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Biomedical subjects

D Roth

Publications and source records attributed to D Roth.

At least 55 records · Page 3Linked to original sources
PubMed1997

Use of intravenous FK506 to treat acute rejection in simultaneous pancreas-kidney transplant recipients on maintenance oral FK506.

Most recipients of simultaneous pancreas-kidney transplants experience acute rejection in the early postoperative course. We report our experience with four recipients of simultaneous pancreas-kidney transplants with acute rejection who were effectively treated with the combination of intravenous and oral FK506 therapy. This spared these patients an extra course of monoclonal or polyclonal antibody.

Administration, Oral↗
PubMed1997

Identification and characterization of homologues of the Exocyst component Sec10p.

The SEC10 gene product is a member of the Exocyst complex essential for exocytosis in the budding yeast Saccharomyces cerevisiae. We report here the cloning and characterization of human Sec10p (hSec10p; GenBank accession number U85946). hSec10p is a 77-kDa protein with 23% amino acid identity to yeast Sec10p and 37% identity to a C. elegans protein found in the database. Northern and Western blot analyses indicate that hSec10 has a broad tissue distribution. Immunofluorescence staining of COS cells cotransfected with hSec10p and a mammalian Sec8p demonstrates that these two proteins have an identical distribution in the cell including a localization in the peripheral cytoplasm. These data suggest that hSec10p is a component of the mammalian counterpart of the yeast Exocyst complex essential for post-Golgi traffic.

Amino Acid Sequence↗
PubMed1997

The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.

40 recipients of first cadaver kidney transplants were given perioperative donor vertebral bone marrow infusions (DBMC), compared with 100 controls who did not receive donor bone marrow. The immunosuppressive regimen included OKT3, Tacrolimus, and steroid maintenance therapy, and, in some patients, newly introduced mycophenolate mofetil. This report describes the 24-mo actuarial follow-up and several immunological monitoring studies including sequential measurements of donor bone marrow lineage subset chimerism by the recently reported PCR-flow assay. This is a sensitive in situ PCR detection system for donor versus recipient histocompatibility genes as well as cell surface CD epitope markers using flow cytometry. The results indicate (a) the stabilization of the donor CD3+ and CD34+ cells in recipient peripheral blood at levels below 1% between 6 mo and 1 yr postoperatively, with a 10-fold higher level of donor cell chimerism of these lineages in recipient iliac crest marrow; (b) significantly lower levels of chimerism in peripheral blood up to 6 mo postoperatively in patients who had early acute (reversible) rejection episodes compared with those who did not; (c) a higher degree of chimerism seen in patients who were class II MHC HLA DR identical with their donors; (d) the identification of a high proportion of the donor bone marrow derived CD3 dimly staining subset of T cells (to which regulatory functions have been ascribed) in recipient peripheral blood and especially in recipient bone marrow; and (e) an unexpectedly increased susceptibility to clinically significant infections (primarily viral), and even death in the DBMC-infused group, compared with controls, but no graft losses because of rejection in the DBMC-infused group. Mixed lymphocyte culture assays showed a trend toward a greater number of nonspecifically low reactors in the DBMC group, as well as a greater number of nonspecifically high reactors in the controls (P = 0.058). The autologous mixed lymphocyte reaction also indicated a trend towards nonspecific immune activation in the DBMC group. Finally, anti-cytomegaloviral IgG antibody reactivity was significantly inhibited in the DBMC group 4-6 mo postoperatively (P = < 0.05). In the controls, there were no donor cell lineages detected by PCR-flow in the peripheral blood. These rather unexpected findings, indicating a more depressed cellular and humoral immune capacity in the DBMC cadaver kidney transplant recipients in this relatively early follow-up period, are discussed relevant to chimerism, MHC restriction, and suppressor activity brought about by specialized DBMC subsets, which still need to be defined.

Adolescent↗
PubMed1997

Laparoscopic evaluation of liver disease in chronic renal failure prior to renal transplantation.

