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Biomedical subjects

A Davis

Publications and source records attributed to A Davis.

At least 73 records · Page 4Linked to original sources

False positives in universal neonatal screening for permanent childhood hearing impairment.

High rates of false-positive neonatal screens for permanent childhood hearing impairment (PCHI) associated with raised hearing thresholds lead to unnecessary assessments of the baby, which may worry parents. False-positive rates need to be reduced, especially in view of the UK government's announcement that national neonatal screening will be introduced. We report screening criteria that give a six-fold reduction in false-positive rates.

Deafness↗

Why do cytotoxic T lymphocytes fail to eliminate hepatitis C virus? Lessons from studies using major histocompatibility complex class I peptide tetramers.

Hepatitis C virus (HCV) infection is a major public health problem, affecting an estimated 3% of the world's population, and over 10% in some countries. Infection in most cases becomes persistent, and can lead to hepatic inflammation, fibrosis and liver failure. The T lymphocyte reponse, in particular that mediated by cytotoxic T lymphocytes (CTLs), is likely to be involved in determining the outcome of infection, although its overall role is not clear. The use of major histocompatibility complex (MHC) class I peptide tetrameric complexes (tetramers) to study antiviral CTL responses has revolutionized our approach to the study of human infection. We have used a panel of MHC class I tetramers to analyse immune responses in HCV-infected individuals at various stages of disease. We find that the CTL response against HCV is vigorous in its early phases but dwindles over time both in terms of lymphocyte number and function. A number of potential explanations for this 'CTL failure' are discussed.

Adult↗

Survival and reproduction in the first two years following a large-scale primate colony move and social reorganization.

(Macaca nemestrina) and baboon (Papio cynocephalus, Papio anubis, and hybrids) breeding colonies from the Primate Field Station (PFS) (Medical Lake, WA) to the Tulane Regional Primate Research Center (Covington, LA). Colony records on all 598 pigtailed macaques (Macaca nemestrina) and 157 baboons (P. c. anubis) shipped to the Tulane Primate Center from the PFS breeding colony were used for analysis of species, sex, age, origin, current status, and the number of animals born at Tulane and their status. To provide comparative statistics, colony records on all 1,002 macaques and 258 baboons alive on 1 January 1991 at the Field Station were retrieved in the same manner as the Tulane data. Overall survival rates of macaques in the months following the move (71.7%) were similar to those associated with the Arashiyama West colony move from Japan to Texas. In our colony, significantly lower survival following the move was seen only in older (10 years+) macaques, while survival in other age groups was slightly lower than in the comparison year of 1991 at the Primate Field Station. Captive-bred macaques exhibited higher survival than wild-caught animals. Infant survival at Tulane was not significantly different than in pre-move years. Baboons fared well in the move, with no significant differences in mortality or reproduction when compared with the 1991 Medical Lake baboon colony.

Animals↗

Optimization of storage stability of lyophilized actin using combinations of disaccharides and dextran.

The storage stability of a dry protein depends on the structure of the dried protein, as well as on the storage temperature relative to the glass transition temperature of the dried preparation. Disaccharides are known to preserve the native conformation of a dried protein; however, the resulting T(g) of the sample may be too low ensure adequate storage stability. On the other hand, formulations dried with high molecular weight carbohydrates, such as dextran, have higher glass transition temperatures, but fail to preserve native protein conformation. We tested the hypothesis that optimizing both protein structure and T(g) by freeze-drying actin with mixtures of disaccharides and dextran would result in increased storage stability compared to actin dried with either disaccharide or dextran alone. Protein structure in the dried solid was analyzed immediately after lyophilization and after storage at elevated temperatures with infrared spectroscopy, and after rehydration by infrared and circular dichroism spectroscopy. Structural results were related to the polymerization activity recovered after rehydration. Degradation was noted with storage for formulations containing either sucrose, trehalose, or dextran alone. Slight increases in T(g) observed in trehalose formulations compared to sucrose formulations did not result in appreciable increases in storage stability. Addition of dextran to sucrose or trehalose increased formulation T(g) without affecting the capacity of the sugar to inhibit protein unfolding during lyophilization and resulted in improved storage stability. Also, dextran provides an excellent amorphous bulking agent, which can be lyophilized rapidly with formation of strong, elegant cake structure. These results suggest that the strategy of using a mixture of disaccharide and polymeric carbohydrates can optimize protein storage stability.

