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Biomedical subjects

M Gould

Publications and source records attributed to M Gould.

At least 19 recordsLinked to original sources
PubMed1999

Promoting physical activity in general practice: should prescribed exercise be free?

In the UK there are numerous schemes whereby general practitioners can prescribe exercise programmes, usually based in leisure centres. Of the factors that discourage adherence to such programmes in the USA, cost has proved important. We collected demographic and questionnaire data from 152 inner-London patients (108 women, 44 men) before they started an exercise programme on a National Health Service prescription, and analysed the results according to whether they dropped out of the programme (78%) or not. Use of logistic regression revealed only one previous barrier to exercise, 'not knowing about local exercise facilities', as a significant positive determinant of adherence (adjusted odds ratio 3.51, 95% confidence interval, 1.04 to 11.86). For 'lack of money' patients were more likely to drop out of the programme (adjusted odds ratio 0.25, 95% CI 0.07-0.85). The very low cost of participation in this scheme, did not encourage adherence, particularly by those who had cited 'lack of money' as a previous barrier. The case of making prescribed exercise free or even low-cost remains unproven.

Adolescent↗
PubMed1999

Impact of genetic counseling on primary and preventive care in obstetrics and gynecology.

OBJECTIVE: To evaluate the utility of the prenatal three-generation pedigree in assessment of the obstetric patient's primary medical risks. STUDY DESIGN: In a case series, 250 charts of patients referred for amniocentesis on the basis of advanced maternal age were reviewed for a significant genetic risk of a primary care disorder. RESULTS: A total of 40 patients (16%) were at significantly increased risk for a primary care disorder. Thirty-eight patients (15.2%) were at increased risk for medical conditions for which early screening, detection and/or intervention are established. CONCLUSION: For the advanced maternal age population, formal genetic risk assessment performed prior to amniocentesis can be beneficial in primary care risk assessment.

Adult↗
PubMed1998

Ultra low dose interleukin-2 therapy promotes a type 1 cytokine profile in vivo in patients with AIDS and AIDS-associated malignancies.

This study was undertaken to determine if prolonged daily subcutaneous administration of ultra low dose IL-2 could influence the constitutive endogenous production of a type 1 (IFN-gamma) cytokine in patients with AIDS or AIDS-associated malignancies. Using a quantitative reverse transcription PCR assay, we demonstrate that daily administration of one type 1 cytokine, IL-2, for 3 mo increases significantly the constitutive endogenous gene expression of another type 1 cytokine, IFN-gamma, in vivo. The predominant source of IFN-gamma appears to be IL-2-expanded natural killer cells and CD8(+) T cells. Moreover, PBMC obtained from these patients during IL-2 therapy showed normalization of a profound deficit in IFN-gamma protein production after stimulation with extracts from infectious agents in vitro. Our data suggest that prolonged exogenous administration of a type 1 cytokine in a nontoxic fashion to patients with AIDS and AIDS-associated malignancies can enhance significantly the endogenous type 1 cytokine profile in vivo. Consequently, ultra low dose IL-2 therapy has the potential to improve the immunodeficient hosts' immune response to infectious pathogens that require IFN-gamma for clearance.

Acquired Immunodeficiency Syndrome↗
PubMed1997

The angiotensin-converting enzyme gene and the angiotensin II type I receptor gene as candidate genes for microalbuminuria. A study in nondiabetic and non-insulin-dependent diabetic subjects.

Familial clustering of microalbuminuria with cardiovascular disease suggests a possible common genetic antecedent. We have tested the hypothesis that the angiotensin-converting enzyme (ACE) DD genotype and the angiotensin II type I receptor (AT1R) gene C allele represent the common link between microalbuminuria and coronary heart disease. The frequency of polymorphisms of the ACE and AT1R genes were investigated in 509 nondiabetic white subjects and in 86 non-insulin-dependent diabetic white patients. There was no significant difference in albumin excretion rate between the genotypes in nondiabetic subjects on either a daytime or an overnight sample or in diabetic subjects expressed as a normalized albumin concentration on an untimed morning urine collection. We have found no evidence for an association between polymorphism of the ACE or AT1R genes and microalbuminuria in two groups of subjects without insulin-dependent diabetes.

Adult↗
PubMed1997

Promoting healthy exercise among older people in general practice: issues in designing and evaluating therapeutic interventions.

