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P David

Publications and source records attributed to P David.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Von Hippel-Lindau disease and central nervous system hemangioblastoma. Progress in genetics and clinical management].

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder, predisposing to the development of various tumors (central nervous system and retinal hemangioblastomas, endolymphatic sac tumors, renal cell carcinoma and/or renal cysts, pheochromocytomas, pancreatic cysts and/or tumors). Incidence of the disease is 1/36,000. Central nervous system hemangioblastomas and renal cell carcinoma are the main causes of death. The VHL gene, located on chromosome 3p25-26, is a tumor-suppressor gene encoding for a 213 amino acid protein which plays a major role in regulation of VEGF expression. Germline mutations of the VHL gene are identified in about 75-80% of the patients. Somatic mutations of the VHL gene are found in both sporadic central nervous system hemangioblastomas and sporadic "clear" renal cell carcinomas. For neurosurgeons search for VHL disease should be imperative in presence of a patient with apparently "sporadic" central nervous system or endolymphatic sac tumor.

Central Nervous System Neoplasms↗
PubMed1997

DNA replication and postreplication mismatch repair in cell-free extracts from cultured human neuroblastoma and fibroblast cells.

DNA synthesis and postreplication mismatch repair were measured in vitro using cell-free extracts from cultured human SY5Y neuroblastoma and WI38 fibroblast cells in different growth states. All extracts, including differentiated SY5Y and quiescent WI38 fibroblasts, catalyzed SV40 origin-dependent DNA synthesis, totally dependent on SV40 T-antigen. Thus, although differentiated neuroblastoma and quiescent fibroblasts cells were essentially nondividing, their extracts were competent for DNA replication using DNA polymerases delta, alpha, and possibly epsilon, with proliferating cell nuclear antigen. Nonreplicative DNA synthesis and lesion bypass by either alpha- or beta-polymerases were detected independently in extracts using primed or gapped single-stranded DNA templates. Long-patch postreplication mismatch repair was measured for the first time in neuroblastoma cell-free extracts. Extracts from subconfluent and high-density SY5Y cells catalyzed postreplication mismatch repair with efficiencies comparable to those of HeLa cell extracts. No significant differences were observed in repair between SY5Y differentiated and undifferentiated cell extracts. Mismatch repair efficiencies were threefold lower in extracts from subconfluent WI38 cells, and repair in WI38 quiescent cells was fourfold less than in subconfluent cells, suggesting that mismatch repair may be regulated. The spectrum of mismatch repair in SY5Y extracts closely resembled the mismatch removal specificities of HeLa extracts: T . G and G . G mismatches were repaired most efficiently; C . A, A . A, A . G and a five-base loop were repaired with intermediate efficiency; repair of G . A, C . C, and T . T mismatches was extremely inefficient.

Antineoplastic Agents↗
PubMed1997

Stereotactic brain biopsy guided by positron emission tomography (PET) with [F-18]fluorodeoxyglucose and [C-11]methionine.

The aim of the present study was to compare the contribution of the labelled tracers [C-11]methionine (Met) and [F-18]-fluorodeoxyglucose (FDG) in positron emission tomography (PET)-guided stereotactic biopsy of non resectable brain lesions. Twenty-five patients underwent combined Met-PET-, FDG-PET- and computerized tomography (CT)- or magnetic resonance (MR)-guided stereotactic biopsy according to a previously described technique for stereotactic FDG-PET. Met-PET and FDG-PET images were analyzed to determine which tracer offers the best information to guide at least one stereotactic biopsy trajectory. Histological diagnosis was obtained in all patients (23 tumours and 2 non-tumorous lesions). All tumours had an area of abnormal Met uptake and were biopsied under PET-guidance. FDG uptake in the tumour was higher than in the grey matter and was used for target selection in 12 of 23 tumours. Eleven of them were located in the basal ganglia or the brainstem. Met was used for target selection in 11 of 23 tumours where there was no FDG uptake or where FDG uptake was equivalent to that of the grey matter. Ten of them were located in the cortex. Two nontumoral lesions had no Met uptake and were biopsied under CT- or MR-guidance only. Forty-three out of 53 stereotactic trajectories obtained in these 25 patients were based on PET-defined targets and had an area of abnormal Met uptake. These trajectories always yielded a diagnosis of tumour. Moreover, all tumorous trajectories had an area of abnormal Met uptake. Finally, all non-diagnostic trajectories (n = 4) were CT/MR-defined because there was no area of abnormal Met uptake. These results suggest that patients who can benefit the most from Met-PET guidance could be selected pre-operatively. In conclusion, this work shows that Met is a good alternative to FDG for target selection in PET-guided stereotactic brain biopsy.

