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Biomedical subjects

D Morgan

Publications and source records attributed to D Morgan.

At least 73 records · Page 4Linked to original sources

Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study.

BACKGROUND: An association between HIV-1 and malaria is expected in theory, but has not been convincingly shown in practice. We studied the effects of HIV-1 infection and advancing immunosuppression on falciparum parasitaemia and clinical malaria. METHODS: HIV-1-positive and HIV-1-negative adults selected from a population-based cohort in rural Uganda were invited to attend a clinic every 3 months (routine visits) and whenever they were sick (interim visits). At each visit, information was collected on recent fever, body temperature, and malaria parasites. Participants were assigned a clinical stage at each routine visit and had regular CD4-cell measurements. FINDINGS: 484 participants made 7220 routine clinic visits between 1990 and 1998. Parasitaemia was more common at visits by HIV-1-positive individuals (328 of 2788 [11.8%] vs 231 of 3688 [6.3%], p<0.0001). At HIV-1-positive visits, lower CD4-cell counts were associated with higher parasite densities, compared with HIV-1-negative visits (p=0.0076). Clinical malaria was significantly more common at HIV-1-positive visits (55 of 2788 [2.0%] vs 26 of 3688 [0.7%], p=0.0003) and the odds of having clinical malaria increased with falling CD4-cell count (p=0.0002) and advancing clinical stage (p=0.0024). Participants made 3377 interim visits. The risk of clinical malaria was significantly higher at visits by HIV-1-positive individuals than HIV-1-negative individuals (4.0% vs 1.9%, p=0.009). The risk of clinical malaria tended to increase with falling CD4-cell counts (p=0.052). INTERPRETATION: HIV-1 infection is associated with an increased frequency of clinical malaria and parasitaemia. This association tends to become more pronounced with advancing immunosuppression, and could have important public-health implications for sub-Saharan Africa.

Adolescent↗

Case-control study of risk factors for incident HIV infection in rural Uganda.

OBJECTIVE: To identify risk factors associated with HIV incidence in a rural Ugandan population. DESIGN: Case-control study. METHODS: Men and women who seroconverted between 1990 and 1997 (cases) and seronegative subjects (controls) were drawn from a general population cohort of approximately 5000 adults in rural, southwestern Uganda. Information on risk factors was ascertained through a detailed interview and physical examination by clinicians who were blind to the study subjects' HIV status. All patients were interviewed within 2 years of their estimated date of seroconversion. RESULTS: Data were available on 130 men (37 cases, 93 controls) and 133 women (46 cases, 87 controls). There was a significantly higher risk of infection in men (odds ratio [OR], 6.51; 95% confidence interval [CI], 1.06-39.84) and women (OR, 4.75; 95% CI, 1.26-17.9) who were unmarried and in a steady relationship, and in men who were divorced, separated, or widowed (OR, 4.33; 95% CI, 1.32-14.25) compared with those who were married. There was a significantly higher risk of HIV infection in men (OR, 3.78; 95% CI, 1.20-11.93) and women (OR, 20.78; 95% CI, 2.94-141.2) who reported > or =5 lifetime sexual partners compared with those who reported at most 1 partner. For men, there was an increased risk of infection associated with receiving increasing numbers of injections in the 6 months prior to interview (p < .001 for trend). Women reporting sex against their will in the year prior to interview were at higher risk of infection (OR, 7.84; 95% CI, 1.29-47.86; p = .020). CONCLUSIONS: The strongest risk factor for HIV incidence in this rural Ugandan population is lifetime sexual partners. The increased risks found for women reporting coercive sex and men reporting injections require further investigation.

Adolescent↗

First Results from Viper: Detection of Small-scale Anisotropy at 40 GHz.

Results of a search for small-scale anisotropy in the cosmic microwave background (CMB) are presented. Observations were made at the South Pole using the Viper telescope, with a 0&fdg;26 (FWHM) beam and a passband centered at 40 GHz. Anisotropy band-power measurements in bands spanning the range of l in which the first acoustic peak is expected (bands centered at l=108, 173, 237, 263, 422, and 589) are reported. Statistically significant CMB anisotropy is detected in all bands.

Journal Article↗

Molecular epidemiology of HIV type 1 in a rural community in southwest Uganda.

