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Biomedical subjects

J Solomon

Publications and source records attributed to J Solomon.

At least 91 records · Page 5Linked to original sources

Quantitative determination of the 5-(hydroxymethyl)uracil moiety in the DNA of gamma-irradiated cells.

5-(Hydroxymethyl)uracil (HMUra) is a chemically stable derivative of thymine formed through the action of ionizing radiation which we previously identified in the DNA of gamma-irradiated HeLa cells [Teebor, G. W., Frenkel, K., & Goldstein, M. S. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 318-321]. In this report, we determine whether HMUra can be used as a marker of exposure of DNA to ionizing radiation. Dose-response curves for its formation in [3H]thymidine-labeled DNA were constructed by exposing the DNA to increasing amounts of gamma-radiation and measuring the HMUra content. DNA was irradiated both in solution and in intact cells. HMUra was identified as the 2'-deoxyribonucleoside 5-(hydroxymethyl)-2'-deoxyuridine (HMdU) by subjecting the irradiated DNA to enzymatic digestion and analyzing the mixture of 2'-deoxyribonucleosides by high-pressure liquid chromatography. The identity of the radiogenically formed HMdU was confirmed by acetylation and the structure of the acetyl derivative obtained by mass and nuclear magnetic resonance spectroscopies. At two different DNA concentrations in solution, the same number of thymidine moieties were converted to HMdU, indicating that within this range of concentration the formation of HMdU was mediated through the indirect action of ionizing radiation. Equal amounts of HMdU were formed in single- and double-stranded DNA at each radiation dose, indicating that DNA conformation did not affect HMdU formation. Surprisingly, the G value (number of HMdU molecules formed/100 eV) was higher in irradiated cellular DNA than in DNA irradiated in solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

Basal forebrain innervation of rodent neocortex: studies using acetylcholinesterase histochemistry, Golgi and lesion strategies.

Acetylcholinesterase (AChE)-rich projections from basal forebrain to neocortex cerebri were characterized in the present study. The purpose was to investigate 3 aspects of these projections in rats and mice that have been incompletely described in previous work: intracortical organization of the fibers, subcortical pathways and axonal branching patterns of individual basal forebrain neurons. AChE histochemistry, lesions and Golgi impregnations were the principal strategies employed in this light microscopic study. The moderately dense, AChE-stained innervation of neocortex can be altered by intracortical lesions. The results depended on the region involved and the orientation of the lesion. Sagittal knife cuts had barely detectable effects, regardless of sites. Coronal knife cut lesions in medial cortex resulted in substantial loss of staining in cingulate and medial occipital fields. In contrast, coronal lesions of lateral or anterior cortex produce only small zonal reductions in staining. The interpretation of the latter findings that we favor is that AChE-rich basal forebrain fibers enter lateral/anterior cortex and branch densely there, but in tangentially limited and overlapping terminal domains. Observations on the topography and targets of AChE-rich basal forebrain cortical afferents revealed that the fibers could be grouped based on certain characteristics. Three sets of fibers were distinguishable: anterior pathway innervating cortex of the frontal pole. These fibers were traceable to the region of the substantia innominata/nucleus basalis. They crossed the neostriatum and external capsule in the sagittal plane, forming in 3 dimensions an orderly sheet-like array of fibers bridging the anteroventral surface of the neostriatum with nearby polar cortex medial pathway innervating cingulate and medial occipital cortex. Emerging predominantly from the region of the diagonal band, the fibers run caudally as a triangular bundle in deep layer VI of cingulate cortex. lateral pathway innervating most of remaining lateral neocortex. The fibers radiate out from substantia innominata/nucleus basalis with a complex 3-dimensional organization. In all pathways, fibers enter and initially run within layer VI before ascending pialward, although the intracortical course in layer VI differs between pathways. These fibers primarily terminate in layer V with a secondary concentration in layer I. However, the latter appears to receive substantial AChE-stained inputs from other sources, possibly intracortical, as well. The pathways overlap at their respective boundary zones. This system is comparably organized in rats and mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗

Pancreas divisum and its association with choledochal sphincter stenosis. Diagnosis by endoscopic retrograde cholangiopancreatography and endoscopic biliary manometry.

Choledochal sphincter stenosis was demonstrated in 37 of 90 patients with pancreas divisum. In 21 of the patients, stenosis was diagnosed during ERCP by endoscopic calibration of the choledochal sphincter, delayed drainage of contrast material from the bile duct, or a dilated common duct with or without elevation of the serum alkaline phosphatase level. In 12 patients, stenosis was diagnosed during endoscopic manometry with the demonstration of elevated basal choledochal sphincter pressures. Stenosis was initially diagnosed during surgery in four patients. Common duct diameters were normal in all patients who had not had cholecystectomy. Choledochal sphincter stenosis was confirmed in all patients who subsequently underwent sphincteroplasty. The surgical approach to patients with pancreas divisum and intractable obstructive pain should include sphincteroplasty of both the major and minor sphincters rather than the minor sphincter alone.

Adolescent↗

Visually perceiving distance: a comment on Shebilske, Karmiohl, and Proffitt (1983).