Adolescent↗
PubMed1997

Context-dependent survival differences among electrophoretic genotypes in natural populations of the marine bivalve Spisula ovalis.

We investigated the relationships between allozyme genotypes at nine polymorphic loci and survival in a natural population of the bivalve Spisula ovalis sampled on three occasions (1993, 1994, and 1995) in three different sites (2855 individuals analyzed). This species displays annual growth lines allowing identification of annual cohorts. Therefore we could avoid cohort mixing, a frequent bias in such studies, and evaluate the consistency of the observed effects across cohorts and sites. Significant viability differences were observed both among alleles and between heterozygotes and homozygotes at some loci. Multiple-locus heterozygosity was positively correlated with viability in the 1993-1994 period, but not in the 1994-1995 interval. The observed selective effects were significantly dependent on the cohort and the site considered. A bibliographic survey suggests that such variability is a common feature of studies analyzing heterozygosity-survival relationships. Two explanations are consistent with our results. First, allozyme genotypes may have direct effects on viability that interact with subtle environmental variation in a complex and unpredictable way. Second, allozyme genotypes may be transiently associated with other viability genes responsible for heterotic effects. In any case, the results militate against allozyme loci being themselves consistently overdominant for viability in natural populations.

Alleles↗
PubMed1997

The effect of skull-pin insertion on cerebrospinal fluid pressure and cerebral perfusion pressure: influence of sufentanil and fentanyl.

This randomized prospective study measured the effects of an intravenous opioid bolus on cerebrospinal fluid pressure (CSFP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) during skull-pin insertion. Twenty-two adult patients scheduled for elective craniotomy for supratentorial lesions were studied. Outcome variables were MAP, heart rate (HR), and lumbar CSFP. The standardized anesthetic regimen included fentanyl (2 microg/kg), thiopental (5-7 mg/kg), lidocaine (1.5 mg/kg), isoflurane (0.3-0.7 minimum alveolar anesthetic concentration), and vecuronium (0.1 mg/kg). During stable anesthesia, sufentanil (0.8 microg/kg) or fentanyl (4.5 microg/kg) was given as a bolus before skull-pin insertion. The hemodynamic effects of the opioid injection were modified with phenylephrine and/or atropine when indicated. CSFP remained unchanged in both treatment groups. MAP and CPP increased approximately 10 mm Hg after skull-pin insertion (P<0.001). In the sufentanil group, HR decreased approximately 10 bpm after opioid injection and remained decreased throughout the study. In fentanyl-treated patients, HR decreased 8 bpm after opioid injection but returned to preopioid rates after skull-pin insertion. In conclusion, in anesthetized patients, an intravenous bolus of fentanyl or sufentanil prior to skull-pin insertion results in stable values of CSFP, CPP, BP, and HR when the hemodynamic effects of the opioid are modified with phenylephrine and atropine.

Adjuvants, Anesthesia↗
PubMed1997

Intracerebral transplantation of fetal ventral mesencephalon for patients with advanced Parkinson's disease. Methodology and 6-month to 1-year follow-up in 3 patients.

