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Biomedical subjects

J Ruiz

Publications and source records attributed to J Ruiz.

At least 217 records · Page 12Linked to original sources

Evidence for a circadian rhythm of insulin secretion.

Insulin secretion was studied in healthy volunteers at three different levels of glycemia. Plasma glucose was clamped at approximately 5, approximately 8.8 and approximately 12.6 mM for 68 h. Measured were serum insulin concentration and insulin secretion rates (ISR), the latter by deconvolution of plasma C-peptide concentration. Rhythmic patterns of ISR were identified (with a refined first-order Fourier transform) at all three glucose concentrations tested but were most clearly seen at 12.6 mM. ISR and serum insulin concentration changed in a circadian (approximately 24 h) rhythm, increasing from a nadir between midnight and 6 A.M. and reaching a peak between noon and 6 P.M. At 12.6 mM hyperglycemia, the amplitude of the insulin concentration cycles was greater than that of the ISR cycles (+/- 13.0 vs. +/- 8.7%) due to a decrease in insulin clearance (from 1.55 to 0.5 l/min, P < 0.01). Plasma melatonin levels (a marker of light-dark rhythmicity) changed in the opposite direction, i.e., they peaked when ISR bottomed and bottomed when ISR peaked. We concluded that normal human subjects have a circadian rhythm of insulin secretion, which becomes more apparent with rising ISR, and that circadian changes in ISR, rising during the day and falling during the night, may be one explanation for the well-established observation that glucose tolerance and insulin responses to glucose and meals are higher in the morning than at night.

Adult↗

[Efficacy and tolerance of the treatment of tuberculosis in the aged].

We analyzed 55 confirmed cases of tuberculosis in patients over 65, a sample that amounted to 9% of all patients seen in our practice over a period of 5 years. Mean age was 72.4 and the male/female ratio was 4/1. The most frequently associated diseases were tobacco addiction (49%), chronic obstructive pulmonary disease (33%), alcoholism (25%) and prior diagnosis of tuberculosis (20%). Lung involvement was the most common clinical presentation (76%), followed by pleural (9%) and skeletal (7%) involvement. The clinical picture was non specific, with 13% remaining asymptomatic. Cough was the most frequent symptom (45%) and unilateral apical fibrosis with ulceration was the most frequent radiological finding. Pleural discharge and cavitation were demonstrated in 14 and 22%, respectively. Scarring was visible on X-rays in 44%. The tuberculin test was positive in 88% of the cases in which it was performed. Mean delay in diagnosis was 3.4 months; 62% were diagnosed by sputum test, 11% by culture, and 27% histology. In 4% death was directly caused by tuberculosis. Three patients withdrew from treatment, in one case treatment failed, and there was one relapse detected at follow-up. We observed adverse side effects in 33%, and found no statistically significant differences between the 2 therapeutic protocols used (2 months RHS/7 months RH and 2 months RHZS/4 months RH). The incidence of tuberculosis among the elderly is low in our practice and the entity behaves much as it does in the rest of the adult population. Both the efficacy and tolerance of treatment can be considered optimal.

Adult↗

Epidemiology of sarcoidosis in Catalonia: 1979-1989.

For the purpose of estimating the incidence rate and clinico-epidemiological characteristics of sarcoidosis in Catalonia (a country comprising the provinces of Barcelona, Tarragona, Lleida and Girona, with a total population of 6 million people), we did a retrospective study of new cases diagnosed in the country's qualified hospitals during 1979 and the three-year period from 1986 to 1988. The annual incidence rate in the province of Barcelona was 1.2/100,000 in 1979 and 1.5/100,000 in 1988. 245 cases were diagnosed in Catalonia in the three-year period covering 1986-88, the annual incidence rate being 1.36/100,000 inhabitants. We describe here the characteristics of this series of 245 cases (which is the first one representative of the whole of Catalonia), and compare them with those of other series published previously. We conclude that the incidence of sarcoidosis in our country is one of the lowest in Europe, with no significant variations observed over ten years. The most relevant clinico-epidemiological characteristics are its clear predominance in women (3:1), and the high frequency of Löfgren's syndrome (48% of cases), whose incidence is significantly higher in springtime.

Adolescent↗

Additive effect of A-->G (-3826) variant of the uncoupling protein gene and the Trp64Arg mutation of the beta 3-adrenergic receptor gene on weight gain in morbid obesity.

