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Biomedical subjects

S Stern

Publications and source records attributed to S Stern.

At least 73 records · Page 4Linked to original sources
PubMed1996

Efficacy of agents counteracting hypoxia in fractionated radiation regimes.

BACKGROUND AND PURPOSE: Solid tumours contain hypoxic cells which are resistant to radiotherapy. This study compares the efficacy of several strategies to counteract diffusion-limited hypoxia, or intermittent hypoxia in a fractionated regimen of 1 to 6 x 2 Gy. MATERIALS AND METHODS: Nicotinamide (250 mg/kg), perflubron emulsion (Oxygent) (4 ml/kg), tirapazamine (SR4233) (0.10 mmol/kg) and carbogen breathing, administered alone or in combination, were investigated on two tumour cell lines: EMT6 (a rodent mammary carcinoma) and HRT18 (a human rectal adenocarcinoma) using a clonogenic assay. The radiosensitizing effect of the agents was assessed after 1 and 6 x 2 Gy for drugs used alone, and 1, 2, 4, 6 x 2 Gy for drugs used in combination. RESULTS: At the end of the fractionated radiation regimen, the combination of nicotinamide + carbogen induced the greatest radiosensitization for EMT6 tumours, while greatest radiosensitization of HRT18 was obtained with nicotinamide + carbogen + tirapazamine. CONCLUSION: The efficacy of the strategies for overcoming hypoxia using a fractionated regimen depends on the tumour cell line. These differences could be linked to differences in the initial percentages of acute and chronic hypoxic cells, and to changes in the two types of hypoxia during treatment.

Adenocarcinoma↗
PubMed1996

HLA-DR expression and lymphocytic infiltration in metastatic and non-metastatic papillary carcinoma of the thyroid.

Thyrocyte HLA-DR expression in association with lymphocytic infiltration has been demonstrated in autoimmune diseases of the thyroid. HLA-DR expression has been noted both in association with lymphocytic infiltration and in its absence. However, no prognostic significance was attributed to these findings. The purpose of this study on papillary carcinoma of the thyroid was to examine how tumour behaviour relates independently to HLA-DR expression and lymphocytic infiltration. Fifty patients with papillary carcinoma with known metastatic status were examined for HLA-DR expression utilizing the immunoperoxidase conjugated indirect method. The patients were divided into three groups: no metastases (n = 16), regional lymph node metastases only (n = 25), and distant haematogenous metastases (n = 9). Overall HLA-DR expression was noted in 6, 36 and 55% of the respective groups. Tumour HLA-DR expression without lymphocytic infiltration was noted in 0, 4 and 33% of the respective groups. Tumour HLA-DR expression with lymphocytic infiltration occurred in 6, 32 and 22% of the respective groups. From these findings we conclude that HLA-DR expression with lymphocytic infiltration occurs more frequently than HLA-DR expression in the absence of infiltration. The concurrence of HLA-DR expression and lymphocytic infiltration is most commonly associated with regional lymph node metastasis. HLA-DR expression in the absence of lymphocytic infiltration occurs in tumours with distant haematogenous metastases and is an uncommon feature of tumours that have not metastasized or have metastasized only to lymph nodes. Tumour HLA-DR expression in the absence of lymphocytic infiltration may indicate the potential for more aggressive behaviour.

Adolescent↗
PubMed1996

Measuring child work and residence adjustments to parents' long-term care needs.

This article estimates the effects of various parent and child characteristics on the choice of care arrangement of the parent, taking into account the potential endogeneity of some of the child characteristics. Three equations are estimated: a care choice equation, a child location equation, and a child work equation. Results suggest a hierarchy of family decision making; child locations affect the care decision, which affects child work decisions. The results also question previous research attempting to explain causes of secular trends in long-term care.

Activities of Daily Living↗
PubMed1996

Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma.

