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Biomedical subjects

J Donohoe

Publications and source records attributed to J Donohoe.

At least 19 recordsLinked to original sources

Implications of colonization of vancomycin-resistant enterococci (VRE) in renal dialysis patients. Learning to live with it?

Vancomycin-resistant enterococci (VRE) commonly colonize, but less frequently infect, debilitated patients, such as those on chronic renal dialysis. The emergence of VRE amongst our cohort of renal replacement therapy patients posed considerable challenges in our attempts to prevent spread. Although 60 of 451 (13%) patients became colonized, only two patients required systemic antibiotics for confirmed or suspected invasive infection. Mortality and inpatient stay was greater in VRE-positive compared with VRE-negative patients (50% versus 10%) and patients who were screened on three or more occasions were likely to remain positive (e.g. 56% of patients screened on six occasions were positive). The application of recommended guidelines for the control of VRE, however, severely disrupted our renal dialysis programme and therefore had to be abandoned. As patients on renal dialysis are more likely to acquire VRE, remain colonized, require antibiotics and require regular inpatient or outpatient care more frequently than other patients, control measures should be adapted to minimize spread but not disrupt important and essential medical services.

Adolescent↗

Improved patient survival in recipients of simultaneous pancreas-kidney transplant compared with kidney transplant alone in patients with type 1 diabetes mellitus and end-stage renal disease.

BACKGROUND: There are emerging data that simultaneous pancreas-kidney transplant (SPK) prolongs life compared with kidney transplant alone (KTA) in type 1 diabetics with end-stage renal disease. This study was a retrospective comparison of SPK with KTA in patients with type 1 diabetes. METHODS: Between 1 January 1992 and 30 April 2002, 101 patients with type 1 diabetes were transplanted. Fifty-one of these patients received a KTA and 50 had a SPK. All patients underwent coronary angiography with surgical correction of any coronary artery disease before being listed. All patients who underwent SPK received quadruple immunosuppressive therapy consisting of antilymphocyte globulin, calcineurin inhibitor (tacrolimus or cyclosporin), azathioprine and steroids. Those who underwent KTA received calcineurin inhibitor (tacrolimus or cyclosporin), azathioprine and steroids. RESULTS: Patient survival at 1, 3, 5 and 8 years was 96, 93, 89 and 77 per cent respectively after SPK, and 93, 75, 57 and 47 per cent respectively after KTA (P = 0.018 at 8 years). CONCLUSION: The addition of pancreatic transplantation prolongs life in type 1 diabetic patients with renal failure compared with renal transplantation alone.

Adult↗

A review of urologic cancer patients with multiple primary malignancies.

Much has been written on the treatment of solitary or multiple metastatic nodules that sometimes present in patients with urological malignancies. However, relatively little has been published regarding those patients with urological cancer who have another concomitant primary non-urologic tumor. We describe several cases of patients who presented with a urologic malignancy and a secondary non-urologic tumor. We also reviewed the literature using MEDLINE to gather information concerning this rare occurrence. We found that secondary malignancies, although not very common, are being increasingly reported. They are usually detected during the preoperative work-up of the primary tumor, usually by CT scan, ultrasound, or chest X-ray. Most authors suggest that treatment should be directed at the more aggressive lesion first, which would improve the overall status of the patient, and thus allow a better response from therapy for the secondary lesion. While patients with multiple primary malignancies are rare, the urologist should be alerted to this possibility when evaluating the patient for the initially presenting or detected tumor.

Adenocarcinoma↗

Cutaneous abnormalities and metabolic disturbance of porphyrins in patients on maintenance haemodialysis.

Blistering disorders may occur in patients with chronic renal failure. Photoactive medication may account for some, and others may be attributable to porphyria cutanea tarda (PCT), but most appear idiopathic. Seventy haemodialysis patients at the National Renal Transplant Centre were therefore screened to determine the prevalence of cutaneous disease and to establish a reference range for plasma porphyrins in this population. The possible contribution of hepatitis C virus (HCV) infection to increased porphyrin levels in this group was also investigated. Ninety four percent of patients on haemodialysis had dermatoses associated with chronic uraemia, and the plasma porphyrin levels in those patients (mean +/- 2 S.D.: 19.1 +/- 13.5 nmol/L) were significantly higher than those of a normal population (n = 40; mean +/- 2 S.D.: 5.5 +/- 3.2 nmol/L) (p < 0.05). Only 2 patients (2.9%), however, had antibodies to HCV and although three others had blistering on light-exposed skin, none of these had PCT or was on photoactive medication, nor did they differ from the rest of the haemodialysis population with regard to erythropoietin or alcohol ingestion. For patients on haemodialysis, therefore, in whom urinary porphyrin estimation is impossible or unreliable, it is recommended that plasma porphyrin profiles be checked where necessary with reference to the range for a haemodialysis population, in addition to assessment of the faecal porphyrin profile. Abnormal porphyrin levels in this group may not, however, be explained by HCV infection, but the occurrence of blistering on the sun-exposed sites of 3 patients suggests that ultraviolet radiation may be implicated in those instances.

Adolescent↗

Glomerulonephritis after ventriculo-atrial shunt.

