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Biomedical subjects

R Warburton

Publications and source records attributed to R Warburton.

18 recordsLinked to original sources
PubMed2001

Randomized placebo-controlled trial of testosterone replacement in men with mild Leydig cell insufficiency following cytotoxic chemotherapy.

OBJECTIVE: Testosterone deficiency is associated with significant morbidity, and androgen replacement in overt hypogonadism is clearly beneficial. However, there are few data concerning the response to therapy in young men with mild testosterone deficiency. DESIGN AND PATIENTS: We have identified a cohort of 35 men, mean age 40.9 years, with mild Leydig cell dysfunction, defined by a raised LH level (LH >or= 8 IU/l) and a testosterone level in the lower half of the normal range or frankly subnormal (testosterone < 20 nmol/l), following treatment with cytotoxic chemotherapy for malignancy. Patients were assigned randomly to 12 months treatment with transdermal testosterone (n = 16) (Andropatch 2.5 mg patches, 1-2 patches per day) or placebo patches (n = 19) in a single blinded manner. MEASUREMENTS: Measurements of bone mineral density (BMD) and body composition were performed at baseline, 6 months and 12 months using single and dual energy X-ray absorptiometry (SXA, DXA). In addition, spinal BMD was assessed at baseline and 12 months by quantitative CT (QCT). Subjects were reviewed at 3-monthly intervals; at each visit blood was taken for measurement of testosterone, SHBG, LH, FSH, oestradiol, lipids and IGF-1 and patients completed three questionnaires which assessed energy levels, mood and sexual function. RESULTS: Total testosterone and calculated free testosterone increased significantly in the testosterone-treated group compared with the placebo-treated group (13.3 nmol/l and 342.9 pmol/l at baseline compared with 17.3 nmol/l and 454.8 pmol/l during the study period in the testosterone-treated group; P = 0.05 and P = 0.02, respectively). LH was suppressed into the normal range in 15 of the 16 testosterone-treated men and mean LH significantly reduced from 11.1 IU/l at baseline to 6.8 IU/l during the study. There was no significant change in BMD at the hip, spine or forearm and no change in fat or lean body mass. There was a significant reduction in physical fatigue in the testosterone-treated group compared with the placebo-treated group (P = 0.008) and a borderline improvement in activity score (P = 0.05). There were no significant effects of treatment on mood or sexual function. Neither oestradiol nor IGF-1 levels differed between the two groups during the study. There was no significant change in mean total cholesterol, HDL cholesterol or triglyceride levels, but there was a small, but significant reduction in LDL cholesterol levels in the testosterone-treated group compared with the placebo group (P = 0.02). CONCLUSIONS: These results suggest that testosterone therapy in young men with raised LH levels and low/normal testosterone levels does not result in significant changes in BMD, body composition, lipids or quality of life, apart from a reduction in physical fatigue and a small reduction in LDL cholesterol. This implies that mild hypogonadism defined on this basis is not of clinical importance in the majority of men, and that androgen replacement cannot be recommended for routine use in these patients.

Adult↗
PubMed2001

Reduced oxygen tension increases atrial natriuretic peptide release from atrial cardiocytes.

To test the hypothesis that reduced oxygen tension stimulates cardiac atrial natriuretic peptide (ANP) secretion, we measured ANP release and expression in neonatal rat atrial and ventricular cardiac myocytes exposed to 45 min and 3, 6, and 24 hr of 3% or 21% oxygen. In atrial cardiocytes, the percentage of increase in culture media ANP concentration from baseline was greater in cells exposed to 3% than in cells exposed to 21% oxygen after 3 hr (814% +/- 52% vs. 567% +/- 33%, P < 0.05) and 6 hr of exposure (1639% +/- 91% vs. 1155% +/- 73%, P < 0.05). No differences in the percentage of increase in culture media ANP concentration was seen at 45 min (284% +/- 27% vs. 201% +/- 16%, P = NS) or 24 hr (2499% +/- 250% vs. 2426% +/- 195%). There was a significant increase in cellular ANP content between 3 and 24 hr in atrial cardiocytes exposed to 21% oxygen (105% +/- 40% vs. 296% +/- 60%, P < 0.05), but not in atrial cardiocytes exposed to 3% oxygen (118% +/- 20% vs. 180% +/- 26%, P = NS). Steady-state ANP mRNA levels in atrial cardiocytes were not affected by oxygen tension. In ventricular cardiocytes, oxygen tension did not affect ANP secretion, cellular ANP content, or steady-state ANP mRNA levels. We conclude that reduced oxygen tension increases release of ANP from atrial, but not ventricular cardiocytes and that this mechanism may contribute to the elevation in plasma ANP seen during acute hypoxia.