Chronic lymphocytic leukemia (CLL) and immunocytoma (IC) are remarkably heterogeneous with regard to their clinical course. The current staging systems can distinguish prognostic subgroups, but do not seem to predict the risk of disease progression of an individual patient with sufficient accuracy. Given the increase of treatment options for CLL and IC, additional parameters are needed to decide which patients may benefit from early or intensified treatment. It has been shown that two biochemical markers, serum beta 2-microglobulin (s-beta 2M) and serum thymidine kinase (s-TK), might identify CLL and IC patients at high risk of disease progression. Therefore, the prognostic value of these two serum parameters was compared with a panel of several established prognostic factors in a prospective clinical trial. 113 patients with CLL and 41 patients with IC (mean age +/- SD 63.9 +/- 10.7 years) were included. The following parameters were determined: histopathological diagnosis (IC vs. CLL), age, sex, performance status (Karnofsky index), B symptoms, peripheral blood lymphocyte count, platelet count, blood hemoglobin, serum lactate dehydrogenase (s-LDH), s-beta 2M, s-TK, serum creatinine, number of lymph node areas involved, prior therapy, and the time from diagnosis to inclusion in the study. Univariate analyses showed that nine parameters (Karnofsky index, peripheral blood lymphocytosis, platelet count, blood hemoglobin, lymph node areas involved, pretreatment, s-LDH, s-beta 2M, and s-TK) significantly predicted progression-free survival. In a Cox regression model, only four of these parameters provided independent prognostic information on progression-free survival: 1. s-beta 2M, 2. Karnofsky index, 3. platelet count, and 4. s-TK. The results show that s-beta 2M and s-TK independently predict progression-free survival in patients with CLL and IC, and suggest that these prognostic factors may allow an improved prediction of progression-free survival, particularly in early disease stages.

Biomarkers, Tumor↗
PubMed1996

Developmental neurotoxicity of methanol exposure by inhalation in rats.

The possibility of widespread methanol exposure via inhalation stemming from its adoption as an automotive fuel or fuel component arouses concerns about the potential vulnerability of the fetal brain. This project was designed to help address such concerns by studying the behavior of neonate and adult rats following perinatal exposure to methanol vapor. Four cohorts of pregnant Long-Evans hooded rats, each cohort consisting of an exposure and a control group, were exposed to 0 parts per million (ppm) (control) or 4,500 ppm methanol vapor for six hours daily beginning on gestation day (GD) 6 with dams and pups then being exposed postnatal day (PND) 21. Exposures took place in 2-m3 Rochester-type inhalation chambers while the animals remained in their plastic breeder cages. Prenatal and postnatal blood methanol concentrations were determined by gas chromatography. Blood methanol concentrations of the dams, measured immediately following a six-hour exposure, were approximately 500 to 800 micrograms/mL throughout gestation and lactation. Average blood methanol concentrations of the pups were about twice those of the dams. Because such results appeared consistently across the other cohorts, we decided to obtain additional data with Cohort 4. Once it had undergone the standard exposure protocol, we selected sets of extra pups from those that had not been assigned previously to the adult phase of behavioral testing. Each set was exposed once, at ages that extended out to PND 52, for one additional six-hour session of exposure to 4,500 ppm methanol. The blood methanol concentrations of these pups declined until about PND 48, at which time they approximated those of the dams. These findings might be accounted for by a process of metabolic maturation in the pups that remains to be identified.

Animals↗
PubMed1996

[Measurement of oxygen tension in normal and varicose vein walls].

Oxygen tension (PO2) was investigated in vivo in the long saphenous vein from 21 varicose patients (31 veins) during venous surgery and 7 patients with normal venous network undergoing popliteo-femoral by-pass. Measurement was achieved using computerized polarographic system Kimoc 6650 (Eppendorf, Hamburg) providing a microdriven stepwise progression of a needle probe. Oxygen tension profile was similar in both groups of patients. A slow PO2 decrease was observed from adventitia up to the union of the middle and inner thirds of the media where values were at the lowest then followed by a marked increased in the intima and the saphenous lumen. Oxygenation of the two external thirds of the venous wall was provided by vasa vasorum. The average minimum values in the media was significantly reduced in varicose veins compared to no-varicose veins (7,9 mmHg versus 13,4 mmHg; p < 0,05). These results indicated the key role of vasa vasorum flux in the long saphenous vein nutrition and suggest a primary or secondary deficiency in oxygen supply in varicose veins.

