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Biomedical subjects

R H Rubin

Publications and source records attributed to R H Rubin.

At least 55 records · Page 3Linked to original sources
PubMed2000

Regional pharmacokinetics of orally administered PET tracers.

Positron emission tomography (PET) is currently the most useful imaging technique for noninvasive measurement of drug pharmacokinetics regionally in a variety of tissues. Over the past decade, PET measurements have provided many critical insights about the tissue distribution of several classes of drugs; neuroleptics, antimicrobials, antineoplastics, etc. PET measurements can be performed after any route of drug administration, intravenous, inhalation or oral, however, intravenously administered drugs have been the most extensively evaluated. Studies of orally administered drugs are clearly of great interest; however, formulation issues have precluded widespread applications in these areas. In this report, we discuss the unique problems associated with studying orally administered drugs and review the results of recent studies performed in our laboratory.

Administration, Oral↗
PubMed2000

Physician expression of empathy and positiveness to Hispanic and non-Hispanic white patients during medical encounters.

BACKGROUND: This study examined the extent to which physicians expressed empathy and positiveness to Hispanic and non-Hispanic white patients during primary care visits. METHODS: Twenty-seven family practice and internal medicine resident physicians at the University of New Mexico Health Sciences Center were audiotaped in 1995 with 427 adult patients who were fluent in English or Spanish. The tapes were reviewed and organized to measure how frequently physicians expressed empathy and positiveness to patients. RESULTS: Physicians expressed empathy at equal rates to Hispanic and non-Hispanic white patients. When examining only Hispanic patients, physicians were significantly more likely to express empathy to patients who they knew better. Physicians expressed positiveness to non-Hispanic white patients more often than to Hispanic patients. When examining only Hispanic patients, physicians were more likely to express positiveness to patients who they knew better, who rated their health better, and who were more educated. When examining only non-Hispanic white patients, physicians were more likely to express positiveness to older and male patients than to younger and female patients. Also, female and younger physicians were significantly more likely to express positiveness to non-Hispanic white patients than male and older physicians were. CONCLUSIONS: Our findings illustrate that the resident physicians expressed empathy equally well to Hispanic and non-Hispanic white patients but that resident physicians need further training on how to express positiveness to patients from different ethnic backgrounds, especially Hispanic patients.

Adult↗
PubMed2000

Recent advances in the diagnosis and management of infection in the organ transplant recipient.

Infection remains a significant cause of morbidity and mortality in organ transplant patients, with significant infection being found in more than half of these individuals posttransplant. The most important principles of patient treatment are prevention, early diagnosis, and specific therapy. The nature of the antimicrobial therapy required both for infection prevention and treatment is closely linked to the immunosuppressive therapy being administered. A particular challenge in the transplant patient is that the antiinflammatory effects of antirejection therapy tend to obscure the manifestations of infection until relatively late in the disease process, thus putting particular emphasis on more aggressive diagnostic approaches-imaging procedures, biopsy, and new techniques for microbial detection (antigen and DNA detection). Antimicrobial therapy can be administered in three ways: therapeutically, prophylactically, and preemptively. Particularly given the propensity for adverse interactions between antimicrobial agents and cyclosporine and tacrolimus, there is a particular emphasis on prophylactic and preemptive use of antimicrobials.

Anti-Infective Agents↗
PubMed2000

Prevention of primary cytomegalovirus disease in organ transplant recipients with oral ganciclovir or oral acyclovir prophylaxis.

BACKGROUND: Optimal prophylaxis against cytomegalovirus (CMV) disease for organ transplant patients at risk for primary infection (donor seropositive, recipient seronegative, D+R-) remains to be determined. We hypothesized that prolonged oral ganciclovir therapy following intravenous therapy would provide increased protection. METHODS: A total of 155 evaluable D+R- organ transplant recipients from 13 transplant centers were entered into the study: all received intravenous ganciclovir (5 mg/kg/day) for 5-10 days and then either oral acyclovir (400 mg tid) or oral ganciclovir (1 g tid) for an additional 12 weeks. Patients were assigned to their treatment groups at a central randomization site, with a separate randomization scheme for each of the organs transplanted (kidney, heart, or liver). In the case of kidney transplants, the patients were stratified according to source of the kidney (living related vs. cadaveric donor). The primary endpoint was the incidence of CMV disease in the first six months post-transplant. RESULTS: Treatment with oral ganciclovir was associated with a significant decrease in the incidence of symptomatic disease or viremia when compared with the oral acyclovir group (32% vs. 50%, P<0.05). This difference was most marked in terms of tissue invasive disease: only 3 of 15 symptomatic patients in the ganciclovir group vs. 10 of 21 in the acyclovir group developed tissue-invasive infection (P<0.05). There was a significant difference in the time to CMV disease or viremia in the two groups: mean time 212+/-17 days post-transplant for the acyclovir group vs. 291+/-13 days for the ganciclovir group (P<0.001). The incidence of allograft rejection was 34% in the ganciclovir group and 46% in the acyclovir group (P=NS). Leukopenia was more common in the ganciclovir group (P<0.05), but in no case did it require drug discontinuation. Ganciclovir resistance did not develop in this study. CONCLUSION: Prophylaxis with oral ganciclovir following a brief course of intravenous ganciclovir provides useful protection against primary CMV disease.

