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Biomedical subjects

R Greenberg

Publications and source records attributed to R Greenberg.

At least 109 records · Page 6Linked to original sources
PubMed1990

Value of electrophysiologic testing in patients with previous myocardial infarction and nonsustained ventricular tachycardia. Philadelphia Arrhythmia Group.

Previous studies of the value of electrophysiologic studies in patients with nonsustained ventricular tachycardia (VT) have been hampered by the inclusion of a small number of patients with various types of heart disease. This retrospective study was designed to assess the value of programmed stimulation in 205 asymptomatic patients who had had an acute myocardial infarction greater than 1 month before study. Inclusion was based on 24-hour Holter monitoring during which patients had to manifest greater than or equal to 3 consecutive ventricular beats at a rate greater than 135 beats/min. Forty-seven (23%) patients had normal, 70 (34%) mildly impaired and 88 (43%) severely impaired left ventricular function. Programmed stimulation, using up to 3 extrastimuli, was used in each. Seventy-five patients (36%) were noninducible, 59 (29%) had nonsustained VT (less than 30 seconds), 67 (33%) had sustained monomorphic VT and 4 (2%) had either polymorphic VT or ventricular fibrillation. Eighty-two patients were not treated with antiarrhythmic drugs, 57 others were placed on a program selected empirically and 66 had therapy guided by electrophysiologic testing. Satisfactory follow-up information was gathered in 187 of the 205 patients, with a mean follow-up of 18 months. One hundred forty-two patients are alive and well, 39 had sustained VT or sudden death and 6 others had a cardiac death. Only left ventricular function discriminated those who had a sustained arrhythmia or died from those who did not. Thus, programmed stimulation did not have independent predictive value in patients with nonsustained VT. However, definitive conclusions can be reached only with a large prospective study carried out in untreated patients.

Anti-Arrhythmia Agents↗
PubMed1990

Cytoplasmic and periplasmic expression of a highly basic protein, human interleukin 4, in Escherichia coli.

Human IL-4 (hIL-4) has been cloned from a human T cell line based on its homology to the murine IL-4 cDNA sequence. We have compared cytoplasmic and extra-cytoplasmic expression of this basic protein in Escherichia coli using various combinations of promoters, replicons and host strains. Strains producing a cytoplasmic product were most successful at heterologous protein expression, producing up to 500 mg/l of an inactive aggregated form of the protein. The biological activity of the protein could be restored by refolding the protein with guanidine hydrochloride and glutathione giving a specific activity identical to that of IL-4 derived from CHO cell lines stably transformed with an hIL-4 expression plasmid. Strains designed to secrete human IL-4 into the periplasmic space produced far less protein (approximately 5 mg/l). However, a significant fraction of this protein was detected in the culture medium. This fraction appeared to be soluble after ultracentrifugation, and demonstrated high specific activity without refolding. Leakage of heterologous protein into the culture medium may be a viable way to recover biologically active products without relying on the denaturation and refolding in vitro that can, at times, yield incorrectly folded gene product.

Amino Acid Sequence↗
PubMed1990

Exploiting the cell membrane for the production of heterologous proteins in Escherichia coli.

The bacterial membrane serves both as a cell organelle and as a barrier for segregating the metabolically active cytoplasm from the extracellular milieu. Thus we can use plasmid vectors designed to produce a hybrid protein containing an efficient signal peptide coupled to the amino terminus of the cloned heterologous protein (secretion cloning vectors) for the production of proteins which are insoluble, proteolytically sensitive, or bacteriocidal when produced in the cytoplasm of Escherichia coli. We demonstrate that human granulocyte-macrophage colony stimulating factor can be isolated as an active species only after transport into the bacterial periplasm. Production of the protein in the bacterial cytoplasm is bacteriocidal. We also demonstrate that biologically active human interleukin 4 appears only after transport of the protein into the bacterial growth medium. The protein forms membrane-associated aggregates in the cytoplasm, and demonstrates an active but nonnative conformation when expressed in the periplasm. This may correlate with the affinity of the interleukin 4 molecule for negatively charged macromolecules, including bacterial membrane components and bacterial lipopolysaccharides, which may alter the folding pathway inside the cell.

Animals↗
PubMed1989

Safety of endoscopy in the immediate postoperative period following gastric anastomosis.

The safety of gastrointestinal endoscopy in the immediate postoperative period following partial gastrectomy was assessed in ten dogs. Endoscopy was performed preoperatively and at 1, 2, 3, and 7 days postoperatively. The mean pressures required to perform an adequate endoscopy varied from 17 to 20 mm Hg. Following partial gastrectomy, the abdominal wall was closed with a zipper to facilitate inspection of the gastric anastomosis. No leakage of air or intra-abdominal abscesses were seen following endoscopy. The results of this study suggest that endoscopy can be safely performed in the immediate postgastrectomy period.

Animals↗
PubMed1989

Gastroenterology, diagnosis-related groups, and age.

