Lifestyle factors including less cutaneous sun exposure contribute to starkly lower vitamin D levels in U.K. South Asians compared with the white population.

BACKGROUND: Long-standing concerns over the vitamin D status of South Asian adults in the U.K. require studies using statistically valid sample sizes to measure annual variation and contributory lifestyle factors. OBJECTIVES: To measure annual variation in the vitamin D status of U.K. South Asians, to determine the associated lifestyle influences, and to compare these with a similar study of white adults. METHODS: A single-centre, prospective cohort study measuring circulating 25-hydroxyvitamin D [25(OH)D], sunlight exposure levels and lifestyle factors for 1 year in 125 ambulant South Asian adults with sun-reactive skin type V, aged 20-60 years, in Greater Manchester, U.K. (53·5°N). RESULTS: The 25(OH)D levels of South Asians were alarmingly low. In summer, their median 25(OH)D level was 9·0 ng mL(-1) , [interquartile range (IQR) 6·7-13·1], falling to 5·8 ng mL(-1) (IQR 4·0-8·1) in winter. This compared with values in the white population of 26·2 ng mL(-1) (IQR 19·9-31·5) in summer and 18·9 ng mL(-1) IQR (11·6-23·7) in winter. Median daily dietary vitamin D was lower in South Asians (1·32 µg vs. 3·26 µg for white subjects) and was compounded by low supplement use. Despite similar times spent outdoors, ultraviolet (UV) dosimeters recorded lower personal UV exposure among South Asians, indicating sun avoidance when outside, while sun exposure diaries recorded lower amounts of skin surface exposure. CONCLUSIONS: The majority of South Asians never reached sufficiency in vitamin D status. Lifestyle differences, with lower oral intake, sun exposure and rates of cutaneous production due to darker skin, indicate that standard advice on obtaining sufficient vitamin D needs modification for the South Asian community in the U.K.

The impact of photosensitivity disorders on aspects of lifestyle.

BACKGROUND: Photosensitivity disorders involve an abnormal skin reaction to sunlight exposure and affect a substantial percentage of the population. No previous studies have directly compared lifestyle attributes between photosensitive and healthy individuals. OBJECTIVES: To assess the impact of photosensitivity on time spent outdoors in the U.K., holiday behaviour, use of sunscreens and vitamin D supplements, and employment status. METHODS: Questionnaires were completed by ambulant photosensitive and healthy adults aged 18-60 years residing in Greater Manchester. RESULTS: Forty-five adults with moderate-severe photosensitivity and 124 healthy adults completed the questionnaire. This revealed that photosensitive subjects spent significantly less time outdoors in the U.K. on both summer weekdays (P < 0·01) and summer weekends (P < 0·0001) than healthy subjects, took fewer holidays per year (P < 0·05), and spent less time outdoors on a sunny holiday (P < 0·0001). They wore clothing that covered a wider skin area (P < 0·0001), and use of sunscreen was greater (both frequency of application and area covered) in the photosensitive group outside of holiday time (P < 0·0001), but not when on a sunny holiday, as healthy people increased their sunscreen use at this time. Despite the reduced sun exposure, photosensitive subjects were no more likely to take vitamin D supplements than healthy subjects were; they also exhibited a significantly higher rate of unemployment (P < 0·05). CONCLUSIONS: Photosensitivity disorders negatively influence lifestyle including employment status; more attention is required to the socioeconomic impact of these conditions.

Prenatal and postnatal risk factors for mental retardation among children in Bangladesh.

This study evaluated the contribution of prenatal, perinatal, neonatal, and postnatal factors to the prevalence of cognitive disabilities among children aged 2-9 years in Bangladesh. A two-phase survey was implemented in 1987-1988 in which 10,299 children were screened for disability. In multivariate analyses, significant independent predictors of serious mental retardation in rural and urban areas included maternal goiter (rural odds ratio (OR) = 5.14, 95% confidence interval (CI): 1.23, 21.57; urban OR = 4.82, 95% CI: 2.73, 8.50) and postnatal brain infections (rural OR = 29.24, 95% CI: 7.17, 119.18; urban OR = 13.65, 95% CI: 4.69, 39.76). In rural areas, consanguinity (OR = 15.13, 95% CI: 3.08, 74.30) and landless agriculture (OR = 6.02, 95% CI: 1.16, 31.19) were also independently associated with the prevalence of serious mental retardation. In both rural and urban areas, independent risk factors for mild cognitive disabilities included maternal illiteracy (OR = 2.48, 95% CI: 0.86, 7.12), landlessness (OR = 4.27, 95% CI: 1.77, 10.29), maternal history of pregnancy loss (OR = 2.61, 95% CI: 0.95, 7.12), and small for gestational age at birth (OR = 3.86, 95% CI: 1.56, 9.55). Interventions likely to have the greatest impact on preventing cognitive disabilities among children in Bangladesh include expansion of existing iodine supplementation, maternal literacy, and poverty alleviation programs as well as prevention of intracranial infections and their consequences. Further population-based studies are needed to confirm and understand the association between consanguinity and serious cognitive disability.

