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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

Peripheral versus central manifestations in the toxic interaction of lithium and pilocarpine.

Administration of a cholinomimetic agent 24 hr after a single injection of lithium chloride results in a profoundly toxic interaction. The lethality of the interaction was completely blocked by prior administration of scopolamine, but was not reduced by the peripherally acting cholinergic antagonist methscopolamine. Examination of the relative time courses of central neurotoxic and peripheral cholinergic manifestations showed that the peripheral manifestations were transient and were not enhanced by lithium pretreatment. The profoundly toxic consequences of lithium-cholinomimetic interaction may thus occur in the absence of enhanced cholinergic function in the periphery.

Animals

A multicenter randomized trial of ionic (ioxaglate) and nonionic (iopamidol) low-osmolality contrast agents in cardiac angiography.

A multicentered double-blind randomized study was performed comparing the electrocardiographic and hemodynamic changes induced by two new low osmolar contrast agents used for cardiac angiography. The low osmolar ionic (ioxaglate) contrast agent was compared with a low osmolar nonionic (iopamidol) contrast agent in 150 patients with angina pectoris undergoing angiography. Systolic blood pressure, left ventricular end-diastolic pressure, heart rate, and QT interval were measured just before and for 90 s following the left ventricular angiography and selective coronary angiography. Each group was also evaluated for adverse events and quality of radiographic images. Following left ventricular angiography, the systolic blood pressure dropped slightly in both groups with a greater decrease seen in the iopamidol group at 5 s (p less than 0.05). After selective right and left coronary angiography, systolic blood pressure decreased transiently and equally in both treatment groups. The left ventricular end-diastolic pressure increased after the ventriculogram in both groups (15.9 +/- 6.3 to 18.9 +/- 8.6 mmHg in the ioxaglate group and 16.1 +/- 6.7 to 20.1 +/- 7.8 mmHg in the iopamidol group), the change being significant only in the iopamidol group (p less than 0.05). Heart rate increased slightly but significantly in the ioxaglate-treated patients following left ventricular angiography (71.4 +/- 15.2 to 74.4 +/- 13.7 beats/min) (p less than 0.01). QT interval transiently increased following left ventriculography with ioxaglate (407 +/- 59.5 to 420 +/- 58.3 ms) (p less than 0.05) compared with iopamidol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Long-term results of kidney transplantation at the University of Miami.

Of 631 renal allografts performed at our center between January 1, 1979 and June 30, 1989, 368 were from cadaver donors (CAD) and 263 were from living-related donors (LRD). The recipients were almost equally divided among 3 ethnic groups: Black, Hispanic, and non-Hispanic, non-Black (primarily of northern European background). Recipient ages ranged between 1 and 70 years. In the CAD group HLA matching was emphasized so that no patient received a kidney with less than a 1 DR match, and for the entire series there was a mean of 2.4 of 6 HLA antigens matched between donor and recipient. All patients (LRD and CAD) received at least 3 pretransplant blood transfusions. Overall actuarial 10-year patient and graft survival were 68% and 48% respectively, with 72% patient and 56% graft survival for LRD and 58% patient and 36% graft survival for CAD recipients. Factors adversely affecting long-term graft outcome were: a) Black race. Overall 10-year graft survival was 23% versus 55% for non-Blacks (p = 0.008); b) Type I Diabetes before transplant. Overall 10-year graft survival was 35% versus 51% for nondiabetics; and c) Compliance. This was the most significant factor influencing long-term survival, other than death due to cardiovascular disease. In a non-Black, nondiabetic category of less than 36 years of age at transplantation (n = 169), 10-year patient survival in LRD and CAD groups was 95% and 85%, respectively, and graft survival was 78% and 70%, respectively. This was markedly different from the entire series (p = 0.008). Even in this group, 4 of the 17 graft losses (including mortality) were due to documented prolonged noncompliance in teenagers. The 6 other deaths that occurred were due to hepatitis/cirrhosis (2), CMV (3), and AIDS (1). Among the factors not influencing graft survival in the CAD group was HLA matching after the minimum requirements were fulfilled, either by comparing 1 with 2 DR antigens, or total HLA (1-6) antigens matched.

