Search PubMed⌕ Search

Biomedical subjects

R Kaufman

Publications and source records attributed to R Kaufman.

At least 55 records · Page 3Linked to original sources
PubMed1990

Association of disease-free survival and percent of ideal dose in adjuvant breast chemotherapy.

The relationship between percent of ideal dose and disease-free survival was examined in 256 Stage II and III patients who participated in a 2-year breast adjuvant chemotherapy trial consisting of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) given postoperatively. When analyzed analogously to previous work, the results confirmed a dose-response relationship: that is, there appeared to be an improved disease-free survival for patients receiving higher doses of adjuvant chemotherapy. The major criticism of such an analysis is its bias. This bias was addressed by considering only patients who were still receiving therapy at 6, 12, and 24 months; then, the dose-response relationship was no longer seen. Although causality cannot be inferred, the apparent differences in disease-free survival among the dose groups can be attributed to recurrences in the first 2 years among patients receiving lower doses of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

A naturally occurring gamma globin gene mutation enhances SP1 binding activity.

Transcription of the human fetal globin genes in erythroid cells is tightly regulated during different stages of development and differentiation. Two naturally occurring mutations 202 base pairs upstream of the duplicated gamma globin genes are associated with incorrectly regulated gamma globin gene gene expression; elevated levels of fetal globin are synthesized during adult life. A C-to-G base substitution upstream of the G gamma-globin gene is highly correlated with a dramatic increase in gene expression. It increases the similarity of the region to the consensus Sp1 recognition site. We determined that the mutated DNA had a 5- to 10-fold-higher affinity for Sp1 than did normal gamma globin gene sequence. We also observed a reduction in normal factor-binding activity. A different substitution at -202, C to T, upstream of the A gamma-globin gene was associated with a more moderate increase in fetal globin expression. This mutation decreased the similarity of the sequence to an Sp1 recognition site. We determined that it did not result in enhanced Sp1 binding but did alter normal factor binding. We suggest that these changes in nuclear protein-binding properties detected in vitro are responsible for the enhanced gamma globin gene expression found in -202 G gamma beta + patients with hereditary persistence of fetal hemoglobin.

Base Sequence↗
PubMed1989

Substituting diagnostic services. New tests only partly replace older ones.

Hospitals' patterns of ancillary service use were examined to determine whether new technologies replace older, more outmoded technologies, and to explore the factors associated with adoption of newer services and abandonment of older services. Annual inpatient use of five pairs of ancillary services was measured for 1978 through 1980 at 63 hospitals in five regions. The diagnostic test pairs consisted of one well-established diagnostic test and one newer service that could largely substitute for the older one and included (1) oral cholecystogram and gallbladder ultrasound; (2) brain scan and computed tomographic head scan; (3) skull roentgenogram and brain scan; (4) bone survey and bone scan; and (5) blood type/cross and type/screen. Use of gallbladder ultrasound increased significantly after its adoption, with small decreases in the use of oral cholecystogram, its paired test. For the other newer tests examined, increased use was not accompanied by significantly decreased use of the paired older service. The strongest predictors of change in patterns of test use were hospital size, number of residencies, occupancy, urban location, and the proportion of specialists on staff. We conclude that diffusion of new diagnostic services occurs gradually and often without concomitant decrease in older, outmoded services; new services generally seem to complement rather than substitute for older ones. Larger hospitals with a greater teaching commitment make a faster transition to the use of new technologies and the abandonment of older ones.

Diagnostic Services↗
PubMed1989

Synthesis, in vitro acetylcholine-storage-blocking activities, and biological properties of derivatives and analogues of trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol).

Eighty-four analogues and derivatives of the acetylcholine-storage-blocking drug trans-2-(4-phenylpiperidino)-cyclohexanol (vesamicol) were synthesized, and their potencies were evaluated with the acetylcholine active-transport assay utilizing purified synaptic vesicles from Torpedo electric organ. The parent drug exhibits enantioselectivity, with (-)-vesamicol being 25-fold more potent than (+)-vesamicol. The atomic structure and absolute configuration of (+)-vesamicol were determined by X-ray crystallography. The absolute configuration of (-)-vesamicol is 1R,2R. Structure-activity evidence indicates that (-)-vesamicol does not act as an acetylcholine analogue. Alterations to all three rings can have large effects on potency. Unexpectedly, analogues locking the alcohol and ammonium groups trans-diequatorial or trans-diaxial both exhibit good potency. A potent benzovesamicol family has been discovered that is suitable for facile elaboration of the sort useful in affinity labeling and affinity chromatography applications. A good correlation was found between potencies as assessed by the acetylcholine transport assay and LD50 values in mouse.

