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Biomedical subjects

K Houston

Publications and source records attributed to K Houston.

At least 19 recordsLinked to original sources

Deliberate self-harm is associated with allelic variation in the tryptophan hydroxylase gene (TPH A779C), but not with polymorphisms in five other serotonergic genes.

BACKGROUND: There is a heritable component to suicidal behaviour, encouraging the search for the associated risk alleles. Given the putative role of the 5-HT (5-hydroxytryptamine; serotonin) system in suicidal behaviour, serotonergic genes are leading candidates. In particular, several studies have reported an association with variants in the tryptophan hydroxylase (TPH) gene. METHOD: We studied six serotonergic gene polymorphisms in a well-characterized sample of 129 deliberate self-harm subjects and 329 comparison subjects. The polymorphisms were TPH (A779C), 5-HT transporter (5-HTT, LPR S/L), monoamine oxidase A (MAOA G941T), 5-HT1B receptor (HTR1B G861C), 5-HT2A receptor (HTR2A T102C), and 5-HT2C receptor (HTR2C Cys23Ser). Genotyping was done using polymerase chain reaction (PCR)-based assays. The primary analyses compared allele and genotype frequencies between cases and controls. There were a limited number of planned secondary analyses within the deliberate self-harm group. RESULTS: The TPH A779 allele was more common in deliberate self-harm subjects than in controls (OR 1.38, 95% CI 1.02-1.88; P = 0.03). None of the other polymorphisms was associated with deliberate self-harm. Within the deliberate self-harm group there were no associations with impulsivity, suicide risk, lifetime history of depression, or family history of deliberate self-harm. CONCLUSIONS: Our data extend the evidence that allelic variation in the TPH gene is a risk factor for deliberate self-harm. No evidence was found to implicate the other polymorphisms.

Adult↗

General practitioner contacts with patients before and after deliberate self harm.

BACKGROUND: Deliberate self harm (DSH) is an increasingly common problem. Although much attention is focused on suicide prevention by psychiatric services, the role of the general practitioner (GP) in the prevention of suicidal behaviour and in the aftercare of DSH patients is also important. AIM: To examine the nature and timing of GP contacts with DSH patients before and after an episode of DSH, and patients' satisfaction with these contacts. DESIGN OF STUDY: Structured interviews with patients shortly after an episode of DSH and again approximately one year later. SETTING: A representative sample of 139 DSH patients presenting to a district general hospital. METHOD: Patients were interviewed shortly after DSH and at follow-up about GP contacts, prescribed medication and psychiatric symptoms. RESULTS: At the time of DSH, 91.4% of patients were diagnosed with a psychiatric disorder (depression 69.8%), with 28% receiving treatment from psychiatric services. Two-thirds of patients had been in contact with their GP in the month before DSH, but only 13.3% reported expressing suicidal thoughts. Patients consulted their GP in the week following DSH in 40.6% of cases. Over half (57.9%) the patients discussed the reasons for their DSH at the first consultation and 69.5% reported that this was helpful. Overall, 64.3% of patients were satisfied with the follow-up consultations. CONCLUSIONS: The major role of the GP in the prevention of suicidal behaviour is in the detection and treatment of depression, and in the aftercare of DSH patients.

Adolescent↗

Suicide in young people aged 15-24: a psychological autopsy study.