The molecular epidemiology of a population-based cohort in a cluster of 15 villages in southwestern Uganda was investigated by sequencing part of the p24 gag gene and performing heteroduplex mobility assays (HMAs) of the V3 region of the env gene. Sequence and HMA data, obtained for 69 and 88 proviruses, respectively, showed that the clade A and D viruses were present at a ratio of about 0.67:1. No other clades were detected. Thirteen (22%) of 59 proviruses for which both gag and env data were obtained appeared to be recombinants. Although both clade A and D viruses were present in 13 of the villages, their distribution was unequal: for example, from env data 59% of clade A viruses were found in the eastern villages, compared with only 27% of clade D viruses. Phylogenetic (maximum likelihood) analysis of the p24 gag sequences showed a total of five clusters supported by bootstrap resampling values above or close to 75%. Four clusters were sexual partners, but there was no known sexual contact between the persons in the other cluster. The DNA sequences showed between 0.5 and 8.3% divergence from the cohort clade A or D consensus sequences. The sequences were not closely related to those published for other clade A or D proviruses.

Acquired Immunodeficiency Syndrome↗

Ring chromosome 8 syndrome: further characterization.

We describe two de novo cases of extra r(8) confirmed by fluorescent in situ hybridization (FISH). Based on these two and eight additional cases of extra r(8) confirmed by FISH, the phenotype is better documented. One of our patients had minor facial anomalies, near-normal growth, and neurological development. She had a ring in each cell analyzed. The second had minor craniofacial anomalies and growth and mental retardation. He had a small or double-sized ring in each cell. The phenotype of these 10 cases ranges from almost normal in an adult with 10% mosaicism to variable degrees of minor anomalies, growth retardation, and mental retardation overlapping the mosaic +8 syndrome.

Chromosomes, Human, Pair 8↗

Predictors of social status in cynomolgus monkeys (Macaca fascicularis) after group formation.

The purpose of the present study was to determine whether various behavioral and hormonal markers obtained in individually housed monkeys would be predictive of social rank following group housing. Body weight, serum cortisol and testosterone levels, and locomotor activity in an open-field apparatus were examined in 20 experimentally naive male cynomolgus monkeys (Macaca fascicularis) while they were individually housed. It was hypothesized that eventual subordinate monkeys would have higher cortisol levels and increased locomotor activity scores. These monkeys were then placed in social groups of four (five pens of four monkeys), and social rank was determined based on outcomes of dyadic agonistic encounters. Body weight correlated significantly with eventual social rank. In general, the heavier the monkey the higher the social rank. Locomotor activity in an open-field apparatus following administration of a low dose of cocaine (0.01 mg/kg, i.v.), which has been shown to increase CNS dopamine, correlated with eventual social rank such that individually housed monkeys with high levels of locomotion were more likely to become subordinate. Serum cortisol and testosterone levels failed to correlate with eventual social rank. Hypothalamic-pituitary feedback sensitivity and adrenal responsiveness were examined by measuring cortisol levels after administration of dexamethasone and following ACTH challenge. Cortisol responses in these tests were not associated with eventual social rank. These results suggest that, in addition to body weight, the level of reactivity in a novel environment after administration of a low dose of cocaine is a potential trait marker for social rank. This trait is apparently not associated with hormone levels, but may involve other CNS mechanisms.

Animals↗

Biochemical responses of bone metabolism to 1,25-dihydroxyvitamin D administration in black and white women.

The basis for the racial difference in bone mass between black and white women is not known. Lower bone turnover, better renal calcium conservation, and decreased sensitivity to parathyroid hormone (PTH) have been proposed as explanations. A dynamic comparison of osteoblast function, utilizing stimulation by 1,25-dihydroxyvitamin D [1,25(OH)2D], has not been tested between these two ethnic groups. We compared well-matched black (n = 15) and white (n = 15) premenopausal women, before and during 5 days of 1,25(OH)2D administration (1.0 microgram/day) in order to assess dynamic indices of bone metabolism. As expected, at baseline, black women had lower levels of serum 25-hydroxyvitamin D and biochemical markers of bone turnover with slightly higher levels of PTH. Black women also had superior renal calcium conservation than white women at baseline. In response to 1,25(OH)2D administration, black women had a slightly greater increase in serum calcium and greater decrement in PTH. Moreover, black women showed a lesser increment in urinary calcium than white women and a more robust increase in two markers of bone formation--osteocalcin and carboxyterminal propeptide of type 1 procollagen--than white women. There were no changes in bone resorption indices in either race upon 1,25(OH)2D administration. These data provide preliminary evidence that black women conserve calcium more efficiently under both static and dynamic conditions, and also appear to have better osteoblastic functional reserve than white women.

