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Biomedical subjects

J Cunningham

Publications and source records attributed to J Cunningham.

At least 181 records · Page 10Linked to original sources
PubMed1987

Serum aluminum levels and erythrocyte dihydropteridine reductase activity in patients on hemodialysis.

Aluminum intoxication due to aluminum-containing antacids or dialysate can cause encephalopathy in patients undergoing hemodialysis, but the biochemical mechanism has not been defined. The enzyme dihydropteridine reductase (DHPR) is essential for the maintenance of normal brain concentrations of tetrahydrobiopterin, which is itself required for the synthesis of specific neurotransmitters. This enzyme is also present in erythrocytes. We measured erythrocyte DHPR activity and concentrations of the biopterin derivatives of its substrate and of aluminum in 38 patients on hemodialysis who had no clinical evidence of encephalopathy. Serum aluminum levels ranged from 15 to 190 micrograms per liter (mean, 67.6 +/- 7.7) as compared with 4.9 +/- 0.99 micrograms per liter in normal subjects. DHPR activity was inversely related to the serum aluminum concentration (r = -0.61, P less than 0.001) and was less than the activity predicted from the hemoglobin concentration in these patients. Serum concentrations of biopterin derivatives were markedly elevated. Eighteen patients were given the aluminum-chelating agent deferoxamine in a single dose, after which DHPR activity doubled. These studies suggest that aluminum inhibits DHPR activity in erythrocytes and that aluminum chelation reverses this effect. Although we did not directly measure DHPR activity in the brains of dialysis patients without encephalopathy, we propose that the reduction in activity in erythrocytes may reflect a similar reduction in the brain. Our findings could help to explain the encephalopathy associated with aluminum intoxication.

Adult↗
PubMed1987

Effect of dietary acid and calcium on 25-hydroxyvitamin D metabolism by chick kidney.

Studies of the effects of acidosis and dietary calcium on 25-hydroxyvitamin D3 (25OHD3) metabolism were conducted utilizing assays of mitochondrial 1-hydroxylase and 24-hydroxylase activity following 96 hours of acid loading. The results showed decreased 1-hydroxylase (206 +/- 6 vs. 132 +/- 22 fmol min-1 mg/mitochondrial protein-1, p less than 0.01), augmented 24-hydroxylase (48 +/- 14 vs. 180 +/- 30 fmol min-1 mg-1, p less than 0.001) and increments in plasma calcium and phosphate following acidosis. High calcium diet also increased 24-hydroxylase activity (48 +/- 14 vs. 160 +/- 24 fmol min-1 mg-1, p less than 0.001) and plasma calcium, but decreased plasma phosphate. The extramitochondrial concentrations of calcium, potassium, and phosphate which maximally stimulated the hydroxylases in vitro were not altered by the in vivo dietary perturbations. The increments in 1-hydroxylase and 24-hydroxylase resulting from the presence of calcium, potassium, or phosphate in optimal concentrations (10(-5) M, 100 mM, and 100 mM, respectively) were changed by both acid loading and high calcium diet, decreasing in the case of 1-hydroxylase and increasing in that of 24-hydroxylase. The data indicate that the suppression of 1-hydroxylase and augmentation of 24-hydroxylase following these dietary perturbations may depend on both changed total enzyme capacity and altered enzyme sensitivity to extramitochondrial ions and are consistent with mediation by calcium of the effects of acidosis.

Acidosis↗
PubMed1987

Simulated acidosis does not impair 1,25-dihydroxyvitamin D3 production by cultured kidney cells.

Cultured mouse kidney cells grown in serum-free medium were used to assess the metabolism of 25-hydroxyvitamin D3 in the presence of simulated metabolic acidosis. Kidney epithelial cells isolated from 4-6 week old mice were grown to confluence in a defined serum-free medium at pH 7.4. The confluent monolayers were incubated with tritiated 25-hydroxyvitamin D3 for 6 hours, the samples were extracted, and vitamin D metabolites were separated and quantitated by high pressure liquid chromatography (HPLC). The pH of the incubation medium was set at 6.9, 7.1, 7.4, or 7.7 by adjusting the bicarbonate concentration, using chloride as the balancing anion at constant Pco2. When pH was altered at the beginning of the 6 hour assay, production of 1,25-dihydroxyvitamin D3 was the same at each pH. More prolonged pH perturbation for a total of 30 hours likewise had no influence on 1,25-dihydroxyvitamin D3 production. These results confirm that intact mammalian kidney cells in serum-free culture possess an active 25-hydroxyvitamin D3-1-hydroxylase and that the activity of the enzyme is unaffected by pH over the range 6.8-7.7. In experiments where acidosis has been shown to alter 1,25-dihydroxyvitamin D3 production, the mechanism was probably indirect.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1987

Residual renal function in hemodialysis patients may protect against hyperaluminemia.

We investigated 106 home hemodialysis patients whose mean [+/- SEM] serum aluminum (Al) concentration was 60.9 +/- 4.1 micrograms/liter. Serum Al concentration was inversely related to daily urine output (r = -0.52, P less than 0.001). Urine volume and measurements of Al exposure were included in a multivariate analysis of serum Al concentration in the 62 patients whose urine output was greater than 10 ml/day. The multiple correlation coefficient (r) was 0.70 (P less than 0.001) and the percentage contributions to r2 (indicating the relative importance of each factor) were: urine output 57%, oral Al intake 36%, total dialysis hours 7%. The additional contribution from cumulative water Al was negligible. In a subgroup of 26 patients with a urine output exceeding 10 ml/day, urinary Al excretion averaged 15.4 micrograms/day, and renal Al clearance and serum Al concentration were inversely related (r = -0.69, P less than 0.001). We conclude that Al-containing phosphate binders were a more important source of Al than was dialysate in these patients and that residual renal function can reduce the severity of hyperaluminemia in hemodialysis patients.

