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Biomedical subjects

L R Baker

Publications and source records attributed to L R Baker.

At least 19 recordsLinked to original sources
PubMed1992

Reactogenicity and immunogenicity of a double-strength acellular pertussis vaccine.

The reactogenicity and immunogenicity of a double-strength acellular pertussis vaccine were evaluated after administration to 16 4-6-year-old children. The vaccine contained toxoided lymphocytosis-promoting factor (6.0 micrograms/dose), filamentous haemagglutinin (70 micrograms/dose), agglutinogens (1.4 micrograms/dose) and the 69 kDa protein (approximately 8.0 micrograms/dose). The vaccine was extremely well tolerated with few minor side effects following immunization. Significant increases in antibodies to all pertussis vaccine components were noted. In summary, this double-strength acellular pertussis vaccine, containing a very high dose of filamentous haemagglutinin, had minimal reactogenicity and was immunogenic. These findings, as well as other studies with this vaccine, indicate that filamentous haemagglutinin is not a major determinant of vaccine reactogenicity.

Antibodies, Bacterial↗
PubMed1992

Effects of oxygen breathing and erythropoietin on hypoxic vasodilation in uremic anemia.

Loss of hypoxic vasodilation has been proposed as a causative factor in the development of hypertension in dialysis patients treated with recombinant human erythropoietin (rHuEPO). Venous occlusion plethysmography was therefore performed on 22 dialysis patients (aged 23 to 71 years, dialysis duration 6 to 260 months, 8 males) before and after correction of anemia with rHuEPO, 50 U/kg 3x/week (Hb: 7.4 +/- 0.3 vs. 10.8 +2- 0.3 g/dl, P less than 0.0001). Hypertension (greater than 15 mm Hg rise in mean BP) occurred in 11 patients. The study was performed while breathing room air and repeated after breathing 60% O2 for 10 to 12 minutes. Before rHuEPO therapy, total blood O2 content increased from 10.01 +/- 0.39 to 10.32 +/- 0.29 ml O2/100 ml blood with breathing 60% O2 (P less than 0.01). After correction of anemia it was 14.65 +/- 0.40 ml O2/100 ml blood on room air (P less than 0.001). There was a significant decrease in forearm blood flow (7.9 +/- 0.5 vs. 6.5 +/- 0.6 ml/min/100 ml tissue, P less than 0.05) and increase in forearm vascular resistance (12.8 +/- 0.1 vs. 16.8 +/- 0.2 mm Hg/ml/min/100 ml tissue, P less than 0.05) with O2 breathing prior to rHuEPO therapy in the blood pressure responders, but no change in these parameters in the group in which blood pressure remained unchanged. When all patients were studied on room air, forearm vascular resistance rose significantly after correction of anemia (13.0 +/- 0.8 vs. 16.3 +/- 0.8 mm Hg/ml/min/100 ml tissue, P less than 0.05), compared with that prior to rHuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Platelet cytosolic free calcium concentration and parathyroid hormone: changing relationships with haemodialysis in end-stage renal disease.

1. Twelve patients receiving haemodialysis for end-stage renal failure were studied at a single dialysis session. Platelet cytosolic calcium concentration, plasma ionized calcium concentration and serum parathyroid hormone concentration were measured before dialysis, mid-dialysis and 30 min after dialysis. 2. Plasma ionized calcium concentration increased towards dialysate calcium concentrations, falling insignificantly after cessation of dialysis. Serum parathyroid hormone concentration fell by 39% during dialysis, with incomplete recovery afterwards. There was no overall change in platelet cytosolic calcium concentration. 3. Patients were divided into two subgroups: low parathyroid hormone (serum parathyroid hormone concentration less than 10 pmol/l) and high parathyroid hormone (serum parathyroid hormone concentration greater than 10 pmol/l). Before dialysis, values of platelet cytosolic calcium concentration or plasma ionized calcium concentration were not statistically different between the subgroups, but the platelet cytosolic calcium concentration was higher in the high-parathyroid hormone subgroup during and after dialysis. 4. Before haemodialysis there was a linear correlation between plasma ionized calcium concentration and platelet cytosolic calcium concentration, which disappeared during dialysis. In contrast, there was no relationship between serum parathyroid hormone concentration and platelet cytosolic calcium concentration before dialysis, but after dialysis a hyperbolic relationship was evident. 5. These results suggest that uraemic toxins may interfere with cytosolic calcium homoeostasis, allowing passive diffusion of extracellular calcium to influence the resting concentration, and that this effect is reversible by haemodialysis.

Adult↗
PubMed1992

Comparison of haemostatic activity in haemodialysis and peritoneal dialysis patients with a novel technique, haemostatometry.

