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Biomedical subjects

H Pickering

Publications and source records attributed to H Pickering.

At least 19 recordsLinked to original sources

Regional lung deposition of a technetium 99m-labeled formulation of mometasone furoate administered by hydrofluoroalkane 227 metered-dose inhaler.

BACKGROUND: A new inhaled suspension formulation of mometasone furoate (MF), a potent corticosteroid with minimal systemic availability, has been developed for the treatment of asthma. This formulation is delivered by metered-dose inhaler (MDI) using the nonchlorofluorocarbon propellant hydrofluoroalkane 227 (HFA-227). OBJECTIVE: The primary goal of this study was to determine the respiratory tract deposition of this formulation of MF. A secondary objective was to measure plasma concentrations of MF and a putative metabolite, 6-X-OH MF, to determine the systemic exposure to corticosteroid. METHODS: This was a single-dose, open-label study in which 200 microg of technetium 99m (99mTc)-radiolabeled MF was administered to patients with asthma. Gamma scintigraphy was used to quantify lung, oropharyngeal, stomach, and MDI mouthpiece deposition patterns of MF. RESULTS: Eleven patients, aged 21 to 47 years, with a history of asthma were enrolled in and completed the study. The mean (+/- SD) whole lung deposition of MF was 13.9%+/-5.7% of the metered (ex-valve) dose. The central lung zone received 5.3%+/-2.8% of the dose; the intermediate zone received 4.7%+/-1.9%; and peripheral lung deposition was 4.0%+/-1.5%. The mean (+/- SD) ratio of peripheral to central lung deposition was 0.8+/-0.2. Oropharyngeal deposition was 79.1%+/-8.7% of the ex-valve dose, with 6.3%+/-7.8% deposited on the MDI mouthpiece and 0.7%+/-0.5% exhaled. The majority of plasma samples taken for analysis of MF and 6-13-OH MF concentrations were below the limit of quantification (50 pg/mL) in all patients after inhalation of 200 microg 99mTc-labeled ME CONCLUSION: The lung deposition of MF when administered via HFA-227 MDI is comparable to the 10 to 20% lung deposition seen with other corticosteroid suspension for- mulations administered by MDI that have demonstrated effectiveness in the treatment of asthma.

Administration, Inhalation↗

Determinants of attendance and patient satisfaction at eye clinics in south-western Uganda.

PURPOSE: To identify the reasons for subjects deciding to attend or not attend local and referral ophthalmology clinics in south-west Uganda, and to establish the levels of satisfaction of clinic attenders with the services they received. METHODS: A population survey identified subjects with ocular conditions who were referred to the local clinic or the district hospital. All non-attenders and a group of attenders were interviewed at home. RESULTS: 31% of those referred did not attend the local clinic. The most common reasons were 'too busy' (29%) or 'unwilling to buy spectacles' (17%). Less than half of attenders were satisfied, mainly because of no perceived clinical improvement or having to buy spectacles. Only 13% of those referred to the district hospital clinic attended. The main reasons for non-attendance were high transport cost and fear of the clinic. CONCLUSION: Attendance and satisfaction with the community ophthalmology service could be improved by more intensive motivation and explanation for patients, and assistance with spectacle and transport costs. The use of aphakic motivators should be tested in this context.

Community Health Centers↗

Molecular epidemiological analysis of HIV in sexual networks in Uganda.

OBJECTIVE: To investigate the suitability of HIV sequence analysis, based on the p17 region of the gag gene, to characterize the sexual networks in and around a trading town in south-west Uganda. METHODS: Blood samples were obtained from 54 HIV-seropositive members of three distinct sexual networks and phylogenetic analysis carried out on proviral DNA sequences obtained from the p17 region of gag from 53 individuals. RESULTS: Despite documented evidence of very little sexual mixing between residents of the trading town, fishing village and surrounding rural area, there was no evidence of clustering of sequences associated with place of residence. More strikingly, known sexual partners failed to show significantly related sequences, and the two pairs of sequences that did show significant similarity came from individuals who had no known social or sexual contact. CONCLUSIONS: Sequence analyses such as those described here have proved effective in confirming or identifying epidemiological links not only following single transmission events but also within risk groups. However, the results from Uganda contrast markedly with those from Europe and the United States. The length of time that the community has been infected, the number of occasions when the virus has been introduced and the high degree of partner change may contribute to the lack of supportive evidence for sociological studies of sexual networks in Uganda.

