Search PubMed⌕ Search

Biomedical subjects

M McCarthy

Publications and source records attributed to M McCarthy.

At least 325 records · Page 18Linked to original sources
PubMed1990

Synergism through direct covalent bonding between agents: a strategy for rational design of chemotherapeutic combinations.

Self-assembling chemotherapeutic agents are mixtures of relatively nontoxic precursors that can combine chemically under physiological conditions to form products with greater cytotoxic and/or antimicrobial activity than either of the precursors. Combinations that form products more rapidly in or near the target (tumor, pathogen, virally infected cell) than in normal tissues will exhibit target-selective synergism, thus exhibiting an antitarget selectivity that is greater than the selectivities of the product (e.g., a hydrazone) and of either precursor (e.g., a hydrazine derivative or ketone) used singly. This paper describes the target-selective cytotoxic synergism of a cationic aldehyde (A) and a cationic acylhydrazine (B) containing a triarylalkylphosphonium moiety against Ehrlich ascites carcinoma cells (ELA) in culture, in addition to reviewing previous work on self-assembling cytotoxins. The synergism between A and B is carcinoma selective when the ELA cells (the target) are compared to CV-1, an untransformed African green monkey kidney epithelial line. Like tetraphenylphosphonium and rhodamine 123, which are selectively concentrated in ELA cells relative to CV-1, A, B and the hydrazone C resulting from their reaction are lipophilic delocalized cations that selectively inhibit ELA growth relative to CV-1 growth. The hydrazone C is more growth inhibitory than either A or B for both cell lines. A combination of A with an unreactive analogue of B and a combination of B with an unreactive analogue of A did not synergistically inhibit ELA proliferation. The degree of synergism is greater against the ELA cells than against the CV-1 cells. These data, together with hydrazone formation kinetics, suggest that A and B are both concentrated together selectively inside the ELA due to the transmembrane potentials, reacting inside the ELA cells at a higher velocity than inside the CV-1 cells to form the more growth-inhibitory hydrazone C.

Animals↗
PubMed1990

Effect of the steroidal androgen receptor antagonist Win 49,596 on steroid-induced benign prostatic hyperplasia in the castrate beagle dog.

The effects of the steroidal androgen receptor antagonist Win 49,596 on steroid-induced prostatic growth, histomorphology, and secretory function were studied in the castrate male beagle dog. At oral doses ranging from 0.625 to 40 mg/kg/day for 12 weeks, Win 49,596 inhibited prostatic growth in terms of both weight and total DNA in a dose-dependent manner. In addition, both the incidence and severity of diffuse glandular hyperplasia/hypertrophy were dose-dependently inhibited by Win 49,596, resulting in diffuse glandular atrophy. Prostatic secretory function was also inhibited by Win 49,596 treatment. The effects of Win 49,596 at a dosage of 40 mg/kg/day were similar to that observed for the nonsteroidal androgen receptor antagonist flutamide at 10 mg/kg/day. Oral administration of Win 49,596 to castrate dogs at a dosage of 40 mg/kg/day for 12 weeks failed to produce any evidence of agonist activity. These results demonstrate that Win 49,596 prevented the experimental induction of benign prostatic hyperplasia in dogs and suggest that on further evaluation this compound may be efficacious in the treatment of the human disease.

Androgen Antagonists↗
PubMed1990

The thin ideal, depression and eating disorders in women.

It is proposed that a cultural ideal of thinness for women causes depression at a higher rate among women than among men. This model accounts for five currently unintegrated trends in the epidemiology of depression. It explains why: (1) twice as many women as men are likely to be depressed; (2) this sex difference emerges at puberty; (3) this sex difference is only found in western countries; (4) there is more depression today; (5) the average age of onset for depression is younger now than in the past. Four parallel trends in eating disorders can also be accounted for by the same factor.

Adolescent↗
PubMed1990

Herpes simplex virus type 1 infection of rat astrocytes in primary culture: effects of dibutyryl cyclic AMP.

