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Biomedical subjects

M Quigley

Publications and source records attributed to M Quigley.

At least 37 records · Page 2Linked to original sources

Whole-brain functional MR imaging activation from a finger-tapping task examined with independent component analysis.

BACKGROUND AND PURPOSE: Independent component analysis (ICA), unlike other methods for processing functional MR (fMR) imaging data, requires no a priori assumptions about the hemodynamic response to the task. The purpose of this study was to analyze the temporal characteristics and the spatial mapping of the independent components identified by ICA when the subject performs a finger-tapping task. METHODS: Ten healthy subjects performed variations of the finger-tapping task conventionally used to map the sensorimotor cortex. The scan data were processed with ICA, and the temporal configuration of the components and their spatial localizations were studied. The locations with activation were tabulated and compared with locations known to be involved in the organization of motor functions in the brain. RESULTS: Components were identified that correlated to varying degrees with the conventional boxcar reference function. One or more of these components mapped to the sensorimotor cortex, supplementary motor area (SMA), putamen, and thalamus. By means of ICA components, sensorimotor cortex, supplementary motor area, and superior cerebellar activation were identified bilaterally in 100% of the subjects; thalamus activation was contralateral to the active hand in 80%; and putamen activation was contralateral to the active hand in 60%. CONCLUSION: ICA processing of multislice fMR imaging data acquired during finger tapping identifies the sensorimotor cortex, SMA, cerebellar, putamen, and thalamic activation. ICA appears to be a method that provides information on both the temporal and spatial characteristics of activation. Multiple task-related components can be identified by ICA, and specific activation maps can be derived from each separate component.

Brain↗

A new pressure attenuation index to evaluate retinal circulation. A link to protective factors in diabetic retinopathy.

BACKGROUND: Low ocular perfusion pressure (two thirds of mean arterial pressure minus intraocular pressure) and myopia have been associated with protection of the retina from clinical diabetic retinopathy. This prompts the question as to whether myopia's protective role could also be a pressure effect, given that pressure could be dissipated in the longer arteriole tree of the myopic eye. METHODS: We combined the Ohm, Poiseuille, and Murray laws to derive the following new formulation: the pressure attenuation along a vessel varies directly with its length and inversely with its diameter. A mean pressure attenuation index was calculated for 22 healthy control subjects, 25 patients with axial myopia, and 6 patients with retinitis pigmentosa using digitized fundus images. RESULTS: The myopic arteriolar tree would produce a 16% greater pressure attenuation than that of controls (P = .002), with a linear relationship between mean pressure attenuation index and axial length (r = 0.93). Mean pressure attenuation index of the group with retinitis pigmentosa is increased 67% above that of controls, which is calculated to contribute an additional 10 mm Hg of pressure dissipation along their retinal arteriolar system. CONCLUSIONS: Pressure attenuation in retinal arterioles is directly proportional to the length and inversely proportional to the diameter of the arteriole segment being measured. CLINICAL RELEVANCE: A pressure attenuation index may be important in light of the entities known or presumed to protect the retina from diabetic retinopathy. The results support the hypothesis that low-end arteriolar pressure is a common denominator for many protective conditions in diabetic retinopathy.

Blood Circulation↗

Functional food properties of non-digestible oligosaccharides: a consensus report from the ENDO project (DGXII AIRII-CT94-1095).

This paper results from the final phase of the ENDO project (DGXII AIRII-CT94-1095), a European Commission-funded project on non-digestible oligosaccharides (NDO). All participants in the programme met to perform a consensus exercise on the possible functional food properties of NDO. Topics studied during the project (including a workshop on probiotics and prebiotics) and related aspects, for which considerable evidence has been generated recently, were evaluated on the basis of existing published scientific evidence. There was a general consensus that: (1) there is strong evidence for a prebiotic effect of NDO in human subjects. A prebiotic effect was defined as a food-induced increase in numbers and/or activity predominantly of bifidobacteria and lactic acid bacteria in the human large intestine; (2) there is strong evidence for the impact that NDO have on bowel habit; (3) there is promising evidence that consumption of inulin-type fructans may result in increased Ca absorption in man; (4) there are preliminary indications that inulin-type fructans interact with the functioning of lipid metabolism; (5) there is preliminary evidence in experimental animals of a preventive effect against colon cancer. Human nutrition studies are needed to substantiate these findings. It was concluded that the nutritional properties of NDO may prove to be a key issue in nutritional research in the future.

Animals↗

The role of urine cytology in the assessment of lower urinary tract symptoms.