In order to launch a new transplantation program for Parkinson's disease (PD), we evaluated the safety and efficacy of fetal ventral mesencephalic grafts in 3 patients with advanced PD. Inclusion criteria and clinical evaluation followed strictly the Core Assessment Program for Intracerebral Transplantation. The transplantation procedure was based on the technique previously described by the groups in Lund (Sweden) and Créteil (France). The putamen contralateral to the site of predominant symptoms was unilaterally grafted in all patients. Magnetic resonance (MR)-based stereotactic guidance with multiplanar correlation was used to define 3 implantation trajectories in the precommissural, commissural, and postcommissural putamen. Fetal ventral mesencephalon was prepared from 6- to 8-week-old human embryos obtained from same-day abortions. Under general anesthesia, 8 deposits of 3 microliters of the fetal tissue were placed 1 mm apart along each implantation trajectory using a customized microsyringe and needle attached to the stereotactic frame. The patients recovered uneventfully from the neurosurgical procedure. Early postoperative MR clearly showed the implantation trajectories reaching the putamen in all patients. The follow-up period was of 12, 9 and 6 months, for each of the 3 patients, respectively. Clinical changes appeared between 3 and 6 months after transplantation and consisted of an increase in the 'on' periods and in quantitative bilateral improvement in the motor timed tests. There was an improvement of the Unified Parkinson's Disease Rating Scale score and an improvement of rigidity. Tremor was unchanged, and there was a slight and transient increase in dyskinesias. Neuropsychological follow-up revealed slight frontal alterations in 2 patients. Positron emission tomography demonstrated an increase of 18F-fluorodopa uptake in the grafted site. Adverse events include a reversible Cushing syndrome secondary to immunosuppression in 1 patient and a transient episode of confusion in another. The results of this study, designed as a prerequisite for a wider transplantation program, are in accordance with those previously reported by others and show that, using standardized neurosurgical techniques and methods of evaluation, transplantation is a reproducible and safe therapeutic approach which provides clinical benefits to patients with advanced PD.

Brain Tissue Transplantation↗
PubMed1996

Vanadate inhibits vacuolar H(+)-ATPase-mediated proton transport in chicken kidney microsomes by an ADP-dependent mechanism.

Recent reports indicate that vacuolar-type proton ATPases from chicken osteoclasts (Chatterjee et al. (1992) Proc. Natl. Acad. Sci. USA 89, 6257-6261), yeast vacuoles and chromaffin granules (Beltran and Nelson (1992) Acta Physiol. Scand. Suppl. 607, 41-47) can be inhibited by vanadate, albeit at a concentration much higher than that required to inhibit P-type ATPases. We have characterized the mechanism by which vanadate inhibits vacuolar-type ATPase-mediated proton transport by chicken kidney microsomes. The initial rate of proton transport is somewhat less sensitive to vanadate than the total acidification, with IC50 values of 1.58 mM and 0.78 mM vanadate, respectively. The inhibition of both the initial rate and total acidification is noncompetitive with respect to ATP. The inhibition is abolished when ADP is removed by an ATP-regenerating system, and the addition of exogenous ADP increases the vanadate inhibition of proton transport in a synergistic manner, thus demonstrating that inhibition by vanadate is dependent on the presence of ADP and explaining the lower effect of vanadate on the initial rate of acidification. Phosphate protects proton transport activity from inhibition by vanadate. These effects of ADP and phosphate suggest that inhibition by vanadate may involve the formation of a complex with ADP at a nucleotide binding site, possibly at the catalytic site of the enzyme.

Adenosine Diphosphate↗
PubMed1996

The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)-ATPase.

