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Biomedical subjects

M Cox

Publications and source records attributed to M Cox.

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

Outcome of infants of very low birth weight: a geographically based study.

The outcome of 143 live-born infants of very low birth weight (defined as less than 1500 g) who were born in 1980-81 to women resident in Newfoundland and Labrador is described. Sixty-one infants (43%) died during the first year of life. Of the 82 surviving infants 79 were followed for 18 months to 3 years. Eight (10%) were found to have evidence of severe neurodevelopmental abnormality, and nine (11%) were found to have various minor problems, including seizures, developmental delay and behavioural disorders. There was an inverse association between birth weight and mortality. Neonatal pneumothorax, seizures and clinical evidence of intraventricular hemorrhage were more commonly seen among infants who died; these factors also seemed to be predictive of an adverse long-term outcome. Continuous monitoring of the rates of death and disability among infants of very low birth weight born within a defined region should provide the basis for rational planning and delivery of neonatal intensive care.

Developmental Disabilities↗
PubMed1987

Regional blood flow and skeletal muscle energy status in endotoxemic rats.

Endotoxins induce muscle wasting in part as a result of depressed protein synthesis. To investigate whether these changes reflect impaired energy transduction, blood flow, O2 extraction, and high-energy phosphates in muscle and whole-body O2 consumption (VO2) have been measured. VO2 was measured for 6h after an initial sublethal dose of endotoxin (Escherichia coli lipopolysaccharide 0.3 mg/100 g body wt sc) or saline and during 6h after a second dose 24 h later. In fed or fasted rats, VO2 was either increased or better maintained after endotoxin. In anesthetized fed rats 3-4 after the second dose of endotoxin VO2 was increased, and this was accompanied by increased blood flow to liver (hepatic arterial supply), kidney, and perirenal brown adipose tissue and a 57 and 64% decrease in flow to back and hindlimb muscle, respectively, with no change in any other organ. Hindlimb arteriovenous O2 was unchanged, indicating markedly decreased aerobic metabolism in muscle, and the contribution of the hindlimb to whole-body VO2 decreased by 46%. Adenosine 5'-triphosphate levels in muscle were unchanged in endotoxin-treated rats, and this was confirmed by topical nuclear magnetic resonance spectroscopy, which also showed muscle pH to be unchanged. These results show that although there is decreased blood flow and aerobic oxidation in muscle, adenosine 5'-triphosphate availability does not appear to be compromised so that the endotoxin-induced muscle catabolism and decreased protein synthesis must reflex some other mechanism.

Animals↗
PubMed1987

Disorders of potassium homeostasis in critically ill patients.

Disorders of potassium homeostasis can be life-threatening. This is especially true in critically-ill patients, in whom concurrent disorders may exacerbate the adverse effects of both hyper- and hypokalemia. Alterations in potassium balance are usually multifunctional in origin. Four broad categories encompass the most common diseases and syndromes seen in the intensive care setting: pharmacologic agents, acid-base disturbances, hypomagnesemia, and renal insufficiency. The various influences that disturb the serum potassium concentration may either potentiate or counter-balance one another. The most important clinical manifestations of disorders of potassium homeostasis are those involving the heart: both hyper- and hypokalemia can be associated with lethal arrhythmias. Neuromuscular, renal and metabolic effects are also seen. Severe hyper- and hypokalemia, irrespective of cause, should be treated as medical emergencies.

Acid-Base Imbalance↗
PubMed1987

Effects of guanabenz on sodium and water homeostasis.

Sodium retention may partially offset the therapeutic action of some antihypertensive agents. To assess the effects of guanabenz on sodium balance, six men with mild to moderate hypertension were placed on diets with constant sodium intake (120 mEq/day) for approximately 4 weeks. After achieving sodium balance, the subjects received guanabenz (16-24 mg daily) for approximately 2 weeks. Mean supine blood pressure decreased from 144/93 to 133/86 mmHg during guanabenz treatment (p less than 0.001). Guanabenz therapy was associated with a decrease in body weight (mean +/- SE) from 85.4 +/- 7.0 to 84.4 +/- 6.8 kg (p less than 0.01). Sodium balance, glomerular filtration rate, plasma renin activity, mean maximal urine osmolality, fluid intake, urine volume, and serum sodium concentration were unchanged during guanabenz therapy. Three additional balance studies were performed during a period of greater sodium intake (180 mEq/day). Although higher doses of guanabenz were required to achieve blood pressure control, sodium balance still was not affected by the drug. Thus, an effective therapeutic dose of guanabenz administered for 2 weeks had no clinically significant effects on sodium or water homeostasis in patients with mild to moderate hypertension.

Adult↗
PubMed1986

Diffuse choroidal melanocytoma in a child. A lesion extending the spectrum of melanocytic hamartomas.

