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Biomedical subjects

S Wolff

Publications and source records attributed to S Wolff.

At least 73 records · Page 4Linked to original sources
PubMed1993

Effects of histamine type 2-receptor antagonists cimetidine and famotidine on left ventricular systolic function in chronic congestive heart failure.

Twelve patients with stable congestive heart failure and left ventricular dysfunction were enrolled in a double-blind, randomized crossover trial of famotidine, cimetidine and placebo to determine whether histamine type 2 (H2) antagonists adversely affect left ventricular systolic performance. Two-dimensional echocardiograms were obtained at baseline, after 4 days of oral treatment with standard doses of famotidine and cimetidine, and placebo, and at the conclusion of the trial. The baseline mean ejection fraction was 19 +/- 7%. The changes in ejection fraction were +2 +/- 11% (95% confidence interval [CI] -5 to 9%) with famotidine, +3 +/- 10% (95% CI -3 to 10%) with cimetidine, and -3 +/- 7% (95% CI -8 to 2%) with placebo. There were no significant differences in changes in ejection fraction among the 3 experimental treatments (p = 0.22; analysis of variance). The changes in end-systolic wall stress/volume ratios from baseline were +6 +/- 21% (95% CI -6 to 18%) for famotidine, +8 +/- 29% (95% CI -8 to 25%) for cimetidine, and +2% +/- 29% (95% CI -15 to 18%) for placebo (p = 0.69; analysis of variance). No patient had a worsening of symptoms during therapy. Despite previous reports that H2 antagonists may depress left ventricular systolic function, at standard doses these agents result in no decrease in left ventricular systolic function in patients with chronic congestive heart failure.

Aged↗
PubMed1993

Depletion of cellular polyamines by alpha-difluoromethylornithine increases 1,3-bis(2-chloroethyl)-1-nitrosourea-induced sister-chromatid exchanges.

Treatment of cells with alpha-difluoromethylornithine (DFMO), which leads to the intracellular depletion of the polyamines putrescine and spermidine, is known to increase the cell killing induced by the DNA cross-linking chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). This has been attributed to a change in DNA conformation that is related to the intracellular polyamine content and a concomitant change in accessibility of BCNU to reactive sites in DNA. Cytogenetic experiments were previously carried out showing that DFMO pretreatment also increased sister chromatid exchanges (SCEs) induced by BCNU. Subsequently, there was difficulty in repeating this phenomenon, which led to retraction of the results. More recent information indicates, however, that a change in protocol occurred between the time of the original experiments and the repeat experiments. Because cell killing by genotoxic agents, such as X-rays, can be related to cytogenetic damage, and agents that cause deformation of DNA do lead to SCEs, experiments have now been carried out to see whether or not the subtle deformation caused by polyamine depletion could, indeed, lead to the induction of increased SCEs by BCNU, as had been originally postulated. When the experiments were carried out with the original protocols, pretreatment with DFMO did increase BCNU-induced SCEs. Modification of the protocols, especially washing of the cells before the addition of BCNU, which reduces the toxicity, reduced the DFMO effect and in some experiments even obliterated it.

Animals↗
PubMed1993

Left ventricular hypertrophy and morphology in familial hypertrophic cardiomyopathy associated with mutations of the beta-myosin heavy chain gene.