Monolayer cultures of primary rat astrocytes grown with or without dibutyryl cyclic AMP (dBcAMP) for two weeks or longer were infected with round plaque-forming (Rd) or syncytia-forming (Syn) variants of herpes simplex virus type 1 (HSV-1). Infection with HSV-1 did not stimulate synthesis of glial fibrillary acidic protein (GFAP) or alter the general organization of the intermediate (glial) filaments in astrocyte cultures. However, the dBcAMP-treated astrocytes produced 10- to 100-fold lower titers of cell-free progeny HSV-1 than the untreated astrocyte cultures. Radiolabeled amino acid or glucosamine incorporated into acid precipitable cellular or viral glycoproteins was decreased by 10-25% in dBcAMP-treated astrocytes. Distinctive cell-rounding or syncytial cytopathology was produced by HSV-1 strains infecting untreated astrocytes, but the infected dBcAMP-treated astrocytes displayed only cell-rounding cytopathology. The dBcAMP-related effects on HSV-1 infection were specific to primary astrocyte cultures; they were not observed in HSV-1-infected human fibroblast cultures treated with dBcAMP. Comparison of HSV-1 infection of untreated versus dBcAMP-treated astrocytes suggests that the dBcAMP-induced "reactive" or differentiated state of the astrocyte can affect expression of virus-induced cytopathology and virus-specific polypeptide synthesis. The dBcAMP-treated primary astrocyte culture may afford a non-neoplastic, differentiated in vitro system for studying HSV-neural cell interactions.

Animals↗
PubMed1990

Ammonia induced decrease in glial fibrillary acidic protein in cultured astrocytes.

Previous studies of human hepatic encephalopathy (HE) have shown decreased levels of glial fibrillary acidic protein (GFAP) in Alzheimer type II astrocytes. In view of the important role of ammonia in the pathogenesis of HE, we carried out immunocytochemical and enzyme-linked immunosorbent assay (ELISA) studies on the effect of ammonium chloride (10 mM) on GFAP content in primary astrocyte cultures. There was a 39% loss of GFAP after a four day treatment. There was no fall in total cell protein. Potential mechanisms for this apparent selective loss of GFAP are discussed.

Ammonia↗
PubMed1990

Mycobacterial infection in patients infected with the human immunodeficiency virus.

Of 207 homosexual or bisexual patients with the acquired immune deficiency syndrome (AIDS), 24 with the AIDS related complex, and 39 with asymptomatic HIV infection, 32 patients were found to have mycobacterial infection. Mycobacterium tuberculosis was found in 13 patients with AIDS and in two with the AIDS related complex. M avium-intracellulare was found in 15 patients with AIDS and was disseminated in 12. One patient was infected with M kansasii and one with M ulcerans. Invasive procedures were frequently required to obtain positive bacteriological results. Subclinical carriage of M avium-intracellulare and other mycobacteria thought to be nonpathogenic was common in patients seronegative for the human immunodeficiency virus and at all stages of human immunodeficiency virus infection. All but one isolate of M tuberculosis were fully sensitive to standard antimycobacterial antibiotics. Response to treatment was usually rapid. M avium-intracellulare isolates were all resistant to first line agents in vitro, and antibiotics such as ansamycin and amikacin were required to obtain a clinical response.

AIDS-Related Complex↗
PubMed1990

The effect of the steroidal androgen receptor antagonist, Win 49,596, on the prostate and testis of beagle dogs.

