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Biomedical subjects

A L Friedman

Publications and source records attributed to A L Friedman.

At least 37 records · Page 2Linked to original sources
PubMed1998

A pilot study of soluble adhesion molecules as surrogate markers for acute liver allograft rejection.

BACKGROUND: Tissue endothelial adhesion molecule expression is increased during acute liver allograft rejection. Soluble forms exist, but their correlation to rejection and their clinical value have not been determined. METHODS: We studied endothelial adhesion molecule tissue expression and soluble levels in blood and bile and correlated these to the clinical course of 11 adult patients followed for 30 consecutive days after liver transplantation. RESULTS: Three biopsies showing acute rejection demonstrated increased intercellular adhesion molecule (ICAM)-1 but not endothelial leukocyte adhesion molecule-1 expression on hepatic endothelial cells during rejection. Vascular cell adhesion molecule (VCAM)-1 staining was focally increased in two of three specimens. Levels of soluble ICAM-1 or soluble VCAM-1 by ELISA did not distinguish acute rejection from nonrejection conditions. CONCLUSION: We confirmed that endothelial ICAM-1 expression is more intense in rejecting allografts and is more sensitive than changes in VCAM-1 or endothelial leukocyte adhesion molecule-1. However, soluble adhesion molecule determination was not useful in the accurate detection of acute rejection.

Adult↗
PubMed1998

Pleurotomy, pneumothorax, and surveillance during living donor nephroureterectomy.

OBJECTIVES: To determine the incidence of and risk factors associated with pneumothorax after donor nephroureterectomy and to determine the utility of postoperative chest roentgenography. METHODS: A retrospective review was made of 130 living donor nephroureterectomies performed at one institution (Yale-New Haven Hospital) using an extraperitoneal flank incision. RESULTS: Incidental pleurotomy occurred in 11 cases (8.5%). Rib resection was associated with pleurotomy. Patient age, sex, and side of operation were not associated with pleurotomy. Ten (91 %) of the 11 cases were identified intraoperatively. One unrecognized pneumothorax was identified postoperatively with chest roentgenography; no specific intervention was necessary. CONCLUSIONS: The extraperitoneal flank incision poses a significant risk for pneumothorax. Most pneumothoraces will be recognized intraoperatively. No adverse effects were noted secondary to pneumothorax.

Adolescent↗
PubMed1998

Urinary tract infection.

The approach to urinary tract infection remains a difficult and sometimes controversial issue. One area in particular is accurate diagnosis. In a recent article it was suggested utilizing the "enhanced" urinalysis, not as a replacement to culture but as a potential sensitive predictor to allow therapy to be given while awaiting culture results. Another difficult area is the issue of radiologic evaluation for underlying urologic abnormalities following a urinary tract infection. Previous discussion on this topic has pointed to early evaluation, even after the first urinary tract infection. There now seems to be some reconsideration of when to evaluate children following urinary tract infection. Some reviews, however point to a less aggressive approach. Another area of discussion is the evaluation of siblings of index cases with reflux. Here there is new data suggesting that evaluation of young siblings (under 6 years of age) may yield a relatively high incidence of reflux whereas evaluation of siblings over 6 years of age yields a small percentage of patients with reflux. The question of circumcision is another area of long-term interest in the study of urinary tract infections. Still more data published recently suggests that uncircumcised males have a higher incidence of urinary tract infection. However, this continues to be a point of controversy.

