A baseline survey of dissolved methane in aquifers of Great Britain.

Interest in dissolved methane (CH4) concentrations in aquifers in England, Scotland and Wales ('Great Britain' or GB) has grown concurrently with interest in the exploitation of unconventional gas sources (UGS). Experience, mainly from North America, has shown the importance of a pre-production baseline against which changes possibly due to UGS extraction can be compared. The British Geological Survey, aided by water utilities, private users and regulators, has compiled a unique dataset for CH4 in groundwaters of GB. This focuses principally on areas where UGS exploration is considered more likely, as indicated by the underlying geology. All the main water supply aquifers (Principal aquifers) were targeted, plus Secondary aquifers where locally important. The average dissolved CH4 concentration across GB in the aquifers sampled was 45µg/l. Out of a total of 343 sites, 96% showed dissolved CH4 concentrations <100µg/l, 80% <10µg/l, and 43%<1µg/l. No site had a CH4 concentration above the US Department of the Interior suggested risk action level of 10,000µg/l. While most sites were sampled only once, a subset was monitored quarterly to determine the magnitude of seasonal or other variations. Generally these variations were minor, with 84% of sites showing variations within the range 0.5-37µg/l, but some aquifers where the porosity was primarily fracture-related showed larger changes (0.5-264µg/l). This may have been due to the nature of sampling at these sites which, unlike the others, did not have installed pumps. Since the regulatory compliance monitoring attending UGS operations will include the measurement of parameters such as dissolved CH4, it is essential that sampling methods are tested to ensure that reliable and comparable datasets can be obtained.

Unsaid but not forgotten: patients' unvoiced desires in office visits.

OBJECTIVES: To examine patient, physician, and health care system characteristics associated with unvoiced desires for action, as well as the consequences of these unspoken requests. PATIENTS AND METHODS: Patient surveys were administered before, immediately after, and 2 weeks after outpatient visits in the practices of 45 family practice, internal medicine, and cardiology physicians working in a multispecialty group practice or group model health maintenance organization. Data were collected at the index visit from 909 patients, of whom 97.6% were surveyed 2 weeks after the outpatient visit. Before the visit, patients rated their trust in the physician, health concerns, and health status. After the visit, patients reported on various types of unexpressed desires and rated their visit satisfaction. At follow-up, patients rated their satisfaction, health concerns, and health status, and also described their postvisit health care use. Evaluations of the visit were also obtained from physicians. RESULTS: Approximately 9% of the patients had 1 or more unvoiced desire(s). Desires for referrals (16.5% of desiring patients) and physical therapy (8.2%) were least likely to be communicated. Patients with unexpressed desires tended to be young, undereducated, and unmarried and were less likely to trust their physician. Patients with unvoiced desires evaluated the physician and visit less positively; these encounters were evaluated by physicians as requiring more effort. Holding an unvoiced desire was associated with less symptom improvement, but did not affect postvisit health care use. CONCLUSIONS: Patients' unvoiced needs affect patients' and physicians' visit evaluations and patients' subjective perceptions of improvement. Implications of these findings for clinical practice are examined.

Associations between alcohol consumption and insulin sensitivity and cardiovascular disease risk factors: the Insulin Resistance and Atherosclerosis Study.

OBJECTIVE: Light-to-moderate alcohol consumption has been associated with reduced cardiovascular disease (CVD) mortality, which may be explained by increased insulin sensitivity (SI) and an improved lipoprotein and blood pressure profile. Prior research has shown improved SI with light-to-moderate alcohol intake even though somewhat imprecise measures of SI were used. RESEARCH DESIGN AND METHODS: Relationships between alcohol use and SI and CVD risk factors were assessed in a cross-sectional analysis of 1,196 white, African-American, and Hispanic men and women from the Insulin Resistance and Atherosclerosis Study (IRAS). Five categories of previous-year alcohol use (never, <0.5 drinks/day, 0.5-0.99 drinks/day, 1-2.99 drinks/day, and > or =3 drinks/day) and log SI + 1 (frequently sampled intravenous glucose tolerance test with Bergman minimal model analysis), log fasting insulin, log triglycerides, HDL cholesterol, and systolic/diastolic blood pressure were examined using analysis of variance. RESULTS: Univariate analysis showed an inverse U-shaped relationship between SI and alcohol intake, with a peak at the 0.5-0.99 drinks/day category. A U-shaped relationship was observed between fasting insulin and the lipid and blood pressure measures. After adjustment for demographic (clinic, sex, ethnicity, age), lifestyle (smoking, dietary energy/fat intake, physical activity), and physical (BMI, waist circumference) variables, the alcohol/insulin association was attenuated, but the association with lipids and blood pressure remained for high-intake categories. CONCLUSIONS: These data suggest that the enhanced SI associated with light-to-moderate alcohol consumption may be a function solely of a BMI and central adiposity profile more favorable to higher SI.