Adolescent

Posttransplant hyperglycemia. Increased incidence in cyclosporine-treated renal allograft recipients.

The incidence of posttransplant diabetes mellitus (PTDM) was compared in two groups of renal allograft recipients. These were all nondiabetic patients who had been transplanted between 1979 and 1987 and received either azathioprine-methylprednisolone (group 1) or cyclosporine-methylprednisolone (group 2) therapy as maintenance immunosuppression. The incidence of PTDM in group 1 was 9.1% vs. 18.6% in group 2 (P less than .05). The mean daily dose of methylprednisolone during the initial 2 months posttransplant was not greater among the PTDM patients of groups 1 or 2. Cyclosporine levels and mean daily CsA doses during the initial 2 posttransplant months were also not different among the CsA-PTDM and euglycemic CsA patients. Posttransplant diabetes mellitus occurred rapidly (less than 2 months) and required insulin therapy in the majority of cases. Increased age (greater than 40 years) was associated with a higher risk for PTDM, however, the greater incidence accompanying increased body weight only approached significance. Patient gender and donor source were not associated with significant risk for PTDM. The development of PTDM was accompanied by a significant decrease in graft survival at 3 years in the entire PTDM population and at 4 years in the CsA-PTDM subgroup. Actuarial patient survival was not adversely affected. The current study suggests that CsA may be diabetogenic when administered with methylprednisolone to renal allograft recipients. The adverse effect on allograft survival requires further investigation. These results may also have important implications for pancreatic and islet cell transplantation.

Actuarial Analysis

Acute rhabdomyolysis associated with cocaine intoxication.

Because an increasing number of patients were arriving at our emergency room with cocaine intoxication and rhabdomyolysis, we reviewed our experience with such patients. We identified 39 patients seen at our institution over an eight-year period with acute rhabdomyolysis after cocaine use. The patients' mean creatine kinase level was 12,187 U per liter (range, 1756 to 85,000). Thirteen of the 39 patients (33 percent) had acute renal failure; 6 of them died. In comparison to the patients with normal renal function, those with renal failure were more often admitted with profound hypotension (46 vs. 4 percent; P less than 0.001), hyperpyrexia (69 vs. 15 percent; P less than 0.001), and markedly elevated serum creatine kinase levels (mean, 28,084 vs. 7931 U per liter; P less than 0.01). Disseminated intravascular coagulation developed in seven patients with renal failure. All six deaths were in this group. Severe hepatic dysfunction was found in 11 patients with renal failure. We conclude that cocaine intoxication can cause acute rhabdomyolysis with acute renal failure, severe liver dysfunction, and disseminated intravascular coagulation and that the mortality rate among patients with this syndrome is high.

Acute Disease

Complementary oligodeoxynucleotide mediated inhibition of tobacco mosaic virus RNA translation in vitro.

Two different "antisense" oligodeoxynucleotides and their RNA analogues, each complementary to non-overlapping sequences of 51 bases near the 5' end of TMV RNA, inhibit in vitro translation of the genomic RNA in a rabbit reticulocyte lysate. Inhibition is dependent upon complementarity, concentration, and hybridization of the oligomers with TMV RNA. Inhibition is observed at molar ratios of TMV RNA to antisense oligomers as low as 1:1.5. A plateau of inhibition at which 10-25% of the control signal remains is achieved by molar ratios of TMV RNA:antisense DNA or RNA greater than or equal to 1:15. The extent of inhibition is not increased by the simultaneous presence of both complementary fragments. Oligodeoxynucleotides and their RNA analogues identical to the same regions of TMV RNA have no direct effect on translation, however, they can block inhibition by the antisense fragments. Translation of BMV RNA is not affected by any of the oligodeoxynucleotides. Polyacrylamide gel electrophoresis shows translation of TMV p126 is selectively inhibited. We conclude that the observed inhibition of translation is due to direct interference with ribosome function.

