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Biomedical subjects

J Lambert

Publications and source records attributed to J Lambert.

At least 19 recordsLinked to original sources

Effects of therapy with didanosine on hematologic parameters in patients with advanced human immunodeficiency virus disease.

Myelosuppression is associated with human immunodeficiency virus (HIV) infection and may also be produced by agents used for the treatment of the disease or the treatment of its complications. Didanosine (ddl; 2',3'-dideoxyinosine) is a newer purine nucleoside that has recently become available for therapy for HIV infection. The effects of didanosine on peripheral blood counts have been retrospectively evaluated in the first 170 patients treated with this new agent in four phase I trials. Patients treated with didanosine showed statistically significant improvements in hemoglobin levels, white cell counts, and granulocyte and platelet numbers as compared with baseline values. These changes were seen with or without prior therapy with zidovudine, were somewhat more pronounced at higher doses of didanosine, and persisted for up to 1 year. Reported adverse events included peripheral neuropathy, diarrhea, and most notably, pancreatitis. It is concluded that, while some toxic side effects occur, didanosine therapy in HIV infection is associated with an amelioration of HIV-induced myelosuppression.

AIDS-Related Complex

Effects of residency training in family medicine v. internship training on professional attitudes and practice patterns.

OBJECTIVES: To determine whether the professional attitudes and practice patterns of physicians with residency training in family medicine differ from those of generalists with internship training. DESIGN: Mail survey conducted in 1985-86. SETTING: Province of Quebec. PARTICIPANTS: A stratified random sample of French-speaking family and general practitioners who graduated after 1972 (325 physicians with residency training and 304 with internship training) (response rate 82%). MAIN RESULTS: Physicians with residency training were 3 years younger on average than those with internship training, were more likely to be female (38% v. 18%, p less than 0.001) and were more likely to work on a salaried basis in CLSCs (public community health centres) (36% v. 14%, p less than 0.001). Even after these confounding factors were controlled for, physicians with residency training seemed to be more sensitive to the psychosocial aspects of patient care and tended to attach more importance to informing patients about useful materials and resources concerning their health problems. They were not, however, more likely to value health counselling or integrate it in medical practice. CONCLUSION: Our findings provide some evidence that the new requirement that physicians complete a residency in family medicine to obtain medical licensure in general practice in Quebec may foster a more patient-centred approach to health care.

Adult

Metabolism of androstenedione and 11-ketotestosterone in the kidney of the three-spined stickleback, Gasterosteus aculeatus.

Stickleback kidneys were incubated with tritiated androstenedione (A4) or 11-ketotestosterone (OT). After the A4 incubations the following steroids were found, testosterone (T), 5 beta-androstane-3,17-dione (5 beta Ad), etiocholanolone (Et), 5 beta-dihydrotestosterone (5 beta DHT), 5 beta-androstane-3 alpha,17 beta-diol (5 beta A3 alpha 17 beta diol), androsterone, 5 alpha-androstane-3,17-dione, 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha A3 alpha 17 beta diol), as well as glucuronides of T, Et, 5 beta DHT, 5 beta A3 alpha 17 beta diol, and 5 alpha A3 alpha 17 beta diol. The metabolites found in the largest amounts were usually T, 5 beta Ad, Et, and the glucuronides of T, Et, and especially of 5 beta A3 alpha 17 beta diol. These results suggest the main pathway to be A4-5 beta Ad-Et-5 beta A3 alpha 17 beta diol-5 beta A3 alpha 17 beta diol-glucuronide or Et-Et-glucuronide-5 beta A3 alpha 17 beta diol-glucuronide. The formation of 5 beta-reduced compounds was larger in postbreeding males and females than in breeding males. The opposite was the case for 5 alpha-reduced compounds. The total formation of glucuronides was lower in the breeding males than in the other groups. After the OT incubations 11-ketoandrostenedione, 17 beta-hydroxy-5 beta-androstane-3,11-dione (tentatively identified), and OT-glucuronide were found. 17 beta-Hydroxy-5 alpha-androstane-3,11-dione was not present.

Androstane-3,17-diol

Apparent HLA DR triplet due to the coexpression of a DRB5-encoded molecule on a DR1 haplotype.

HLA DR1 molecules are coded by a single polymorphic DRB1 gene. We have observed rare DR1 cells in one Caucasoid family and three unrelated individuals that also reacted with some anti-DR2 sera. Since the second DR antigen was normally expressed, these cells appeared as triplets. Contrary to serology, the cells were not typed by HTCs defining Dw2, Dw12, and Dw21. Further investigations on these unusual DR1+2* haplotypes were conducted by DNA oligotyping and by sequencing of the DRB first-domain exon. The results showed that these DR1 haplotypes, besides their DRB1*0101 allele, carried also a DRB5*0101 allele.