The effect of the steroidal androgen receptor antagonist Win 49,596 on the prostate and testis was studied in beagle dogs and was compared to the effects of the nonsteroidal androgen receptor antagonist ICI 176,334 and the steroidal 5 alpha-reductase inhibitor MK-906. Win 49,596 was shown to bind to the androgen receptor from normal canine prostate with a Ki of 2.2 microM. After 16 weeks of treatment, prostate size, as estimated by transrectal ultrasonography, was unchanged in intact controls and was 26% of the initial size in castrate controls. Oral doses of Win 49,596 from 0.625-40 mg/kg.day for 16 weeks caused dose-dependent prostatic regression and a dose-related increase in both the incidence and severity of glandular atrophy of the prostate. Prostatic secretory function was also inhibited by Win 49,596 treatment. The effects of Win 49,596 at 40 mg/kg.day on prostatic weight, total DNA, histomorphology, and secretory function were similar to those of castration, while the effects of Win 49,596 at 10 mg/kg.day were similar to those of ICI 176,334 at 0.25 mg/kg.day and MK-906 at 1.0 mg/kg.day. No effects on testicular weight, daily sperm production, or spermatogenesis were observed; however, mild Leydig cell hyperplasia was observed in two dogs treated with 40 mg/kg.day Win 49,596. In addition, at 10 and 40 mg/kg.day Win 49,596, moderate but variable increases in serum testosterone levels were observed. In summary, Win 49,596 caused regression of the hypertrophic canine prostate without effects on spermatogenesis and/or sexual function, supporting its possible use in the treatment of human benign prostatic hypertrophy/hyperplasia.

5-alpha Reductase Inhibitors↗
PubMed1990

Telephone advice for out of hours calls in general practice.

Telephone advice in out of hours general practice consultations has been infrequently described in the United Kingdom. Data from 13 general practices (77 doctors) in north London were collected over four-week periods. Of the 970 calls recorded, 86% were managed directly by the practice, and 14% by a deputizing service. The percentage of calls managed by telephone advice varied from 5% to 57% (mean 37%). Use of deputies increased at night, but general practitioners remaining on call maintained their telephone advice rates. In all but one practice trainees also gave telephone advice, but the overall proportion of calls managed by trainees (33%) was lower than that of principals (48%). Children and adults under 60 years, more frequently received telephone advice than elderly patients, as did patients noted by the general practitioners as habitual callers compared with other patients.

Family Practice↗
PubMed1990

Exposure to a chloride-deficient formula during infancy: outcome at ages 9 and 10 years.

A school-based survey of the 1978 to 1979 birth cohort of two metropolitan Washington, DC, counties was conducted to find children who had been exposed to the chloride-deficient formulas Neo-Mull-Soy and Cho-Free during infancy. Children who had ingested other soy formulas that had an adequate chloride content were also found and matched to the exposed children by sex, race, birth weight, the age of the child, the mixed feeding status of the child, and maternal education. One hundred seventy-one of the exposed children and 261 soy control children were given a battery of psychologic tests in their homes to determine whether there had been any effect on intellectual development as a result of exposure to the chloride-deficient formulas. There were no differences in scores between the groups on the Wechsler Intelligence Scale for Children-Revised, the Boston Naming Test, the Rey-Osterrieth Test, or the FAS Verbal Fluency Test. There was no correlation between duration of exclusive exposure to the chloride-deficient formulas and the Wechsler Intelligence Scale for Children-Revised Full-Scale IQ Score (Pearson product-moment r = -.0825, P = .28). These results cannot be extrapolated to exposed children with documented hypochloremic metabolic alkalosis. It is concluded that in children without documented evidence of hypochloremic metabolic alkalosis, exposure to the chloride-deficient formulas Neo-Mull-Soy or Cho-Free during infancy has not resulted in any long-term adverse effects on cognitive development.

Child↗
PubMed1990

Serosurvey of prevalence of human immunodeficiency virus amongst high risk groups in Port Sudan, Sudan.

During October, 1987, 593 sera were collected from risk groups in Sudan's only major deepwater port, Port Sudan. The risk groups included prostitutes, lorry drivers and prisoners. A large proportion of the study participants practised high risk behaviour which included sexual promiscuity, medical treatment by injection, scarification and tattooing. Despite high risk behaviour and evidence of a high prevalence of hepatitis B infection, a virus transmitted in a manner similar to HIV, no study participants were positive for HIV infection. This data suggests that the prevalence of HIV infection amongst high risk groups in Port Sudan is very low. These findings confirm a lack of clinical cases of AIDS in hospitalized patients in Port Sudan and the small number of reported cases in other areas of northern Sudan.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Population-based study of the developmental outcome of children exposed to chloride-deficient infant formula.

