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Biomedical subjects

C B Brown

Publications and source records attributed to C B Brown.

At least 91 records · Page 5Linked to original sources

Tenckhoff catheter replacement or intraperitoneal urokinase: a randomised trial in the management of recurrent continuous ambulatory peritoneal dialysis (CAPD) peritonitis.

A randomised trial, comparing Tenckhoff catheter replacement as a one-stage procedure and i.p. urokinase, was undertaken in the management of recurrent continuous ambulatory peritoneal dialysis (CAPD) peritonitis. In addition to appropriate i.p. antibiotic treatment, 17 patients received i.p. urokinase (5000 i.u.) on the second and fourth days of antibiotic treatment, and 14 patients underwent CAPD catheter replacement. An additional six patients also underwent catheter replacement following the recurrence of peritonitis after urokinase treatment. The subsequent recurrence rate of peritonitis following CAPD catheter replacement (5%) was significantly less than after urokinase (41%) (p less than 0.001). Fourteen patients remained free of peritonitis for at least three months after catheter replacement, and five patients were peritonitis-free following urokinase for this period.

Catheters, Indwelling↗

Glycosylated and carbamylated haemoglobin in uraemia.

Glycosylated and carbamylated haemoglobin were determined in patients with uraemia and/or diabetes mellitus. Glycosylated haemoglobin measured by ion-exchange chromatography (HbA1, HbA1c, HbA1a + b) was elevated in non-diabetic uraemic patients, while colorimetrically determined glycosylated haemoglobin was similar to controls. Patients with diabetes mellitus and normal renal function had similar glycosylated haemoglobin concentrations to those with renal failure. Both methods showed an excellent correlation, independent of renal function, in patients with diabetes mellitus. The HbA1c component was more influenced by diabetes and the HbA1a + b component was relatively more dependent on renal function. Carbamylated haemoglobin was detected in all subjects, but was grossly elevated in uraemia. Carbamylated haemoglobin significantly correlated with renal function and chromatographically determined glycosylated haemoglobin. Data from this study strongly suggests that the apparent elevation of chromatographically determined glycosylated haemoglobin in uraemia is due to the increased formation of carbamylated haemoglobin. However, in patients with diabetes mellitus, independent of renal function, both the chromatographic and colorimetric methods of determining glycosylated haemoglobin are equally valuable and reliable. The non-enzymatic formation of carbamylated haemoglobin in uraemia has several similarities to glycosylated haemoglobin in patients with diabetes mellitus. Carbamylated haemoglobin may have a clinical role as a marker of uraemia and may also have a pathophysiological relevance.

Adult↗

Intravenous calcitriol lowers serum calcium concentrations in uraemic patients with severe hyperparathyroidism and hypercalcaemia.

We studied the effects of intravenous calcitriol in four persistently hypercalcaemic patients established on haemodialysis. All had marked hyperparathyroidism and had been previously shown to be intolerant to vitamin D by mouth. Calcitriol was administered at the end of each dialysis session in doses of 0.5-2.5 micrograms for 2 months and continued for 7 and 8 months in two patients. A significant decrease in serum calcium was observed after 2 weeks, which was maintained throughout treatment despite increasing the dose of calcitriol. This was associated with a decrease in serum concentrations of iPTH (28% of the initial value at 4 weeks), suggesting a shift in the set-point for PTH secretion. During longer-term treatment, serum calcium values increased, but lower concentrations of iPTH were maintained. We conclude that an increment in serum calcium is not a prerequisite for the suppressive action of calcitriol on parathyroid secretion and that the presence of hypercalcaemia does not preclude its use. Longer-term studies on a larger number of patients are required to assess the therapeutic potential of intravenous calcitriol in hypercalcaemic patients.

Adult↗

Phosphate binding efficiency of a polyuronic acid in normal subjects.

We evaluated the phosphate-binding efficiency of Sorbiphos, a non-toxic aluminium-free natural polymer, in five volunteers aged 28-34 years with normal renal function. After an overnight fast, a placebo, 2 g of Sorbiphos or a therapeutic dose of Alu-Cap (950 mg) were given, 30 min before a dietary load of phosphorus. Serum and urinary phosphate were measured on hourly samples. A similar increment in serum and urine phosphate was noted after the ingestion of placebo or Sorbiphos, but both serum and urine phosphate increased less after Alu-Cap. Since the recommended dose of Sorbiphos is half that of Alu-Cap, we conclude that Sorbiphos has little phosphate-binding efficiency in normal subjects given moderate phosphate loads.

Adult↗

Interleukin-6 and granulocyte-macrophage colony-stimulating factor are candidate growth factors for chronic myelomonocytic leukemia cells.

Previous studies suggest that malignant cells from some patients with myeloid leukemias produce colony-stimulating factors (CSFs) that can function as autocrine growth factors in vitro. We have examined the roles of interleukin-6 (IL-6) and granulocyte-macrophage CSF (GM-CSF) in the proliferation of myeloid leukemia cells. IL-6 activity was assessed in conditioned medium (CM) from myeloid leukemia cell cultures or cell lysates using IL-6-dependent KD83 and 7TD1 murine cell lines. Media conditioned by cells from patients with chronic myelomonocytic leukemia (CMMoL), but not by normal monocytes, chronic myelogenous leukemia (CML), or acute myelogenous leukemia (AML) cells, contained substantial levels (50 to 1,000 U/10(6) cells) of IL-6. The IL-6 content of CM correlated directly with donor peripheral blood WBC count. CM from two of five CMMoL samples also contained greater than 350 pg/mL GM-CSF. Moreover, CMMoL cells spontaneously formed colonies in semisolid medium. CMMoL colony formation could be partially inhibited by antibodies to IL-6 or GM-CSF, whereas combination of these antibodies gave additive, and nearly complete (greater than 93%), inhibition of spontaneous colony formation. Cell lysates from uncultured CMMoL cells from one patient contained abundant GM-CSF protein but no detectable IL-6. These data suggest that IL-6 and GM-CSF act in vitro as autocrine growth factors for CMMoL cells, and that CMMoL cells in vivo may represent a GM-CSF-dependent autocrine growth system.

Antibodies, Monoclonal↗

Carbamylated haemoglobin in chronic renal failure.

Carbamylated haemoglobin was measured by quantifying the release of isopropyl hydantoin by the acid hydrolysis of globin using gas liquid chromatography. Carbamylated haemoglobin was evaluated in 167 subjects including patients with a wide spectrum of renal disease. Grossly elevated concentrations of isopropyl hydantoin (mean values greater than 80 ng IPH/mg globin) were found in chronic renal failure, dialysis and transplant patients with renal failure compared to healthy subjects (15-39 ng IPH/mg globin). The elevated carbamylated haemoglobin correlated with renal function. Carbamylated haemoglobin may act as an indicator of uraemic status and has a potential clinical usefulness and may also have a pathophysiological significance.

Adult↗

Pancreatic beta-cell function in CAPD.

Pancreatic beta-cell function was evaluated in uraemic patients by measuring beta-cell peptides in the peripheral blood after intravenous glucagon (1 mg) stimulation. Patients in chronic renal failure, patients on haemodialysis, and both new and established subjects on continuous ambulatory peritoneal dialysis (CAPD) (10 in each group) were studied and compared to 8 healthy controls. Fasting glucose (3.6-4.4 mmol/l) and insulin concentrations (9.5-11.7 mU/l) were normal and did not differ between the uraemic groups, but c-peptide concentrations were markedly increased in uremia (1.84-2.38 nmol/l) compared to controls (0.48 nmol/l). Following glucagon stimulation an exaggerated blood glucose response with delayed glucose peak was observed, while the peak insulin response to glucagon was normal; however, the return to basal concentrations was delayed in uraemia. The c-peptide response was also exaggerated and peak concentrations in uraemic subjects (3.0-4.3 nmol/l) were significantly greater than controls (1.5 nmol/l). The response of CAPD patients was similar to those on haemodialysis and non-dialysed uraemic patients. The abnormalities seen were due to uraemia, and CAPD treatment had no specific adverse effect on beta-cell function. Thus, from this data there was no evidence that CAPD per se is detrimental to beta-cell integrity.

C-Peptide↗

Long-term CAPD--some U.K. experience.

As many UK renal units commence more patients on CAPD than hemodialysis (HD) as the first mode of therapy a retrospective study of long-term CAPD (greater than 4 years continuous CAPD) was performed in 4 centers with substantial CAPD programs. One hundred and seventy-seven patients (103M, 74F) started CAPD before December, 1981. There was no difference in primary renal disease. Age was significantly greater in 2 units (51.9 +/- 11.7 and 53.2 +/- 12.1 vs 40.6 +/- 16.2 and 42.5 +/- 14.6 years, p less than 0.05) and correlates with pre-CAPD activity scores (Scale 3-0). After 4 years: 34 patients (19.2%) remained on CAPD: the proportion was similar in all centers. Sixty-five percent of patients were alive but 54% transferred to HD mainly due to peritonitis (overall 2.0 episodes/intercenter variation p less than 0.001). Fourty-four patients were transplanted. Significant increases occurred in hemoglobin, albumin, calcium and creatinine; a decrease in activity score (2.4 +/- 0.7 to 1.5 +/- 0.9, p less than 0.005); no change in weight, BP, urea or bone disease. Thirty-eight patients died, mainly cardiac (14) or sepsis (11). Using Cox's method of analysis significant risk multipliers were age (2.07 per decade), male sex (2.18), frequency of peritonitis (1.36), activity score less than 2 (4.45) and amyloidosis (12.45). Despite differing techniques in different centers CAPD offered a satisfactory mode of therapy for many patients; peritonitis was the main reason for transfer to HD and several significant factors were identified.

Adult↗

Von Hippel-Lindau disease in a large British family: clinicopathological features and recommendations for screening and follow-up.

We describe the clinical and pathological features in nine members of a large British family with von Hippel-Lindau disease. Twenty living family members underwent detailed assessment for features of the disease, including retinal examination and computed tomography of the head and abdomen. The hospital records of three deceased family members were reviewed and detailed information about a fourth was obtained from members of the family. As a result of this study, three asymptomatic family members were found to have features of the disease and all three living affected family members were found to have additional features. Lesions discovered included retinal angiomas requiring treatment in four family members, one asymptomatic renal cell carcinoma and one asymptomatic pancreatic endocrine tumour. We also report the occurrence of a spermatic cord mesenchymal hamartoma in von Hippel-Lindau disease.

Adolescent↗

Late-onset cerebellar degeneration in mice induced transplacentally by methylnitrosourea.

A late-onset degenerative disease in the cerebellum was produced in the offspring of mice exposed to 1 mg/kg of the direct-acting DNA alkylating agent methylnitrosourea (MNU) on day 16 of gestation. This intrauterine exposure to MNU also provoked a progressive retinal degeneration that was described elsewhere. Mild ataxia in the MNU-exposed animals was expressed by 20 weeks of age. Although animals appeared normal in the immediate post-natal period, quantitative histological evaluation of cerebellar coronal sections indicated that MNU-exposed animals had a significantly greater number of pyknotic Purkinje cells than age-matched controls. The number of pyknotic Purkinje cells declined with age in the drug exposed animals; however, the percentage of pyknotic Purkinje cells to total number of Purkinje cells still was greater in MNU-induced animals at 36 weeks than in controls, suggesting that a slow degenerative process was ongoing in the MNU-exposed animals. Furthermore, the folia were grossly disrupted in 90% of the older MNU-exposed animals (ages greater than 12 weeks), suggesting permanent cerebellar disruption macroscopically. Such intrauterine exposure to low doses of alkylating agents may be potentially useful in modeling degenerative neuronal diseases.

Animals↗

Cortical and vascular prostaglandin synthesis during renal allograft rejection in the rat.

Alterations in local prostacyclin and thromboxane synthesis could mediate the changes in vascular perfusion and platelet deposition in acutely rejecting renal allografts and prostaglandin E2 (PGE2) has been implicated in the regulation of the immune response. 6-Keto-prostaglandin F1 alpha (6 KetoPGF1 alpha), thromboxane B2 (TxB2) (the stable degradation products of prostacyclin and thromboxane A2 [TxA2], respectively) and PGE2 were measured in incubates of cortical slices taken from rat renal allografts or isografts one to seven days after transplantation. 6 KetoPGF1 alpha and TxB2 synthesis was also measured in incubates of blood vessels supplying and transplanted with the kidney in these animals. During the phase of cellular rejection (3-5 days), TxB2 synthesis was selectively elevated in allografted renal cortex, renal artery, renal vein, and abdominal aorta in comparison with isografted tissues. There was also a small but significant rise in cortical PGE2 synthesis at this time, but vascular and cortical 6 KetoPGF1 alpha production remained unchanged. Renal infarction, occurring 7 days after transplantation, was accompanied by a nonspecific rise in the synthesis of all three prostaglandins by renal cortical slices. Increased tissue TxA2 synthesis may contribute to local thrombosis and decreased graft perfusion during acute rejection, thereby potentiating graft destruction.

