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Biomedical subjects

S Fox

Publications and source records attributed to S Fox.

At least 19 recordsLinked to original sources
PubMed1996

A mixed-metal pentanuclear complex containing linked NiIIN2S2 and CuII units.

Bis[(1S,2S)-trans-3,3'-(1,2-cyclohexanediyldinitrilo)bis- (2-methylpropane-2-thiolato)]-1 kappa 4N1,N1',S1,S1';2 kappa 4N2,- N2',S2,S2';3 kappa 2S1,S2';4 kappa 2S1',S2;5 kappa 2S1',S2'-triiodo-3 kappa I, 4 kappa I,- 5 kappa I-tricopper(I)dinicke1(II) bis(acetonitrile) solvate, [[Ni(C14H28N2S2)]2(CuI)3]. 2CH3CN, is one of a number of possible novel pentanuclear complexes formed from MIIN2S2 units with available donating thiolate ligands. In the title compound, three CuII groups bridge thiolate ligands from two approximately square-planar [NiIIN(amine)2S(thiolate)2] units to form the pentanuclear complex. The coordination geometry of each Cu atom is approximately trigonal planar.

Crystallography, X-Ray↗
PubMed1996

Normethylclozapine potentiates the action of quinpirole in the 6-hydroxydopamine lesioned rat.

Systemic administration of the 5-HT2c receptor antagonist, normethylclozapine, to previously untreated unilaterally 6-hydroxydopamine-lesioned rats elicits rotations contraversive to the lesion when given with a subthreshold dose of the dopamine D2 receptor agonist, quinpirole. Normethylclozapine alone does not possess any anti-parkinsonian action. In animals which have previously received dopamine replacement therapy, i.e. primed, normethylclozapine potentiates the contraversive rotations induced by quinpirole. We speculate that these actions may result from reduced excitation of the output regions of the basal ganglia. 5-HT2c receptor antagonists may have potential as treatment for Parkinson's disease in combination with dopamine receptor agonists.

Animals↗
PubMed1996

Prognostic value of angiogenesis in operable non-small cell lung cancer.

Tumour angiogenesis is an important factor for tumour growth and metastasis. Although some recent reports suggest that microvessel counts in non-small cell lung cancer are related to a poor disease outcome, the results were not conclusive and were not compared with other molecular prognostic markers. In the present study, the vascular grade was assessed in 107 (T1,2-N0,1) operable non-small cell lung carcinomas, using the JC70 monoclonal antibody to CD31. Three vascular grades were defined with appraisal by eye and by Chalkley counting: high (Chalkley score 7-12), medium (5-6), and low (2-4). There was a significant correlation between eye appraisal and Chalkley counting (P < 0.0001). Vascular grade was not related to histology, grade, proliferation index (Ki67), or EGFR or p53 expression. Tumours from younger patients had a higher grade of angiogenesis (P = 0.05). Apart from the vascular grade, none of the other factors examined was statistically related to lymph node metastasis (P < 0.0001). A univariate analysis of survival showed that vascular grade was the most significant prognostic factor (P = 0.0004), followed by N-stage (P = 0.001). In a multivariate analysis, N-stage and vascular grade were not found to be independent prognostic factors, since they were strongly related to each other. Excluding N-stage, vascular grade was the only independent prognostic factor (P = 0.007). Kaplan-Meier survival curves showed a statistically significant worse prognosis for patients with high vascular grade, but no difference was observed between low and medium vascular grade. These data suggest that angiogenesis in operable non-small cell lung cancer is a major prognostic factor for survival and, among the parameters tested, is the only factor related to cancer cell migration to lymph nodes. The integration of vascular grading in clinical trials on adjuvant chemotherapy and/or radiotherapy could substantially contribute in defining groups of operable patients who might benefit from cytotoxic treatment.

Aged↗
PubMed1996

Phase II trial of topotecan in advanced or metastatic adenocarcinoma of the pancreas.

PURPOSE: A phase II trial of topotecan, an inhibitor of topoisomerase I, was conducted in patients with advanced or metastatic adenocarcinoma of the pancreas to determine the activity and toxicity of topotecan. PATIENTS AND MATERIALS: 35 patients, previously untreated with chemotherapy, received topotecan 1.5 mg/m2/d for five days intravenously and repeated every 21 days. Patients were assessed for response after 3 cycles. Those with either clinical response or stable disease received additional cycles of the drug until toxicity developed or disease progression occurred. RESULTS: Among 30 patients evaluable for response there were no complete responses and 3 partial responses (10%) for a total response rate of 10% (95% confidence interval = 0-20.6%). Stable disease for at least eight weeks was seen in 11 patients (36%). Median survival was 19 weeks (95% confidence interval 11 to 26 weeks). Therapy was generally well tolerated, with reversible granulocytopenia being the most common toxicity. CONCLUSION: Topotecan given on a 5 day, short infusion schedule, demonstrated limited activity in pancreatic carcinoma with minimal toxicity. Further exploration of topotecan in pancreatic carcinoma using different dosing schedules is warranted.

