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Biomedical subjects

J Andrews

Publications and source records attributed to J Andrews.

At least 253 records · Page 14Linked to original sources

Renin-angiotensin-aldosterone system in nephrotic syndrome.

Previous studies on the renin-angiotensin-aldosterone system and fluid volumes in patients with nephrotic syndrome have not considered the nature of the underlying renal lesion. We compared plasma renin concentration (PRC), plasma aldosterone (PA), and plasma volume in three groups of patients: five nephrotic patients with minimal change disease on renal biopsy, seven nephrotic patients with other renal histopathology, and a control group of eight patients investigated for glomerulonephritis with no past or present nephrosis. PRC and PA were significantly greater in nephrotic patients with minimal change disease than other renal histopathology (Supine PRC 42 +/- 7 microIU/mL compared with 14 +/- 4, P less than 0.01; ambulant PRC 56 +/- 7 microIU/mL compared with 29 +/- 10, P less than 0.05; supine PA 158 +/- 55 pg/mL compared with 53 +/- 13, P less than 0.05; and ambulant PA 167 +/- 57 pg/mL compared with 29 +/- 10, P less than 0.05. Plasma volume was similar in all three groups, contrary to predictions from the Starling capillary fluid exchange hypothesis. Nephrosis may be characterized by different pathophysiologic groups according to the underlying renal histopathology. High plasma renin and aldosterone levels may be markers for minimal change disease.

Adolescent↗

Can mixed venous blood be used to measure insulin action during the hyperinsulinemic clamp?

Mandatory use of arterialized venous blood for glucose measurement during insulin clamp studies can preclude its use in obese subjects. In order to assess the distortion produced by performing clamp studies with mixed venous blood, we have carried out the present study. Sixteen subjects (BMI range 21-53 kg/m2) whose glucose tolerance varied from normal to diabetic, had hyperinsulinemic clamps performed at plasma insulin concentrations approximately 250 microU/ml above basal, using arterialized venous (a.v.) blood for plasma glucose and insulin measurements. The test was repeated on the same subjects, but mixed venous (m.v.) blood was substituted for a.v. blood to determine plasma glucose and insulin concentrations. During the two studies, the mean (+/- SEM) steady state plasma glucose (a.v. = 110.6 +/- 8.8 mg/dl; m.v. = 111.3 +/- 9.8 mg/dl) and the mean incremental increases in insulin concentrations (a.v. = 263 +/- 20 microU/ml; m.v. = 273 +/- 21 microU/ml) were essentially identical. Furthermore, there was almost a perfect correlation between the individual values obtained for both SSPG (r = 0.97, p less than 0.001) and incremental insulin levels (r = 0.98, p less than 0.001) with the two methods. In addition, the amounts of glucose metabolized calculated from the two methods were very similar (a.v. = 4.96 +/- 0.67 mg/kg/min; m.v. = 5.25 +/- 0.76 mg/kg/min) and the two determinations of M were highly correlated (r = 0.97, p less than 0.001). Finally, the relative rank order of the M values obtained for the 16 subjects during the two studies were extremely comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

S1 nuclease-sensitive sites in yeast DNA: an assay for radiation-induced base damage.

DNA has been isolated from gamma-irradiated yeast cells and then treated with the enzyme S1 nuclease. This enzyme cleaves DNA specifically at sites where localized denaturation has occurred and can therefore be used as a lesion probe to identify regions in the DNA where base-pairing has been disrupted. By analysing the number of single strand breaks, double strand breaks and alkali-labile sites in the DNA before and after treatment with S1 nuclease, it has been possible to calculate the number of S1 nuclease-sensitive sites induced as a result of exposure to ionizing radiation. These sites were found to occur with a frequency about twice that of the double strand break and are thought to result from a primary ionization event in the DNA.

Cobalt Radioisotopes↗

Thermolysin is a suitable protease for probing the surface of intact pea chloroplasts.

Several proteases, i.e., pronase, a mixture of trypsin and chymotrypsin, and thermolysin were screened as potential surface probes of isolated intact pea (Pisum sativum var Laxton's Progress No. 9) chloroplasts. Of these, only thermolysin met the criteria of a suitable probe. Thermolysin destroyed outer envelope polypeptides, but did not affect inner envelope polypeptides, envelope permeability properties or such chloroplast activities as metabolite transport and O(2) evolution.

