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Biomedical subjects

S A Beck

Publications and source records attributed to S A Beck.

At least 19 recordsLinked to original sources
PubMed2006

Getting strategic about the environment and health.

Historically, the physical environment has been a target for public health policy across the globe. This remains the case in developing countries where the enduring infectious and toxic challenge posed by the environment is tangible and its health impact is manifest. However, in Western societies, the relevance of the environment to health has become obscured. Even when this is not the case, the perspective is usually narrow, centering on specific toxic, infectious or allergenic agents in particular environmental compartments. It is rare for importance to be given to a health-determining role for the environment acting through broader psychosocial mechanisms. The result is that environmental manipulation is seen as a cornerstone of the public health response for comparatively few health concerns. This paper considers how public health policies and action on the physical environment may be pursued more optimally. The need for a more strategic approach, which employs a new conceptual model that recognizes the complexity and contextual issues affecting the relationship between the environment and health but retains sufficient flexibility and simplicity to have practical application, is identified. Building on recent work, a model is proposed and pointers are given for its use in a practical context.

Causality↗
PubMed2004

Effect of cancer cachexia on triacylglycerol/fatty acid substrate cycling in white adipose tissue.

The effect of cancer cachexia on the TAG/FA substrate cycle in white adipose tissue was determined in vivo using the MAC16 murine model of cachexia. When compared with non-tumor-bearing animals, the rate of TAG-glycerol production was found to be increased almost threefold in animals bearing the MAC13 tumor, which does not induce cachexia, but was not further elevated in animals bearing the MAC16 tumor. In both cases TAG-glycerol production and de novo synthesis of TAG-FA were also increased above non-tumor-bearing animals. In animals bearing the MAC16 tumor, the TAG-FA rates were significantly higher than in animals bearing the MAC13 tumor. This suggests that the presence of the tumor alone is sufficient to cause an increase in cycling rate, and in the absence of an elevated energy intake (MAC16) this may contribute to the depletion of adipose tissue.

Adipose Tissue↗
PubMed1998

Multiagency outcome evaluation of children's services: a case study.

Outcome monitoring has become a focus of accountability for public and nonprofit human service agencies. Besides providing answers to funders' questions about the services' impact, outcome monitoring helps administrators improve program effectiveness. After a three-year development period and a one-year implementation experience, SumOne for Kids represents a technically advanced outcome-monitoring system for children's mental health and/or child welfare services. Initiated, designed, and tested by 31 children's service agencies throughout Pennsylvania, and with state bureaucrats' and policy makers' encouragement, SumOne for Kids represents an effort to create a bottom-up/top-down process for implementing a statewide outcome-monitoring system. This article describes the genesis of this outcome-monitoring system, primary design principles, use of social validation for outcome selection, resolution of methodological difficulties, and reasons for selecting functional over clinical outcomes. The article reviews lessons learned through the development experience instructive to children's service managers, program evaluators, and industry leaders interested in establishing outcome-monitoring systems.

Child↗
PubMed1997

Sub-Tenon's versus peribulbar anaesthesia for cataract surgery.

We present a comparison of one quadrant sub-Tenon's anaesthesia and peribulbar anaesthesia. Patient discomfort during injection of anaesthetic and during cataract surgery was assessed using a 10-point visual analogue scale ranging from no pain to the worst pain imaginable. Data are available for 74 patients undergoing cataract surgery under peribulbar anaesthesia and for 55 patients in whom sub-Tenon's anaesthesia was used. Pain scores for administration of anaesthetic were significantly lower (Kruskal-Wallis H-test, p < 0.01) for sub-Tenon's anaesthesia (mean 1.4) compared with the peribulbar technique (mean 2.4). However, a similar number of patients experienced pain of greater than 3 for the two techniques (10 (18.5%) for sub-Tenon's and 14 (18.9%) for peribulbar). Per-operative pain scores for sub-Tenon's anaesthesia (mean 0.5) were lower than those for peribulbar anaesthesia (mean 1.2) but not significantly so (Kruskal-Wallis H-test, p = 0.073). Significantly fewer patients, however, experienced pain of greater than 3 (Fisher exact test, p < 0.05) in the sub-Tenon's group. In addition less anaesthetic solution and a shorter interval from administration to surgery was required in the sub-Tenon's group. Sub-Tenon's anaesthesia appears to be a more effective method of anaesthesia than the peribulbar method.