OBJECTIVE: To evaluate the role of urine cytology in the investigation of men with lower urinary tract symptoms (LUTS) in the absence of haematuria. PATIENTS AND METHODS: The study comprised 336 men attending a LUTS assessment clinic, who had neither macroscopic nor microscopic haematuria. One sample of urine was collected for cytology. Those with suspicious urine cytology were investigated with intravenous urography and cystoscopy. RESULTS: Five men had abnormal urine cytology results; on further investigation one of them was found to have carcinoma in situ (CIS) and one to have a transitional cell carcinoma. Three had false-positive urine cytology results. CONCLUSION: A bladder tumour or CIS was detected in 0.6% of the population tested. The cost per cancer diagnosed was GB pound 2020. Urine cytology is a simple noninvasive way of assisting accurate diagnosis of men who have LUTS in the absence of haematuria.

Carcinoma in Situ↗

Antibody to herpes simplex virus type 2 as a marker of sexual risk behavior in rural Tanzania.

A serosurvey was conducted in a random sample of 259 women and 231 men in 12 rural communities in Mwanza Region, Tanzania, using a type-specific ELISA for Herpes simplex virus type 2 (HSV-2) infection. Seroprevalence rose steeply with age to approximately 75% in women >=25 years old and 60% in men >=30. After adjusting for age and residence, HSV-2 prevalence was higher in women who were married, in a polygamous marriage, Treponema pallidum hemagglutination assay (TPHA)-positive, had more lifetime sex partners, or who had not traveled. Prevalence was higher in men who were married, had lived elsewhere, had more lifetime partners, had used condoms, or were TPHA-positive. HSV-2 infection was significantly associated with recent history of genital ulcer. The association between HSV-2 infection and lifetime sex partners was strongest in those <25 years old in both sexes. This association supports the use of HSV-2 serology as a marker of risk behavior in this population, particularly among young people.

Adolescent↗

Blood glucose awareness training and epinephrine responses to hypoglycemia during intensive treatment in type 1 diabetes.

OBJECTIVE: To determine the effect of blood glucose awareness training (BGAT) on epinephrine and symptom responses to hypoglycemia in patients with type 1 diabetes enrolled in an intensive diabetes treatment (IDT) program. RESEARCH DESIGN AND METHODS: A total of 47 subjects with uncomplicated diabetes (duration 9 +/- 3 years: HbA1c 9.0 +/- 1.2%; reference range 4-6%) enrolled in a 4-month outpatient IDT program were randomized to classes in BGAT (n = 25) (BGAT group) or cholesterol awareness (n = 22) (control group). Subjects underwent stepped hypoglycemic clamp studies before and at completion of IDT. Plasma glucose was lowered from 6.7 mmol/l (baseline) to 4.4, 3.9, 3.3, 2.8, and 2.2 mmol/l over 190 min. Symptoms, counterregulatory hormones, and ability of the subject to estimate their glucose level were assessed at each plateau. At home, subjects used a handheld computer to first estimate and then measure and record blood glucose levels for 70 trials over a 4-week period immediately before IDT and again immediately following the educational intervention. RESULTS: HbA1c decreased in both BGAT group (9.1 +/- 1.4 to 7.9 +/- 1.1%; P < 0.001) and control group (9.0 +/- 1.1 to 7.8 +/- 0.8%; P < 0.001) (NS between groups). Frequency of hypoglycemia (< 3.9 mmol/l) increased in both groups, from 0.45 +/- 0.06 to 0.69 +/- 0.07 episodes per day (P < 0.001) in the BGAT group and from 0.50 +/- 0.08 to 0.68 +/- 0.06 episodes per day (P < 0.05) in the control group NS between groups). Epinephrine responses after IDT were greater in the BGAT group (repeated measure analysis of variance [ANOVA], F = 3.5, P < 0.05). A separate analysis of subjects n = 26) most at risk for hypoglycemia (HbA1c after IDT < 7.8% or an HbA1c improvement of > 2 percentage points) showed that frequency of hypoglycemia increased in both the groups: from 0.50 +/- 0.09 to 0.80 +/- 0.11 episodes per day (P < 0.01) in the BGAT group (n = 14) and from 0.43 +/- 0.11 to 0.75 +/- 0.07 episodes per day (P < 0.05) in the control group (n = 12) (NS between groups). However, the epinephrine response in control subjects decreased with IDT while the response in the BGAT subjects was preserved (repeated measure ANOVA, F = 4.4, P < 0.02). CONCLUSIONS: BGAT is a useful intervention to decrease blunting of counterregulatory responses associated with improved glycemic control and may modify the severity of hypoglycemia associated with improved glycemic control in type 1 diabetes.