Journal Article↗

Mitoxantrone treatment in advanced breast cancer.

Half of our patients presenting with breast cancer will eventually require cytotoxic chemotherapy. In searching for an effective drug with low toxicity, many new drugs have been investigated. Seventeen patients with advanced breast cancer were treated with mitoxantrone, an analogue of adriamycin. The response rate was 44% (CR 6% + PR 38%). Side effects were fewer than those normally anticipated for most cytotoxic chemotherapy in that only two patients suffered hair loss and three nausea and vomiting. There was, however, significant bone marrow depression with granulocytopenia and two patients died of septicaemia following treatment. Cardiac toxicity occurred in two patients: of these, both had prior treatment with adriamycin, and one had prior radiotherapy to the chest wall. Both of these patients died.

Adult↗

Hereditary coproporphyria: incidence in a large English family.

In a family inheriting the hereditary coproporphyria (HCP) gene, where 414 descendants have been traced through six generations and 135 members screened for faecal porphyrins, 27 subjects were found to have inherited the gene as well as the proband. Seven (six female and one male) in retrospect had probably previously suffered from a clinical attack of porphyria. Enzymological studies were carried out on 15 members and two unaffected parents and these results in general agreed with the faecal coproporphyrin readings. Symptomatic illness is low in HCP and is almost always precipitated by drugs known to have an adverse effect on the condition. If the gene is inherited, an attack can occur at any time between puberty and old age, such as in the proband at 84 years. We have detected abnormal faecal coproporphyrin levels in members of this pedigree as young as 12 years and as old as 87 years. Recommendations are given concerning the necessity of tracing relatives who may have inherited the gene and arranging for their biochemical screening and genetic counseling if indicated.

Adolescent↗

Lower respiratory tract infections in an acute geriatric male ward: a one-year prospective surveillance.

A prospective study of 340 patients admitted to an acute geriatric male ward for a 12-month period was carried out to determine the aetiology and incidence of lower respiratory tract infection (LRTI) acquired either prior or after admission to the hospital. Over the year, 120 patients (35%) were found to have LRTI; a specific aetiology was found in 44 (37%) patients. The pathogens most frequently isolated were Haemophilus influenzae (11 patients), Streptococcus pneumoniae (9 patients) and influenza A (4 patients). A further 8 (7%) patients had antibody titres sufficiently raised to indicate a recent infection (influenza A6, Chlamydia psittaci 2). A marked difference in the aetiology between community- and hospital-acquired infection was demonstrated. Cross-infection was not found, although patients with influenza A infection were admitted to the ward. Mortality showed a high correlation with current and ex-smokers.

Aged↗

Mild splenic sequestration crises in sickle-hemoglobin C disease.

Acute splenic sequestration crisis ( ASSC ), a common complication in homozygous sickle cell anemia, has been described infrequently in sickle-hemoglobin C (SC) disease in the absence of high altitude exposure. In this report, we describe three children with hemoglobin SC disease who developed episodes of ASSC that were milder than those generally described in sickle cell anemia. In one patient, an antecedent triggering event was not recognized. The other two children may have had a predisposing cause for massive intrasplenic sickling in that one had an associated mononucleosis syndrome and the other an episode of hypovolemic shock following severe epistaxis. ASSC may occur in patients with SC disease and does not necessarily require a hypoxic trigger associated with high altitudes.

Acute Disease↗

Effects of four-day fast on triglyceride mobilization in human adipocytes.