Actins↗

Outcome from complex neurosurgery: an evidence based approach.

BACKGROUND: The aim of this study was to determine outcome, including quality of life, after surgery for petroclival meningioma using a standard skull base approach and to carry out an evidence based appraisal of the relevant literature. METHOD: Pre- and post-operative data including adverse events were prospectively recorded in 19 patients (15 females, age range 29-63) undergoing a transpetrous approach for a petroclival meningioma. Patients were assessed using the GOS and SF-36 post operatively. FINDINGS: 24 operations were done. 6 patients developed a new permanent neurological deficit and 10 experienced a temporary deficit or exacerbation of existing deficits. At 1 year 15 patients had made a good/moderate recovery, 3 were severely disabled and 1 died--in keeping with other studies. By contrast the SF-36 showed that in all 8 categories of the SF-36 between 39-72% of surviving patients were functioning below the accepted norms. INTERPRETATION: After transpetrous excision of a petroclival meningioma the quality of life for the patient is worse than that indicated in surgeons' reported results. This paper represents an attempt to address the issue of evidence-based medicine and finds that such an approach is not apparent in the medical literature on this pathology. While we argue that methods for measuring outcome should be refined and carers input recognised it does raise certain philosophical considerations. It is the counsel of perfection and if achieved may lead to surgeons operating on fewer patients, more petroclival cases being viewed as inoperable because of the higher morbidity, despite there being an inescapable pathway to surgical intervention.

Adult↗

Development of a modified picture-sort food frequency questionnaire administered to low-income, overweight, African-American adolescent girls.

There is essentially no ideal method of dietary assessment. Physiologic methods (i.e., doubly labeled water) probably come closest, but high cost, participant burden, and limited information limit their use. Furthermore, most dietary assessment methods have been designed for and tested in white adults. Very few have been designed for and tested in African-American adolescents. This study examined validity and reliability of a modified picture-sort food frequency questionnaire (FFQ) administered to 22 low-income, overweight, African-American adolescent girls, aged 11 to 17 years. The FFQ was administered to subjects twice during a 2-week period, and evaluated using the mean values of three 24-hour recalls. The natural log-transformed energy-adjusted, deattenuated correlation coefficients between the second FFQ and the mean from 3 recalls exceeded 0.50 for most nutrients, ranging from 0.32 (protein) to 0.87 (saturated fat). The energy and nutrient values from the first FFQ were greater than those from the second FFQ. Most correlation coefficients for the test-retest reliability of the FFQ were not significant. We conclude that although larger samples are needed to generalize results, the picture-sort dietary assessment method appears to be promising and merits further research.

Adolescent↗

Selected topics related to occupational exposures.

The auditory and nonauditory effects of noise can be quite profound, affecting approximately 15 to 20 million Americans. As with most occupational toxins, recognition and careful assessment of noise exposure are the foundation on which preventive measures and treatment are based. Dosimeters can measure noise exposure over specific time periods. Pure tone air conduction audiometric monitoring should be performed on an annual basis in workers at risk for significant noise exposure. Occupational infectious disease involves far more than hepatitis and tuberculosis. Periodic fever, dermatologic manifestations and other symptoms peculiar to a specific disease may be important clues to an occupationally related exposure. Whereas strict attention to hand washing and isolation are cornerstones of prevention, use of protective gear is mandated in certain situations. Zoonotic disease, agriculture exposure, water transmission, and biologic contaminants in buildings can be important but subtle exposures sources. Recognition of these infections often depends on the alertness of the primary care giver.

