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Biomedical subjects

J Wade

Publications and source records attributed to J Wade.

At least 127 records · Page 7Linked to original sources
PubMed1987

Acute nonlymphocytic leukemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung.

Combination chemotherapy is frequently used in the therapy of advanced non-small-cell lung cancer (NSCLC), but late complications are rarely recognized because of the short survival of most patients. Of 119 patients with advanced NSCLC treated with cisplatin and other drugs, four patients developed acute nonlymphocytic leukemia (ANLL). All four patients received etoposide and cisplatin with or without vindesine. Leukemia was diagnosed at 13, 19, 28, and 35 months after start of treatment. Three patients had morphologic and/or cytogenetic features of acute leukemia with significant monoblastic involvement; the fourth patient had trilineage dysplasia and cytogenetic abnormalities more commonly associated with therapy-related leukemia. Detailed analysis of the subgroup who survived longer than 1 year (24 patients) suggests that high cumulative doses of etoposide are leukemogenic; the median etoposide dose was 6,795 mg/m2 (first year only) in the four leukemic patients compared with 3,025 mg/m2 in the 20 nonleukemic patients (P less than .01). The rate of ANLL was 0.30 per person-year after the first year (95% confidence limits 0.11 to 0.90), with a cumulative risk of 15% +/- 11% at 2 years, and 44% +/- 24% at 2.5 years. We conclude that high doses of etoposide are potentially leukemogenic, and can induce a syndrome with features of acute monoblastic leukemia de novo that is distinct from other secondary leukemias.

Acute Disease↗
PubMed1986

Impairment of cerebral blood flow autoregulation in the newborn lamb by hypoxia.

Autoregulation of cerebral blood flow has been demonstrated in both fetal and newborn animal models under normoxic conditions. In the present experiments we have attempted to define the minimal hypoxic insult which impairs autoregulation in the newborn lamb and to assess the time to recovery. We measured cerebral blood flow by the intracarotid 133Xe method in fifteen 4- to 9-day-old lambs and tested autoregulation of cerebral blood flow by increasing blood pressure 20-30% with phenylephrine. Autoregulation was tested in the control state and at successive time intervals after an hypoxic stress (PaO2 of 30 mm Hg) of 10 or 20 min. We found that cerebral autoregulation was abolished after 20 min of hypoxia and recovered within 7 h. Since this model identifies the minimal hypoxic insult to abolish autoregulation it might be used to study means to protect autoregulation or to hasten its recovery after hypoxia.

Animals↗
PubMed1985

How accurate are quotations and references in medical journals?

The accuracy of quotations and references in six medical journals published during January 1984 was assessed. The original author was misquoted in 15% of all references, and most of the errors would have misled readers. Errors in citation of references occurred in 24%, of which 8% were major errors--that is, they prevented immediate identification of the source of the reference. Inaccurate quotations and citations are displeasing for the original author, misleading for the reader, and mean that untruths become "accepted fact." Some suggestions for reducing these high levels of inaccuracy are that papers scheduled for publication with errors of citation should be returned to the author and checked completely and a permanent column specifically for misquotations could be inserted into the journal.

Information Services↗
PubMed1985

Pharmacokinetics of ceftazidime, alone or in combination with piperacillin or tobramycin, in the sera of cancer patients.

We administered 2 g of ceftazidime intravenously every 8 h to cancer patients for the empiric therapy of febrile episodes. Ceftazidime was administered as monotherapy for patients with granulocyte counts in excess of 1,000/microliter. Febrile, neutropenic patients were randomized to also receive either piperacillin or tobramycin. The pharmacokinetic profile of ceftazidime during a steady-state dosing interval was ascertained in 21 patients. No differences were seen between groups for any of the pharmacokinetic parameters examined. As expected, the observed half-life was longer, the serum clearance was smaller, and the volumes of distribution were larger than in previously reported studies of volunteers. Serum concentrations remained above the MIC for inhibition of 90% of strains of the most common bacteremic pathogens seen in our cancer center for the entire 8-h dosing interval.

Adolescent↗
PubMed1985

Effects of adrenalectomy and chronic adrenal corticosteroid replacement on potassium transport in rat kidney.

Clearance experiments were carried out in pair-fed rats to examine the long-term effects of adrenalectomy and selective adrenal corticosteroid replacement in physiological amounts on renal potassium transport. To this end, clearance studies were conducted in rats that were sham operated, or adrenalectomized (ADX). ADX animals were given either vehicle, aldosterone (0.5 microgram/100 g body wt per day), dexamethasone (1.2 micrograms/100 g body wt per day), or aldosterone and dexamethasone, by osmotic minipump for 7-9 d whereupon clearance experiments were conducted. After chronic hormone treatment, during basal conditions when only Ringers solution was infused, all groups excreted similar amounts of potassium. However, in all ADX animals without mineralocorticoid replacement, the maintenance of urinary potassium excretion at control levels was associated with hyperkalemia, increased urine flow, and natriuresis; all are factors known to stimulate urinary potassium excretion. During acute potassium infusion, the increase in urinary potassium excretion was less in ADX rats than in controls. This functional deficiency in potassium excretion was partially corrected by dexamethasone and was uniformly associated with a significant increase in urine flow. Aldosterone replacement or aldosterone and dexamethasone given together chronically, sharply increased potassium excretion but did not restore excretion to control levels. Only acute aldosterone infusion (0.2 microgram/100 g body wt bolus plus 0.2 microgram/100 g body wt per hour), superimposed upon chronic aldosterone and dexamethasone treatment, fully restored potassium excretion to control levels. This aldosterone induced enhancement of potassium excretion, both chronic and acute, was not associated with hyperkalemia, and increased urine flow or natriuresis. Thus, physiological levels of both classes of adrenal corticosteroids stimulate renal potassium excretion albeit by different mechanisms. Mineralocorticoids stimulate tubular potassium excretion directly, whereas glucocorticoids augment excretion indirectly by increasing fluid and sodium delivery along the distal nephron.