BACKGROUND: Diagnostic laparoscopy with liver biopsy has been shown to be safe and effective in the evaluation of patients with chronic liver disease. Patients with end-stage renal disease may be more prone to bleeding complications secondary to liver biopsy as a result of multiple factors directly related to their underlying renal condition. METHODS AND PATIENTS: From January 1994 to June 1996, 16 patients with end-stage renal disease and hepatic dysfunction (6 women and 10 men) underwent diagnostic laparoscopy with liver biopsy prior to renal transplantation at the University of Miami School of Medicine. Laparoscopy was performed using a 5 mm video laparoscope with a left paramedian approach. The mean patient age was 46 years. Fourteen patients had chronic hepatitis C with a reactive anti-HCV by ELISA; one patient had chronic hepatitis B with reactive HBsAg, and one patient was co-infected with both hepatitis B and C viruses. RESULTS: Two patients developed hypotension related to the procedure and one patient developed an intra-abdominal hemorrhage 5 days after laparoscopy that did not require surgical intervention. Biopsy findings were as follows: 13 patients had mild chronic hepatitis; 2 patients had chronic hepatitis with bridging fibrosis; and 1 patient was cirrhotic. Prior kidney transplantation or peritoneal dialysis did not preclude the performance of laparoscopy. CONCLUSION: Diagnostic laparoscopy can be safety performed in patients with end-stage renal disease with acceptable morbidity and mortality.

Abdomen↗
PubMed1997

Unexpected augmentation of mycophenolic acid pharmacokinetics in renal transplant patients receiving tacrolimus and mycophenolate mofetil in combination therapy, and analogous in vitro findings.

Mycophenolate mofetil (MMF) a potent immunosuppressive agent, has recently been approved for clinical use (CellCept) in renal transplant patients in combination with cyclosporine (CsA). With the expanded use of tacrolimus (Prograf) as well in renal transplant patients, there is a lack of pharmacokinetic studies clarifying drug interactions between the three agents. A pharmacokinetic study was performed on 18 stable renal transplant patients receiving MMF and tacrolimus together, and four control groups, one receiving tacrolimus alone, two receiving CsA, in combination with MMF (1.0 or 1.5 g bid), and one receiving CsA microemulsion (Neoral). Area-under-the-curve values were calculated for each drug to assess if there was a reciprocal effect on the respective bioavailability of each. In vitro, the immunosuppressive effect of trough level plasma from each patient group was studied using mixed lymphocyte culture (MLC), as well as MLC reactions spiked with various combinations of each drug. There was a minimal effect of MMF on tacrolimus pharmacokinetics. However, patients receiving tacrolimus and MMF displayed significantly higher levels (Cmin and area under the curve) of mycophenolic acid (MPA) than those receiving CsA (Sandimmune or Neoral) and the same dose of MMF (50.2 +/- 16.5 vs 32.1 +/- 16.7 micrograms h/ml AUC, p < 0.02). Equivalent MPA levels could be attained in patients receiving CsA if the MMF dose was increased by 50% (1.5 g bid). There were also significantly lower levels of the glucuronide metabolite of MPA (MPAG) (755 +/- 280 vs 1230 +/- 250 micrograms h/ml AUC, p = 0.02), suggesting a specific inhibition (either direct or indirect) of the conversion of MPA to MPAG in tacrolimus patients, as opposed to those receiving CsA. For each drug combination, there was a positive correlation between the plasma immunosuppressive effect seen in MLC assays and the MMF dose. In addition, trough plasma from patients receiving tacrolimus and MMF was significantly more MLC inhibitory than from those receiving CsA or CsA microemulsion and equivalent-dose MMF. Culture media containing MPA and tacrolimus equal to clinical therapeutic trough concentrations (10 ng/ml) were significantly more MLC inhibitory than CsA at equivalent clinical therapeutic trough concentrations (200 ng/ml) with equivalent MPA levels. These studies in renal transplant patients suggest that tacrolimus in combination with MMF may result in a greater degree of immunosuppression than may be anticipated.

Adult↗
PubMed1997

Impact of state mental health reform on patterns of service delivery.

Legislation enacted in 1988 in Ohio, aimed at redistributing funding from state hospitals to community support services and prioritizing the funding for treatment of individuals with severe mental disabilities (SMD), raises important questions from a service system perspective. To assess the impact of this reform legislation on Ohio's mental health service delivery system, cluster analyses of community mental health service data were conducted for five yearly samples of approximately 4,000 adults with SMD. An analysis of resulting service patterns demonstrated a decrease in service clusters comprised of individuals receiving little more than medication check-ups and an increase in clusters comprised of individuals receiving combinations of two or more services. Increases were found in most community mental health services; however, in each year, approximately 50% of the sample received few services of any kind, while approximately 10% of the sample received voluminous amounts of highly individualized services.

Adult↗
PubMed1997

The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage.

