fas-fas-ligand antigen expression and its relationship to increased apoptosis in acute renal transplant rejection.

BACKGROUND: To examine the role of fas-fas-ligand interaction and apoptosis in acute transplant rejection. METHODS: Pre- and posttransplant renal allograft biopsies were stained by in situ 3-end labeling of DNA for detection of apoptotic cells (TUNEL) and immunohistochemistry techniques were used for demonstration of fas and fas-ligand antigen expression. RESULTS: Posttransplantation apoptosis was significantly increased in acute rejection and acute tubular necrosis (P<0.0001) compared to preimplantation biopsies and biopsies taken from grafts showing dysfunction not attributed to rejection. Fas and fas-ligand expression was demonstrated predominantly in the tubular epithelium. In preimplant biopsies fas was expressed in 11% (4/37) of cases; posttransplantation expression increased to: 44% (8/18) acute rejection, 63% (5/8) acute tubular necrosis, and 38% (5/13) dysfunction without evidence of rejection. Fas-ligand was expressed by 30% (11/37) of preimplant biopsies, posttransplantation expression was reduced in all groups: 17% (3/18) acute rejection, 13% (1/8) acute tubular necrosis, delayed xenograft rejection and 15% (2/13) dysfunction without evidence of rejection. A correlation with fas-1 expression preimplantation and a subsequent absence of acute rejection post transplant was noted (P<0.001). CONCLUSIONS: Apoptosis is a feature of acute rejection and acute tubular necrosis. Fas expression is uncommon preimplantation and increases non-specifically post transplant. Fas-1 was expressed by a third of preimplantation biopsies and expression was lost non-specifically post transplant. The expression of fas-ligand preimplantation correlated with an absence of acute rejection episodes posttransplant, suggesting some degree of immune privilege. These data suggest that the fas-fas-1 mediated pathway does not play a specific role in apoptosis during acute rejection. We were unable to find any evidence that the fas-fas-1-mediated pathway has a role in the increased apoptosis seen during acute rejection.

In vitro production of tumor necrosis factor by monocytes cultured from dialysis patients.

Cellular release of cytokines may be responsible for certain complications of extracorporeal dialysis including the increased susceptibility to infection found in dialysis patients. In order to study this further, we have evaluated the in vitro production of tumor necrosis factor (TNF) by peripheral blood monocytes (PBMC) to stimulation by lipopolysaccharide (LPS) from dialysis patients with end-stage renal failure (ESRF). The patients were subdivided into two groups according to the type of dialysis; those undergoing hemodialysis (HD) (N = 12) and those performing continuous ambulatory peritoneal dialysis (CAPD) (N = 9). Results were compared with those of controls taken from healthy laboratory staff (N = 7). The experiments show that the secretion of TNF by PBMC's in response to LPS is significantly augmented in patients undergoing HD when compared to those on CAPD (81.3 +/- 38.7 U/ml vs. 18.2 + 13.3 U/ml, mean +/- SD, P < 0.001); and controls (81.3 +/- 38.7 U/ml vs. 18.1 +/- 6.6 U/ml, P < 0.001). There was no significant difference between the CAPD group and controls. In vitro monocyte production of TNF fell following a single HD session (81.3 +/- 38.7 U/ml before HD and 50.5 +/- 28.7 U/ml after HD, P < 0.05). We conclude from this study that TNF release from PBMC's in vitro is augmented in patients with chronic renal failure receiving chronic HD but not in a similar group receiving CAPD. Interestingly, TNF release from monocytes collected immediately following a dialysis was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Hidden Markov based autoregressive analysis of stationary and non-stationary electrophysiological signals for functional coupling studies.

In this paper, we apply multivariate autoregressive (MAR) models to problems of spectral estimation for stationary and non-stationary electrophysiological data. We describe how to estimate spectral matrices and approximate confidence limits from MAR coefficients, and for stationary data spectral results obtained from the MAR approach are compared with fast Fourier transform (FFT) estimates. The hidden Markov MAR (HMMAR) model is derived for spectral estimation of non-stationary data, and traditional model order selection problems such as the number of states to include in the hidden Markov model or the choice of MAR model order are addressed through the use of a Bayesian formalism.

Crescentic nephritis at Groote Schuur Hospital, South Africa--not a benign disease.