BACKGROUND: The suicide rate in young people in the United Kingdom has increased over the last decade. As there is a paucity of information about the characteristics of young suicides we have undertaken a detailed investigation of suicides in people aged 15-24 years by means of the psychological autopsy approach. METHODS: The sample consisted of 27 subjects (25 males, two females) whose deaths received a verdict of suicide (N=24) or undetermined cause (N=3). Information was collected from informant interviews, coroners' inquest notes, medical records and psychiatric case notes. A sub-sample of 22 male subjects was compared with an age-matched sample of male deliberate self-harm (DSH) patients. RESULTS: Psychiatric disorders were diagnosed in 19 (70.4%) subjects. These were most commonly depressive disorders (55.5%). Very few individuals were receiving treatment for their disorders. Substance abuse disorders were uncommon but a substantial proportion of individuals had problems with alcohol or drug misuse. Personality disorders were present in 29.6% of subjects and disorders or personality trait accentuation in 55.6%. Comorbidity of psychiatric disorders was found in a third of subjects. The suicides were often the end-point of long-term difficulties extending back to childhood or early adolescence. In addition to mental disorders, relationship and legal difficulties were identified as relatively common contributory factors to the suicides. In comparison to deliberate self-harm patients, male suicides were more likely to use dangerous methods and live alone. LIMITATIONS: Several potential informants could not be interviewed and there was no general population control sample. CONCLUSIONS: The process leading to suicide in young people is often long term, with untreated depression in the context of personality and/or relationship difficulties being a common picture at the time of death. The prevention of suicide in the young clearly requires multiple strategies.

Adolescent↗

Deliberate self-harm patients with alcohol disorders: characteristics, treatment, and outcome.

Deliberate self-harm (DSH) patients with alcohol problems present a considerable challenge for clinical services. In a study of a sample of 150 DSH patients who were representative of all such patients seen at a general hospital during the study period, 40 patients with an ICD-10 diagnosis of alcohol dependence or harmful use of alcohol were compared with the remainder of the sample. The treatment of the patients with alcohol disorders before and after the episode of DSH and the outcome 12-20 months later were also investigated. Compared with other DSH patients, those with an alcohol diagnosis were older and more often male, living alone, unemployed, sick, disabled, or with a past history of DSH. They also had higher scores on measures of anger, aggression, and impulsivity. Comorbid psychiatric disorder was present in 37 (92.5%) patients, this being depression in three-quarters of those cases. Fourteen (35.0%) patients were receiving treatment from the psychiatric services prior to DSH, and 33 (82.5%) were subsequently offered treatment. Of the patients who were followed up, 37.9% remained in contact with psychiatric services, 55.2% showed poor compliance with treatment and 44.8% reported a further episode of DSH. All patients presenting after DSH need to be carefully screened for alcohol disorders and for comorbid psychiatric diagnoses. Treatment of DSH patients with alcohol disorders should include the treatment of any comorbid depressive illness.

Adolescent↗

Psychiatric and personality disorders in deliberate self-harm patients.

BACKGROUND: Previous UK studies have reported much lower rates of psychiatric and personality disorder in those who attempt suicide than in those who die by suicide. AIMS: To determine the nature and prevalence of psychiatric and personality disorders in deliberate self-harm (DSH) patients. METHOD: A representative sample of 150 DSH patients who presented to a general hospital were assessed using a structured clinical interview and a standardised instrument. Follow-up interviews were completed for 118 patients approximately 12-16 months later. RESULTS: ICD-10 psychiatric disorders were diagnosed in 138 patients (92.0%), with comorbidity of psychiatric disorders in 46.7%. The most common diagnosis was affective disorder (72.0%). Personality disorder was identified in 45.9% of patients interviewed at follow-up. Comorbidity of psychiatric and personality disorder was present in 44.1%. CONCLUSIONS: Psychiatric and personality disorders, and their comorbidity, are common in DSH patients. This has important implications for assessment and management.

Adolescent↗

An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region.