The potential health benefits derived from sustained physical activity in older people are numerous; however, whether exercise promotion should take place in general practice is unsubstantiated. Exercise promotion should use existing research evidence of the advantages of exercise for various conditions, and target those inactive individuals who currently have no intention of changing their level of physical activity. Research has also raised methodological issues and questions about the feasibility of exercise interventions which still need to be tested in exercise trials conducted in general practice.

Aged↗
PubMed1996

The usefulness of a prenatal genetic questionnaire in genetic risk assessment.

OBJECTIVE: To evaluate a prenatal questionnaire as a genetic screen and as an aid in pre-amniocentesis genetic risk assessment. METHODS: In a retrospective cohort study, charts were reviewed for 158 consecutive women of advanced maternal age referred for genetic counseling. Genetic risks identified by use of a questionnaire completed by 79 consecutive patients were compared with those risks identified by the referring physician, those identified during subsequent three-generation pedigree analysis, and to genetic risks identified by pedigree evaluation of 79 consecutive individuals who underwent genetic counseling without the aid of a questionnaire (controls). RESULTS: Sixteen (20%) of the questionnaires revealed a previously unidentified genetic risk. The sensitivity and specificity of the questionnaire were determined to be 40.0 and 97.4%, respectively. Pedigree analysis alone (control group) identified significantly more at-risk pedigrees than did the questionnaire alone (34 versus 20%, P < .05), but identified significantly fewer at-risk pedigrees than obtained from the study group patients who completed a questionnaire and pedigree evaluation (34 versus 50.6%, P < .05). Of all 158 patients, 15.2% (n = 24) underwent additional testing on the basis of genetic risk assessment. There was no difference between the study and control groups in additional evaluations performed (P = 1.0). CONCLUSION: A three-generation pedigree is superior to a questionnaire in genetic risk assessment. The questionnaire was not sufficiently sensitive to serve independently as an adequate genetic screen or risk assessment tool and did not influence subsequent fetal evaluation. Assessment of the sensitivity and specificity of prenatal genetic questionnaires should be undertaken before their routine clinical use.

Adult↗
PubMed1995

Prolonged administration of low-dose interleukin-2 in human immunodeficiency virus-associated malignancy results in selective expansion of innate immune effectors without significant clinical toxicity.

Ten adult patients with human immunodeficiency virus (HIV)-associated malignancies (five with lymphoma and five with Kaposi's Sarcoma) were treated with a daily subcutaneous injection of interleukin-2 (IL-2) for 90 consecutive days in a phase I dose-escalation study. Seven patients had absolute CD4 counts below 200/mm3 at the time malignancy was diagnosed. Each lymphoma patient had obtained a complete or partial remission with standard chemotherapy before initiating IL-2. The daily dose of IL-2 did not change during the 90-day course of therapy. Seventeen courses of IL-2 therapy were completed at doses ranging from 0.4 x 10(6) U/m2/d to 1.2 x 10(6) U/m2/d without significant (grade III) toxicity. Two of two patients experienced grade III toxicity within 21 days of initiating IL-2 at a dose of 1.4 x 10(6) U/m2/d, but both patients subsequently completed 90 days of therapy at the maximum tolerated dose (MTD) of 1.2 x 10(6) U/m2/d. Although there were no significant increases or decreases in T-cell subsets at any dose level, there was an increase in absolute natural killer (NK) cell number at the three highest doses of IL-2 (mean percent increase 247; 95% confidence interval, 124 to 369) that was statistically significant (Wilcoxon one-sample signed rank test, P = .015). One patient developed an anti-IL-2 antibody titer that correlated with minimal NK cell expansion in vitro and in vivo. An increase in eosinophils was noted during 9 of 17 courses of IL-2 therapy without correlation to IL-2 dose, prior course of IL-2, or NK cell expansion. At the MTD, there was no consistent increase in the plasma HIV RNA level over time. Three of 10 patients had progressive disease while on study. During 50 months of IL-2 therapy, no patient was treated for an opportunistic infection. We conclude that daily low dose subcutaneous IL-2 can be self-administered safely with good compliance for prolonged periods of time to patients with HIV-associated malignancies, including those with profound immune deficiency. The majority of patients show selective expansion of innate immune effectors, ie, NK cells and/or eosinophils, in the absence of significant clinical toxicity or increased viral burden. These results suggest that low-dose IL-2 therapy should be studied further in phase II clinical trials for evidence of activity against malignancy and opportunistic infection in this patient population.