OBJECTIVES: The purpose of this study was to determine the spectrum of left ventricular hypertrophy and ventricular morphology in adults with hypertrophic cardiomyopathy due to mutations of the beta-myosin heavy-chain gene. BACKGROUND: Although echocardiography is an important test in diagnosing hypertrophic cardiomyopathy, the lack of an independent diagnostic criterion has been an obstacle in determining the full echocardiographic spectrum of this disease. Mutations in the beta-myosin heavy chain gene occur in approximately 50% of familial cases; in members of families with a known mutation, the diagnosis can be made with certainty. METHODS: Echocardiograms from 39 genetically affected and 30 genetically unaffected adult family members over age 16 years from 10 families were analyzed. Left ventricular wall thickness was measured at 10 separate locations, and the presence of systolic anterior motion of the mitral valve, right ventricular hypertrophy and left ventricular morphology was evaluated independently by three separate observers without knowledge of the genetic diagnosis. RESULTS: The mean maximal wall thickness in the genetically affected group was 24 +/- 8 mm (range 11 to 40), compared with 11 +/- 2 mm (range 7 to 16) in the unaffected group (p < 0.0001). Systolic anterior motion of the mitral valve or chordae tendineae with or without leaflet-septal contact was present in 62% of the affected group and in none of the unaffected group. The morphologic finding of reversed septal curvature was present in 79% of the affected group and in none of the unaffected group. Seventy-seven percent of patients in the affected group had a septal/free wall ratio > or = 1.3 compared with 6% in the unaffected group, with a septal/posterior wall ratio > or = 1.3 associated with only a 55% probability of being affected. CONCLUSIONS: The two-dimensional echocardiographic spectrum of hypertrophic cardiomyopathy in a genetically defined adult population is broad. Previous echocardiographic criteria may be too strict to diagnose the disease in some patients who are genetically affected and therefore at risk for adverse events related to the disease. Ultimately, genetic testing may supersede echocardiography in diagnosing hypertrophic cardiomyopathy.

Adolescent↗
PubMed1993

Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia.

PURPOSE: To determine the toxicities and maximum-tolerated dose of cyclosporine (CsA) administered with daunorubicin as a modulator of multidrug resistance (MDR) in acute leukemia, and to evaluate response to treatment and its relationship to mdr1 gene expression. PATIENTS AND METHODS: Patients with poor-risk acute myeloid leukemia (AML) received sequential treatment with cytarabine (3 g/m2/d intravenously [i.v.]) days 1 to 5, and daunorubicin (45 mg/m2/d) plus CsA as a 72-hour continuous infusion (CI) days 6 through 8 in a phase I/II trial. A loading dose of CsA administered over 1 to 2 hours preceded the CI. CsA dose escalations ranged from 1.4 to 6 mg/kg (load) and 1.5 to 20 mg/kg/d (CI). Whole-blood concentrations of CsA were monitored by immunoassay; plasma concentration of daunorubicin and daunorubicinol were determined by high-pressure liquid chromatography (HPLC). Specimens were analyzed for P-glycoprotein expression, and results confirmed by a quantitative RNA polymerase chain reaction (PCR) assay for the mdr1 gene transcript. RESULTS: Forty-two patients are assessable for toxicity and response. P-glycoprotein was detected in 70% of cases. Dose-dependent CsA toxicities included nausea and vomiting (22%), hypomagnesemia (61%), burning dysesthesias (21%), and prolongation of myelosuppression. Transient hyperbilirubinemia developed in 62% of treatment courses and was CsA-dose-dependent. Reversible azotemia occurred in three patients receiving concurrent treatment with potentially nephrotoxic antibiotics. Steady-state blood concentrations of CsA > or = 1,500 ng/mL were achieved in all patients receiving CI doses > or = 16 mg/kg/d. Mean plasma daunorubicin, but not daunorubicinol, levels were significantly elevated in patients who developed hyperbilirubinemia (P = .017). Twenty-six (62%) patients achieved a complete remission (CR) or restored chronic phase and three patients achieved a partial remission (PR) for an overall response rate of 69% (95% confidence interval, 54% to 84%). The response rate was higher in patients who developed hyperbilirubinemia (P = .001), whereas MDR phenotype did not influence response to treatment. Among five patients with MDR-positive leukemia, cellular mdr1 mRNA decreased (n = 1) or was absent from relapsed specimens (n = 4), while mdr1 RNA remained undetectable at relapse in two patients who were MDR-negative before treatment. CONCLUSION: High doses of CsA, which achieve blood concentrations capable of reversing P-glycoprotein-mediated anthracycline resistance in vitro, can be incorporated into induction regimens with acceptable nonhematologic toxicity. Transient hyperbilirubinemia occurs commonly with CsA administration and may alter daunorubicin pharmacokinetics. Recommended doses of CsA for phase II and III trials are a load of 6 mg/kg and CI of 16 mg/kg/d.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Indications of repair of radon-induced chromosome damage in human lymphocytes: an adaptive response induced by low doses of X-rays.