Adenocarcinoma↗
PubMed1996

Breast cancer angiogenesis--new approaches to therapy via antiangiogenesis, hypoxic activated drugs, and vascular targeting.

Several groups have shown that quantitation of tumor angiogenesis by counting blood vessels in primary breast cancer gives an independent assessment of prognosis. Poor prognosis is associated with high blood vessel counts. We have shown that the rate of cell division in endothelial cells is much higher in breast tumours than in normal breast. Breast cancer cell lines and primary human breast tumours express a wide range of vascular growth factors, including VEGF, placenta growth factor, pleiotrophin, TGF beta 1, acidic and basic FGF, and platelet-derived endothelial cell growth factor. Inhibiting angiogenesis by blocking vascular growth factors would be difficult with highly specific agents, but drugs with a broader spectrum of antagonism may be effective. We have developed several suramin analogues which are less toxic than suramin in vivo but more potent in inhibiting angiogenesis, and these have been developed for Phase I. A combination of anti-angiogenesis agents with drugs activated by hypoxia may also be useful, because anti-angiogenesis alone may not kill cells, whereas activation of hypoxic drugs could synergize. New endpoints may be necessary because inhibition of new blood vessel formation may not cause tumour regression. Thus, the endpoint of stable disease and biochemical assessment of inhibition of angiogenesis may be much more important in therapeutic studies and for drug development in the future. The prognostic importance of angiogenesis suggests that this should be a major new therapeutic target.

Angiogenesis Inducing Agents↗
PubMed1996

Bcl-2 and p53 expression in node-negative breast carcinoma: a study with long-term follow-up.

Bcl-2 and p53 gene products (Bcl-2, p53) are important regulators of apoptosis and cell proliferation, and their immunohistochemical expression may help to identify high-risk breast cancer patients. The authors evaluated p53 and Bcl-2 immunoreactivity in 178 node-negative breast cancers (NNBC) with long-term follow-up (median, 60 months). Bcl-2 was seen in 111 (62%) cases, and was significantly associated with small tumor size, nonductal morphology, low tumor grade, estrogen-receptor (ER) positivity, and p53 negativity. p53 overexpression (ie, > 15% reactive nuclei) was observed in 31 (17%) cases, and was associated with lower age, large tumor size, ductal morphology, high tumor grade, negative ER status, and lack of Bcl-2 immunoreactivity. In univariate analysis, the variables associated with short relapse-free survival (RFS) were large tumor size (P = .002), high histological grade (P = .01), high mitotic count (P = .03), and high Nottingham prognostic index (NPI) (P = .0002). In multivariate analysis (final model), only the NPI was of independent prognostic value concerning RFS.

Analysis of Variance↗
PubMed1996

Treatment of acute gastroenteritis: too much and too little care.

This paper reviews the health services literature regarding care for gastroenteritis in children. United States health care utilization, use of oral rehydration therapy (ORT), and quality of care considerations are described. The literature suggests that some US children may receive too much care while others may not be getting enough and that physician practices continue to differ from expert recommendations.

Acute Disease↗
PubMed1995

Three-dimensional treatment planning and conformal radiation therapy: preliminary evaluation.

Preliminary clinical results are presented for 209 patients with cancer who had treatment planned on our three-dimensional radiation treatment planning (3-D RTP) system and were treated with external beam conformal radiation therapy. Average times (min) for CT volumetric simulation were: 74 without or 84 with contrast material; 36 for contouring of tumor/target volume and 44 for normal anatomy; 78 for treatment planning; 53 for plan evaluation/optimization; and 58 for verification simulation. Average time of daily treatment sessions with 3-D conformal therapy or standard techniques was comparable for brain, head and neck, thoracic, and hepatobiliary tumors (11.8-14 min and 11.5-12.1, respectively). For prostate cancer patients treated with 3-D conformal technique and Cerrobend blocks, mean treatment time was 19 min; with multileaf collimation it was 14 min and with bilateral arc rotation, 9.8 min. Acute toxicity was comparable to or lower than with standard techniques. Sophisticated 3-D RTP and conformal irradiation can be performed in a significant number of patients at a reasonable cost. Further efforts, including dose-escalation studies, are necessary to develop more versatile and efficient 3-D RTP systems and to enhance the cost benefit of this technology in treatment of patients with cancer.

