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Biomedical subjects

J Cunningham

Publications and source records attributed to J Cunningham.

At least 73 records · Page 4Linked to original sources

Effect of heavy exercise on mineral metabolism and calcium regulating hormones in humans.

The relationship between acid base status and mineral metabolism after heavy exercise has been examined in 12 healthy subjects. Following burst exercise (duration 60-130 sec) to the point of exhaustion, blood pH had decreased (7.42 +/- 0.01 vs. 7.18 +/- 0.02, P less than 0.001) and plasma ionized calcium had increased (1.09 +/- 0.01 vs. 1.22 +/- 0.02 mmol/liter, P less than 0.001). Log ionized calcium concentration showed a significant negative correlation with pH (r = -0.90). Although plasma total calcium increased after exercise (2.47 +/- 0.05 vs. 2.67 +/- 0.04 mmol/liter, P less than 0.001), this change was not seen if the observed values were corrected for the accompanying increase in plasma protein concentration, suggesting that hemoconcentration accounted for these increments. Significant increases were also seen in plasma inorganic phosphate concentration, though not in plasma magnesium. Radioimmunoassay of parathyroid hormone using two different region-specific assays, one directed at the mid-region/carboxy-terminal and the other at the amino-terminal portion of the molecule, and of calcitonin, showed no change during exercise-induced hypercalcemia. The results do not suggest significant skeletal buffering of this type of acidosis and indicate that the changes in ionized calcium associated with short bursts of intense exercise are directly related to acidosis and that those in total calcium are a consequence of hemoconcentration.

Acidosis

Serum immune complexes in systemic sclerosis: relationship with precipitating nuclear antibodies.

In a comparative study of antinuclear antibodies (ANA) and immune complexes in the serum of 43 patients with systemic sclerosis (SS) ANA were detected by indirect immunofluorescence on Hep 2 cells and/or double immunodiffusion in 90% of patients, while immune complex assays were positive in 32% of patients. The immune complex assays were positive only in sera containing antibodies to Scl 70, n-RNP, Ro, and La. The presence of immune complexes in SS sera is therefore related to ANA specificity. This might explain the variable findings of several previous studies of immune complexes in SS.

Adult

Cytomegalovirus infection in dialysis patients.

We have studied cytomegalovirus (CMV) infection in 197 patients on regular dialysis treatment and 170 healthy platelet donors. Evidence of past CMV infection was found significantly more often in patients than in controls (137 of 197 v 60 of 170; p less than 0.001) at the commencement of the study. During a 12 month period 4 of the 60 dialysis patients initially found to be seronegative, but none of the 110 seronegative controls, developed primary CMV infection. Five of the 137 dialysis patients and one of the 60 controls initially found to be seropositive showed evidence of recurrent infection. Typically, there was only a transient elevation of CMV IgM antibody titer in both primary and recurrent infection. However, one dialysis patient with recurrent infection and another 5 initially seropositive patients showed persistence of CMV:IgM antibody production suggesting that they were experiencing chronic active infection. Neither primary nor recurrent infection was invariably a consequence of transfusion of blood or blood products. There were no clear-cut clinical sequelae from any of the three forms of infection documented.

Adolescent

Effect of dialysate buffer on potassium removal during haemodialysis.

There is a linear relationship between potassium removal during haemodialysis and plasma potassium (Kp). Kp falls rapidly during the first hour of dialysis but very little during the last two hours of a five hour dialysis. There is a fairly constant movement of potassium from the intracellular to extracellular space throughout dialysis. Total potassium removal is best predicted by pre-dialysis Kp, but change in Kp is related to the impact of dialysis on acid-base status. The choice of acetate or bicarbonate buffered dialysate does not effect potassium removal during dialysis.

Acetates

5-Fluorouracil and folinic acid: a Phase I-II trial in gastrointestinal malignancy.

Fifty-one patients with metastatic adenocarcinoma received Folinic Acid (FA) combined with 5-Fluorouracil (5FU) in a Phase I-II clinical trial. Two different schedules were used: (a) bolus infusion--5FU 7-12 mg/kg/d I.V. d1-5, FA 1.6 mg/kg/d I.V. d1-5; (b) continuous infusion--5FU 600-1200 mg/m2/d I.V. d1-4, FA 60 mg/m2/d I.V. d1-4. Mucositis and myelosuppression were dose-limiting, with recommended dose levels of 5FU for further trials being 10 mg/kg/d I.V. d1-5 and 1000 mg/m2/d I.V. d1-4 on the bolus and continuous infusion schedules, respectively. Forty-one evaluable patients with measurable disease were treated. Thirty-six had metastatic colorectal carcinoma, and 14/36 patients responded (CR-1, PR-13), including responses in three patients who had previously failed 5FU treatment alone. In the two patients with unknown primary sites and three with gastric cancer, no response were seen. 5FU and FA have activity equivalent to 5FU alone, and the responses in patients receiving prior 5FU suggest it may be superior. The possibility that toxicity may be enhanced does exist. Further trials of these two agents are warranted.