Shebilske, Karmiohl, and Proffitt (1983) interpret their data as showing that (a) the reference tonus level of the extraocular muscles controlling vergence is affected by everyday conditions of close viewing, and (b) this naturally induced phoria affects the visual perception of distance under natural viewing conditions. We note that these interpretations do not fully concur with the data presented--for example, the second conclusion favorably conflates partial results from two separate experiments--and we identify a number of confoundings that reduce the likelihood that the reported inaccuracies in distance judgments were due to variations in efference.

Distance Perception↗

Cervical carcinoma: a drug-responsive tumor--experience with combined cisplatin, vinblastine, and bleomycin therapy.

Thirty-five patients with advanced cervical cancer were treated with a combination chemotherapy regimen comprising cisplatin, vinblastine, and bleomycin (PVB). Sixty-six percent of 33 evaluable patients showed objective tumor response and complete remissions were seen in six (18%) patients. The median duration of tumor response in patients with recurrent cervical cancer was 24 weeks (range 8 to 104 weeks). Multivariate analysis of pretreatment variables including prior radiotherapy did not identify patients with a higher response probability. Nausea and vomiting were usual side effects of chemotherapy and there was one definite treatment-related death. Cervical cancer is responsive to cisplatin based combination chemotherapy. The role of chemotherapy in conjunction with radiotherapy or surgery in the treatment of locally advanced cervical cancer remains to be defined.

Adult↗

On the receiving end--II. Linear analogue self-assessment (LASA) in evaluation of aspects of the quality of life of cancer patients receiving therapy.

Linear analogue self-assessment (LASA) scales were used to measure general well-being and specific factors (mood, pain, nausea and vomiting, appetite, breathlessness, physical activity) in patients receiving therapy for malignant melanoma, small cell bronchogenic carcinoma (SCBC) or ovarian cancer. Among the patients with SCBC and melanoma, high correlations were observed between LASA scores for general well-being, mood and appetite. There was a significant relationship between performance status and LASA scores for general well-being, pain and appetite. Among patients with ovarian cancer, there was a significant association between performance status and LASA scores for general well-being, breathlessness and physical activity. Objective response category was related to change in LASA scores for pain. Changes in LASA scores during treatment reflected increased morbidity during radiotherapy in patients also receiving chemotherapy for SCBC. The LASA technique provides a convenient method for the assessment of quality of life in patients receiving cancer therapy, and potentially allows comparison of patient perception of treatment-related morbidities.

Antineoplastic Combined Chemotherapy Protocols↗

A follow-up survey of drug abuse and alcoholism teaching in medical schools.

The authors sent a questionnaire regarding the teaching of drug abuse and alcoholism to a stratified random sample of 40 U.S. medical schools, and 35 provided usable replies. The findings are summarized and are contrasted with replies received five years earlier from the same schools. During these five years, there were notable improvements in the teaching of these topics, as reflected by increases in required teaching hours, percentage of total required hours, number of elective courses offered, and number of affiliated clinical programs. The effect of the presence of a career teacher in the addictions is also evaluated.

Alcoholism↗

Double-blind comparison of lorazepam and chlordiazepoxide in the treatment of the acute alcohol abstinence syndrome.

The anxiolytic efficacy and safety of lorazepam and chlordiazepoxide were evaluated and compared during a five-day double-blind trial in 50 male inpatients who were experiencing acute alcohol withdrawal symptoms. The total daily doses of lorazepam and chlordiazepoxide were tapered from 6 to 2 mg and from 150 to 50 mg, respectively, during the first four days; no medication was given on day 5. Drug effectiveness was measured by improvements in the total severity assessment score (TSAS), in the three composite TSAS factors, and by the physician's global rating. No drug-related adverse effects occurred during treatment. Vital signs remained stable, and laboratory test results remained within normal limits. The results indicate that lorazepam was as effective as chlordiazepoxide in reducing the symptoms of acute alcohol withdrawal. Because of its simpler and more predictable metabolic pathway and its insignificant accumulation in plasma during multiple-dose therapy, lorazepam may be the drug of choice if benzodiazepine therapy is required for chronic alcoholics with acute withdrawal symptoms.

Acute Disease↗

Phase I clinical trial of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum(IV) (CHIP).

cis-Dichloro-trans-dihydroxy-bis-isopropylamine platinum(IV) (CHIP), a second-generation platinum complex with little or no nephrotoxicity in preclinical studies, has undergone phase I clinical testing and initial pharmacokinetic evaluation in 26 patients with solid tumors who received 40 courses of treatment. Doses of 20-350 mg/m2 were evaluated as single 2-hr infusions given every 3 weeks for two doses, with 2 L of pretreatment hydration (but no diuretics) in all but five patients. Nausea and vomiting was almost universal but was severe in only three courses. The dose-limiting toxic effect was myelosuppression, with a median wbc count nadir of 2500/mm3 and a median platelet count nadir of 32,000/mm3 at the maximum tolerated dose of 350 mg/m2. No increase in serum creatinine or decrease in creatinine clearance was seen. No pretreatment hydration was given in five of the seven patients treated at 350 mg/m2. Two cases of hypersensitivity were seen. No hearing loss was observed and no other toxic effects were noted. Plasma decay of total platinum was biexponential with a prolonged beta phase. Recovery of platinum in the urine was rapid up to 8-10 hrs and slow thereafter. Recoveries were incomplete and variable (16.5%-62% of the dose at 48 hrs).

