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Biomedical subjects

B Waters

Publications and source records attributed to B Waters.

At least 19 recordsLinked to original sources

Black patients with chronic hepatitis C have a lower sustained viral response rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin*.

In previous hepatitis C virus (HCV) treatment studies, Black patients not only had a lower sustained viral response (SVR) rate to interferon and ribavirin (RBV) than non-Black patients but also a higher frequency of HCV genotype 1 (GT-1) infection. The aim of this community-based study was to determine whether Black patients have a lower SVR rate independent of genotype. We prospectively enrolled 785 patients (24.8% Black, 71.5% White, 3.7% others) who received interferon alpha-2b 3 MU three times weekly + RBV 1000-1200 mg/day for 24 weeks (GT-2/3) or 48 weeks (GT-1). Black patients were more commonly infected with GT-1 (86.8%vs 64.8%, P < 0.001) and less frequently had an SVR compared with non-Black patients (8.4%vs 21.6%, P < 0.001). Within GT-1, Black patients had a lower SVR rate than non-Black patients (6.1%vs 14.1%, P = 0.004) but not within GT-2/3 (50.0%vs 36.5%, P = 0.47). Black patients had lower baseline haemoglobin levels (14.8 vs 15.3 g/dL, P < 0.001) and neutrophil counts (2900 vs 4100/mm(3), P < 0.001) and required more frequent dose reductions of RBV (29.8%vs 18.5%, P < 0.001) and interferon (4.7%vs 1.6%, P = 0.012). However, dose reductions were not associated with lower SVR rates while early treatment discontinuations were (2.9%vs 25.7%, P < 0.001). Independent predictors of SVR were GT-1 [odds ratio (OR) 0.33; 95% confidence interval (CI) 0.20-0.55; P < 0.001], Black race (OR 0.45; 95% CI 0.22-0.93; P = 0.030), and advanced fibrosis, stages 3 + 4 (OR 0.53; 95% CI 0.31-0.92; P = 0.023). In conclusion, Black patients infected with HCV GT-1 (but not GT-2/3) have a lower SVR rate than non-Black patients. This is not explained by their lower baseline haemoglobin levels and neutrophil counts that lead to higher rates of ribavirin and interferon dose reductions.

Alanine Transaminase↗

Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a common but poorly understood liver disease. Our aim was to study a large group of patients referred for Hepatology consultation to further characterize this disorder, in particular its demographics and range of severity. We also sought to better understand its etiology and its relationship to the insulin resistance syndrome, known as the metabolic syndrome or syndrome X. METHODS: Retrospective review of 90 patients seen over a 4-yr period. RESULTS: Ninety patients aged 14-70 with NASH seen at the Liver Clinics at either the University of Tennessee or the Medical University of South Carolina. Eleven had complications of portal hypertension and seven of these had undergone or were awaiting transplantation. NASH was seen in nine families either in siblings or in subsequent generations. Diabetes or insulin resistance were present in almost all in this cohort of patients with NASH. Diabetes, hyperlipidemia, hypertension, and atherosclerotic disease, the components of syndrome X, were common in this population. CONCLUSION: NASH affects males and females equally, and presents over a wide age range. Despite its usually benign course, 28% of patients had cirrhosis and almost half of those had complications of portal hypertension, necessitating liver transplantation. Obesity was common in affected patients and cirrhosis was more common in the morbidly obese. Familial clustering was common, with 18% of patients having a similarly affected first degree relative. The clinical features that define syndrome X (diabetes, hypertension, hyperlipidemia, and atherosclerotic disease) are common in affected patients. Studies of glucose tolerance demonstrated unsuspected diabetes in six, and insulin resistance (the hallmark of syndrome X) in 85% of those tested. We hypothesize that NASH is a disorder of genetic etiology and is the hepatic manifestation of syndrome X, the insulin resistance syndrome.

Adolescent↗

Novel natural products from soil DNA libraries in a streptomycete host.

As a route to accessing the potential chemical diversity of uncultivable microbes from the soil, combinatorial biosynthetic libraries were constructed by cloning large fragments of DNA isolated from soil into a Streptomyces lividans host. Four novel compounds, terragines A (1), B (2), C (3), and D (4), were isolated from recombinant 436-s4-5b1, and another novel compound, terragine E (5), was isolated from 446-s3-102g1. The structures were determined by a combination of spectroscopic techniques, primarily 2D NMR.

Amides↗

Hepatitis C infection among survivors of childhood cancer.