Animals↗
PubMed1996

Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder.

OBJECTIVE: Despite the increasing awareness of attention deficit hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder; most of the trials have focused on the psychostimulants. Because the tricyclic anti-depressant desipramine has been found to be effective in treating ADHD in pediatric groups, the authors tested its efficacy in adults with ADHD. METHOD: The authors conducted a randomized, 6-week, placebo-controlled, parallel-design study of desipramine at a target daily dose of 200 mg in 41 adult patients with DSM-III-R ADHD. They used standardized structured psychiatric instruments for diagnosis and, as the dependent variables (outcome), used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. RESULTS: There were highly significant differences in the reduction of ADHD symptoms between adults receiving desipramine and placebo. Within the desipramine-treated group, there were clinically and statistically significant differences between baseline and the week 6 end point for 1) reduction of 12 of 14 symptoms of ADHD and 2) decreases in the broad categories of hyperactivity, impulsivity, and inattentiveness. In contrast, placebo-treated patients showed no differences between baseline and end point for any of the ADHD symptoms assessed. According to strict, predefined criteria for response, 68% of desipramine-treated subjects and no subjects in the placebo group were considered positive responders. Response to desipramine was independent of dose, level of impairment, gender, or lifetime psychiatric comorbidity with anxiety or depressive disorders. CONCLUSIONS: These results, similar to findings in children and adolescents with ADHD, indicate that desipramine is effective in the treatment of ADHD in adults.

Adolescent↗
PubMed1995

Family-environment risk factors for attention-deficit hyperactivity disorder. A test of Rutter's indicators of adversity.

BACKGROUND: This study investigated whether family-environment risk factors are associated with attention-deficit hyperactivity disorder (ADHD). Compelling work by Rutter and coworkers revealed that it was the aggregate of adversity factors (severe marital discord, low social class, large family size, paternal criminality, maternal mental disorder, and foster care placement) rather than the presence of any single factor that led to impaired development. Based on the work of Rutter, we hypothesized a positive association between indicators of adversity and the diagnosis of ADHD and ADHD-associated impairments. METHODS: We studied 140 ADHD and 120 normal control probands. Subjects were non-Hispanic white boys between the ages of 6 and 17 years. Rutter's indicators of adversity were used to predict ADHD-related psychopathology as well as impaired cognitive and psychosocial functioning. RESULTS: The odds ratio for the diagnosis of ADHD increased as the number of Rutter's adversity index predicted ADHD-related psychopathology (depression, anxiety, and conduct disorder), learning disabilities, cognitive impairment, and psychosocial dysfunction. CONCLUSIONS: A positive association appears to exist between adversity indicators and the risk for ADHD as well as for its associated psychiatric, cognitive, and psychosocial impairments. These findings support the work of Rutter and stress the importance of adverse family-environment variables as risk factors for children with ADHD.

Adolescent↗
PubMed1995

Impact of adversity on functioning and comorbidity in children with attention-deficit hyperactivity disorder.

OBJECTIVE: Prior research on risk factors for attention-deficit hyperactivity disorder (ADHD) has shown that familial risk factors play a role in the disorder's etiology. This study investigated whether features of the family environment were associated with ADHD. METHOD: One hundred forty children with ADHD and 120 normal control probands were studied. Subjects were Caucasian, non-Hispanic males between the ages of 6 and 17 years. Exposure to parental psychopathology and exposure to parental conflict were used as indicators of adversity, and their impact on ADHD and ADHD-related psychopathology and dysfunction in children was assessed. RESULTS: Increased levels of environmental adversity were found among ADHD compared with control probands. The analyses showed significant associations between the index of parental conflict and several of the measures of psychopathology and psychosocial functioning in the children. In contrast, the index of exposure to parental psychopathology had a much narrower impact, affecting primarily the child's use of leisure time and externalizing symptoms. CONCLUSIONS: A relationship appears to exist between adversity indicators and the risk for ADHD as well as for its associated impairments in multiple domains. These findings confirm previous work and stress the importance of adverse family-environment variables as risk factors for children who have ADHD.