Cardiovascular Diseases↗

Selected topics related to occupational exposures. Part III. Occupational dermatology

Occupational skin disorders are very common and are a surprisingly frequent cause of lost work time. Failure to suspect an occupational cause can lead to repeated treatment failure and needlessly prolong patient misery and frustration. Primary care providers play a key role in recognizing possible occupational causes and arranging appropriate education, preventive measures, and treatment. Occupational skin conditions often occur in nonindustrial settings in workers such as hairdressers, health care personnel, and food handlers. Irritant contact dermatitis is by far the most prevalent occupational skin condition and is emphasized in this article. Allergic contact dermatitis, infections, skin cancers, and acneform eruptions may also have significant occupational associations. We will present criteria that suggest on occupational exposure, list common offending agents, and review the clinical presentations and relevant pathophysiology. We provide guidance on a directed history and physical examination and suggest when diagnostic testing is most likely to have value. Finally we outline preventive measures such as contact avoidance, barrier creams, and protective gloves and address therapy and indications for referral.

Journal Article↗

Selected topics related to occupational exposures. Part IV. Occupational liver disease

Occupational and environmental substances associated with liver injury include industrial chemicals, drugs, certain bacterial and viral infections, and other physical agents. Hepatotoxic chemical agents can be classified as direct hepatotoxins, indirect hepatotoxins, or agents that cause liver injury as a result of host idiosyncrasy. More than 100 industrial chemicals have been shown to be acutely hepatotoxic. Occupations with hepatotoxin exposures are numerous and include farm workers, chemists, dry cleaners, electroplaters, garage workers, health care workers, nurses, painters, printers, rayon makers, and others. Clinical presentation of occupational liver disease may be acute/subacute or chronic but is often insidious. Some hepatotoxins are capable of causing malignancy. The key to diagnosis of occupational liver disease is exposure history. The occupational and environmental history should include a brief description of the patient's current and recent jobs to the extent necessary to assess their potential for workplace hepatotoxic exposures. Confounders such as obesity, alcohol, and viral hepatitis are common, and a careful history and examination are essential. A variety of tests are used to evaluate liver disease and may include serum markers, tests of synthetic liver function, clearance tests, and anatomic tests. A key responsibility of the primary care provider is to prevent further liver injury from preventable occupational exposures; not only the patient but also coworkers may be at risk. Efforts should be made to ensure that patients with potential hepatotoxic exposures are working or living in safe conditions. Collaboration with an occupational specialist may be especially useful in this regard.

Journal Article↗

Selected topics related to occupational exposures. Part V. Occupational cardiovascular disease

Cardiovascular disease is common in the United States. Several occupational exposures, such as carbon disulfide and organic nitrates, are believed to cause occupational cardiovascular disease. In addition some other agents, such as lead and cadmium, may indirectly cause cardiovascular disease through their effects on blood pressure. For other agents (ie, carbon monoxide, solvents, and chlorofluorocarbons), acute exposure and high levels may cause cardiovascular disease but may not cause cardiovascular disease through long-term or low levels. A primary care physician who has a patient with a new or unstable cardiovascular disease should obtain an occupational history to assess whether occupational exposures may be playing a role. An occupational history may indicate potential cardiovascular risks. Such risks can include exposure to certain chemicals and metals, physical factors, exertion, or psychological stress. The primary care physician should be able to assess the situation and advise the patient, as well as the employer, about restrictions or accommodations that may need to be made.

Journal Article↗

Tubal sterilization: focus on the U.S. experience.

OBJECTIVE: To review the frequency, effectiveness, and clinical sequelae of tubal sterilization with a focus on the U.S. experience. DESIGN: A review of U.S. health care statistics and English-language literature using a MEDLINE search, bibliographies of key references, and U.S. government publications. PATIENT(S): Women seeking tubal sterilization. INTERVENTION: Tubal sterilization. MAIN OUTCOME MEASURE(S): Effectiveness and long-term risks and benefits. RESULT(S): Half of the 700,000 annual bilateral tubal sterilizations (TS) are performed postpartum and half as ambulatory interval procedures. Eleven million U.S. women 15-44 years of age rely on TS for contraception. Failure rates vary by method with one third or more resulting in ectopic pregnancy. Reversal is most successful after use of methods that destroy the least tube. Evidence of menstrual or hormonal disturbance after TS is weak, although some studies find higher rates of hysterectomy among previously sterilized women. Decreased risk of subsequent ovarian cancer has been observed among sterilized women. CONCLUSION(S): Tubal sterilization is highly effective and safe. Failures, although uncommon, occur at higher rates than previously appreciated. Evidence for hormonal or menstrual changes due to TS is weak. Tubal sterilization is associated with decreased risk of ovarian cancer.