Bleeding due to impaired primary haemostasis is common in uraemia. However, thrombo-embolic episodes are also a clinical problem in dialysis patients. Platelet reactivity to shear stress (haemostasis, H1 and H2), exposure to collagen fibre (thrombus growth) and coagulation of flowing blood (clotting time, CT1 and CT2) were measured in non-anticoagulated blood samples taken immediately before and 18-24 h after haemodialysis (n = 26) and from patients maintained on continuous ambulatory peritoneal dialysis (CAPD, n = 30). H1 (p < 0.001), H2 (p < 0.01), percent thrombus growth rate (p < 0.03), CT1 (p < 0.01 and CT2 (p < 0.05) were restored towards normal after haemodialysis. Results obtained in the CAPD patients demonstrated that the mean values for formation of the haemostatic plug lay between the pre- and posthaemodialysis values; however, CT1 (p < 0.01) and CT2 (p < 0.05) were prolonged in CAPD compared with values after haemodialysis. These data, which indicate platelet function from non-anticoagulated blood and coagulation under flow conditions, (1) confirm that there is impaired haemostasis in uraemia; (2) demonstrate an improvement in haemostasis after haemodialysis; (3) show that peritoneal dialysis results in a haemostatic profile which falls between the pre- and posthaemodialysis pattern, and (4) show that neither dialysis modality returns haemostasis to normal.

Adult↗
PubMed1991

Recurrent CAPD peritonitis caused by coagulase-negative staphylococci: re-infection or relapse determined by clinical criteria and typing methods.

Four hundred consecutive episodes of continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis in 105 patients were analysed. Of these episodes 161 (40.25%) were caused by coagulase-negative staphylococci (CNS). Thirty-seven patients developed recurrent attacks (3-10) of peritonitis and CNS accounted for 72 (60%) of these episodes. Classification of reinfection or relapse in 67 of these recurrent episodes of peritonitis was based on clinical criteria alone. This was compared with the results of three typing methods of CNS strains: biotyping plus antibiograms, immunoblotting and 35S-methionine-labelled protein patterns (radio-PAGE). Radio-PAGE was the most discriminatory method followed by biotyping with antibiograms and then immunoblotting. There was total agreement between clinical diagnosis and the three typing methods in 67.2% of episodes but there was total disagreement between the clinical diagnosis and the three typing methods in 11.9%, suggesting inaccurate clinical diagnosis, and in 20.8% typing by at least one method differed from the clinical criteria. Thus, clinical criteria alone are inadequate for the accurate distinction of reinfection from relapse in recurrent CNS peritonitis. This distinction is desirable for optimal management and accurate assessment of different therapies. We suggest that CNS strains from peritoneal dialysate are stored for future typing should the patient develop repeated episodes of peritonitis, to aid in the diagnosis and management of such patients.

Autoradiography↗
PubMed1991

Epidemiology of CAPD-associated peritonitis caused by coagulase-negative staphylococci: comparison of strains isolated from hands, abdominal Tenckhoff catheter exit site and peritoneal fluid.

We identified twenty patients maintained on continuous ambulatory peritoneal dialysis who suffered repeated episodes of peritonitis caused by coagulase-negative staphylococci. We documented hand and exist-site coagulase-negative staphylococcus-associated peritonitis over a total period of 32 months, and compared hand and exit-site strains with strains isolated from dialysate fluid using three typing methods: biotyping using the API Staph kit plus antibiograms, immunoblotting using sera raised in rabbits to three standard strains of coagulase-negative staphylococci, and 35S-methionine-labelled coagulase-negative staphylococcal profiles separated on sodium dodecylsulphate polyacrylamide gel electrophoresis and visualised by autoradiography (radioPAGE). In 5 of 84 episodes, strains isolated from skin were indistinguishable by all three typing methods from the dialysate strain. In a further two episodes, hand or exit-site isolates were indistinguishable by all three typing methods from the dialysate strain isolated in the subsequent, but not the same, episode. Thus in the majority of episodes, no inference of hand or exit-site origin of dialysate infection could be drawn.

Adult↗
PubMed1991

Pitfalls after total parathyroidectomy and parathyroid autotransplantation in chronic renal failure.

We have described 4 patients with chronic renal failure receiving regular haemodialysis treatment who underwent total parathyroidectomy with autotransplantation of parathyroid fragments into the forearm musculature for hypercalcaemic hyperparathyroidism. In all, there was an immediate and profound fall in plasma calcium levels. Hypercalcaemia recurred 1-5 years post-operatively and was resistant to resection of the autograft. In 3 cases, thallium-technetium subtraction scanning and multiple venous sampling for estimation of parathyroid hormone levels suggested multiple sites of hypersecretion of parathyroid hormone in the neck. In 1 case, these investigations revealed a mediastinal adenoma which was successfully removed. These cases reinforce previous suggestions that total parathyroidectomy is frequently incomplete and undermine the procedure of total parathyroidectomy with autotransplantation in patients with persisting uraemia.

Adult↗
PubMed1991

Prevention of renal osteodystrophy.

