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Biomedical subjects

P Muller

Publications and source records attributed to P Muller.

At least 19 recordsLinked to original sources

Role of reactive O2 in phagocyte-induced hypermetabolism and pulmonary injury.

Activated phagocytes possess an enormous capacity for O2 consumption via NADPH oxidase. NADPH oxidase partially reduces O2, forming superoxide (O2-). Host enzymes rapidly complete O2- reduction to H2O, leaving little trace of its prior existence. Our objectives were to estimate the magnitude of whole body phagocyte respiration and determine the contribution of NADPH-derived O2- to the ensuing phagocyte-induced pulmonary injury. These objectives were accomplished using specific inhibitors of NADPH oxidase, diphenyl iodonium (DPI) and di-2-thienyl iodonium (DTI). Guinea pigs received intravenous injections of DPI (3.5 mg/kg), DTI (7.5 mg/kg), or vehicle followed by phorbol myristate acetate (PMA). Phagocyte activation by PMA immediately increased whole body respiration from 13.6 to 16.1 ml O2.kg-1.min-1 (P < 0.05). DPI and DTI completely blocked the increase in respiration induced by PMA injection (P < 0.05). Baseline respiration was unchanged by the NADPH oxidase inhibitor alone. Likewise, there was no effect on the respiration of isolated heart and kidney mitochondria from animals receiving the inhibitor with or without PMA. DPI attenuated the pulmonary injury induced by PMA. DPI attenuated the pulmonary injury induced by PMA. The ratio of lung water weight to dry weight was lower (6.4 +/- 0.3 vs. 8.3 +/- 0.6) and arterial PO2 was higher (86 +/- 9 vs. 56 +/- 6 Torr) in animals receiving DPI plus PMA than in those receiving PMA alone. In conclusion, phagocyte activation in vivo increased total body respiration by approximately 18%. The burst in respiration is attributed to the phagocyte respiratory burst in which NADPH oxidase partially O2 to O2-.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Latero-cervical thyroid tissue and congenital hypothyroidism revealed in adult age].

It is generally admitted that in front of tissues of thyroid origin found in latero-cervical position, the clinician should look for the presence of an occult thyroid carcinoma. This position is therefore against the diagnosis of lateral aberrant thyroids or benign metastatic thyroidosis that have been evocated in the past. We present the case of a 59 yr old woman in whom the diagnosis of benign latero-cervical mass of thyroid origin was made in association of an undiagnosed congenital hypothyroidism due to an ectopic thyroid gland in a sub-lingual position. This observation as well as recent published observations are in contrast with the current medical practices which should be discussed according to the location of the cervical mass and to precise histopathological features.

Age Factors

Relative potency of eltanolone, propofol, and thiopental for induction of anesthesia.

BACKGROUND: The primary purpose of this investigation was to determine the relative potency of eltanolone, a new steroid hypnotic, and propofol and thiopental when used for induction of general anesthesia. In addition, the induction characteristics of propofol and eltanolone were compared. METHODS: One hundred seventy-five patients, premedicated with lorazepam 1 mg orally, randomly received one of six different doses of either eltanolone or propofol. The probability of successful induction (defined as not responsive to verbal commands within 2 min) was related to the logarithm of the dose for each drug by means of logistic regression analysis. Estimates of ED50 and ED95 for each drug were obtained. The incidence of side effects was compared for eltanolone and propofol. The potency of thiopental was determined in a parallel study, using an identical methodology in 105 patients receiving one of seven different doses of the barbiturate. RESULTS: The relative potency of eltanolone was 3.2 times (95% confidence interval 2.7-3.8) greater than propofol and 6.0 times (5.3-6.9) greater than thiopental. ED50 and ED95 values for eltanolone were 0.46 (0.40-0.52) and 0.82 (0.68-1.28) mg.kg-1, respectively. Compared to propofol, induction of anesthesia with eltanolone is characterized by a lower incidence of injection pain (3.5% vs. 58%) and apnea (1.2% vs. 11.2%). CONCLUSIONS: Eltanolone appeared to be an effective induction agent that is 3.2 times more potent than propofol and 6 times more potent than thiopental. Its use was associated with less pain on injection than was propofol.

Adolescent

Microassay of decarboxylation reactions in cultured cells.