A contiguous sequence of nearly 3 Mb from the genome of Drosophila melanogaster has been sequenced from a series of overlapping P1 and BAC clones. This region covers 69 chromosome polytene bands on chromosome arm 2L, including the genetically well-characterized "Adh region." A computational analysis of the sequence predicts 218 protein-coding genes, 11 tRNAs, and 17 transposable element sequences. At least 38 of the protein-coding genes are arranged in clusters of from 2 to 6 closely related genes, suggesting extensive tandem duplication. The gene density is one protein-coding gene every 13 kb; the transposable element density is one element every 171 kb. Of 73 genes in this region identified by genetic analysis, 49 have been located on the sequence; P-element insertions have been mapped to 43 genes. Ninety-five (44%) of the known and predicted genes match a Drosophila EST, and 144 (66%) have clear similarities to proteins in other organisms. Genes known to have mutant phenotypes are more likely to be represented in cDNA libraries, and far more likely to have products similar to proteins of other organisms, than are genes with no known mutant phenotype. Over 650 chromosome aberration breakpoints map to this chromosome region, and their nonrandom distribution on the genetic map reflects variation in gene spacing on the DNA. This is the first large-scale analysis of the genome of D. melanogaster at the sequence level. In addition to the direct results obtained, this analysis has allowed us to develop and test methods that will be needed to interpret the complete sequence of the genome of this species. Before beginning a Hunt, it is wise to ask someone what you are looking for before you begin looking for it. Milne 1926

Alcohol Dehydrogenase↗

Suicide in young people. Study of 174 cases, aged under 25 years, based on coroners' and medical records.

BACKGROUND: Suicide rates in young males in the UK have risen markedly in recent years. AIMS: To investigate the characteristics of a series of consecutive suicides in under-25-year-olds. METHOD: We studied coroners' inquest notes, general practitioners' records and psychiatric case notes of 174 individuals (148 males and 26 females) whose deaths received a verdict of suicide or an open or accidental verdict (excluding traffic accidents) where the circumstances strongly suggested suicide. RESULTS: More individuals were of lower social class and unemployed than in the local population. Hanging and carbon monoxide poisoning were the most frequent methods of suicide, and coproxamol was the drug most often used in overdoses. Previous self-harm had occurred in 44.8%, nearly half of these having carried out multiple episodes and 80% having self-harmed within the previous year. Little support was found for an earlier finding of increasing frequency of general practitioner visits shortly before death. Only 22.4% of individuals were in the care of psychiatric services. CONCLUSIONS: Diverse strategies are required to prevent suicide in the very young.

Adolescent↗

Radiofrequency catheter ablation for paroxysmal supraventricular tachycardia in children and adolescents without structural heart disease. Pediatric EP Society, Radiofrequency Catheter Ablation Registry.

Since 1990, management options available for children with paroxysmal supraventricular tachycardia (PSVT) have included radiofrequency catheter ablation (RCA). To determine the efficacy and safety of the procedure and to maintain a database for long-term follow-up, the Pediatric Electrophysiology Society began a Pediatric RCA Registry on January 1, 1991, to which 46 centers have submitted data from 4,135 total children and adolescents (patient age 0.1 to 20.9 years) who underwent 4,651 RCAs (through September 15, 1996). Of the 88% with a structurally normal heart, PSVT mechanisms (n = 4,030) included 3,110 accessory pathways and 920 atrioventricular node reentry tachycardia (AVNRT) during 3,653 procedures for 3,277 patients. During the 7 years of the Registry, analysis of indications for the procedure has shown a gradual shift. During the first year of the Registry for this PSVT group, "medically refractory tachycardia" was listed as the indication for 44% and "patient choice" was listed as 33%, compared with 29% and 58%, respectively, for the years 1995 to 1996 (p <0.005). Registry results were: 90% immediate success for accessory pathways (95% for left lateral; 87% for septal; 86% for right free wall) and 96% for AVNRT; mean fluoroscopy time 47.6 +/- 40 SD minutes; procedure time 257 +/- 157 SD minutes; major complication rate at the time of the procedure 3.2%. Procedure-related deaths included 1 immediate and 3 at 2, 12 and 68 weeks after the procedure (2 were infants). Follow-up revealed 77% and 71% freedom from recurrence at 3 years for accessory pathways AVNRT, respectively, and rare (<1%) detection of additional complications. RCA has evolved into a standard management option for PSVT in children with a structurally normal heart. RCA for children and adolescents should be recommended after consideration of the procedural risk/benefit compared with that of other management options, the natural history, and individual tolerance/symptoms related to PSVT.