The etiology of crescentic nephritis (CN) in the developing world differs from that of Europe and North America. This retrospective study of 73 patients is the largest series of CN in the developing world. The records of all renal biopsies performed at Groote Schuur Hospital, Cape Town, South Africa, over thirteen years, between January 1977 and April 1991, were reviewed. Specimens selected for this study had six or more glomeruli and over 50% of these glomeruli had crescent formation. It confirms that post infectious glomerulonephritis (PIGN) (n = 21) is the commonest cause of CN in this setting. In addition there were 15 patients with CN associated with systemic lupus erythematosus (SLE). These two groups make this study unique as they are the largest series of each described in the literature. Thirty-nine (53%) patients in this series progressed to end-stage renal failure (ESRF) and only nine (12%) patients recovered renal function to a normal serum creatinine. Eight (38%) patients in the PIGN group developed ESRF, indicating the poor prognosis of this condition. Six of eight patients in the PIGN group treated with steroids and cyclophosphamide recovered to a serum creatinine level less than 200 mumol/l and only one progressed to ESRF, which may indicate that this form of therapy is beneficial. Thirteen (87%) patients with SLE either developed ESRF or died which suggests that the presence of crescents in this condition is associated with a poor prognosis.

Is preliminary binephrectomy necessary in patients with autosomal dominant polycystic kidney disease undergoing renal transplantation?

Patients with end-stage chronic renal failure due to autosomal dominant polycystic kidney disease who underwent renal transplantation with or without preliminary binephrectomy were retrospectively studied to determine the effect of binephrectomy on outcome. Nineteen patients were identified. Thirteen patients had no surgery prior to transplantation and six underwent preliminary binephrectomy. One patient died as a result of the nephrectomy. Twenty-one renal allografts were performed on 18 patients of whom seven have died of sepsis; 10 have functioning grafts and one has returned to dialysis. Patients not undergoing preliminary binephrectomy had a statistically significant (p less than 0.05) increase in mortality and morbidity due to septic complications related to polycystic kidney disease. Indications for bilateral nephrectomy should be reconsidered.

Dialysis in the elderly. New possibilities, new problems.

In the last 2 decades, there has been a phenomenal increase in the number of incident and prevalent elderly patients receiving renal replacement therapy (RRT) and this trend is likely to continue. This article reviews the changing demographics of the renal patient population and discusses the possible reasons for this. The profile of the older adult patient group is discussed, and specific demands and requirements of this patient group are explained. In particular, the authors concentrate on dialysis mode and vascular access; malnutrition; falls and fractures; cognitive impairment and depression and drugs and pain. It is clear that the ''old old'' can benefit significantly from dialysis despite an increasing burden of comorbidity and prognosis on dialysis is discussed. In order to properly inform patients about treatment options it is essential to provide information about prognosis. For some patients dialysis may not be the preferred option and for others withdrawal from dialysis may be appropriate. Nephrologists therefore also need to be familiar with end of life issues and palliative symptom control.

Therapy of hepatocellular cancer with combined intrahepatic arterial chemotherapy and whole liver irradiation.

Hepatocellular cancer provides an ideal model for studying combined modality chemotherapy and radiation interactions. We have treated 20 evaluable patients. All patients received intrahepatic arterial (IA) 5 FU (10 mg/kg/d continuous infusion times 5 minus 9 d) + Adriamycin (3-5 mg/m(2)/d bolus times 5 minus 7 d), and 1,500 and 2,100 rads whole liver radiation (300 rads/day). Additionally, 3 patients have received IA Mitomycin C (8 mg/m(2)). After this "induction" therapy patients usually received IV Adriamycin + 5FU +/- Mitomycin monthly. Objective regressions occurred in 9/20 (45%) and another 9/20 (45%) and stable disease. Median duration of response is 5+ months (range 1+ to 8 months). Improvement in liver function tests occurred in 11/19, and local symptomatic relief in 12/15. Median WBC nadir = 4,000; platelet nadir = 115,000. Mild anorexia, fever, and nausea were frequent, but no radiation hepatitis has been detected. This program seems to result in significant clinical benefit (subjective and objective) in this refractory neoplasm.

Towards a more rapid diagnosis of rapidly progressive glomerulonephritis.

An attempt was made to provide simple practical guidelines to alert general practitioners to the diagnosis of rapidly progressive glomerulonephritis and lead to early referral to hospital. The duration of illness before referral to this hospital and its effect on outcome in patients with crescentic nephritis were assessed retrospectively from the case notes of 24 patients referred over two years. Four patients had Goodpasture's syndrome, 11 Wegener's granulomatosis, seven microscopic polyarteritis, and two idiopathic progressive glomerulonephritis. The duration of symptoms before referral to the local hospital was similar in the four groups of patients and varied from one week to 28 months (mean 10 months). The duration of stay in the local hospital was two, nine, 11, and 180 days in the patients with Goodpasture's syndrome and a mean of four days (range one to eight) in those with Wegener's granulomatosis and 10 days (one to 18 days) in those with microscopic polyarteritis. In the local hospital the diagnosis was based on the results of renal biopsy and detection of antibodies to glomerular basement membrane in two patients with Goodpasture's syndrome and on the results of renal biopsy in seven of the other patients aided by the detection of antibodies to the cytoplasm of neutrophils (ANCA) in 10. Three of the 24 patients died and four required maintenance haemodialysis. Patients who present to their general practitioners with persistent non-specific symptoms should have a urine dipstick test and then blood tests and emergency referral to hospital if necessary. Hospital physicians should be aware of the speed and accuracy with which current assays can confirm a diagnosis of rapidly progressive glomerulonephritis.