We describe five patients with glomerulonephritis (GN) associated with cerebrospinal fluid shunt insertion to relieve hydrocephalus. A ventriculo-atrial (V-A) shunt had been placed on average 12.5 years prior to the diagnosis of nephritis (range 0.5-21 years). Four patients developed membranoproliferative glomerulonephritis (MPGN) with associated hypocomplementaemia. A single patient developed focal proliferative glomerulonephritis. Coagulase-negative staphylococci were cultured in four patients, either from blood or from the shunt. Four patients had their shunts removed, two of whom also received antibiotics. The other patient received antibiotics alone for infective endocarditis due to staphylococcal bacteraemia which originated in the shunt. All patients had substantial renal impairment at the time of diagnosis (GFR, glomerular filtration rate, 20-45 ml/min). There was significant improvement in renal function after appropriate treatment; four of the five patients doubled their GFRs and two patients regained normal function.

Adolescent↗

Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice.

The physiological role of insulin-like growth factor (IGF) II (IGF-II) in adult humans is poorly understood. Rather high levels of IGF-II persist in adult human serum, whereas, in rodents, IGF-II levels are very low. To investigate the physiological and carcinogenic effects of persistently elevated IGF-II in adults, we have produced two lines of transgenic mice in which high levels of IGF-II (20- or 30-fold increase above normal) are persistently maintained in the blood. The transgene is driven by the major urinary protein promoter, and it is highly expressed in the liver and perputial glands in both lines. The adult transgenic mice are smaller than controls, and their body composition is altered. Their lean body mass is reduced by 5-8%, whereas fat mass is reduced between 44 and 77%. The mice expressing the highest level of IGF-II (30x) develop hypoglycemia and hypoinsulinemia and IGF-I levels are normal. Mice in the lower expression line (20-fold elevated IGF-II) develop hypoglycemia progressively over their lifetime. Mice from both lines also develop a diverse spectrum of tumors at a higher frequency than controls after 18 months of age, and the most frequent types of tumors are hepatocellular carcinomas and lymphomas. Squamous cell carcinoma, sarcoma, and thyroid carcinomas also occurred in our test group. The long latent period before tumors arise and the wide spectrum of tumor types suggest that IGF-II may function primarily as a tumor progression factor in mice via autocrine and endocrine mechanisms of action.

Animals↗

Antiglomerular basement membrane disease: the long-term pulmonary outcome.

We have evaluated long-term pulmonary function in 14 patients who were treated for anti-glomerular basement membrane disease at our institution during the last 17 years. Eight of these patients had evidence of pulmonary involvement, as manifested by hemoptysis, pulmonary infiltrates on chest x-ray film, or anemia. These patients were compared with a control group of 15 patients who had renal disease and who were matched for degree and duration of renal disease, age, smoking history, and method of renal replacement. The following variables were measured in each patient: forced vital capacity, forced expiratory volume in 1 minute, vital capacity, total lung capacity, residual volume, functional residual capacity, single-breath carbon monoxide transfer factor, and single-breath carbon monoxide transfer factor corrected for alveolar volume (KCO). These patients also participated in a graded exercise test and measurements of oxygen uptake, carbon dioxide production, minute ventilation, and oxygen saturation were taken. Patients with anti-glomerular basement membrane disease and a prior history of pulmonary hemorrhage had a significantly reduced KCO (46% +/- 10% v 68.7% +/- 14.7%) compared with the control group. There was no difference in any of the other measured parameters.

Adult↗

Chronic occult intra-alveolar hemorrhage: a rare cause of failure to respond to erythropoietin.

Recombinant human erythropoietin (EPO) is an effective and safe therapy for correction of anemia in end-stage renal disease (ESRD). Clinical trials reported to date suggest that EPO improves anemia in over 90% of hemodialysis patients with anemia (Eschbach 1989). Factors which have been identified that appear to inhibit the effectiveness of EPO are infection [Muirhead N et al. 1990], iron deficiency, hyperparathyroidism, aluminium excess [Casati 1991] and persistent GIT bleeding. The development of reticulocytosis in response to EPO in the absence of a rise in hematocrit should alert the clinician to the possibility of either hemolysis or occult blood loss. We present a case in which, despite the development of a reticulocytosis of 5% in response to EPO and the absence of hemolysis, we had difficulty in identifying the presumed source of blood loss.

Anemia↗

Lower prevalence of anti-hepatitis C antibody in dialysis and renal transplant patients in Ireland.

It is well recognised that haemodialysis and renal transplant patients are at increased risk of developing non-A, non-B hepatitis. Recently the genome of hepatitis C virus (HCV), the major causative agent for non-A, non-B hepatitis, has been isolated. Anti-HCV seroprevalence was assessed in all haemodialysis patients (266) in Ireland who in March 1990 had been dialysed for at least 6 months. For comparative purposes, 272 patients who had functioning renal transplants for greater than 6 months were also studied. Potential risk factors such as age, number of blood transfusions and time on dialysis were evaluated. The prevalence of HCV infection as evidenced by antibody detection was only 1.1% for transplant and 1.7% for haemodialysis patients. This compares to a reported incidence of between 10% and 50% found elsewhere. Two of the 5 anti-HCV positive haemodialysis patients and 2 of the 3 transplant patients had biochemical evidence of liver disease. From stored sera it was possible to ascertain when patients acquired HCV. Whether the very low prevalence of anti-HCV in Irish patients is due to the low prevalence of the virus in the general population, the policy of non reimbursement of blood donors, genetic or other factors, remains to be determined.