OBJECTIVE: Obesity results from an imbalance between caloric intake and energy expenditure, which is partly genetically determined. We have investigated, using a PCR-RFLP assay, the effects on weight gain of two genetic variants of the uncoupling proteins and the beta 3-adrenoceptor, two major expressed proteins of the brown adipose tissue (BAT) involved in thermo-genesis. SUBJECTS: 238 morbidly obese and 91 non obese Caucasian subjects. RESULTS: A high prevalence (27%) in French Caucasians of the A-->G change variation located in the 5' flanking domain of the UCP gene was observed with no significant difference between morbidly obese patients and non obese subjects, suggesting that UCP gene is not a major gene for obesity. However, in the population of morbidly obese subjects, the presence of the A-->G allelic variant of the UCP gene showed to be an associated factor of high weight gain during adult life (odd-ratio: 1.4, P = 0.02). Such an association was previously described for the Trp64Arg mutation of the beta 3-AR gene. Furthermore, an additive effect of these two gene variants on weight gain was observed (Odd-Ratio: 4.95, trend test: P = 0.05). The attributable risks for UCP gene and beta 3-AR gene variants were respectively: 25% and 9%. CONCLUSION: These data support the hypothesis of a possible link between energy balance, BAT and weight gain in human.

Adipose Tissue, Brown↗

Serotonin uptake and its kinetics in platelets of women with Alzheimer's disease.

The uptake of serotonin (14C-5-hydroxytryptamine, 5HT) in platelets and its kinetic characteristics were investigated in a group of women (n = 20) with probable Alzheimer's Disease (mean age = 76.0, years, SD = 8.27, range = 63-88) and in healthy normal women (n = 18, mean age = 72.6 years, SD = 7.24, range = 61-84). Both the apparent affinity of binding of 5HT to the platelet membrane (Km) and the maximum velocity (Vmax) of the rate of transport of 14C-5HT into platelets were significantly higher in the Alzheimer's Disease group than in the normal comparison group. Initial velocity of 14C-5HT uptake not passive diffusion (nonspecific uptake of 14C-5HT at 4 degrees C) differed significantly in the two groups. Our findings suggest abnormalities in the kinetic mechanisms involved in the uptake of 14C-5HT by platelets in women with Alzheimer's Disease.

Aged↗

Gln-Arg192 polymorphism of paraoxonase and coronary heart disease in type 2 diabetes.

Paraoxonase is a high-density-lipoprotein-associated enzyme capable of hydrolysing lipid peroxides. Thus it might protect lipoproteins from oxidation. It has two isoforms, which arise from a glutamine (A isoform) to arginine (B isoform) interchange at position 192. The relevance of this polymorphism to coronary heart disease (CHD) in non-insulin-dependent diabetic patients was investigated in case-control study. Of the 434 patients, 171 had confirmed coronary artery disease; the other 263 had no history of such disease. The B allele and AB+BB genotypes were associated with an increased risk of coronary heart disease. Compared with subjects homozygous for the A allele (AA genotype), the odds ratio of CHD for subjects homozygous for the B allele was 2.5 (95% CI 1.2-5.3) and that for those heterozygous for the B allele was 1.6 (95% CI 1.1-2.4), suggesting a codominant effect on cardiovascular risk. When subjected to multivariate analysis, the B allele remained significantly associated with CHD (odds ratio 1.94, p = 0.03). The paraoxonase gene polymorphism is thus an independent cardiovascular risk factor in non-insulin-dependent diabetic patients. A possible explanation for this finding is that activity of the paraoxonase B isotype does not protect well against lipid oxidation, a major atherogenic pathway.

Arginine↗

Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity.

BACKGROUND: The beta 3-adrenergic receptor, located mainly in adipose tissue, is involved in the regulation of lipolysis and thermogenesis. The potential relevance of this receptor to obesity in humans led us to screen obese French patients for a recently identified mutation in the gene for the receptor. METHODS: We used the polymerase chain reaction to amplify a region of the gene for the beta 3-adrenergic receptor encoding amino acid residues 27 to 110 in genomic DNA extracted from leukocytes from 185 patients with morbid obesity (body-mass index [the weight in kilograms divided by the square of the height in meters], > 40) and 94 normal subjects. A mutation resulting in the replacement of tryptophan by arginine at position 64 (Trp64Arg) was detected by an analysis of restriction-fragment-length polymorphisms with the use of the endonuclease BstNl, which discriminates between the normal and mutant sequences. RESULTS: The frequency of the Trp64Arg allele was similar in the morbidly obese patients and the normal subjects (0.08 and 0.10, respectively). However, the patients with morbid obesity who were heterozygous for the Trp64Arg mutation had an increased capacity to gain weight; the mean weight in the 14 heterozygous patients was 140 kg, as compared with 126 kg in the 171 patients without the mutation (P = 0.03). There were no homozygotes in this sample. The cumulative 25-year change in weight (from the age of 20 years) was 67 kg in the Trp64Arg heterozygotes, as compared with 51 kg in those without the mutation. The maximal weight differential (the maximal lifetime weight minus the weight at 20 years of age) in the Trp64Arg heterozygotes was 74 kg, as compared with 59 kg in the patients without the mutation (P = 0.02). CONCLUSIONS: People with the Trp64Arg mutation of the gene for the beta 3-adrenergic receptor may have an increased capacity to gain weight.

