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Biomedical subjects

R L Wagner

Publications and source records attributed to R L Wagner.

At least 91 records · Page 5Linked to original sources

Nosocomial Legionella pneumonia in a population of head and neck cancer patients.

A prospective study of nosocomial pneumonia following major head and neck surgery was conducted when it was recognized that Legionella contaminated the hospital water supply. Legionella pneumonia had not previously been diagnosed in our hospital. Every head and neck patient with nosocomial pneumonia had specialized tests performed. During the 18-month study period, 29% of patients with nosocomial pneumonia (7 of 27) had evidence of legionellosis. The sero-group of the infecting Legionella was the same as the Legionella in the water supply. Legionella was seen exclusively in patients with clinically evident aspiration. Legionella pneumonia was not demonstrated in patients undergoing laryngectomy. We conclude that specialized testing must be employed to avoid delay in diagnosis and failure to administer specific antibiotic therapy. Legionellosis may be underdiagnosed in hospitalized patients.

Antibodies, Bacterial↗

Inhibition of adrenal steroidogenesis by the anesthetic etomidate.

The use of the intravenous anesthetic etomidate for prolonged sedation has been associated with low levels of plasma cortisol and increased mortality. We measured the cortisol and aldosterone responses to ACTH stimulation in five patients receiving etomidate, and we also studied the direct effects of etomidate on enzymes in the rat steroidogenic pathway. One patient who was receiving a 20-hour infusion of etomidate (1.3 to 1.5 mg per kilogram of body weight per hour) had marked adrenocortical suppression that was still evident four days after etomidate was discontinued. Four surgical patients receiving etomidate during their operations were all found to have adrenal suppression four hours after the operation; mean (+/- S.D.) increases in cortisol and aldosterone after ACTH stimulation were only 1.8 +/- 0.5 micrograms per deciliter and 0.5 +/- 1.1 ng per deciliter, respectively. In rat adrenal cells, etomidate produced a concentration-dependent blockade of the two mitochondrial cytochrome P-450-dependent enzymes, cholesterol-side-chain cleavage enzyme, and 11 beta-hydroxylase, without evident inhibition of the microsomal enzymes in the glucocorticoid pathway. Physicians should be aware that etomidate inhibits adrenal steroidogenesis, and they should consider treating selected patients with corticosteroids if etomidate is used.

Adrenal Cortex↗

Etomidate inhibits adrenocortical function in surgical patients.

Postoperative adrenocortical function was compared in 23 out-patients receiving either thiopental, 4 mg/kg, for induction and a thiopental infusion, 0.26 mg . kg-1 . min-1, in combination with nitrous oxide 70% for maintenance of anesthesia (control); etomidate, 0.4 mg/kg, for induction followed by an etomidate infusion, 0.02 mg . kg-1 . min-1, and nitrous oxide 70% for maintenance (etomidate I); or etomidate, 0.4 mg/kg, for induction and a thiopental infusion, 0.22 mg . kg-1 . min-1, in combination with nitrous oxide 70% for maintenance (etomidate II). The norepinephrine response to anesthesia and surgery did not differ significantly between the three groups. The postoperative cortisol response to ACTH stimulation was normal in the control group (maximum rise in plasma cortisol was 20.1 +/- 2.9 micrograms/dl [mean +/- SEM] ), however, it was decreased in all patients receiving etomidate, whether by a short infusion (mean change in plasma cortisol was -3.8 +/- 1.9 micrograms/dl) or as a single induction dose (mean change in plasma cortisol was -4.0 +/- 2.0 micrograms/dl). Similarly, the postoperative aldosterone levels in the control group increased normally in response to ACTH (+ 10.2 +/- 3.0 ng/dl) but decreased in both the etomidate I and etomidate II groups (-3.0 +/- 0.7 ng/dl and -3.3 +/- 1.0 ng/dl, respectively). Because ACTH was administered exogenously, etomidate-induced suppression of adrenocortical response appeared to be a direct effect on the adrenal gland, which was present at a time when the serum etomidate levels were in the subhypnotic range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cost-effectiveness of prophylactic antibiotics in head and neck surgery.