Liver infiltrating lymphocytes (LIL) were isolated from HCV-positive (+) and HCV-negative (-) end-stage livers. Phenotypic analysis and functional studies using proliferative and lymphocytotoxic assays were performed with the isolated LIL. Two CD3+ lymphocyte populations were found in LIL using FITC anti-CD3 monoclonal antibodies (mAb). One was a bright fluorescence intensity population (as in PBL), and the other dim. We calculated the number of FITC-anti-CD3 mAbs bound per lymphocyte on PBL and LIL and found 80,040 +/- 4628 and 39,615 +/- 3932, respectively. Therefore, HCV+ and HCV- patient PBL contained approximately twice the number of CD3 molecules per cell than patient CD3+ LIL. LIL also contained approximately a threefold higher concentration of TCR alpha beta +, CD4-CD8-, and CD56,16 (NK) cells than the patient PBL. Thus, a major subset of LIL is phenotypically similar to mouse NK1.1+ "intermediate" T cells. LIL freshly isolated from HCV+ livers exhibited weak CTL activity against EBV- or Con A-transformed lymphoblast targets infected with vaccinia-HCV recombinant virus (rHCV) or primary hepatocyte cultured cells. However, after in vitro coculture of LIL with rHCV, these cells developed a strong cytotoxicity for the above targets. In contrast, LIL from HCV- livers were not cytotoxic against the same targets. Histochemical studies (in situ) demonstrated that these hepatocytes express CD95, and stains demonstrated apoptosis. The HCV+ hepatocytes also express class I MHC molecules and ICAM-1. The addition of mAb specific for these adhesion molecules inhibited CML activity. Short-term cultured hepatocytes (targets) from HCV+ and HCV- patients produced low levels of cytokines IL-1 beta, IL-2, IL-6, TNF alpha, and IFN-gamma but a high level of IL-8. It is speculated that LIL expressing reduced numbers of CD3 molecules may even function as immune regulators as proposed for intermediate T cells in mice.

Antibodies, Monoclonal↗
PubMed1997

Cognitive impairment in the Amish: a four county survey.

BACKGROUND: The prevalence of probable dementia was determined in a rural, homogeneous community of Amish individuals in the Midwestern USA. The Amish are a genetically isolated group with a low level of formal education (< or = 8 years) and few exposures to modern life, who live in intergenerational setting and have strong social support networks. METHODS: Using community directories, trained interviewers administered the Mini Mental State Examination (MMSE) and a medical history survey to all Amish over 64 years old in a four county area. Individuals with scores < 27 (out of a maximum of 30 points) were given additional neuropsychological tests. Results were reviewed by a neuropsychologist and subjects were classified with regard to probable cognitive impairment. RESULTS: The MMSE scores were inversely related with age and directly with education. The Amish have higher MMSE scores than reported for the general US population. The overall prevalence of probable cognitive impairment for those over 64 years was 6.4%. The prevalence increased with age and lower education and was lowest among married individuals. CONCLUSIONS: The MMSE scores among the Amish were higher than the general population despite their low level of formal education. The lower level of cognitive impairment among the Amish could reflect a lack of inherited susceptibility to dementing diseases, or environmental factors characteristic of their traditional lifestyle. Even among this population with < or = 8 years of formal education, education may protect against cognitive impairment.

Age Distribution↗
PubMed1997

Psychiatric collaboration in a paediatric department.

OBJECTIVE: To review the impact of integrating child psychiatry services into a paediatric department. METHOD: Following the arrival of a new head of paediatrics, a mandatory multidisciplinary meeting was set up to review, diagnose and manage selected patients under the care of the paediatricians and/or a child psychiatrist. A prospective audit was undertaken of the patients discussed with a brief review of their outcome. The educational value of the meetings and their overall impact on the department was reviewed. RESULTS: Over an 8-month period 30 patients were discussed in some detail with diagnoses ranging from a psychiatric disorder to a chronic organic illness, each subjected to the deliberations of the multidisciplinary team of the attending paediatrician, resident staff, child psychiatrist/psychologists, nurses, social worker, etc. Recommendations included further assessment by the psychiatric team, or management by the paediatricians with or without guidance of the former, involvement of an outside agency, etc. Such interventions generally had positive outcomes: at times dramatic, although early discharge often resulted in limited goals. There was also an overall increased awareness within the department of the psychological needs of the child and family and the importance of serious physical illness; this awareness is essential in the training of paediatricians and psychiatric staff. CONCLUSION: Closer integration of the two disciplines led to benefits both to the patients and staff. The initiation of a mandatory multidisciplinary meeting facilitated the process, overseen by a psychologically-minded new head of paediatrics. His departure led to a loss of some goals achieved, raising the question as to how such collaboration may be self-generating and ongoing. In addition, the issue of how to deal with those patients with ongoing difficulties not addressed during their limited inpatient stay was unresolved.