The currently described methods for determination of decarboxylation reaction rates in cultured cells require large quantities of cells and often involve cell manipulation prior to assay. We describe a simple microassay for the rapid measurement of various decarboxylation reaction rates in intact cultured cells. The assay is based on the traditional measurement of 14CO2 generated from 14C-labeled substrates. Key to the method is a novel modification of the standard petri dish. Pyruvate dehydrogenase, branched chain alpha-ketoacid dehydrogenase, alpha-ketoglutarate dehydrogenase, and ornithine decarboxylase activities were determined in adult cardiomyocyte cultures containing only 0.1-0.5 mg of protein per culture dish. Efficiency of 14CO2 collection ranged between 94 and 100%. Pharmacological enhancement or inhibition of pyruvate dehydrogenase activity was easily detected in the culture system. This new method simplifies the measurement of various decarboxylation reaction rates in cultured cells and allows rapid, reproducible measurements to be made on small numbers of cells without perturbation of the culture conditions or the cells themselves.

Animals

Human pituitary null cell adenomas and oncocytomas in vitro: effects of adenohypophysiotropic hormones and gonadal steroids on hormone secretion and tumor cell morphology.

Human pituitary null cell adenomas and oncocytomas are not associated with evidence of excess hormone secretion in vivo; their cellular derivation has not been clarified by morphologic investigation. In this study we examined 41 null cell adenomas and 58 oncocytomas in vitro to determine hormone release and its response to several adenohypophysiotropic hormones and gonadal steroids. In vitro, 96/99 tumors released LH, FSH, and/or alpha-subunit of glycoprotein hormones. TSH was released by 11 tumors. GH, PRL, and ACTH were found in small quantities in 11, 8, and 5 tumors, respectively. Only 3 tumors released no detectable hormones. Incubations with test substances were examined at 2- and 24-h periods for up to 72 h. All but 3 of 53 tumors showed marked and persistent increases in the release of LH, FSH, and/or alpha-subunit in response to GnRH in short and long duration experiments. Secretion of LH, FSH, or alpha-subunit was stimulated to more than 150% of control by TRH in 37/48 tumors, by CRH in 10/20, by GRH in 7/20. Estradiol, progesterone, and testosterone increased release of FSH, LH, and/or alpha-subunit in 23/32, 3/12, and 3/12 tumors, respectively, and reduced their release in 6/32, 5/12, and 7/12, respectively. In tumors which showed no response to gonadal steroids, GnRH in combination with estradiol, progesterone, or testosterone yielded the same result as GnRH alone; in tumors inhibited by gonadal steroids, GnRH in combination with one of those substances reduced the response to GnRH. No secretion of GH, PRL, ACTH, or TSH was detected after incubation with GRH, estradiol, CRH, or TRH except in the tumors which initially released GH, PRL, or TSH. Ultrastructural examination of cultured cells from 15 cases revealed morphologic alterations that correlated with changes in hormone release and could be quantified by morphometry. This study represents the largest analysis of hormone production and release in vitro and morphologic correlation of clinically nonfunctioning pituitary adenomas. The responsiveness of gonadotropin secretion by null cell adenomas and oncocytomas to GnRH and gonadal steroids resembles that of gonadotroph adenomas. However, the unexpected increases in gonadotropin release attributable to several other adenohypophysiotropic hormones and the release of multiple hormones suggests that null cell adenomas and oncocytomas may represent neoplasms derived from uncommitted or committed precursor cells that can undergo differentiation towards several cell lines.

Adenoma

[Tracheotomy in children. Indications, major surgical principles, importance of nursing].

Tracheotomy in children has two main fields of indication: 1) obstructions of the upper respiratory tract, the main cause being today the post-intubation stenosis; 2) long term mechanical ventilation. When performed in good conditions, with adapted care, there are few complications, among them the accidental denaculation being the most worrying. When long-term tracheotomy is needed, parent-education, together with special equipment and adapted environment may allow the return of the tracheotomised child at home in secure conditions. Special attention with preventive measures during intubation is recommended in order to reduce the number of tracheotomies for post-intubation stenosis.

Child

Chronic hyperdynamic sepsis in the rat. II. Characterization of liver and muscle energy metabolism.