Adult

Efficacy of cimetidine for gastric acid suppression in pediatric patients.

The efficacy of oral cimetidine for gastric acid suppression in pediatric patients was examined in a double-blind study. Twenty-seven patients with gastroesophageal reflux-related gastrointestinal symptoms, pulmonary symptoms, or both were given randomly determined doses of cimetidine. Response was evaluated by continuous intragastric monitoring with a pH probe. Twenty-three patients were given cimetidine doses of 5,7.5, and 10 mg/kg; eight of these patients were also given additional doses of 15 mg/kg. Four patients received only 10 and 15 mg/kg, because of previous poor clinical response to the lower dosages. The onset of gastric pH greater than 4 was delayed more than 2 hours in 50% of patients with responses to the 5 mg/kg dose. Of the patients with responses to the 10 mg/kg dose, 75% had showed a rise in gastric pH greater than 4 within 2 hours. With respect to the duration of gastric acid suppression, 70% of patients receiving 5 mg/kg doses and 52% of those receiving 7.5 mg/kg doses did not have a sustained a response for more than 2 hours, whereas 75% of patients receiving 10 mg/kg doses had gastric acid suppression for longer than 2 hours. Of the patients receiving 15 mg/kg doses, 75% had a response for more than 2 hours; 50% of these patients had a response for more than 3 hours. We conclude that recommended doses of cimetidine for children may not be optimal for adequate gastric acid suppression.

Administration, Oral

Epidemiological evidence of an interaction between calcium and sodium intake impacting on blood pressure. A Montréal study.

Nutritional calcium and sodium are considered to be important regulators of blood pressure. This study was performed on 182 randomly selected Canadians from Montréal to test the relative contribution of these ions to systolic and diastolic blood pressure, as well as their interaction with other demographic indices. Multiple analysis of the total study population revealed that 28% (P less than .001) of systolic blood pressure was predicted by gender sodium, and calcium interaction (P = .003), weight, and the additive effect of age and weight. The same characteristics contributed to 37% (P less than .001) of diastolic blood pressure with an additional contribution of alcohol intake. Analysis by terciles of sodium and calcium intake indicated that the positive effect of sodium on blood pressure occurred only in subjects given a low calcium diet, whereas blood pressure was lowest in the tercile of both high calcium and sodium intake. The impact of the sodium and calcium interaction on blood pressure represented as much as a 10 mm Hg decrement of systolic blood pressure with 400 mg calcium/1000 kcal intake at the highest level of sodium consumption and a 6 mm Hg decrease for diastolic blood pressure. In subjects without a family history of hypertension, the same indices contributed up to 53% of systolic and 55% of diastolic blood pressure with a synergetic effect of sodium and calcium, indicating that blood pressure was lowest in subjects given a high calcium and sodium diet. For subjects with a family history of hypertension, there was no significant impact of sodium, whereas calcium intake contributed negatively to both systolic and diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Alloantisera can detect some of the variants of HLA DRw13 identified by oligotyping.

Oligotyping has revealed a considerable polymorphism of HLA DRw13; so far, 5 alleles coded by DRB1 have been identified. An even greater number of haplotypes are apparent when considering the association of DRw13 with alleles coded by DRB3 and DQB1. Serology can now define some of these variants which had formerly escaped detection. We have tested by serology and by oligoprobes 66 genotyped Caucasoid cells comprising the known DR and DQ alleles. Among the 28 DRw6 cells, 10 different haplotype patterns were selected, of which 8 concern DRw13 and 2 DRw14. Four variants of DRw13 were represented: DRB1 *1301, *1302, *1303 and *1305 associated with usual and with uncommon alleles belonging to DRB3 and to DQB1. We have centered our analysis on 19 sera of the XIth Workshop defining DRw6. Two sera (639, 826) were noteworthy since they reacted with certain subtypes of DRw13 and with DRB1 *1102, *1103 only, the other DR specificities remaining negative.

Amino Acid Sequence

Ribotyping of Helicobacter pylori from clinical specimens.