In 1978 and 1979 a large number of US children were fed chloride-deficient soy-based infant formula. A representative sample of such children was identified in a southern county through a mailing to the homes of 3639 first- and second-grade children in the public schools. Of the 2329 (64%) who responded, 56 reported use of deficient formula and were invited to have developmental testing by one of four study psychologists at their school. Of the 310 users of other soy formulas, 112 were selected for testing as matched controls on the basis of their sex, feeding history, age, birth weight, and socioeconomic status (as indicated by school attended). After exclusions and refusals, 42 children who used deficient formula and 66 control children were tested using the McCarthy Scales of Children's Abilities. Examiners were unaware of the child's history of formula use. The mean General Cognitive Index was 102.8 in those using deficient formula and 105.4 in controls. After adjustment for demographic differences the children who used chloride-deficient formula were found to average 4.9 points less than the controls (P = .04, 1-tailed). The largest difference was in the Quantitative subscale (P = .005). These data show a statistically significant although small effect of chloride-deficient formula on the long-term developmental outcome of exposed children; however, further study of these results is needed for full confirmation.

Child↗
PubMed1989

The benefit of seat belt legislation in the United Kingdom.

Legislation for compulsory wearing of seat belts by car drivers and front seat passengers has been acclaimed as a major public health advance. Reports from other countries, and two recent evaluative studies in the United Kingdom, have suggested that legislation reduces both deaths and injuries. To assess the effect of the UK law 5 years after its implementation, trends in routine data for 1976-1987 have been reviewed. There were two sources of data: mortality statistics, published by the Office of Population Censuses and Surveys in the quarterly Monitor DH4, and road accident statistics, recorded by the police and published by the Department of Transport. There is a downward trend in deaths over the period, but the data show little impact from the law. One explanation for this lack of effect is the risk compensation hypothesis, which suggests that "safety" improvements are transferred by drivers into increased performance--the amount and speed of travel. Public health policies need to take into account the complex behavioural interactions between travel and safety choices if they are to affect underlying trends.

Accidents, Traffic↗
PubMed1989

Measuring symptoms in terminal cancer: are pain and dyspnoea controlled?

The symptoms of 86 patients referred to a district terminal care support team were rated throughout care using a standardized schedule. Pain was the most common main symptom at referral, occurring in 35 (41%) of the patients. The assessment scores for pain showed significant improvements after one week of care (P less than 0.01) and there was a further improvement into the week of death. However, towards death, 18 (21%) patients developed dyspnoea as their main symptom, and this became the most severe symptom at death. The symptom assessment scores for patients with dyspnoea showed no change over time, suggesting that existing methods to control dyspnoea are ineffective and that new interventions are needed.

Dyspnea↗
PubMed1989

Community psychiatric care for homeless people in inner London.

Data about 'homeless' and 'home-based' clients referred to and recorded by community psychiatric nurses (CPNs) in Bloomsbury, an inner London health district, in 1985 and 1986 were reviewed. Of the 974 people seen, 642 were home-based and 322, homeless at time of referral. The homeless were more commonly under 65-years-of-age, living alone and unemployed. Two thirds of both groups had a psychiatric history, with half also having been admitted to a mental hospital. CPNs identified mental health problems in both groups with equal frequency, but homeless people were more likely to express their main problem as related to housing, finance or unemployment. Four out of five home-based clients were referred by statutory services compared with only two out of five homeless clients. The latter were less likely to receive supportive care from the CPN service and were more often referred to other agencies; these differences remained after controlling for the presenting problems. One in three people referred to this service were homeless. The social aspects of their problems, and their lack of contact with statutory services, suggest that homeless people need a multi-disciplinary approach for mental health care.

Community Mental Health Services↗
PubMed1988

DF-2 infection.

Explore the source record for details and available documents.

Animals↗