Preliminary reports have suggested that survivors of childhood cancer and aplastic anemia who are infected with the hepatitis C virus (HCV) have a low risk for progression to significant liver disease. Among our surviving patients who were transfused between 1961 and March 1992, 77 (6.6% of surviving patients tested thus far) have evidence of HCV infection, whereas 4 surviving patients who were transfused after March 1992 are HCV-infected. One patient chronically infected with HCV died of liver failure, and 2 patients died of hepatocellular carcinoma. To characterize the risk for these and other complications, 65 patients are enrolled in a longitudinal study of HCV infection, of whom 58 (89.2%) had circulating HCV RNA at the time of protocol enrollment, with genotypes 1A and 1B most commonly isolated. Most enrolled patients have few or no symptoms, carry out normal activities, and have normal liver function. To date, 35 patients have undergone liver biopsy for abnormal liver function since the diagnosis of primary malignancy; central pathology review shows 28 (80%) have chronic active hepatitis, 25 (71%) have fibrosis, and 3 (9%) have cirrhosis. These preliminary data suggest that though most survivors of childhood cancer who are infected with HCV are clinically well, some are at risk for clinically significant liver disease. Identification of other HCV-infected patients and prospective monitoring of this cohort are ongoing to determine the risk for, and to identify factors associated with the progression of, liver disease.

Adult↗

Paternal and maternal depressed mood during the transition to parenthood.

BACKGROUND: The course of postnatal depression was examined in first-time mothers and fathers with emphasis on the role of personality and parental relationships as risk factors. METHOD: 157 couples were assessed at four points: antenatally and at 6, 12 and 52 weeks postnatally. Various measures of mood and personality were administered at each of these assessment points. RESULTS: Examination of the factors associated with depressed mood suggested that a woman's relationship with her own mother was important in the early postpartum stage, and also her level of interpersonal sensitivity and neuroticism. For the father, his relationship with either his mother or father and his level of neuroticism were associated with his mood level early on. By the end of the first year couple morbidity increased, with rates of distress being at their highest for both parents, and factors associated with depressed mood being linked to partner relationship variables, at least for mothers. At most time points, antenatal mood and partner relationship were significant predictor variables for the postnatal mood of both mothers and fathers. LIMITATIONS: The sample had a relatively high level of education and this should be taken into account when considering the generalisation of findings to less educated populations. At the time of conducting this study, the Edinburgh Postnatal Depression Scale (EPDS) had only been validated for use in the first few months postpartum, and thus we used another scale to measure the mother's mood at the other assessment points (the Beck Depression Inventory). Current research would suggest that the EPDS is valid both antenatally and at other times in the first year postpartum. CONCLUSION: Whilst there was some consistency for mothers and fathers in the variables that predict their postpartum adjustment, these being antenatal mood and partner relationship, there is also evidence that adjustment to parenthood was related to different variables at different times. Early adjustment was related to the couple's relationship with their own parents, as well as their own personality. Later adjustment was related to the couple's functioning and relationship.

Adult↗

Enhanced production of microbial metabolites in the presence of dimethyl sulfoxide.

Bacterial strains grown in the presence of low concentrations of dimethyl sulfoxide (DMSO) exhibit significant qualitative and quantitative alterations in the production of secondary metabolites. This effect was confirmed for a variety of biosynthetic families, including chloramphenicol (chorismate), thiostrepton (peptide) and tetracenomycin (polyketide), and for natural and recombinant strains of streptomycetes; a similar effect was seen with antibiotic-producing bacilli such as B. circulans. Increase in antibiotic production was not the result of a change in the growth rate of these organisms, since yields of biomass were similar in media with and without DMSO (up to 3%). We suggest that the addition of compounds such as DMSO provides a means of examining the full biosynthetic potential of microbes and might be used to promote secondary metabolite production. The mode of action of DMSO is not known, but in the cases studied it may act at the level of translation.

Anti-Bacterial Agents↗

Serious hepatitis A: an analysis of patients hospitalized during an urban epidemic in the United States.

BACKGROUND: Memphis and Shelby County, Tennessee, experienced an epidemic of hepatitis A in 1994 and 1995. More than 1700 cases were reported. OBJECTIVE: To characterize the clinical features of patients hospitalized during a large urban epidemic of hepatitis A. DESIGN: Retrospective chart review. SETTING: 15 acute care hospitals in Shelby County, Tennessee. PATIENTS: 256 patients hospitalized with acute hepatitis A. MEASUREMENTS: Laboratory findings (such as prothrombin time and bilirubin level), complications, and mortality. RESULTS: The median patient age was 26 years. Thirty-nine complications occurred in 35 patients. Twenty patients (8%) had extrahepatic complications, and 5 (2%) died. Patients 40 years of age and older were more likely to have serious complications, including death (P = 0.014). Sixty-seven patients (26%) presented with coagulopathy (prothrombin time > or = 3 seconds prolonged). Fifty-four patients (21%) had a bilirubin level greater than 170 micromol/L (10 mg/dL). CONCLUSIONS: During this epidemic, hepatitis A caused serious illness and death. Complications were more frequent in patients 40 years of age and older, but young, healthy persons were also at risk for severe complications.