Tracing enteric pathogen contamination in sub-Saharan African groundwater.

Quantitative PCR (qPCR) can rapidly screen for an array of faecally-derived bacteria, which can be employed as tracers to understand groundwater vulnerability to faecal contamination. A microbial DNA qPCR array was used to examine 45 bacterial targets, potentially relating to enteric pathogens, in 22 groundwater supplies beneath the city of Kabwe, Zambia in both the dry and subsequent wet season. Thermotolerant (faecal) coliforms, sanitary risks, and tryptophan-like fluorescence, an emerging real-time reagentless faecal indicator, were also concurrently investigated. There was evidence for the presence of enteric bacterial contamination, through the detection of species and group specific 16S rRNA gene fragments, in 72% of supplies where sufficient DNA was available for qPCR analysis. DNA from the opportunistic pathogen Citrobacter freundii was most prevalent (69% analysed samples), with Vibrio cholerae also perennially persistent in groundwater (41% analysed samples). DNA from other species such as Bifidobacterium longum and Arcobacter butzleri was more seasonally transient. Bacterial DNA markers were most common in shallow hand-dug wells in laterite/saprolite implicating rapid subsurface pathways and vulnerability to pollution at the surface. Boreholes into the underlying dolomites were also contaminated beneath the city highlighting that a laterite/saprolite overburden, as occurs across much of sub-Saharan aquifer, does not adequately protect underlying bedrock groundwater resources. Nevertheless, peri-urban boreholes all tested negative establishing there is limited subsurface lateral transport of enteric bacteria outside the city limits. Thermotolerant coliforms were present in 97% of sites contaminated with enteric bacterial DNA markers. Furthermore, tryptophan-like fluorescence was also demonstrated as an effective indicator and was in excess of 1.4µg/L in all contaminated sites.

Emerging contaminants in urban groundwater sources in Africa.

The occurrence of emerging organic contaminants within the aquatic environment in Africa is currently unknown. This study provides early insights by characterising a broad range of emerging organic contaminants (n > 1000) in groundwater sources in Kabwe, Zambia. Groundwater samples were obtained during both the dry and wet seasons from a selection of deep boreholes and shallow wells completed within the bedrock and overlying superficial aquifers, respectively. Groundwater sources were distributed across the city to encompass peri-urban, lower cost housing, higher cost housing, and industrial land uses. The insect repellent DEET was ubiquitous within groundwater at concentrations up to 1.8 µg/L. Other compounds (n = 26) were detected in less than 15% of the sources and included the bactericide triclosan (up to 0.03 µg/L), chlorination by-products - trihalomethanes (up to 50 µg/L), and the surfactant 2,4,7,9-tetramethyl-5-decyne-4,7-diol (up to 0.6 µg/L). Emerging contaminants were most prevalent in shallow wells sited in low cost housing areas. This is attributed to localised vulnerability associated with inadequate well protection, sanitation, and household waste disposal. The five-fold increase in median DEET concentration following the onset of the seasonal rains highlights that more mobile compounds can rapidly migrate from the surface to the aquifer suggesting the aquifer is more vulnerable than previously considered. Furthermore it suggests DEET is potentially useful as a wastewater tracer in Africa. There was a general absence of personal care products, life-style compounds, and pharmaceuticals which are commonly detected in the aquatic environment in the developed world. This perhaps reflects some degree of attenuation within the subsurface, but could also be a result of the current limited use of products containing emerging contaminants by locals due to unaffordability and unavailability. As development and population increases in Africa, it is likely a wider-range of emerging contaminants will be released into the environment.

