Co-trimoxazole in HIV-1 infection.
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Biomedical subjects
Publications and source records attributed to R Wood.
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Novel 3-substituted quinuclidine inhibitors of cholesterol biosynthesis are reported. Compounds were optimized against oxidosqualene cyclase-lanosterol synthase (OSC) inhibition in vivo, rather than by the conventional optimization of structure-activity relationship information based on in vitro OSC inhibition. Thus, examination of HPLC lipid profiles from orally dosed rats showed cholesterol biosynthetic intermediates and whether cholesterol levels were reduced. A new substituted quinuclidine pharmacophore 18a-c was rapidly found for the inhibition of OSC, and the most promising inhibitors were validated by the confirmation of potent OSC inhibition. Compound 16 gave an IC50 value of 83 +/- 11 nM for human and an IC50 value of 124 +/- 14 nM, for rat, coupled with oral and selective inhibition of cholesterol biosynthesis derived from OSC inhibition (rat, ED50 = 1.3 +/- 0.7 mg/kg, n = 5; marmoset, 15 mg/kg dose, n = 3, caused complete inhibition). These 3-substituted quinuclidines, which were derived from a quinuclidine series previously known to inhibit cholesterol biosynthesis at the squalene synthase step, may afford a novel series of hypocholesterolemic agents acting by the inhibition of OSC.
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BACKGROUND: Studies of occupation and health commonly examine only men. This paper draws on reviews of inequalities in health carried out by the Office for National Statistics in London which in recent years have focused more on women. METHODS: Many sources of official statistics such as censuses, surveys, vital registration and health service records are used to explore different ways of measuring and monitoring economic activity, education, socio-economic, and family status and their impact on fertility and health among women. RESULTS: Taking a life cycle approach we first look at fertility and family formation, the time around childbirth, age 15-49, and finally 50+. Some relevant health issues are used to illustrate how we use available data to describe and monitor inequalities in health. CONCLUSIONS: In Britain, there is a wealth of information and linked data sources which enable us to analyze patterns and trends in fertility, morbidity, and mortality. Nevertheless, none of the traditional data sources or methods of analysis are suitable for all purposes nor for keeping up with changes in society. Sources of official statistics and ways of linking and analyzing need then to be continuously developed.
The fatty acid composition and structure of pawpaw fruit (Asimina triloba) triglycerides were examined and found to contain fatty acids ranging from C6 to C20. Octanoate represented 20% of the fatty acids while other medium-chain fatty acids were present in low amounts. Analysis of the intact triglycerides by high-temperature gas-liquid chromatography gave an unusual three-cycle carbon number distribution. Analysis of triglyceride fractions separated according to degree of unsaturation suggested that one octanoate was paired with diglyceride species containing long-chain fatty acids. Determination of the double-bond positions of monoene fatty acids revealed cis delta9 and cis delta11 hexadecenoate and cis delta9, cis delta11, and cis delta13 octadecenoate isomers were present in significant quantities. Octanoate and positional monoene fatty acid isomers were found only in the fruit lipids and not in the seed lipids. Phenacyl esters of fatty acids were found to be useful derivatives for structure determination using multiple types of analyses.
A rapid method for identification of human immunodeficiency virus Type 1 (HIV-1) gag subtypes was developed based on restriction fragment length polymorphism (RFLP) analysis of 400 or 650 bp long polymerase chain reaction (PCR) fragments encompassing the start of the p17 (400 bp) and part of the p24 (650bp) regions. The consensus sequences of subtypes A-D, the only subtypes identified in South Africa, were analyzed to detect restriction endonucleases which generate unique patterns for each subtype. Four restriction endonucleases were identified: AluI, AccI, SwaI and XmnI. Digestion of a 400 bp fragment with AluI allowed identification of subtype C. Samples not identified were then reamplified, and a 650 bp fragment digested with AccI to identify subtype B, followed by SwaI and XmnI to distinguish between subtypes A and D. This strategy was applied to 87 samples previously subtyped by either sequence analysis of the gag p17 region (n = 33); or heteroduplex mobility assay (HMA) based on the env gene (n = 75); or both (n = 21). Out of the 87 samples, RFLP identified two samples as subtype A, 28 as subtype B, 56 as subtype C and one as a subtype D virus. No discrepancies were found between RFLP gag subtypes and gag sequence subtypes demonstrating the reliability of this method. There was also no discordance between gag RFLP subtypes and env HMA subtypes, suggesting that there were no recombinant viruses detected relating to the genomic regions analyzed. RFLP is an effective technique for the rapid screening in an HIV epidemic of limited diversity, such as in South Africa.