Studies undertaken at the Eye and Ear Hospital of Pittsburgh indicate that antibiotic prophylaxis can reduce the incidence of patient morbidity. In this article we will demonstrate the effect of antibiotic prophylaxis on the economics of major head and neck surgery. One hundred and one patients were assigned to one of four treatment protocols, three of which entailed 1 day of a perioperative prophylactic antibiotic and the fourth a placebo. The study was conducted in a double-blind, randomized fashion. Patients receiving a placebo experienced an infection rate of 78%. Patients receiving cefazolin experienced an infection rate of 33%. Ten percent of patients treated with cefoperazone or cefotaxime developed postoperative wound infection. Postoperative hospitalization averaged 17.9 days for patients who did not develop postoperative wound infection, in contrast to an average of 32.6 days for patients with postoperative would infection. The added cost of postoperative infection justifies the added use of the newer, more expensive antibiotics in view of the reduced postoperative morbidity and postoperative hospitalization.

Anti-Bacterial Agents↗

3-carboethoxy-beta-carboline (beta-CCE) elicits electroencephalographic seizures in rats: reversal by the benzodiazepine antagonist CGS 8216.

Intravenous administration of 3-carboethoxy-beta-carboline (beta-CCE, 10 mg/kg) to rats resulted in multiple bursts of rhythmic waves (2-4 second duration, 5-7 Hz) with amplitudes of 100-250 microV. Pretreatment of animals with the benzodiazepine receptor antagonists CGS 8216 prevented the electroencephalographic seizures elicited by beta-CCE. This dose of CGS 8216 did not produce any electroencephalographic abnormalities when administered alone. These observations suggest that the electroencephalographic seizures elicited by beta-CCE are mediated via an interaction with benzodiazepine receptors. An in vitro study of the rate of degradation of beta-CCE and 3-carbomethoxy-beta-carboline (beta-CCM) in rat plasma demonstrated that the rate of degradation of the former compound was three times more rapid than the latter. These observations, taken together with previous studies demonstrating that parenteral administration of beta-CCM elicits tonic and clonic seizures, suggests that pharmacokinetic factors may be involved in defining the pharmacologic profile of beta-carboline-3-carboxylic acid esters.

Animals↗

Neuropathological studies of schizophrenia: a selective review.

Over the past 20 years, there has been a relatively quiet but persistent effort to investigate anatomical neuropathology in schizophrenia. This effort has involved post-mortem histopathology using novel preparation procedures, pneumoencephalography, and computed tomography. The bulk of this research is critically reviewed here. The evidence presented suggests that the brains of schizophrenic patients frequently contain abnormalities. The limbic region is especially likely to show pathological changes. However, the changes are variable and nonspecific. The implications of these findings are discussed in terms of our limited knowledge of the clinical manifestations of subtle limbic pathology. It is concluded that pathology of limbic regions is associated with schizophrenia and that the more gross the pathology, the more neurologically impaired are the patients.

Adult↗

Serum neuroleptic concentrations and tardive dyskinesia.

Using a liquid chromatographic assay, we measured serum neuroleptic concentrations in eight middle-aged or elderly female inpatients with tardive dyskinesia (TD) and eight controls. All 16 patients were receiving either thioridazine or mesoridazine at stable doses. TD patients were found to have a significantly higher ratio of serum concentration to daily dose of neuroleptics compared with controls. A 1-year follow-up revealed that this ratio did not change appreciably in those patients who continued to receive neuroleptics. Differences in serum neuroleptic levels were not related to peripheral inflammatory activity as indicated by serum alpha-1-acid glycoprotein concentrations. Of the various thioridazine metabolites, sulforidazine (which is reportedly the most potent in terms of affinity for dopaminergic and alpha-noradrenergic receptors) seemed to be significantly elevated in the serum of TD patients as compared with non-TD patients. Our data suggest a need for further pharmacokinetic investigations to study neuroleptic metabolism in patients with TD.

Aged↗

Enzyme studies in tardive dyskinesia. III. Noradrenergic hyperactivity in a subgroup of dyskinetic patients.

This study was undertaken to test a hypothesis that tardive dyskinesia (TD) patients with high plasma dopamine-beta-hydroxylase (DBH) activity would also have other enzymatic alterations suggestive of noradrenergic hyperactivity. Plasma renin activity was chosen as a peripheral indicator of noradrenergic function. We measured plasma renin activity in three groups of female psychiatric inpatients over the age of 50: a TD group with high plasma DBH activity, a TD group with low plasma DBH activity, and a non-TD group. The high-DBH TD group had significantly greater plasma renin activity than the other two groups. Our results are consistent with the hypothesis that a subgroup of TD patients has relative noradrenergic hyperactivity.

Aged↗

Enzyme studies in tardive dyskinesia. I. One-year biochemical follow-up.