Naturally occurring radon is a relatively ubiquitous environmental carcinogen to which large numbers of people can be exposed over their lifetimes. The accumulation of radon in homes, therefore, has led to a large program to determine the effects of the densely ionizing alpha particles that are produced when radon decays. In human lymphocytes, low doses of X-rays can decrease the number of chromatid deletions induced by subsequent high doses of clastogens. This has been attributed to the induction of a repair mechanism by the low-dose exposures. Historically, chromosome aberrations induced by radon have been considered to be relatively irreparable. The present experiments, however, show that if human peripheral blood lymphocytes are irradiated with low doses of X-rays (2 cGy) at 48 hr of culture, before being exposed to radon at 72 hr of culture, the yield of chromatid deletions induced by radon is decreased by a factor of two. Furthermore, the numbers of aberrations per cell do not follow a Poisson distribution but are overdispersed, as might be expected because high-linear energy transfer (high LET) alpha particles have a high relative biological effectiveness compared to low-LET radiations such as X-rays or gamma rays. Pretreatment with a low dose of X-rays decreases the overdispersion and leads to a greater proportion of the cells having no aberrations, or lower numbers of aberrations, than is the case in cells exposed to radon alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1991

Both cross-links and monoadducts induced in DNA by psoralens can lead to sister chromatid exchange formation.

The relative importance of DNA-DNA cross-links and bulky monoadducts in sister chromatid exchange (SCE) formation was investigated in three human fibroblast cell lines with different repair capabilities. These cell lines included normal cells, which can repair both classes of lesions; xeroderma pigmentosum (XP) cells, which cannot repair either psoralen-induced cross-links or monoadducts; and an XP revertant that repairs only cross-links and not monoadducts. SCEs were induced by two psoralen derivatives, 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) and 5-methylisopsoralen (5-MIP). After activation with long-wave ultraviolet light, HMT produces cross-links and monoadducts in DNA, whereas 5-MIP produces only monoadducts. In normal human cells both psoralens induced SCEs, but if cells were allowed to repair for 18 h before bromodeoxyuridine (BrdUrd) was added for SCE analysis, the SCE frequency was significantly reduced. XP cells showed an SCE frequency that remained high regardless of whether SCEs were analyzed immediately after psoralen exposure or 18 h later. In the XP revertant that repairs only cross-links, both psoralens induced a high yield of SCEs when BrdUrd was added immediately after psoralen treatment. When XP revertant cells were allowed 18 h to repair before addition of BrdUrd, the SCEs induced by HMT were greatly reduced, whereas those induced by 5-MIP were only slightly reduced. These observations indicate that both cross-links and monoadducts are lesions in DNA that can lead to SCE formation.

Bromodeoxyuridine↗
PubMed1991

'Schizoid' personality in childhood and adult life. II: Adult adjustment and the continuity with schizotypal personality disorder.

In a controlled follow-up study into adulthood of 32 children diagnosed 'schizoid', three-quarters fulfilled DSM-III criteria for schizotypal personality disorder and two developed schizophrenia. Overall their psychosocial adjustment was somewhat, but not markedly, worse than that of other attenders at a child psychiatry clinic, although as a group they remained more solitary, lacking in empathy, oversensitive, with odd styles of communicating, and often with circumscribed interests.

Adolescent↗
PubMed1991

'Schizoid' personality in childhood and adult life. III: The childhood picture.

The childhood case records of 32 'schizoid' children and 32 matched controls were analysed. 'Schizoid' children were characterised by solitariness, unusual fantasies, special interests, and specific developmental delays, especially of language-related skills. They were of average or above-average IQ, and half presented with other, common, child psychiatric syndromes. It is important to distinguish 'schizoid' children from children with reactive psychiatric disorders.

Adolescent↗
PubMed1991

Biological dosimetry with cytogenetic endpoints.