Adult↗

Self-administration of two long-acting monoamine transport blockers in rhesus monkeys.

RATIONALE: 2beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) is a cocaine analog with high affinity at and selectivity for the dopamine transporter (DAT). 2beta-propanoyl-3beta-(2-naphthyl)-tropane (HD-23), like cocaine, binds with approximately equal affinity to the DAT, the serotonin transporter, and the norepinephrine transporter but has over a 100-fold higher affinity for these monoamine transporters than cocaine. The reinforcing effects of these drugs have not been evaluated in cocaine-na nonhuman primates. OBJECTIVE: The primary goal of the present study was to examine the reinforcing effects of PTT and HD-23 in rhesus monkeys before and after a history of intravenous cocaine self-administration. METHODS: Monkeys (n=4) were initially trained to respond under a fixed-ratio 30 schedule of food presentation. When responding was stable, saline, PTT (0.001-0.03 mg/kg per injection), and HD-23 (0.0003-0.0056 mg/kg per injection) were made available for self-administration for least five sessions per dose. Next, a cocaine dose-effect function (0.0003-0.3 mg/kg per injection) was determined and then

Animals↗

Ex vivo canine lens capsular sac explants.

BACKGROUND: Lens capsular sac explants from human cadaver eyes were used to investigate posterior capsular opacification (PCO). The purpose of this study was to characterize a similar model using canine tissue and to determine whether transferrin (Tf), transforming growth factor beta-2 (TGF-beta2), and insulin-like growth factor-1 (IGF-1) are secreted by lens epithelial cells (LEC) of these ex vivo sacs. METHODS: The lens from canine eyes was removed by extracapsular cataract extraction, the lens sac dissected free, pinned to a petri dish, and cultured in either serum-supplemented or serum-free medium. Morphologic characteristics and growth rate to confluence on the posterior capsule were studied by phase-contrast microscopy. Vimentin, alpha smooth muscle actin, and panTGF-beta expression by LEC were determined by immunohistochemistry. Tf, TGF-beta2, and IGF-1 levels were measured by ELISA in the supernatant of sacs cultured in serum-free medium. RESULTS: The mean time to confluence of LEC onto the posterior capsule was 5.4+/-1.1 days (n=22) and 14.7+/-3.7 days (n=14) for sacs in serum-supplemented and serum-free medium, respectively. Following development of confluence, explants displayed opacification and light scatter from cellular proliferation and capsular contraction. Confluent LEC expressed vimentin, alpha smooth muscle actin, and TGF-beta2, and both Tf and TGF-beta2 were secreted into the culture supernatant. CONCLUSION: Canine lens sac explants have characteristics virtually identical to those of human origin, and appear to be a useful alternative tissue source for this model when human cadaver eyes are unavailable. Tf and TGFbeta-2, but not IGF-1, are secreted by LEC in explanted lens sacs and may influence the proliferation and metaplasia of LEC during the development of PCO.

Actins↗

Purified mariner (Mos1) transposase catalyzes the integration of marked elements into the germ-line of the yellow fever mosquito, Aedes aegypti.

Derivatives of the mariner transposable element, Mos1, from Drosophila mauritiana, can integrate into the germ-line of the yellow fever mosquito, Aedes aegypti. Previously, the transposase required to mobilize Mos1 was provided in trans by a helper plasmid expressing the enzyme under the control of the D. psuedoobscura heat-shock protein 82 promoter. Here we tested whether purified recombinant Mos1 transposase could increase the recovery of Ae. aegypti transformants. Mos1 transposase was injected into white-eyed, kh(w)/kh(w), Ae. aegypti embryos with a Mos1 donor plasmid containing a copy of the wild-type allele of the D. melanogaster cinnabar gene. Transformed mosquitoes were recognized by partial restoration of eye color in the G(1) animals and confirmed by Southern analyses of genomic DNA. At Mos1 transposase concentrations approaching 100 nM, the rate of germ-line transformants arising from independent insertions in G(0) animals was elevated 2-fold compared to that seen in experiments with helper plasmids. Furthermore, the recovery of total G(1) transformants was increased 7.5-fold over the frequency seen with co-injected helper plasmid. Southern blot analyses and gene amplification experiments confirmed the integration of the transposons into the mosquito genome, although not all integrations were of the expected cut-and-paste type transposition. The increased frequency of germ-line integrations obtained with purified transposase will facilitate the generation of Mos1 transgenic mosquitoes and the application of transgenic approaches to the biology of this important vector of multiple pathogens.