Identification and characterization of two G protein-coupled receptors for neuropeptide FF.

The central nervous system octapeptide, neuropeptide FF (NPFF), is believed to play a role in pain modulation and opiate tolerance. Two G protein-coupled receptors, NPFF1 and NPFF2, were isolated from human and rat central nervous system tissues. NPFF specifically bound to NPFF1 (K(d) = 1.13 nm) and NPFF2 (K(d) = 0.37 nm), and both receptors were activated by NPFF in a variety of heterologous expression systems. The localization of mRNA and binding sites of these receptors in the dorsal horn of the spinal cord, the lateral hypothalamus, the spinal trigeminal nuclei, and the thalamic nuclei supports a role for NPFF in pain modulation. Among the receptors with the highest amino acid sequence homology to NPFF1 and NPFF2 are members of the orexin, NPY, and cholecystokinin families, which have been implicated in feeding. These similarities together with the finding that BIBP3226, an anorexigenic Y1 receptor ligand, also binds to NPFF1 suggest a potential role for NPFF1 in feeding. The identification of NPFF1 and NPFF2 will help delineate their roles in these and other physiological functions.

Expression of a novel neuropeptide Y receptor subtype involved in food intake: an in situ hybridization study of Y5 mRNA distribution in rat brain.

Our group has reported on the cloning of a novel rat neuropeptide Y (NPY) receptor involved in NPY-induced food intake, the Y5 receptor. The distribution in rat brain of the mRNA encoding this receptor has been determined by in situ hybridization histochemistry, using radiolabeled oligonucleotide probes. Control experiments were carried out in cell lines transfected with either rat Y1 or rat Y5 cDNAs. With the exception of the cerebellum, only the antisense probes yielded hybridization signal in rat brain tissue sections. A number of brain regions contained hybridization signals indicative of Y5 mRNA localization. Chief among these were various hypothalamic nuclei, including the medial preoptic nucleus, the supraoptic nucleus, the paraventricular nucleus, and the lateral hypothalamus. Other regions with substantial hybridization signals included the midline thalamus, parts of the amygdala and hippocampus, and some midbrain and brain-stem nuclei. In general a low density of Y5 mRNA was observed in most cortical structures, with the exception of the cingulate and retrosplenial cortices, each of which contained a moderate abundance of Y5 hybridization signal. The distribution of this receptor mRNA is consistent with a role for the Y5 receptor in food intake and also suggests involvement in other processes mediated by NPY.

Comparison of the echinocandin caspofungin with amphotericin B for treatment of histoplasmosis following pulmonary challenge in a murine model.

Twenty clinical isolates of Histoplasma capsulatum were tested for their in vitro susceptibilities to caspofungin in comparison to those to amphotericin B by following National Committee for Clinical Laboratory Standards guidelines for yeasts. The mean MICs were 16.6 microgram/ml (range, 8 to 32 microgram/ml) for caspofungin and 0.56 microgram/ml (range, 0.5 to 1.0 microgram/ml) for amphotericin B. Survival experiments used a 10(5) dose in a pulmonary challenge model with B6C3F(1) mice. All mice that received amphotericin B at 2 mg/kg of body weight every other day (q.o.d.), 30% of mice that received caspofungin at 8 mg/kg/day, and 20% of mice that received caspofungin at 4 mg/kg/day survived to day 15, while mice that received caspofungin at 2 mg/kg/day and all control mice that received the vehicle died by day 14. Amphotericin B at 2 mg/kg q.o.d. markedly reduced the fungal burden in the lungs and spleens, as measured by Histoplasma antigen detection techniques and quantitative cultures, for each comparison. Caspofungin at 10 mg/kg twice a day (b.i.d.) did not reduce the fungal burden, as measured by antigen detection techniques, but slightly reduced the levels of fungi in both the lungs and spleens, as determined by quantitative cultures. Caspofungin at 5 mg/kg b.i.d. did not affect fungal burden. Overall, caspofungin had only a slight effect on survival or fungal burden.