Adenocarcinoma

The plasma amino acid response to cafeteria feeding in the rat: influence of hyperphagia, sucrose intake, and exercise.

The plasma amino acid response to voluntary hyperphagia was evaluated in rats fed a "cafeteria" diet for 4 to 8 weeks and compared to chow-fed controls. The influence of the sucrose content of the cafeteria diet was examined by studying rats given a low-sucrose, highly palatable, liquid diet (Magnacal). In a second series of studies the cafeteria diet was fed to rats housed in wheel cages and who ran 2.0 +/- 0.1 milles per day and compared with a sedentary cafeteria-fed group housed in standard cages. As expected, the cafeteria diet resulted in hyperphagia (45% to 55%) and in increased weight gain (35% to 50%). In response to cafeteria feeding there was an increase in plasma threonine, serine, proline, citrulline, alpha-amino butyric acid (ABA), and tyrosine. Significant decreases were observed in the branched chain amino acids (BCAA), valine and leucine. All of these changes were also observed when hyperphagia was induced with the low-sucrose diet, with the exception of the rise in ABA. In the exercised cafeteria-fed rats, excessive weight gain did not occur. Nevertheless, the amino acid response to the cafeteria diet was the same as in sedentary rats with excessive weight gain. The plasma amino acid pattern in those rats that developed glucose intolerance during cafeteria feeding and those that maintained normal glucose tolerance was similar. We conclude that hyperphagia induced by cafeteria feeding in the rat results in a specific plasma amino acid profile characterized by elevations in some amino acids (threonine, serine, proline, citrulline, ABA, and tyrosine) and reductions in the BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Acute, but not chronic, metabolic acidosis disturbs 25-hydroxyvitamin D3 metabolism.

Previous studies in vitamin D deficient animals showing that acidosis may impair the production of 1,25(OH)2D3 are in conflict with studies in humans which have not shown convincing disturbances of 25OHD3 metabolism during acidosis. We have investigated the effect on renal 25OHD3 1- and 24-hydroxylase of acid loading for periods of 24 hr to 21 days. Acid loading resulted in immediate and sustained decrements in arterial pH and bicarbonate and increments in blood-ionized calcium. Acute (24-hr) acid loading decreased 1- and increased 24-hydroxylase activity. After 6 days of acid loading, no effect on 1- hydroxylase activity was observed and that on 24-hydroxylase activity was reduced. By 21 days the effect of acidosis on 24-hydroxylase activity was no longer observed. The results show that acidosis disturbs 25OHD3 metabolism in the physiological vitamin D and calcium replete state as well as in the vitamin D deficient state, but only acutely. Our data are consistent with studies in humans and suggest that, while short-term disturbances of 25OHD3 metabolism occur early in acidosis, they are transient and may not be causally related to the development of metabolic bone disease during chronic acidosis.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase

Effect of histamine H2-receptor blockade on parathyroid status in normal and uraemic man.

Reports of parathyroid suppression during cimetidine therapy suggest that prolonged therapy with H2 antagonists may, by inducing relative hypoparathyroidism, compromise skeletal homeostasis and that under appropriate circumstances, these drugs may serve as a new modality in treating hyperparathyroidism. Using three different region-specific immunoassays, we have been unable to show an effect of cimetidine (1,800 mg/day) on parathyroid hormone concentration, or on urinary cyclic adenosine monophosphate and renal threshold phosphate concentration in 4 normal subjects. Ranitidine given for 8 weeks to 4 haemodialysed patients likewise failed to decrease parathyroid hormone concentration. H2 antagonists appear not to alter parathyroid status in either normal subjects or in uraemics and therefore are unlikely to influence skeletal metabolism in either instance.

Adult

Esophageal perforation.

A brief synopsis of the clinical and radiographic features of esophageal perforation, including barogenic rupture, is outlined. The dependence of the thoracic surgeon on roentgenograms and their interpretation by the radiologist is emphasized.

Esophageal Perforation

Antibody-dependent cellular cytotoxicity of human vascular endothelium in systemic sclerosis.

Sera from 39 patients with systemic sclerosis were examined for a cytotoxic effect on human umbilical vein endothelium. Although none of the sera produced direct cytotoxicity of 51Cr-labelled endothelial cells, even with added complement, nine sera did produce increased 51Cr release when co-cultured with endothelial cells and normal human peripheral blood mononuclear cells. The effector cells involved in this cytotoxicity possessed Fc receptors but were non-T and non-adherent while the responsible serum factor(s) was present in IgG containing fractions. This cytotoxicity tended to occur in patients with both circulating immune complexes and precipitating antibodies to nuclear and cytoplasmic antigens who, as a group, had more severe and extensive visceral disease than those without such serological abnormalities. Control studies using sera from both 27 normal controls and 19 patients with either diabetes or extensive athero-sclerotic vascular disease failed to reveal any similar cytotoxicity.

Adult

Successful combination chemotherapy for metastatic parathyroid carcinoma.

