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Biomedical subjects

D Roth

Publications and source records attributed to D Roth.

At least 37 records · Page 2Linked to original sources

Consumer turnover in service utilization patterns: implications for capitated payment.

Risk-adjusted capitation rates based on a group's expected cost to a provider have been proposed to create incentives for including people with severe mental disabilities in managed healthcare systems. The most appropriate methods for classifying people according to levels of risk, however, have yet to be determined. This research employed cluster analysis statistical techniques to identify patterns of services delivered to a sample of 4,346 consumers in Ohio. Findings about the extent of client movement in and out of service clusters over time suggest caution in the implementation of risk-adjusted capitation plans, particularly those based primarily on past service utilization.

Capitation Fee↗

Dominant negative alleles of SEC10 reveal distinct domains involved in secretion and morphogenesis in yeast.

The accurate targeting of secretory vesicles to distinct sites on the plasma membrane is necessary to achieve polarized growth and to establish specialized domains at the surface of eukaryotic cells. Members of a protein complex required for exocytosis, the exocyst, have been localized to regions of active secretion in the budding yeast Saccharomyces cerevisiae where they may function to specify sites on the plasma membrane for vesicle docking and fusion. In this study we have addressed the function of one member of the exocyst complex, Sec10p. We have identified two functional domains of Sec10p that act in a dominant-negative manner to inhibit cell growth upon overexpression. Phenotypic and biochemical analysis of the dominant-negative mutants points to a bifunctional role for Sec10p. One domain, consisting of the amino-terminal two-thirds of Sec10p directly interacts with Sec15p, another exocyst component. Overexpression of this domain displaces the full-length Sec10 from the exocyst complex, resulting in a block in exocytosis and an accumulation of secretory vesicles. The carboxy-terminal domain of Sec10p does not interact with other members of the exocyst complex and expression of this domain does not cause a secretory defect. Rather, this mutant results in the formation of elongated cells, suggesting that the second domain of Sec10p is required for morphogenesis, perhaps regulating the reorientation of the secretory pathway from the tip of the emerging daughter cell toward the mother-daughter connection during cell cycle progression.

Alleles↗

Illness intrusiveness in individuals with panic disorder, obsessive-compulsive disorder, or social phobia.

To measure the extent to which anxiety disorders interfere with various domains of functioning, the Illness Intrusiveness Ratings Scale (IIRS) was completed by individuals with a DSM-IV principal diagnosis of panic disorder (PD; N = 35), obsessive-compulsive disorder (OCD; N = 51), or social phobia (SP; N = 49). Although the three groups did not differ on total IIRS scores, group differences did emerge for particular domains of functioning. Patients with OCD reported significantly more interference with respect to passive recreation (e.g., reading) than did SP patients and with respect to religious expression compared with both PD and SP patients. Patients with SP reported more impairment with respect to social relationships and self-expression/self-improvement compared with the other two groups. When compared with populations with a variety of other chronic illnesses, patients in the present study reported much higher levels of illness intrusiveness. The implications of these findings and future directions for research are discussed.

Adult↗

Treatment of hepatitis C infection in patients with renal disease.

Hepatitis C virus infects 20-40% of the end-stage renal disease population, and has been associated with essential mixed cryoglobulinemia and several forms of immune-complex glomerulonephritis. Overall, treatment with interferon alpha has been disappointing, although certain situations may benefit from dosing regimens that differ in the amount of drug and duration of treatment from the conventional interferon doses currently recommended for non-renal patients.

Antiviral Agents↗

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↗

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↗

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↗

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↗