Aedes↗

First- versus last-session substitution: an evaluation of the reinforcing effects of cocaine and the cocaine analogue 2beta-propanoyl-3beta-(4-tolyl)-tropane.

Research has shown that many variables influence the reinforcing effects of drugs. The purpose of the present study was to compare the reinforcing effects of cocaine and the long-acting cocaine analogue 2beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) in rhesus monkeys during the 1st versus the last day of substitution. When PTT and cocaine were initially substituted for food or the training dose of cocaine, a large number of injections were self-administered. However, when the 1 st day of substitution was compared with the last day, the number of injections obtained with PTT but not cocaine were significantly lower. This effect was observed under different schedule conditions and in cocaine-naive and cocaine-experienced monkeys. These results suggest that when studying long-acting cocaine analogues, unlike cocaine itself, quantitative differences may be seen early in substitution testing compared with stable performance after multiple-session substitution.

Animals↗

Acquisition of intravenous cocaine self-administration with concurrent access to food in cynomolgus monkeys.

The present study used a concurrent schedule of food and drug delivery in socially housed male cynomolgus monkeys (Macacafascicularis; N = 15) to study variables that influence cocaine acquisition. Each monkey was implanted with subcutaneous vascular access ports, and responding was maintained under a concurrent food, saline schedule with the lever associated with each stimulus presentation varied daily. Next, increasing cocaine doses (0.003-0.3 mg/kg/inj) were concurrently available with food for at least 5 consecutive sessions per dose. Under these conditions, an unexpected lever bias emerged in all 15 monkeys. The development of the lever bias could not be predicted on the basis of cocaine dose or total intake and was not related to social rank. These findings suggest that in monkeys, concurrent fixed-ratio schedules of food and cocaine presentation may result in persistent biased responding that overshadows cocaine preference in studies of acquisition.

Animals↗

The spirochete FlaA periplasmic flagellar sheath protein impacts flagellar helicity.

Spirochete periplasmic flagella (PFs), including those from Brachyspira (Serpulina), Spirochaeta, Treponema, and Leptospira spp., have a unique structure. In most spirochete species, the periplasmic flagellar filaments consist of a core of at least three proteins (FlaB1, FlaB2, and FlaB3) and a sheath protein (FlaA). Each of these proteins is encoded by a separate gene. Using Brachyspira hyodysenteriae as a model system for analyzing PF function by allelic exchange mutagenesis, we analyzed purified PFs from previously constructed flaA::cat, flaA::kan, and flaB1::kan mutants and newly constructed flaB2::cat and flaB3::cat mutants. We investigated whether any of these mutants had a loss of motility and altered PF structure. As formerly found with flaA::cat, flaA::kan, and flaB1::kan mutants, flaB2::cat and flaB3::cat mutants were still motile, but all were less motile than the wild-type strain, using a swarm-plate assay. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis indicated that each mutation resulted in the specific loss of the cognate gene product in the assembled purified PFs. Consistent with these results, Northern blot analysis indicated that each flagellar filament gene was monocistronic. In contrast to previous results that analyzed PFs attached to disrupted cells, purified PFs from a flaA::cat mutant were significantly thinner (19.6 nm) than those of the wild-type strain and flaB1::kan, flaB2::cat, and flaB3::cat mutants (24 to 25 nm). These results provide supportive genetic evidence that FlaA forms a sheath around the FlaB core. Using high-magnification dark-field microscopy, we also found that flaA::cat and flaA::kan mutants produced PFs with a smaller helix pitch and helix diameter compared to the wild-type strain and flaB mutants. These results indicate that the interaction of FlaA with the FlaB core impacts periplasmic flagellar helical morphology.

Alleles↗

Measuring injury risk factors: question reliability in a statewide sample.

BACKGROUND: Recently (1996-98), Colorado added 15 questions pertaining to injury related risks and behaviors to the behavioral risk factor surveillance system (BRFSS). Questions addressed bicycle helmet use, traffic crashes, exposure to violence, suicidal behavior, and gun storage. OBJECTIVE: To measure the test-retest reliability of these injury related questions. METHODS: Of 330 BRFSS participants, 229 (69%) were called a second time and reasked nine selected injury questions. Retests were completed 7-28 days after the original interview. RESULTS: Test-retest agreement was very high (kappa >0.80) for bicycle helmet use, domestic police visits, and gun ownership. All other injury risk questions had substantial agreement (kappa >0.60). CONCLUSIONS: The injury related questions added to the Colorado BRFSS have high test-retest reliability.