Hospitals are now being reimbursed by a prospective Diagnosis-Related Group (DRG) classification system. There have been no major changes in the Federal Medicare DRG classification system since its inception 5 years ago. In this project, we analyzed all gastrointestinal (GI) medicine admissions by age and resource utilization at a large academic medical center. Total hospital costs for the 3,598 GI patients (January 1, 1985, through December 31, 1987) were $18,460,604. Although DRG reimbursement for all patients for the 3-year period would have generated an aggregate profit of $957,760, four out of five age categories of patients 65 years of age and above would have generated losses; the highest loss was for patients 85 years and over, at $2,235 per patient. Older GI patients (i.e., 65 years and over) had higher hospital costs, longer lengths of stay, more diagnoses and procedures per patient, and a higher mortality rate than younger patients. Both intensive care unit (ICU) and blood utilization rose with age. Thus, older GI patients consumed a disproportionately larger share of hospital resources. Our study suggests that the current DRG reimbursement scheme may be inequitable relative to the older GI medicine patient; financial disincentives from DRGs may affect elderly patients' access to and quality of care in the future.

Academic Medical Centers↗
PubMed1988

Accessibility and mobility of lysine residues in beta-lactoglobulin.

N epsilon-[2H6]Isopropyllysyl-beta-lactoglobulin was prepared by reductive alkylation of beta-lactoglobulin with [2H6]acetone and NaBH4 to provide a 2H (NMR) probe for the study of lysine involvement in lipid-protein interactions. Amino acid analysis showed 80% of the protein's 15 lysine residues to be labeled. Unmodified lysine residues were located through peptide maps produced from CNBr, tryptic, and chymotryptic digests of the labeled protein. Lys47 was not modified; Lys135,138,141, located along an amphipathic helical rod, were each partially unmodified. All other lysine residues were at least 90% modified. Average correlation times calculated from 2H NMR spectra were 20 and 320 ps for 8.7 and 3.3 residues, respectively, in 6 M guanidine hydrochloride; in nondenaturing solution, values of 70 and 320 ps were obtained for 6.5 and 3.2 residues, respectively, with the remaining 2.3 modified residues not observed, suggesting that side chains of lysine residues in unordered or flexible regions were more mobile than those in stable periodic structures. 2H NMR spectra of the protein complexed with dipalmitoylphosphatidylcholine confirmed the extrinsic membrane protein type behavior of beta-lactoglobulin previously reported from 31P NMR studies of the phospholipids complexed with beta-lactoglobulin. Although no physiological function has yet been identified, comparison of these results with the X-ray structure [Papiz et al. (1986) Nature (London) 324, 383-385] supports the hypothesis that residues not accessible for modification may help to stabilize the cone-shaped beta-barrel thought to contain binding sites for small lipid-soluble molecules.

Amino Acid Sequence↗
PubMed1988

Effects of reductive alkylation on peptide retention times.

Reductive alkylation of primary amino groups is used to introduce nuclear magnetic resonance or radioactive probes into proteins. Because of electrostatic and conformational effects, reductive alkylation is not always complete. We describe herein a rapid high-performance liquid chromatographic method for separating and quantitating mixtures of native and reductively alkylated peptides. Small synthetic peptides were chosen to illustrate the effects of methylation and isopropylation of primary amino groups on chromatographic retention times. Mixtures of unmodified and reductively methylated or isopropylated peptides (Gly-Leu-Tyr, Gly-Gly-Lys-Arg, Arg-Lys-Asp-Val-Tyr and Pro-Gly-Lys-Ala-Arg) could be separated. Chromatography was on a 5-micron, 25 cm x 0.4 I.D., C18 reversed-phase column with 0.1% trifluoroacetic acid in a 10 to 80% linear gradient of acetonitrile in water, a system appropriate for protein digests. The relative concentrations of native, and singly and doubly alkylated peptide were determined as well as the effective retention coefficients for dimethyl and isopropyl groups. The method shows promise for the peptide mapping of partially alkylated proteins.

Alkylation↗
PubMed1988

Phase I study of a murine monoclonal anti-lipid A antibody in bacteremic and nonbacteremic patients.

Nine patients with suspected gram-negative bacterial sepsis were studied to determine the safety, pharmacokinetics, and immunogenicity of XMMEN-0E5, a murine immunoglobulin M monoclonal antibody directed against the core lipid A region of bacterial endotoxin. Antibody was administered by single intravenous infusion of 1 to 4 h duration at doses ranging from 0.1 to 15 mg/kg. Five patients had positive blood cultures for gram-negative bacteria, one patient had Torulopsis septicemia, one patient had gram-negative bacterial meningitis, and two patients were culture negative. No evidence of antibody-mediated toxicity was observed at any dose level. The serum half-life of the antibody was approximately 10 h at doses of 0.1 to 7.5 mg/kg and approximately 18 h at a dose of 15 mg/kg. No apparent difference in clearance of antibody was observed between bacteremic and nonbacteremic patients. Human anti-mouse antibodies were detected in the sera of three evaluable patients that received doses equal to or greater than 2.0 mg/kg but not in patients that received lower doses of antibody. This study demonstrates that XMMEN-0E5 is well tolerated at doses from 0.1 to 15 mg/kg and may be immunogenic at doses of 2.0 mg/kg and above. Controlled trials to establish the efficacy of this antibody in the treatment of gram-negative bacteremia are indicated.

