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Biomedical subjects

P Steele

Publications and source records attributed to P Steele.

At least 37 records · Page 2Linked to original sources

Aiding troubled employees: the prevalence, cost, and characteristics of employee assistance programs in the United States.

OBJECTIVES: Employee assistance programs (EAPs) are job-based programs designed to identify and assist troubled employees. This study determines the prevalence, cost, and characteristics of these programs in the United States by worksite size, industry, and census region. METHODS: A stratified national probability sample of more than 6400 private, nonagricultural US worksites with 50 or more full-time employees was contacted with a computer-assisted telephone interviewing protocol. More than 3200 worksites responded and were eligible, with a response rate of 90%. RESULTS: Approximately 33% of all private, nonagricultural worksites with 50 or more full-time employees currently offer EAP services to their employees, an 8.9% increase over 1985. These programs are more likely to be found in larger worksites and in the communications/utilities/transportation industries. The most popular model is an external provider, and the median annual cost per eligible employee for internal and external programs was $21.83 and $18.09, respectively. CONCLUSIONS: EAPs are becoming a more prevalent point of access to health care for workers with personal problems such as substance abuse, family problems, or emotional distress.

Adult↗

Rationale and design of the Dietary Approaches to Stop Hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure.

Epidemiologic studies have found that dietary patterns characterized by high intakes of certain minerals and fiber are associated with low blood pressure. Dietary Approaches to Stop Hypertension (DASH) is a multicenter, randomized, controlled-feeding trial designed to test the effects on blood pressure of two such dietary patterns consumed for 8 weeks. The two experimental diets will be compared with each other and with a control dietary pattern that is relatively low in potassium, magnesium, calcium, and fiber, and has a fat and protein profile mirroring current consumption. The first experimental diet, arguably termed "ideal," is high in fruits, vegetables, whole cereal products, low-fat dairy products, fish, chicken, and lean meats designed to be low in saturated fat and cholesterol; moderately high in protein; and high in minerals and fiber. The second experimental diet tests the effect of fruits and vegetables alone. Its potassium, magnesium, and dietary fiber content will be at the same high levels as the ideal dietary pattern, while its fat, protein, and calcium content will resemble that of the control dietary pattern. The study population will consist of 456 healthy men and women, aged 22 years or older, with systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. African-American and other minority groups will comprise 67% of the population. Participants will eat one of the three dietary patterns. The DASH trial has unique features. First, dietary patterns rather than single nutrients are being tested. Second, all food for the experimental diets is provided to the participants using a standardized multicenter protocol. Because the dietary patterns are constructed with commonly consumed food items, the results, if positive, may be conveniently implemented in dietary recommendations to the general public.

Adult↗

Adoptive transfer of lymphocytes sensitized to the major surface glycoprotein of Pneumocystis carinii confers protection in the rat.

Pneumocystis carinii is a major opportunistic pathogen and a leading cause of morbidity in patients with AIDS. CD4+ cells have been shown to be important in host defenses against P. carinii, but the antigen(s) involved with this response have not been identified. We undertook the present study to determine whether the major surface glycoprotein (MSG) of P. carinii contains epitopes that can elicit a protective cellular immune response. Spleen cells and purified CD4+ cells isolated from Lewis rats, pulsed 1-4 d with MSG, and injected into corticosteroid-treated Lewis rats with pneumocystosis resulted in significant reduction in the P. carinii burden, as judged by organism quantitation and lung histology. The protective response demonstrated by the donor cells was dependent on previous exposure to P. carinii, cell concentration, and time of incubation with MSG. In addition, reconstitution with MSG-specific CD4+ cells resulted in an early hyperinflammatory response within the lungs of these animals with a high percentage of mortality. Thus, in this model, MSG can elicit an immune response mediated by CD4+ cells, which has a harmful as well as helpful effect on the host, and these responses occur despite the presence of corticosteroids.

Animals↗

Guanylhydrazones in therapy of Pneumocystis carinii pneumonia in immunosuppressed rats.

Guanylhydrazones are cationic heteroaromatic drugs similar to the diamidines which are effective in the treatment of African trypanosomiasis and pneumocystosis. On the basis of their antitrypanosomal activity, different guanylhydrazones were selected for evaluation in a rat model of Pneumocystis carinii pneumonia. The most active compounds were the 2-(4'-formylphenyl)-1-methylimidazo-[1,2-a] pyridinium guanylhydrazones which, at a dose of 2 mg/kg/day, were about as effective as trimethoprim-sulfamethoxazole at a dose of 50 mg of trimethoprim per kg/day plus 250 mg of sulfamethoxazole per kg/day. The anti-P. carinii activity of these guanylhydrazone derivatives was found with parenteral but not with oral administration. The 1,3-arylene diketone bis(guanylhydrazones) were generally ineffective, although a triacetyl derivative showed some anti-P. carinii activity. Nitroimidazole guanylhydrazone derivatives were also ineffective. Attempts to improve the therapeutic efficacy of the different guanylhydrazones were limited by problems of toxicity. We conclude that some guanylhydrazone derivatives are potent anti-P. carinii drugs and that further studies should be pursued to develop safer compounds and investigate structure-activity relationships.