Prevention of bone disease associated with impairment of the renal function is desirable. Attempts at such prevention inevitably also embrace prevention of the extraosseous consequences of autonomous hyperparathyroidism, such as the effects of hypercalcaemia, need for parathyroid surgery, and, perhaps, toxic effects of the parathyroid hormone. Strategies for prevention in early, moderate, and end-stage renal failure are reviewed and discussed with particular reference to dietary phosphorus restriction, use of gut phosphorus binders, control of acidosis, calcium supplementation, use of oral and intravenous calcitriol, and use of synthetic analogues of 1,25-dihydroxyvitamin D3. The onset of severe renal osteodystrophy can be delayed. Early attempts at prevention are logical, but we do not know whether these will reduce the need for parathyroid surgery or will make patients feel better or live longer. The costs of prophylaxis--both financial and in terms of incidence and severity of complications--remain to be defined. An individual approach to each patient with renal impairment seems at present appropriate.

Aluminum↗
PubMed1991

Combined hepatic and renal transplantation in primary hyperoxaluria type I: clinical report of nine cases.

PURPOSE AND PATIENTS AND METHODS: The purpose of this article is to report the experience of three centers with combined hepatic and renal transplantation for pyridoxine-resistant primary hyperoxaluria type I (alanine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency), with particular emphasis on the selection criteria and timing of the operation. Nine patients with this inherited disease were treated by combined hepatic and renal transplantation. The former replaces the enzyme-deficient organ while the latter replaces the functionally affected organ. RESULTS: One patient with gross systemic oxalosis died in the immediate postoperative period and another died 8 weeks postoperatively of a generalized cytomegalovirus infection, having shown evidence of biochemical correction. One patient with particularly severe osteodystrophy at the time of the operation died 14 months postoperatively from renal failure due to progressive calcium oxalate nephrocalcinosis involving the transplanted kidney, plus thromboembolic disease. He also had very extensive systemic oxalosis. An additional patient with severe osteodystrophy died 9 months postoperatively. One patient developed hyper-rejection of the kidney and died later of gastrointestinal hemorrhage. The four long-term survivors (22 to 38 months) have remained asymptomatic from the standpoint of their renal disease, with resolution of any manifestations of systemic oxalosis that they may have had. They are either employed or continuing their education. CONCLUSIONS: A prolonged period of end-stage renal failure treated by dialysis regimens that are suitable for non-hyperoxaluric renal failure and extensive systemic oxalosis, particularly oxalotic osteodystrophy, are poor prognostic features. We propose that hepatic transplantation should be considered as definitive treatment before end-stage renal failure develops. This should be supplemented by renal transplantation with vigorous pre- and perioperative hemodialysis to deplete the body stores of oxalate. Although some authorities would reserve hepatic transplantation for patients in whom renal transplantation has failed, we suggest that combined liver and kidney transplantation is appropriate in patients who have never had a renal graft. Furthermore, the time has come to consider hepatic transplantation before any irreversible renal damage has occurred in these patients.

Adolescent↗
PubMed1990

Enhanced in vitro hemostasis and reduced thrombolysis in cyclosporine-treated renal transplant recipients.

In vitro hemostatometry and assessment of thrombolysis was carried out in three groups of 72 renal transplant recipients. In one (triple, n = 21) immunosuppression was with cyclosporine, azathioprine, and prednisolone, while a second group (CsA, n = 29) received cyclosporine and prednisolone alone, and the third group (Aza, n = 22) azathioprine and prednisolone. Results were compared with those in 30 normal controls. A statistically significant increase in hemostasis compared with controls was seen in the triple group and in patients in the CsA group studied within 2 years of transplantation. Hemostasis in the Aza group did not differ from normal. All patients in this group had been transplanted more than 2 years before study. Thrombolysis times were significantly prolonged compared with controls in all three groups. Cyclosporine treatment is associated with enhanced hemostasis and reduced thrombolysis, especially during the first 2 years after renal transplantation. If these in vitro findings reflect events in vivo, this may throw light upon the pathogenesis of the obliterative arteriolopathy that is a feature of cyclosporine nephrotoxicity.

Azathioprine↗
PubMed1989

1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial.

This study represents the first randomized prospective, double-blind, placebo-controlled trial of the efficacy of 1,25(OH)2D3 on bone histology and serum biochemistry in patients with mild to moderate renal failure. Sixteen patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min) received either 1,25(OH)2D3, at a dose of 0.25 to 0.5 microgram daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. 1,25(OH)2D3 treatment was associated with a significant fall in serum phosphorus and alkaline phosphatase concentrations as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of 1,25(OH)2D3 was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.

Adult↗
PubMed1989

Silicone in the liver: possible late effects.

We describe two renal transplant recipients who presented with clinical and biochemical abnormalities of liver function in whom liver scarring and silicone particles were identified in the liver by light microscopy. The presence of silicon in the particles was confirmed by x-ray energy dispersive spectroscopy. In one patient liver abnormalities were first noted more than two years after haemodialysis was discontinued and in a second patient abnormalities were still present more than four years after successful kidney transplantation. No other specific cause for the chronic liver abnormalities was determined and we consider that these may be related to the presence of silicone degradation products in the liver. Other patients haemodialysed using a siliconised peristaltic blood pump insert system may also be a risk of developing similar late complications.

Adult↗