In-situ tryptophan-like fluorescence: A real-time indicator of faecal contamination in drinking water supplies.

Enteric pathogens are typically inferred from the presence of surrogate indicator organisms such as thermotolerant (faecal) coliforms (TTCs). The analysis of TTCs requires time-consuming incubation in suitable laboratories, which can limit sampling resolution, particularly during critical pollution events. Here, we demonstrate the use of in-situ fluorimeters targeting tryptophan-like compounds as a rapid, reagentless indicator of TTCs in groundwater-derived potable water supplies in Africa. A range of other common indicators of TTCs were also determined including nitrate, turbidity, and sanitary risk survey scores. Sampling was conducted during both the dry and wet seasons to investigate seasonality. Tryptophan-like fluorescence was the most effective predictor of both presence/absence and number of TTCs during both seasons. Seasonal changes in tryptophan-like fluorescence in deeper supplies suggest it is transported more efficiently through the aquifer than TTCs. Moreover, the perennial elevated concentrations in some wells suggest it is more resilient than TTCs in groundwater. Therefore tryptophan-like fluorescence could also be a better indicator of some smaller, more easily transported, and long-lived, pathogenic enteric viruses. These sensors have the potential to be included in real-time pollution alert systems for drinking water supplies throughout the world, as well as for mapping enteric pathogen risks in developing regions.

Molecular cloning of a cDNA encoding the nerve growth factor precursor from Mastomys natalensis.

Mastomys natalensis is an African rat that has high levels of nerve growth factor (NGF) in its submaxillary glands. Like in the mouse, Mastomys NGF is found as a high-molecular-weight complex. However, the Mastomys complex differs from the mouse complex, in that the gamma-subunit is either missing or is less tightly bound in the Mastomys NGF complex. In the mouse, the gamma-subunit has been implicated in the processing of the beta-NGF precursor. The possible lack of gamma-subunits in the Mastomys NGF high-molecular-weight complex suggested that the Mastomys beta-NGF precursor might differ from the mouse beta-NGF precursor in some of its processing sites. In particular, Mastomys beta-NGF might lack the C-terminal dipeptide cleavage site implicated in beta-gamma subunit interactions in mouse NGF. In order to test this hypothesis, we isolated and sequenced a cDNA clone for Mastomys beta-NGF. We report here the cloning and sequencing of a cDNA coding for beta-NGF from Mastomys natalensis. The cDNA library was prepared from Mastomys submaxillary gland mRNA and the beta-NGF clone was isolated using a mouse cDNA as a probe. The nucleotide sequence of Mastomys beta-NGF is 95% homologous to that of mouse beta-NGF. In particular, the Mastomys beta-NGF precursor contains the same three C-terminal residues as the mouse, suggesting that the Mastomys beta-NGF precursor could interact with a gamma-like subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

An immunoglobulin switchlike sequence is linked with canine narcolepsy.

Canine narcolepsy is an animal model of the human disorder that is transmitted as a single autosomal recessive gene with full penetrance (canarc-1) in Dobermans and Labradors. In previous experiments, we have identified a very tight linkage marker for canarc-1. This marker, a 0.85-kb band cross reacting with a human mu-switch Heavy-Chain Immunoglobulin probe (maximum logarithm of odds [LOD] score Zmax = 10.8 at 0% recombination), has now been cloned and sequenced. The gene, composed of GC rich repeats, is 75% homologous to the human mu-switch gene and is similar in organization to immunoglobulin switch genes. Curiously, however, this mu-switchlike segment appears to be unlinked with other switchlike polymorphisms detected at high stringency with the human mu-switch probe. Because in most animal species all switch genes are located within 300-500 kb and show tight linkage in families, this result suggests two possible hypotheses: 1) Our 0.85 kb is a true immunoglobulin switch segment, but the map of the canine Variable Heavy-Chain loci is organized in unlinked clusters, or 2) our 0.85-kb segment is not an immunoglobulin switch segment and is located elsewhere in the genome in all species. We are now using chromosome walking and Yeast Artificial Chromosome Cloning techniques, together with corresponding studies in humans to identify the pathological gene.