Comparison of a new triazole antifungal agent, Schering 56592, with itraconazole and amphotericin B for treatment of histoplasmosis in immunocompetent mice.

A murine model of intratracheally induced histoplasmosis was used to evaluate a new triazole antifungal agent, Schering (SCH) 56592, for treatment of histoplasmosis. MICs were determined for SCH 56592, amphotericin B, and itraconazole by testing yeast-phase isolates from 20 patients by a macrobroth dilution method. The MICs at which 90% of the isolates are inhibited were for 0.019 microgram/ml for SCH 56592, 0.5 microgram/ml for amphotericin B, and < or = 0.019 microgram/ml for itraconazole. Survival studies were done on groups of 10 B6C3F1 mice with a lethal inoculum of 10(5). All mice receiving 5, 1, or 0.25 mg of SCH 56592 per kg of body weight per day, 2.5 mg of amphotericin B per kg every other day (qod), or 75 mg of itraconazole per kg per day survived to day 29. Only 44% of mice receiving 5 mg of itraconazole/kg/day survived to day 29. Fungal burden studies done in similar groups of mice with a sublethal inoculum of 10(4) showed a reduction in CFUs and Histoplasma antigen levels in lung and spleen tissue in animals treated with 2 mg of amphotericin B/kg qod, 1 mg of SCH 56592/kg/day, and 75 mg of itraconazole/kg/day, but not in those treated with lower doses of the study drugs (0.2 mg of amphotericin B/kg qod, 0.1 mg of SCH 56592/kg/day, or 10 mg of itraconazole/kg/day). Serum drug concentrations were measured 3 and 24 h after the last dose in mice (groups of five to seven mice), each treated for 7 days with SCH 56592 (10 and 1 mg/kg/day) and itraconazole (75 and 10 mg/kg/day). Mean levels measured by bioassay were as follows: SCH 56592, 10 mg/kg/day (2.15 micrograms/ml at 3 h and 0.35 microgram/ml at 24 h); SCH 56592, 1 mg/kg/day (0.54 microgram/ml at 3 h and none detected at 24 h); itraconazole, 75 mg/kg/day (22.53 micrograms/ml at 3 h and none detected at 24 h); itraconazole, 10 mg/kg/day (1.33 micrograms/ml at 3 h and none detected at 24 h). Confirmatory results were obtained by high-pressure liquid chromatography assay. These studies show SCH 56592 to be a promising candidate for studies of treatment of histoplasmosis in humans.

GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2.

The principal inhibitory neurotransmitter GABA (gamma-aminobutyric acid) exerts its effects through two ligand-gated channels, GABA(A) and GABA(C) receptors, and a third receptor, GABA(B) , which acts through G proteins to regulate potassium and calcium channels. Cells heterologously expressing the cloned DNA encoding the GABA(B)R1 protein exhibit high-affinity antagonist-binding sites, but they produce little of the functional activity expected from studies of endogenous GABA(B) receptors in the brain. Here we describe a new member of the GABA(B) polypeptide family, GABA(B)R2, that shows sequence homology to GABA(B)R1. Neither GABA(B)R1 nor GABA(B)R2, when expressed individually, activates GIRK-type potassium channels; however, the combination of GABA(B)R1 and GABA(B)R2 confers robust stimulation of channel activity. Both genes are co-expressed in individual neurons, and both proteins co-localize in transfected cells. Moreover, immunoprecipitation experiments indicate that the two polypeptides associate with each other, probably as heterodimers. Several G-protein-coupled receptors (GPCRs) exist as high-molecular-weight species, consistent with the formation of dimers by these receptors, but the relevance of these species for the functioning of GPCRs has not been established. We have now shown that co-expression of two GPCR structures, GABA(B)R1 and GABA(B)R2, belonging to the same subfamily is essential for signal transduction by GABA(B) receptors.

A receptor subtype involved in neuropeptide-Y-induced food intake.

Neuropeptide Y (NPY) is a powerful stimulant of food intake and is proposed to activate a hypothalamic 'feeding' receptor distinct from previously cloned Y-type receptors. This receptor was first suggested to explain a feeding response to NPY and related peptides, including NPY2-36, that differed from their activities at the Y1 receptor. Here we report the expression cloning of a novel Y-type receptor from rat hypothalamus, which we name Y5. The complementary DNA encodes a 456-amino-acid protein with less than 35% overall identity to known Y-type receptors. The messenger RNA is found primarily in the central nervous system, including the paraventricular nucleus of the hypothalamus. The extent to which selected peptides can inhibit adenylate cyclase through the Y5 receptor and stimulate food intake in rats correspond well. Our data support the idea that the Y5 receptor is the postulated 'feeding' receptor, and may provide a new method for the study and treatment of obesity and eating disorders.