The induction of chromosome aberrations in the lymphocytes of people who have been exposed to ionizing radiation has provided a much-used quantifiable biological dosimeter with which it is possible to obtain a reliable estimate of the dose of radiation to which the people have been exposed. The induction of aberrations by truly radiomimetic (non-S-dependent) chemicals should also be capable of leading to an estimate of the amount of the chemical that has reached the nuclei of the target cells, and thus give a measure of the damage inflicted. In this case, however, it is not yet possible to relate aberration yield to the initial exposure in a quantifiable manner. Other cytogenetic endpoints, such as micronuclei and sister chromatid exchanges (SCEs), can also be used to estimate whether or not exposures have occurred. Since micronuclei are the result of broken or lagging chromosomes, they too can be used to estimate the dose of ionizing radiation to which a person has been exposed. The use of aberrations or micronuclei for estimating the dose of S-dependent chemicals, however, still remains problematical. SCEs, which are not readily induced by ionizing radiations, have proved to be the most sensitive mammalian endpoint for determining exposure to such S-dependent chemicals. Nevertheless, the utility of SCEs, or any cytogenetic endpoint for that matter, for estimating the dose of any S-dependent chemical has not been shown because of dosimetric problems and because DNA repair can remove many of the adducts before the cells enter S, both of which preclude the use of these endpoints as biological dosimeters for such agents.

Chromosome Aberrations↗
PubMed1990

Long-term efficacy of nitroglycerin patch in stable angina pectoris.

Subchronic and chronic efficacy of a 10 mg of nitroglycerin (NTG) patch was studied in 30 patients with stable angina pectoris. The trial consisted of 2 periods of study: 1 period of 2 months with a double-blind, crossover, placebo-controlled design and a second period of open treatment with verum patch. Two 7-day washout periods were performed at entry and at the end of the study. Efficacy was evaluated by clinical assessment of anginal attacks and NTG consumption and by means of multistage treadmill exercise testing. Exercise tests were performed at time 0 (24 hours from application of last patch), at 4 and 12 hours after dosing at the end of first 7-day washout, at the end of the first month of treatment, at the end of the second month of treatment after crossover, at the end of 3 months of treatment with active patch and at the end of the second 7-day washout period. Statistics were obtained by multivariate analysis of difference. In 27 patients whose records were available for final analysis the daily attacks of angina and NTG consumption decreased significantly during both the subchronic and chronic phases of the trial compared with placebo (p less than 0.001). Subchronic study showed significant improvement of maximal exercise duration, time to onset of angina, time to ST-segment depression of 1.0 mm, time to regression of angina and time to regression of ST depression, compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1990

Family characteristics of autistic children: a further report.

The personality features of parents of a group of 21 well-functioning autistic children have been described previously. The main characteristics of these parents were social gaucheness and a tendency towards the single-minded pursuit of special, often intellectual, interests. We now present the agreement between research interviewers and clinician in the diagnosis of these parents as schizoid, together with clinical details of those parents rated by both as having definite schizoid traits. The educational functioning of the siblings of the autistic children compared with that of siblings of a matched control group is also reported.

Achievement↗
PubMed1990

Direct evidence of a functional separation of alloreactive T lymphocytes from bystander cells infiltrating rat allografts. Interleukin 2 receptor-positive cells reacting with the monoclonal antibody ART 18 mediating second-set rejection.

In this study we examined the functional capacity of unseparated, IL-2R positive and IL-2R negative leukocytes infiltrating BN rat hearts or kidneys grafted into allogeneic LEW rats. Upon adoptive transfer into syngeneic LEW recipients, splenocytes or day-3 graft infiltrate cells of either cardiac or renal transplants were ineffective to alter BN cardiac test graft survival (controls 7.8 +/- 0.8 day). However, adoptive transfer of day-5 heart infiltrate cells resulted in a delay of test graft rejection (9.4 +/- 0.7 day, P less than 0.001), while day-5 kidney-graft-infiltrating cells produced second set rejection (6.2 +/- 0.5, P less than 0.001). Specificity controls of day-5 cells infiltrating DA heart or kidney grafts rejected at 7.8 +/- 0.8 or 7.7 +/- 0.5 days. Following separation into IL-2R positive and negative subpopulations by use of the mAB ART 18, IL-2R positive but not IL-2R negative cells caused second set rejection in both the renal and the cardiac model (6.2 +/- 0.4, respectively, 6.3 +/- 0.5 days, P less than 0.001 or P less than 0.005). Furthermore, in the kidney model IL-2R positive nylon-wool nonadherent cells also caused second set rejection (6.2 +/- 0.4, P less than 0.005) suggesting that IL-2R positive T cells present in the graft at maximal infiltration are the mediators of rejection. Thus, it appears that these cells can be phenotypically and functionally separated from bystander cells.

Animals↗