Acyclovir↗
PubMed1999

Evolving trends in liver transplantation: an outcome and charge analysis.

BACKGROUND: Due to the limited supply and increased demand for donor livers, waiting times are progressively lengthening, which may lead to transplantation at more advanced and less cost-effective stages of disease. The purpose of this study was to evaluate the outcomes and hospital charges of liver transplantation during two recent eras to identify areas for providing more cost-effective care. METHODS: A total of 144 primary liver allografts were performed from 1991 to 1996. Patient characteristics, outcome measures, and hospital charges were compared for patients receiving allografts between 1991 and 1993 (group A) versus those receiving grafts between 1994 and 1996 (group B) using unpaired Student t tests for continuous data and chi-squared tests for categorical data. RESULTS: In comparing groups A and B, no significant differences in patient demographics, relative contraindications, or indication for transplantation existed; median waiting time from date of listing until transplant increased from 88 days to 159 days; and a shift in UNOS priority status at time of transplantation occurred, as the percentage of patients requiring inpatient care increased from 58% to 75% (P=0.034). Despite this, patient hospital and 1-year survival significantly improved from 75.0% to 90.3% (P=0.016), and from 68.1% to 88.9% (P=0.002), respectively. Total hospital charges, without correction for inflation, were $174,908+/-16,388 in A and $193,525+/-14,444 in B (P=0.288). The increased charges were associated with longer inpatient length of stay (LOS) before transplant, resulting in increased pretransplant charges from $24,088+/-4134 (A) to $39,490+/-6,196 (B) (P=0.011). Room and service (54%) was the largest pretransplant contributor to charges, while blood products (23%), room and service (21%), organ acquisition (13%), and operating room charges (11%) contributed the most after transplant. CONCLUSIONS: Longer waiting times resulting in transplantation at later stages of disease have occurred, leading to longer pretransplant LOS and its associated charges. Despite more advanced disease, patient survival rates have significantly improved with fewer infection-related deaths. LOS pretransplant, blood products, and operating room services represent potential areas for providing more cost-effective care.

Adolescent↗
PubMed1999

The therapeutic prescription for the organ transplant recipient: the linkage of immunosuppression and antimicrobial strategies.

Infection and rejection, the two major barriers to successful organ transplantation, are closely linked, with immunosuppressive therapy being central to the pathogenesis of both. After almost two decades when azathioprine and prednisone, supplemented by antilymphocyte antibody therapy, were the cornerstones of post-transplant immunosuppressive programs, there has been a major increase in the therapeutic armamentarium available to treat rejection: cyclosporine, tacrolimus, mycophenolate mofetil, rapamycin, and antibodies directed against the interleukin-2 receptor. These agents are potent inhibitors of microbial specific T cell function, thus potentiating opportunistic infection with herpes group viruses, fungal and mycobacterial species, Strongyloides stercoralis, and a variety of intracellular pathogens. The mechanisms by which each of these drugs exerts its effects are an important determinant of the antimicrobial strategies that will be necessary to combat infection. Indeed, strategies to limit these infections are being linked to the nature of the immunosuppressive therapy required in a particular patient. Thus, the therapeutic prescription for the transplant patient is said to have two components: an immunosuppressive component to prevent and treat rejection, and an antimicrobial one to make it safe. In addition to using antimicrobial agents therapeutically, in the transplant patient prevention is stressed in which antibiotics are deployed prophylactically or preemptively.

Anti-Infective Agents↗
PubMed1999

A murine model of myocardial microvascular thrombosis.

Disorders of hemostasis lead to vascular pathology. Endothelium-derived gene products play a critical role in the formation and degradation of fibrin. We sought to characterize the importance of these locally produced factors in the formation of fibrin in the cardiac macrovasculature and microvasculature. This study used mice with modifications of the thrombomodulin (TM) gene, the tissue-type plasminogen activator (tPA) gene, and the urokinase-type plasminogen activator (uPA) gene. The results revealed that tPA played the most important role in local regulation of fibrin deposition in the heart, with lesser contributions by TM and uPA (least significant). Moreover, a synergistic relationship in fibrin formation existed in mice with concomitant modifications of tPA and TM, resulting in myocardial necrosis and depressed cardiac function. The data were fit to a statistical model that may offer a foundation for examination of hemostasis-regulating gene interactions.