Child↗
PubMed1997

Reduced incidence of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder using preemptive antiviral therapy.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) has been observed with increasing frequency consequent to the availability of more effective and potent immunosuppression. Prior work suggested that a peripheral blood monitoring strategy detecting peripheral B lymphoproliferation was effective in the early diagnosis of PTLD among 7 of 179 (3.9%) consecutive transplant recipients. Each of those seven patients received at least one course of antithymocyte globulin, Minnesota antilymphocyte globulin, or OKT3 before developing PTLD. METHODS: To determine whether antiviral prophylaxis might reduce the incidence of PTLD, a subsequent group of 198 consecutive recipients received either ganciclovir or acyclovir during antilymphocyte antibody administration. When the donor or recipient were cytomegalovirus-seropositive, ganciclovir was given; acyclovir was used when both were cytomegalovirus-seronegative. Baseline and protocol posttransplant cell surface profiles were obtained using immunofluorescence and flow cytometry to detect T cells, lymphocyte activation markers, and the CD19 B cell antigen. RESULTS: Demographic factors, including the incidence of recipients more than 50 years of age, non-Caucasians, previous transplantation, and diabetes mellitus, were similar in both groups. Additionally, the number of patients receiving antilymphocyte preparations was similar. However, only one patient (0.5%) from the latter group who received preemptive antiviral therapy developed PTLD. Although elevations in CD19+ B cells preceded clinical PTLD among each of the seven earlier patients, evidence of peripheral B cell proliferation was not demonstrated for the sole patient from the latter group, which suggests a possible effect of antiviral therapy. CONCLUSIONS: Prophylactic antiviral therapy may reduce the sensitivity of peripheral monitoring for B lymphoproliferation, but the dramatic reduction in PTLD incidence strongly supports its use among transplant recipients at risk.

Acyclovir↗
PubMed1997

Growth hormone is not safe for children with renal transplants.

Growth failure is an important problem in children with renal failure. Even after renal transplantation their growth rates may be lower than normal, and "catch-up" growth does not occur. Therefore there is great interest in giving growth hormone (GH) after transplantation. Clinical observations and theoretic considerations call into question whether GH after transplantation is safe. Studies have shown a more rapid than normal decline in renal function after the initiation of GH therapy. This result could be explained by the effects of GH on the immune response. Growth hormone is known to modulate (usually upregulate) the immune response and could be a reason for the increased loss of renal function caused by rejection. It could also be explained by the long-term effects of GH on the injured kidney. Experimental data (generally not in the transplantation model) suggest that exogenous GH given after renal injury or reduced renal mass leads to a more rapid development of glomerular sclerosis and reduced renal function. GH should not be administered to children after renal transplantation until all safety questions have been answered in prospective clinical trials.

Animals↗
PubMed1997

Stress and genetic testing for disease risk.

Healthy people who believe they are at risk for a life-threatening disease appear to carry a substantial stress burden because of threat of disease and uncertainty of risk. Testing for risk factors may be helpful by reducing this uncertainty, but diseases with multiple causes, like breast cancer, appear to be determined by genetic factors and by age, reproductive behavior, exposure to environmental toxins, or unknown antecedents. For diseases caused by inherited genetic defects, testing brings different benefits and stressors. A model is proposed that predicts long-term distress when risk analysis suggests a very high risk, when uncertainty is not reduced, when results of testing are at odds with preventive actions already taken, and when people who receive a positive, risk-increasing result lack strong social support, coping skills, other psychosocial resources, or all of these.

Adaptation, Psychological↗
PubMed1997

Immunology of liver transplantation: clinical management aspects.

Orthotopic liver transplantation has developed into the treatment of choice for many patients who develop complications of end-stage liver disease. With improvements in surgical technique and overall survival since the inception of liver grafting, a major consideration in the longterm care of liver transplant patients has become the management of allograft rejection and immunosuppressive therapy. With an increasing number of patients having undergone successful transplantation in the community, practicing gastroenterologists will likely be called upon more frequently to render care to these patients. In this article, the immunobiology of transplantation and rejection is discussed with an emphasis placed on the T-cell-major histocompatibility complex interaction, cytokine stimulation, and adhesion molecule binding. Commonly used immunosuppressive medications and promising ones for the future are reviewed. Also, clinical aspects of the short- and long-term management of immunosuppression are explored.

Graft Rejection↗
PubMed1996

The cerebellum and cognitive function: implications for rehabilitation.

