Search PubMed⌕ Search

Biomedical subjects

R Bruno

Publications and source records attributed to R Bruno.

At least 145 records · Page 8Linked to original sources
PubMed1987

[Radiological changes in the nasal and paranasal cavities of patients having undergone laryngectomy].

A greater incidence of nasal sinus lesions is revealed in patients operated for laryngectomy than in healthy subjects. The radiographs of the paranasal sinuses of 49 patients laryngectomized for laryngeal cancer and 71 smokers, over 40, were compared. Thirty-six (73.5%) of the operated patients showed a reduction in the lucency of the sinuses (opacities, sinusitis, mucocele) and 21 (42.9%) inferior concha hypertrophy. In the control group 23 (32.4%) and 12 (16.9%) cases had the same lesions. Chi2 statistical analysis was performed on both groups. The results show a significant increase in lesions of the nasal sinuses in the group of operated patients. The reduction in the air flow through the nose and the sinus cavities during breathing seems to be the pathogenic mechanism responsible for such findings.

Adult↗
PubMed1986

Steady-state dosage regimen calculations in linear pharmacokinetics.

This paper describes a general approach to compute steady-state dosage regimens. The method deals with individual linear compartmental mammillary pharmacokinetic models and requires estimated values of model parameters. It is based on the linearity principle and computes dosage regimens to achieve and maintain specified steady-state plasma concentrations, e.g. mean value or minimum effective and maximum safe levels. An interactive computer program performing the calculations has been developed.

Administration, Oral↗
PubMed1986

Effect of insulin on pyruvate dehydrogenase in a mixture of plasma membranes and mitochondria from normal and alloxan treated rat brains.

In a mixture of plasma membranes/mitochondria from normal rat brain, pyruvate dehydrogenase (PDH) is present in the active (PDHa) and the inactive (PDHi) form; the latter is converted into the former by preincubation with Ca2+ and Mg2+ and represents about 40% of total PDH (PDHt = PDHa + PDHi). Incubation with increasing insulin concentrations activates PDHa and PDHt, the maximum being reached at 25 microU/ml insulin; inhibition appears with further insulin increase. In a mixture of plasma membranes and mitochondria from alloxan rat brain PDHa activity markedly decreases; no activation is achieved by preincubation with Ca2+ and Mg2+. However an activating effect of Ca2+ and Mg2+ appears when the mixture is added and incubated with increasing insulin concentrations. PDHa and PDHt activity reaches a maximum of stimulation at 25 microU/ml insulin; the activation is reduced at higher concentrations of insulin though no inhibition appears. ATP partially inhibits PDHa in normal and alloxan rat brain plasma membrane/mitochondria mixtures; this effect is completely cancelled by 25 microU/ml insulin.

Animals↗
PubMed1985

Bayesian estimation and prediction of clearance in high-dose methotrexate infusions.

Much attention has been paid to the problem of estimating the pharmacokinetic parameters of individual patients in order to optimize dosage choices. Individual kinetics determined by test-dose bolus injection are a basis for predicting drug concentrations after high-dose methotrexate infusion and for computing appropriate dosages. Simplifications may be attempted, even allowing the test-dose to be omitted by using Bayesian estimation rather than likelihood estimation. To individualize pharmacokinetic parameters, Bayesian estimation combines information about population characteristics and those of individuals based on few measured plasma levels during high-dose infusion. Application of this procedure to methotrexate reveals interesting predictive performances and ability to handle variation due to intraindividual time variability without using test doses. The methodology promises to be more efficient in computing dosages in order to avoid toxic levels and will be less expensive in routine clinical use.

Aged↗
PubMed1985

Dosage predictions in high-dose methotrexate infusions. Part 1: Evaluation of the classic test-dose protocol.