Adolescent↗
PubMed1997

Post-transplant lymphoproliferative disease in kidney transplant patients in the new immunosuppressive era.

Although the kidney transplant program at this center has been active for the past 18 yr, five out of the seven cases of post-transplant lymphoma in kidney transplant patients were observed over the past 2 yr. During this period, we have shifted from cyclosporine to tacrolimus (FK506 or prograf) for maintenance immunosuppression and for rescue therapy. We have also introduced mycophenolate (RS-61443) and have continued an antibody induction regimen in the immediate postoperative period. FK506 is 50-100 times more potent than cyclosporine. We have reported a decreased incidence of rejection, improved graft survival, and a general optimalization of patient survival with these newer regimens. Nonetheless, five cases of post-transplant lymphoma out of 233 kidney transplants (2.1%) performed during this time period (December 1993 to December 1995) occurred between 3 months to 1 yr after the transplant. Four of the five patients are still alive between 12 and 24 months after the diagnosis of lymphoma was made. All were without evidence of ongoing disease. Three of the five have grafts with excellent function for longer than 18 months after transplantation, while one is marginal and one patient expired on dialysis. The third and fourth patients had severe rejection before the diagnosis of PTLD was made. While the occurrence of five cases of post-transplant lymphoma over a 2 yr period is alarming, this is still within the 2-4% incidence of post-transplant lymphoma that has been reported in the literature in kidney transplant patients. Our results probably reflect the increasing potency of our immunosuppressive protocols but do not show any increase in the aggressiveness of this entity of post-transplant lymphoma during the continued follow up.

Adolescent↗
PubMed1997

The use of tacrolimus as induction and maintenance immunosuppression in renal cadaveric transplant recipients over the age of 60.

Renal transplantation is a treatment option that should be considered for the elderly (> or = 60 years old) with end-stage renal disease. Little is known regarding the use of tacrolimus (as induction and maintenance immunosuppression) in this age group. We report the outcome of kidney transplantation in 21 patients aged 60 years or more with tacrolimus. During the past few years in kidney transplant maintenance immunosuppressive regimens, we have revised our standard general protocol from cyclosporine to tacrolimus-based therapy for maintenance immunosuppression and for rescue therapy. We also introduced mycophenolate (RS-61443) while we have continued to use ATGAM/OKT3 as induction regimen in the immediate postoperative period. We treated these renal recipients with tacrolimus and steroids in combination with azathioprine or mycophenolate mofetil without antibody induction. This was well tolerated and not associated with a higher rate of rejection (20%) whereas the potential toxicity of antilymphocyte preparations was avoided.

Administration, Oral↗
PubMed1997

Rapid HIV testing and counseling for voluntary testing centers in Africa.

OBJECTIVE: Voluntary HIV testing and counseling (VTC) has been shown to reduce the incidence of HIV in cohabiting couples who now represent the majority of new infections in many African cities. Community and client perceptions of a 1-day voluntary testing and counseling program in Lusaka, Zambia, were assessed, and a rapid HIV-testing algorithm was evaluated for VTC centers. METHODS AND DESIGN: Between May 1995 and June 1996, outreach workers distributed written invitations door to door. The 1-day program was held 6 days/week including weekends. Transport, child care and lunch were provided. Community and client surveys followed in July 1996. RESULTS: Over 3500 couples married for a median of 4-5 years requested testing: 23% were HIV+/+, 57% were HIV-/- and 20% were discordant with one HIV+ and one HIV- partner. Sixty-eight per cent of couples surveyed had made the decision to be tested before attending the 1-day program and 80% had not previously known where to obtain HIV testing. Knowledge that couples could show discordant results rose from 29 before to 88% after pretest counseling. Clients reported high levels of satisfaction with the services and 90 out of 99 (92%) preferred to receive their results the same day. Clients at another center who waited 10 days for their results reported more fear, and 19 out of 31 (61%) would have preferred to get their results the same day. Over 99% of those who attended the program thought active promotion of voluntary HIV testing in the community was a positive thing, as did 90% of those who were invited but did not attend. Sensitivity and specificity of the rapid test algorithm were both 99.4% in this setting. CONCLUSIONS: Active promotion of voluntary HIV testing and counseling in couples is needed to reduce the spread of HIV in high-prevalence areas. The use of rapid, on-site HIV testing allows clients to receive result-specific counseling in a single visit. Ongoing quality control of a subset of samples at an outside laboratory is essential.

Acquired Immunodeficiency Syndrome↗