Sepsis was induced in male rats by injections of live Escherichia coli No. 4 (or E. coli No. 3) and Bacteroides fragilis organisms into a preformed subcutaneous abscess. Body weight, food and water intake, and cardiac output were measured daily. After 1, 2, or 3 weeks, animals were sacrificed, and blood, liver, and muscle were collected for measurements of plasma glucose and carnitine, mitochondrial respiratory activity, mitochondrial cytochrome concentrations, and tissue adenine nucleotides. Compared with sham controls, no significant differences were found in state 3 respiratory activities of liver mitochondria isolated from rats with moderate (no weight loss, cardiac output increased to 150% of control) or severe (0.5% weight loss/day, cardiac output increased to 200% of control) sepsis at any time. After 1 week of severe, but not moderate, sepsis, pyruvate-supported respiration in muscle mitochondria was significantly decreased, while branched-chain ketoacid and beta-hydroxybutyrate-supported respiration remained unchanged. After 2 weeks of severe, but not moderate, sepsis, beta-hydroxybutyrate and branched-chain ketoacid oxidation increased severalfold; pyruvate utilization remained depressed. Severe or moderate sepsis did not uncouple mitochondrial respiration at any time. Total muscle carnitine concentration was significantly decreased after long-term but not short-term severe sepsis. Severe short-term sepsis caused a significant increase in liver short-chain acyl and total carnitines. Muscle energy charge was unaltered by either moderate or severe sepsis. These results represent the first demonstration of sepsis-induced fuel shifts at the mitochondrial level in muscle: Severe hyperdynamic sepsis is characterized by the reduced ability of muscle mitochondria to utilize pyruvate with a simultaneous increase in branched-chain ketoacid and ketone body utilization. These changes were not observed in liver mitochondria.

Adenine Nucleotides

Mechanism of peroxide-induced cellular injury in cultured adult cardiac myocytes.

Reactive oxygen species contribute to the tissue injury seen after reperfusion of ischemic myocardium. We propose that toxicity originates from the effect that mitochondrial peroxide metabolism has on substrate entry into oxidative pathways. To support our contention, cultured adult rat cardiomyocytes were incubated with physiological concentrations of peroxide. The cellular extract and incubation medium were analyzed for adenine nucleotides and purines by reverse-phase high-pressure liquid chromatography. Cellular glutathione efflux was determined by enzymatic analysis of the incubation medium. Pyruvate dehydrogenase (PDH) activity was determined in the cultured myocytes as well as in freshly isolated cardiac mitochondria using [1-C14]pyruvate. Extracellular glutathione rose 3.3-fold in response to small doses of peroxide (approximately 108 nmol/mg protein). Likewise, small quantities of peroxide reduced total cellular adenine nucleotides to 50-60% of control values with only a modest (0.95-0.91) reduction in energy charge [ATP + 1/2 ADP)/(ATP + ADP + AMP]. Peroxide-treated myocytes selectively release inosine and adenosine, as only these two purine degradation products were detected in the incubation medium. The most dramatic response was a peroxide dose-dependent inhibition of PDH activity in cultured myocytes as well as freshly isolated mitochondria; just 65 and 30 nmol peroxide/mg protein induced a 50% reduction in cellular and mitochondrial PDH activity, respectively. In conclusion, physiological quantities of peroxide potently inhibit PDH in cultured cardiomyocytes and isolated cardiac mitochondria. PDH inhibition blocks the aerobic oxidation of glucose and inhibits the oxidative phosphorylation of ADP, which in turn leads to cellular adenine nucleotide degradation.

Adenine Nucleotides

"Newstreaming" in the 90s.

Provided is a brief discussion of some of the trends for the 1990s that will be important to health care managers as they attempt to effect creative change while meeting the day-to-day requirements of their jobs.

Decision Making, Organizational

[Treatment of gynecomastia using a trans-areolar incision].

Thirty cases of gynecomastia treated surgically in Rio de Janeiro are presented. Possible aetiological factor are discussed and the technique employed, trans-areolar incision and preparation of two retro-areolar flaps, described. The technique may be associated or not with liposuction.

Adult

Analysis of hormone secretion by clinically nonfunctioning human pituitary adenomas using the reverse hemolytic plaque assay.

The reverse hemolytic plaque assay was used to study hormone release in vitro by seven clinically nonfunctioning human pituitary adenomas associated with no clinical or biochemical evidence of hormone excess. Four of seven tumors were oncocytomas, one a null cell adenoma, and two gonadotroph adenomas based on immunocytochemical and ultrastructural features. In all seven tumors, plaques were formed with antiserum against beta FSH; four produced plaques for beta LH, and five for glycoprotein hormone alpha-subunit. The percentage of plaque-forming cells and the mean size of plaques were smaller than those of clinically functioning adenomas studied for comparison (five GH- and/or PRL-producing adenomas). These results correlated with those of hormone release in tissue culture, immunocytochemistry on paraffin secretions of the tumors, and immunocytochemistry after reverse hemolytic plaque assay. We conclude that clinically nonfunctioning pituitary adenomas release small quantities of hormones, primarily gonadotropins, and that hormone release is attributable to only a small percentage of tumor cells.

Adenoma

Gastrointestinal bleeding after craniotomy: a retrospective review of 518 patients.

