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Biomedical subjects

S Wolff

Publications and source records attributed to S Wolff.

At least 91 records · Page 5Linked to original sources

Linear drive birdcage coil for 23Na human head studies at 1.5 T.

Progress in the development of non-proton NMR applications in medical research has been hampered by the generally low sensitivity of these nuclides as well as the lack of instrumentation readily available for studying these spins. For example, custom head coils suitable for sodium imaging of the human head are either not available or very expensive, making research startup costs high or impossible. Herein the detailed design and construction of a research 23Na head coil for MRI imaging is presented. 23Na NMR images collected with the coil are presented as well as a discussion of design modifications for other nuclides.

Head↗

Intravenous amiodarone in acute anterior myocardial infarction: a controlled study.

A randomized, single-blind controlled study intended to assess the potential benefits of intravenous amiodarone in anterior myocardial infarction is presented. Three hundred nineteen patients entered the study, 159 received amiodarone infusion, and 160 received glucose-insulin-potassium (GIK) infusion. Basal characteristics were similar in the two experimental groups, who were randomized on a consecutive basis. Exclusion criteria were shock or pulmonary edema, hypotension, inferoposterior infarction, bradycardia, antrioventricular block, severe diabetes, and other major diseases. Patients aged 27 to 70 years, with a Q-wave anterior infarction, initiated 12-40 hours earlier at the time of admission, entered the trial. Other entry criteria were heart rate higher than 80 beats/min and systolic blood pressure higher than 100 mmHg. Amiodarone was administered in saline infusion 10-20 mg/kg, within 4 to 10 hours, through a central vein. GIK infusion consisted of 150-300 g of glucose, 25-50 IU of insulin, and 80-120 mEq of KCl in 1000 cc of water at a rate of 1.5-2.0 ml/g/hour. Both groups received digitalis, nitrates, sedatives, and diuretics as needed. Although individually the major endpoints of death, reinfarction, and sustained supraventricular and ventricular arrhythmias did not differ significantly, each was less in the amiodarone group than in the control, and the sum of all adverse events was significantly lower for the amiodarone patients (p less than 001). Heart failure and conduction disturbances were not different in the two groups. This study shows that amiodarone, with its vasodilating and antiarrhythmic properties, may be beneficial in acute anterior infarction, but further studies on larger populations will be necessary in order to show a reduction of mortality rate.

Acute Disease↗

Inhibition of the adaptive response of human lymphocytes to very low doses of ionizing radiation by the protein synthesis inhibitor cycloheximide.

When human lymphocytes are preirradiated with 1 cGy of X-rays, the cells become less sensitive to subsequent exposures to high doses of about 150 cGy in that approximately one-half as many chromatid aberrations are induced as expected. This adaptation has been attributed to the induction of repair enzymes (proteins) some 4-6 h after the initial low-dose exposure. Experiments have now been carried out showing that application of the protein synthesis inhibitor cycloheximide at this time, but not earlier, prevents the adaptive response.

Adaptation, Physiological↗

Antipain-mediated suppression of X-ray-induced chromosomal aberrations in human lymphocytes.

The protease inhibitor antipain is known to modulate the number of chromosomal aberrations induced by the S-phase-dependent alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Experiments have now been carried out to see if antipain might also effect the yield of aberrations induced by X-rays, which are S-independent and thus produce chromosomal aberrations by a different mechanism. The results show that human lymphocytes exposed to 0.4 or 1.5 Gy of X-rays at 48 h of culture and fixed at 3, 6, 8, 10 or 12 h thereafter contain 27-52% fewer chromatid breaks if the cells are also treated with antipain before irradiation. Because previous studies postulated that antipain could affect the induction of chromosomal aberrations by suppressing free radical reactions within cells, we also tested whether antipain affects X-ray-induced aberrations when present only during the time of irradiation, as is the case for free radical scavengers, such as L-cysteine. The results indicate that, in contrast to L-cysteine, antipain can suppress the induction of X-ray-induced aberrations even when administered as late as 2 h after irradiation, suggesting that the effects of antipain on aberrations are not attributable to its interference with short-lived radicals within the cells. Although the exact mechanism whereby antipain decreases the yield of chromosome aberrations induced by the S-independent agent X-rays is unknown, these data indicate that the formation of chromosome aberrations by S-independent agents too can involve an antipain-sensitive process.

Antipain↗

Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer.