Adolescent↗

Triphasic norgestimate-ethinyl estradiol for treating dysfunctional uterine bleeding.

OBJECTIVE: To compare the efficacy of a triphasic combination oral contraceptive (OC) containing norgestimate and ethinyl estradiol (E2) and placebo in the treatment of metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding (DUB). METHODS: In this multicenter, randomized, double-masked study, 201 women (15-50 years of age) with DUB received triphasic norgestimate-ethinyl E2 or placebo, for three consecutive 28-day treatment cycles. Efficacy was determined by evaluating investigator and subject assessments of DUB resolution, abnormal uterine bleeding patterns during an 84-day reference period, and change from baseline in subjects' quality of life. The sample size was based on the assumption that the proportions of subjects exhibiting treatment success (percentage of subjects with investigator and subject overall assessments of DUB resolution of "improved") were 65% for the active group and 40% for the placebo group (alpha = 0.05, 1 - beta = 0.80). RESULTS: More than 80% of subjects receiving triphasic norgestimate-ethinyl E2 had improvements in their abnormal bleeding patterns as assessed by investigators, and the subjects themselves compared with fewer than 50% of subjects in the placebo treatment group (P <.001). Abnormal bleeding patterns were reported by significantly fewer subjects receiving triphasic norgestimate-ethinyl E2 than in the placebo treatment group (P <. 001). Change from baseline in physical functioning (eg, self-care, walking, lifting, exercising) was significantly more improved in the triphasic norgestimate-ethinyl E2 group than in the placebo group. CONCLUSION: The triphasic combination of norgestimate and ethinyl E2 is an effective treatment for metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding.

Adolescent↗

Elucidating the contributions of processing speed, executive ability, and frontal lobe volume to normal age-related differences in fluid intelligence.

One theory of normal cognitive aging asserts that decreases in simple processing speed mediate the age-related decline of fluid intelligence. Another possibility is that age-related atrophic changes in frontal brain structures undermine the functioning of executive abilities, thereby producing the same decline. In this study, we used principal components analysis to derive a measure of fluid-spatial intelligence in 197 normal adults between 20 and 92 years of age. Measures of perceptual comparison speed, working memory, and executive ability, as well as regional brain volumes based on high resolution magnetic resonance imaging were obtained from a subsample of 112 participants. We then conducted a series of hierarchical multiple regression analyses to test whether (1) the processing speed theory, (2) frontal-executive theory, or (3) some combination of these best accounted for age-related variation in fluid intelligence. The results showed that perceptual comparison speed, executive ability, and frontal lobe volume each made significant contributions to a regression equation that explained 57% of the variance in fluid intelligence. These findings suggest that both the processing speed and frontal-executive theory of cognitive aging are partially correct and complement one another.

Adult↗

Defective insulin receptors in Rabson-Mendenhall syndrome cause complete peripheral insulin resistance but minimal hepatic insulin response remains.

