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Biomedical subjects

F David

Publications and source records attributed to F David.

At least 37 records · Page 2Linked to original sources
PubMed2001

[The Lateglacial sequence of the Etelles (northern French Alps): climate instability and vegetation dynamics].

A detailed pollen analysis has been conducted in a new sedimentary sequence taken at Les Etelles (700 m), in the hill vegetation belt in the Chaîne des Hurtières (Northern French Alps). The Lateglacial history of the vegetation has been supported by 10 AMS datings. Variations in relative abundance of main pollen taxa were compared with variations in [symbol: see text] 18O in Swiss lacustrine sediments and with the GRIP ice-core record. Those highlight how the vegetation reacted to minor climatic oscillations. The Lateglacial spread of Quercus, Alnus and Corylus in the region is confirmed, thus allowing a new interpretation of some Lateglacial sedimentary sequences at an adjacent region (Bas-Dauphiné).

Climate↗
PubMed2001

Treatment intensification with abacavir in HIV-infected patients with at least 12 weeks previous lamivudine/zidovudine treatment.

OBJECTIVES: To demonstrate that lamivudine and zidovudine, given separately (lamivudine/zidovudine) or as a single combination tablet (Combivir), had equivalent efficacy. To evaluate the safety and antiretroviral activity of intensification with abacavir in patients treated with lamivudine/zidovudine for > or = 12 weeks. DESIGN: A 12-week, equivalence study of lamivudine/ zidovudine versus Combivir. Patients who completed this study could enter a 48-week, intensification study of Combivir plus abacavir. METHODS: In the equivalence study, treatment-naive patients were assessed for HIV-1 RNA, CD4 cell count and genotype. The same assessments plus phenotype were made in the intensification study. Serious adverse events were recorded in the equivalence study and all adverse events in the intensification study. RESULTS: Lamivudine/zidovudine (n=40) and Combivir (n=35) gave equivalent reductions in plasma HIV-1 RNA levels at week 12. An identical proportion of patients (74%) in each treatment group harboured virus with the M184V mutation after 12 weeks. Fifty-two patients entered the intensification study and 44 completed 48 weeks of treatment. At the time of intensification with abacavir, all 35 patients with evaluable isolates harboured HIV-1 containing M184V. Addition of abacavir to Combivir led to further decreases in plasma HIV-1 RNA and increases in CD4 cell counts compared with the start of intensification (P<0.001 at week 48). After 48 weeks of triple therapy, multi-nucleoside resistance mutations at codons 69 and 151 were not detected in any patients. All treatment regimens were generally well tolerated. CONCLUSION: Lamivudine/zidovudine and Combivir have equivalent antiretroviral activity over 12 weeks. Adding abacavir to Combivir can be a safe and effective therapeutic option for patients, including those harbouring virus with the M184V mutation.

Administration, Oral↗
PubMed2000

Potential prognostic value of mitogen-activated protein kinase activity for disease-free survival of primary breast cancer patients.

Signaling through pathways involving mitogen-activated protein kinases (MAP kinases) has been implicated in the pathogenesis of cancer. Thus, the activity of MAP kinase is essential in the malignant potential of human breast tumors. p42/44(MAPK) was significantly higher expressed in tumor samples than in matching normal tissues adjacent to the tumor. p42/44(MAPK) protein expression correlated with enhanced MAP kinase activity only in a subset of tumors, indicating that over-expression of MAP kinases does not reflect the activation status of these enzymes. MAP kinase activity was significantly elevated in 131 tissue samples from primary breast tumors when compared to 18 normal tissues adjacent to tumors. A trend for higher MAP kinase activity in primary tumors of node-positive patients was observed when compared with tumors from node-negative patients. Similarly, higher MAP kinase activities were observed in specimens from patients who had a relapse within the follow-up time of 40 months when compared with patients with no relapse. A survival analysis demonstrated that the MAP kinase activity in primary breast tumors is potentially prognostic for relapse-free survival of patients.

Breast↗
PubMed2000

Dog model of therapeutic ketosis induced by oral administration of R,S-1,3-butanediol diacetoacetate.