Ribotyping is a method used to type strains of bacteria by analyzing the restriction enzyme digestion patterns of the rRNA genes. This method was applied to 126 strains of Helicobacter pylori from 100 unrelated symptomatic patients who had endoscopies done and to 15 strains from 15 infected subjects from seven families. Analysis of the rRNA gene patterns revealed 77 distinct ribotypes from the 100 patients. From 15 of these subjects, isolates were recovered from antral mucosal biopsies at follow-up endoscopy. All follow-up isolates from the same patient, with one exception, yielded identical digest patterns. This patient had strains with two distinct digest patterns obtained from a set of three isolates cultured from biopsy specimens taken at different times. Five patients who had isolates recovered from different sites in the stomach (antrum, gastric body, duodenum, and pyloric channel) showed ribotyping patterns which were identical for each patient yet distinct between patients. In seven family groups studied, identical digest patterns were detected in members of two families, with variability in strains detected among members of the remaining families. This study demonstrates that ribotyping provides a useful, reliable, reproducible, and highly discriminatory typing scheme for the study of H. pylori infection.

Bacterial Typing Techniques

Characterization of a tumor necrosis factor-alpha inhibitor activity in cancer patients.

To evaluate the feasibility of tumor necrosis factor-alpha (TNF-alpha) treatment of lung cancer patients, we chose the malignant cells contained in their pleural effusions as a first convenient target. We found, however, that a TNF-alpha inhibitor (TNF-alpha I) activity was present in both patient sera and pleural fluids. We therefore compared the TNF-alpha I activity present in patients with benign or malignant pleural effusions using a bioassay of TNF-alpha inhibition and partially characterized it. A high TNF-alpha I activity characterizes cancer patients with sera levels twice as high as the control level measured for blood bank donors (2.54 +/- 1.28 versus 1.19 +/- 0.38) and with even higher levels in pleural fluids (3.75 +/- 1.83). In contrast, patients with benign pleural effusions present similar levels of TNF-alpha I activity, at about the control level, in both their sera and pleural fluids (1.37 +/- 0.98 versus 1.16 +/- 0.85). A high TNF-alpha I activity is consistently found in cancer patients but is only released in vitro by leukocytes. It is most likely related to recently purified TNF-alpha inhibitors that, as soluble shed fragments of TNF receptors, may function as traps for TNF molecules. This study suggests that tumors may evade TNF cytotoxic action by modulating systemic levels of TNF and implies a reassessment of TNF therapy in cancer patients.

Adult

Dexamethasone modulation of tumour necrosis factor-alpha (cachectin) release by activated normal human alveolar macrophages.

Recurrent infections of the lower respiratory tract are a frequent and serious side-effect of chronic corticosteroid treatment. Since alveolar macrophages (AM) are currently thought to play a central role in the protection of the lower respiratory tract against infectious agents, it is likely that a steroid-induced deficiency of AM is involved in this process. In this respect, when activated, AM are major producers of tumour necrosis factor-alpha (TNF or cachectin), a versatile cytokine with several biological properties including antiviral and anti-infectious activities. A deficit of TNF production induced by corticosteroid may be one mechanism of the sensitivity to infections. Thus normal human AM obtained by bronchoalveolar lavage were pretreated with dexamethasone (DXM) before activation with lipopolysaccharides (LPS) and the amounts of TNF released in culture were quantified. Pretreatment with DXM resulted in a marked decrease of TNF release in a dose-dependent fashion. In contrast, when AM were activated with LPS before DXM treatment, TNF release by AM was suppressed in a more limited fashion. Thus DXM suppression of LPS-activated AM ability to release TNF may play a role in the susceptibility to infections of patients chronically treated with corticosteroids.

Adult

Insect immunity. Isolation from a coleopteran insect of a novel inducible antibacterial peptide and of new members of the insect defensin family.

Injection of heat-killed bacteria into larvae of the large tenebrionid beetle Zophobas atratus (Insecta, Endopterygota, Coleoptera) results in the appearance in the hemolymph of a potent antibacterial activity as evidenced by a plate growth inhibition assay. We have isolated three peptides (A-C) from this immune hemolymph which probably account for most of this activity. Their primary structures were established by a combination of peptide sequencing and molecular mass determination by mass spectrometry. Peptide A, which is bactericidal against Gram-negative cells, is a 74-residue glycine-rich molecule with no sequence homology to known peptides. We propose the name coleoptericin for this novel inducible antibacterial peptide. Peptides B and C are isoforms of a 43-residue peptide which contains 6 cysteines and shows significant sequence homology to insect defensins, initially reported from dipteran insects. This peptide is active against Gram-positive bacteria. The results are discussed in connection with recent studies on inducible antibacterial peptides present in the three other major orders of the endopterygote clade of insects: the Lepidoptera, Diptera, and Hymenoptera.

Amino Acid Sequence

Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes.