Aged↗
PubMed1995

Purification and characterization of a lipid-mobilizing factor associated with cachexia-inducing tumors in mice and humans.

A scheme is described for the purification of a lipid-mobilizing factor from a cachexia-inducing murine tumor (MAC16) using a combination of ion exchange (Mono Q), exclusion (Superose), and hydrophobic (C8) chromatography. This process yields an active material with an apparent molecular weight of 24,000 with an overall purification of 3,500 from the tumor homogenate and representing 0.005% of the total protein present. The material tends to aggregate to high molecular mass, is acidic (pI < 4), and displays heterogeneity of charge as evidenced by a broad elution profile on ion exchange and exclusion chromatography and multiple peaks on hydrophobic columns. The purified material was heat and alkali (pH 10.4) labile and activity could be completely inhibited by sulfatase, suggesting that the negative charge could arise from sulfate residues. There was no evidence that the material possessed triglyceride lipase activity. Animals transplanted with the MAC16 tumor and with a delayed weight loss contained in their serum antibodies that recognized a M(r) 24,000 band on Western blots. This material copurified with the lipid-mobilizing factor. Such antibodies were not present in the serum of mice transplanted with the MAC13 tumor, which does not induce cachexia, suggesting that the antibodies were directed to the induction of cachexia rather than the tumor itself. Urine from patients with cancer cachexia also contained a lipid-mobilizing factor which adhered to DEAE-cellulose and gave an apparent M(r) of 24,000 by exclusion chromatography. Western blotting using serum from MAC16 tumor-bearing animals showed the presence of a band of M(r) 24,000 in such fractions, which was not detected using serum from mice bearing the MAC13 tumor. This band was not present in Western blots of urine from normal subjects. The fact that serum from mice bearing the MAC16 tumor can detect the human lipid-mobilizing activity suggests a high degree of structural similarity between the two and raises the possibility that cachexia in humans may be caused by the same species as in the mouse.

Animals↗
PubMed1993

Kinetics of the inhibition of tumour growth in mice by eicosapentaenoic acid-reversal by linoleic acid.

Oral administration of eicosapentaenoic acid (EPA) (2.0 g/kg) by gavage to female NMRI mice bearing the MAC16 colon adenocarcinoma and with weight loss, prevented further loss in body weight and produced a delay in the growth of the tumour. Cell production and loss were determined by the [125I]5-iodo-2'-deoxyuridine method during the stationary and growth phase of the tumour in animals treated with EPA. Tumour stasis appeared to arise from an increase in the rate of cell loss from 38 to 71% without a significant change in the potential doubling time. During the subsequent growth phase the cell loss factor was reduced to 52% and this was combined with a reduced potential doubling time from 32 to 26 hr. The antiproliferative, but not the anticachectic effect of EPA could be reversed by oral administration of pure linoleic acid (LA), (1.9 g/kg) which acted to increase tumour growth by reducing the cell loss factor to 45%. Despite this reversal, incorporation of EPA into tumour cell lipids was not significantly different in animals administered with either EPA alone or combined with LA. This suggests that the antiproliferative effect of EPA in this system may arise from an indirect effect through the blocking of the catabolic effect of the tumour on host adipose tissue, which normally supplies fatty acids essential for tumour growth. This suggests that LA may be required by some tumours to prevent cell loss and that the catabolism of adipose tissue, which accompanies cancer cachexia effectively supplies this fatty acid to the tumour.

Adenocarcinoma↗
PubMed1992

Lipid metabolism in cancer cachexia.