A high-fat, almost carbohydrate-free diet is used in children with intractable epilepsy to help control seizures by inducing a permanent state of ketosis. Esters of ketone bodies have been previously studied for their potential as parenteral and enteral nutrients. We tested in conscious dogs whether ketosis could be induced by repeated ingestion of R,S-1,3-butanediol diacetoacetate with or without carbohydrates. This ester is a water-soluble precursor of ketone bodies. Two constraints were imposed on this preclinical study: The rate of ester administration was limited to one half of the daily caloric requirement and to one half of the capacity of the liver to oxidize butanediol derived from ester hydrolysis. Under these conditions, the level of ketosis achieved in this dog model (0.8 mM) was lower than the level measured in children whose seizures were controlled by the ketogenic diet (1-3 mM). However, because humans may have a lower capacity for ketone body utilization than dogs, the doses of R,S-butanediol diacetoacetate used in the present study might induce higher average ketone body concentrations in humans than in dogs.

Journal Article↗
PubMed2000

Hospitalizations due to falls in Jewish and Arab children in northern Israel.

In Israel, there are no epidemiological data regarding nonfatal childhood falls. A retrospective survey was conducted in order to find epidemiological characteristics of childhood falls among the different populations of northern Israel. During the years 1993 through 1995, 3082 children were hospitalized in Rambam Medical Center (RMC) due to injury. The children were subdivided into the four main populations: Jewish and Arab residents of Haifa region (the main metropolitan area) and Jewish and Arab residents of the Galilee region (the rural region). All of the children who suffered injury that required mechanical ventilation and careful assessment were admitted to the PICU. The charts of the children admitted to the PICU were then further studied. The demographic characteristics of all the cases of falls were statistically analyzed and the annual admission rates due to falls were calculated using the national statistical registrations of children in Israel. Falls were responsible for 1049 admissions due to injury, one third of the total number of children who were admitted due to an injury. Most of the children were five years of age or younger. Two thirds of the total childhood falls were of Arabs. The majority of the admissions were of two major sub-populations of northern Israel: Arab residents of Galilee region (66%) and Jewish residents of Haifa region (34%). Higher admission rate was found among Arab children of the Western Galilee district in comparison with Jewish children of the Haifa district. Most of the children who were admitted to the PICU were Arabs: nearly all of these children were from the rural region. More Arab than Jewish children who fell were admitted to the PICU and the majority of these cases were falls from buildings (private houses). Arab children of the rural region were responsible for 95% of the cases. These falls were mainly in staircases (46%) and from balconies (21%), roofs (11%) and windows (11%). The findings of the present study suggest that young Arab rural children in northern Israel are at high risk to a severe injury due to fall. Possible causes are discussed and a preventative intervention is suggested.

Accidental Falls↗
PubMed2000

The influence of excitotoxic basal ganglia lesions on motor performance in the common marmoset.

Huntington's disease is a genetically inherited neurodegenerative disorder for which currently there is no effective treatment or cure. In order to gauge the potential therapeutic benefits of neuroprotective or restorative treatments, it is necessary to create an animal model that is associated with readily measurable and long-lasting functional impairments. The undifferentiated neostriatum and limited behavioural repertoire of rodents have led to the extension of our investigations into the common marmoset. We have used quinolinic acid to create unilateral excitotoxic lesions of the caudate nucleus or the putamen in this small non-human primate. Following rigorous investigation of each monkey on a battery of behavioural tests, we found that the unilateral putamen lesion was associated with a contralateral motor impairment that persisted for at least 9 months and withstood repeated testing. However, the unilateral caudate nucleus lesion did not appear to be associated with any detectable motor deficit. The stability and the reproducibility of the unilateral putamen lesion in the marmoset provide a suitable tool for the investigation of potential treatments for neurodegenerative disorders that attack this region of the brain.

Amphetamine↗
PubMed2000

Integrative physiology of splanchnic glutamine and ammonium metabolism.

The substrates for hepatic ureagenesis are equimolar amounts of ammonium and aspartate. The study design mimics conditions in which the liver receives more NH(+)(4) than aspartate precursors (very low-protein diet). Fasted dogs, fitted acutely with transhepatic catheters, were infused with a tracer amount of (15)NH(4)Cl. From arteriovenous differences, the major NH(+)(4) precursor for hepatic ureagenesis was via deamidation of glutamine in the portal drainage system (rather than in the liver), because there was a 1:1 stoichiometry between glutamine disappearance and NH(+)(4) appearance, and the amide (but not the amine) nitrogen of glutamine supplied the (15)N added to the portal venous NH(+)(4) pool. The liver extracted all this NH(+)(4) from glutamine deamidation plus an additional amount in a single pass, suggesting that there was an activator of hepatic ureagenesis. The other major source of nitrogen extracted by the liver was [(14)N]alanine. Because alanine was not produced in the portal venous system, we speculate that it was derived ultimately from proteins in peripheral tissues.