Adult↗
PubMed1988

Hospital costs, resource characteristics, and the dynamics of death for hospitalized gastroenterology patients.

The federal Medicare diagnosis-related group (DRG) hospital payment system has been on-line for 5 yr with no major adverse effects on either access or quality of care. The hospital industry contends that DRGs are underpaying for hospital care, especially for certain types of patients. Analysis of 2,500 gastroenterology patients by outcome (i.e., survivors vs mortalities) demonstrated that the 122 mortalities had a much greater intensity of hospital resource utilization, and generated substantial financial risk under DRG pricing schemes, compared with the 2,378 survivors. Only mortalities that occurred within 1 wk of admission to the hospital were profitable under DRGs. A long hospital length of stay (LOS) for mortalities was very unprofitable (mortalities with more than a 60-day LOS generated $20,210 loss per patient). Emergency gastroenterology admissions who died had greater financial risk under DRGs, compared to nonemergency mortalities. Those mortalities referred to gastroenterology from other clinical services tended to have greater resource utilization and financial risk under DRGs, compared with nonreferred mortalities. These data suggest significant inequities in the current DRG prospective payment system vis-a-vis gastrotenterology mortalities. Predictive variables of greater hospital resource utilization for gastroenterology mortalities include longer hospital lengths of stay, emergency admission, and referral from another clinical service. If equity of DRG payment is not improved by the federal government, certain groups of patients likely to be mortalities may suffer a decline in access and/or the quality of medical care in the future.

Adult↗
PubMed1988

Aortoesophageal fistula: early and late endoscopic features.

Endoscopic photographs were obtained in a patient with back pain and hematemesis. External compression of the mid-esophagus and small esophageal diverticula was noted, as well as a small erosion oozing bright red blood in otherwise normal mucosa. Angiography revealed an aneurysm of the thoracic aorta without leak. Surgical closure of the aneurysm was initially successful; however, the patient developed recurrent bleeding one month later. Repeat endoscopy revealed a recurrent fistula with an intramural mass in the mid-esophagus, oozing blood with adherent clot. These findings are the earliest endoscopic features of aortoesophageal fistula described, and this is the only case with subsequent reendoscopy, demonstrating previously reported findings in an advanced stage of fistula formation. Flexible endoscopy is a safe, valuable diagnostic study in suspected aortoesophageal fistula. The literature on endoscopy in aortoesophageal fistula is reviewed.

Aorta, Thoracic↗
PubMed1987

The identifier concept: clinical parameters to stratify hospital costs within gastroenterology DRGs.

Prospective payment systems using the diagnostic related group (DRG) payment mechanism are changing the incentives offered to hospitals. We studied hospital costs of all gastroenterological (GI) patients (n = 2500) treated during a 2-yr period at our academic medical center. We showed that patients within GI DRGs could be grouped regarding hospital costs by four clinical variables: intensive care unit or emergency admission, and blood or plasma product consumption. Patients within each DRG with the variable usually had higher total hospital costs, a longer stay in the hospital, a greater number of diagnoses, more outliers, and a poorer outcome than patients without the variables. As the variables accumulated, these differences became more pronounced. This study demonstrated that hospital costs may be stratified within GI DRGs by clinical parameters that occur during the patient's hospital stay. These four variables could identify higher cost patients within a DRG; cost containment could then be directed at these patients with, hopefully, resultant savings.

Blood Transfusion↗
PubMed1987

Statistical methods for the practical clinical application of morphometric measurements.

Four statistical methods are presented to determine the practical clinical value of measurements made from malignant tumors and to translate these measurements into a prediction of survival for each patient: the Cox statistical model, which must be derived from a data base of cases with known outcome; the null-rank test, a modified rank-sum test that provides an overall measure of the effectiveness of the Cox model; the predicted survival curve, an estimate of survival derived for each new patient from measurements of the primary tumor; and the standard error of measurement, an empirical method for estimating the variability introduced into predicted survival by errors in measurement. The value of these statistical methods was demonstrated by application to 200 cases of human intraocular melanoma, with the two predictive morphometric measurements used being the standard deviation of nucleolar area (SDNA) and the largest tumor dimension (LTD) derived from a single histologic slide of each tumor. Sufficient references and mathematical details are provided to allow anyone with moderate skills as a computer programmer to construct or obtain all of the relevant algorithms.

Biometry↗
PubMed1986

A method for assessing potential bias among cancer patients recorded as "dead of other causes." Application to cases of intraocular melanoma.

By applying the Cox regression model to 226 cases of intraocular melanoma, the authors detected a statistical association between tumor-related measurements and 42 deaths that were recorded as due to causes other than melanoma within 10 years of follow-up. This association may reflect a number of events, including errors in assignment of cause of death and confounding from any one of several sources.

Eye Neoplasms↗