An epidemiologic review of dietary intake studies among American Indians and Alaska Natives: implications for heart disease and cancer risk.

PURPOSE: Dietary factors play an important role in the occurrence of heart disease and cancer. While American Indians and Alaska Natives (AIANs) have unique heart disease and cancer mortality profiles, little is known about the effect of diet on heart disease and cancer risk in these populations. This paper reviews existing nutritional intake data from adult AIANs, and considers the potential impact of diet on heart disease and cancer in these communities. METHODS: A review of the literature was conducted using the Medline database system and other reference materials. Studies documenting nutrient intakes only were included in this review. Studies were limited to those among healthy, non-pregnant adults. RESULTS: A total of twelve reports from 1959 to 1996 were found. Sample sizes for the studies ranged from 20 to 575 subjects. Most studies were done among women, and a variety of nutritional assessment techniques (24 hour recall, food frequency questionnaire, multiple-day food record) were used. Most studies also had limited nutrient intake data, especially for dietary fiber and vitamin E. The majority of studies reported moderately high intakes of fat and saturated fat, and low intakes of polyunsaturated fat and fiber. CONCLUSIONS: Based on the limited data, diet may play an important role in the heterogeneity of heart disease and cancer mortality in AIAN communities. More research is needed to assess the impact of diet on heart disease and cancer risk, including more longitudinal data, and data to assess the validity and reliability of traditional methods of dietary assessment.

Phenylethanolamine N-methyltransferase gene expression: synergistic activation by Egr-1, AP-2 and the glucocorticoid receptor.

The gene encoding the epinephrine synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT), is transcriptionally activated by Egr-1, AP-2, and the glucocorticoid receptor (GR). Stimulation by AP-2 requires its synergistic interaction with an activated GR. The present studies show that the GR also cooperates with Egr-1 or the combination of Egr-1 and AP-2 to activate the PNMT promoter. Together Egr-1, AP-2, and the GR can induce PNMT promoter-mediated luciferase reporter gene expression beyond the sum of their independent contributions as well as synergistically activate the endogenous PNMT gene leading to marked increases in PNMT mRNA. Examination of the effects of mutation of the AP-2 or Egr-1 binding sites on PNMT promoter activation by DEX and the factor binding to the remaining intact site or by all three transcriptional activators showed changes in luciferase reporter gene expression which suggest that DNA structure may be altered thereby reducing or enhancing synergistic activation. It also appears that the -165 bp Egr-1 site may not be critical for the synergism observed between Egr-1, AP-2 and the GR. When the glucocorticoid response element (GRE) within the PNMT promoter was mutated, PNMT promoter activation by Egr-1 and DEX, AP-2 and DEX or all three showed both inhibition and enhancement, even when the GRE was completely eliminated. These observations indicate that induction of PNMT gene transcription may occur either through GR interaction with other transcriptional proteins after binding to its cognate GRE or through direct protein-protein interaction in the absence of GRE binding. While the mechanisms by which Egr-1 and the GR and Egr-1, AP-2 and the GR function cooperatively to stimulate PNMT promoter activity remain to be elucidated, this synergistic stimulation of the PNMT promoter by these factors may provide important in vivo and in vitro regulatory control of the PNMT gene.

Ciliary muscle dysfunction in Adie's syndrome.

Ciliary muscle function in patients with Adie's syndrome was studied retrospectively in 122 patients and prospectively in 17 patients. When a careful history was taken, two thirds of the patients had ciliary muscle-related symptoms. Most of the patients with Adie's syndrome had a moderate accomodative paresis, but there was a strong tendency for the ciliary muscle to recover with time. Many patients showed a tonicity of accommodation, especially those who had had the condition for several years. Astigmatism could be induced with accommodation in one third of patients. This may be related to segmental paralysis of the ciliary muscle. Seventy-three percent of the patients showed supersensitivity of the ciliary muscle in the involved eye, when both eyes were treated with a mixture of 0.25% pilocarpine hydrochloride and hydroxypropyl methylcellulose (Isopto Carpine). This may be a clinical aid in diagnosing Adie's syndrome. Two patients were found to have bilateral ciliary muscle dysfunction but only unilateral pupillary abnormalities. These two patients may have had a "pupil-sparing" Adie's syndrome.