OBJECTIVE: To characterize the cognitive effects of isolated cerebellar lesions. DESIGN: Review of two inpatient cases. SETTING: The rehabilitation unit of a tertiary general hospital. PATIENTS OR OTHER PARTICIPANTS: Two patients with acute ischemic strokes who had solitary cerebellar infarcts. INTERVENTIONS: Assessment with standard neuropsychological tests. Scores were compared with patients' premorbid levels and standardized test norms. A classical conditioning eyeblink paradigm was performed. MAIN OUTCOME MEASURES: Neuropsychological measures of intellectual and executive functions, learning and memory, visual-spatial abilities, language functioning, fine motor speed, and dexterity. RESULTS: Test findings suggested lesion-associated deficits in higher aspects of cognition (visuospatial reasoning, verbal and visual memory, and intellectual and executive functions). These functions are not usually associated with the fundamentally motoric role of the cerebellum. CONCLUSIONS: (1) Lesions in the cerebellum can be associated with impairments in higher cognitive functioning. (2) Such effects may be severe enough for a diagnosis of dementia under current diagnostic criteria. (3) These rehabilitation patients may benefit from comprehensive cognitive examination to determine if cognitive effects will detract from their participation. (4) Further research is needed to localize which cerebellar areas affect which cognitive abilities.

Aged↗
PubMed1996

Mechanical characterization of skeletal muscle myofibrils.

A new instrument, based on a technique described previously, is presented for studying mechanics of micron-scale preparations of two to three myofibrils or single myofibrils from muscle. Forces in the nanonewton to micronewton range are measurable with 0.5-ms time resolution. Programmed quick (200-microseconds) steps or ramp length changes are applied to contracting myofibrils to test their mechanical properties. Individual striations can be monitored during force production and shortening. The active isometric force, force-velocity relationship, and force transients after rapid length steps were obtained from bundles of two to three myofibrils from rabbit psoas muscle. Contrary to some earlier reports on myofibrillar mechanics, these properties are generally similar to expectations from studies on intact and skinned muscle fibers. Our experiments provide strong evidence that the mechanical properties of a fiber result from a simple summation of the myofibrillar force and shortening of independently contracting sarcomeres.

Animals↗
PubMed1996

Carcinoid tumor of the common bile duct producing gastrin and serotonin.

Carcinoid tumors of the biliary tract are rare. We report a 47 year-old man who was unexpectedly found to have a nonobstructing carcinoid tumor of the common bile duct during orthotopic liver transplantation for decompensated cirrhosis. No metastases were noted. Five months after resection of the common bile duct and liver transplantation, the patient had no evidence of residual tumor. The carcinoid was a sclerotic tumor of insular type and was immunoreactive for gastrin and serotonin, but nonfunctional. We review the literature on carcinoids of the extrahepatic bile duct.

Adult↗
PubMed1996

Etiology, pathophysiology, diagnosis, and management of chronic renal failure in children.

There are a large number of causes of chronic renal disease in children. This review updates recent findings on conditions that arise in childhood that lead to chronic kidney disease in adulthood (eg, polycystic kidney disease, reflux nephropathy) or cause chronic kidney disease in childhood. Recent studies addressing the etiology and genetics of chronic kidney disease, as well as its pathophysiology, prognosis, and treatment, are discussed.

Antihypertensive Agents↗
PubMed1996

Delayed function reduces renal allograft survival independent of acute rejection.

BACKGROUND: Mechanisms by which delayed allograft function reduces renal allograft survival are poorly understood. This study evaluated the relationship of delayed allograft function to acute rejection and long-term survival of cadaveric allografts. METHODS: 338 recipients of cadaveric allografts were followed until death, resumption of dialysis, retransplantation, loss to follow-up, or the study's end, which ever came first. Delayed allograft function was defined by dialysis during the first week following transplantation. Multivariate Cox proportional hazards survival analysis was used to assess the relationship of delayed allograft function to rejection and allograft survival. RESULTS: Delayed allograft function, recipient age, preformed reactive antibody levels, prior kidney transplantation, recipient race, rejection during the first 30 days and rejection subsequent to 30 days following transplantation were predictive of allograft survival in multivariate survival models. Delayed allograft function was associated with shorter allograft survival after adjustment for acute rejection and other covariates (relative rate of failure [RR]+1.72 [95% CI, 1.07, 2.76]). The adjusted RR of allograft failure associated with any rejection during the first 30 days was 1.99 (1.23, 3.21), and for rejection subsequent to the first 30 days was 3.53 (2.9 08, 6.00). The impact of delayed allograft function did not change substantially (RR=1.84 [1.15, 2.95]) in models not controlling for acute rejection. These results were stable among several subgroups of patients and using alternative definitions of allograft survival and delayed allograft function. CONCLUSIONS: This study demonstrates that delayed allograft function and acute allograft rejection have important independent and deleterious effects on cadaveric allograft survival. These results suggest that the effect of delayed allograft function is mediated, in part, through mechanisms not involving acute clinical rejection.