The effect of cancer cachexia on the oxidative metabolism of lipids has been studied in mice transplanted either with the MAC16 adenocarcinoma, which induces profound loss of body weight and depletion of lipid stores, or the MAC13 adenocarcinoma, which is the same histological type, but which grows without an effect on host body weight or lipid stores. While oxidation of D-[U-14C]glucose did not differ between animals bearing tumours of either type and non-tumour bearing controls, oxidation of [1-14C]triolein administered by intragastric intubation was significantly (P less than 0.05) higher in animals bearing the MAC16 tumour than in either non tumour-bearing controls or in animals bearing the MAC13 tumour. Intestinal absorption of [14C]lipid was significantly (P less than 0.05) reduced in animals bearing the MAC13 tumour when compared with either non tumour-bearing animals or MAC16 tumour-bearing animals, but was not significantly different in the latter two groups. The level of labelled lipids in heart and adipose tissue after an oral [14C]lipid load was significantly lower in animals bearing the MAC16 tumour compared with the other two groups. The level of tumour lipids was also higher in the MAC16 than in the MAC13 tumour after both an oral [14C]lipid load or by direct injection of [U-14C]palmitate complexed to albumin into epididymal fat pads. Oxidation of [U-14C]palmitate was also significantly enhanced in liver and heart homogenates from animals bearing the MAC16 tumour. These results suggest that in cachectic tumour-bearing animals mobilisation of body lipids is accompanied by an increased utilisation.

Adenocarcinoma↗
PubMed1991

Anticachectic and antitumor effect of eicosapentaenoic acid and its effect on protein turnover.

The effect of the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) on host body weight loss and tumor growth has been investigated in mice bearing a cachexia-inducing colon adenocarcinoma, the MAC16. EPA effectively inhibited both host weight loss and tumor growth rate in a dose-related manner with optimal effects being observed at a dose level of 1.25 to 2.5 g/kg. At these concentrations host body weight was effectively maintained, and there was a delay in the progression of growth of the tumor, such that overall survival was approximately doubled in EPA-treated animals, using the criteria dictated by the United Kingdom Coordinating Committee for the welfare of animals with neoplasms. Even when tumor growth resumed, weight loss did not occur. Animals bearing the MAC16 tumor showed a decreased protein synthesis and an increased degradation in skeletal muscle. Treatment with EPA significantly reduced protein degradation without an effect on protein synthesis. The effect of GLA on both host body weight loss and tumor growth was much less pronounced than that of EPA, with an effect only being seen at a dose of 5 g/kg, at which some toxicity was observed. In vitro studies showed that while EPA was effective in inhibiting tumor-induced lipolysis, GLA was ineffective in this respect. However, prostaglandin E1, which is formed from GLA in vivo, showed partial reversal of tumor-induced lipolysis and probably accounted for the anticachectic effect of GLA. These results suggest that EPA as the pure fatty acid should be considered for clinical investigation as both an anticachectic and antitumor agent, since prior work has shown that the other major component of fish oil docosahexaenoic acid is without pharmacological activity in this system.

Animals↗
PubMed1991

Inhibition of tumour-induced lipolysis in vitro and cachexia and tumour growth in vivo by eicosapentaenoic acid.

Stimulation of lipolysis in murine adipocytes in response to a lipid-mobilizing factor produced by a cachexia-inducing murine adenocarcinoma was inhibited by eicosapentaenoic acid (EPA) with a Ki value of 104 microM. The inhibitory effect was strictly structurally specific, since other related fatty acids of both the (n-3) and (n-6) series were ineffective as inhibitors of the lipolytic process. Induction of lipolysis by both salbutamol and ACTH was also inhibited by EPA, suggesting that the effect is exerted on a step central to the process of lipolysis. Lipolysis induced with the tumour lipid-mobilizing factor was associated with a prolonged elevation of the intracellular level of cyclic AMP in adipocytes, in contrast with ACTH and salbutamol. The elevation of adipocyte cyclic AMP in response to the tumour lipid-mobilizing factor and lipolytic hormones was inhibited by EPA. In vivo, administration of pure EPA to weight losing mice bearing the MAC16 adenocarcinoma completely prevented weight loss and tumour growth rate. In contrast both the other (n-3) fatty acid present in fish oil, docosahexaenoic acid (DHA), and linoleic acid were ineffective in inhibiting weight loss or the growth of the MAC16 tumour. This suggests that inhibition of tumour lipolytic activity accounts for the anticachectic effect of EPA, and that a correlation may exist between the inhibition of cachexia and the inhibition of tumour growth.

Adenocarcinoma↗
PubMed1991

Changes in activity of lipoprotein lipase, plasma free fatty acids and triglycerides with weight loss in a cachexia model.