Adrenocorticotropic Hormone↗

Twice weekly tuberculosis preventive therapy in HIV infection in Zambia.

BACKGROUND: A randomized double-blind placebo-controlled trial was conducted to estimate the efficacy of preventive therapy for tuberculosis (TB) in HIV-infected adults in Lusaka, Zambia. The main outcome measures were the incidence of TB, mortality and adverse drug reactions. METHODS: During a 2 year period, 1053 HIV-positive individuals without evidence of clinical TB were randomly assigned to receive 6 months of isoniazid twice a week (H), or 3 months of rifampicin twice a week (R) plus pyrazinamide (Z), or a placebo. Therapy was taken twice a week and was self administered. Subjects presenting with symptoms during the follow-up period were investigated for TB. RESULTS: The 1053 subjects in the study were followed up for a total of 1631 person-years (median = 1.8 years). Twenty-nine subjects were taken off treatment as a result of adverse drug reactions. A total of 96 cases of TB/probable TB (59 TB and 37 probable TB) were diagnosed during the study period and 185 deaths were reported. One hundred and fifteen subjects (11%) did not return to the study clinic at any time after enrolment. The incidence of TB was lower in those subjects on preventive therapy (H and RZ groups combined) compared with those on placebo (rate ratio = 0.60, 95% CI: 0.36-1.01, P = 0.057), as was the incidence of TB/probable TB (rate ratio = 0.60, 95% CI: 0.40-0.89, P = 0.013). The effect of preventive therapy was greater in those with a tuberculin skin test (TST) of 5 mm or greater, in those with a lymphocyte count of 2x10(9)/l or higher, and in those with haemoglobin of 10 g/dl or higher. There was no difference in mortality rates between the preventive therapy and placebo groups. The effect of preventive therapy declined after the first year of the study so that by 18 months the rates of TB in the treated groups were similar to that in the placebo group. CONCLUSION: This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia. No effect was observed on mortality. The effect was greatest in persons who had a positive TST or a lymphocyte count of 2x10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression. The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis.

AIDS-Related Opportunistic Infections↗

Risk factors for concordant HIV infection in heterosexual couples in Trinidad.

Risk factors for HIV infection in partners of HIV-seropositive index cases were investigated in a cross-sectional survey. Between September 1992 and April 1994 a total of 251 HIV-infected persons and 76 of their sexual partners were interviewed at the main sexually transmitted diseases (STDs) clinic in Trinidad. All participants gave signed consent and responded to a questionnaire. Sixty-four couples had risks for HIV infection through heterosexual intercourse only. However, many recruited sex partners (57/64) reported heterosexual intercourse with persons in addition to the index cases. Overall HIV concordance (both index case and partner HIV infected) was 45% in the couples. HIV concordance was not found to be related to the sexual practices within the studied unions nor to the clinical status of the index case. After allowing for confounding factors there was an increased risk for HIV concordance in couples in unions for > or = 1 year (adjusted OR 3.48; 95% CI 0.89-13.69, P = 0.055), and in those in which sex partners had a past history of genital sores (adjusted for prostitution: OR 4.50; 95% CI 1.01-20.4). Interventions targeted at reducing high-risk sexual behaviour, prostitution and cocaine use could be beneficial in reducing the spread of STDs and HIV in Trinidad.

Adolescent↗

Patterns of sexual behaviour in a rural population in north-western Tanzania.

The HIV epidemic in sub-Saharan Africa has been characterised by the predominance of heterosexual transmission. Patterns of sexual behaviour have been implicated in the spread of the epidemic, but few quantitative data are available on sexual behaviour in rural populations in Africa. This paper reports data from a survey of 1117 adults aged 15-54 years selected randomly from twelve rural communities in Mwanza Region, Tanzania. Sexual debut occurred early, 50% of women and 46% of men reporting first sex before age 16. On average, women married 1.8 years and men 6.1 years after their sexual debut. In women, age at sexual debut appears to have increased over time, in parallel with an increase in age at first marriage. Men were generally married later, to women around five to ten years younger than themselves. Marital dissolution and remarriage were common in both sexes. Reported numbers of sexual partners were compared with those recorded in a population survey in Britain. More men reported 10 or more lifetime partners, or three or more partners in the past year, in rural Mwanza (48% and 29%) than in Britain (24% and 6%). Women reported fewer partners, and results were broadly similar to British data. Casual sex during the past year was reported by 53% of the men and 15% of the women, but only 2% of men reported sexual contact with bar girls or commercial sex workers. Only 20% of men and 3% of women had ever used a condom. Interventions are needed to reduce the high levels of sexual partner change and casual sex, and low levels of condom use, recorded in this rural population. Targeting of interventions to traditional "core groups" may be of limited value in rural areas, and additional strategies are needed, focusing particularly on teenagers who are at high risk of HIV and other sexually transmitted diseases.