Acid-Base Equilibrium↗
PubMed1999

On the performance and inertness of different materials used for the enrichment of sulfur compounds from air and gaseous samples.

The performance of the sorbent polydimethylsiloxane (PDMS) is compared to that of the adsorbents Carbotrap and Tenax for the enrichment of volatile and reactive sulfur compounds. These included: 1- and 2-propanethiol, tetrahydrothiophene, 2-thioethanol and 2-ethylthioethanol. Several artifact-forming reactions were identified on both Tenax and Carbotrap including: H2S elimination and dimerization of thiols. Additionally, permanent adsorption was also observed for heavier solutes. These effects are absent when PDMS is applied. This superior performance is explained by the absence of catalytic or adsorptive activity on PDMS.

Adsorption↗
PubMed1999

15N enrichment of ammonium, glutamine-amide and urea, measured via mass isotopomer analysis of hexamethylenetetramine.

Ammonium is an important intermediate of protein metabolism and is a key component of acid-base balance. Investigations of the metabolism of NH(4)(+) in vivo using isotopic techniques are difficult because of the low concentration of NH(4)(+) in biological fluids and because of frequent artifactual isotopic dilution of the enrichment of NH(4)(+) during the assay. A new gas chromatographic mass spectrometric method was designed to monitor the (15)N enrichment and concentration of NH(4)(+) in vivo. These are both calculated from the mass isotopomer distribution of hexamethylenetetramine (HMT) formed by reacting NH(4)(+) with formaldehyde. The enrichment of NH(4)(+) is amplified four times since the HMT molecule contains four atoms of nitrogen derived from NH(4)(+). This allows the measurement of low (15)N enrichment of NH(4)(+), down to 0.1%. (15)N enrichment of urea and of the amide N of L-glutamine are measured by enzymatic release of NH(4)(+) and conversion of the latter to HMT. These new techniques facilitate in vivo investigations of the metabolism of NH(4)(+) and related compounds.

Amides↗
PubMed1999

Zonation of acetate labeling across the liver: implications for studies of lipogenesis by MIDA.

Measurement of fractional lipogenesis by mass isotopomer distribution analysis (MIDA) of fatty acids or cholesterol labeled from [(13)C]acetate assumes constant enrichment of lipogenic acetyl-CoA in all hepatocytes. This would not be the case if uptake and release of acetate by the liver resulted in transhepatic gradients of acetyl-CoA enrichment. Conscious dogs, prefitted with transhepatic catheters, were infused with glucose and [1, 2-(13)C(2)]acetate. Stable concentrations and enrichments of acetate were measured in artery (17 microM, 36%), portal vein (61 microM, 5. 4%), and hepatic vein (17 microM, 1.0%) and were computed for mixed blood entering the liver (53 microM, 7.4%). We also measured balances of propionate and butyrate across gut and liver. All gut release of propionate and butyrate is taken up by the liver. The threefold decrease in acetate concentration and the sevenfold decrease in acetate enrichment across the liver strongly suggest that the enrichment of lipogenic acetyl-CoA decreases across the liver. Thus fractional hepatic lipogenesis measured in vivo by MIDA may be underestimated.

Acetates↗
PubMed1998

Limitations of the mass isotopomer distribution analysis of glucose to study gluconeogenesis. Heterogeneity of glucose labeling in incubated hepatocytes.