Animals↗

Synergistic combinations of Ro 11-8958 and other dihydrofolate reductase inhibitors with sulfamethoxazole and dapsone for therapy of experimental pneumocystosis.

We compared Ro 11-8958, an analog of trimethoprim (TMP) with improved antimicrobial and pharmacokinetic properties, other dihydrofolate reductase (DHFR) inhibitors, sulfamethoxazole (SMX), and dapsone (DAP) in the treatment of Pneumocystis carinii pneumonia in an immunosuppressed rat model. In contrast to previous reports, high dosages of the DHFR inhibitors were used in combination with fixed, low dosages of SMX (3 mg/kg of body weight per day) or DAP (25 mg/kg/day). When administered alone at these dosages, SMX and DAP reduced the median P. carinii cyst count about 5- to 15-fold. Ro 11-8958, TMP, and diaveridine used at a dosage of 20 mg/kg/day with SMX were only slightly more effective than SMX used alone. However, administration of these DHFR inhibitors at a dosage of 100 mg/kg/day with SMX lowered the cyst count about 500- to 1,000-fold, indicating a synergistic effect. Little or no synergism was found when other DHFR inhibitors (pyrimethamine, cycloguanil, and tetroxoprim) were combined with SMX. Regimens of Ro 11-8958 at a dosage of 20 mg/kg/day with DAP and of TMP or diaveridine used at a dosage of 100 mg/kg/day with DAP showed comparable anti-P. carinii activity, lowering the cyst count 100- to 200-fold. By contrast, Ro 11-8958 administered at a dosage of 100 mg/kg/day with DAP reduced the cyst count > 1,000-fold. Thus, the experimental approach used here enables the rat model of pneumocystosis to be used to compare synergistic combinations of antifolate drugs. The favorable results achieved with Ro 11-8958 indicate that it should be considered for clinical trials.

AIDS-Related Opportunistic Infections↗

Abnormal regulation of the myc gene in myeloid leukemia.

To study the regulation of expression of the myc protooncogene, cells from normal individuals and patients with acute myelogenous leukemia (AML), and chronic phase and blastic crisis of chronic myeloid leukemia (CML) cells were put in overnight culture in the presence or absence of fetal calf serum. Myc expression in normal marrow cells and chronic phase CML cells fell after culture in vitro. In contrast, myc expression was maintained or increased in a majority of the AML and blastic crisis CML specimens. These data demonstrate that the regulation of myc expression is disordered in many AML and blastic crisis specimens but not in chronic phase CML cells.

Base Sequence↗

A lupinosis-associated myopathy in sheep and the effectiveness of treatments to prevent it.

A lupinosis-associated myopathy occurred in 26 of 48 sheep given a crude toxic extract of Phomopsis leptostromiformis, and in 18 of 34 sheep that grazed a toxic lupin stubble. Treatment with selenium or alpha-tocopherol alone neither prevented nor cured the myopathy, but selenium and alpha-tocopherol together may have been partially effective. Among the group of 48 intoxicated sheep, those with myopathy had a significantly lower mean terminal concentration of alpha-tocopherol in their livers than those with no myopathy. There was no relationship between the severity of liver injury and the occurrence of the myopathy. It was considered that this lupinosis-associated myopathy may have a similar pathogenesis to nutritional myopathy. Data on plasma creatine phosphokinase and erythrocyte glutathione peroxidase activities, plasma alpha-tocopherol concentrations and terminal tissue concentrations of selenium and alpha-tocopherol are presented.

Animals↗

Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia.

The efficacy of antifolate, antiviral, and other drugs was compared in an experimental model of pneumocystosis. Sulfamethoxazole (SMX) administered alone in doses of greater than or equal to 60 mg/kg/day was highly effective in treatment and prophylaxis. Low (less than or equal to 15 mg/kg/day) doses of SMX showed limited, dose-related anti-Pneumocystis carinii activity in therapy but were more effective in prophylaxis. The dihydrofolate reductase (DHFR) inhibitors trimethoprim (TMP), pyrimethamine, and trimetrexate exhibited little anti-P. carinii activity when administered alone and did not enhance the efficacy of SMX; the effects of the DHFR inhibitors could not be related to the dose or the concentration in serum. These data suggested that the rat model is an excellent system for studying the anti-P. carinii activity of sulfonamides but is of limited value in studying DHFR inhibitors. The antiviral drugs azidothymidine, dideoxyinosine, inosine pranobex (Isoprinosine), amantadine, and acyclovir displayed little or no activity against P. carinii; however, azidothymidine did not impair the efficacy of SMX or TMP-SMX. These results supported the clinical practice of giving antiviral agents together with antifolate drugs to patients infected with human immunodeficiency virus and suggested that the beneficial effects of antiviral agents on the occurrence of pneumocystosis are due mainly to their effects on the virus or the host immune response. In contrast to the antiviral drugs, 9-deazainosine, a nucleoside analog with antiprotozoal properties, demonstrated marked activity against P. carinii which was related to dose and route of administration. These data raised the possibility that anti-P. carinii activity is a general property of purine nucleosides and suggested that further exploration of this class of compounds might lead to clinically useful agents.