DNA, Viral↗

Melatonin receptor pharmacology: toward subtype specificity.

The recent cloning of three distinct melatonin receptor subtypes (Mel1a, Mel1b and Mel1c) which are part of a new family of G-protein coupled receptors, and probably mediate the physiological actions of the hormone, has spurred interest in the design of analogues with subtype selectivity. The 5-methoxyl and N-acetyl groups of melatonin are important for binding to and activation of the receptor. The indole nucleus serves to hold these two groups at the correct distance from one another and allows them to adopt the required orientation for interaction with the receptor binding pocket. We have investigated the subtype selectivity of a number of analogues of melatonin in which the structure has systematically been modified in order to probe the similarities and differences in the interaction of ligand and receptor subtype. At all three subtypes 5-methoxyl and N-acetyl groups of melatonin are important for high affinity binding. However, replacing the 5-methoxyl group (eg with 5-H, 5-OH, 5-Me or 5-BzO) reduces affinity much less at the Mel1b receptor subtype than at either Mel1a or Mel1c cloned subtypes. This suggests differences between the Mel1b and Mel1a/1c subtypes in the size and shape of the binding pocket or in the manner in which melatonin interacts with the receptor at this position. Further studies have revealed that analogues with longer N-acyl carbon chains behave similarly at each subtype. These observations suggest that the 'pocket' into which the N-acetyl group fits is very similar for each subtype. Substitutions at the 2-position on the indole ring improved affinity at each receptor subtype but did not give selective analogues. The systematic 'mapping' of the requirements for binding at each receptor subtype should allow the design of more selective agonists and antagonists, which will be valuable tools for the characterization and classification of functional melatonin receptors.

3T3 Cells↗

Social aspects of AIDS-related stigma in rural Uganda.

In the process of collecting sexual behaviour data through in-depth interviews, 24 respondents offered information on stigma related to HIV-1 infection. Observations of social relations in public places and families of infected individuals were made. The findings suggest that although HIV/AIDS-related stigma has had adverse effects on treatment seeking behaviour of PWAs and coping mechanisms of their families, a more tolerant attitude is starting to emerge in this area. Probably, due to improvements in counselling services and home care schemes for those with AIDS. This supports the call for increased investments in counselling and community development aimed at caring for people with AIDS (PWAs).

Acquired Immunodeficiency Syndrome↗

Sexual networks in Uganda: casual and commercial sex in a trading town.

A longitudinal study of the sexual behaviour of high-risk men and women living in a trading town on the trans-Africa highway showed that distinct sexual networks operated within the town. Forty-eight prostitutes kept daily records for 6 months of all their sexual contacts including the occupation and place of residence of each client and the price paid. Details of 4573 sexual contacts of the women were recorded. Three classes of women were identified: (1) 20 "high-class' women who charged a mean price of over US $4/- per contact. The majority of their clients were from large urban areas of Uganda (55%) or neighbouring countries (32%)-70% were truck-drivers or their mates; (2) 18 "low-class' women, charging an average of US $0.4 per contact, who were patronized predominantly by men resident in the town (71%) who were unskilled casual workers (58%); (3) 10 women fell into an intermediate category in terms of price and the residence of their clients. Thirty-eight male potential clients were recruited in low-cost bars where some of the women worked. They provided similar details of their daily sexual contacts. All were resident in the town and 22 had occupations which were classified as unskilled. Of the 1621 sexual contacts recorded by the men 25% were with new partners.

Adult↗

Sexual networks in Uganda: mixing patterns between a trading town, its rural hinterland and a nearby fishing village.

The study was based in south-west Uganda where significant differences in HIV prevalence have been found between urban and rural areas. Longitudinal data collected in a diary format was used to determine the extent to which high-risk men and women living in a truck stop/trading town had sexual contact with people from surrounding rural areas and a nearby fishing village. Study participants were 143 men, 75 of whom were resident in the town, 40 in a fishing village and 28 in rural areas, and 81 women, of whom 47 were resident in the town, 25 in the fishing village and 9 in a rural area. During 1687 man weeks the 143 men made 3149 trips and had 5189 sexual contacts. Ninety-two per cent of these sexual contacts occurred in the man's current place of residence and 21% were with a new partner. The 81 women participated for 1280 women weeks during which they recorded 6378 sexual contacts. Women who lived in the fishing village and the rural area had around 90% of their contacts with local men while those who lived in the town fell into 3 categories: women who charged a relatively high price for commercial sex had only 11% of contacts with men living in the town, while those who charged a tenth of the price had 71% of contacts with town men. The small number of women who fell into an intermediate category, in terms of price, had sexual contact with a wide variety of men. These findings show that there is little scope for HIV infection to spread between different residential or occupational groups. This may help to explain how large differences in HIV seropositivity between neighbouring localities can be maintained for long periods, despite considerable social and economic mixing between groups and high levels of sexual partner change within groups.