Achievement↗
PubMed1995

High risk for attention deficit hyperactivity disorder among children of parents with childhood onset of the disorder: a pilot study.

OBJECTIVE: Although well-documented in clinical and epidemiological studies of attention deficit hyperactivity disorder (ADHD) in children, the familial nature of the adult syndrome has not been well investigated. One approach to evaluate the familial nature of adult ADHD is through a high-risk design aimed at estimating the risk for the disorder in children of parents with child-hood-onset ADHD. METHOD: Children at risk for ADHD were ascertained from the study group of 84 referred adults with clinical diagnoses of childhood onset of the disorder, confirmed by structured interviews. Diagnostic information on the disorder was derived from the ADHD module of the Schedule for Affective Disorders and Schizophrenia for School Age Children--Epidemiologic Version, supplemented with information regarding treatment for ADHD for the affected child and school history including repeated grades, placement in special classes, and tutoring. RESULTS: Of the 84 children at risk, 48 (57%) met criteria for ADHD. The rate of the disorder in children of adults with the disorder was significantly higher than the previously reported rate of ADHD among siblings of children with the disorder. Of the 48 ADHD children of parents with the disorder, 36 (75%) were treated for it. The rates of school failure were almost identical to those previously reported in a group of referred children and adolescents with ADHD. CONCLUSIONS: These results support the validity of the adult diagnosis of ADHD and suggest that the adult form of this disorder may have stronger familial etiological risk factors than its pediatric form. If these results are confirmed, families selected through adult probands with ADHD might be especially useful for testing genetic hypotheses about the disorder.

Achievement↗
PubMed1994

Analysis of mutant HLA-A2 molecules. Differential effects on peptide binding and CTL recognition.

Previous studies have identified several residues lining the groove of the HLA-A2.1 molecule that are critical for Ag presentation. However, it is not clear whether these residues are critical for binding of the peptide epitope per se or for determining the appropriate conformation of bound peptide. To distinguish between these possibilities, mutations at eight of these residues have been tested for their effects on the ability of the molecule to bind and present two known peptide epitopes--one derived from the influenza A matrix protein, the other from HIV pol. With only one exception, the mutations were found to affect the binding of the two peptides similarly. Most of the mutations resulted in intermediate deleterious effects on binding, with the B pocket mutant F9Y having the most dramatic negative effect on binding for both peptides. Two of the mutations significantly enhanced binding of both peptides and a peptide-specific effect on binding was seen with the substitution, Y99H, which enhanced binding of the matrix peptide yet diminished binding of the pol peptide. In contrast to the effects on binding, the effects of the mutations on presentation differed considerably for the two peptides. The most striking difference was seen with two alpha 2 alpha helix mutants that are fully recognized by pol peptide-specific CTL but not recognized by matrix peptide-specific CTL even though levels of binding were comparably diminished for the two peptides. These results suggest that some interactions, although not critical for binding per se, are critical for functional binding and the importance of these interactions differs among peptide epitopes.

Amino Acid Sequence↗
PubMed1994

Insulin resistance, high prevalence of diabetes, and cardiovascular risk in immigrant Asians. Genetic or environmental effect?