To examine the effect of a four-day fast on neutral glyceride mobilization in human adipocytes, subcutaneous abdominal fat tissue was obtained from ten human volunteers after an overnight fast and then after four days of fasting. Plasma insulin concentration decreased from 31 +/- 5 microU/ml before the four-day fast to 9 +/- 1 microU/ml after the fast (P less than 0.05). Plasma free fatty acid concentration increased from 13.9 +/- 1.3 to 23.6 +/- 3.2 mg/dl (P less than 0.05). Mean average cell size was similar before and after the four-day fast. Basal lipolysis increased threefold (P less than 0.005) regardless of cell size after four days of fasting. In contrast, isoproterenol (2 microM) stimulated maximum lipolysis was not increased after a four-day fast. The concentrations of isoproterenol required for a half maximum stimulation in the presence of 50 (7 microU/ml) and 8000 pM (1150 microU/ml) insulin were lower after a four-day fast (P less than 0.05, P less than 0.03, respectively) and were uninfluenced by average cell size. Basal and maximum insulin-stimulated glucose transport were similar after a four-day fast. However, glucose incorporation into neutral glycerides was reduced by 50 percent (P less than 0.02) following a four-day fast. The reduction was uninfluenced by average cell size. The data indicate that abdominal adipocytes after a four-day fast are metabolically adapted towards increased neutral glyceride mobilization by reducing glucose incorporation into neutral glycerides, increasing sensitivity of lipolysis to isoproterenol, and increasing basal lipolysis.

Adipose Tissue↗

Drug compliance not so bad, knowledge not so good--the elderly after hospital discharge.

Thirty-five consecutive discharges from three admission wards were seen in hospital shortly before discharge and followed up 3-12 days after returning home. Various aspects of after-care were assessed, particularly in relation to drug compliance and understanding of treatment. Of the 30 on regular medication, 92% of those visited at home achieved over 95% compliance, despite the fact that most did not understand the purpose of their drug therapy. Much additional information was discovered, including the fact that many family doctors visited patients fairly soon when informed of discharge by telephone instead of by the normal posted discharge summary.

Aged↗

Acyl-CoA Synthetase Is Located in the Outer Membrane and Acyl-CoA Thioesterase in the Inner Membrane of Pea Chloroplast Envelopes.

Both acyl-CoA synthetase and acyl-CoA thioesterase activities are present in chloroplast envelope membranes. The functions of these enzymes in lipid metabolism remains unresolved, although the synthetase has been proposed to be involved in either plastid galactolipid synthesis or the export of plastid-synthesized fatty acids to the cytoplasm. We have examined the locations of both enzymes within the two envelope membranes of pea (Pisum sativum var Laxton's Progress No. 9) chloroplasts. Inner and outer envelope membranes were purified from unfractionated envelope preparations by linear density sucrose gradient centrifugation. Acyl-CoA synthetase was located in the outer envelope membrane while acyl-CoA thioesterase was located in the inner envelope membrane. Thus, it seems unlikely that the synthetase is directly involved in galactolipid assembly. Instead, its localization supports the hypothesis that it functions in the transport of plastid-synthesized fatty acids to the endoplasmic reticulum.

Journal Article↗

Comparison of an elemental and polymeric enteral diet in patients with normal gastrointestinal function.

In a prospective controlled clinical trial, 70 patients with normal gastrointestinal function were randomised to receive either an elemental diet based on Vivonex HN or an isonitrogenous isocalorie polymeric diet based on Clinifeed 400, administered by continuous 24 hour nasogastric infusion. The two groups of patients were well matched for age, sex, diagnosis, prior starvation, duration of feeding, initial nutritional status, and metabolic status. Nitrogen losses were significantly less on the polymeric feed, despite similar intakes. Serum transferrin rose significantly (1.85 +/- 0.2 to 2.30 +/- 0.2 g/l, p less than 0.05) only in the Clinifeed group, but nutritional parameters were otherwise maintained in both groups. The incidence of diarrhoea (Vivonex, 23.5%; Clinifeed, 30.6%) was not significantly different and was attributable to antibiotics in most cases. Hypokalaemia, which occurred in nearly half the patients, was equally distributed in the two groups, but hypophosphataemia occurred more often in the Vivonex group (p less than 0.05). Liver enzyme disturbances were similar in both groups. The present findings, therefore, provide no evidence that chemically defined 'elemental' diets containing free amino acids as their nitrogen source are in any way superior to polymeric diets containing whole protein and fat when administered to patients with normal gastrointestinal function.

Clinical Trials as Topic↗

In vitro insulin resistance of human adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus.