We previously reported (Previs, S. F., Fernandez, C. A., Yang, D., Soloviev, M. V., David, F., and Brunengraber, H. (1995) J. Biol. Chem. 270, 19806-19815) that glucose made in isolated livers from starved rats perfused with physiological concentrations of lactate, pyruvate, and either [2-13C]- or [U-13C3]glycerol had a mass isotopomer distribution incompatible with glucose being made from a homogeneously labeled pool of triose phosphates. Similar data were obtained in live rats infused with [U-13C3]glycerol. We ascribed the labeling heterogeneity to major decreases in glycerol concentration and enrichment across the liver. We concluded that [13C]glycerol is unsuitable for tracing the contribution of gluconeogenesis to total glucose production. We now report isotopic heterogeneity of gluconeogenesis in hepatocytes, even when all cells are in contact with identical concentrations and enrichments of gluconeogenic substrates. Total rat hepatocytes were incubated with concentrations of glycerol, lactate, and pyruvate that were kept constant by substrate infusions. To modulate competition between substrates, the (glycerol)/(lactate + pyruvate) infusion ratio ranged from 0.23 to 3. 60. Metabolic and isotopic steady states were achieved in all cases. The apparent contribution of gluconeogenesis to glucose production (f) was calculated from the mass isotopomer distribution of glucose. When all substrates were 13C-labeled, f was 97%, as expected in glycogen-deprived hepatocytes. As the infusion ratio ([13C]glycerol)/(lactate + pyruvate) increased, f increased from 73% to 94%. In contrast, as the infusion ratio (glycerol)/([13C]lactate + [13C]pyruvate) increased, f decreased from 93% to 76%. In all cases, f increased with the rate of supply of the substrate that was labeled. Variations in f show that the 13C labeling of triose phosphates was not equal in all hepatocytes, even when exposed to the same substrate concentrations and enrichments. We also showed that zonation of glycerol kinase activity is minor in rat liver. We conclude that zonation of other processes than glycerol phosphorylation contributes to the heterogeneity of triose phosphate labeling from glycerol in rat liver.

Animals↗
PubMed1998

A sensitive HPLC method for the quantification of free and total p-cresol in patients with chronic renal failure.

Para-cresol (4-methylphenol) is a volatile phenolic compound which is retained in chronic renal failure. Several recent studies suggest that p-cresol interferes with various biochemical and physiological functions at concentrations currently observed in uremia. Only a few methods are available for the determination of p-cresol concentration in serum. In addition, these methods have only been used for the determination of total p-cresol. In particular, the evolution of free (non-protein bound) p-cresol is of concern, because conceivably this is the biologically active fraction. The concentration of free p-cresol, is, however, markedly lower than that of total p-cresol, in view of its important protein binding. We report a method enabling the measurement of total and free p-cresol concentration in serum of healthy controls and uremic patients. Deproteinization, extraction and HPLC procedure are efficient, without interference of other protein bound ligands and/or precursors of p-cresol or phenol. By means of spiking experiments, the measurement of the UV absorbance over the 200-400 nm wavelength range, and capillary gas chromatography-mass spectrometry, the considered compound is identified as p-cresol. With a fluorescence detection at 284/310 nm as extinction/emission wavelengths the detection limit of p-cresol is 1.3 micromol/l (0.14 microg/ml). Recovery of added p-cresol to normal serum is 95.4+/-4.1%. For free p-cresol and total p-cresol determinations, intra-assay and day-to-day variation co-efficients are 3.2%, 4.2%, 6.9% and 7.3%, respectively. Compared to healthy controls, the serum p-cresol levels are 7-10 times higher in continuous ambulatory peritoneal dialysis patients (CAPD), uremic outpatients, and hemodialysis patients: 8.6+/-3.0 vs. 62.0+/-19.5, 87.8+/-31.7 and 88.7+/-49.3 micromol/l (0.93+/-0.32 vs. 6.70+/-2.11, 9.49+/-3.43, and 9.60+/-5.30 microg/ml) (p<0.05), respectively. The difference is even more important if free p-cresol is considered. This corresponds to a decreased protein binding in uremic patients. We conclude that the present method allows an accurate measurement of both total and free p-cresol, and that the measured concentrations in uremia are in the range which may cause biochemical alterations.

Artifacts↗
PubMed1998

[Peripheral adrenal insufficiency in AIDS].