Adrenal Cortex Hormones↗
PubMed1985

Ultrastructure of rat initial collecting tubule. Effect of adrenal corticosteroid treatment.

This study examines the effects of adrenalectomy and physiological replacement of mineralocorticoids and glucocorticoids on the cellular ultrastructure of the rat initial collecting tubule (late distal tubule). Animals were adrenalectomized (ADX) and for 10 d received by osmotic minipump either: vehicle, aldosterone (0.5 micrograms X 100 g-1 X d-1), aldosterone (2.0 micrograms X 100 g-1 X d-1), dexamethasone (1.2 micrograms X 100 g-1 X d-1), or aldosterone (0.5 micrograms X 100 g-1 X d-1) with dexamethasone (1.2 micrograms X 100 g-1 X d-1). Radioimmunoassay revealed that the low dose of aldosterone restored plasma aldosterone to control levels. The higher dose of aldosterone increased plasma levels by threefold. Morphometric techniques were used to measure membrane length of individual principal and intercalated cells in each condition. The basolateral membrane length of principal cells decreased by 35% in ADX animals. Low dose aldosterone replacement (0.5 micrograms X 100 g-1 X d-1) in ADX animals maintained membrane length at control values; at a higher level of aldosterone (2.0 micrograms X 100 g-1 X d-1) membrane length increased by 111% compared with control. Dexamethasone treatment, at a level that restored glomerular filtration rate to normal, had no effect on cellular ultrastructure. Combined aldosterone and dexamethasone replacement had no greater effect on basolateral membrane length than aldosterone alone. The length of the luminal membrane of the principal cell type was not affected by ADX or hormone treatment. Intercalated cell membrane length was not affected by ADX or hormone replacement. Thus, chronic aldosterone levels have an important, selective effect on the basolateral membrane of the principal cell. The correlation between these morphological results and the steroid hormone effects on renal electrolyte excretion, reported in the companion paper (15), suggests that basolateral membrane length is an important factor controlling the rate of sodium and potassium transport by the initial collecting tubule.

Adrenal Cortex Hormones↗
PubMed1983

A twin study examining the genetic influence on food selection.

Taste sensitivity, preference and use of 24 foods were studied to identify the extent of genetic influence. Thirteen monozygotic (MZ) and ten dizygotic (DZ) adult, female twin-pairs of comparable family background participated in the research. Heritability was demonstrated for phenylthiocarbamide (PTC) sensitivity and was found in both preference and use for unsweetened grapefruit juice and green beans. In terms of preference and use separately, a heritability component was indicated in one-third and one-eighth of the foods respectively. Environmental adaptation and learning, unmeasured in the present study, would appear to exert a stronger influence than the genetic component on food-related behaviour.

Adult↗
PubMed1981

Evidence for a physiological regulation of food selection and nutrient intake in twins.

Making use of the Holzinger Index of Heritability, the genetic effect on nutrient intake was assessed in 13 monozygotic and 10 dizygotic pairs of healthy female adult Caucasian twins. From 3-day food records, intakes of total energy, protein, fat, carbohydrate, and alcohol as well as the concentrations of the energy sources as percentage of calories, were calculated. The diets of monozygotic twins were significantly more similar than were those of dizygotic twins for the protein concentration, the carbohydrate concentration, and the absolute intake of carbohydrate per day. The present findings support the hypothesis that in the free-living human primitive physiological mechanisms influencing food selection independent of total food intake are operative and that these mechanisms are subject to genetic influence.

Adult↗
PubMed1980

Alternatives to total parenteral nutrition in the critically ill patient.

Alternatives to total parenteral nutrition (TPN) can play an invaluable role in the support of the critically ill patient. However, the efficacy of this depends on: (1) early nutritional assessment; (2) sequential nutritional assessment as dictated by the clinical condition of the patient; (3) careful estimation of requirements based on calculated energy expenditure and use of the "stress-index"; (4) early use of enteral feedings in combination with peripheral and central intravenous routes, especially with the use of "feeding modules" to provide patient's specific concentrated diet; (5) use of intravenous fat as an isotonic supplement to dextrose in the presence of carbohydrate intolerance; (6) avoid overfeeding as rigorously as underfeeding; (7) continued clinical trials to determine optimal nutritional/metabolic support of the critically ill.

Amino Acids↗