Adult↗
PubMed1995

Sexual orientation in adolescents who commit suicide.

It has been suggested that there is a strong relationship between suicidal behavior and homosexuality in adolescence. It has been further suggested that it is due to the stigmatization and feelings of isolation that are experienced by many gay adolescents. Much of the literature that has given support to these hypotheses has been conducted on uncontrolled nonrepresentative samples and its generalizability is open to question. An opportunity to examine the relationship in an unselected sample arose in a case control, psychological autopsy study of 120 of 170 consecutive suicides under age 20 and 147 community age, sex, and ethnic matched controls living in the Greater New York City area. Homosexuality was defined as having had homosexual experiences or having declared a homosexual orientation. Three teenagers and no controls met these criteria. The difference was not significant. The circumstances of death were examined and are described. In no instance did suicide directly follow an episode of stigmatization. All three suicides had evidence of significant psychiatric disorder before death. In spite of opportunities for biased reporting, it is concluded that this study finds no evidence that suicide is a common characteristic of gay youth, or that when suicide does occur among gay teenagers, that it is a direct consequence of stigmatization or lack of support.

Adolescent↗
PubMed1994

Worsening suicide rate in black teenagers.

Over the past 30 years the incidence of suicide in older adolescents in the United States has shown marked gender and ethnic variations. The rate has remained largely stable among females of all ethnic groups. Among white males it reached a peak in 1988 but has since stabilized. The rate for black and other minority males, however, has increased markedly since 1986. Increases have been more rapid in regions where the incidence was historically low. One effect of these changes has been to reduce the discrepancy between white and black teen suicide rates. The perception that young blacks are at much lower risk for suicide than whites requires revision.

Adolescent↗
PubMed1994

Fetal oculocerebrorenal syndrome of Lowe associated with elevated maternal serum and amniotic fluid alpha-fetoprotein levels.

OBJECTIVE: To report an association between fetal oculocerebrorenal syndrome of Lowe and elevations in maternal serum alpha-fetoprotein (MSAFP) and amniotic fluid alpha-fetoprotein (AFAFP). METHODS: Case 1 was identified during routine MSAFP screening. Cases 2-5 were identified through review of a data base of individuals with oculocerebrorenal syndrome enrolled at the National Institutes of Health. To estimate the frequency of this association, only those whose mothers would have been in the early second trimester from February 1987 to August 1993 were enumerated. The MSAFP was assumed to be normal unless explicitly reported or unless information outside the data base confirmed that MSAFP was not determined. RESULTS: An elevated MSAFP (2.5 multiples of the median [MoM] or greater) was detected in five of 20 pregnancies with a fetus affected by oculocerebrorenal syndrome. Maternal serum alpha-fetoprotein was greater than 5.0 MoM in three pregnancies undergoing amniocentesis, and all had an elevated AFAFP without significant acetylcholinesterase activity. No abnormalities were found by ultrasound, and there was no other cause of elevated AFP identified postnatally. Family history was positive in three of the five cases. The mothers were carriers in four of the five cases, whereas the fifth case appeared to be a spontaneous mutation. CONCLUSIONS: Elevated MSAFP and AFAFP appear to occur at a higher than expected frequency in pregnancies carrying an oculocerebrorenal syndrome fetus. The mechanism of elevation of AFP may be related to fetal renal tubular dysfunction. A directed interview, focusing on a maternal family history of male relatives with unexplained mental retardation, early institutionalization, or congenital rubella, is appropriate with unexplained MSAFP elevations and, particularly, with unexplained AFAFP elevations without acetylcholinesterase activity.

Acetylcholinesterase↗
PubMed1994

Evaluation of the use of brief screening instruments for dementia, depression and problem drinking among elderly people in general practice.