Evidence for a central cholinergic effect of high-dose thiamine.

In vitro animal studies have suggested that thiamine is involved in the presynaptic release of acetylcholine. Total thiamine content in cholinergic nerve terminals is comparable with that of acetylcholine, and the phosphorylation state of thiamine changes with release of acetylcholine. Thiamine binds to nicotinic receptors and may exhibit anticholinesterase activity. Based on these observations, we investigated the effects of pharmacological doses of thiamine on the cognitive deficits induced by the anticholinergic scopolamine in healthy young adults using a randomized, double-blind, placebo-controlled, double-crossover design. Drug effects were assessed by P3 event-related potential, quantitated electroencephalography, and free recall memory. Conditions included (1) baseline, (2) thiamine 5 gm p.o. and scopolamine 0.007 mg/kg IM, and (3) lactose PO and scopolamine 0.007 mg/kg IM. Thiamine significantly reduced adverse effects of scopolamine on P3 latency, spectral components of electroencephalography, and memory recall. The results are consistent with a cholinomimetic effect of thiamine in the central nervous system. Additional studies are needed to delineate the basic mechanisms and possible therapeutic efficacy of thiamine at pharmacological dosages.

Autologous predonation, haemodilution and intraoperative blood salvage in elective abdominal aortic aneurysm repair.

The feasibility of predonated autologous blood transfusion and intraoperative blood salvage in elective abdominal aortic aneurysm repair was studied. Twenty consecutive patients were evaluated, of whom five were excluded according to protocol criteria. Patients each donated 1 unit blood 14 and 7 days before operation. A third unit was withdrawn in the anaesthetic room and replaced with Hartmann's solution, producing a haemodiluted state. Intraoperative losses were minimized using the Haemonetics Cell Saver III Plus autotransfusion system. Predonated blood from two patients passed its expiry date owing to repeated operation postponements, leaving 13 patients for study. The mean(s.d.) intraoperative blood loss was 700(300) ml with a mean(s.d.) intraoperative salvage of 420(300) ml. Two patients were transfused intraoperative salvage of 420(300) ml. Two patients were transfused according to clinical need. Thus nine patients safely avoided homologous transfusion. With autologous predonation, haemodilution and intraoperative blood salvage, elective aortic aneurysm repair can be performed safely with minimal need for homologous blood.

Gastrointestinal complications and endoscopic findings in heart transplant patients.

To determine the scope of gastrointestinal complications in heart transplant recipients, we examined the frequency and nature of gastrointestinal complications by reviewing the indications and findings of endoscopic and surgical procedures involving the gastrointestinal tract in 159 patients. All patients were treated with prednisone, azathioprine, and cyclosporine after transplantation. Sixty-seven patients (42%) had gastrointestinal symptoms significant enough to warrant either endoscopic, radiologic, or surgical procedures. Forty-seven patients (30%) underwent esophagogastroduodenoscopy or upper gastrointestinal roentgenography with a high frequency of esophagitis, gastritis, duodenitis, and gastroduodenal ulcers. Thirty-two patients (20%) underwent barium enema or endoscopic procedures of the lower gastrointestinal tract, with the most frequent findings being benign polyps and colitis. Opportunistic infections, especially with cytomegalovirus, were frequent and were only diagnosed by endoscopic procedures, indicating an advantage of endoscopy over barium studies in these patients. Twenty-three patients (15%) underwent surgical procedures for gastrointestinal complications with 2.5% mortality. Hence, significant gastrointestinal complications that are common in heart transplant recipients, can be safely managed surgically when surgical intervention is indicated.

A community of caring. Patients in a rehabilitation unit experience holistic healing through a spiritual support group.

Empowered by empathic knowledge of the pain and suffering endured by patients, a pastoral care giver can foster holistic healing, integrating a spiritual dimension into the lives of responsive individuals by helping them form a circle of love, a Community of Caring. A Community of Caring can be effective in many specialized hospital units or long-term care centers. In a hospital physical rehabilitation unit, for example, a chaplain successfully provided a time, place, and ambience where patients could share their deepest feelings, thoughts, and concerns and learn together techniques of coping. This Community of Caring helped patients overcome feelings of inadequacy and low self-esteem, encouraged self-acceptance despite physical losses, and stimulated new concepts of spirituality, notably the importance and the sacredness of the present time spent in recuperation. Participants in the Community of Caring discussed ideas such as the concept that all activity, even mundane rejuvenative therapy exercises, can be--at least potentially--sacramental activity; the importance of fully using all facets of physical therapy; and the idea that days spent in recuperation can be a time for deepened relationship with self, others, and a compassionate God. The sessions helped many patients mobilize their inner resources and assume greater personal responsibility for their healing and recovery.