Adult↗
PubMed1994

Interactions of a small RNA with antibiotic and RNA ligands of the 30S subunit.

It is now generally accepted that 16S and 23S ribosomal RNA play important roles in the decoding and peptidyl transferase activities of ribosomes. Despite their complex structures and numerous associated proteins it is possible that small domains of these rRNAs can fold and function autonomously, particularly those that appear devoid of protein interactions. One candidate for such a domain is the decoding region, located near the 3' end of 16S rRNA (Fig. 1a, b). Consistent with this hypothesis, aminoglycoside antibiotics that interact with the decoding region in 30S subunits interact with other RNAs in the absence of proteins. In addition, certain activities of self-splicing introns, at least superficially, resemble translational decoding. We report here that an oligoribonucleotide analogue of the decoding region interacts with both antibiotic and RNA ligands of the 30S subunit in a manner that correlates with normal subunit function. The activities of the decoding region analogue suggest that the intimidating structural complexity of the ribosome can be, to some degree, circumvented.

Anti-Bacterial Agents↗
PubMed1994

Correlation of exercise-induced ST depression in precordial electrocardiographic leads after inferior wall acute myocardial infarction with thallium-201 stress scintigraphy, coronary angiography and two-dimensional echocardiography.

Fifty-eight of 220 consecutive patients had exercise-induced ST depression in some or all precordial leads 3 to 12 months after a first inferior myocardial infarction. All 58 patients underwent thallium-201 exercise testing, 2-dimensional echocardiography and coronary angiography. ST depression was confined to leads V1-4 in 22 patients (group A); thallium-201 exercise testing showed reversible anterior perfusion defects and left anterior descending coronary artery disease in 11 of the 22 patients (50%). None of the other 11 with negative thallium-201 exercise test results had significant left anterior descending narrowing, and the anterior ST depression could be explained by asynergy of the posterior wall found on 2-dimensional echocardiography in 10. ST depression appeared in leads V5-6 in 22 patients (group B); reversible anterior perfusion defects and left anterior descending disease was demonstrated in 18 patients (82%). In the other 4 patients posterior wall asynergy was demonstrated. ST depression was seen from leads V1-6 in 14 patients (group C); reversible anterior perfusion defects were seen in 6 patients (43%), 5 of whom had significant left anterior descending disease. Among the other 8 patients without reversible anterior perfusion defects, posterior wall asynergy was found in 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Inhibition of cisplatin toxicity without decreasing antitumor efficacy. Use of a dithiocarbamate.

OBJECTIVE: To demonstrate whether a dithiocarbamate derivative, N-methyl-D-glucaminedithiocarbamate, could prevent anorexia and weight loss and enhance survival without decreasing the antitumor efficacy of high-dose cisplatin therapy. DESIGN: One hundred forty-two mice were randomized into groups receiving cisplatin, 5 mg/kg per day, 7.5 mg/kg per day, or 10 mg/kg per day for three days with or without N-methyl-D-glucaminedithiocarbamate, 1000 mg/kg per day. Weight loss and morbidity were examined between groups. Antitumor efficacy of cisplatin combined with N-methyl-D-glucaminedithiocarbamate was examined using a subcutaneous melanoma model. SETTING: Institutional laboratory. MAIN OUTCOME MEASURES: N-methyl-D-glucaminedithiocarbamate intervention would decrease morbidity, weight loss, and increase survival without decreasing the antitumor efficacy of cisplatin. RESULTS: Weight loss and morbidity were significantly reduced when N-methyl-D-glucaminedithiocarbamate was coadministered with cisplatin (P < .05) at all doses of cisplatin. The antitumor efficacy of high-dose cisplatin therapy (7.5 mg/kg per day and 10 mg/kg per day) was not significantly decreased (P > .05) at all doses of cisplatin. CONCLUSION: As N-methyl-D-glucaminedithiocarbamate seems to limit morbidity and mortality of high-dose cisplatin administration without decreasing its antitumor efficacy, this drug deserves further investigation in the treatment of cancer.

Animals↗
PubMed1994

Aborted sudden death in a young patient with isolated granulomatous myocarditis.