Adult↗

Effect of grapefruit juice on blood cyclosporin concentration.

Grapefruit juice increases blood concentrations of some dihydropyridine calcium-channel blockers, which are metabolised by the P450 enzymes that also metabolise cyclosporin. We evaluated, in a randomised cross-over study, the effect of grapefruit juice on blood cyclosporin concentrations in 14 healthy adults. Each subject was given oral cyclosporin 300 mg with 250 mL grapefruit juice, orange juice, or water. Area-under-the-curve (AUC) was significantly higher with grapefruit juice than with water or orange juice (means 7057, 4871, and 4932 ng h/mL, respectively; p < 0.0001). Thus grapefruit juice may provide a non-toxic and inexpensive alternative to drugs that are used to reduce cyclosporin dose.

Adolescent↗

Detection of coronary artery disease in diabetic patients.

Coronary artery disease may be difficult to detect in diabetic patients. This study was designed to determine the specificity and sensitivity of three noninvasive tests. Accordingly, the results of 48-h ambulatory electrocardiogram (ECG) monitoring, maximal ECG exercise test, and intravenous dipyridamole myocardial thallium scintigraphy were compared in 59 middle-aged diabetic patients who were consecutively selected for suspected coronary artery disease. All patients also underwent coronary angiography, which was performed regardless of the results of the non-invasive tests. Twenty patients (34%) had significant coronary lesions, i.e. stenosis equal to or greater than 70%, and 16 of these 20 patients (80%) had double or triple vessel disease. Sensitivity and specificity were, respectively, 25% and 88% for ambulatory ECG monitoring, 75% and 77% for the exercise test and 80% and 87% for thallium myocardial scintigraphy. This observation strongly supports the use of non-invasive tests for the detection of coronary artery disease in those diabetic patients at high risk of such disease. As the exercise test is cheaper and more widely available than thallium myocardial scintigraphy it should be used as a first line examination. Dipyridamole myocardial scintigraphy may provide an alternative solution for those patients who cannot perform maximal exercise, or with atypical clinical presentation.

Adult↗

Effect of lipid oxidation on the regulation of glucose utilization in obese patients.

The effect of changes in lipid oxidation on glucose utilization (storage and oxidation) was studied in seven nondiabetic obese patients. They participated in three protocols in which: (1) Intralipid (to raise plasma FFA concentrations), (2) beta-pyridylcarbinol [a precursor of nicotinic acid, to lower plasma free fatty acids (FFA) concentrations], or (3) isotonic saline were infused over 2 h. Thereafter, these infusions were discontinued, and a 2-h euglycemic, hyperinsulinemic clamp was performed to measure glucose uptake. All studies were carried out in combination with indirect calorimetry to measure oxidative and nonoxidative glucose disposal (glucose storage). The high plasma FFA concentrations (1024 +/- 57 mumol/l) and lipid oxidation rates (1.1 +/- 0.1 mg/kg.min) found at the end of the Intralipid infusion and the low plasma FFA concentrations (264 +/- 26 mumol/l) and lipid oxidation rates (0.7 +/- 0.1 mg/kg.min) found at the end of the beta-pyridylcarbinol infusions resulted in significantly different rates of total and nonoxidative glucose disposal during the insulin clamp. The values were 2.6 +/- 0.6 mg/kg.min after Intralipid and 4.1 +/- 1.0 mg/kg.min after beta-pyridylcarbinol for total glucose disposal, and 0.4 +/- 0.4 and 1.6 +/- 0.8, respectively for nonoxidative glucose disposal. In conclusion, these observations show that changes in lipid oxidation rates preceding a glucose load influence glucose disposal and glycogen storage in obese subjects.

Adult↗