Ayurvedic treatment for jaundice in Nepal.

This paper describes beliefs and practices associated with jaundice and its treatment by ayurvedic physicians (vaidyas) in Kathmandu. It documents continuity of ancient ayurvedic ideas and practices as well as syncretism between ayurvedic and allopathic (Western, biomedical) traditions in modern Nepal. Popular beliefs about the cause of jaundice appear to have evolved to fit therapeutic practices adopted by vaidyas from allopathy. An implication of this finding is that beliefs about causation do not necessarily precede and channel therapeutic choices; they may also function to rationalize and provide meaning to experiences of illness and therapy. The data also suggest a number of hypotheses about the efficacy of ayurvedic treatment for jaundice.

Carboxyl-terminal sequence of entactin deduced from a cDNA clone.

Entactin is a widely distributed basement membrane sulfated glycoprotein of approximately equal to 150 kDa. The entactin gene is expressed early in mouse embryogenesis. Two cDNA clones complementary to rat entactin mRNA were isolated by antibody screening of an oligo(dT)-primed cDNA library constructed in the lambda gt11 expression vector. One of the clones, lambda 1E, was subcloned into plasmid pBR322 and further characterized. The clone contained sequences complementary to an mRNA species 6 kilobases in length. This mRNA was translated in rabbit reticulocyte lysates to yield a polypeptide of 143 kDa that was precipitated with anti-entactin antiserum. The cDNA insert, 1328 base pairs long, was sequenced and found to contain an open reading frame of 729 base pairs that coded for 243 amino acids at the carboxyl terminus of entactin. Analysis of the peptide revealed no extended alpha-helical or beta-sheet secondary structures. Radiolabeled probes prepared by nicktranslation of p lambda 1E were used to monitor the steady-state levels of entactin mRNA in F9 embryonal carcinoma cells that were induced to differentiate by exposure to retinoic acid and dibutyryl cyclic AMP. The increase in steady-state levels of entactin mRNA lagged behind the increase in mRNA for the B2 chain of laminin, suggesting that laminin and entactin are independently rather than coordinately regulated.

Control of laminin synthesis during differentiation of F9 embryonal carcinoma cells. A study using cDNA clones complementary to the mRNA species for the A, B1 and B2 subunits.

Molecular clones complementary to the mRNA species for the A, B1 and B2 chains of murine laminin were identified by hybrid-selection and in vitro translation. Northern blot analysis demonstrated that the three clones, p59 (A), p2 (B1) and p16 (B2) hybridized to mRNA species 9.8, 6.0, and 8.0 kb in length, respectively. The three clones were used as probes to monitor the steady-state levels of laminin mRNA species during differentiation of F9 embryonal carcinoma cells induced by treatment with retinoic acid and dibutyryl cyclic AMP. The steady-state levels of the three mRNA species appeared to increase in a coordinate manner. Undetectable levels at the beginning of induction were followed by a dramatic increase in the levels of the three mRNA species between 48 and 72 h. The kinetics parallel the increase in laminin synthesis and the striking morphological changes previously reported.

New Testament story presents model for health care ministry.

Those who minister to the sick and the aged can learn several lessons from the experience of two disciples who met Jesus on the road to Emmaus. Though the men, who were leaving Jerusalem to escape the confusion caused by Jesus' crucifixion, did not initially recognize him, Jesus walked alongside them and drew them into conversation about the preceding days' events. His attentive listening and perceptive questioning, which allowed them to vent their feelings, helped the men to deal with the reality of their suffering. When they asked Christ to remain, he accepted their invitation, knowing that they needed additional support. As they broke bread together that evening, the disciples recognized Jesus, "whereupon he vanished from their sight." Care givers, too, at times need to walk away from their work, not only to allow time for reflection but also to enable patients to experience God's presence. They must be alert to everything a patient says so that words meant to comfort do not cause suffering, and they must learn to recognize the subtle ways in which patients ask them to stay with them. Helping patients face the truth requires courage and the ability to help another appreciate his or her self-worth. Just as the disciples recognized Jesus' presence in those they encountered, so, too, must care givers allow themselves to be transformed at the eucharistic table and to see in others--even the unlovely-an existential, holistic love.