Three hundred twenty-five women with metastatic adenocarcinoma of the breast who had failed one prior chemotherapeutic regimen for advanced disease were randomized to receive 14 mg/m2 of mitoxantrone or 75 mg/m2 of doxorubicin intravenously (IV) every 3 weeks. Enrollment was closed on October 31, 1984, after 165 patients were randomized to mitoxantrone and 160 patients to doxorubicin. Patients randomized to the two treatment groups were compared for response rate, duration of response, time to progression or death, time to treatment failure (TTF), and survival. The response rate to mitoxantrone was 20.6%, to doxorubicin 29.3% (P = .07). The median response duration was 151 days for the mitoxantrone group and 126 days for the doxorubicin group (P = .16). The median TTF was 70 days in the mitoxantrone group and 104 days in the doxorubicin group (P = .36). The median survival of patients initially randomized to receive mitoxantrone was 273 days; for doxorubicin 268 days (P = .40). There were three responses among 77 patients crossed over to mitoxantrone after initial treatment with doxorubicin. The major dose-limiting toxicity for both drugs was leukopenia. There was significantly less severe and less frequent toxicity with mitoxantrone administration. Severe nausea and vomiting occurred in 9.5% of mitoxantrone patients and 25.3% of doxorubicin patients (P less than .001). The incidence of severe stomatitis and mucositis was 0.6% in the mitoxantrone group and 8.4% in the doxorubicin group (P = .001). Severe alopecia occurred in 5.1% of mitoxantrone patients and 61.0% of doxorubicin patients (P less than .001). A life-table comparison of the cumulative dose to the development of a cardiac event showed that mitoxantrone had significantly less cardiotoxicity than doxorubicin (P = .0005). This study demonstrates that mitoxantrone is active as a single agent in the treatment of metastatic breast cancer. Compared with doxorubicin it appears to be marginally less active and significantly less toxic. We conclude that mitoxantrone can be used alone or with other standard drugs to palliate the symptoms of metastatic breast cancer, especially in settings where drug toxicity is an important consideration.

Adenocarcinoma↗

Human lymphocytes exposed to low doses of ionizing radiations become refractory to high doses of radiation as well as to chemical mutagens that induce double-strand breaks in DNA.

Human lymphocytes exposed to low doses of ionizing radiation from incorporated tritiated thymidine or from X-rays become less susceptible to the induction of chromatid breaks by high doses of X-rays. This response can be induced by 0.01 Gy (1 rad) of X-rays, and has been attributed to the induction of a repair mechanism that causes the restitution of X-ray-induced chromosome breaks. Because the major lesions responsible for the induction of chromosome breakage are double-strand breaks in DNA, attempts have been made to see if the repair mechanism can affect various types of clastogenic lesions induced in DNA by chemical mutagens and carcinogens. When cells exposed to 0.01 Gy of X-rays or to low doses of tritiated thymidine were subsequently challenged with high doses of tritiated thymidine or bleomycin, which can induce double-strand breaks in DNA, or mitomycin C, which can induce cross-links in DNA, approximately half as many chromatid breaks were induced as expected. When, on the other hand, the cells were challenged with the alkylating agent methyl methanesulfonate (MMS), which can produce single-strand breaks in DNA, approximately twice as much damage was found as was induced by MMS alone. The results indicate that prior exposure to 0.01 Gy of X-rays reduces the number of chromosome breaks induced by double-strand breaks, and perhaps even by cross-links, in DNA, but has the opposite effect on breaks induced by the alkylating agent MMS. The results also show that the induced repair mechanism is different from that observed in the adaptive response that follows exposure to low doses of alkylating agents.

Adult↗

Personality characteristics of parents of autistic children: a controlled study.

Parents of 21 autistic children and of 21 children with other handicaps, matched for sex, age, IQ and father's occupation, were interviewed with a schedule known to discriminate between schizoid and non-schizoid people. Ratings were reliable and the interviewers remained "blind". Parents of autistic children, especially fathers, were significantly more often rated as having schizoid traits. They were also more intellectual.

Adolescent↗

A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma.

Three hundred thirty-one women with metastatic breast cancer were randomized to receive combination chemotherapy with either cyclophosphamide, Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ), and fluorouracil (CNF) or cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and fluorouracil (CAF). Patients could not have had prior chemotherapy, although adjuvant chemotherapy was acceptable. Initial doses were 500 mg/m2 of cyclophosphamide and 500 mg/m2 of fluorouracil with either 10 mg/m2 of mitoxantrone or 50 mg/m2 of doxorubicin, administered intravenously (IV) on day 1 and repeated every 3 weeks. There were no statistically significant differences in pretreatment or prior therapy characteristics between the groups. For patients assigned to the CNF and CAF groups, respectively, 25 (18%) were premenopausal, 39 (40%) were estrogen receptor (ER) negative, 39 (38%) had a disease-free interval less than 1 year, and 24 (26%) had received prior adjuvant chemotherapy. All patients were compared for response rate, duration of response, time to progression or death, time to treatment failure (TTF), and survival. None of these parameters were statistically significant favoring one regimen over the other. The response rate (complete [CR] and partial response [PR]) was 29% for the CNF group (95% confidence interval of 22% to 37%) and 37% for the CAF group (95% confidence interval of 29% to 45%). The median response duration and TTF were 171 days and 125 days for the CNF group and 254 days and 147 days for the CAF group, respectively. The median survival times for the CNF group and the CAF group were 377 and 385 days, respectively. The major dose-limiting toxicity for both regimens was leukopenia, manifested as granulocytopenia. The incidence of stomatitis/mucositis was 10% in the CNF group and 19% in the CAF group. Alopecia occurred in 49% of CNF patients (severely for 4%) and in 86% of CAF patients (severely for 39%). Nausea/vomiting occurred in 80% of CNF patients and in 81% of CAF patients; the degree of severity was also comparable. There was significantly less cardiotoxicity observed in the CNF group compared with the CAF group. Although CNF is somewhat less effective in overall response rate, survival curves are identical. CNF can be offered to patients who reject anthracycline-containing regimens because of fear of alopecia.