A preliminary methotrexate (MTX) kinetic evaluation following administration of an IV bolus (test-dose) allowed individualization of high-dose infusions (HD-MTX). This approach combined with therapeutic drug monitoring was found to have good performance over a large scale of predicted steady-state levels (Css) (10(-5) to 10(-4) M over 24 to 36 h) corresponding to 17 to 650 mg/h deliveries (root mean squared error : rmse (precision) = 1.54 X 10(-5) M (21.4%) and mean error : me (bias) = 0.043 X 10(-5) M (NS)). However a significative (p less than 0.05) but rather low over-estimation of dosage (me = 7.38 X 10(-5) M (14.8%)) associated to a decrease in the prediction precision (rmse = 13.3 X 10(-5) M (26.6%)) occurred in 5 X 10(-4) M predicted Css over 8 h (970 to 1970 mg/h deliveries). However in a number of cases (6 out of 29) important deviations from predicted Css occurred, implying the need to stop the infusion before 8 h. These results indicated that MTX pharmacokinetics was linear from low test-dose bolus injections to high-dose infusions. This allowed dosage predictions based upon preliminary estimation of MTX clearance and associated to therapeutic drug monitoring during and following infusion.

Head and Neck Neoplasms↗
PubMed1985

Dosage predictions in high-dose methotrexate infusions. Part 2: Bayesian estimation of methotrexate clearance.

Population pharmacokinetics of methotrexate (MTX) was evaluated from intravenous test-dose (TD) data (n = 20 corresponding to 174 measured samples). Bayesian prediction of MTX clearance from TD experiments combining population data with measured levels (at times 0.5 and 6 h) was found to be feasible in routine situations with good performance (root mean squared error : rmse (precision) = 1.14 1.h-1 (11.2%) and mean error : me (bias) = 0.06 1.h-1 (NS) relatively to weighted least-square estimates, n = 50). The precision of Bayesian prediction was comparable to that of the model independent which is used in routine practice and involves 9 measured levels over 30 h, (rmse = 1.35 1.h-1 (10.9%), n = 50). However, the routine method presented a significative bias (me = -0.81 1.h-1, n = 50).

Humans↗
PubMed1985

Lumbar spinal stenosis: analysis of pre- and postoperative somatosensory evoked potentials.

Cortical somatosensory evoked potential (CSEP) examinations were performed of 20 patients with lumbar spinal stenosis a day prior to surgery and 10 to 12 days after spinal decompression and bilateral lateral fusion. CSEPs were recorded to Cz-Fz (10-20 international EEG system) following stimulation of 32 tibial, peroneal and sural nerves and 16 saphenous nerves. A total of 110 nerves were examined. Using CSEP P1 latency as criteria for inclusion in the study, 21 tibial, 20 peroneal and 17 sural nerves were subjected to paired two-tailed t tests to determine whether the CSEP changes that occurred postoperatively were statistically significant (p less than 0.05). Postoperative P1 latencies of tibial, peroneal, and sural nerves changed significantly as well as N1 latencies and P1-N1 amplitudes of tibial and peroneal nerves. Nineteen patients improved clinically. It is postulated that pathologic narrowing of the spinal canal in spinal stenosis leads to nerve root compression and ischemia with resultant dysfunction primarily affecting large diameter myelinated fibers and that decompression procedure may adequately relieve the underlying pathologic processes. Improvement in CSEPs may be from increase in available numbers of functioning large diameter myelinated fibers, conversion to normal from a conduction block, and, perhaps, improved axoplasmic flow.

Adult↗
PubMed1985

A pilot study of the pharmacokinetics and triglyceride lowering activity of acipimox in dialyzed uremic patients.

The pharmacokinetics of acipimox was studied in 6 dialyzed uremic patients given single oral doses of 50 mg. Acipimox was not significantly eliminated outside dialysis, whereas during dialysis it was efficiently cleared with plasma, t 1/2 is about 2.6 hours. Accordingly, a dosage schedule of 50 mg or 100 mg of acipimox after each dialysis session was selected for a second, 4-week study in 14 uremic patients with hypertriglyceridemia. Acipimox plasma levels, monitored during the study, proved in agreement with those expected on a theoretical pharmacokinetic basis. A clear-cut reduction of serum triglyceride levels was also achieved.