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BACKGROUND: Eosinophils are a prominent feature of chronic hyperplastic sinusitis with nasal polyposis (CHS/NP). Our previous studies showed that their presence was associated with the expression of GM-CSF and RANTES mRNA. In allergic NP, increased expression of IL-5 was also found. OBJECTIVE: We wished to examine cytokine immunoreactivity for IL-5, GM-CSF and RANTES mRNA in allergic and non-allergic NP and compare immunoreactivity with expression of cytokine mRNA by in situ hybridization. Methods NP were obtained from five allergic and eight non-allergic subjects with CHS/ NP. Middle turbinate tissue from eight normal subjects were used as controls. Cell-associated cytokine mRNA was detected by in situ hybridization (ISH). Cytokine immunoreactive cells were enumerated by immunostaining. Colocalization immunostaining was also performed to identify specific cell types producing IL-5. RESULTS: Immunostaining for GM-CSF, IL-5 and RANTES protein was increased in both allergic and non-allergic NP compared with control middle turbinates. Allergic polyps contained greater numbers of IL-5 immunoreactive cells (P = 0.01), whereas non-allergic polyps contained greater numbers of GM-CSF immunoreactive cells (P = 0.04). Immunostaining was primarily associated with inflammatory cells, but immunostaining for RANTES and, to a lesser extent GM-CSF, was also seen in the epithelium. The density of immunoreactive cells was variably correlated with cytokine mRNA+ cells (GM-CSF: R=0.56, P=0.05; IL-5: R=0.76, P=0.003; and RANTES: R=0.89, P=0.0005). Colocalization immunostaining revealed that the majority of IL-5 immunoreactive cells in both allergic and non-allergic NP were T lymphocytes. However, allergic NP contained greater numbers of IL-5+/CD3+ T lymphocytes and IL-5+ mast cells, whereas non-allergic NP contained greater numbers of IL-5+ eosinophils. CONCLUSION: We conclude that GM-CSF, IL-5 and RANTES are produced in increased amounts in both allergic and non-allergic NP. Distinguishing features of non-allergic NP include fewer numbers of CD3 T lymphocytes, fewer IL-5+/CD3+ T lymphocytes and greater numbers of IL-5+ eosinophils. These differences may suggest different mechanisms of eosinophil accumulation and activation in allergic vs non-allergic NP.
BACKGROUND: Abdominal pain in acquired immunodeficiency syndrome (AIDS) patients is often a marker of an underlying opportunistic pathologic condition. There are no data on HIV-related abdominal pain in Africa. METHODS: Forty-four consecutive Cape Town patients with advanced human immunodeficiency virus (HIV) infection (CD4 < 200) and abdominal pain were studied prospectively to determine aetiology and survival. RESULTS: A probable cause of pain was identified in 37 (84%): disseminated Mycobacterium tuberculosis infection in 11, cryptosporidiosis in 6, cytomegalovirus infection in 6, and atypical mycobacterial infection in 2. Gastrointestinal lymphoma and pancreatitis were not seen. Fever, hepatomegaly, respiratory symptoms, abnormal chest radiograph, and adenopathy, ascites, or abscesses on ultrasound had predictive diagnostic value for disseminated M. tuberculosis. Fifty-one per cent of abdominal pain patients survived 6 months, compared with 73% of all AIDS patients (P < 0.001). CONCLUSIONS: The aetiology of HIV-related abdominal pain in Cape Town reflects the high local prevalence of tuberculosis. Clinical and ultrasound features facilitate diagnosis. Abdominal pain is associated with poor survival.
We present a new combined approach to primary bilateral cleft lip, nose, and alveolus repair using presurgical nasoalveolar molding combined with a one-stage lip, nose, and alveolus repair. Presurgical alveolar molding is used to bring the protruding premaxilla back into proper alignment with the lateral segments in the maxillary arch. Presurgical nasal molding produces tissue expansion of the short columella and nasal lining. A coordinated surgical approach involves a one-stage repair of the lip, nose, and alveolus. The nasal repair uses a retrograde approach in which the prolabial flap and columella are reflected over the nasal dorsum by continuing the dissection behind the prolabium up the membranous septum and over the septal angle. Tissues are dissected out from between the tip cartilages, and the domes are sutured together in the midline. This method joins a new class of bilateral cleft repairs that place the primary emphasis on correction of the deformity of the nasal tip cartilages.
Methods for meeting the research needs of rural/remote health workers have been assessed on the assumption that these workers form a seemingly homogeneous group. This paper provides a picture of locational-occupational diversity not previously considered when addressing the needs of rural health workers writing research and project grant submissions. Rural/remote health workers and researchers were surveyed about their needs when seeking assistance with the development, implementation and evaluation of funded project/program proposals. New South Wales respondents were differentiated according to five geographical locations and 10 occupational categories. The results suggest that geographical location and occupational category are major factors in determining research requirements for rural/remote health workers and researchers, and should be considered when identifying barriers to the development and implementation of research projects in rural/remote health care issues. Those health workers most isolated required access to resource information and research and grant writing skills development, while researchers in metropolitan areas were more inclined to seek funding information and general assistance. Those in occupational categories who do not generally receive research and grant writing skills training are less likely to attract funding than their more 'academic' counterparts.
Teenage mothers continue to present challenges to social policy and remain of topical interest to the media. This article discusses trends in teenage conception rates, their outcomes and long term consequences. In 1996, 7 per cent of all births were to girls aged under 20. On average children born to teenage girls have lower birthweights, increased risk of infant mortality and an increased risk of some congenital anomalies. They are less likely to be breastfed and more likely to live in deprived circumstances. These factors in turn influence their health and long term opportunities.
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This article summarises recent trends in birth statistics in England and Wales. Particular attention is given to the characteristics of conceptions in 1996 and births in 1997, the latest years for which figures are available. The article examines changes in the number of births outside marriage, the age women become mothers and the number of women expected to remain childless throughout their lives. It also analyses differences in the timing of childbearing between women from different social classes or living in different regions of the UK. Finally it describes changes in the overall and underage conception rates between 1995 and 1996.
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