Adult↗

Survival by AIDS defining condition in rural Uganda.

OBJECTIVES: To report the initial AIDS defining conditions, CD4 lymphocyte counts around the time of AIDS diagnosis, and survival by AIDS defining condition in a population based cohort in rural Uganda. METHODS: Participants in an HIV natural history cohort in rural Uganda were reviewed every 3 months at routine visits and at other times when they were ill. The date and nature of the first AIDS defining condition in participants developing AIDS during follow up between the start of the cohort in 1990 and the end of 1998 were noted. The CD4 count at, or within, 3 months of this time was recorded for those participants who developed AIDS (WHO stage 4) after 1993. RESULTS: The median survival from developing AIDS to death was 9.3 months and the median CD4 lymphocyte count around the time of developing AIDS was 150 cells x 10(6)/l. The most frequent AIDS defining conditions were wasting syndrome, oesophageal candidiasis, and mucocutaneous herpes simplex virus infection (HSV) for more than 1 month. The median survival with wasting syndrome, Kaposi's sarcoma, and oesophageal candidiasis was less than 3.5 months; however, survival with cryptosporidial diarrhoea, chronic HSV, and extrapulmonary tuberculosis was greater than 20 months. There was little relation between CD4 count around the time of development of the AIDS defining condition and the median survival with that condition. CONCLUSIONS: The survival for most AIDS defining conditions was generally shorter and the median CD4 lymphocyte count higher than studies reported from developed countries. However, the conditions with the longest survival (cryptosporidial diarrhoea, chronic HSV, and extrapulmonary tuberculosis) had a similar survival to that in developed countries and these conditions have a high background level in this population.

Acquired Immunodeficiency Syndrome↗

Physical activity for the chronically ill and disabled.

Exercise prescription principles for persons without chronic disease and/or disability are based on well developed scientific information. While there are varied objectives for being physically active, including enhancing physical fitness, promoting health by reducing the risk for chronic disease and ensuring safety during exercise participation, the essence of the exercise prescription is based on individual interests, health needs and clinical status, and therefore the aforementioned goals do not always carry equal weight. In the same manner, the principles of exercise prescription for persons with chronic disease and/or disability should place more emphasis on the patient's clinical status and, as a result, the exercise mode, intensity, frequency and duration are usually modified according to their clinical condition. Presently, these exercise prescription principles have been scientifically defined for clients with coronary heart disease. However, other diseases and/or disabilities have been studied less (e.g. renal failure, cancer, chronic fatigue syndrome, cerebral palsy). This article reviews these issues with specific reference to persons with chronic diseases and disabilities.

Adolescent↗

Estimating the balance of general practice versus family planning clinic coverage of contraception services in London.

OBJECTIVE: To compare levels of provision of contraception from general practice and family planning clinics for the populations of the 32 London Boroughs. METHOD: Retrospective analysis of routine activity data, including the estimated numbers of first attendance, for 295 family planning clinics (managed by 28 NHS Trusts) and more than 1800 GP partnerships in Greater London, supplemented by data from a survey of family planning clinics. The results were expressed as the estimated percentage of women aged 16-49 obtaining advice on contraception from GPs and family planning clinics. These results were compared to those expected based on results in the General Household Survey. RESULTS: Across London in 1995/96, 12% of women aged 16-49 obtained contraception services from family planning clinics, and 24% obtained contraception services from a GP. At a borough level there was variation from 11% to 25% in coverage by family planning clinics, and from 11% to 41% in coverage by GPs. Estimates of the proportion of women in this age group not using NHS-provided medical or surgical contraception ranged from 0 to 30%. Across all boroughs, there was no consistent relationship between levels of GP activity and family planning clinic activity. CONCLUSION: The results indicate substantial variations between boroughs in the proportion of women using NHS-provided medical or surgical methods of contraception. The absence of any clear inverse relationship between activity in family planning clinics and activity in general practice suggests that changes to one will not be compensated by changes in the other. More specifically, health authorities that opt to purchase lower levels of family planning clinic activity cannot assume that women may opt to use GPs as an alternative. Such a strategy may increase the likelihood that women who would have used family planning clinic services will either not use contraception at all, or will use less effective 'over the counter' methods.

Adolescent↗