Adult↗

The use of recombinant human erythropoietin in end stage renal disease.

We treated 57 patients who suffered from end stage renal disease (ESRD) with recombinant human erythropoietin (EPO) for a mean period of 56 weeks. Patients were aged between 18 and 81 years. Forty three patients were on haemodialysis and 14 on continuous ambulatory peritoneal dialysis (CAPD). Despite regular transfusions, the mean haemoglobin prior to EPO therapy was 7.4 g/dl +/- 1.7. The target haemoglobin of 10 g/dl was reached at a mean of 12 weeks for the CAPD patients and at 14 weeks for the haemodialysis population. Patients were noted during the study to have a progressive rise in mean red cell volume, and this appeared to be related to their level of iron stores. The mean dose EPO used to reach the target haemoglobin was 8,700 u/week (125 u/kg/week) for the haemodialysis patients and 7,200 u/week (102 u/kg/week) for the CAPD patients. Three patients (7%) developed thrombosis of their A/V fistula. Hypertension was exacerbated in 28% of the patients. We conclude that EPO is a very effective but not inexpensive therapy for the anaemia of ESRD.

Adolescent↗

Skin cancer in an Irish renal transplant population.

One hundred and forty-nine renal transplant patients attending 2 centres in Dublin were examined. Twelve patients (8.1%) were found to have cutaneous malignancy while dysplastic lesions (premalignant and/or malignant) were identified in 34 (22.8%). The prevalence of cutaneous malignancy in this study is substantially greater than that of previous Irish studies. The introduction of cyclosporin A (CyA) as a new and more effective immunosuppressive agent in renal transplantation may in part explain this increase.

Adult↗

Cytomegalovirus infection as a complication of OKT3 therapy in kidney transplant recipients.

We compared the incidence of clinical CMV illness in 25 renal transplant recipients treated with OKT3 for steroid resistant cellular rejection with 88 renal transplant patients treated only with conventional immunosuppression (cyclosporin A and steroids). Nine (36%) patients in the OKT3 group developed CMV illness compared to (2.3%) amongst those treated conventionally (p < 0.0005). Patients who received OKT3 were divided into four groups according to the CMV antibody status of the donor and recipient. Six of the 9 episodes of CMV infection occurred in patients not previously exposed to CMV, who received a kidney from a CMV positive donor. Three (12%) of the patients treated with OKT3 died of CMV disease. A further 2 patients died of other causes giving an overall mortality in the OKT3 treated group of 20%. We concluded that when OKT3 therapy is used in association with donor/recipient CMV mismatch it is associated with a high CMV morbidity and mortality.

Adolescent↗

The use of cyclosporin A in adult nephrotic syndrome: nine cases and literature review.

Nine adult patients with resistant nephrotic syndrome were treated with cyclosporin A (CyA). All had failed to respond to high dose corticosteroids with or without cyclophosphamide. Three patients had minimal change disease, 3 had focal sclerosing glomerulosclerosis (FSGS), 2 had mesangiocapillary GN, and one had membranous nephropathy. The mean age of the patients was 26.4 years (range 16 to 39 years). CyA was given orally twice daily at a mean dose of 6.7 mg/kg/24 hours (range 6-10 mg/kg/24 hours). Four patients achieved full remission, two patients went into partial remission and three failed to respond. Two patients developed clinical nephrotoxicity, which reversed on dose reduction or cessation of CyA. All 3 patients with minimal change disease who responded subsequently relapsed after stopping CyA, but remitted rapidly on reintroduction of the drug. We suggest that the mode of action of CyA in nephrotic syndrome may be related to intra-renal vasoconstriction in addition to its direct immunosuppressive effect. In this limited series, we found that CyA can be an effective therapy for otherwise refractory nephrotic syndrome, although relapse on withdrawal of CyA may well be a significant clinical problem.

Adult↗

Clinical and histopathologic findings in adults with the nephrotic syndrome.

The clinical and histopathologic findings in 225 Irish adults with nephrotic syndrome were reviewed. Membranous nephropathy was the most common lesion found (28%), followed by proliferative glomerulonephritis (17%), and focal sclerosing glomerulonephritis (16%). Minimal change disease was the least frequent cause for idiopathic nephrotic syndrome (12%). The major secondary cause of nephrotic syndrome was amyloidosis (13%). The patients were analysed for the predictive value of the level of renal function, presence or absence of hypertension, and the degree of proteinuria. It was not possible to determine the nature of the underlying lesion giving rise to the nephrotic syndrome using any of these variables. There was also no significant difference between primary and secondary glomerular disease with regard to these factors. It is concluded that renal biopsy remains the only definitive method of establishing the underlying lesion causing idiopathic nephrotic syndrome.

Adolescent↗