Over a 1-year period we followed 12 female in-patients with and 13 without persistent tardive dyskinesia. Clinical signs of tardive dyskinesia as well as plasma dopamine-beta-hydroxylase and platelet monoamine oxidase activities remained stable over time in spite of medication changes. Tardive dyskinesia was associated with higher plasma dopamine-beta-hydroxylase and lower monoamine oxidase activities, both initially and at follow-up. In two patients, an apparent elevation in dopamine-beta-hydroxylase activity preceded the onset of clinical dyskinesia, suggesting that elevated plasma dopamine-beta-hydroxylase activity might be a potential risk marker for the development of tardive dyskinesia.

Aged↗

A probable neuroleptic effect on platelet monoamine oxidase in chronic schizophrenic patients.

Platelet monoamine oxidase activity (MAO) was studied serially over time in 16 chronic schizophrenic patients when medication free and then when medicated. Thirteen of the 16 patients had significant decreases in platelet MAO activity following neuroleptic drug treatment. The change in MAO activity was found to be correlated with response to treatment and to dose of medication.

Adult↗

Lymphocyte monoamine oxidase and plasma prolactin and growth hormone in tardive dyskinesia.

Twelve elderly women with tardive dyskinesia were matched with 12 patients without dyskinesia. Lymphocyte monoamine oxidase (MAO) activity and plasma prolactin and growth hormone concentrations were determined "blind" in these 12 pairs of patients. Chronic schizophrenic patients with tardive dyskinesia had significantly lower lymphocyte MAO activity as compared to controls. Organic brain syndrome patients with dyskinesia did not differ from controls in the lymphocyte MAO activity. These results with lymphocyte MAO parallel our earlier findings on platelet MAO. No significant differences were found between dyskinesia group and controls in the plasma prolactin and growth hormone concentrations. Possible implications of our findings are discussed.

Aged↗

Right and left ventricular compliance in the hereditary cardiomyopathy of the Syrian hamster.

Ventricular pressure-volume curves were examined in 10 pre-oedematous cardiomyopathic Syrian hamsters, aged 120 d, and 10 oedematous cardiomyopathic hamsters, aged 210 d, and compared with 10 and 8 age-matched controls, respectively. Previous studies had shown filling pressures and cardiac output to be normal in the pre-oedematous stage. In contrast, the oedematous stage was characterised by elevated filling pressures and increased cardiac output, raising the question whether this stage represents true myocardial failure or circulatory congestion associated with decreased ventricular compliance. Compliance, defined as dV/dP, was derived simulataneously for both ventricles from post-mortem pressure-volume curves from 0 to 2.66 kPa (0 to 20 mmHg). Left ventricular tissue elastic modulus, E, defined as dsigma/depsilon or the incremental stress (sigma) for an increment of strain (epsilon), was derived from the compliance curves and certain linear dimensions of the heart. At isobaric intervals, compliance did not differ between control and myopathic ventricles. At pressures corresponding to previously measured, naturally prevailing end-diastolic pressures, the myopathic ventricles were significantly dilated in both stages; end-diastolic compliance was normal in pre-oedematous hamsters, but was significantly decreased in the oedematous animals. Left ventricular elastic modulus was elevated at all values of sigma in both groups of myopathic animals.

Animals↗

Ventricular elastic modulus as a function of age in the Syrian golden hamster.

Analysis of passive right and left ventricular pressure-volume curves for hearts of 72 Syrian golden hamsters studied in vitro showed increases in ventricular weight, volume, and compliance at mid-age. Both ventricles were filled by syringe pumps at a constant rate. Ventricular compliance (dV/dP) was determined by electronic differentiation of the intraventricular pressures and formation of the ratio (dV/dt)/(dP/dt) as a continuous function of intraventricular pressure between 0 and 30 mm Hg. By relating, with justification, the left ventricle to a thin-walled elastic sphere, ventricular elastic moduli, E, for different ages were compared at constant levels of myocardial wall stress, sigma. The elastic modulus E proved to be a linear function of sigma. The slope of the E-sigma plot yielded a stiffness constant, K, for each age group. Body weight, heart weight, end-diastolic volume, and dV/dP all varied by more than 200% up and then down as a function of age, but K was not a significant function of age. These results suggest that the aging heart does not normally undergo substantial alterations in passive properties that affect the muscle cells and fibers themselves, but rather that the observed changes in compliance are primarily attributable to alterations in ventricular size.

Aging↗