Although bisphosphonates have been shown to be potent inhibitors of osteoclast-mediated bone resorption in vivo and in vitro and are used as therapeutic agents in hyper-resorptive bone diseases such as Paget disease or hypercalcemia of malignancy, their exact biochemical target(s) and mode(s) of action are for the most part still unknown. The resorption of bone requires solubilization of the mineral component of the matrix, achieved by acidification of the resorbing compartment by a vacuolar-type proton ATPase (V-ATPase) present in the ruffled border membrane of osteoclasts. Since we have shown that the V-ATPase is inhibited by both ADP and phosphate, which share structural characteristics with bisphosphonates, we hypothesized that inhibition of the osteoclast V-ATPase could be one of the mechanism(s) by which bisphosphonates inhibit bone resorption. Pyrophosphate and the bisphosphonates etidronate, alendronate, and YM-175 inhibited proton transport in membrane vesicles derived from chicken kidney and osteoclasts but with very low potency (IC50 > or = 5 mM). In contrast, the ability of tiludronate to inhibit proton transport was 5-fold higher in kidney-derived vesicles (IC50 = 1.1 mM) and 10,000-fold higher in vesicles derived from osteoclasts (IC50 = 466 nM). Tiludronate also potently inhibited proton transport in yeast microsomal preparations (IC50 = 3.5 microM) and inhibited the activity of purified yeast V-ATPase. The inhibition of the osteoclast V-ATPase-mediated proton transport by tiludronate was rapid, pH-dependent, and reversible. No change in membrane vesicle permeability to protons was detected. The inhibition was noncompetitive with respect to ATP, and tiludronate did not protect the pump from inactivation by N-ethylmaleimide, strongly suggesting that tiludronate does not bind to the catalytic site of the enzyme. It is concluded that tiludronate is a significantly more potent inhibitor of V-ATPase than other bisphosphonates and that it has a significant degree of selectivity for the avian osteoclast V-ATPase relative to the avian kidney V-ATPase.

Alendronate↗
PubMed1996

Child and maternal mortality during a period of conflict in Beira City, Mozambique.

BACKGROUND: Child mortality rates have been declining in most developing countries. We studied child and maternal mortality risk factors for child mortality in Beira city in July 1993, after a decade of conflict in Mozambique. METHODS: A community-based cluster sample survey of 4609 women of childbearing age was conducted. Indirect techniques were used to estimate child mortality ('children ever born' method and Preceding Birth Techniques (PBT) and maternal mortality (sisterhood method). Deaths among the most recent born child, born since July 1990, were classified as cases (n = 106), and two controls, matched by age and cluster, were selected per case. RESULTS: Indirect estimates of the probability of dying from birth to age 5 (deaths before age 5 years, (5)q(0) per 1000) decreased from 246 in 1977/8 to 212 in 1988/9. The PBT estimate of 1990/91 was 154 (95 percent confidence interval [CI]: 124-184), but recent deaths may have been underreported. Lack of beds in the household (odds ratio [OR] = 2.0, 95 percent CI: 1.1-3.8), absence of the father (OR = 2.4, 95 percent CI : 1.2-4.8), low paternal educational level (OR = 2.1, 95 percent CI: 0.8-5.4), young maternal age (OR = 2.0, 95 percent CI: 1.0-3.7), self-reported maternal illness (OR = 2.4, 95 percent CI : 1.2-4.9), and home delivery of the child (OR = 2.3, 95 percent CI : 1.2-4.5) were associated with increased mortality, but the sensitivity of risk factors was low. Estimated maternal mortality was 410/100 000 live births with a reference date of 1982. CONCLUSIONS: Child mortality decreased slowly over the 1980s in Beira despite poor living conditions caused by the indirect effects of the war. Coverage of health services increased over this period. The appropriateness of a risk approach to maternal-child-health care needs further evaluation.

Adult↗
PubMed1996

Congenital bilateral perisylvian syndrome in a monozygotic twin with intra-uterine death of the co-twin.

Congenital bilateral perisylvian syndrome was diagnosed in a two-year- old boy with signs of pseudobulbar and diplegic cerebral palsy presenting on MRI a polymicrogyric appearance of the perisylvian regions. He was born from a monochorionic bi-amniotic twin pregnancy complicated by twin-twin transfusion syndrome and death of the co-twin between the 16th and 18th weeks of gestation. Ventricular enlargement and hepatic hyperechogenic lesions were seen during his sonographic intra-uterine follow-up. The authors suggest that ischaemic injury occurred in this patient as a consequence of acute haemodynamic changes induced by the death of his co-twin.

Cerebral Aqueduct↗
PubMed1996

Biomass accumulation in hydroponically grown sweetpotato in a controlled environment: a preliminary study.