A 10-year-old white boy presented with a diffuse pigmented lesion of the choroid of his right eye that had led to a partial secondary retinal detachment. Because of the fear of a diffuse choroidal melanoma (a lesion never before reported in an individual within the first two decades of life), the eye was enucleated. An incisional P-32 study, compared with an uninvolved region, was positive at 154% uptake. Pigmented tissue was discovered surrounding the distal meninges of the optic nerve, on the posterior surface of the eye, and within the orbital soft tissues adherent to the globe. This led to fear of extraocular extension of a malignant melanoma. Light microscopic examination of the enucleated globe demonstrated that the choroid was diffusely and massively thickened by polygonal, hyperpigmented tumor cells that were also present in compressed spindled forms between the lamellae of scleral collagen, in the scleral emissaries, on the surface of the eyeball, and in the distal optic nerve dura. The choroidal tumor cells had the features of those normally encountered in localized optic nerve head benign melanocytomas. Electron microscopy demonstrated the presence of large, well-melaninized melanosomes (but no macromelanosomes), confirming the diagnosis of a diffuse uveal melanocytoma. The differential diagnosis of this new entity and its relationship to previously reported pigmented lesions of the uvea is discussed.

Child↗
PubMed1985

Demeclocycline-induced natriuresis and renal insufficiency: in vivo and in vitro studies.

We examined renal function and Na+ balance in a patient with congestive heart failure who was treated with demeclocycline (DMC) on three separate occasions under strict metabolic balance conditions. Natriuresis and reversible renal insufficiency, which could not be explained solely on the basis of negative Na+ balance, developed on each occasion. In contrast to reports of an association between elevated serum DMC levels and renal insufficiency in patients with cirrhotic edema, the renal insufficiency in this patient with cardiac edema occurred in the absence of high DMC levels. Consequently, markedly elevated serum DMC levels do not appear to be a prerequisite for the development of natriuresis or renal insufficiency in edematous patients receiving this drug. In an attempt to clarify the mechanism of the natriuresis, we also examined the effects of DMC on Na+ transport in an in-vitro model system, the toad urinary bladder. DMC inhibited aldosterone-stimulated Na+ transport, but had no effect on Na+ transport when the latter was jointly stimulated by ADH and theophylline. Despite this selective inhibition of the natriferic effect of aldosterone in vitro, it is unlikely that such a mechanism completely accounts for the natriuresis observed in-vivo since the natriuresis is generally of large magnitude and is usually accompanied by some degree of kaliuresis, and DMC had no consistent effect on urinary aldosterone excretion. Consequently, other mechanisms must be sought to explain the natriuretic effect of DMC in edematous patients. Likewise, mechanisms other than negative Na+ balance (perhaps primary alterations in renal hemodynamics) must underly the development of renal insufficiency in such individuals.

Administration, Oral↗
PubMed1985

The effect of catabolic doses of corticosterone on heat production in the growing rat.

The effect of corticosterone treatment on energy balance and heat production was investigated in growing rats. Animals were treated with daily subcutaneous injections of a vehicle containing 0, 50 or 100 mg corticosterone/kg for 5 d. Measurements of digestible energy intake and urinary energy losses showed that corticosterone treatment resulted in a depression of metabolizable energy intake due to elevated urinary energy losses resulting from massive glucosuria. Measurements of the metabolizable energy intake and the change in carcass energy indicated that at 50 mg/kg energy deposition and heat production were reduced, whilst at 100 mg/kg energy deposition was completely abolished with heat production increased. Postprandial oxygen consumption was unchanged at 50 mg/kg and increased at 100 mg/kg. Factorial analysis of these results based on reported values for the energy cost of protein and fat deposition indicated that (a) the depression of total heat production at 50 mg/kg could be entirely accounted for by the concomitant suppression of growth, and (b) the elevation of total and postprandial heat production at 100 mg/kg reflected a specific influence of corticosterone on thermogenesis. The significance of these findings is discussed in the light of reports that corticosterone in low doses suppresses heat production.

Adipose Tissue, Brown↗
PubMed1985

Physical, chemical, and physiological characteristics of isolates of pulmonary surfactant from adult rabbits.

Physical and chemical characteristics of two types of preparations of surface active material from adult rabbits were determined. A procedure using multiple centrifugations produced a surface active material (type A) which had 6.6% by weight protein and a phosphorus/protein ratio of 13.1 nmol P/microgram protein. A simpler protocol involving two centrifugations yielded a surface active material (type B) with more protein (10.8%) and a lower phosphorus/protein ratio (8.4 nmol/micrograms). Lipid compositions of both types were similar with phosphatidylcholine being the major phospholipid (80%) and palmitate the major fatty acid in the total lipid (65-71%) and in phosphatidylcholine (80%). Both types exhibited broad thermotropic phase transitions encompassing 37 degrees C. Measurements of aqueous dispersions of surface active material on the surface of a Langmuir-Whilhelmy balance or in a pulsating bubble apparatus indicated that there was variability both between types and between batches of the same type in the capacity to reach low surface tension on the surface balance and in the rates at which low surface tension was achieved on the bubble apparatus. Type A preparations were somewhat more reliable in meeting these ends than were type B. Both types of isolates were effective in normalizing pressure-volume characteristics when instilled into the lungs of immature rabbit fetuses.