The effect of weight loss during cancer cachexia on the plasma levels of free fatty acids (FFA) and triglycerides, and on the tissue levels of lipoprotein lipase (LPL), has been studied in mice bearing an experimental colon adenocarcinoma (MAC16). Despite extensive mobilisation of host body fat reserves, plasma levels of triglycerides were reduced irrespective of the extent of weight loss. The plasma levels of FFA also showed an initial decrease with weight loss, followed by a rise peaking at a weight loss of about 2 g, and thereafter the levels decreased with increasing weight loss. The level of LPL in both heart and adipose tissue showed an initial rise with increasing weight loss also peaking at a weight loss of approximately 2.5 g, followed by a decrease with further weight loss. The increased LPL would provide an increased level of fatty acids for oxidation in the cachectic state and would account for the effect on plasma FFAs and triglycerides.

Adenocarcinoma↗
PubMed1991

Lipid mobilising factors specifically associated with cancer cachexia.

Both urine and plasma from mice and humans with cancer cachexia have been shown to contain higher levels of lipid mobilising activity than normal controls, even after acute starvation. There was no significant increase in the urinary lipid mobilising activity of either mice or humans after acute starvation, suggesting that the material in the cachectic situation was probably not due to an elevation of hormones normally associated with the catabolic state in starvation. Further characterisation of the lipid mobilising activity in the urine of cachectic mice using Sephadex G50 exclusion chromatography showed four distinct peaks of activity of apparent molecular weights of greater than 20, 3, 1.5 and less than 0.7 kDa. No comparable peaks of activity were found in the urine of a non tumour-bearing mouse. The high molecular weight activity was probably formed by aggregation of low molecular weight material, since treatment with 0.5 M NaCl caused dissociation to material with a broad spectrum of molecular weights between 3 and 0.7 kDa. Lipolytic species of similar molecular weights were also found in the urine of cachectic cancer patients, but not in normal urine even after 24 h starvation. The lipid mobilising species may be responsible for catabolism of host adipose tissue in the cachectic state.

Adipose Tissue↗
PubMed1991

Egg hypersensitivity and measles-mumps-rubella vaccine administration.

Because reports have described egg-sensitive individuals in whom anaphylaxis developed after measles vaccination, current recommendations include delaying administration of egg-derived vaccines until skin testing can be performed. Specifically, the 1988 Red Book recommends skin testing via scratch, prick, or puncture with 1:10 dilution of the vaccine and, if the result is negative, intradermal testing is suggested. The purpose of this study was to evaluate the likelihood of reaction to measles-mumps-rubella (MMR) vaccine in patients with documented egg sensitivity and to delineate the efficacy of skin-prick testing (SPT) to MMR as a predictor of hypersensitivity to the vaccine. Egg sensitivity was documented by initial SPT to egg and then, if possible, double-blind placebo-controlled food challenge (DBPCFC). Patients with a positive DBPCFC to egg or a history of anaphylactic egg sensitivity had a SPT with the MMR vaccine and then were given the MMR vaccine. Additionally, children with atopic dermatitis who had been previously proven egg sensitive via DBPCFCs were evaluated retrospectively for sensitivity to the MMR vaccine. Sixteen children with a history of egg sensitivity underwent SPT to egg, with a positive result 3 mm greater than the negative control found in 12 patients. Eight of these children had a positive DBPCFC to egg. The SPT to MMR vaccine was negative in all 16 children; vaccine administration followed with no resultant systemic problems. Three children had a local reaction at the site of injection. Twelve additional children with atopic dermatitis and egg sensitivity were reviewed. Each child had a positive SPT and DBPCFC to egg.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1990

Lipolytic factors associated with murine and human cancer cachexia.

We have identified a lipolytic factor in extracts of a cachexia-inducing murine carcinoma (MAC16) that shows characteristics of an acidic peptide and appears to be composed of three fractions of apparent molecular weights corresponding to 3 kd, 1.5 kd, and 0.7 kd, as determined by exclusion chromatography. Material with identical chromatographic and molecular weight characteristics was also present in the serum of patients with clinical cancer cachexia but absent from normal serum, even under conditions of starvation. The MAC16 lipid factor, when injected into animals bearing the non-cachexia-inducing tumor MAC13, was capable of inducing weight loss without a significant reduction in food intake. Similar lipolytic material, although in lower concentration, was also found in the MAC13 tumor extracts. These findings suggest that cachexia may arise from the enhanced expression of a lipolytic factor associated with tumor cells.