A young athlete was successfully resuscitated from ventricular fibrillation. Subsequently severe heart failure developed and endomyocardial biopsy showed granulomatous myocarditis. Following steroid therapy, repeated biopsies demonstrated partial resolution of the inflammatory changes and mild myocardial fibrosis; the granulomas disappeared, and the patient recovered both clinically and haemodynamically. Three years later, the patient is asymptomatic, is practising long distance jogging, has a normal left ventricular ejection fraction and no evidence of arrhythmias.

Adult↗
PubMed1994

A genetic study of estrus symptoms at puberty and their relationship to growth and leanness in gilts.

Puberty traits of 740 Yorkshire gilts from a selection experiment were analyzed. Heritabilities were estimated to be .32 for pubertal age, .23 for length of proestrus, .16 for length of standing estrus, .29 for ability to show standing reflex, and .24 for intensity of vulvar symptoms. Genetic correlations between length of proestrus, intensity of vulvar symptoms, and ability to show standing reflex were positive. There seemed to be a negative genetic correlation between percentage of lean and intensity of vulvar symptoms. There were negative genetic correlations between growth rate and length of standing estrus, and between growth rate and ability to show standing reflex.

Animals↗
PubMed1994

[The role of psychosocial factors in a chronic course after injuries of the lower spine].

Clinical experience has often demonstrated the inadequate relationship between degree of injury and rehabilitation outcome. The aim of this study is to investigate the importance of different psychosocial factors in coping behaviour after lower back injury. 194 patients of three nationalities (Swiss, Italian, Yugoslavian) were examined, 70 in an acute and 124 in a chronic phase of injury. A semistructured interview, followed by a physical examination, was used to gather the needed information; a follow-up examination was done one year afterwards. Factors shown to contribute to poor outcome were: reduced sense of wellbeing, pessimistic self-prognosis of outcome, poor job security, migration, social status, insufficient doctor-patient relationship, lack of social support and limitations in certain physical parameters. The most reliable predictor for poor outcome was the patients evaluation of job security. In addition to diagnosis of existing chronification, resumption of work "for therapeutic purposes" after thorough preparation of the patient and conclusion of cases within the shortest possible time with definitive settlement of insurance payments were proposed as concluding steps.

Adaptation, Psychological↗
PubMed1993

Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production.

Replication of RNA viruses, such as the human immunodeficiency virus (HIV), is dependent upon multiple specific interactions between viral RNAs and viral and cellular proteins. A small molecule that interferes specifically with one or more of these RNA-protein interactions could be an efficacious antiviral agent. Here we show that certain aminoglycoside antibiotics, in particular neomycin B, can block binding of the HIV Rev protein to its viral RNA recognition element. Inhibition appears to be highly selective, resulting from competitive binding of the drug to a small viral RNA region within the Rev-binding site. We further demonstrate that neomycin B can specifically antagonize Rev function in vitro and in vivo and can inhibit production of HIV. Our results establish the feasibility for developing antiviral drugs that act by selectively blocking RNA-protein interactions.

Anti-Bacterial Agents↗
PubMed1993

Silent myocardial ischemia.

The documentation of abnormalities related to myocardial ischemia, whether symptomatic or silent, is of central importance. Whenever this information is available, it should be used in the overall assessment of the patient at risk for adverse outcome. The level of concern for treatment of CAD should be based on the risk implications associated with the ischemia-related abnormalities detected during objective testing rather than on the presence or absence of pain. The exercise stress test is still the single most useful test to begin the evaluation of a patient with an analyzable ST segment. In persons suspected of having CAD, the detection of ischemic-type ST-segment depression, at a low workload (e.g., < 120 beats/min or < 6.5 METS) of > 2 mm magnitude or persisting for more than 6 min implies high risk for adverse outcome. Asymptomatic ischemia during everyday activities, detected by Holter monitoring, in the high-risk patient, most probably adds additional risk beyond the risk of an abnormal stress test alone. Left ventricular imaging by two-dimensional echocardiography, RNA, angiogram, vest, etc, showing an ejection fraction > or = 40%, reversible wall motion abnormalities in multiple regions and redistribution defects or a failure to increase ejection fraction during exercise even if the patient remains asymptomatic, also imply high risk. The presence of any of these abnormal findings, regardless of symptoms, should therefore prompt as high a degree of concern as with ischemia-related signals associated with pain. Thus any therapy chosen should be directed toward elimination of transient ischemia, not just relief of symptoms that may or may not be ischemia related. If this course is chosen, the efficacy of the therapeutic regimen and possible progression of CAD should be assessed with follow-up testing for ischemia. We believe that risk factor modification and aspirin should be considered for most, if not all, patients in whom ischemia, silent or symptomatic, is suspected or detected. If symptoms or ischemia suggesting low risk is present, anti-ischemic medical therapy may be considered, but follow-up is advised. If a high-risk ischemic signal, even without symptoms, is detected, medical therapy should be used to attempt to modify the signal. If the ischemic signal suggesting high risk persists despite medical therapy, revascularization should be considered. Until additional data from large clinical trials are available, this approach appears to have the greatest likelihood of modifying the adverse outcome of CAD.