Adolescent↗

A review of data-derived methods for assigning causes of death from verbal autopsy data.

BACKGROUND: Verbal autopsy (VA) is an indirect method for estimating cause-specific mortality. In most previous studies, cause of death has been assigned from verbal autopsy data using expert algorithms or by physician review. Both of these methods may have poor validity. In addition, physician review is time consuming and has to be carried out by doctors. A range of methods exist for deriving classification rules from data. Such rules are quick and simple to apply and in many situations perform as well as experts. METHODS: This paper has two aims. First, it considers the advantages and disadvantages of the three main methods for deriving classification rules empirically; (a) linear and other discriminant techniques, (b) probability density estimation and (c) decision trees and rule-based methods. Second, it reviews the factors which need to be taken into account when choosing a classification method for assigning cause of death from VA data. RESULTS: Four main factors influence the choice of classification method: (a) the purpose for which a classifier is being developed, (b) the number of validated causes of death assigned to each case, (c) the characteristics of the VA data and (d) the need for a classifier to be comprehensible. When the objective is to estimate mortality from a single cause of death, logistic regression should be used. When the objective is to determine patterns of mortality, the choice of method will depend on the above factors in ways which are elaborated in the paper. CONCLUSION: Choice of classification method for assigning cause of death needs to be considered when designing a VA validation study. Comparison of the performance of classifiers derived using different methods requires a large VA dataset, which is not currently available.

Algorithms↗

Sexual behaviour patterns and other risk factors for HIV infection in rural Tanzania: a case-control study.

OBJECTIVE: To examine the association between HIV infection and patterns of sexual behaviour and other risk factors in a rural Tanzanian population in a case-control study, nested within a randomized trial of improved sexually transmitted disease treatment. METHODS: All HIV-positive patients from the baseline survey of the randomized trial were eligible as cases. Cases (n = 338) and controls (a random sample of one in eight HIV-negative persons; n = 1078) were interviewed about risk factors for HIV infection using a structured questionnaire. RESULTS: A significantly higher HIV prevalence was found among men and women not currently employed in farming [men: odds ratio (OR), 2.08; women: OR, 3.65], women who had travelled (OR, 3.27), educated women (OR, 4.51), and widowed/ divorced people compared with those currently married (men: OR, 3.10; women: OR, 3.54). Two spouse-related factors were significantly associated with HIV, even after adjustment for the sexual behaviour of the index case: HIV was more prevalent in men with younger spouses (P = 0.020 for trend) and in women married to men currently employed in manual work, office work or business (OR, 2.20). In women only, blood transfusions were associated with a higher HIV prevalence (OR, 2.40), but only a small population attributable fraction (4%). There was an increased HIV prevalence associated with increasing numbers of injections. Reported number of lifetime sexual partners was significantly associated with HIV infection (women: OR, 7.33 if > or = 10 lifetime partners compared with < or = 1; men: OR, 4.35 for > or = 50 compared with < or = 1). After adjustment for confounders, male circumcision was associated with a lower HIV prevalence (OR, 0.65; P = 0.11). CONCLUSIONS: In these rural communities, many HIV infections occur through sexual transmission. Some people are at high risk of HIV infection through large numbers of sex partners, whereas some are at risk through their spouse or regular partner. The role of circumcision in HIV transmission is unclear. Commercial sex seems to play a negligible role in HIV transmission in these communities. Our results confirm marked heterogeneity in HIV risk, indicating the scope for risk reduction strategies.

Adolescent↗

Drinking water sources, mortality and diarrhoea morbidity among young children in northern Ghana.

In the Upper East Region of Ghana, considerable resources have been invested in the provision of boreholes. As part of the Ghana Vitamin A Supplementation Trials' Survival Study which was carried out in one of the districts of the Upper East Region between January 1989 and December 1991, data were collected over a period of one calendar year on the drinking water sources used by approximately 13,000 mothers/guardians of over 20,000 children and on the morbidity and mortality experiences of these children. These data were used to describe seasonal and geographical variations in drinking water sources; to look for other predictors of water source use; and to establish whether the drinking water source was associated with the risk of child death or the period prevalence of diarrhoea among young children. Boreholes were used as the main source of drinking water by about 60-70% of respondents. They were used slightly more frequently in the dry season. In the rainy season, the use increased of more traditional sources such as rainwater or holes dug in stream beds. The use of boreholes was greatest in the northern zone of the study area and was more common in those who had had some formal education and were of higher socioeconomic status. Some association was found between reported drinking water source and diarrhoeal morbidity, although this association appeared to be seasonal. No significant association was found between drinking water source and child mortality.