Animals↗
PubMed1985

Aldosterone-induced proteins: characterization using lectin-affinity chromatography.

Aldosterone-stimulated Na+ transport in toad urinary bladder is associated with the synthesis of a specific group of proteins whose induction appears to be related to the natriferic effect of the hormone. These aldosterone-induced proteins (AIPs) occur in two slightly different molecular weight classes (around 70 kDa), each class being composed of several proteins with discrete isoelectric points (range, 5.5-6.0). Because glycosylation is a common cause of such electrophoretic polymorphism and microheterogeneity, we examined whether these proteins are glycoproteins. Tunicamycin (a specific inhibitor of N-linked glycosylation) inhibited aldosterone-stimulated Na+ transport and AIP synthesis without affecting overall protein synthesis. The vast majority of epithelial cell proteins did not bind to the mannose-specific lectin, concanavalin A-sepharose. In contrast, both classes of AIPs bound to concanavalin A-sepharose, but the affinities of the higher and lower molecular weight proteins were markedly different: the former were readily eluted with 0.2 M alpha-methyl-D-mannoside alone, whereas the latter could only be eluted with 0.4 M alpha-methyl-D-mannoside in combination with high concentrations of NaCl (2.5-5.0 M). These studies indicate that 1) glycosylation is important in the natriferic response to aldosterone, 2) the AIPs are N-linked mannose-containing glycoproteins, and 3) the electrophoretic polymorphism of the AIPs is due, at least in part, to differences in glycosylation. Furthermore, concanavalin A-affinity chromatography provides a simple means for the partial purification of these putative "effectors" of the cellular action of aldosterone.

Aldosterone↗
PubMed1985

Differential effects of corticosteroids on Na+ transport in rat distal colon in vitro.

We studied rat distal colon during in vitro incubation with aldosterone and dexamethasone. Both hormones caused short-circuit current (Isc) to increase with a latency period of approximately 3 h. At the 7th h of incubation, control colons had a Isc of 72 +/- 8 microA . cm-2 while tissues incubated with 10(-5) M aldosterone and 10(-8) M dexamethasone, the respective maximal stimulatory concentrations, had similarly increased Isc, 211 +/- 21 and 185 +/- 18 microA . cm-2, respectively. The increase in Isc induced by steroids reflected increased net sodium transport: control, 3.4 +/- 0.8; aldosterone, 6.7 +/- 0.7 (P less than 0.05); and dexamethasone, 7.5 +/- 1.0 mueq . h-1 . cm-2 (P less than 0.025). Spironolactone inhibited the response to both steroids, but the molar ratio of antagonist to agonist was less for aldosterone (approximately 5,000:1) than for dexamethasone (approximately 50,000:1). Amiloride inhibited a greater fraction of aldosterone-induced Isc (0.70 +/- 0.07) than that of dexamethasone (0.37 +/- 0.07; P less than 0.025). The latter value was similar to the effect of amiloride on control tissues (0.35 +/- 0.04). These data provide evidence that the cellular mechanisms by which aldosterone and dexamethasone induce Na+ transport are different.

Aldosterone↗
PubMed1985

Synthetic lipopeptide analogs of bacterial lipoprotein are potent polyclonal activators for murine B lymphocytes.

The lipoprotein from the outer membrane of Escherichia coli and other Enterobacteriaceae is a potent polyclonal activator for B lymphocytes. To determine the molecular structure responsible for the biologic activity of lipoprotein, a well-defined series of analogs of its N-terminal part was synthesized: S-(2,3-bis(palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-cysteine, -cysteine methyl ester, -cysteinyl-serine, -cysteinyl-seryl-serine, -cysteinyl-seryl-seryl-asparagine, and -cysteinyl-seryl-seryl-asparaginyl-alanine. All compounds were tested for mitogenic activity toward spleen cells from BALB/c, LPS-non-responder C3H/HeJ, and congenitally athymic C3H/Tif/Bom/nu/nu mice, measuring the incorporation of [3H]thymidine into DNA. Lymphocyte activation was confirmed by determination of the incorporation of [3H]uridine into RNA and [3H]leucine into protein. The synthetic lipopeptides were also investigated for their ability to stimulate B lymphocytes into immunoglobulin secretion, as shown by a hemolytic plaque assay. Throughout our studies, the compounds carrying two to five amino acids exhibited strong stimulation activity toward B lymphocytes comparable to native lipoprotein. In contrast, products containing only one amino acid, cysteine or cysteine methyl ester, were only marginally active, indicating that to obtain full biologic activity the presence of the hydrophilic dipeptide structure is necessary. All compounds exhibited only a marginal effect on thymocytes. Thus, a series of defined synthetic fragments of a bacterial outer membrane component exhibits a pronounced mitogenic and polyclonally stimulating activity towards B lymphocytes. The substances will be valuable tools for more detailed investigations on the molecular mechanisms of B cell activation.

Animals↗