Adult↗
PubMed1984

[Activation of pyruvate dehydrogenase by addition of insulin to a mixture of cell membranes and mitochondria from the brain of normal and alloxan treated rats. (Preliminary note)].

The effect of insulin and ATP on pyruvate dehydrogenase activity has been studied in a mixture of plasma membranes/mitochondria from normal and diabetic rat brain. In both enzymatic preparations ATP inhibits almost completely pyruvate dehydrogenase activity; insulin on the contrary induces a conspicuous activation and removes the inhibiting action of ATP.

Animals↗
PubMed1984

Changes in the activities of NADP+-linked dehydrogenases during ontogenesis in the chicken.

Changes in the activities of glucose-6-phosphate dehydrogenase [EC 1.1.1.49], 6-phosphogluconate dehydrogenase [EC 1.1.1.44] and cytoplasmic and mitochondrial "malic" enzyme [EC 1.1.1.40] and NADP+- linked isocitrate dehydrogenase [EC 1.1.1.42] were measured in the liver, heart, lung and brain during ontogenesis in the chicken. In the liver the cytoplasmic malic enzyme was constant during embryonal development, increasing suddenly and markedly thereafter and isocitrate dehydrogenase increased in the embryo and decreased after hatching while their mitochondrial isoenzymes showed parallel but less marked changes. Activities of the other dehydrogenases were essentially unchanged. In the heart only cytoplasmic isocitrate dehydrogenase showed important changes, increasing three-fold during growth after hatching. In the lung, glucose-6-phosphate dehydrogenase and cytoplasmic malic enzyme attained their maximum activities respectively at 16 to 18 d and 14 d of development. Mitochondrial malic enzyme did not change, while isocitrate dehydrogenase reached its maximum between 14 and 18 d. In the brain cytoplasmic malic enzyme was activated only after hatching, while its mitochondrial isoenzyme and isocitrate dehydrogenase showed discontinuous variations of an insignificant magnitude. Other activities were unchanged.

Animals↗
PubMed1984

[Plasma acetate and bicarbonate kinetics and intolerance to acetate during and after renal dialysis].

Plasma acetate kinetics, acid-base homeostasis and clinical tolerance were monitored in 7 patients with chronic renal failure during and after hemodialysis with standard conditions. In 6 patients, without severe clinical symptoms acetate levels became stable during the last hour of dialysis (4.86 +/- 0.44 mmol/l) and decreased according to first order kinetics (half-life (8.82 +/- 3.42 mn). Simultaneously bicarbonate levels significantly increased (p less than 0.005). At the opposite the 7th patient has been characterised by a continuous rise in acetate levels (12.3 mmol/l at the end of the dialysis), a slower elimination (half-life: 31.0 mn), a collapse of plasma bicarbonate and severe acetate intolerance. Moreover symptomatic patients were characterised by an increase of plasma levels and half-lives. Therefore it seems that during dialysis of comparable efficiency, an insufficient rate of acetate metabolism may be at the origin of a worsening of metabolic acidosis as well as an increase of acetate load, responsible for severe acetate intolerance.

Acetates↗
PubMed1983

[Levels of glutathione and anaerobic glycolysis in the kidney and liver of rats treated with chloroethanol].

Chloroethanol administration produces in rats a strong fall of glutathione levels in liver and kidney tissues. In liver, such a modification does not imply alterations in the levels of glucose, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-biphosphate, lactate and pyruvate and in the glycolytic activity. In kidney, the glycolytic activity does not result modified, while it appears a reduction in levels of glucose, glucose-6-phosphate, fructose-1,6-biphosphate and triose phosphates and a remarkable increase of pyruvate. The administration of chloroethanol produces a strong fall of glutathione in the soluble and nuclear fractions of liver and in the soluble and mitochondrial fractions of kidney.

Anaerobiosis↗
PubMed1983

[Effect of insulin on brain pyruvate dehydrogenase in the rat. (Preliminary note)].

