Immune activation markers and AIDS prognosis.

Four assays for serum levels of cellular products of immune activation were examined as prognostic markers for AIDS in a prospective study of asymptomatic HIV-seropositive homosexual men. Baseline serum values of beta 2-microglobulin (beta 2M), neopterin, soluble CD8 (sCD8), and soluble interleukin-2 receptor (sIL-2R) for 185 men were examined univariately and multivariately as predictors of AIDS during 36 months of follow-up. Thirty-three cases of AIDS (18%) were diagnosed during the follow-up period. All four assays correlated highly with each other (r = 0.48-0.63), and all four were good univariate predictors of AIDS and comparable to CD4 lymphocyte count. beta 2M, neopterin, and sCD8 predicted AIDS independently of both CD4 count and HIV p24 antigen or p24 antibody in multivariate analysis. Within the range of CD4 count 200-499 x 10(6) cells/l, an immune activation marker used in combination with an assay for p24 antigen identifies those at 3-6% risk of AIDS over 36 months (low risk on both assays) and those at 63-86% risk (high risk on both assays). These results can be used to guide physicians and patients making decisions about treating asymptomatic HIV infection with zidovudine in individuals with CD4 lymphocyte count of 200-499 x 10(6) cells/l.     

Renal transplant function after ten years of cyclosporine.

Although the nephrotoxic side effects of cyclosporine are well known, the impact of long-term CsA on renal transplant function is uncertain. We studied 5-10-year renal function in 347 CsA-treated patients, and in 64 randomly selected non-CsA-treated patients who had a minimum of 55 months of graft function. Non-CsA patients had a lower creatinine (Cr) level at one year than CsA patients (P = .001), with no change in renal function over time (P = .6). In CsA-treated patients there was also no suggestion of progressive renal damage, as evidenced by no change in Cr or 1/Cr. Simple linear regression models of 1/Cr vs. time for the first 10 years posttransplant were fit to the data for each patient. Analysis of the Y-intercept estimates from these regressions showed that age (P = .001), sex (P = .001), cyclosporine toxicity (P = .024), and initial cyclosporine dosage (P = .016) significantly affected the one-year serum Cr. Variables not affecting one-year Cr included donor source, early rejection episodes, late rejection episodes, ATN, diabetes, transplant number, HLA ABDR mismatch (for cadaver transplants), maximum PRA, and PRA at transplant. Analysis of the slope estimates from the regressions revealed that only age (P = .001) and late rejection episodes (P = .001) significantly affected the rate of change in 1/Cr over time. We conclude that, in long-term renal transplant patients, there is no evidence of progressive deterioration in renal function due to CsA nephrotoxicity.     

Total parenteral nutrition promotes bacterial translocation from the gut

Bacterial translocation from the gut may be the primary event in many disease processes. The purpose of this study was to examine the route of nutrient administration on bacterial translocation from the gut. Each of 90 female Fischer rats underwent placement of a central venous catheter and was randomized to one of three groups. Group I (control) received food and water ad libitum. Group II received standard TPN solution orally from a bottle sipper and drank the solution ad libitum. Group III underwent TPN via the central catheter by pair feeding of the animals with group II. Animals were fed for 2 weeks, and liver, spleen, mesenteric lymph nodes, blood, and cecum were aseptically obtained for culture. A statistically significant difference (p less than 0.014) was found between translocation rates of parenterally fed animals compared with enterally fed animals. Two thirds of the animals (18/27) fed parenterally had culture-positive mesenteric lymph nodes compared with one third (9/27) of the enterally fed group and none (0/30) of the control group. A statistically significant increase in the cecal bacterial count was demonstrated in the animals fed the TPN solution, independent of route. Parenteral nutrition promotes bacterial translocation from the gut by increasing the cecal bacterial count and impairing intestinal defense.     

Immunological characterization of guanine nucleotide-binding proteins: effects of a monoclonal antibody against the gamma subunit of transducin on guanine nucleotide-binding protein-receptor interactions.

Guanine nucleotide-binding proteins (G proteins) transduce signals from agonist- and light-sensitive receptors. In the visual excitation system, the photon receptor rhodopsin is coupled to the G protein Gt (transducin). Gt is composed of alpha, beta, and gamma subunits; the alpha subunit binds guanine nucleotide, whereas the beta and gamma subunits, which are tightly associated, appear to facilitate interaction of alpha with receptor and pertussis toxin-catalyzed ADP-ribosylation of alpha. To study the function of transducin, monoclonal antibodies were developed against the purified protein. Monoclonal antibody 2H3 reacted with Gt gamma but not G gamma from bovine brain or rabbit liver. In the absence of photolyzed rhodopsin, both intact 2H3 and Fab fragments of 2H3 were able to inhibit completely, in a concentration-dependent manner, ADP-ribosylation of transducin by pertussis toxin 2H3 had no effect on ADP-ribosylation in the presence of photolyzed rhodopsin. The GTPase activity of transducin, which is dependent on rhodopsin, was inhibited only 50% by 2H3. These data are consistent with the hypotheses that an epitope recognized by 2H3 may be important in the formation of the alpha beta gamma complex or that interaction of 2H3 with gamma may alter conformation of the latter and, thereby, inhibit complex formation. Further, reactions of gamma with 2H3 appear to be prevented by interaction with rhodopsin, suggesting that its interaction either shields or alters the epitope recognized by 2H3.     