Bile Duct Neoplasms↗
PubMed1995

The effects of albuterol on power output in non-asthmatic athletes.

The purpose of this study was to evaluate the effect of the beta 2-agonist albuterol (salbutamol) at twice the normal dosage (360 micrograms) on power output during a 30-second Wingate test and pulmonary function in highly trained cyclists (4 category 1 and 10 category II U.S.C.F. track cyclists). The cyclists did not have a history of exercise induced bronchial spasms, and a 5 step methacholine challenge confirmed all subjects to be non-asthmatic. The project was performed in a random block, double blind design. Twenty minutes before the 30-second Wingate cycle ergometer exercise, albuterol (90 micrograms per dose) or a saline placebo was administered by inhaler in 4 metered doses. Pulmonary function tests were performed at rest, 20 minutes post-inhalation, and 5, 10, 15 minutes post-exercise. After a standard warm-up, a 30-second Wingate anaerobic power test was performed on a cycle ergometer at a resistance of 0.10 kg (kg body mass)-1. Multi-variate ANOVA revealed no significant difference between the albuterol and placebo treatment for the anaerobic power measures: peak power (1,136.7 +/- 40.9 vs 1,124.8 +/- 39.8 W, mean +/- s.e.), total work (27,213.6 +/- 653.1 vs 27,093.3 +/- 677.4j), time to peak power (4.5 +/- 0.2 vs 4.8 +/- 0.5 s), and fatigue index (16.5 +/- 1.8 vs 16.6 +/- 1.8 W.s-1). Peak heart rate (181.6 +/- 3.7 vs 181.4 +/- 3.8 bpm), or blood lactate (14.0 +/- 0.9 vs 13.8 +/- 0.8 mmol.l-1) 3 min after the exercise bout were not significantly different between treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Gene therapy through signal transduction pathways and angiogenic growth factors as therapeutic targets in breast cancer.

Angiogenesis is a major new prognostic factor in breast cancer. Small vessels quantitatively assessed by staining with anti-CD31 antibodies correlate with lymph node involvement and are a better independent predictor of survival. There are many vascular growth factors, but predominant in primary tumors assessed by nuclease protection assays are vascular endothelial growth factor and platelet-derived endothelial cell growth factor. Acidic and basic fibroblast growth factor are also detectable. A common feature of these angiogenic factors is heparin binding, so novel analogues of suramin that can compete for heparin binding have been developed. These are more potent in vitro against endothelial cells and are less toxic in vivo, thereby giving a much better therapeutic ratio. Protein kinase C is also important in endothelial growth, as it is in carcinoma growth. Thus, a novel agent inhibiting this pathway, and inducing transforming growth factor-beta production has been assessed in a Phase I trial; this agent is bryostatin. It does not cause marrow suppression and has stimulatory effects of tumor necrosis factor-alpha and interleukin (IL)-6 production. High expression of epidermal growth factor (EGF) receptors and erbB-2 has been related to poor prognosis. EGF receptors are mainly regulated by transcription, as are some cases of high erbB-2 expression. Thus, a novel approach to gene therapy is being developed using direct tumor injection of cDNA, with a tumor specific promoter ligated to the IL-2 gene. This avoids many problems associated with targeting. Because IL-2 stimulation of cytotoxic T-cells will depend on appropriate antigen presentation, human lymphocyte antigen Class I expression was studied, as was the peptide transporter system RING4 (TAP1). Losses were found in 50% of cases, and in some cases only in lymph nodes but not primary cancers, thereby providing evidence for a role in suppressing metastasis. Thus, many new approaches to therapy are possible as a result of understanding growth factors and intracellular signaling pathways.

Angiogenesis Inducing Agents↗
PubMed1994

Clonal chromosome abnormalities in 54 cases of ovarian carcinoma.