BACKGROUND: Lesions of adrenal glands are common findings at autopsy of patients with acquired immunodeficiency syndrome (AIDS). In contrast the diagnosis of symptomatic adrenal insufficiency is rarely established during the lifetime of these patients. PATIENTS: We report four new cases and review the literature. All four patients had full blown AIDS with a mean CD4 cell count of 19 mu/L. One or more opportunistic disease was present at the time of diagnostic: cytomegalovirus retinitis in two cases, disseminated Mycobacterium avium infection in two, Kaposi's sarcoma in two and Candida esophagitis in one. RESULTS: The clinical presentation constantly included fatigue, weight loss, severe orthostatic hypotension and gastrointestinal disturbances. Cutaneous hyperpigmentation was present in three cases. In most cases biological abnormalities were typical, such as hyponatremia, urinary Na/K ratio > or = 1, and hyperkalemia. Serum cortisol levels were within the range of normal in three cases but response to the cosyntropin challenge was typically impaired in all cases. Clinical and biological manifestations returned to normal in 1 to 3 weeks after initiation of therapy with cortisol, associated to fludrocortisone in three cases. However, 13 months after diagnosis, three patients were dead. CONCLUSION: Usually asymptomatic, diagnostic of symptomatic adrenal insufficiency must be suspected even when clinical presentation is atypical because rapid efficiency of hormonal treatment.

AIDS-Related Opportunistic Infections↗
PubMed1998

[A method of isothermal gene amplification].

A gene amplification technique applied to the detection of HIV and which can be implemented without programmable thermocyclers is described. The reaction products are high molecular weight strands of DNA that can be detected using simple methods, even without electrophoresis. This is a promising technique for in situ amplification experiments. Our findings show that this amplification method is compatible with the temperature levels encountered in living cells. This technology could thus be the basis for a new class of drugs intended for treatment by gene therapy of certain diseases, including malaria and AIDS.

Base Sequence↗
PubMed1998

Determination of types of Enterocytozoon bieneusi strains isolated from patients with intestinal microsporidiosis.

To determine the types of Enterocytozoon bieneusi strains associated with intestinal microsporidiosis, we developed a rapid and efficient approach for typing parasites obtained from stool specimens by PCR-restriction fragment length polymorphism (PCR-RFLP). Typing was based on DNA polymorphism of the ribosomal DNA internal transcribed spacer (ITS) region of E. bieneusi. RFLPs generated with two restriction enzymes (NlaIII and Fnu4HI) in PCR-amplified ITS products were used to classify strains into different lineages. This approach was successfully used to differentiate 78 strains that had been obtained from the stools of 65 patients with intestinal microsporidiosis. Among the 78 strains, we found four genetically unrelated lineages, showing the genetic diversity of E. bieneusi. Type I strains of E. bieneusi were found in a majority of the samples, accounting for 51 (78%) of the 65 microsporidiosis cases. In contrast, type II, III, and IV strains were found in only 8 (12%), 3 (5%), and 3 (5%) cases, respectively. All strains of E. bieneusi we have tested so far fall into one of four different lineages, and this study shows that human intestinal microsporidiosis is most often associated with type I strains. PCR-RFLP analysis of the ITS region of E. bieneusi should be useful for epidemiological studies.

AIDS-Related Opportunistic Infections↗
PubMed1997

Tracing gluconeogenesis with deuterated water: measurement of low deuterium enrichments on carbons 6 and 2 of glucose.

The contribution of gluconeogenesis to glucose production in vivo can be measured by enriching body water with 0.5% 2H2O and measuring the glucose labeling ratio C6/C2 (Landau et al., J. Clin. Invest. 95, 172-178, 1995). We present further refinements of the measurements of the 2H enrichments on C6 and C2 of glucose. The transfer of 2H from C6 of glucose to hexamethylenetetramine (HMT) and extraction in preparation for gas chromatography-mass spectrometry can be done in a single test tube, without distillation of the intermediate formaldehyde. In addition, extraction of small amounts of HMT is greatly improved by making a HMT-iodine adduct. For C2, glucose is reduced to sorbitol, and 2H on C2 is transferred enzymatically to [U-13C3]pyruvate, forming [U-13C3,2-2H]lactate. The latter is assayed by negative chemical ionization gas chromatography-mass spectrometry of the pentafluorobenzyl derivative. The natural enrichment of the [U-13C3]lactyl ion is only 0.4%, allowing measurements of 2H enrichment down to 0.1%. These techniques were used in dogs infused with 2H2O and in isolated rat livers perfused with buffer containing 1 to 5% 2H2O. Our data reveal a difference in the rate of labeling of C6 and C2 of glucose in vivo. Lastly, in cows infused with [6,6-2H2]glucose, we show that the turnover of glucose can be economically measured by assaying low tracer enrichment (down to 0.1%) via hexamethylenetetramine.

Animals↗