OBJECTIVES: To compare the prevalence of diabetes, hyperinsulinaemia, and associated metabolic abnormalities in immigrant Asians, Asians in India, and native white British men. DESIGN: Case control study. SETTING: Wythenshawe Hospital, Manchester, United Kingdom, and Maulana Azad Medical School, New Delhi, India. SUBJECTS: Men with angiographically proved coronary artery disease; 83 British Asians, 87 white men, and 30 Indian Asians with age matched controls. INTERVENTIONS: Fasting lipid concentrations, serum glucose, and total insulin concentrations were measured in the fasting state and one and two hours after a 75 g glucose load by mouth. All subjects had a physical examination by the same observer. RESULTS: Asians in the United Kingdom and in India had a higher prevalence of diabetes and impaired glucose tolerance than the white British men. Patients in all three ethnic groups had higher total insulin concentrations than their controls in the fasting state and after the glucose load. British Asian and Indian Asian patients and controls had higher total insulin concentrations than the white men in the fasting state and after the glucose load. Total insulin concentrations were similar in British and Indian Asians, though fasting concentrations were higher in British Asians than Indian Asians. White men had similar cholesterol, lower triglyceride, and higher high density lipoprotein cholesterol concentrations than Asians in the United Kingdom and in India. British Asian patients had higher cholesterol concentrations and British Asian controls had higher triglyceride concentrations than the Indian Asian groups. Asian patients and controls were more active. British and Indian Asian patients had higher waist to hip ratios than controls. The waist to hip ratio was positively correlated with insulin and triglyceride concentrations and negatively correlated with the high density lipoprotein cholesterol concentration. Fasting insulin and high density lipoprotein concentrations were independent predictors of coronary artery disease in white men, whereas in British Asians the waist to hip ratio was the strongest independent predictor. In Indian Asians the waist to hip ratio and high density lipoprotein concentration were independent predictors of coronary artery disease. CONCLUSIONS: Central obesity in the subgroups of Asians studied showed a close association with hyperinsulinaemia and the risk of coronary artery disease. A predisposition to insulin resistance and its metabolic abnormalities in this group of Asians seems to be genetically determined, environmental changes after migration having only a small additional effect.

Asia↗
PubMed1993

Case report: chronic sub-dural hematoma following high-speed ejection.

This paper reports a case of chronic sub-dural hematoma occurring in a pilot after a high-speed ejection that was within the survival envelope of the Mark 10 Martin Baker ejection seat. The events leading up to the ejection, his subsequent hospitalization for treatment of immediate injuries and late development of neurological signs, 6 weeks after the ejection, are presented. (A thorough search of literature has failed to reveal any previously published account of chronic sub-dural hematoma as a post-ejection complication.) His surgical treatment, recovery, and final assessment are discussed together with the possible causes of his sub-dural hematoma. Flight surgeons should take careful note of the events in this case. Sub-dural hematoma is frequently difficult to diagnose but it should not be discounted as a potential late complication from an ejection which is within the parameters of survivability and which yields, initially, only signs of relatively minor injury.

Accidents, Aviation↗
PubMed1992

Overview of CAPACITY data.

This paper presents an overview of the data from 15 cases collected with the CAPACITY software for cost analysis of PACS. The data suggest that both hospital wide and partial PACS implementations do not pay back yet. Only Nuclear Medicine PACS systems may be introduced cost-neutral in the near future. Because of the assumed price drop of hardware components of 5-25% per year, hospital wide and partial PACS may allow cost savings within the next 10-20 years. There are major differences in viewpoints concerning the required PACS configurations and their costs. The experiences with the CAPACITY software suggest the need for the establishment of key rules, for designing a PACS configuration and for estimating PACS costs.

Computer Systems↗
PubMedDate not supplied

Associations between childhood asthma and ADHD: issues of psychiatric comorbidity and familiality.

OBJECTIVE: In this paper we evaluate the association between asthma and attention-deficit hyperactivity disorder (ADHD), addressing issues of comorbidity and familiality by formulating and testing competing hypotheses. METHOD: Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (N = 140) and normal controls (N = 120) and their first-degree relatives. Information on asthma was obtained from the mothers in a standardized manner blind to the proband's clinical status. RESULTS: The risk for asthma did not meaningfully differ between ADHD and control children. Relatives of ADHD probands with and without asthma were at significantly greater risk for ADHD than relatives of normal controls. In contrast, the risk for asthma was significantly elevated only among relatives of children with ADHD plus asthma. CONCLUSIONS: These findings argue against a substantial etiological or pathophysiological relationship between the two conditions but suggest that ADHD and asthma are independently transmitted in families. Thus, the observation of ADHD symptoms in an asthmatic child should not be dismissed out of hand as being a consequence of asthma since many asthmatic ADHD children may actually have ADHD.

Adolescent↗