Adolescent↗

Sexual behaviour in a fishing community on Lake Victoria, Uganda.

This study describes the sexual behaviour of men and women in a fishing village on the shores of Lake Victoria in southwest Uganda. The village is near a well known trading town-truckstop on the main trans-Africa highway with a high recorded prevalence of HIV infection. Data were obtained on the daily travel and sexual activities of 26 women and 54 men with particular attention paid to the rate of partner change and the proportion of sexual contacts with people outside the village. During a total of 587 person weeks the men made 1086 trips, mostly returning home the same day. They had a total of 1226 sexual contacts, most of which occurred either in their own village (83%) or a neighbouring fishing village (11%); 17 per cent of sexual contacts were with new partners. Fifteen of the women described themselves as married; 42 per cent of their sexual contacts were casual, paying partners. Of the eleven women who were single, between 80 and 100 per cent of contacts were with paying partners. Most of the women's partners were resident in the village. These data show a very high rate of sexual mixing within the village. Such communities should be targeted in future STD control programs.

Adolescent↗

A three-year follow-up survey of demographic changes in a Ugandan town on the trans-African highway with high HIV-1 seroprevalence.

A 1991 serosurvey in a Ugandan trading town on the trans-African highway reported a 40 per cent HIV-1 prevalence in adults. Three years later in a repeat survey of the 531 adults resident in 1991, 279 (53%) were still present, 196 (37%) had left and 56 (11%) had died. There were 138 new residents and 46 children had become adults, making a total of 463 adults in 1994, 13 per cent less than 1991. Most immigrants (91%) came from the surrounding rural district whereas 38 per cent of emigrants went to an urban area. A significant inverse association between wealth and seropositivity was found for women but not men. Of the original residents 157 were known to be HIV-1 positive in 1991; 31 (20%) had died compared to 10 (4%) of the 232 known to be seronegative, representing an HIV-1 attributable mortality fraction of 60 per cent.

Adult↗

Sexual mixing patterns in Uganda: small-time urban/rural traders.

OBJECTIVE: To document the extent to which rural and urban-based male traders have sexual contacts away from their place of residence. METHODS: Fifty-one traders (46 who travel by bicycle and five others) kept daily diaries of all their journeys and sexual contacts for a total of 584 person-weeks. Twenty-five were resident in a trading town where HIV prevalence was about 40% and 26 lived up to 25 km away in rural areas where HIV prevalence was approximately 8%. RESULTS: A total of 2147 return trips were made (mean, 3.7 per week). Eighty per cent were between the trading town and the surrounding rural area. A total of 1377 sexual contacts were recorded (mean, 2.3 per week); 95% of the contacts of urban-based men occurred in the town, 3% in other urban areas and 2% in a rural area. For rural-based men 82% of sexual contacts took place in their home village, 14% in a neighbouring village, 2% in the trading town and 3% in other urban centres. CONCLUSION: Despite considerable economic interaction there is very little sexual mixing between the town and surrounding rural areas. This may explain why the high HIV prevalence found in some trading towns in Africa has not diffused out to rural areas.

Adult↗

Analogues of diverse structure are unable to differentiate native melatonin receptors in the chicken retina, sheep pars tuberalis and Xenopus melanophores.