A retrospective review of the medical records of 518 patients who underwent craniotomy over a 3 year interval was carried out to determine the rate of gastrointestinal bleeding and its relationship to the Glasgow Coma Score. There were 288 [55.5%] males and 230 [44.5%] females in the series; the mean age was 51.5 +/- 18.9 years. Forty percent had brain tumours, 18% had subarachnoid hemorrhage, 14% had spontaneous intracerebral hemorrhage, 19% had head injury and 8% had other diagnoses. Forty-eight [9.3%] of the patients had significant gastrointestinal bleeding, the distribution of which was as follows: hematemesis [37/518], melena [11/518] and/or hematochezia [4/518]. A further 51 [9.8%] had evidence of "coffee ground emesis" only. Of those with a Glasgow Coma Score of less than 10, 21% had significant GI bleeding while only 7% of patients with a Glasgow Coma Score greater than 10 had such a bleed [p less than 0.005]. Further analysis showed that the incidence of GI bleeding in patients who underwent craniotomy increased with decreasing GCS. GI bleeding did not correlate with age, sex, steroid administration or casual use of anti-ulcer medication.

Adult

A study of ligamentous growth.

Scant data are available on the growth of ligament. This study answers basic questions concerning mechanisms of ligament growth and determines the location of longitudinal ligament growth. Growing rabbits had metal marking sutures implanted, at measured intervals, along the length of their medial collateral ligament. Separate metal markers were inserted in the epiphysis and metaphysis of the femur and tibia. Changes in marker intervals were measured radiographically after growth. Measurements revealed that growth occurred throughout the length of the ligament, with somewhat greater growth occurring in the distal segment. Total ligament growth was much less than that occurring at the tibial physis (which the ligament crosses). The magnitude of total ligament growth was proportional to the enlargement of the joint itself, as measured by changes in the distance between epiphyseal markers. The most distal suture inserted in the ligament became incorporated in bone and moved rapidly away from the ligament insertion. This rapid displacement of the distal suture was not responsible for enlargement of the ligament itself, but rather a phenomenon of the maintenance of the position of the ligament insertion on the proximal metaphysis, as the epiphysis grows away from the original site of ligament insertion.

Animals

Flow cytometric analysis and sorting of plant chromosomes from Petunia hybrida protoplasts.

A method to obtain a high metaphase index and thereafter a plant chromosome suspension is described for Petunia hybrida (2n = 14). Mesophyll protoplast cultures have been used, giving easily disrupted cell walls and a high percentage of dividing cells after 42 h. On 2.5 mM colchicine-treated cells, metaphase indexes reaching 10% were routinely obtained. The lysis medium in which the protoplast-derived cells were disrupted was a simplified culture medium. After chromosome release, samples were stained with Hoechst 33342 dye and analysed by flow cytofluorometry. The histogram of fluorescence intensities included three peaks of metaphase chromosomes and a duplication of this flow karyotype provoked by "monochromatid chromosome." This interpretation was established after flow sorting; micronuclei could also be observed and sorted. Of the 7 chromosomes, only the largest formed a distinct peak while the others were incompletely resolved, due to the similar DNA content of various chromosomes. Model distributions of Petunia hybrida chromosomes have been computed according to the relative chromosome length. The theoretical histograms indicated that low variability is indispensable for resolving distinctive chromosome peaks. The experimental flow karyotype was consistent with one of the models having CV of 2.5%.

Benzimidazoles

Immediate effects of bumetanide on systemic haemodynamics and left ventricular volume in acute and chronic heart failure.

1 The haemodynamic and radionuclide effects of i.v. bumetanide (25 micrograms kg-1) were prospectively studied in 24 patients with angiographically documented coronary artery disease and either acute exercise-induced (Group I, n = 12) or chronic (Group II, n = 12) heart failure. 2 Bumetanide at rest increased systemic arterial blood pressure and vascular resistance index; cardiac index and pulmonary artery occluded pressure (PAOP) were reduced at an unchanged heart rate in all patients. The left ventricular ejection fraction fell in patients with normal resting left ventricular filling pressure without change in those with chronic heart failure. The cardiac volumes were unchanged in either group. 3 During constant-load supine bicycle exercise, there were similar effects on systemic arterial pressures, vascular resistance index and PAOP; however the cardiac index was maintained at a reduced left ventricular filling pressure and unchanged ejection fraction and volumes. 4 These data demonstrate immediate mild pressor and vasoconstrictor actions of bumetanide which appear independent of the state of cardiac function; they suggest that any immediate improvement in patient symptomatology following bumetanide may be consequent on the reduction in PAOP; short-term reductions in volume may not occur.

Acute Disease