Angina Pectoris↗
PubMed1993

Ischemic threshold during two exercise testing protocols and during ambulatory electrocardiographic monitoring.

OBJECTIVES: The aim of this study was to examine the dependence of the ischemic threshold during exercise testing on the exercise protocol employed and to determine the relation between the ischemic thresholds observed during exercise and during daily activity. BACKGROUND: The ischemic threshold (heart rate at 1-mm ST segment depression) during daily activity has been reported to be lower than that observed during exercise testing. Recent reports have hypothesized that this difference is probably dependent on the exercise protocol employed. METHODS: Twenty-two patients with known coronary artery disease, not receiving antianginal medications, were evaluated by repeated exercise testing according to the Bruce and the modified Davidson protocols and by 48-h ambulatory electrocardiographic monitoring. RESULTS: Although the heart rate at 1-mm ST segment depression was somewhat lower with the Davidson than with the Bruce protocol (112 +/- 14 vs. 115 +/- 14 beats/min), the rate-pressure product at 1-mm ST segment depression was similar during the two protocols (16,900 +/- 4,000 vs. 17,700 +/- 3,600). The mean heart rate (100 + 12 beats/min) at 1-mm ST segment depression during ambulatory ischemic episodes (n = 137) was significantly lower than that observed during both exercise protocols (p < 0.001 for both comparisons). CONCLUSIONS: Exercise-induced ischemia occurs at a relatively fixed threshold that is mainly dependent on myocardial oxygen demand and is independent of the exercise protocol employed. Ischemia on ambulatory monitoring, however, occurs at a much more variable threshold that is commonly lower than that observed during exercise and is therefore dependent on other factors in addition to increased demand.

Aged↗
PubMed1993

Differential positive control by Oct-1 and Oct-2: activation of a transcriptionally silent motif through Oct-1 and VP16 corecruitment.

Transcriptional regulation by the ubiquitous human POU homeo domain protein Oct-1 and the related B-cell protein Oct-2 is a model for understanding how proteins that recognize the same regulatory site elicit different programs of gene transcription. Here, we describe a mechanism for differential promoter activation whereby only Oct-1, through selective corecruitment with the herpesvirus trans-activator VP16, acquires the ability to stimulate transcription from a TAATGARAT-containing site that responds to neither Oct-1 nor Oct-2 alone. To measure differential in vivo activation by human Oct-1 and Oct-2 in response to VP16, we have developed a transient assay in murine NIH-3T3 cells. Surprisingly, murine Oct-1 associates with VP16 much less effectively than its human counterpart, most likely because the murine Oct-1 homeo domain differs at four positions from the human Oct-1 homeo domain. The murine cell transient assay shows directly that human Oct-1, but not human Oct-2, can respond to VP16 in vivo. The Oct-1 DNA-binding POU domain is sufficient and the Oct-1 homeo domain is critical for this response, because an Oct-1 POU domain containing the Oct-2 homeo domain fails to respond to the VP16-induced positive control of transcription. Thus, by selective homeo domain interaction and corecruitment to an otherwise silent regulatory element, VP16 expands the repertoire of sites responsive to Oct-1 without affecting the activity of its close relative Oct-2.

3T3 Cells↗