Animals↗

Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.

Over a 7-year period, we analyzed 261 dose regimens of antimicrobial drugs in the treatment and prevention of Pneumocystis carinii pneumonia in an immunosuppressed rat model. These compounds ranged from drugs in clinical use to newly synthesized agents. Drug efficacy was expressed as the magnitude of the reduction in median P. carinii cyst or nucleus counts on a scale ranging from inactive (less than 5-fold) to very markedly active (greater than or equal to 1,000-fold). The classification system was reproducible and allowed drugs studied at different times to be compared with each other. The system demonstrated a hierarchy of anti-P. carinii activity not only among classes of compounds but also among individual members of a drug class. Sulfonamides, sulfones, and diamidines were the most active agents; some purine nucleosides and nitrofurans also showed promising activity; and most antiparasitic, antifungal, antibacterial, and antiviral drugs were inactive. We conclude that this classification system represents a simple, quantitative method of comparing the activities of antimicrobial drugs against P. carinii. Information gained from this system should be helpful in developing new anti-P. carinii compounds and establishing standard procedures for their evaluation.

Animals↗

Who eats what? A comparison of dietary patterns among men and women in different occupational groups.

Dietary data were obtained during a community-based study of risk factors for heart disease in 1983. Results were compared for men and women in broadly defined socioeconomic groups based on occupation and education. People in higher status occupation groups and with more education, and women more than men, had food consumption patterns more consistent with current health promotion messages. For example, they reported eating more wholemeal or brown bread and more fresh fruit and vegetables, drinking more skim or low-fat milk, eating fewer eggs and having less sugar in hot drinks or on cereals. There was some evidence, however, of an interplay of influences of cost and health awareness. For example, retired men were less likely than employed men to eat butter, cream, fresh fruit and vegetables, while men in the upper socioeconomic groups reported relatively higher consumption of butter and cream. The results emphasise the need for a range of strategies aimed at specific subgroups in order to improve national dietary patterns in Australia.

Adult↗

Plasma and liver concentrations of alpha-tocopherol in weaner sheep after vitamin E supplementation.

Changes in the plasma and liver concentrations of alpha-tocopherol in sheep kept in an animal house, grazed on pasture, grazed on pasture and fed an oat/lupin grain supplement, or grazed on toxic lupin stubble were monitored following no, oral or intramuscular administration of alpha-tocopherol. It was concluded that intramuscular administration was most effective because it caused longer periods of elevated plasma alpha-tocopherol concentrations in most situations investigated and consistently higher concentrations of alpha-tocopherol in the liver, compared to oral administration. The dose rates of alpha-tocopherol given, the vehicle for alpha-tocopherol in the injectable preparation, the different diets consumed and the concurrent occurrence of lupinosis all influenced the results. In spite of this a significant positive correlation existed between the terminal liver and plasma alpha-tocopherol concentrations.

Animals↗

Acceptability of a 7-day higher-carbohydrate, lower-fat menu: the Beltsville Diet study.

For 13 weeks, 20 men (aged 23 to 56), 19 premenopausal (aged 21 to 48), and 14 postmenopausal women (aged 49 to 65) consumed a 7-day rotation menu conforming to dietary recommendations of several research and health organizations. The diets were designed to make minimal changes in the standard American diet by the use of well-accepted normal foods. The average daily composition of the diet was 50% carbohydrate (complex 35%, simple 15%), 35% fat (P:S 0.7), and 15% protein; it contained 100 mg cholesterol, 1 gm sodium, and 14.5 gm neutral detergent fiber per 1,000 kcal. The acceptability of the menus was examined through questionnaires administered after the experimental diet period. Subjects rated the menus and individual foods and made recommendations for improvement of the menus. Most subjects (33 of 41 responding) rated the menu better than or almost as good as their usual diet. Few (9) were ever hungry during the 13-week period. During the study, a number of biochemical parameters were measured; the measurements indicated beneficial results. Blood pressure, cholesterol levels, and glucose responses were all improved after consumption of the menu. The results indicate that with minimal changes in the normal U.S. diet, acceptable menus that have beneficial effects on risk factors for heart disease and diabetes can be developed.

Adult↗

The urinary excretion of albumin in normal pregnancy.

The urinary excretion of albumin was measured in a group of normal pregnant women at 14, 28 and 36 weeks gestation and 6 weeks postpartum. Using 2-h urine collections, the excretion rate was not found to increase during pregnancy or to differ from that in a group of non-pregnant controls. The urinary albumin to creatinine concentration ratio was greater at all stages of pregnancy than in the non-pregnant controls and greater at 36 weeks than at 14 weeks gestation. Correcting for the observed changes in serum albumin and creatinine clearance produced evidence consistent with the hypothesis that mean glomerular permeability to albumin rises progressively during pregnancy. Reasons are given why the measurement of urinary albumin excretion may be a useful screening test in some pregnant women, and may also yield useful information on the effect of multiple pregnancies on renal function. One grand multipara was studied and found to have an increased excretion of albumin at each stage of pregnancy.

Albuminuria↗