Timely initiation of dialysis--single-exchange experience in 39 patients starting peritoneal dialysis.

OBJECTIVE: To establish the effectiveness and patient acceptability of initiating peritoneal dialysis (PD) according to published guidelines. SETTING: A university teaching hospital and a neighboring district general hospital. DESIGN: Nonrandomized prospective pilot study. PATIENTS: 39 patients with a Kt/V > 2.0 attending predialysis clinics at both hospitals agreed to participate in this study. METHODS: Patients were started on a single exchange of dialysate overnight. Dialysis adequacy was monitored at least every 2 months and incremental increases in dialysis were used to maintain combined urinary and dialysis Kt/V above 2.0. Routine laboratory parameters and complications of dialysis were monitored during the follow-up period. RESULTS: The mean weekly Kt/V at initiation of dialysis was 2.09. Median actuarial survival on a single exchange before requiring incremental dialysis was 297 days. At the end of the study period, all patients were still alive: 8 remained on 1 exchange, 18 were on more than 1 exchange, 8 had switched to hemodialysis, and 5 had received renal transplants. During the 12,665 patient-days on single-exchange dialysis, there were 14 hospital admissions of 12 patients. This resulted in a mean of 1.64 hospital days per patient-year for the whole group. During the follow-up period there were 2 episodes of bacterial peritonitis, 3 pleural leaks, 1 patent processus vaginalis, and 1 inguinal hernia that required surgical intervention. The use single daily icodextrin exchanges was associated with a 46% incidence of culture-negative peritonitis. CONCLUSIONS: This pilot study has shown that a timely start of dialysis with a single overnight PD exchange is acceptable to patients. Incremental dialysis as residual renal function falls is easily managed and patients also find this acceptable. Complication and hospitalization rates were low. The presence of residual renal function often allows complications to be managed without the need for hemodialysis. The use of icodextrin as a single-exchange dialysate is associated with sterile peritonitis in a significant proportion of cases.     

Subclinical hepatic encephalopathy: relationship between neuropsychological deficits and standard laboratory tests assessing hepatic status.

A multivariate analysis of the relationship between biochemical measures of hepatic function and neuropsychological assessments of specific cognitive domains was performed on data obtained from 74 patients with chronic liver disease and subclinical hepatic encephalopathy. Biochemical tests of hepatic protein synthesis correlated significantly with measures of impaired language efficiency, perceptual speed, and psychomotor efficiency. Biochemical indices of impaired processing of nitrogenous compounds correlated with visuopractic deficits. Hepatic blood flow indices correlated with language inefficiency. Interestingly, biochemical measures of hepatic injury did not demonstrate a significant association with any neuropsychological parameter assessed. These results suggest that subclinical hepatic encephalopathy is the consequence of a multifactorial hepatic dysfunction, and that acute hepatic injury, as assessed by elevation of aminotransferases, does not appear to be involved in the pathogenesis of subclinical hepatic encephalopathy.     

Change in glycemia in a four-year interval in younger-onset insulin-dependent diabetes.

Hyperglycemia is an important risk factor for the development of retinopathy and nephropathy in people with diabetes mellitus. There are few population-based data on changes in glycemia over time. The purpose of this study was to examine changes in glycemia, as measured by glycosylated hemoglobin in 1980 to 1982 and in 1984 to 1986, in a large population-based study of people who were diagnosed to have diabetes before the age of 30 years and who used insulin (n = 697). Glycosylated hemoglobin was measured by a microcolumn technique at both examinations. There was a significant (P < .001) fall in the mean glycosylated hemoglobin from 10.8 to 10.1% over the 4-year interval of the study. In contrast, there was no change in the glycosylated hemoglobin (6.2%) in a similarly aged nondiabetic comparison group over the same period. The decrease in mean glycosylated hemoglobin over the 4-year period in the diabetic group was associated with several characteristics of diabetes management. These include changes in the insulin regimen (going from intermediate- or long-acting insulin only to combinations with short-acting insulin), an increase in the number of doses of insulin per day, and a higher frequency of self-monitoring of blood glucose level. It was also associated with an increased number of reported insulin reactions. These data suggest that recent changes in treatment and management of diabetes may be related to a significant decrease in glycemia.     

Aspergillus osteomyelitis of the thumb in a 5-year-old child

Aspergillus osteomyelitis is a rare condition and is a recognized infection of the immunosuppressed. The pediatric cases that were documented suggest that in children, chronic granulomatous disease is the major underlying disease [Tack et al.1982 73(2):295–300, Baez-Escudero et al. 2000 Case report—primary sternal Aspergillus osteomyelitis. Infect Med 17(7):505–516]. We report an interesting case of Aspergillus osteomyelitis of the thumb in a 5-year-old boy with aplastic anemia. The infection progressed despite a combination of antifungal therapy with Voriconazole and surgical debridement. The thumb was amputated and the child recovered. This case highlights the difficulty in diagnosing Aspergillus osteomyelitis and also the failure of conventional management in this child, which resulted in the amputation of the thumb as a life-saving measure. We believe this to be the first case report of Aspergillus osteomyelitis in the thumb.