Child↗

Idoxifene: report of a phase I study in patients with metastatic breast cancer.

Idoxifene, a novel antiestrogen with reduced estrogenic activity when compared to tamoxifen, has been given to 20 women with metastatic breast cancer, 19 of whom had received tamoxifen previously, in doses between 10-60 mg. Idoxifene had an initial half-life of 15 h and a terminal half-life of 23.3 days. At a maintenance dose of 20 mg, a mean steady-state level of 173.5 ng/ml was achieved. Significant falls in luteinizing hormone and follicle-stimulating hormone were seen, but the falls were not dose related. Idoxifene was well tolerated, with 11 patients complaining of mild symptoms similar to those seen with tamoxifen. Fourteen patients continued idoxifene therapy for 1-56 weeks; 4 patients showed stabilization of disease for 6-56 weeks and 2 patients showed a partial response.

Adult↗

Analysis of polysulfate-binding domains in porcine proacrosin, a putative zona adhesion protein from mammalian spermatozoa.

Proacrosin is one of the major proteins found within the acrosomal vesicle of mammalian spermatozoa. Previous work has shown that it binds non-enzymatically and with high affinity to polysulfate groups on zona pellucida glycoproteins (ZPGPs) thereby leading to the hypothesis that at fertilization it functions as a secondary ligand molecule to retain acrosome-reacted spermatozoa on the surface of the egg. In the present work we have investigated the nature and extent of the polysulfate binding domain on boar sperm proacrosin using a combination of group-specific modifying reagents, fragmentation analysis, peptide synthesis and expression of deletion recombinants in E. coli bacteria. Taken overall, our results show that arginine, lysine and histidine residues located between Gly 93 and Ala 275, together with the participation of His 47 and Arg 50, are necessary for maximum polysulfate binding activity. The secondary and tertiary structure of this central peptide domain is also important to ensure correct alignment of basic residues with complementary sulfate groups on ZPGPs. Proacrosin, therefore, has many properties in common with other polysulfate binding proteins, such as antithrombin III and sea urchin sperm binding, in having a conformation-dependent domain containing basic amino acids that mediates specific protein-protein interactions. These observations strengthen the hypothesis that proacrosin is a multifunctional protein with a major role as a ligand molecule at fertilization.

Acrosin↗

Clinical and histologic involvement of regional lymph nodes in malignant melanoma. Adjuvant vindesine improves survival.

BACKGROUND: This report is a study of prognostic factors, including adjuvant chemotherapy, that influence survival of patients with malignant melanoma who have clinical and pathologic involvement of regional lymph nodes. METHODS: A total of 169 evaluable patients with malignant melanoma metastatic to regional lymph nodes were registered consecutively and prospectively between June 1977 and December 1986 in the computerized data base of the melanoma registry at Westminster Hospital. Eighty-seven of these patients received adjuvant chemotherapy with vindesine after resection of palpable metastatic lymph nodes, and 82 had no systemic treatment after surgery. All were followed up for at least 2 years (median, 8 years) after involvement of regional lymph nodes was noted or until death. Statistical analyses included simple life-table comparisons, unadjusted for covariates. In addition, Breslow's thickness, ulceration of the primary lesion, its anatomical location, number of regional lymph nodes histologically involved, dissection site, patient age and sex, and adjuvant vindesine therapy were included as covariates in Cox regression models. RESULTS: The disease-free interval (P = 0.0001), time to dissemination from lymph node metastases (P < 0.0001), survival time after lymph node dissection (P = 0.0227) and overall survival time after initial diagnosis of malignant melanoma (P = 0.0095, log-rank chi-square test) were superior for the 87 patients who received adjuvant chemotherapy with vindesine. Cox regression analysis confirmed adjuvant vindesine as a highly significant variable influencing all of these outcomes, including overall survival time after first diagnosis (P = 0.003). CONCLUSIONS: The apparent effect of adjuvant vindesine on overall survival in this study is large (hazard ratio, 0.52) and highly statistically significant. Adjuvant vindesine therapy merits consideration for malignant melanoma metastatic to regional lymph nodes. However, these results observed in concurrent, but nonrandomized, patients clearly require confirmation.

Adult↗