Omentopexy for the difficult perigraft lymphocele after renal transplantation.

Between January 1977 and October 1992, 6 patients who had undergone renal transplantation presented with a symptomatic lymphocele that failed to resolve after conventional therapy and eventually required surgical intervention. This complication developed between 7 and 36 months postoperatively. Patients presented with local discomfort combined with deteriorating graft function caused by ureteric obstruction. The lymphoceles recurred after aspiration or external drainage and resolved after omentopexy. We conclude that omentopexy is a satisfactory procedure for the treatment of lymphoceles which fail to resolve after aspiration or external drainage.

Stress, social support and biopsychosocial dynamics in HIV-AIDS.

PIP: Early research on HIV/AIDS had a mainly biomedical orientation. From 1984, however, consideration has also been given to the psychosocial aspects of HIV/AIDS. A more integrated view of the biological, psychological, and social aspects of HIV/AIDS has been increasingly evident in research agendas. The argument that HIV is a necessary, but insufficient cause of symptomatic disease development has led to extensive commentary upon the possible etiological significance of cofactors. This paper reviews research trends in the psychosocial aspects of HIV-AIDS and explores the role of psychosocial cofactors in disease progression. This is done with a biopsychosocial model with recognition of the role of psychosocial stress, social support, and emotional adjustment. Research data from a study of biopsychosocial interrelationships in a sample of HIV-positive patients show a significant correlation between social support and emotional adjustment and that social support exerts a mediatory, stress-buffering effect in these patients. Observations are made upon aspects of the social conditions of South Africans with HIV/AIDS.^ieng

Vitamin D status in renal transplant recipients.

Vitamin D plays an important role in calcium homeostasis. Renal transplant recipients may be more susceptible to reduced levels because of decreased sun exposure and steroid therapy. This study aimed to determine vitamin D status after renal transplantation and its effect on parathyroid hormone (PTH) and bone mineral density (BMD). We measured serum 25-hydroxyvitamin D levels (25-OHD) in 244 renal transplant recipients, divided into two groups, 104 recently transplanted (less than 1 year) and 140 long-term. Vitamin D status was defined according to NKF/KDOQI guidelines. Mean 25-OHD levels were 33 +/- 19 nmol/L and 42 +/- 20 nmol/L, respectively, for the recent and long-term transplant recipients. Vitamin D insufficiency was present in 29% and 43%, deficiency in 56% and 46% and severe deficiency in 12% and 5%, respectively. An inverse correlation was found between logPTH and 25-OHD (r=-0.2, p= 0.019) in long-term but not in recently transplanted patients. No correlation was found between 25-OHD levels and BMD. Hypercalcaemia was present in 40% of the recently transplanted recipients and 25% of the long-term. In conclusion 25-OHD was low in virtually all of our renal transplant recipients and may aggravate secondary hyperparathyroidism, but its correction may be difficult in patients with hypercalcaemia.

Renal functional reserve in live related kidney donors.

Renal function in 12 live kidney donors who had donated a kidney to a relative 3 to 10 years previously was studied. No clinically significant impairment of renal function was observed in the group. A significant rise in creatinine clearance (P = less than 0.01) occurred after a meat-protein load. When compared with 12 healthy controls with two kidneys, there was no significant difference in the percentage change in clearance after the meat load. In both groups there was an inverse correlation between the percentage change in creatinine clearance and the baseline creatinine clearance (P = less than 0.01), with no significant difference in the regression lines of the two groups. In conclusion, it appears that the single kidney responds appropriately to a meat-protein load and that there is no evidence from this study to suggest that hyperfiltration damaged the remaining kidney.

Diagnosis and monitoring of renal osteodystrophy.

A variety of biochemical investigations and radiological techniques are available to assist in the diagnosis and monitoring of renal osteodystrophy. Measurement of serum parathyroid hormone remains the single most useful biochemical test in predicting bone histology in an individual patient. Newer biochemical markers of bone turnover are unlikely to supplant this in everyday practice, but may provide useful supplementary information in the future. The present review discusses the role of radiological investigation, including bone densitometry and quantitative ultrasound. Bone biopsy remains the 'gold standard' investigation. Its invasive nature and the need for specialized processing and interpretation limits its use in clinical practice, although it still has a role particularly in the investigation of low turnover states. Also, as molecular biological techniques are increasingly being used, the evaluation of biopsy specimens will in the future provide new insights into the disordered bone cell function that occurs in renal osteodystrophy.