Adenocarcinoma↗
PubMed1990

Effect of megestrol acetate on weight loss induced by tumour necrosis factor alpha and a cachexia-inducing tumour (MAC16) in NMRI mice.

The effect of the synthetic progesterone, megestrol acetate, on weight loss induced by both tumour necrosis factor alpha (TNF) as a model for the cachexia accompanying the acquired immunodeficiency syndrome and by a cachexia-inducing tumour (MAC16) has been studied in NMRI mice. Megestrol acetate was effective in preventing weight loss in both model systems with treated animals having an increase in intake of both food and water. Megestrol acetate was unable to prevent loss of body weight in animals pair-fed with TNF treated animals, suggesting that the increase in food and water intake was responsible for the increase in body weight. Analysis of body composition showed that the major contribution to the increase in body weight in animals treated with megestrol acetate was an increase in water content, although there was also an increase in carcass fat in animals bearing the MAC16 tumour given the high dose of megestrol acetate. Animals bearing the MAC16 tumour had a significant increase in tumour weight after treatment with megestrol acetate, possibly owing to the increased plasma glucose levels. These results suggest that an increase in appetite and weight gain alone are not sufficient to justify the anticachectic effect of a particular agent and that body composition analysis and tumour growth rate are very important parameters.

Adenocarcinoma↗
PubMed1990

Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients.

The possibility that weight loss in cancer patients may be augmented by tumour produced catabolic factors, which stimulate lipid mobilisation, was investigated in a group of cancer patients with total body weight loss ranging from 0 to 50%. The serum and urine lipolytic activity has been determined using freshly isolated murine adipocytes in an in vitro assay. As a control group, we have used patients with Alzheimer's disease, in which some patients may lose a considerable amount of weight, without an obvious cause. The serum lipolytic activity for the Alzheimer's group with weight loss (0.11 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1 serum) was not significantly different from the group without weight loss (0.11 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1) or from a healthy control group (0.07 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1), but all three groups were significantly (P less than 0.005) lower than the cancer patient group (0.20 +/- 0.03 mumols glycerol 10(5) adipocytes-1 ml-1), irrespective of weight loss. A similar difference between the cancer and the control group was observed for the urinary lipolytic activity (0.67 +/- 0.03 versus 0.28 +/- 0.03 mumols glycerol released 10(5) adipocytes-1 mg creatinine-1 respectively, P less than 0.01). Weight loss in animals bearing the MAC16 adenocarcinoma was paralleled by a corresponding rise in serum lipolytic activity which peaked when the loss of carcass weight was 16%. A similar decrease in serum lipolytic activity was also observed in cancer patients at high percentages loss in body weight. However, a linear relationship was observed between both the serum and urinary lipolytic activity and weight loss in cancer patients (correlation coefficients 0.79 and 0.70 respectively) when the total body weight loss did not exceed 20%. This suggests that weight loss in cancer patients may be attributed, at least in part, to an, as yet, unidentified lipolytic factor.

Adipose Tissue↗
PubMed1990

Alterations in serum lipolytic activity of cancer patients with response to therapy.

The effect of chemotherapy on the serum lipid mobilising activity of a group of cancer patients with or without weight loss has been determined. The pre-treatment level of serum lipolytic activity in all cancer patients, with or without weight loss, was higher than normal controls (0.22 +/- 0.01 versus 0.06 +/- 0.01 mumols glycerol released ml-1 serum respectively). The pre-treatment levels of lipid mobilising activity in the patients serum was proportional to the extent of weight loss (correlation coefficient 0.81), if the extent of weight loss was small (less than 14 kg). Patients who showed a positive response to chemotherapy also showed a decrease in their plasma levels of lipolytic activity, while a patient who showed no response to therapy also showed no change in the serum lipolytic activity. There was no correlation between the serum lipolytic activity and response to megestrol acetate, a synthetic orally active progestogen, which is currently under investigation as an anticachectic agent. Serum from cancer patients showed lipolytic activity which was retained on a DEAE cellulose column and eluted by a salt gradient, in contrast with normal controls. Response to chemotherapy was associated with a decrease of the retained material, although the profile did not return to the normal state. These results need confirmation in a larger group of patients using more specific methods to determine tumour lipolytic activity, but suggest that it may be possible to monitor response to therapy by measurement of the serum lipolytic activity.

Female↗