Base Sequence

Effects of in vitro and in vivo anticanine T lymphocyte and anticanine class II-specific monoclonal antibodies in the beagle.

Two murine anticanine lymphocyte monoclonal antibodies, designated T83 and B1F6, were assessed for (1) in vitro antiepitope activity to circulating lymphocyte subsets, their functional effects on lymphoproliferative assays and binding specificities to diverse cell suspensions and tissue sections; (2) in vivo effects after administration on cells expressing the target epitopes, lymphoproliferation, and allograft survival; and (3) the host immune response to the injected murine immunoglobulins. The monoclonal antibody T83 (IgG3) appeared to be specific for a T cell subset with an up-regulating function on lymphoproliferation. It caused a profound depletion of cells with the appropriate epitope after intravenous administration but it bound to lymphocyte membrane epitopes on some cells in peripheral blood that did not become depleted and putatively caused other modulating effects on lymphocyte function. The monoclonal antibody B1F6 (IgG2a, previously described) was immunologically specific in vitro for cells expressing class II major histocompatibility complex antigens. In the dog, this also consisted of 50% of T lymphocytes. After intravenous administration, there were functional effects similar to those of T83. A modest prolongation of survival of renal allografts was observed when both mAbs were used as the sole immunosuppressive agent. These studies also demonstrated the occurrence of natural canine antimurine IgG antibodies. Administration of either monoclonal antibody was followed by a rapid increase in the concentration of the antimouse antibody(s). We postulate that the presence of canine natural antimouse IgG markedly influenced the biologic effects of in vivo administered monoclonals.

Animals

Sequential thallium-201 myocardial perfusion studies after successful percutaneous transluminal coronary artery angioplasty: delayed resolution of exercise-induced scintigraphic abnormalities.

To characterize the sequential changes of myocardial perfusion scintigraphy in patients with coronary artery disease (CAD) after complete revascularization, 43 patients underwent exercise thallium-201 (201Tl) myocardial perfusion scintigraphy before and at 9 +/- 5 days, 3.3 +/- 0.6, and 6.8 +/- 1.2 months after percutaneous transluminal coronary angioplasty (PTCA). Only patients with single-vessel CAD, without previous myocardial infarction, and without evidence of restenosis at 6 to 9 months after PTCA were included. Perfusion scans were analyzed blindly with the use of a new quantitative method to define regional myocardial perfusion in the topographic distribution of each coronary artery, which was shown to be reproducible (r = .94 or higher and SEE of 7% or less, between repeated measures by one and two operators). At 4 to 18 days after PTCA, the mean treadmill walking time increased by 123 +/- 42 sec, mean exercise-induced ST segment depression decreased by 0.6 +/- 0.3 mm, group maximal heart rate increased by 20 +/- 9 beats/min, and group systolic blood pressure at peak exercise increased by 24 +/- 10 mm Hg, compared with pre-PTCA values (p less than .001). However, no group differences were noted in these variables between the three post-PTCA stages. Myocardial perfusion in the distribution of the affected (dilated) coronary artery, on the other hand, improved progressively. In the 45 degree left anterior oblique view for instance, myocardial perfusion increased at 9 days after PTCA (from 68 +/- 24% before PTCA to 91 +/- 9%, p less than .001) and at 3.3 months after PTCA (101 +/- 8%, p less than .05 vs 9 days after PTCA), but no further significant changes were seen at 6.8 months after PTCA (102 +/- 8%). Similar changes were noted in the other two views. No relationship between minor complications during PTCA and delayed improvement on the 201Tl was observed. Myocardial ischemia was diagnosed in 12 of the 43 scans recorded a few days after PTCA, but in none recorded at later stages. We conclude that 201Tl scans after PTCA often show delayed improvement and therefore, an abnormal myocardial perfusion scan soon after PTCA does not necessarily reflect residual coronary stenosis or recurrence.

Adult