The activity of both active and total pyruvate dehydrogenase (E.C.1.2.4.1) is substantially reduced in the rat brain 24h after alloxan administration. Effects are partially removed by insulin administration. Ca++ and Mg++ produce: a) a considerable conversion of the inactive form of pyruvate dehydrogenase into its active form in a preparation from the brain of normal rats and of rats treated with insulin; b) no conversion in a preparation from the brain of rats treated with alloxan; c) some conversion in a preparation from the brain of rats treated with both alloxan and insulin. Active and total pyruvate dehydrogenase from the brain of rats treated with alloxan are activated by a preparation obtained from a mixture of entire plasma membranes-mitochondria from normal and from alloxan-treated rats, or from insulin-treated and alloxan treated rats. The oxygen uptake, the respiratory control index and the ADP/O ratio in mitochondrial preparations obtained from the brain of rats treated with alloxan show no modification at all.

Animals↗
PubMed1983

Randomized controlled trial of a nonpharmacologic cholesterol reduction program at the worksite.

Under experimental clinical conditions diet modification has been shown to reduce serum cholesterol levels. This paper reports such a positive response to a nonpharmacologic, behavioral education program at the worksite. Employees at the New York Telephone Company corporate headquarters were assigned randomly to treatment and control groups. Treatment consisted of an 8-week group cholesterol reduction program conducted during employee lunch hours. It comprised a multiple-treatment approach--food behavior change techniques combined with nutrition education, physical activity planning, and self-management skills. The treatment group showed substantial change compared with the control group at the program's completion. Those treated displayed a significant 6.4% reduction in total serum cholesterol (266 mg% average at baseline) as compared with control subjects with a corresponding decrease in high-density lipoprotein levels. A significant increase in nutrition knowledge and moderate weight loss were also documented for this group. The magnitudes of a participant's baseline serum cholesterol level and his/her reduction in percentage of ideal body weight were positively and independently correlated with percentage changes in serum cholesterol levels. Over the same period, decreases in high-density lipoprotein levels and no changes in serum cholesterol, weight, and nutrition knowledge were observed for the control group. Overall, participants in the treatment program successfully reduced the coronary heart disease risk factors of elevated cholesterol and weight. Directions for future study are suggested.

Behavior Therapy↗
PubMed1983

Antiaggregant effect of indobufen (K3920) measured by the platelet aggregate filtration pressure test (PAFP).

The platelet aggregate filtration pressure test (PAFP) was used to study the aggregant activity of single doses of 200 mg indobufen, administered either orally or by i.v. injection. This double-blind study using placebo in a crossover design was conducted in twelve patients whose baseline aggregation values were high. The compound showed markedly different antiaggregant activity from placebo at the various observation times after administration. The two administration routes did not produce any significant differences. The PAFP test can be useful in identifying atherosclerotic patients with platelet hyperaggregation, and for clinical pharmacology studies with platelet antiaggregant drugs.

Administration, Oral↗
PubMed1983

Pharmacokinetic study of ethanol after oral administration: a new approach to enzymatic elimination.

A new approach to the enzymatic elimination of ethanol in vivo allows us by means of a one-compartment model to take into account all the phases of the ethanol concentration-time curve after oral administration. The Michaelis-Menten equation is an approximation of this model; indeed it constituted the only non-linear approach to the kinetic study of ethanol. To express the model in the form of an equation leads to a third-order system of bilinear differential equations which has no analytical solution. The identification of the model is based on the optimization of a conformity criterion between experimental values and those predicted by the model. Optimization is performed by means of an iterative algorithm minimizing non-linear functions. This method permits the estimation of initial concentrations of products involved in the enzymatic reaction (substrate, enzyme) and kinetic constants (characterizing absorption and enzymatic reaction). Kinetics in nonalcoholics, alcoholics, and former alcoholics were identified using this new model. A good fit between the experimental values and the simulated curve was obtained. The in vivo estimation of the kinetic constants of each elementary step of the enzymatic reaction represents an original approach likely to provide more knowledge of ethanol metabolism.

Adult↗