Preparing for health care reform: basic strategies.
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Biomedical subjects
Publications and source records attributed to R Kohli.
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The relation between coronary artery lesion morphology and associated segmental left ventricular (LV) dysfunction in patients with unstable angina is unclear. Fifty-two patients with angina occurring at rest who underwent cardiac catheterization within 3 days of the last episode of pain and had no enzymatic evidence for myocardial necrosis were evaluated. Coronary artery narrowings deemed responsible for the ischemic episodes were analyzed with regard to the artery involved, maximal diameter of the narrowing, presence of thrombus, and complex appearance. Time to catheterization, age, sex and electrocardiographic evidence of ischemia were also noted. Segmental LV dysfunction in the territory supplied by the "culprit lesion" was present in 58% of patients. It occurred significantly more often with lesion location in the left anterior descending coronary artery, and was less frequent with lesions in the left circumflex and ramus coronary arteries. Ischemic electrocardiographic changes were more sensitive in predicting LV dysfunction with culprit lesion location in the left anterior descending or right coronary artery. LV dysfunction could not be predicted by any other parameter analyzed. It is concluded that postischemic LV dysfunction occurs frequently in rest angina, especially when the severest narrowing is in the left anterior descending coronary artery.
The effectiveness of intracoronary urokinase infusion as an adjunct to percutaneous transluminal coronary angioplasty (PTCA) was studied in 50 patients who underwent angioplasty for complex coronary narrowings or had thromboembolic complications during PTCA (29 [58%] men, 3 [6%] stable and 37 [74%] unstable angina, and 16 [32%] prior coronary bypass surgery). The primary indications for intracoronary urokinase infusion were intracoronary thrombus in 27 patients (54%), distal coronary embolization in 9 (18%), and abrupt reclosure in 14 (28%). Urokinase was infused in a mean (+/- standard deviation) dosage of 399,000 +/- 194,000 IU (range 150,000 to 1,000,000) at an average rate of 5,000 to 20,000 IU/min. Angiographic success was achieved in 43 patients (86%). Complications included the need for urgent bypass surgery in 3 patients, Q-wave myocardial infarction in 2, and non-Q-wave myocardial infarction in 12 (8 of whom had peak creatine kinase less than twice the upper normal limit). The incidence of myocardial infarction was significantly higher in patients with vein grafts (69%) than in those with PTCA of native vessels (14%). Two patients died (1 massive gastrointestinal necrosis 24 hours after angioplasty, and 1 after urgent bypass surgery). Mean (+/- standard deviation) fibrinogen levels were 355 +/- 73 mg/dl before urokinase infusion, and 361 +/- 70, twelve hours afterward. Three patients had local bleeding, but no transfusions were needed. It is concluded that intracoronary urokinase is a safe and effective adjunct to PTCA in patients with associated thrombi and may improve the success rate in angioplasty complicated by thrombus formation.
We describe five patients with IgA-nephropathy complicating diabetes mellitus. In four cases, diabetic glomerulosclerosis was present at the same time. One patient suffered from dermatitis herpetiformis. The observation of the present five cases together with the notion of an increased prevalence in diabetes mellitus of celiac disease and dermatitis herpetiformis suggests that the occurrence of IgA-nephropathy in diabetic patients is not mere coincidence.
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Prolactin (PRL) was purified from freshly frozen pituitary glands of water buffaloes (Bubalus bubalis) by a combination of existing procedures of Ellis and Jiang and Wilhelmi involving serial extraction of different pituitary proteins. The partially purified preparation was further fractionated on DEAE-Sephadex followed by Sephadex G-100 chromatography. This was finally purified on HPLC. This preparation was found to be homogeneous by SDS-PAGE and HPLC and had a single N-terminus amino acid (Threonine). The molecular size was estimated to be 24K +/- 0.5 by SDS-PAGE and approximately 25K by GPC-HPLC. The buffalo PRL gave a dose dependent inhibition curve in a rat liver based radio receptor assay with a potency of 30-35 I.U./mg and also in a partial homologous RIA using 125I-buffalo PRL and rabbit anti-oPRL serum giving a potency of 30 I.U./mg. Metabolic labelling studies using 35SO4(2-) with buffalo pituitary minces showed the incorporation of radioactive sulfate into immunoprecipitable PRL-like material. Physico-chemical characterization of the site of the linkage between sulfate and PRL revealed the presence of Tyr-O-SO4 in bu-PRL. A high affinity monoclonal antibody (MAB) with Ka of 10(10) L/M, belonging to IgG1 isotype, and capable of cross reacting with ovine and bovine PRL was generated. This MAB was conformation specific as reduced and carboxymethylated PRL did not react with it. A homologous RIA system using this MAB has been standardised.