Sympathetic ophthalmia. Histopathologic and fluorescein angiographic correlation.

Sympathetic ophthalmia was found 15 months after cataract extraction in a previously traumatized eye. Histopathologic examination disclosed numerous Dalen-Fuchs nodules with underlying choroidal granulomas causing obliteration of the choriocapillaris and disruption of Bruch's membrane. Prominent Dalen-Fuchs nodules were also observed clinically in the sympathizing eye, and the angiographic findings of initial hypofluorescence followed by late hyperfluorescence correlated with the pathologic findings in the sympathogenic eye. Only ten cases of sympathetic ophthalmia with fluorescein angiography have been reported previously. This is the fifth case accompanied by a histopathologic description of the exciting eye. The finding of breaks in Bruch's membrane has not been previously reported, to the best of our knowledge. This article compares the angiographic and pathologic appearances with those described in previous reports.

Clinical grading of relative afferent pupillary defects.

OBJECTIVES: To assess the validity and reproducibility of quantitating relative afferent pupillary defects with the swinging flashlight test, using a 3-second pause technique, and to compare this grading system with that using neutral density filters. DESIGN: We prospectively studied patients with relative afferent pupillary defects by using the swinging flashlight test with a standardized illumination time of 3 seconds (pause time) for each eye. Each relative afferent pupillary defect was graded as follows: grade I, a weak initial constriction and greater redilatation; grade II, initial stall and greater redilatation; grade III, immediate pupillary dilatation; grade IV, immediate pupillary dilatation following prolonged illumination of the good eye for 6 seconds; grade V, immediate pupillary dilatation with no secondary constriction. The grades on the individual resident evaluations were compared with those on the group evaluations, and the grading system was compared with the neutral density filter grading system. SETTING: Neuro-ophthalmology service of an urban teaching hospital. STUDY PARTICIPANTS: A total of 119 patients. RESULTS: There was a good correlation in all grades between individual resident and group evaluations, with an overall 78% agreement. The five grades had corresponding values in neutral density filter log units: grade I, 0.4; grade II, 0.7; grade III, 1.1; grade IV, 2.0; and grade V, infinity. CONCLUSIONS: The 3-second pause technique for the swinging flashlight test is a reliable method for the detection and quantitation of relative afferent pupillary defects. The grading system can be compared with the neutral density filter grading system, and each grade has a corresponding value in log units.

Optochiasmatic arachnoiditis in multiple sclerosis.

A patient had visual field loss and optochiasmatic arachnoiditis and subsequently developed other evidence of multiple sclerosis. The possibility is raised that many of the "idiopathic" cases of optochiasmatic arachnoiditis may have a similar origin. Special emphasis is placed on the functional role of the fibrosis in the pathogenesis of optochiasmatic arachnoiditis.

Aicardi's syndrome. A clinicopathologic study.

A 9-week-old female infant was seen with typical clinical features of Aicardi's syndrome. At autopsy (at 21 months of age), examination of the brain disclosed polymicrogyria and agenesis of the corpus callosum. Histopathologic studies of the posterior segments showed areas of intact but attenuated and depigmented retinal pigment epithelium, and atypical colobomatous defect of both posterior segments, and ectatic scleral channels lined by a retinal pigment epithelial choriocapillarislike complex in the left eye. The pathogenesis of the ocular defects is discussed.

Alcoholism, life events, and psychiatric impairmant.

A sample of 122 DPs was compared to a "normative" sample of CSRs. The presentation of psychiatric disorder scores and numbers and kind of stressful life events was detailed. Results of this comparative analysis suggest that research that focuses on high psychiatric disorder-controlling for life events is in order. Furthermore, therapeutic intervention must obviously take into account the iterative nature of alcohol and stressful life events. Also, these findings suggest and support the role of life stress in the possible formation of alcoholism.