Adult↗

Coroners' records of rural and non-rural cases of youth suicide in New South Wales.

OBJECTIVE: The aim of this study is to compare the frequency of certain putative risk factors for youth suicide in New South Wales (especially use of alcohol, social class, unemployment, and internal migration) in metropolitan and rural settings. METHOD: A review of 137 files for 10-19-year-old subjects judged by the Coroner to have committed suicide in 1988-1990 was carried out. RESULTS: One hundred and fifteen males and 21 females were identified (one subjects sex was unavailable). The male-female ratio was higher in rural (13.0) areas than non-rural (4.9 chi 2 = 12.14, p < 0.01). Of 27 subjects migrating within Australia, most migrated in a rural direction, and most to rural shires. Unemployment was somewhat more common among rural (38.5%) than non-rural (28.9%) subjects (chi 2 = 0.75, p = 0.39). Eleven of 50 non-rural parents of the deceased, but none of the 11 rural parents, were ranked as being in social classes 2 or 3. Alcohol consumption appeared more common in rural shires (44%) than metropolitan areas (32.9%), but this was not statistically significant. Medical services were less utilised prior to death in rural (15%) than non-rural (25%) areas (chi 2 = 1.69, p = 0.19), and a psychiatric diagnosis was recorded more commonly in non-rural areas. CONCLUSIONS: Incomplete coronial file data and relatively small numbers limit this study's conclusions. Male suicides, principally by firearms, predominated in rural areas. Youth firearm access remains highly relevant to rural communities. Possible trends among rural subjects toward rural migration, higher unemployment, lower social class and lower medical attendance may point to resource deprivation among this group; these matters require further investigation.

Adolescent↗

Suicide among young rural Australians 1964-1993: a comparison with metropolitan trends.

The study tested hypotheses that from 1964 to 1993: (1) suicide rates among Australian 15- to 24-year-old males rose more sharply in rural than metropolitan areas; (2) firearm suicide rates among 15- to 24-year-old males, declining throughout Australia recently, rose continuously in rural areas; (3) suicide rates among 15- to 24-year-old females did not change significantly in either metropolitan or rural areas. Suicides of those aged 10-24 years recorded by the Australian Bureau of Statistics (ABS) were classified according to the subject's residential grouping. Rates were calculated using ABS population data corresponding to these groupings. Results were analysed using log-linear analysis and chi-square statistics. The results supported the first two hypotheses, but not the third. Suicide rates for 15- to 24-year-old males rose by a factor of 2.2 in metropolitan areas, by 4-fold in towns with populations between 4,000 and 25,000, and by 12-fold in towns with populations less than 4,000. Male firearm suicide rates continued to rise in rural areas, and the greatest proportion of deaths in those locations were by firearms, though male hanging rates increased most in recent years in all locations. Female youth suicide rates did not change overall, but in towns with populations less than 4,000, they increased 4.5-fold. Possible explanations for this epidemic, which are mostly speculative and require confirmation, are discussed.

Adolescent↗

Effect of interferon-alpha treatment of chronic hepatitis C on health-related quality of life.

Studies of interferon-alpha (IFN-alpha) therapy for chronic hepatitis C have focused on viral clearance; however, few have evaluated patient's health-related quality of life during therapy. This study evaluates health-related quality of life and the prevalence of anxiety and depression in patients with chronic hepatitis C before, during, and following IFN-alpha therapy. Patients undergoing IFN-alpha therapy for chronic hepatitis C were asked to complete health status measures as well as anxiety and depression inventories before, during, and following IFN-alpha therapy. These measures were compared to the results of healthy adults in the general US population. Thirty-eight of forty-eight eligible patients (79%) with chronic hepatitis C completed the questionnaires. Respondents demonstrated a significant increase in depression during the sixth month of interferon therapy in comparison to pretreatment results. Anxiety scores improved significantly after one month of IFN-alpha in comparison to pretreatment results. Scores on the health status measures did not vary with IFN-alpha therapy. Patient responses were analyzed with respect to biochemical response (normalized transaminases) to IFN-alpha. IFN-alpha responders, who were aware of their transaminase results, exhibited lower scores on anxiety subscales during and after therapy (P = 0.02-0.04). Scores on the health status subscale, role emotional, improved in IFN-alpha responders compared to nonresponders during the sixth month of therapy (P = 0.02). Response to IFN-alpha therapy was not associated with any other differences on subscale analysis. Patients with chronic hepatitis C exhibited health perceptions similar to the general US population, and these were unchanged during IFN-alpha therapy. However, the incidence of depression significantly increased during the sixth month of IFN-alpha therapy. IFN-alpha responders exhibited fewer emotional problems as well as a lower incidence of anxiety during and following therapy.