Adult↗
PubMed1987

Silicone-induced hypercalcaemia in haemodialysis patients.

Silicone spallation from the roller-pump insert in dialysis blood lines leads to the accumulation of silicone in haemodialysis patients, which in turn leads to a foreign-body reaction with granuloma formation. We have studied two patients in whom documented silicone accumulation has been associated with both granuloma formation and significant, persistent hypercalcaemia. In both patients plasma levels of immunoreactive parathyroid hormone and 1,25-dihydroxyvitamin D were low or undetectable. In one patient, hypercalcaemia responded only partially to corticosteroids, but completely to naproxen. Both patients were changed to silicone-free blood lines and their hypercalcaemia subsequently resolved. The results indicate that in some haemodialysis patients, silicone accumulation and granuloma formation may lead to hypercalcaemia that is independent of 1,25-dihydroxyvitamin D, and that may instead reflect altered prostaglandin metabolism.

Adult↗
PubMed1986

Effects of packed cell volume reduction on renal haemodynamics and the renin-angiotensin-aldosterone system in patients with secondary polycythaemia and hypoxic cor pulmonale.

Polycythaemia was corrected by erythrapheresis in ten patients with hypoxic cor pulmonale who were stable on regular diuretic therapy. Renal haemodynamics, renal function and the renin-angiotensin-aldosterone system were assessed before and afterwards. Before erythrapheresis effective renal plasma flow (ERPF) was reduced (63% predicted) but glomerular filtration rate (GFR) was preserved (88% predicted) by a rise in filtration fraction (FF) (138% predicted). A negative correlation existed between ERPF and packed cell volume (r = -0.723; P less than 0.02) and also between ERPF and PaCO2 (r = -0.710; P less than 0.05). Polycythaemia was sufficient to maintain renal oxygen delivery (97% predicted). After erythrapheresis systemic blood pressure, blood volume and blood viscosity all decreased. ERPF increased by 18% (P less than 0.02). FF fell by 11% (P less than 0.05) and GFR was unchanged. Renal oxygen delivery diminished by 25% (P less than 0.001). Plasma renin activity was increased in five patients and plasma aldosterone increased in two patients before erythrapheresis. No sustained fall occurred in plasma renin activity or plasma aldosterone, possibly because the haemodynamic consequences of the procedure had opposing actions on renin secretion. Although the reduction in FF would per se tend to enhance renal sodium and water excretion, a diuresis or natriuresis did not occur consistently.

Aged↗
PubMed1986

Biliary decompression: an institutional comparison of percutaneous and endoscopic methods.

Endoscopically performed biliary drainage (EPBD) is now an alternative to percutaneous biliary drainage. The morbidity, mortality, and survival statistics of 97 patients with obstructive jaundice who had undergone percutaneous transhepatic biliary drainage (PTBD) and surgery, PTBD alone, EPBD and surgery, or EPBD alone were compared. Overall, the EPBD group had fewer complications and lower mortality than the other groups. When palliative treatment of patients with malignancies was compared, the complication rates associated with EPBD and PTBD were similar; however, mortality was lower with EPBD. No negative effect on survival was found with EPBD. In addition, EPBD offered several additional advantages over PTBD, including fewer bleeding complications, better patient acceptance, and avoidance of external catheter care. EPBD should be considered as a viable alternative to PTBD. Additional studies are needed to determine whether it is to be considered the initial drainage procedure of choice in patients with obstructive jaundice.

Bile Ducts↗
PubMed1986

Partial characterization of the Purkinje cell antigens in paraneoplastic cerebellar degeneration.

Serum from seven patients with paraneoplastic cerebellar degeneration contained anti-Purkinje cell antibodies. The samples were examined by immunoblotting to determine whether they recognized common antigens in isolated human Purkinje cell neurons. Two groups of antigens were detected by all seven sera with Mr 62/64 kd and 34 to 38 kd, both of which contributed to the Purkinje cell antigens detected immunohistochemically. These reactivities were absent from all controls tested. These antibodies may play a role in the pathogenesis of paraneoplastic cerebellar degeneration.

Antibodies↗
PubMed1985

Stimulated release of endogenous GABA and glycine from the goldfish retina.

The release of endogenous gamma-aminobutyric acid (GABA) and glycine from the isolated goldfish retina, measured by high-pressure liquid chromatography (HPLC), was Ca2+-independent when evoked by L-glutamate or L-aspartate and partially Ca2+-dependent when evoked by 50 mM K+. D-Aspartate potentiated GABA and glycine release evoked by L-glutamate and inhibited that evoked by L-aspartate. These data are similar to those reported for radiolabeled GABA and glycine. However, the relative amount released compared to the total amino acid content in the retina was much less (10%) for the endogenous compounds. We suggest that results obtained with [3H]GABA and [3H]glycine can be generalized in a qualitative manner to their endogenous counterparts in goldfish retina.

Animals↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

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↗