A 54-year-old patient with metastatic parathyroid carcinoma and severe hypercalcemia refractory to conventional treatment was treated with chemotherapy consisting of fluorouracil, 500 mg/sq m intravenously (IV) daily for four days (24-hour infusion), cyclophosphamide, 500 mg/sq m IV daily for four days, and dacarbazine (imidazole carboxamide), 200 mg/sq m IV daily for four days. Complete objective and partial biochemical responses were noted, with the response duration being 5.0 + months. The toxic reaction was moderate and predominantly gastrointestinal.

Antineoplastic Combined Chemotherapy Protocols

Carcinoma of the lung and coexistent active pulmonary tuberculosis: diverse morphologic and radiographic presentations.

Five patients with coexistent carcinoma of the lung and active tuberculosis within the same pulmonary lesion were studied. These cases represent five distinctly varying radiographic presentations and point out the extreme diversity of the morphological pictures of this particular disease combination. Physicians who regularly deal with patients who might present with either entity alone are cautioned to be alert to the possibility that these two diseases may be present simultaneously within single, specific pulmonary lesions.

Adenocarcinoma

Laser techniques for the evaluation of wear in Class II restorations.

A technique for the quantitative determination of the changes in surface topography of restorations during wear has been developed. This involves the optical contouring of the surface using a laser, and the generation of contour maps. Several different methods for interpreting these maps are discussed. A computer-aided method is the most consistently accurate and measures wear volume to an accuracy of 2--5%.

Computers

Energy expenditure in obesity in fasting and postprandial state.

Resting metabolic rate (RMR) was determined in 10 obese and 10 nonobese women after an overnight fast and for 3 h after the ingestion of an 800-kcal liquid meal. In the fasting state, absolute energy expenditure in the obese (4.8 +/- 0.2 kJ/min) was 25% greater than in the nonobese (P less than 0.005), but was comparable with the nonobese when expressed in relation to body surface area or lean body mass and was reduced by 20% when expressed per kilogram body weight3/4 (P less than 0.005). Meal ingestion resulted in a 14-16% increase in RMR (postprandial thermogenesis) that was similar in the two groups, so that absolute energy expenditure in the obese remained 22-25% higher than in the nonobese throughout the postprandial period. The estimated overall (fasting and postprandial) increase in resting caloric expenditure in the obese as compared with the nonobese was 350-375 kcal/day.

Adult

Abnormal 24-hydroxylation of 25-hydroxyvitamin D in the X-linked hypophosphatemic mouse.

The effect of extracellular phosphate on the control of 25-hydroxyvitamin D3 24-hydroxylase was studied in normal mice and littermates with X-linked hypophosphatemic rickets (Hyp). 24-Hydroxylase activity and plasma concentrations of 24,25-dihydroxyvitamin D3 were significantly higher in Hyp mice than in normal mice when both groups were fed a normal diet containing 1.22% calcium (Ca) and 0.8% phosphorus (Pi). The differential in 24-hydroxylase activity was exaggerated when serum phosphate was reduced in normal mice by means of a low Pi diet or increased in Hyp mice by means of a high Pi diet. Differences in 24-hydroxylase activity between the two groups of mice were also demonstrated in the presence of varying Pi concentrations in vitro. Thus, in both Hyp and normal mice, 24-hydroxylase activity is influenced in a qualitatively similar manner by serum Pi. Plasma concentrations of 1,25-dihydroxyvitamin D3 were the same in normal and Hyp mice. The data are consistent with the hypothesis that control the renal metabolism of 25-hydroxyvitamin D3 in Hyp mice is reset such tht 24-hydroxylase activity is inappropriate high for the prevailing serum phosphate over a wide range of concentrations.

24,25-Dihydroxyvitamin D 3

Increased efficiency of weight gain and altered cellularity of brown adipose tissue in rats with impaired glucose tolerance during diet-induced overfeeding.

We examined the relationship among glucose tolerance, efficiency of weight gain, and cellularity of brown adipose tissue (BAT) in rats (initial weight: 362 +/- 1 g) made hyperphagic and obese by feeding on a highly palatable "cafeteria" (CAF) diet for 4-8 wk. As compared with chow-fed controls, CAF feeding resulted in a 45-60% increase in caloric intake (P less than 0.01), a 40-50% increase in weight gain (P less than 0.01), and hyperinsulinemia. Glucose disposal rate (K) on intravenous glucose tolerance test (IVGTT) was greater than or equal to 1.4% in all chow-fed rats, but fell to less than or equal to 1.3 in 10 of 23 CAF-fed rats. As compared with the chow-fed controls, rats with normal glucose tolerance demonstrated a 12% decline in efficiency of weight gain (g/100 kcal of food consumed) in response to CAF feeding (P less than 0.05). In marked contrast, in rats with impaired glucose tolerance, efficiency of weight gain failed to decline in response to overfeeding and was 18% higher than in the overfed group with normal glucose tolerance (P less than 0.01). Although CAF feeding increased the mass of interscapular BAT by 110-130% in rats with normal as well as impaired glucose tolerance, DNA content of BAT rose only in the normal-K CAF-fed rats (0.19 +/- 0.01 mg DNA/100 mg versus 0.12 +/- 0.02 in chow-fed controls and 0.12 +/- 0.01 in low-K rats).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown