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Biomedical subjects

J Cunningham

Publications and source records attributed to J Cunningham.

At least 145 records · Page 8Linked to original sources

Does the arteriovenous fistula in chronic haemodialysis patients stimulate endothelin-1 release?

Plasma endothelin-1 (ET-1)-like immunoreactivity was measured by radioimmune assay in predialysis plasma samples from 16 chronic haemodialysis patients (7 dialysing through arteriovenous (AV) fistulae and 9 using central venous cannulae for access), from 10 patients with functioning renal transplants (5 with AV fistulae and 5 without), and from 6 healthy subjects as controls. Among dialysis patients, ET-1 was greater in those with AV fistulae than in those using cannulae for dialysis (median (range), 5.5 (3.1) pM versus 3.7 (2.0) pM, P = 0.02), and in all haemodialysis patients ET-1 values were substantially greater than in normal controls (3.9 (3.2) pM versus 0.5 (0.1) pM; P = 0.001). In patients with functioning AV fistulae, ET-1 concentrations obtained directly from the AV anastomosis of the fistula (4.4 (3.0) pM) were less than those taken simultaneously from the contralateral arm (5.5 (3.1) pM; P = 0.04), while samples drawn from the venous side of the fistula were intermediate (4.6 (3.4) pM). In renal transplant recipients, ET-1 values did not differ significantly from those in control subjects (0.7 (1.9) pM versus 0.5 (0.1) pM, n.s.), but in these patients there was a significant difference between peripheral venous ET-1 in transplant patients with and without AV fistulae (0.8 (1.9) pM versus 0.6 (1.1) pM respectively, P = 0.04). The results suggest that the increased blood flow rate through the arterialized venous circulation in the fistula arm stimulates increased ET-1 release in these patients, and that this accounts, at least in part, for the increased ET-1 found in the patients with functioning AV fistulae.

Adult↗

A prospective randomized trial of routine postoperative nasogastric decompression in patients with bowel anastomosis.

Until relatively recently, the nasogastric (NG) tube has been used routinely for decompression in the patient with small- or large-bowel anastomosis. To determine if routine postoperative NG decompression benefited such patients, 102 patients were randomized prospectively to either NG decompression or no-NG tube. Excluded were patients with chronic bowel obstruction, peritonitis, gross fecal contamination or spillage, and previous abdominal or pelvic irradiation. There were 52 patients in the no-NG group and 50 in the NG group. Patients in the no-NG group had earlier bowel sounds, return of flatus, oral intake and first bowel movement. Four patients (8%) in the no-NG group, compared with one patient (2%) in the NG group, required subsequent decompression. Length of hospital stay was significantly (p < 0.001) shorter in the no-NG group. There were no significant differences in the presence of atelectasis, postoperative fever, wound infections and anastomotic leaks between the two groups. The authors conclude that routine nasogastric decompression is not warranted after elective surgery involving small- or large-bowel anastomosis.

Adolescent↗

Hypoxia-induced von Willebrand factor release is blocked by verapamil.

Hypoxia-induced stimulation of the rate of von Willebrand factor (vWF) release from human umbilical vein endothelial cells in culture, and the influence of the calcium antagonist verapamil, was studied using a system in which a pO2 of 20 mm Hg was achieved over 60 min. The mean +/- SEM rate of vWF release over 60 min in normoxia was 0.42 +/- 0.07% pooled plasma standard. The addition of verapamil did not alter the basal rate of vWF release, but after 60 min of hypoxia, the rate was increased to 0.71 +/- 0.03% plasma standard (p < 0.01). Verapamil at a concentration of 0.1 microgram/ml of media had no influence on the stimulated rate of release (0.78 +/- 0.07%), but increasing concentrations of verapamil up to a maximum of 1 microgram/ml attenuated the hypoxia induced stimulation (0.48 +/- 0.07%; p = 0.04 vs. hypoxic control). Thus, verapamil at this concentration completely blocked the hypoxia-induced stimulation.

Calcimycin↗

Changes in total body bone mineral content and regional bone mineral density in renal patients following renal transplantation.

We performed serial measurements of total body bone mineral content (BMC) and bone mineral density (BMD), and of regional BMD at the lumbar spine and femoral neck using dual energy X-ray absorptiometry. Twenty-six patients (15 females and 11 males) were studied at the time of transplantation, and 3 and 6 months post-transplant. At baseline, the total body BMC and regional BMD values of the patients did not differ significantly from age- and sex-matched controls. Total body BMC had fallen progressively at 3 months, followed by partial recovery at 6 months. Significant decreases of BMD were seen in the lumbar spine and femoral neck at 3 months with no evidence of recovery at 6 months. The changes in these indices correlated well with the duration of hospital stay in the first 3 post-transplant months. This preliminary study demonstrated rapid deterioration of skeletal integrity following renal transplantation and that this might be progressive. Preventative strategies to avoid this early bone loss may need to be investigated.

Absorptiometry, Photon↗

Reserpine-induced post-receptor reduction in muscarinic-mediated airway smooth muscle contraction.

Radioligand binding was conducted on airways of the rat and human, surgically subdivided into trachea, lung airways, and parenchyma. 3H-QNB bound uniformly to receptors in separate sections of the rat and human airway. Receptor densities generally were ranked: lung airways greater than trachea greater than parenchyma. Receptor subtypes were identified mostly by pirenzepine displacement of bound 3H-QNB. The rat trachea, and rat and human lung airways had a uniformly low affinity for pirenzepine while rat and human parenchyma demonstrated both high and low affinity pirenzepine binding. Inhibition of methacholine-stimulated smooth muscle contraction by the M1 receptor antagonist, pirenzepine, and M2 receptor antagonist, gallamine, was studied in rat trachea and bronchus in vitro. Schild plot pA2 values were compatible with low potency antagonism, thereby favoring the presence of M3 receptors at these smooth muscle sites. Reserpine treatment of rats (0.5 mg kg-1 day-1 for 7 days) produced a decrease in peak tension in response to methacholine without changing the muscarinic receptor character (Kd 3H-QNB), population density (Bmax in fmol mg-1 protein), or function (methacholine EC50). These results indicate that muscarinic receptor heterogeneity exists in the airway of both laboratory rat and man. While the muscarinic receptor subserving airway smooth muscle contraction appears to be the M3 subtype, decreased contractile responses to methacholine by trachea and bronchus from reserpine-treated rats were receptor independent.

Animals↗

Mycobacterial infection is an important infective complication in British Asian dialysis patients.

To define the extent and nature of mycobacterial infection in patients on an adult dialysis unit whose catchment population contains a large proportion of non-Caucasian subjects, a retrospective survey of all new patients accepted onto our maintenance dialysis programme between January 1987 and December 1989 was carried out. Twenty-six Asian, 13 Afro-Caribbean, two Oriental and 170 Caucasian patients were accepted onto the dialysis programme in the three-year recruitment period. Eight of the 26 Asian patients, but none of the others, had developed mycobacterial infection by the end of December 1990. One patient had a cerebral tuberculoma with miliary mottling on chest X-ray, one pulmonary tuberculosis, one tuberculous adenitis and 5 tuberculous peritonitis (four due to Mycobacterium tuberculosis and one Mycobacterium kansasii). All the patients had been living in the UK for an average of 15 (range 6-24) years, with no known recent exposure to tuberculosis. Five patients are now alive and well, one developed malabsorption following M. kansasii peritonitis, but two with tuberculous peritonitis died before treatment could be instituted. Mycobacterial infections were associated with a high level of mortality and morbidity. No Asian patient developed mycobacterial infection during post-transplant immunosuppressive therapy in the study period, probably because of the routine anti-tuberculous chemoprophylaxis employed in this group of patients. The diagnosis of mycobacterial infection should be suspected when an Asian dialysis patient develops a pyrexia of unknown origin. It is likely, though not proven, that anti-tuberculous chemoprophylaxis might reduce this high incidence of tuberculous infection in Asian dialysis patients.

Adult↗

Crescentic transformation in primary membranous glomerulonephritis.

A 31 year old man first developed steroid-resistant idiopathic membranous glomerulonephritis in 1981. Stable normal renal function was maintained until August 1988 when he suffered a clinical relapse with heavy proteinuria and declining renal function. Immunosuppressive therapy with prednisolone and cyclophosphamide was instituted in an attempt to arrest this relapse. Despite this, he later developed acute renal failure with histological evidence of crescentic transformation of his nephritis. This unusual transformation was not associated with features of systemic vasculitis or positive anti-glomerular basement membrane and anti-neutrophil cytoplasmic antibodies.

Adult↗

Pneumocystis carinii pneumonia: detection of parasites by immunofluorescence based on a monoclonal antibody.

A monoclonal antibody-based immunofluorescence test for the detection of Pneumocystis carinii was evaluated in comparison with the conventional direct staining by Grocott's silver methenamine technique. A total of 254 respiratory samples from HIV positive and other immunocompromised patients were examined. Cysts were detected in 30 (12%) of samples using the monoclonal test, but only 15 (6%) positives were found using the Grocott method. There is need for a speedy and efficient test for detection of these organisms, and the monoclonal test was found to be more reliable, quicker and more sensitive than the Grocott technique.

Acquired Immunodeficiency Syndrome↗

Sensations during chest tube removal.

Nurses prepare patients for chest tube removal, yet little has been written to indicate the sensations to be expected during this routine procedure. The sensations reported by patients and factors that could influence those sensations were examined in this study. The sample consisted of 36 patients after thoracic surgery (24 men and 12 women), all of whom were scheduled to have either a mediastinal or a pleural tube removed. They reported their sensations and the intensity of those sensations (using a 100 mm visual analog scale) within 15 minutes after tube removal. The most frequently reported sensation during chest tube removal was burning, followed by pain and pulling with mean intensities of 64, 62, and 45, respectively. Subjects reported having few sensations after the tube was removed with only five reporting soreness in the chest. The sensations and intensities did not differ for those who did and did not receive analgesia or for those having a pleural tube versus a mediastinal tube removed. The sensations were similar for the old and young subjects with younger subjects reporting higher intensities. Women reported pain more frequently than men, but the intensities of the sensations reported by men and women were not significantly different. The sensations reported during chest tube removal differ from those described in the literature and can be used to prepare patients more appropriately for chest tube removal.

Analgesia↗

Clinical evaluation of three posterior composite and two amalgam restorative materials: 3-year results.

The clinical performance of three posterior composites and two amalgams was evaluated over 3 years. Three hundred and nine composites and 200 amalgams were reviewed at the 3-year recall. The following parameters were assessed: fractures, gingival condition, interproximal contacts, marginal adaptation, staining and colour match. Although there was no significant difference in the overall failure rate between the two types of material, there was a significantly higher incidence of fracture in the amalgam restorations. The amalgam failures were exclusively mechanical, whereas those affecting composites also included failures that were more biological in nature. A significantly higher proportion of the Class II composites failed to achieve an adequate approximal contact, but this was not reflected in a more adverse gingival response. Colour match, surface and marginal stain varied significantly within the composite group and appeared to be material-related. Overall, the materials Occlusion and P-30 were considered to be performing adequately. The clinical handling, colour match and radiopacity of Clearfil Posterior were considered to be unsatisfactory.

Color↗

Plasma 24,25-dihydroxyvitamin D3 concentrations in X-linked hypophosphatemic mice: studies using mass fragmentographic and radioreceptor assays.

Previous studies have suggested that both plasma 24,25-dihydroxyvitamin D [24,25-(OH)2D] concentrations and renal 25-hydroxyvitamin D-24-hydroxylase activity are increased in mice with X-linked hypophosphatemia (Hyp mice). However, because the plasma levels of 24,25-(OH)2D seemed surprisingly high, we repeated these assays using two different techniques. Mass fragmentographic and radioreceptor assays were employed to compare the plasma concentrations of 25-hydroxyvitamin D (25-OHD) and 24,25-(OH)2D in normal mice with those in Hyp mice. These assays yielded 24,25-(OH)2D concentrations much lower than previously reported in mice (both normal and Hyp). The concentrations of 25-OHD3 and 24,25-(OH)2D3, determined by mass fragmentography, were lower in Hyp mice than in controls [25-OHD3, 9.7 +/- 0.4 versus 14.6 +/- 0.6 ng/ml, p less than 0.01; 24,25-(OH)2D3, 7.1 +/- 0.3 versus 10.4 +/- 0.4 ng/ml, p less than 0.01]. Plasma 25-OHD concentration was the main determinant of plasma 24,25-(OH)2D, and the ratio of 25-OHD3 to 24,25-(OH)2D3 obtained from mass fragmentographic measurements did not differ between the two groups (1.40 +/- 0.05 versus 1.36 +/- 0.03 ng/ml, NS in normal and Hyp groups, respectively). Separate measurement of plasma 25-OHD, 24,25-(OH)2D, and 25-OHD3-26,23-lactone by radioreceptor assay showed no difference between either plasma 24,25-(OH)2D, or the ratio of 25-OHD concentration to 24,25-(OH)2D concentration among Hyp and control animals. In neither study was plasma phosphate concentration related to the 25-OHD3:24,25-(OH)2D3 ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗

Fast (4-h) or slow (24-h) infusions of pamidronate disodium (aminohydroxypropylidene diphosphonate (APD)) as single shot treatment of hypercalcaemia.

Twenty-five patients with hypercalcaemia (ionised calcium, 1.57 +/- 0.04 mM; total calcium, 3.33 +/- 0.06 mM) due to malignancy were randomised to receive pamidronate (1 mg/kg body wt.) by infusion over 4 h (12 patients) or 24 h (13 patients). Forced saline diuresis was not utilised. Two patients died within 24 h and were not included in the analysis. Both groups combined (n = 23) showed a decrease in ionised calcium to 1.44 +/- 0.04 mM by 2 days (P less than 0.05 vs. day 0). By 4 days there had been a further fall to 1.27 +/- 0.05 mM (P less than 0.05 vs. day 2) and 7 days after treatment ionised calcium was 1.19 +/- 0.05 mM (P less than 0.05 vs. day 4). Total calcium declined from 3.33 +/- 0.06 to 2.65 +/- 0.11 mM over 7 days (P less than 0.001). Separate analyses of the two groups showed that the fast (4-h) infusion led to an earlier reduction in calcium than did the 24-h infusion (P less than 0.02), although after 7 days there was little difference between the two groups (4 h, 1.18 +/- 0.09 mM; 24 h, 1.23 +/- 0.06 mM, n.s.). Hypercalcaemic symptoms (analogue rating scale) improved between each of the time intervals 0, 4 and 7 days (P less than 0.05) and did not differ between the two groups. We recommend a single 4-h infusion of pamidronate (1 mg/kg) as primary treatment for malignancy-induced hypercalcaemia.

Calcium↗

Immunoglobulin heavy chain switch region gene polymorphisms in glomerulonephritis.

Much evidence suggests that primary IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN) are immune complex mediated diseases. Moreover, genetic factors may play an important role in their pathogenesis. Recently, restriction fragment length polymorphisms (RFLPs) of the immunoglobulin heavy chain genes have been described which appear to associate with glomerulonephritis. We have studied RFLPs of the switch region of the IgM (S mu) and IgA1 (S alpha 1) heavy chain in MN and IgAN. DNA obtained from British Caucasoids with IgAN (N = 75), MN (N = 43), and normal controls (N = 73), was digested with the restriction enzyme Sac1, and studied using Southern blot techniques and hybridization with a 32P labelled DNA probe homologous to S mu. This probe detects RFLPs at the S mu and S alpha 1 loci. The genotypic and allelic frequencies of the S mu and S alpha 1 alleles in IgAN and MN was similar to normal controls. Caucasoid subjects with IgAN from Northern and Southern Europe (Finland and Italy, respectively) were also studied to determine whether an ethnic variation in genetic susceptibility to IgAN exists. The frequency of the S mu and S alpha 1 alleles was similar between the patient groups and their respective local healthy controls. These results do not support the recent findings of an association with RFLPs of the S mu and S alpha 1 loci in IgAN and MN, and suggest that the immunoglobulin heavy chain switch region genes are not important in conferring disease susceptibility to IgAN or MN.

Blotting, Southern↗

Pharmacokinetics of once daily intra-peritoneal aztreonam and vancomycin in the treatment of CAPD peritonitis.

The pharmacokinetics of aztreonam and vancomycin were studied in six adult patients who developed peritonitis during Continuous Ambulatory Peritoneal Dialysis. Aztreonam 3 g was added to the first exchange in each 24 h period with vancomycin 500 mg on the first day and 250 mg on each subsequent day (provided the pre-dose serum vancomycin concentration was less than 10 mg/l) for a total of ten days. Aztreonam and vancomycin concentrations were measured in the serum and dialysate at 1, 2, 6, 12, 18 and 24 h after the initial dose and pre-dose on days 5 and 10. By the end of the ten day study all patients had recovered clinically and had a normal dialysate. For aztreonam, the mean peak serum concentration was 84.3 mg/l (range 59.6-102.8), the mean 24 h pre-dose serum concentration was 23.0 mg/l (range 8.6-39.2) and the mean 24 h pre-dose dialysate concentration was 15.5 mg/l (range 5.0-32.0). For vancomycin, the mean peak serum concentration was 10.2 mg/l (range 8.1-12.6), the mean 24 h pre-dose concentration was 5.5 mg/l (range 3.6-6.4), and the mean 24 h pre-dose dialysate concentration was 3.4 mg/l (range 2.4-4.6). In the treatment of CAPD peritonitis, once daily intra-peritoneal administration of aztreonam 3 g with vancomycin 500 mg initially and 250 mg on subsequent days (serum concentrations permitting) provides concentrations of antibiotic in both the serum and dialysate throughout the 24 h period in excess of the inhibitory concentrations of those organisms most frequently encountered in this condition.

Aztreonam↗