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Biomedical subjects

D Roth

Publications and source records attributed to D Roth.

At least 163 records · Page 9Linked to original sources

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

A receptor binding assay for endoxin in human urine.

Endoxin is an endogenous substance known to participate in the regulation of the sodium balance and hypertension. Its chemical nature remains elusive. Based on its capacity to specifically bind to Na-K ATPase receptors we describe a receptor assay for its measurement in human urine. The endoxin was extracted by methanol and desalted on a silicagel column with a mixture of chloroform-ethanol. Calibration curves have been established by the transformation of the weight of crude extract in actual content of active material expressed in nmol/l as calculated from Scatchard plots analysis. Normal values are given for subjects on regular salt diet. Changes in endoxin urinary elimination after an oral salt load are outlined.

Binding, Competitive

Gastric carcinogenesis: a model for the identification of risk factors.

In a series of extensive studies on gastric carcinogenesis, we have used Sprague-Dawley rats to examine the morphologic, histochemical, and biochemical effects of risk and protective factors on N-methyl-N'-nitro-N-nitroso guanidine (MNNG)-induced tumors in an attempt to link early observations with the end-point lesion, gastric cancer. We have observed that the putative risk factors sodium chloride (NaCl); a mixture of bile acids; aspirin; alcohol; and nitrite enhance MNNG-induced neoplasia of the gastric mucosa. On the other hand butylated hydroxyanisol (BHA), Se and difluromethylornithine (DFMO) were protective and inhibited the induction of gastric mucosal neoplasia. In most cases, early changes detected by a number of criteria correlated with the end-point, gastric neoplasia. This model appears to be useful in screening and evaluating chemicals for risk for or protection against gastric cancer.

Animals

AIDS-related glomerulopathy: occurrence in specific risk groups.

The histopathology and incidence of AIDS-related glomerulopathy was evaluated by renal biopsy (N = 24) or at autopsy in 159 patients, including 131 adults and 28 infants and children with AIDS. Thirty-five patients had overt clinical manifestations of renal disease characterized by a nephrotic syndrome with focal and segmental glomerular sclerosis (FSS). Fifteen patients had diffuse glomerular mesangial hyperplasia (MH) without or with minimal clinical renal disease and 109 had intact or minimally involved glomeruli. Whereas 15 of 30 (50%) i.v. drug users with AIDS had evidence of renal disease, only one of 53 (2%) homosexuals had clinical renal disease and only 6 (11%) had histologic evidence of glomerular pathology. The study confirms the important risk of i.v. drug use as a pathogenic factor of renal disease and shows a rarity of renal disease in homosexual or bisexual men with AIDS. On the other hand, 30% of adult Haitians with AIDS had FSS or diffuse MH, although i.v. drug use is not an important risk factor in this population. Moreover, eight of 28 (29%) children with perinatal AIDS had evidence of renal involvement, including four with a nephrotic syndrome and FSS. The data provide strong evidence for the existence of an AIDS-related glomerulopathy independent of i.v. drug use, but suggest that unrecognized co-factors may be important in the development of renal disease.

AIDS-Related Complex

In vivo and in vitro induction of class II molecules on canine renal cells and their effect on the mixed lymphocyte kidney cell culture.

Canine renal cortical cells were obtained by collagenase extraction from allogeneic haploidentical, donor-recipient beagle littermate pairs and from unrelated mongrels. Peripheral blood lymphocytes (PBL) of the mongrels, as well as of one member of the beagle pair that exhibited high mixed lymphocyte culture (MLC) reactivity against the other were also stimulated by renal cortical cells derived from both normal and rejected transplanted kidneys in mixed lymphocyte kidney cell culture (MLKC). A moderate autologous MLKC reactivity occurred in response to normal renal cortical cells. However, rejected kidney cortical cells were markedly more stimulatory than normal renal cortical cells in both allogeneic and autologous MLKC reactions. Lymphocytes from donor animals responded more strongly to autologous cortical cells isolated during rejection of the transplant than to cortical cells from normal allogeneic kidneys. Recipient infiltrating lymphocytes and propagated T cell lines extracted from the rejected kidney also responded more strongly than PBL to cortical cells from this kidney. Gradient purification of the stimulating cortical cells resulted in one virtually pure preparation of distal tubular epithelial cells, as demonstrated by immunohistochemical stains and electron microscopy, which caused enhanced stimulation in MLKC. Class II marker analysis of the canine renal cells from rejected kidneys revealed the presence of these molecules on tubular cells that were absent on normal kidney cells. A 16-hr coculture of normal renal cortical cells not exhibiting class II surface markers in the presence of allogeneic or autologous lymphocytes induced the expression of these molecules, associated with an increased stimulatory capacity. This also occurred to a lesser extent with MLC (and MLKC) cell culture media supernatants. However, the low level of class II expression by all the various gradient-purified fractions in the absence of rejection or coculture, and the increased but equivalent expression on all fractions after coculture did not correlate with the preferential stimulatory capacity of the purified distal tubular cell layer. We conclude that two signals are necessary for the MLKC reaction, one involving tissue (kidney)-associated epitopes (the nominal antigen demonstrated in this study to be present in normal distal tubular cells), the other involving class II molecules as costimulatory (amplification) moieties.

Animals

Renal transplantation in systemic lupus erythematosus: one center's experience.

A retrospective analysis of 15 renal transplant patients with end-stage renal disease (ESRD) secondary to systemic lupus erythematosus (SLE) was performed. Overall actuarial patient and graft survival at 6 years was 93 and 84%, respectively. Recipients of HLA-identical kidneys did not appear to be at increased risk of allograft failure due to rejection or recurrent disease. Two biopsy-proven cases of recurrent lupus involving the allograft were observed and are discussed. Those patients currently experiencing excellent graft function (creatinine less than 2 mg/dl) had a significantly longer pretransplantation dialytic interval than the group whose most recent serum creatinine exceeds 2 mg/dl (or returned to dialysis). Posttransplantation monitoring of antinuclear antibody, antidouble-stranded DNA, C3, C4, and circulating immune complexes was not predictive of renal or extrarenal disease activity. Renal transplantation should be considered an excellent therapeutic modality for the lupus patient with ESRD, although an interim period on dialysis of at least 1 year seems warranted.

Follow-Up Studies