Animals↗
PubMed1999

Polyclonal, nonspecific 111In-IgG scintigraphy in the evaluation of complicated osteomyelitis and septic arthritis.

BACKGROUND: In this investigation we tested the hypothesis that 111In-IgG scintigraphy can differentiate infectious from sterile inflammatory processes in patients with complicated osteomyelitis or septic arthritis. METHODS: A prospective university hospital based study was performed over 18 months. We studied 31 sites of suspected infection, in 25 adult patients, (age 18 to 74 years, 12 females and 13 males) referred with clinical presentations compatible with complicated osteomyelitis or septic arthritis and in whom proof of the infection was likely to be obtained. The clinical setting in these patients was previous trauma, recent surgery, peripheral vascular disease or adjacent soft tissue infection. Whole body scintigraphy was performed at 1-6, 18-24 and 42-48 hours after administration of 55 MBq of 111In-IgG and results were compared to radiographs, 99mTc-MDP skeletal scintigraphy, biopsy specimens (9 sites) or synovial fluid aspirates (4 sites) and clinical follow-up. RESULTS: Of the 31 sites evaluated, 68% (21/31) were interpreted as negative for abnormal tracer accumulation and 32% (10/31) were considered positive. In patients who underwent biopsy and/or synovial fluid aspiration, 6 of 7 sites were correctly interpreted as positive; sensitivity 86%. Five of 6 sites were correctly interpreted as negative; specificity 83%. When all patients were considered using clinical follow-up in addition to culture results, 9 of 10 sites were correctly interpreted as positive (sensitivity 90%) and 20 of 21 patients were correctly interpreted as negative (specificity 95%). CONCLUSIONS: 111In-IgG scintigraphy is useful for detection of musculoskeletal infection in patients in whom sterile inflammatory events simulate infectious processes.

Adolescent↗
PubMed1999

Importance of CMV in the transplant population.

Cytomegalovirus (CMV) infection can be documented in more than half of patients after organ transplantation; viral replication may persist for the long term. It is known that CMV can affect the capacity of the host to mount a defense against complicating infections, particularly in the presence of a mismatch in major histocompatibility antigens between donor and graft recipient. Additionally, some proposed pathogenic mechanisms suggest that the production of growth factors in response to CMV infection may play a significant role in the indirect effects of CMV infection. The accumulating evidence of the direct effects of CMV on allograft survival as well as on the host immune system should lead to a review of prophylactic and therapeutic measures, with a view toward tailoring antiviral prevention protocols to specific patient, characteristics.

Cytomegalovirus↗
PubMed1998

Effect of oral acyclovir or ganciclovir therapy after preemptive intravenous ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus seropositive renal and liver transplant recipients receiving antilymphocyte antibody therapy.

BACKGROUND: Organ transplant recipients who are seropositive for cytomegalovirus (CMV) and who are treated with antilymphocyte antibody (ALA) therapy have a high rate of symptomatic CMV disease. The intravenous administration of ganciclovir therapy once daily during ALA therapy decreased the incidence from 24% to 10% in patients receiving ALA as an induction therapy and from 64% to 22% in those treated for rejection. The present study was undertaken to determine whether a more intensive and sustained antiviral regimen could be more effective. METHODS: From April 1995 to December 1997, all CMV seropositive renal and liver transplant recipients who received ALA therapy were treated with intravenously administered ganciclovir (5 mg/kg/day with dose adjusted for renal dysfunction) for the length of ALA therapy and then with orally administered acyclovir (400 mg three times/day) or ganciclovir (1 gm twice/day) for 3 to 4 months. The incidence of CMV viremia and of CMV disease was determined during the 6 months after completion of ALA therapy. RESULTS: Forty-one patients (35 renal and 6 liver transplant recipients) were studied. CMV disease occurred in 2 patients (4.9%), both of whom were treated for rejection; it occurred in 1 of 21 patients (4.8%) treated with orally administered acyclovir, and in 1 of 20 patients (5%) treated with orally administered ganciclovir. The only patient who developed CMV disease in the ganciclovir group had received only 26 days of oral antiviral therapy. No CMV disease was documented in the group of patients receiving ALA therapy as induction therapy. CMV viremia occurred in three patients in the acyclovir group (14.3%) and in one patient in the ganciclovir group (5%). Among renal transplant recipients only, 1 of 35 patients developed CMV disease (2.9%) and no case of CMV disease was documented in patients treated with orally administered ganciclovir. All six patients receiving two courses of ALA therapy each were free of CMV disease. Toxicity of the regimen was minimal, and antiviral resistance did not develop. CONCLUSIONS: Preemptive antiviral therapy with intravenously administered ganciclovir during ALA therapy and then orally administered ganciclovir for 3 to 4 months provides virtually complete protection against the excessive rate of CMV disease that occurs in CMV seropositive allograft recipients receiving ALA therapy.

Acyclovir↗