In the development of a plant growth model, the assumptions made and the general equations representing an understanding of plant growth are gradually refined as more information is acquired through experimentation. One such experiment that contributed to sweetpotato model development consisted of measuring biomass accumulation of sweetpotato grown in hydroponic culture in a plant growth chamber. Plants were started from fifteen centimeter long 'TU-82-155' sweetpotato vine cuttings spaced 25 cm apart in each of 18 rectangular growing channels (0.15 by 0.15 by 1.2m) in a system designed to use the nutrient film technique (NFT). Each channel contained four plants. The 3.5m by 5.2m plant growth chamber environmental parameters included an 18h photoperiod, 500 micromoles m-2 s-1 of photosynthetic photon flux (PPF), and a diurnal light/dark temperature of 28 degrees C/22 degrees C. The relative humidity was 80 +/- 5% and the CO2 partial pressure was ambient (350 ppm). The nutrient solution contained in 30L reservoirs was a modified half Hoagland's solution with a 1:2.4 N:K ratio and a pH of 6.2. Solution replenishment occurred when the electrical conductivity (EC) level dropped below 1050. Plants were harvested at 15 days after planting (DAP) and weekly thereafter until day 134. By 57 DAP, stems and fibrous roots had acquired 90% of their total dry biomass, while leaves had reached 84% of their maximum dry biomass. Beginning at 64 DAP dry biomass accumulation in the storage roots dominated the increase in dry biomass for the plants. Dry weight of storage roots at 120 DAP was 165 g/plant or 1.1 kg/m2. Resulting growth curves were consistent with the physiological processes occurring in the plant. Results from this study will be incorporated in a plant growth model for use in conjunction with controlled life support systems for long-term manned space missions.

Biomass↗
PubMed1995

Evaluation of endoscopy in the treatment of rare meningoceles: preliminary results.

BACKGROUND: Endoscopy is used on different occasions-for instance, to open the floor of the third ventricule in triventricular hydrocephalus, to open a cyst into the cerebrospinal fluid circulation, for biopsy or for partial resection of some tumors, or to insert a shunt in hydrocephalus or syringohydromyelia. However, the use of endoscopes for evaluating and treating meningoceles remains to be assessed. METHODS: Five different kinds of rare meningoceles are presented. In each, neuroendoscopy was used as the main tool for exploration and treatment. RESULTS: Two sacral meningoceles and one oral cephalocele were cured through a keyhole opening under endoscopic control. One posterior sacral meningocele was explored and no communication with normal subarachnoid spaces was observed, allowing a simple suture of the posterior to the anterior walls. And, last, a complex case with three intrasacral meningocles was explored and partially treated. CONCLUSIONS: Meningocles with very small communication within the normal subarachnoid spaces appeared the most suitable to be cured by an endoscopic procedure. In case of a larger communication, the meningocele could be treated, or at least the morphology can be better understood, by using a keyhole procedure under endoscopic control. In all cases the surgery was of short duration (less than 1 hour) and very well tolerated.

Adolescent↗
PubMed1995

Mid-portion agenesis of corpus callosum in a presumed Baller-Gerold syndrome.

We report an association of trigonocephaly and thumb hypoplasia in a 6.5-year-old boy, diagnosed as Baller-Gerold syndrome. In addition to craniosynostosis and radial limb defect, which are constant in this syndrome, our patient presents two unusual features: the first is an epidermal nevus and the second is an agenesis of the middle portion of corpus callosum. This unique type of callosal agenesis in the context of a polymalformative disorder supports the hypothesis that partial agenesis of corpus callosum may be due to an event occurring before the 12th week gestation with continued development of the midline structures.

Abnormalities, Multiple↗
PubMed1995

Alternative models for allozyme-associated heterosis in the marine bivalve Spisula ovalis.