Vitamin and mineral supplement use by older rural adults.

BACKGROUND: Vitamin and mineral supplement products are widely consumed by older adults. This study describes supplement product use in a multiethnic rural population, relates supplement usage to dietary nutrient intake, and determines predictors of supplement usage. METHODS: Data are from a population-based sample of 130 community-dwelling adults aged 70 years and older in two rural North Carolina counties. The sample was 34% African American, 36% European American, and 30% Native American. Interviewer-administered semiquantitative food frequency questionnaires were used to obtain data on usual diet and supplement use. In-home interviews allowed verification of supplement composition. Intakes from diet and supplement products were examined for vitamins A, E, B6, C, folate, iron, zinc, and calcium. RESULTS: Of those who participated in the study, 47% reported using one or more supplement products. African Americans were significantly less likely to take supplements than Native Americans or European Americans. Based on dietary intakes, 65% of the participants were deficient (<2/3 recommended dietary allowance [RDA]) for at least one nutrient. The use of supplement products for the eight nutrients investigated was not related to dietary nutrient deficiency. For all nutrients investigated, except iron and calcium, a greater proportion of those without dietary deficiency took a supplement product than those with deficiency. Using logistic regression, ethnicity (European American and Native American), and gender (women) were significant predictors of supplement use. CONCLUSIONS: These findings suggest that although both dietary deficiencies of vitamins and minerals and supplement use are relatively high in this population, there is no association between supplement use and deficient dietary intakes for the eight nutrients examined. Health care providers should be aware that nutritional counseling and guidance on appropriate supplement usage is needed in this population.

A novel low molecular weight ecdysiotropin in post-diapause, pre-hatch eggs of the gypsy moth, Lymantria dispar L. (Lepidoptera: Lymantriidae).

Extracts of post-diapause, pre-hatch eggs of the gypsy moth, Lymantria dispar L. were examined for prothoracicotropic hormone (PTTH)-like activity using an in vitro assay involving last-instar prothoracic glands (PGs). The eggs were extracted in water, eluted from a low-pressure C18-silica cartridge in 60% acetonitrile, and fractionated on a high-performance, size-exclusion column. The primary ecdysiotropic activity eluted with an estimated molecular weight of 2.1 kDa far below the 4-7 kDa size determined for the low molecular weight PTTHs (bombyxins). Dose-response analysis revealed that the maximum activation was reduced by 75% by organic solvent extraction, but the remaining activity retained the ability to maximally activate the PGs 10-fold in vitro. At least some of the ecdysiotropic activity in the post-diapause, pre-hatch egg is localized in the brain of the pharate larva, and this activity increases dramatically prior to hatch when eggs are incubated at 25 degrees C.

Direct-to-consumer prescription drug advertising: trends, impact, and implications.

We provide an overview of what is known about the impact of direct-to-consumer (DTC) advertising of prescription drugs. Specifically, we explore the historical trends that led to the industry's increasing use of this form of promotion. Then, using the published literature to date, we review the impact of DTC advertising on the consumer, the medical profession, and the health care system. We conclude by offering policy suggestions for how the pharmaceutical industry can promote its products more responsibly, how the Food and Drug Administration (FDA) can regulate DTC advertising more effectively, and how the medical and public health communities can educate the public about drug therapies more constructively.

Influence of serum-free culture conditions on steroid 5alpha-reductase mRNA expression in rat C6 glioma cells.

Immunocytochemical studies previously showed that serum deprivation resulted in the appearance of steroid 5alpha-reductase (5alpha-R) in the cytoplasm of rat C6 glioma cells. To determine whether this increase in cytoplasmic 5alpha-R was due to changes in 5alpha-R gene expression, the effect of serum deprivation on 5alpha-R mRNA expression was examined. No significant change in the mRNA levels was observed in cells grown in serum-free culture medium. Therefore, the appearance of 5alpha-R immunoreactivity in the cell cytoplasm observed under serum-free conditions is probably not due to changes in 5alpha-R gene expression.