To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, we studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 micrograms/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group (136 mL/min per 1.73 m2; range, 91 to 158 mL/min per 1.73 m2) than in the placebo group (157 mL/min per 1.73 m2; range, 138 to 184 mL/min per 1.73 m2). Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group (379 mL/1.73 m2; range, 307 to 454 mL/1.73 m2) than in the placebo group (389 mL/1.73 m2; range, 347 to 465 mL/1.73 m2). Glycemic control did not change significantly in either group. We conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

Adult

[Aphasic disorders of written language].

After a short overview of classical neuropsychological knowledge about the disorders of written language, the authors review the data of cognitive psychology in this field. They first consider the general principles of cognitive analysis and then describe the specific syndromes of phonological and lexical routes impairment both in reading and writing. The possible correlations between these syndromes and other higher brain function impairments or anatomical localization are briefly considered. Finally an analysis of the impairments to peripheral writing processes, i.e. graphemic buffer and allographic conversion system syndromes, is given. In conclusion the contribution of cognitive psychology to daily neuropsychological practice is discussed.

Aphasia

HLA-DRw11, DQw7 has four cellular subtypes revealed by homozygous typing cells and undetected by restriction fragment length polymorphism.

HLA-DRw11 is in strong linkage disequilibrium with DQw7. We have investigated the heterogeneity of DRw11, DQw7 by cellular typing and by HLA cDNA probes. The results obtained by local and other homozygous typing cells in four informative Caucasoid families and 20 genotyped individuals demonstrate the existence of at least four different cellular subtypes. The frequency of DRw11, DQw7 is 25.7% with the following distribution of subtypes: Dw5 (17.3%), JAC (4.2%), JVM (2.8%), TIS (0.7%), and blank (0.7%). JVM (10W 9039) has been previously described; TIS (10W 9042) and JAC are postulated new specificities from our laboratory. None of these subtypes typed for DRw11, DQw1 cells. The cellular heterogeneity contrasts with the absence of polymorphism observed by serology and by restriction fragment length polymorphism after hybridization with DRB, DQA, and DQB probes. Variation in amino acids of the DRB1 chain has been reported for at least three variants: Dw5, JVM, and TIS (more recently).

Amino Acid Sequence

Diversity among DRw13 DQw7 haplotypes as revealed by serology Dw typing and restriction fragment length polymorphism.

HLA-DRw13 is in linkage disequilibrium with DQw6; an unusual association, DRw13 DQw7, is found in 2% of our Caucasoid population. Investigation of genotyped individuals and of families by two allosera and by Dw typing revealed two subtypes: one recognized by homozygous typing cell HAG and by two allosera, the other subtype remained unreactive with both reagents. Analysis of DNA fragments with DNA probes indicated that the HAG-negative subset had DNA fragments in common with DRw6 while the HAG-positive subset shared DNA fragments with DR5. However, all DRw13 DQw7 cells are Dw24 as seen by hybridization with DRB probe.

Genetic Variation

The cholinergic regulation of potassium (86Rb+) permeability in sweat glands isolated from patients with cystic fibrosis.

Sweat glands isolated from skin obtained from normal subjects and patients with cystic fibrosis (CF) were pre-loaded with 86Rb+ and superfused with a physiological salt solution and the rate of 86Rb+ efflux was measured as an indicator of cellular potassium permeability. Acetylcholine always evoked a permeability increase in the glands from control subjects and this response could be resolved into calcium-dependent and calcium-independent components. Sweat glands from CF patients did not show such consistent responses. In three individuals the glands were abnormally insensitive to acetylcholine but normal responsiveness was seen in a fourth case. It is proposed that CF can induce dysfunction of calcium-dependent control processes in sweat glands.

Acetylcholine

Interactions among calcium, sodium, and alcohol intake as determinants of blood pressure.

It has been reported that calcium intake may effectively modulate the expression of hypertension affected by sodium. The present study extends our previous analysis of this calcium-sodium interaction, additionally demonstrating that calcium, sodium, and alcohol intake further contribute to both systolic and diastolic blood pressures in normotensive subjects. Calcium intake was related to lower blood pressure over all ranges of sodium and alcohol intake, and alcohol intake contributed positively and significantly to both systolic and diastolic blood pressures. However, sodium was associated with increased blood pressure only at low calcium intake, particularly in subjects who consumed large amounts of alcohol. This study points to a significant interaction among sodium, calcium, and alcohol intake as determinants of blood pressure, which, together with gender and weight, contribute to 31% of systolic blood pressure and with the addition of age to 36% of the variance in diastolic blood pressure.

Adult