Acetylcholine↗
PubMed1989

Fractional vesamicol receptor occupancy and acetylcholine active transport inhibition in synaptic vesicles.

Vesamicol [(-)-(trans)-2-(4-phenylpiperidino)cyclohexanol] receptor binding and inhibition of acetylcholine (AcCh) active transport by cholinergic synaptic vesicles that were isolated from Torpedo electric organ were studied for 23 vesamicol enantiomers, analogues, and other drugs. Use of trace [3H]vesamicol and [14C]AcCh allowed simultaneous determination of the concentrations of enantiomer, analogue, or drug required to half-saturate the vesamicol receptor (Ki) and to half-inhibit transport (IC50), respectively. Throughout a wide range of potencies for different compounds, the Ki/IC50 ratios varied from 1.5 to 24. Compounds representative of the diverse structures studied, namely deoxyvesamicol, chloroquine, and levorphanol, were competitive inhibitors of vesamicol binding. It is concluded that many drugs can bind to the vesamicol receptor and binding to only a small fraction of the receptors can result in AcCh active transport inhibition. Possible mechanisms for this effect are discussed.

Acetylcholine↗
PubMed1989

One-year suppression of frequent recurrences of genital herpes with oral acyclovir.

A double-blind, placebo-controlled study was undertaken to evaluate the long-term efficacy and safety of oral acyclovir suppressive therapy over a 1-year period. Results from the multicenter trials, based on a total of 261 patients with frequently recurring genital herpes, were analyzed. Of the patients enrolled in the study, 131 received oral acyclovir capsules (800 mg) daily and 130 received placebo capsules. Medication was taken twice daily. Analysis of data from patients who completed a full year of therapy demonstrated that only 5% of patients receiving placebo were free from recurrences, as compared with 46% of acyclovir recipients. The mean number of recurrences for patients on acyclovir therapy was 1.8, as compared with a rate of 8.7 recurrences for the placebo group over the course of the year. The mean time to the first recurrent herpes outbreaks was 19 days for the placebo group and 274 days for the acyclovir-treated patients. There were no significant differences between the two groups in laboratory data or in the frequency or nature of side effects reported. Daily administration of acyclovir capsules for 1 year is a safe and effective therapy for control of frequent recurrences of genital herpes.

Acyclovir↗
PubMed1989

Septic ischial bursitis in systemic lupus erythematosus presenting as a perirectal mass.

We describe a patient with systemic lupus erythematosus with dissection of a large ischial bursal cyst which presented as a perirectal mass. Dissecting bursal and articular synovial cysts are known to cause multiple complications including a number of "pseudosyndromes" such as pseudothrombophlebitis. The cyst in this case was initially thought to represent a perirectal abscess and we propose the term "pseudoperirectal abscess" to describe this condition. This cyst was found to be infected and required an extended course of antibiotics and bursectomy.

Abscess↗
PubMed1988

Episodic twice-daily treatment for recurrent genital herpes.

A new dosage regimen of orally administered acyclovir, 800 mg twice daily for five days, for the treatment of recurrent genital herpes was compared with the standard dosage of 200 mg given five times per day. A double-blind study of 157 patients was used to evaluate the safety and efficacy of both regimens. The new regimen was well tolerated, more convenient, and as effective as the standard dosage. In male patients, the new regimen may be more effective than the standard regimen of 200 mg given five times per day to treat lesions that are already present.

Acyclovir↗
PubMed1988

Prolonged continuous versus intermittent oral acyclovir treatment in normal adults with frequently recurring genital herpes simplex virus infection.

