aorta.

BACKGROUND: The aim of this study was to point out the results of different techniques of spinal cord protection in surgically-treated patients with traumatic thoracic aorta (TTA). METHODS: A multicentric study was carried out involving 182 patients with TTA. Four patients died before surgery. Two patients were operated on without any investigation and 2 had no aortic tear at thoracotomy. The remaining 174 patients had aortic isthmus disruption and were included in the study. The mean age was 32.3+/-14.29 years with 126 men (72.4%) and 48 women (27.6%). Road accidents were causal in 163 patients (93.66%); polytraumatism was frequent. A standard chest roentgenogram led to a diagnosis which was confirmed with aortography in 94.8% of cases. Surgical repair of visceral lesions was performed in 52 patients (29.9%) for traumatic spleen, liver, diaphragm, mesentery, and gut. These operations were done before or after aortic operation in 21.3% and 8.6% of cases, respectively. Thirty-three patients (19%) died and 9 (5.2%) had paraplegia. Sixty-nine patients had clamp and sew technique (group 1). Ninety-three patients had different types of extracorporeal circulation (group 2), and 12 patients had Gott shunt (group 3). No difference appeared between the 3 groups according to mortality and paraplegia. But the sex ratio, age, visceral lesions, craniocerebral lesions, the type of aortic repair, and cross-clamp time were discriminative. RESULTS: The univariate analysis point out age, cross-clamp time, hemothorax, and anatomical type of aortic injury as the risk factors of death. This was confirmed by a multivariable test which retained age, cross-clamp time, and hemothorax as risk factors. When not diagnosed in time, TTA is serious and has a bad prognosis. In spite of a high mortality and morbidity, the surgical management has improved. Immediate operation and medullar protection are the stumbling block in this operation. CONCLUSIONS: Operation can be delayed in some cases, but one must take care of hemodynamic instability. This calls for a repair of the serious associated lesions first, or of a quick performing of a thoracotomy for ruptured aorta. The question remains, is it better to protect the spinal cord with the lower aortic perfusion and avoid the simple cross-clamp? Clinical studies give few answers to this question, and the best answer has not yet been given, as we lack prospective studies in this field.

Accidents, Traffic↗
PubMed2000

[Personal sports training in the management of obese boys aged 12 to 16 years].

OBJECTIVE: Estimation of both physical and psychological effects of an adapted physical training on children undergoing an obesity treatment. MATERIAL AND METHODS: The survey was carried out on 36 obese boys (ages = 12-16 years) who stayed in the medical center for at least four months. Eighteen of them were trained with the SELF method (the SELF-training is global, progressive, adapted to each boy, controlled and takes place within a ten-week period with five sessions a fortnight, each session lasting 30 to 40 minutes). The parameters that were studied concerned auxology, breathing function exploration, aerobic and anaerobic capacities, muscle strength and psychomotor qualities; the subjective effects of the training were estimated with a questionnaire about life quality, and the hand test. At inclusion the results were reported to a standard kind of population. At the end of the training the results of the 18 boys that were trained were compared to those of the 18 controls. RESULTS: Compared to a standard population, the obese children' aerobic capacity is diminished for the maximum power but is identical in absolute value for the VO2 max; their anaerobic capacities, muscle strength and psychomotor capacities are lower and their psyche is affected by the disease. After a three-month training period and after comparison with the 'control' group, there can be noticed a significant improvement in the psychomotor capacities, a major tendency for the improvement of the aerobic capacities and very positive effects on the psyche. CONCLUSION: SELF-training in association with dietetics appears to be very useful in the therapeutic care of obese children. For the follow-up at home it would need to be registered within the domain of physiotherapy.

Adolescent↗