As a prelude to assessing the relationship of chromosome alterations to clinical outcome in ovarian carcinoma, we report on the cytogenetic analysis on short-term cultures from 54 patients. All patients had histopathologically confirmed malignancy, with the majority of cases demonstrating serous ovarian adenocarcinomas. Structural alterations were evident in 52 cases, whereas numeric changes were identified in 13 cases. The most notable numeric abnormalities were loss of the X-chromosome (9/13 total cases) and +7 (3/9 diploid cases). Structural alterations most frequently involved chromosomes 1, 3, 6, 7, 11, and 12. Chromosomal breakpoints were shown to cluster in several chromosomal banding regions, including 1p36, 1p11-q21, 3p23-p10, 7p (especially 7p22), 11p, 11q, 12p13-q12, and 12q24. The frequency of structural alterations involving the following chromosome arms was found to be significantly increased: 1p (p < 0.01), 7p (p < 0.01), 11p (p < 0.01), 11q (p < 0.05), and 12p (p < 0.05). An analysis of the net gain or loss of chromosome segments was also performed, with the most consistent tendency observed being over-representation of 1q and chromosome 7, deletion of 1p, and loss of the X chromosome.

Adult↗
PubMed1994

Age and the false-consensus effect.

Israeli participants in four age groups (older adolescents, adults, residents of an old-age home, and older participants in a university program) answered a 12-item false-consensus questionnaire and Davis's (1980) Interpersonal Reactivity Index measuring empathy-egocentrism. The false-consensus effect (FCE) was found in all four age groups. The effect was significantly weaker among the older students, which was also the group lowest on egocentrism. Older adolescents were more egocentric than adults, who were less egocentric than residents of the old-age home, who were the highest on egocentrism. No correlation was found between the strength of the FCE and the egocentrism score.

Adolescent↗
PubMed1994

Association between reported use of inhaled triamcinolone and differential short-term responses to aerosolized albuterol in asthmatics in an emergency department setting.

Forty-four adult patients with acute asthma were treated with albuterol at a rate of 15 mg/h over 2 h. Analysis of covariance showed a significantly higher baseline adjusted mean for both percent predicted forced expiratory volume in 1 s (PFEV1) (p = 0.045) and percent predicted forced vital capacity (PFVC) (p = 0.022) at 50 and 110 min for the patients who reported triamcinolone use. Although heart rates decreased overall during the first hour of albuterol treatment, a rise in mean heart rate occurred during the second hour of treatment only in patients reporting triamcinolone use (p = 0.005). After accounting for the effects of parenteral corticosteroids, the effect of reported triamcinolone use remained significant. These data suggest that use of inhaled corticosteroids in this context may be associated with enhanced local and systemic beta-responsiveness, and if a causal relationship could be confirmed, this may constitute yet another advantage of early inhaled corticosteroid treatment in asthma. These data also suggest that chronotropic effects of high-dose albuterol should be monitored in patients using inhaled triamcinolone.

Acute Disease↗
PubMed1993

Cost accounting in radiation oncology: a computer-based model for reimbursement.

PURPOSE: The skyrocketing cost of medical care in the United States has resulted in multiple efforts in cost containment. The present work offers a rational computer-based cost accounting approach to determine the actual use of resources in providing a specific service in a radiation oncology center. METHODS AND MATERIALS: A procedure-level cost accounting system was developed by using recorded information on actual time and effort spent by individual staff members performing various radiation oncology procedures, and analyzing direct and indirect costs related to staffing (labor), facilities and equipment, supplies, etc. Expenditures were classified as direct or indirect and fixed or variable. A relative value unit was generated to allocate specific cost factors to each procedure. RESULTS: Different costs per procedure were identified according to complexity. Whereas there was no significant difference in the treatment time between low-energy (4 and 6 MV) or high-energy (18 MV) accelerators, there were significantly higher costs identified in the operation of a high-energy linear accelerator, a reflection of initial equipment investment, quality assurance and calibration procedures, maintenance costs, service contract, and replacement parts. Utilization of resources was related to the complexity of the procedures performed and whether the treatments were delivered to inpatients or outpatients. In analyzing time motion for physicians and other staff, it was apparent that a greater effort must be made to train the staff to accurately record all times involved in a given procedure, and it is strongly recommended that each institution perform its own time motion studies to more accurately determine operating costs. Sixty-six percent of our facility's global costs were for labor, 20% for other operating expenses, 10% for space, and 4% for equipment. Significant differences were noted in the cost allocation for professional or technical functions, as labor, space, and equipment costs are higher in the latter. External beam treatment-related procedures accounted for more than 50% of all technical and professional revenues, simulation for 8% to 10%, and other physics/dosimetry procedures for 11% to 14% of revenues. Some discrepancies were identified between the actual cost and level of reimbursement of various procedures. Details are described in the manuscript. CONCLUSION: It is imperative to develop an equitable reimbursement system for radiation oncology services, based on cost accounting and other measures that may enhance productivity and reduce the cost per procedure unit, while at the same time preserving the highest quality of service provided to patients.

Accounting↗