BACKGROUND: Use of brief screening instruments for detection of psychological morbidity among elderly people is being promoted, although the appropriateness and effectiveness of available instruments have not been evaluated in general practice. AIM: This study set out to determine the outcome of opportunistic use of brief screening instruments for dementia, depression and problem drinking in randomized trials in two group practices in north west London. METHOD: Screening instruments were inserted into a random sample of medical records for people aged 75 years and over in each practice. Medical records of those seen by their general practitioners over a six month period were reviewed for new diagnoses of dementia (or confusion), depression or problem drinking, and the scores obtained on screening instruments noted. The records of all those identified as possibly demented, depressed or drinking heavily were reviewed one year after screening and all relevant referrals and new treatments were noted. RESULTS: In one practice use of screening instruments resulted in a significant increase in the detection of possible dementia, but not of depression. In the second practice screening instruments yielded significantly higher numbers with possible dementia or depression. Heavy drinking was uncommon in either population. There was no difference in the proportions of cases identified by screening instrument or by clinical judgement alone who received treatment or referral. CONCLUSION: These results suggest that in the absence of agreed guidelines and resources, information derived from screening instruments may not alter clinical practice.

Aged↗
PubMed1990

The internal consistency and concurrent validity of a Spanish translation of the Child Behavior Checklist.

The Child Behavior Checklist's applicability to a Hispanic sample was assessed by an examination of the instrument's internal consistency and concurrent validity. The CBCL and TRF were administered to a community sample representative of children of Puerto Rico aged 4 to 16. Cronbach's alpha was used to assess the internal consistency of empirically derived scales. The relation of CBCL and TRF scores to clinical diagnosis, adaptive functioning, and need for services served as indicators of the concurrent validity of the instrument's Spanish version. The results indicate that the total behavior problem scores on the instruments are good continuous measures of maladjustment for children in Puerto Rico. A child with high values on the scales has a high probability of being classified as a case by a psychiatrist. High levels of internal consistency were found in most subscales. Only scales comprising low prevalence problems showed poor internal consistency.

Adolescent↗
PubMed1989

Elevated intracellular Ca2+ acts through protein kinase C to regulate rabbit ileal NaCl absorption. Evidence for sequential control by Ca2+/calmodulin and protein kinase C.

Calcium/calmodulin is involved in the regulation of basal rabbit ileal active Na and Cl absorption, but the mechanism by which elevated intracellular Ca2+ affects Na and Cl transport is unknown. To investigate the roles of the Ca2+/calmodulin and protein kinase C systems in ileal NaCl transport, two drugs, the isoquinolenesulfonamide, H-7, and the naphthalenesulfonamide, W13, were used in concentrations that conferred specificity in the antagonism of protein kinase C (60 microM H-7) and Ca2+/calmodulin (45 microM W13), respectively, as determined using phosphorylation assays in ileal villus cells. W13 but not H-7 stimulated basal active NaCl absorption. H-7 inhibited changes in Na and Cl absorption caused by maximal concentrations of Ca2+ ionophore A23187 and carbachol and serotonin, secretagogues that act by increasing cytosol Ca2+, while W13 had no effect. In contrast, neither H-7 nor W13 altered the change in NaCl transport caused by the cyclic nucleotides 8-Br-cAMP and 8-Br-cGMP. These data suggest that: (a) basal rabbit ileal NaCl absorption is regulated by the Ca2+/calmodulin complex and not by protein kinase C; (b) the effect of elevating intracellular Ca2+ to decrease NaCl absorption is mediated via protein kinase C but not by Ca2+/calmodulin; (c) the effects of protein kinase C are not overlapping or synergistic with those of Ca2+/calmodulin on either basal absorption or on the effects of increased Ca2+; and (d) neither Ca2+/calmodulin nor protein kinase C are involved in the effects of cAMP and cGMP on ileal active NaCl transport.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Testing for a pulse in seasonal event data.

Most tests for seasonal clustering are sensitive to the peak in incidence in some season (90-day interval) followed by a trough 6 months later. We present two statistics sensitive to a relatively sharp increase in disease incidence for a season superimposed on a constant incidence over the entire year: the ratchet scan, based on the maximum number of events in k consecutive months, and the continuous circular scan, the maximum number of events in d consecutive days. We tabulate the tail distribution of the ratchet scan for N less than or equal to 35 and k = 2 and 3, and find the asymptotic distribution which is applicable for N greater than or equal to 50 when k = 2 or 3. We evaluate an approximation for the distribution of the continuous scan. The statistics are applied to investigate seasonal clustering of adolescent suicide in the United States. An illustration is given of the application of the circular scan, and a small simulation study and the example are used to compare the statistics with others proposed in the literature.

Adolescent↗