Adult↗

Amino acid variation in the GyrA subunit of bacteria potentially associated with natural resistance to fluoroquinolone antibiotics.

In studies of genetic diversity in natural microbial populations, we have analyzed nucleotide sequences in the quinolone resistance-determining region of the bacterial gyrA gene in ciprofloxacin-resistant and nonselected soil bacteria obtained from the environment. It is apparent that this sequence is highly variable, and resistance to fluoroquinolone antibiotics occurring in environmental populations of bacteria is due at least in part to natural sequence variation in this domain. We suggest that the development of new antimicrobial agents, including completely synthetic antimicrobials such as the fluoroquinolones, should incorporate the analysis of resistance mechanisms among microbes in natural environments; these studies could predict potential mechanisms of resistance to be encountered in subsequent clinical use of the agents and would guide chemical modification designed to evade resistance development.

Amino Acid Sequence↗

Hepatitis E virus infection in an immigrant to the United States.

A patient who had recently traveled from India to Tennessee was found to have acute hepatitis E. Improved recognition and serologic testing have increased the diagnosis of hepatitis E in the United States. For those at risk, hepatitis E should be considered in the differential diagnosis of acute hepatitis.

Adult↗

Comparison of bupivacaine plus buprenorphine with bupivacaine alone by caudal blockade for post-operative pain relief after hip and knee arthroplasty.

In a double-blind, parallel group trial, 15 patients who were given a caudal injection of 1.8 mg kg-1 of bupivacaine after induction of anaesthesia, were compared with 15 patients in whom 7.2 mg kg-1 of buprenorphine was added to the same dose of bupivacaine, prior to knee or hip replacement surgery. The duration of analgesia was much longer (mean 606 min vs. 126 min P < 0.001) in those receiving added buprenorphine; mean morphine consumption in the first 24 h was halved (14 mg vs. 28 mg) and patient satisfaction greatly increased. There were no significant differences in the incidence of complications although the group which had added buprenorphine had a lower incidence of vomiting.

Aged↗

Exclusion of close linkage of bipolar disorder to the Gs-alpha subunit gene in nine Australian pedigrees.

Growing evidence suggests that guanine nucleotide binding proteins (G proteins) may be involved in both the pathogenesis and treatment of bipolar affective disorder. Both overactive G proteins and increased levels of the alpha subunit of the stimulatory form (Gs-alpha) have been demonstrated in peripheral leucocytes of manic patients while an increase of Gs-alpha subunit levels has also been found in a postmortem study of bipolar disorder. The function of Gs and Gi alpha subunits has now been shown to be affected by lithium. The present study aimed to determine whether bipolar affective disorder was linked to the Gs-alpha subunit gene which has been mapped to chromosomal region 20q13.2. Linkage analysis utilized the PCR amplification of a portion of the Gs-alpha gene that contains a dinucleotide repeat (CA repeat) polymorphism. Linkage of bipolar disorder and recurrent depression to the Gs-alpha subunit gene was tested using a series of autosomal dominant and recessive models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective illness. Close linkage to the Gs-alpha subunit gene was strongly excluded using each model and definition. Thus, our study indicates that a genetic defect in the Gs-alpha subunit gene is unlikely to be the cause of bipolar disorder.

Adolescent↗

Effect of route of nutrition on recovery of hepatic organic anion clearance after fasting.