To assess possible cellular mechanisms of in vitro resistance in noninsulin-dependent diabetes mellitus (NIDDM), maximum insulin-stimulated glucose transport and utilization and insulin binding were measured in adipocytes isolated from weight-matched normal glycemic subjects and patients with NIDDM. Glucose transport rate was determined by measuring the amount of [U-14C]-D-glucose taken up by incubating adipocytes at trace concentrations of glucose (300 nM), and glucose metabolism by estimating the amount of lactate, CO2, triglyceride, and total glucose carbons retained in the cells following incubating at 5.5 mM glucose. Insulin binding was measured at 50, 100, and 200 pM [mono125I-tyrosinyl A14]insulin. Both maximum insulin-stimulated glucose transport and utilization in adipocytes from diabetic subjects were 40% (P less than 0.01) and 32% (P less than 0.05) lower, respectively, than values obtained for subjects with normal glucose tolerance. In addition, the maximum capacity of glucose transport was correlated with the maximum capacity of glucose utilization (r = 0.81, P less than 0.001). Furthermore, fasting plasma glucose concentrations of diabetic subjects were negatively correlated with both maximum insulin-stimulated glucose transport (r = -0.56, P less than 0.05) and glucose utilization (r = -0.67, P less than 0.05). Since basal glucose transport in adipocytes from diabetic subjects was also 33% lower than in adipocytes from normal subjects, there was no change in the relative ability of insulin to stimulate glucose transport. However, there was a 64% decrease in the sensitivity of the glucose transport system to insulin (P less than 0.05), unrelated to concomitant changes in insulin binding. These results demonstrate that both maximal insulin-stimulated glucose transport and utilization, and the sensitivity of the glucose transport system to insulin, was decreased in adipocytes isolated from subjects with NIDDM. These in vitro defects were associated with impaired glucose metabolism in vivo, consistent with the view that the metabolic alterations observed at the cellular level may contribute to the in vivo insulin resistance of NIDDM.

Adipose Tissue↗

Improvement in in vitro insulin action after one month of insulin therapy in obese noninsulin-dependent diabetics. Measurements of glucose transport and metabolism, insulin binding, and lipolysis in isolated adipocytes.

It has been previously reported that maximum insulin-stimulated glucose transport and utilization were both decreased, while basal lipolysis was increased in adipocytes from obese subjects with noninsulin-dependent diabetes mellitus (NIDDM). To determine whether these values can be returned towards those obtained in equally obese subjects with normal glucose tolerance, these measures of adipocyte metabolism were quantified in 10 NIDDM subjects before and after control of hyperglycemia with insulin. The results demonstrate that maximum insulin-stimulated glucose transport (P less than 0.02) and glucose incorporation into triglyceride (P less than 0.01) and CO2 (P less than 0.05) (at 5.5 mM glucose) increased and basal lipolysis decreased (P less than 0.05) after 4 wk of insulin treatment. In contrast, glucose incorporation into lactate and other glycolytic metabolites (at 5.5 mM glucose), and sensitivity of glucose transport to insulin, did not improve with insulin therapy. The latter occurred despite an increase in insulin binding (P less than 0.01). Finally, the improvement in maximal insulin-stimulated glucose transport correlated with the fall in fasting hyperglycemia (r = 0.77, P less than 0.01). These findings demonstrate that several of the abnormalities of carbohydrate and lipid metabolism recently noted to be present in adipocytes from patients with NIDDM can be shown to significantly improve with insulin treatment.

Adipose Tissue↗

Localization of osteomyelitis with 99mtechnetium sulphur colloid.

Thirty-two patients with fractures of the limbs were studied 15-30 min following 99mtechnetium sulphur colloid injection. In 17 of the 19 patients where osteomyelitis was superimposed on the various fractures, significant uptake of sulphur colloid was noted at the fracture sites. The sensitivity for the test was 89.5%. In 12 of the 13 cases where osteomyelitis was absent, the sulphur colloid scan was negative giving a specificity of 92.3%. Hence a technetium sulphur colloid scan has shown to be a successful method for detecting osteomyelitis complicating a limb fracture.

Adult↗