Acute deterioration of renal function occurred shortly after the angiotensin-converting enzyme (ACE) inhibitor, enalapril, was administered to two renal transplant patients who were also receiving cyclosporine. Renal function recovered completely in both cases upon discontinuation of enalapril. Neither patient had evidence of transplant artery stenosis or chronic rejection, conditions known to predispose to renal failure during ACE inhibitor therapy. The possibility that afferent vasoconstriction induced by cyclosporine may have predisposed these patients to renal failure from enalapril is discussed.
Sheep pituitary cells prelabelled with radioactive [35S] sulfate (35SO4(2-)) were incubated with different concentrations of LH-RH and the release of LH (lutropin) into the medium was monitored in terms of immunoprecipitable [35S] sulfated LH radioactivity and estimation of LH in the same sample by radioimmunoassay. A dose dependent response was obtained with a maximum of a 16 fold increase in immunoprecipitable 35SO4(2-) -labelled LH radioactivity in the medium which was confirmed by radioimmunoassay. Similar results were also obtained for Buserelin, a well known superactive analogue of LH-RH. However, the half maximal response for Buserelin was obtained at 3-5 nM in comparison to 80.5 nM for LH-RH. After the maximal response to LH-RH as well as Buserelin, a further increase in the concentrations caused a decrease in the release of immunoprecipitable [35S]-sulfate labelled LH into the medium. Differential labelling of stored and newly synthesized LH with radioactive [35S] sulfate and [3H]-labelled leucine revealed that there was a dose dependent increase in the [35S] sulfate labelled LH into the medium whereas the release of [3H]-leucine labelled newly synthesized LH did not show a parallel increase either at different concentrations of LH-RH or at different time intervals. The above observations strongly suggest the possibility of sulfation of LH being the potential signal indicating the storage of LH in sheep pituitary cells. Another important observation in our study was that the dose dependent response of LH-RH in the form of release of [35S]-sulfate labelled LH, which was monitored by immunoprecipitation with specific LH antiserum, can be used in an in vitro bioassay for LH-RH. We believe that a new cheap and sensitive in vitro bioassay could be developed on the basis of this observation.
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When the metabolically obtained 35S-labelled sheep pituitary prolactin-rich fraction was subjected to chemical deglycosylation the radioactivity was retained in the immunoprecipitable prolactin. 35S-labelled prolactin-rich pituitary extract was fractionated on SDS-PAGE and protein was extracted from prolactin positive bands. When the extracted 35S-labelled prolactin was hydrolysed by alkali and then chromatographed on a thin layer of silica, it showed the presence of a radioactive compound which had an Rf value identical to the standard Tyr-O-SO4 synthesized and characterized in our laboratory.
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Radioactive sulfate (35SO2-4) has been shown to be incorporated into immunoprecipitable prolactin-like material from incubated minces of sheep and buffalo pituitaries. The 35S-labelled prolactin could be purified by standard procedures. On SDS-PAGE, the 35S-labelled prolactin rich fraction gives two major Coomassie blue bands around 25KDa and these on Western blot analysis gave positive bands. Radioactive [14C]- mannose was also found incorporated into the prolactin like material. The nature of sulphate link to the peptide is not known. It could be sugar-SO4 and/or Tyrosine-SO4.
The effects that renal disease and hemodialysis have on the pharmacokinetics of amoxicillin/clavulanic acid combination were studied in a patient receiving this combination for the treatment of a Nocardia asteroides infection. Hemodialysis increased the clearance of both substances as evidenced by lower serum concentrations during the on-dialysis day, i.e., 2.3 +/- 0.8 vs. 5.9 +/- 1.2 micrograms/ml for clavulanic acid and 8.0 +/- 1.8 vs. 12.4 +/- 0.9 micrograms/ml for amoxicillin. Clavulanic acid appeared to be influenced to a greater extent as compared to amoxicillin because of its higher extraction ratio (0.74 vs. 0.44) as well as a higher observed ratio of amoxicillin to clavulanic acid during the on-dialysis day (3.59 +/- 1.27 vs. 2.28 +/- 0.65; p less than 0.05). Comparison of the area under the serum concentration-time (AUC) during the off-dialysis day with published AUC values suggested accumulation of amoxicillin/clavulanic acid. These data indicate that dosage adjustments for amoxicillin/clavulanic acid may be required in patients with chronic renal failure who are on hemodialysis. Further studies in this patient population are needed before specific dosing guidelines can be provided.