Acute Disease↗
PubMed1996

Must living renal donors be hospitalized overnight prior to surgery?

To determine whether preoperative intravenous hydration was an important determinant of perioperative safety for the kidney donor or of early allograft function, 21 consecutive living donor transplants were assessed retrospectively. Donors hospitalized overnight received 1008 +/- 169 mL of intravenous fluid during the 8 h prior to operation, compared to no preoperative hydration among a cohort of 15 patients. No differences between intraoperative blood pressures, fluid administration, urine output, or time in the operating room were identified between groups. Postoperative allograft function was not compromised by the lack of hydration. We conclude that living kidney donors can safely undergo elective nephrectomy without prior intravenous hydration.

Adult↗
PubMed1995

Effects of lead administration on developing rat kidney. I. Glutathione S-transferase isoenzymes.

The effects of acute and chronic exposure to lead on glutathione S-transferase (GST) isoforms were determined in developing kidney in the rat. The ontogeny of glutathione S-transferase isoforms was characterized as were the effects of depletion of dietary calcium on glutathione S-transferase isoform profiles in control and lead-treated rats. In the acute exposure experiments, rats of 14 and 50 days of age received three daily injections of lead acetate (114 mg/kg) and in the chronic exposure studies, rats received lead acetate at doses ranging from 50 to 500 ppm in their drinking water. Lead acetate administration in these chronic studies began 1 day after conception. Acute and chronic lead exposure had similar effects, causing increases in all but one glutathione S-transferase isoform (Yb3); these increases were markedly exacerbated by dietary calcium depletion. In all lead paradigms, GST subunits Yb1 and Yp showed the largest increases--greater than 25-fold in rats fed a low-calcium diet. GST subunit Yb3 showed small increases in the 14-day acute lead and the 4 week low-calcium animals and did not increase in other groups. Lead-related increases in GSTs were partially reversed by transferring animals previously receiving lead to lead-free water for a 4-week period. Kidneys of rats fed the low-calcium diet did not have detectable GST Yk, but in rats on this low-calcium diet that received 500 ppm lead; this GST isoform was found at levels comparable to those in control rats fed lab chow.

Aging↗
PubMed1995

Effects of lead administration on developing rat kidney. II. Functional, morphologic, and immunohistochemical studies.

The effects of chronic lead administration on renal function and cytoarchitecture and on the immunohistochemical localization of glutathione S-transferase (GST) isoenzymes were determined. Pregnant rats were given 250 ppm lead acetate in drinking water from conception until weaning and mothers and pups received 500 ppm of lead acetate from weaning until termination at either 3 or 7 weeks of age. Light and electron microscopic studies after 3 weeks of lead administration showed tubular injury with frequent mitoses noted in proximal tubular cells and, after 7 weeks of treatment, interstitial fibrosis, characteristic intranuclear inclusions, and tubular injury characterized by both nuclear and cytoplasmic pleomorphism. Rats treated with lead for 7 weeks showed significantly lower body weights and creatinine clearances than age-matched control animals. Immunohistochemical studies of glutathione transferase subunits in control rats showed unique isoform localization in each segment of the nephron; treatment with lead caused large increases in immunoreactive protein of Yc, Yk, Yb1, and Yp GST subunits in proximal tubules. No increases in the antioxidant enzymes copper-zinc superoxide dismutase, catalase, and glutathione peroxidase were found in lead-treated rats, but there was a diffuse lead-related increase in immunoreactive protein for manganese superoxide dismutase throughout the renal cortex. Our results demonstrate large lead-induced increases of specific isoforms of glutathione S-transferase in specific kidney cell types and show that these increases preceded irreversible renal damage.

Aging↗