Correlations between allozyme heterozygosity and fitness-related traits, especially growth, have been documented in natural populations of marine bivalves. However, no consistent pattern has been exhibited, because heterotic effects on size vary with age and individual growth parameters are generally unknown. No consensus has emerged on the genetic basis of allozyme-associated heterosis. The species studied here, Spisula ovalis, displays annual shell growth lines, which allows us to compute individual age and growth dynamics over the whole life span. Our morphological study was coupled to a protein electrophoresis study at seven polymorphic loci. While the maximum size gained is not related to heterozygosity, the age at half maximum size, t1/2, is significantly negatively correlated with heterozygosity, indicating an heterotic effect on initial growth. The correlation between heterozygosity and size is expected to vanish when age increases, due to the form of the growth function. This decreasing correlation is consistent with previous studies. We compare the relative performances of five linear models to analyze the genetic basis of heterosis. Surprisingly, the largest part of variance in t1/2 is due to additive effects, the overdominant components being much weaker. Heterosis is therefore due to general genomic effects rather than to local overdominance restricted to allozymes or small neighboring chromosomal segments. A significant dependence of individual heterotic contributions of the enzyme loci upon expected heterozygosities, rather than metabolic function, further supports the hypothesis of enzymes acting as markers. General genomic effects can hold only if allozyme heterozygosity is positively correlated with heterozygosity at fitness-related genes scattered throughout the genome. This hypothesis is supported here by heterozygosity correlations between enzymatic loci.

Animals↗
PubMed1994

The catalytic cycle of the vacuolar H(+)-ATPase. Comparison of proton transport in kidney- and osteoclast-derived vesicles.

To characterize the catalytic cycle involved in the initial rate of proton transport by the vacuolar ATPases (V-ATPase), we have analyzed and compared the catalytic parameters of V-ATPase-dependent proton transport in vesicles from chicken kidney or purified osteoclasts. The relationship of acidification to ATP obeyed simple Michaelis-Menten kinetics with a single Km for ATP of 62 microM in the kidney and 191 microM in the osteoclast. The activity was dependent on the presence of Mg2+, with a single Km of 258 microM MgCl2 in the kidney and 504 microM MgCl2 in the osteoclast. In both preparations, ADP competed with ATP and inhibited the proton transport (Ki = 37 microM in kidney and 17 microM in osteoclast). Phosphate was found to be a noncompetitive inhibitor of ATP, with a calculated Ki of about 10.5 and 5.5 mM, respectively. In both preparations, the catalytic mechanism determining the V-ATPase-mediated proton transport, fits the model of a "uni-bi-ordered release" mechanism. According to this model, ATP is the single substrate, and P(i) and ADP are the two products where phosphate, being noncompetitive, is released first and ADP, being competitive, second. The findings of an elevated Km for ATP and Mg2+ and a decrease in the Ki of ADP and phosphate in the osteoclast relative to the kidney preparation suggests that the V-ATPases present in these two tissues may differ.

Adenosine Diphosphate↗
PubMed1994

Hyperechoic thickened ependyma: sonographic demonstration and significance in neonates.

In the neonate, hyperechoic thickening of the ependyma is believed to be related to ventriculitis. Yet, in our experience, this sign is much more often observed in association with subacute intraventricular hemorrhage (IVH), without infection. Sixty premature neonates were prospectively studied. The observations of transfontanellar sonograms (intracranial hemorrhage, ependymal echogenicity, and ventriculomegaly) were correlated with the results of MRI, lumbar punctures and clinical work-up. Intracranial hemorrhage was detected in 28 patients, and hyperechoic thickening of the ependyma was observed in 21 of them, all of whom had IVH. In 9 of these 21 patients IVH was diagnosed retrospectively thanks to the visualization of the hyperechoic ependyma. In all but one, this sign persisted for at least 2 months after disappearance of other signs of IVH. MRI demonstrated the presence of hemosiderin and ferritin in ependymal or subependymal location only in patients with hyperechoic ependyma. One of our patients had in utero diagnosis of IVH owing to the visualization of the same hyperechoic aspect of the ependyma. Nine of the neonates with hyperechoic ependyma developed ventriculomegaly, and three underwent surgery. Hyperechoic thickening of the ependyma in prematures often results from a subacute IVH. It is related to hemoglobin catabolites which can be detected by MRI. It does not require immediate potentially harmful diagnostic punctures. The presence of this hyperechoic rim allows a retrospective diagnosis of IVH and indicates a clinical and sonographic follow-up in newborns at risk for secondary hydrocephalus.

Cerebral Hemorrhage↗