In Year 1 of this two-year trial, patients with six or more genital herpes recurrences in the past year received suppressive treatment with either acyclovir, 400 mg, or placebo, orally twice daily for one year, and physician-documented recurrences were treated with open-labeled acyclovir, 200 mg, orally five times per day for five days (acute treatment). In Year 2, patients received open-labeled acyclovir treatment either with daily suppressive therapy or intermittent acute therapy. Among 683 patients who completed two years of treatment, 348 received continuous suppressive treatment for two years, 276 received acute treatment in Year 1 and suppressive treatment in Year 2, 24 received suppressive treatment in Year 1 and acute treatment in Year 2, and 35 received acute treatment for two years. Patient groups receiving intermittent acute acyclovir treatment experienced means of 7.0 to 12.6 recurrences/year during treatment as compared with 1.4 to 1.9 recurrences/year among groups receiving continuous suppressive treatment. No patients who received acute treatment remained recurrence-free for two years as compared with 29 percent of patients receiving continuous acyclovir suppression for two years. There was no evidence of cumulative toxicity detected by clinical, hematologic, or blood chemistry evaluations performed monthly in Year 1 and quarterly in Year 2. Suppressive oral acyclovir therapy remained effective and well-tolerated in this two-year trial.

Acyclovir↗
PubMed1988

Ascorbic acid specifically increases type I and type III procollagen messenger RNA levels in human skin fibroblast.

In cultured human skin fibroblasts, ascorbic acid stimulates collagen production with no apparent change in the intracellular degradation of newly synthesized procollagen. To understand the basis for this effect, we measured the steady-state levels of type I and type III procollagen mRNAs in cells treated with ascorbic acid. A three- to fourfold increase in collagen synthesis was associated with a two- to threefold increase in the levels of mRNAs for both type I and type III procollagens. These effects of ascorbic acid are explained by a translational control linked either to procollagen gene transcription or mRNA degradation.

Ascorbic Acid↗
PubMed1987

Acetylcholine receptor antibodies in myasthenia gravis: use of a qualitative assay for diagnostic purposes.

We have modified the techniques of Lindstrom and of Tindall to measure serum acetylcholine receptor antibody using human antigen bound to 125I-alpha Bungarotoxin. By using 10 microliters of serum and precipitating antigen-antibody complexes with an excess of staph A, we found that only one out of 43 patients with clinically diagnosed active generalized Myasthenia Gravis had no antibodies. In pooling these results with the results of tests done for diagnostic purposes we found positive results in 54/55 generalized active MG, 8/21 MG in remission, 16/37 ocular MG and 0/55 healthy controls. Two out of 38 non MG were also positive and their clinical diagnosis of botulism and penicillamine treated rheumatoid arthritis have been confirmed by a one year follow-up. Most of these sera were also tested for reactivity with fetal calf AchR. Six out of 49 samples positive with the human receptor were negative with calf receptor. We conclude that our technique is extremely useful for the diagnosis of Myasthenia Gravis and that fetal calf antigen cannot replace human antigen in the assay.

Animals↗
PubMed1987

Regulation of erythropoietin production in a human hepatoblastoma cell line.

Production of immuno and biologically active erythropoietin was documented to occur in the human hepatoblastoma cell line HepG-2. The expression of the erythropoietin gene was further verified by Northern blot analysis using a single stranded RNA probe. In vitro studies showed that erythropoietin production by these cells was not stimulated by hypoxia or cobalt chloride, but was related to the proliferative activity of the cells in culture. In addition it was found that the secretion of erythropoietin was almost completely abrogated by tunicamycin, an inhibitor of N-linked glycosylation. This effect of tunicamycin was also observed in a permanently transfected cell line that secretes erythropoietin in large quantities.

Animals↗
PubMed1987

Disability evaluation in arthritis patients.

During the working years, rheumatic conditions are the foremost cause of disability in the United States. Disability evaluation for Social Security applicants and Workers' Compensation patients is commonplace in orthopedic practices. Yet, formal education in this aspect of patient care is rare both during and after residency. Because of a lack of understanding and sophistication the physician who knows the patient better than any other evaluator often play a minor role in the determination of disability. Disability Evaluation Under Social Security--A Handbook for Physicians lists the medical criteria necessary for qualification. Severely disabled arthritis patients will not always fit into these various categories and may have to be considered under the rule of medical equivalency. Workers' Compensation statutes vary somewhat from state to state but generally include disability criteria. Familiarity with these criteria and the process involved will allow the orthopedist to communicate more meaningfully with administrators and will reduce much of the frustration and some of the cost inherent in this system. When subjective complaint (illness) is in excess of apparent organic pathology (disease), team evaluation under the direction of the treating physician will help sort out the dilemma and develop a treatment plan. One hopes that this will bring the illness more in line with the disease, and thus reduce the disability.

Disability Evaluation↗