6-Ketoprostaglandin F1 alpha↗

Screening for polycystic kidney disease: importance of clinical presentation in the newborn.

Fifty per cent of the offspring of adults with the adult (dominant) form of polycystic kidney disease are carriers of the abnormal gene. Clinical symptoms and signs before adolescence are rare, but renal ultrasonography may detect evidence of cyst formation. Twenty two children, all offspring of parents with known adult polycystic kidney disease, have undergone renal ultrasonography. In six cases evidence of disease was detected without clinical manifestations at the ages of 1, 2, 5, 8, 13, and 14 years. There were no renal masses, hypertension, haematuria, or evidence of renal insufficiency. In four children from three sibships, whose families had no previous history of renal disease, bilateral renal masses were noted to be present at birth. In each case one parent was subsequently found to have adult polycystic kidney disease. At the ages of 1, 4, 6, and 20 years, while renal masses were still palpable, there was no evidence of renal insufficiency or hypertension in the younger children, while the oldest had mild renal failure. An analysis of the reported cases in childhood is suggestive of a bimodal distribution of enlarged kidneys, with a number of cases diagnosed at birth or soon after, followed by an increasing incidence during later childhood. Adult polycystic kidney disease presenting at birth may be qualitatively different from the disease detected by screening programmes of children at risk.

Adolescent↗

Clodronate in the medical management of hyperparathyroidism.

The skeletal manifestations of hyperparathyroidism are due to the stimulation of osteoclast-mediated bone resorption by high circulating concentrations of parathyroid hormone (PTH). Since diphosphonates inhibit PTH-mediated bone resorption, we assessed the effects of clodronate in 42 patients with hypercalcaemia and increased bone resorption due to primary hyperparathyroidism (20 patients), secondary hyperparathyroidism in chronic renal failure (12 patients on haemodialysis replacement therapy) and tertiary hyperparathyroidism following successful renal transplantation (10 patients). Clodronate (0.8-1.6 g daily by mouth or 300 mg given as an intravenous infusion following five consecutive dialysis treatments) significantly decreased serum calcium and biochemical indices of bone resorption in the three groups studied. In primary and tertiary hyperparathyroidism, serum calcium values remained above the upper limit of the reference range despite suppression of bone resorption due to the unopposed effect of PTH on renal tubular reabsorption of calcium. Prolonged treatment (3 months) was associated with a partial recurrence of hypercalcaemia in 8 of 12 patients with primary hyperparathyroidism despite continued effects on bone resorption, possibly due to a secondary decrease in bone formation. These studies indicate that clodronate is capable of suppressing PTH-mediated bone resorption in disorders of parathyroid secretion and may prove to be a useful adjunct in their medical management.

Administration, Oral↗

Unmasking of subclavian vein obstruction following creation of arteriovenous fistulae for haemodialysis. A problem following subclavian line dialysis?

We report three cases of subclavian vein obstruction following haemodialysis by a subclavian line. The obstruction only became apparent clinically following the formation of an arteriovenous fistula on the same side as the initial catheterisation. In each case, gross swelling of the arm followed creation of the fistula. One case responded to treatment with anticoagulants, but the other two required ligation of the arteriovenous fistula with rapid resolution of the swelling.

Adult↗

A method for demonstrating subclinical inguinal herniae in patients undergoing peritoneal dialysis: the isotope 'peritoneoscrotogram'.

We report six patients who presented with genital oedema associated with continuous ambulatory peritoneal dialysis (CAPD) who had no clinically detectable inguinal hernia at the time of initial presentation. In the absence of conventional clinical signs of an inguinal hernia, isotope imaging of the pelviscrotal region after introducing technetium-labelled tin colloid through the dialysis tube has proved to be an accurate guide to localisation of the hernia, has avoided unnecessary bilateral explorations, and has facilitated early repair of the hernia, thus allowing reinstitution of CAPD.

Edema↗