Adult↗

Predicting the outcomes of psychotherapy by the Penn Helping Alliance Rating Method.

The Penn Psychotherapy Project reports further progress in its search for the factors predicting the outcomes of psychotherapy through the construction of the Penn Helping Alliance Rating Method. This method is based on the following two types of patients' statements during psychotherapy sessions: type 1, that the therapist is helping the patient, and type 2, that the patient and therapist are working together in a team effort to help the patient. The scales were applied reliably to the transcripts from ten patients who had improved the most and ten who had improved the least among the 73 in the project. Significant predictive correlations were found for the early helping alliance measures (eg, with status at the termination of treatment and with the composite of "success, satisfaction, and improvement"). In contrast, other theoretically important treatment variables were not significant predictors.

Adult↗

Diagnosis of coronary artery disease by multigated radionuclide angiography during right atrial pacing.

Right atrial pacing in conjunction with radionuclide angiography was used as a method to augment gradually myocardial oxygen demand in seven normal subjects and 11 patients with angiographically documented coronary artery disease (CAD). In five of the seven normal subjects the ECG during atrial pacing was normal and falsely pathologic in the two others; in all seven the ejection fraction (64 +/- 8 percent) did not change during the pacing. The atrial pacing was positive in seven of the eleven patients with CAD and falsely negative in four. In comparison, nine of these patients had more than 15 percent reduction in ejection fraction, while only two were regarded as negative. A maximal decrease of 31 percent in the average ejection fraction was observed in CAD patients at a pacing rate of 160/min. Wall motion pattern remained normal in all seven normal subjects, while new wall motion abnormalities developed during the atrial pacing in nine of the 11 CAD patients. We concluded that changes in ejection fraction induced by atrial pacing are sensitive indicators of myocardial ischemia. In patients with CAD, ejection fraction falls during pacing compared with normal subjects in whom ejection fraction remains unchanged.

Adult↗

New perspectives on the similarities and differences of alcoholism and drug abuse.

This article reviews the similarities and differences of alcoholism and drug abuse from a biopsychosocial perspective. Special emphasis is given to newer developments. In biology, the role of endorphins and isoquinolines is considered against the more traditionally recognized clinical differences between alcohol and drug disorders. Consideration is given to psychological themes such as the utility of the addictive personality concept, the impact of more sophisticated prevention strategies, and the combined treatment of alcoholics and drug abusers. Reports from social fields include a cross-cultural view of chemical dependence and an appraisal of legal and political trends which influence chemical use and the civil rights of chemical users. Recent developments in the biologic, psychologic and social sciences have solidified the impression that the chemical dependencies, for all their differences, share a number of important characteristics. The etiology of alcoholism and drug abuse has been attributed to biopsychosocial causes, currently a widely accepted hypothesis. From one perspective, this theory could be seen as a grab bag approach, since no specific universal cause has been discovered while many have been postulated. From another aspect, the hypothesis is a rational synthesis of present knowledge which finds no one etiological factor to be either preeminent or ubiquitous. This article presents in succession an overview of the biology, psychology and sociology of chemical dependence with emphasis on integrating newer developments with familiar knowledge.

Aged↗

Extraction and cleanup of fish, sediment, and water for determination of triaryl phosphates by gas-liquid chromatography.

Several techniques were evaluated for extracting triphenyl phosphate (TPP), 14C-labeled TPP, cresyl diphenyl phosphate, and tricresyl phosphate isomers (o-TCP, m-TCP, and p-TCP) from fish and sediment samples. Extracts of fish samples were cleaned up by gel permeation chromatography/alumina column chromatography; sediment extracts received alumina treatment only. Compounds were determined by gas-liquid chromatography (GLC) with nitrogen-phosphorus detection. Methanol/Polytron and hexane/ball mill extraction of fish samples fortified at 0.01, 0.1, and 1.0 microgram/g levels gave overall recoveries of the 5 compounds of 89 and 97%, respectively. Methanol recovered more radioactivity (97%) from fish exposed to 14C-TPP in aquaria for 24 h than did hexane from fish exposed for 16 h (79%). Refluxing fortified sediment (0.05 and 0.5 microgram/g) with methanol-water (9 + 1) gave significantly higher recoveries (88%) of the 5 triaryl phosphates than did dichloromethane-methanol (1 + 1) reflux or acetone-hexane (1 + 1) Soxhlet extraction. Recoveries of TPP and o-, m- and p-TCP from fortified river water (0.5, 5.0, and 50 microgram/L) by shaking with dichloromethane ranged from 91 to 118%. Some problems were encountered with interfering GLC peaks at low (microgram/g) levels in fish and sediment extracts despite the use of nitrogen-phosphorus specific detectors.

Animals↗