Adult↗

Effect of bezafibrate on serum lipids in normo- and spontaneously hyperlipidemic rats.

Rats, due to their availability and ease of handling, are a frequently used animal model for studying the effects of drugs on lipid metabolism. Hypolipidemic effects showed great variations in different studies. We investigated the effect of bezafibrate on serum concentrations of cholesterol and triglycerides in different strains of rats from several breeders. Under these conditions Lewis rats seemed to be the most suitable strain to investigate drug effects on cholesterol in serum. A hypercholesterolemic male Lewis rat found in a screening program was mated with normolipidemic female Lewis rats. The hyperlipidemia was found in some of the male and female offspring. Cholesterol and triglycerides were dramatically elevated in older animals. Bezafibrate (75 mg/kg/d) produced a marked reduction of lipids in serum in normo- and hyperlipidemic male rats but only in hyperlipidemic female rats, which is in agreement with former findings. These spontaneously hyperlipidemic rats could be a useful tool for investigation of drug effects on disturbed lipid metabolism and its pathophysiology. Therefore, we tried to establish a hyperlipidemic strain of rats.

Animals↗

Effect of exogenous thymidine on sister-chromatid exchange frequency in Chinese hamster ovary cells with bromodeoxyuridine- and chlorodeoxyuridine-substituted chromosomes.

There are conflicting reports on the effect of exogenous thymidine (dThd) on the frequency of sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells. Thymidine has been reported either to increase or to have no effect on SCE frequency under similar experimental conditions. To resolve this controversy, we have carried out a series of experiments to examine the effect of dThd on CHO cells cultured with 5-bromodeoxyuridine (BrdUrd). In addition, we have examined the effect of dThd on CHO cells cultured with 5-chlorodeoxyuridine (CldUrd), a much more potent inducer of SCEs than BrdUrd. The addition of 100 microM dThd to the culture medium caused a consistent decrease in the yield of SCEs in cells grown in BrdUrd for two cell cycles. The decrease was even greater when cells were grown in dThd and CldUrd. Analysis of twin and single SCEs indicated that dThd must be present during the first cell cycle to reduce the frequency of SCEs. Because excess dThd is thought to have an effect when DNA replicates on a template substituted with a halogenated nucleoside, dThd at concentrations from 100 microM to 9 mM was added to cultures for the second cell cycle after a first cell cycle in BrdUrd. In this experiment, the presence of dThd increased SCE frequency in a dose-dependent manner. The results suggest that if dThd competes with halogenated nucleosides and thus decreases their incorporation into DNA, SCEs are suppressed in the subsequent cell cycle, whereas if excess dThd creates a dNTP pool imbalance, SCEs can be increased.

Animals↗

Antisocial conduct: whose concern?

The differing perceptions of practitioners in child psychiatry and general psychiatry of antisocial behaviour are outlined, and an account is given of the change of attitudes towards deviancy that has taken place in the U.K. over the past twenty years. Attention is drawn to the fact that constitutional as well as experimental factors contribute to the causation of delinquent conduct, and the characteristics of "schizoid" antisocial young people are described. A plea is made for strengthening the links in training, research and practice between the subspecialties of psychiatry, and for a renewal of psychiatric interest in the sociopathies.

Antisocial Personality Disorder↗

Very low doses of X-rays can cause human lymphocytes to become less susceptible to ionizing radiation.

Cultured human lymphocytes exposed to very low doses of X-rays become less susceptible to subsequent higher doses of X-rays. Cells exposed to doses as low as 0.5 rad (cGy) or 1 rad of X-rays at 32-34 h of culture become adapted so that less cytogenetic damage in the form of chromosome breakage is induced by 150 rad administered at 48 h. This response, which does not occur after high initial doses of X-rays, can be eliminated by 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase.

Adaptation, Biological↗

Clinical evaluation of a self-rating scale for depressive disorder in childhood (Depression Self-Rating Scale).

The many conceptual and methodological difficulties involved in evaluating depression rating scales for children are discussed. A clinical validation of the Depression Self-Rating Scale for Children (DSRSC) is described. The instrument is easy to use and has a predictive value comparable with that of a psychiatric global rating of depressed appearance and history of depression obtained at interview. There was confirmation that the DSRSC can tap an internal dimension of depression and that children are able to evaluate their feeling states. An examination of misclassified children pointed to diagnostic overlap and some unreliability of diagnosis by clinicians.

Adolescent↗