The serum hemodialysis clearance of theophylline was determined in 4 patients compared to systemic serum clearance off dialysis in 3 patients. The serum extraction ratio values obtained were compared to those of urea. Hemodialysis clearance of theophylline averaged 84.3 +/- 11.6 ml/min (mean +/- SD), and extraction ratios obtained were found to be a fairly consistent fraction of the urea extraction ratio (0.72 +/- 0.08). Hemodialysis clearance increased total body clearance (ClTB) off dialysis by 130%, 387%, and 176% in the patients who had their theophylline serum clearance estimated off dialysis. Difference in reported hemodialysis clearance are probably related to the type of dialyser used. Studies utilizing hollow fiber systems (the present study) consistently yielded higher theophylline dialysis clearance values than those using coil systems (84.3% to 88.1 ml/min versus 32 to 39.4 ml/min). Patients receiving theophylline on hemodialysis should be closely monitored for bronchospasm during and after the hemodialysis procedure. Measurement of serum concentrations should be employed to facilitate dosage increases during hemodialysis.
Acute myoglobinuric renal failure developed in three patients during the course of influenza virus infection. Muscle enzyme levels were elevated in all patients. Myoglobin was detected in the urine or serum by immunodiffusion. Recent influenza infection was documented by elevated hemagglutination inhibition titers. One patient died, whereas the remaining two patients completely recovered renal function. These patients with influenza infection represented more than half of the cases of myoglobinuric renal failure seen on the medical services of the study institutions during ths same period. These observations suggest that the association between influenza infection and myoglobinuric renal failure may be more common than previously suspected.
Using the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transformation (LTF), we studied the humoral antibody and cell-mediated immunity to cytomegalovirus (CMV) in normal subjects, in patients with cancer receiving localized or nonlocalized radiation, and in renal transplant recipients on immunosuppressive chemotherapy. The LTF activity was determined by the whole blood microassay, using four strains of CMV (AD-169, Davis, Veca, and Towne), AD-169 early antigen, and phytohemagglutinin (PAH). The renal transplant subjects manifested significantly depressed LTF responses to PHA and CMV and frequent presence of immunoglobulin M and early antigen-specific antibody response. The depressed LTF response to CMV recovered significantly 2 years after transplantation. The cancer patients were also characterized by a profound drop in LTF responses to PHA and CMV and in immunoglobulin M and early antigen-specific antibody response after nonlocalized radiation. LTF responses to AD-169 and Towne strains were found to be higher than those to Davis and Veca strains. The LTF response to PHA declined with age. However, LTF responses to specific CMV antigens were found to be somewhat increased with advancing age. These observations suggest that transplantation-associated suppression of CMV-specific cell-mediated immunity may improve a few years after transplantation despite continued immunosuppressive therapy.
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Twenty-seven patients with diffuse "crescentic" glomerulonephritis (CSGN) were identified in 1,174 renal biopsies from nephritic patients. Patients were assigned to three groups on the basis of the immunofluorescent study of renal biopsy specimens and serologic findings. Group I included eight patients with antibodies to glomerular (anti-GBM) and tubular (anti-TBM) basement membranes; group II had eight patients with only anti-GBM antibodies; and group III had eleven patients with CSGN unassociated with antibodies to either GBM or TBM. Patients with anti-GBM/anti-TBM antibodies (group I) had severe tubulointerstitial (TI) nephritis, as characterized by the infiltration of polymorphonuclear leukocytes and macrophages along the TBM and peritubular vessels. In some patients, focal proliferation of epithelial cells of proximal convoluted tubules (PCT), gaps or extensive destruction of TBM, lesions in the walls of small peritubular vessels, and interstitial giant cells were also observed. Patients with anti-GBM antibodies (group II) had mild to moderate interstitial cellular infiltration and mild tubular changes. Five patients with CSGN not associated with antibodies to renal basement membranes (group III) had mild to moderate interstitial cellular infiltration and tubular changes. A sixth patient, with Wegener's disease had severe granulomatous TI lesions. The results of this study show that TI nephritis is most frequent and severe with anti-TBM antibodies are demonstrable and suggest that anti-TBM antibodies contribute to the development of TI lesions.