1. The pineal hormone melatonin exerts its biological effects through specific, high affinity G-protein coupled receptors. Recently, three melatonin receptor subtypes (Mel1a, Mel1b and Mel1c) have been cloned. Neither the cloned subtypes, nor the native receptors have yet been compared in a detailed pharmacological analysis. 2. The present study examined the structure-activity relationships of a series of 21 melatonin analogues, by comparing their potency on the pigment aggregation response in Xenopus laevis melanophores with their affinity in radioligand binding competition studies in chicken retina and sheep pars tuberalis (PT), two tissues in which melatonin is known to mediate a biological response. 3. All but four of the analogues were full melatonin receptor agonists producing a concentration-related redistribution of pigment granules in cultured Xenopus melanophores. The remaining analogues produced little pigment aggregation at 10 microM. 4. Saturation studies with 2-[125I]-iodomelatonin identified a single binding site in the chicken retina and sheep PT membranes, with a KD of 36.6 +/- 2.8 and 37.3 +/- 4.3 pM, and a maximal number of binding sites (Bmax) of 16.6 +/- 0.5, and 40.1 +/- 1.7 fmol mg-1 protein, respectively. 5. Comparison of the potency/affinity of the analogues for the binding sites gave a highly significant correlation in each case, retina/melanophore, r = 0.97 (P < 0.001, n = 17), PT/melanophore, r = 0.97 (P < 0.001, n = 17) and PT/retina, r = 0.98 (P < 0.001, n = 21). 6. Despite their large range in affinity and structural diversity these melatonin agonists were unable to distinguish between melatonin receptors in the chicken retina, sheep pars tuberalis and Xenopus melanophores.

Animals↗

Prevalence and demographic factors of stimulant use.

The use of stimulants for recreation purposes has increased considerably during the 20th century. Cocaine was first considered to be a drug of potential abuse during the First World War but was only perceived as a serious threat when it became widely used in socially and economically deprived urban areas of the USA in the 1980s. Use of amphetamines was common among certain occupational groups as a means of remaining alert until the 1950s, when they were seen to be abused by a small minority of recreational users. Controls were then introduced in most developed countries. The public health issue of stimulant use is that of finding a balance between the prevention of serious social or personal harm caused by abuse of these drugs while not impeding their beneficial use.

Adolescent↗

Attitudes to malaria, traditional practices and bednets (mosquito nets) as vector control measures: a comparative study in five west African countries.

Five West African communities were visited to assess the knowledge of the cause of malaria and to document traditional ways of treating and preventing the infection. Knowledge of the cause of malaria was low in the five communities visited. People were more concerned about mosquitoes being a nuisance than a cause of the infection. Various herbs were used as mosquito repellents. Malaria was treated by a number of traditional practices, including herbal remedies. Bednets were used to a varying extent, from 44% Ghana to 86% Gambia, in each community to protect against mosquito bites but also for other purposes such as privacy, decoration and protection from roof debris dropping on the bed.

Adult↗

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 1. A review of the epidemiology and control of malaria in The Gambia, west Africa.

Malaria was recognized as an important cause of death among early European visitors to The Gambia, but the infection was first studied systematically in the local population only in the 1950s. Studies undertaken in the village of Keneba at that time showed that nearly all children under the age of 5 years had parasitaemia throughout the year. More recent surveys in rural areas of The Gambia have shown much lower levels of parasitaemia, probably as a result of a decline in rainfall in The Gambia during the past 30 years and because of an increase in the availability of anti-malarial drugs. Nevertheless, community surveys and reviews of hospital statistics show that malaria is still one of the most important causes of death among Gambian children; about 1 in 25 rural Gambian children die from malaria before reaching the age of 5 years. Until recently, malaria control in The Gambia relied upon prompt treatment of clinical attacks, first with quinine and more recently with chloroquine, and upon some limited vector control in the capital, Banjul. However, during the past few years, it has been shown that mortality in rural children can be reduced substantially by means of chemoprophylaxis given by village health workers. Bed nets (mosquito nets) are used widely in The Gambia and epidemiological surveys have shown an association between the use of bed nets and protection against malaria. This observation led to a series of small scale intervention trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 4. Perceptions of the causes of malaria and of its treatment and prevention in the study area.

Perceptions of the causes of malaria, its treatment and prevention were studied among 996 adults, selected randomly from 73 villages and hamlets in a rural area of The Gambia. Structured questionnaires and other interview techniques were used for data collection. Malaria has no specific name in the study area; it is referred to commonly as Fula kajewo (Fula fever). Only 28% of the respondents knew that mosquitoes transmitted malaria. However, most people believed correctly that August to October was the main malaria season. Eighty-six per cent of the subjects were bed net users. The majority of nets were produced locally, usually white in colour and made of sheeting fabrics. Usage of nets was correlated with ethnic group, age and polygamy but not with education, income, occupation or ownership of certain items which indicate high social status. Analysis of expenditure on mosquito coils indicated that non-users of nets spent 43% more on coils than did users. Bed nets have been used for a long time in the study area; 98% of users saw their parents using them during their childhood.

Adult↗