BACKGROUND: Previous work documented a 40% depression of hepatic indocyanine green (ICG) clearance (ClICG) in pigs fasted to 20% weight loss, with return to normal within 12 days of food refeeding. ClICG in pigs is insensitive to changes in hepatic blood flow but very sensitive to changes in hepatic function (HF). Serial ClICG determinations were performed to quantify the effect of route of nutrient delivery on recovery of HF. METHODS: Fourteen pigs were fasted to 20% weight loss (12.8 days average) with both gastrostomy and intravenous catheters placed in each animal midway through the fast. ClICG was measured before fast, after fast, and after 12 days refeeding through the enteral or parenteral route at 125 kcal/kg/day with isonitrogenous, isocaloric diets containing 9% fat. Urine and stool were analyzed for total nitrogen. RESULTS: No significant differences appeared between groups in nitrogen output during fasting (4.5 +/- 1.2 gm/kg enteral, 4.6 +/- 1.2 gm/kg parenteral), in nitrogen intake (800 +/- 19 mg/kg/day enteral, 810 +/- 10 mg/kg/day parenteral), or in before or after fast ClICG, but enteral feeding produced more positive nitrogen balance. ClICG improved significantly with enteral but not with parenteral feeding. CONCLUSIONS: Enteral feeding produces faster nitrogen accrual and reverses the depression of major pathways of bilirubin and organic anion excretion associated with malnutrition. Parenteral feeding failed to improve organic anion clearance despite weight gain.

Analysis of Variance↗

Exclusion of close linkage of bipolar disorder to the dopamine D3 receptor gene in nine Australian pedigrees.

The recently cloned dopamine D3 receptor (DRD3) gene is of potential relevance to the aetiology of bipolar disorder because of an almost exclusive expression in limbic tissue, the region of the brain putatively responsible for control of emotion. We therefore aimed to determine whether bipolar disorder in nine pedigrees (with 171 members) was linked to this receptor gene, which has been mapped to chromosomal region 3q 13.3. Linkage of bipolar disorder and recurrent depression to the DRD3 gene was tested using a series of autosomal dominant and recessive models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective illness (ranging from bipolar I alone to all affective disorders). Close linkage to the DRD3 gene was strongly excluded using each model and definition, and these conclusions persisted when a wide range of rates of 'sporadic' (non-genetic) presentations of illness were incorporated in the analysis.

Adolescent↗

The genetics of bipolar disorder.

Growing interest in the application of molecular biological techniques to psychiatric disorders has reinvigorated interest in the genetics of the psychoses. It is therefore timely to review the current state of knowledge of the genetics of bipolar disorder. Family, twin and adoption studies are all consistent in confirming the strongly heritable nature of this condition. As segregation analyses have been unable to determine the mode of transmission of bipolar disorder, ongoing linkage analyses using DNA markers will be crucial in determining whether this condition is due to a single major gene, a small number of genes, or multifactorial polygenic inheritance.

Adoption↗

Youth suicide in New South Wales: urban-rural trends.

OBJECTIVE: The study tested the hypotheses that (i) the rate of suicide by firearms among youth (aged 10-19 years) is increasing at a greater rate than rates of suicide by other methods; (ii) the rate of youth suicide in rural New South Wales is significantly higher than those in urban areas; and (iii) the increase in youth suicide by means of firearms is occurring at a greater rate in rural males aged 15-19 years than in other groups. DESIGN: Data were obtained from the NSW Office of the Australian Bureau of Statistics concerning 735 youth suicides in NSW between 1964 and 1988. These were reviewed for information concerning residential area and method of death. Five five-year periods were used, and rates were calculated with population figures obtained in the census years for the same age and sex group. RESULTS: From 1964 to 1988, suicide by firearms has risen most substantially, from 3.4 to 5.6 per 100,000 per year in 15-19-year-old males. There has also been a substantial increase in 15-19-year-old male suicides by hanging (0.7 to 3.4 per 100,000 per year). Poisoning suicides have declined among females and males in the past 15 years. Suicide rates in Sydney, Newcastle and Wollongong have remained stable. In rural cities, they have increased from 1.5 to 4.7 per 100,000 per year (F = 4.9, P less than 0.02) while in rural municipalities and shires they have increased from 1.3 to 6.4 (F = 14.6, P less than 0.0001). The suicide rate of 15-19-year-old males has shown a modest increase in Sydney and no change in Newcastle or Wollongong, but the rate for 15-19-year-old males in rural cities has more than doubled, from 5.1 to 12.5 (F = 7.7, P less than 0.003), while in rural municipalities and shires, the rate has increased more than fivefold, from 3.9 to 20.7 (F = 9.3, P less than 0.001). There has been no significant change in the suicide rates of 15-19-year-old females, or in 10-14-year-olds. The rate of suicide by firearms among 15-19-year-old males has not risen significantly in rural cities, but in rural municipalities and shires the rates have risen fivefold from 2.8 to 14.8 (F = 5.6, P less than 0.01). CONCLUSIONS: Each hypothesis was confirmed. An increase of this magnitude is not an artefact of coroners' verdicts. The findings are believed to be due to ready access to firearms, the use of alcohol and drugs (particularly in firearms suicides) and increasing socioeconomic, health, and identity problems for rural youth, especially males.

Adolescent↗