In Rabson-Mendenhall syndrome, severe insulin resistance is caused by defective insulin receptors. The patient studied lacks insulin receptor binding due to a truncation mutation of one allele and a point mutation of the other allele of the insulin receptor alpha-subunit. He developed pulmonary hypertension and cor pulmonale, and was considered for organ transplantation. A trial of prednisone 1.2 mg/kg/d was initiated to determine if he could tolerate immunosuppressive therapy without deterioration of his pre-existing, difficult to control diabetes mellitus. Insulin responsiveness was measured prior to and after 4 d of glucocorticoid administration ('Before GC' and 'After GC') using the hyperinsulinemic glucose clamp and stable isotope tracer dilution techniques. After a 12-h fast and 24 h of intravenous insulin, a primed continuous infusion of 6,6-(2)H(2)-glucose was administered during a 2-h tracer equilibration period followed by a 2-h insulin-deficient period, and a 2-h hyperinsulinemic glucose clamp period during which insulin was infused at 7 u/kg/h. Blood glucose concentrations during the basal periods, while no insulin was infused, were 245+/-7 and 138+/-8 mg/dL in the studies Before GC and After GC, respectively. During both hyperinsulinemic glucose clamp periods, the blood glucose was 171+/-1 and 167+/-5 mg/dL, respectively. Hepatic glucose production (HGP) was higher during the basal period Before GC than during the same period After GC (7.86+/-0.23 vs. 5.31+/-0.19 mg/kg/min). HGP rate was suppressed by insulin to 1.48+/-0.45 mg/kg/min Before GC, but was not suppressed After GC (4.19+/-0.81 mg/kg/min). The hyperinsulinemic glucose clamp did not increase the glucose utilization rate nor the glucose clearance rate over basal in either Before GC or After GC, indicating complete peripheral insulin resistance. In summary, the liver showed some response to insulin in the absence of insulin receptors but the peripheral tissues had no response to insulin. Glucocorticoids worsened insulin resistance in the liver in this patient.

Journal Article↗

Frequency of fruit and vegetable consumption and blood antioxidants in the Caerphilly cohort of older men.

OBJECTIVE: To assess the number of portions of fruit and vegetables consumed daily by a large representative sample of older men, and to determine how blood antioxidant (vitamins E, A and carotenoids) concentrations vary with fruit and vegetable consumption. DESIGN: Cross-sectional study of free-living men. SUBJECTS: Men aged 55-69 y (dietary data, n=1957; blood data, n=1874) participating in Phase III (1989-1993) of the Caerphilly and Speedwell Collaborative Heart Disease Studies. METHODS: Dietary data were obtained by semi-quantitative food-frequency questionnaire and blood samples were analysed for antioxidant vitamins. Men were subdivided into groups on the basis of portions per day of fruit and vegetables. Within these sub-groups, mean and 95% ranges of intakes and of blood antioxidant levels were obtained. Log transformations were performed where appropriate. RESULTS: Only 4.3% of the men met the recommended target of five portions, while 33.3% of the men consumed one or fewer portions of fruit and vegetables per day. Those men who consumed the poorest diets with respect to fruit and vegetable intakes were more likely to be from lower socio-economic classes, drink more alcohol and be current smokers. Fruit and vegetable intake reflected plasma concentrations of antioxidants, which showed a dose-response relationship to frequency of consumption. CONCLUSIONS: Older men in the UK consume much less fruit and vegetables than current recommendations. Major difficulties are likely to be encountered in trying to meet a dietary target that is clearly much higher than the fruit and vegetable consumption of large sections of the older population in the UK. SPONSORSHIP: This work was supported by the Medical Research Council.

Aged↗

Leptin concentrations in Prader-Willi syndrome before and after growth hormone replacement.

OBJECTIVE: This study explored leptin concentrations in Prader-Willi syndrome (PWS), a genetic disorder characterized by significant obesity and presumed hypothalamic dysfunction. The potential interaction of leptin metabolism with the growth hormone (GH) axis was also studied. STUDY DESIGN: Plasma leptin concentrations and percent body fat were determined by radioimmunoassay and dual energy x-ray absorptionmetry, respectively, in 23 children with Prader-Willi syndrome and 23 children with exogenous obesity. RESULTS: Log plasma leptin concentrations were positively correlated with percentage body fat in PWS (r = 0.844) and exogenous obesity (r = 0.869). When the regression lines for the two groups were compared, there were no differences in their slopes (P = 0.737) or intercepts (P = 0.701). Administration of recombinant human growth hormone to PWS children for 12 months significantly reduced both percentage body fat and plasma leptin concentrations, but the relationship of log plasma leptin to percentage body fat was unchanged. CONCLUSION: Prader-Willi syndrome is not accompanied by deranged leptin concentrations and there was no evidence of an interaction of the GH axis with leptin metabolism in these GH-deficient children.

Body Composition↗