Adolescent↗

Craniofacial morphology of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is the second most common neuromuscular disease of childhood. It is the most common fatal recessive neuromuscular disease. This study is the first to evaluate the craniofacial growth of SMA patients. The results pertain to a sample of 25 SMA patients, between 5 and 32 y of age, who were case matched with unaffected normal controls. Group differences for 25 measures, derived from tracings of standardized cephalometric radiographs, were evaluated using multivariate analysis of variance. The SMA group showed excessive vertical development, particularly of the lower face. They demonstrated relatively larger anterior than posterior facial heights, due in part to a smaller cranial base angulation and a more anteriorly positioned mandibular ramus. Anteroposterior skeletal discrepancies of SMA patients, due to the combined effects of a protrusive maxilla and a retrusive mandible, were moderate. The interincisal angle of the SMA group was smaller than normal, due primarily to proclined maxillary incisors. Relative to palatal length, the SMA group had smaller anterior cranial base and mandibular corpus lengths. These results suggest abnormal craniofacial growth patterns of SMA patients. The etiology of the observed abnormalities seems to be complex and multifaceted, but attention to the treatment of malocclusion may be important for optimal nutrition and respiratory function.

Adolescent↗

Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study.

OBJECTIVE: To examine the effects of testosterone administration to older hypogonadal males (bioavailable testosterone less than 70 ng/dL). DESIGN: Alternate-case controlled trial. SETTING: St. Louis University. PATIENTS: Eight males (mean age 77.6 +/- 2.3 years) who received testosterone and six males (mean age 76 +/- 2.3 years) who served as controls. Selected from alumni of the SHEP trial and attendees at the St. Louis University Impotence Clinic. INTERVENTIONS: Testosterone enanthate (200 mg/mL) was administered intramuscularly to the treatment group every 2 weeks for 3 months. MEASUREMENTS: Serum testosterone, bioavailable testosterone and estradiol, weight, % body fat, right hand muscle strength, balance, cholesterol, HDL-cholesterol, hematocrit, BUN, creatinine, albumin, calcium, PTH, 25(OH) vitamin D, 1,25(OH)2 vitamin D, osteocalcin, prostate-specific antigen, and fructosamine. RESULTS: Males who received testosterone had a significant increase in testosterone and bioavailable testosterone concentration, hematocrit, right hand muscle strength and osteocalcin concentration. They had a decrease in cholesterol (without a change in HDL-cholesterol) levels and decreased BUN/Creatinine ratios. CONCLUSION: These preliminary findings support the need for long term studies of testosterone therapy in older hypogonadal males.

Aged↗

Reciprocal synergy between Escherichia coli and Bacteroides fragilis in an intra-abdominal infection model.

The synergic relationship between Escherichia coli and Bacteroides fragilis was examined in a model of intra-abdominal abscess formation. The addition of B. fragilis to E. coli in the fibrin clot inoculum increased abscess weight and residual numbers of E. coli in the abscess at 7 days. In a reciprocal fashion, E. coli was capable of enhancing B. fragilis persistence in abscesses. Neither heat-killed E. coli nor heat-killed B. fragilis was able to mimic the synergic effect of its live counterpart. Furthermore, B. fragilis culture filtrate was unable to reproduce the ability of live B. fragilis to act synergically with E. coli. For B. fragilis to act synergically with E. coli, it had to be inoculated locally with E. coli in the peritoneal cavity, indicating that an effect on systemic resistance by B. fragilis was an unlikely mechanism for the production of bacterial synergy. These studies suggest that the synergic relationship between bacteria in polymicrobial infections is a complex one, resulting from intimate interactions between bacteria and the host in the local milieu of the infection.

Abscess↗

Control of cytoplasmic pH by Na+/H+ exchange in rat peritoneal macrophages activated with phorbol ester.

The mechanisms underlying cytoplasmic pH (pHi) regulation in elicited rat peritoneal macrophages were investigated by electronic sizing and fluorescence determinations. Acid-loaded cells rapidly regained normal pHi by means of an amiloride-sensitive Na+/H+ exchange. When stimulated by 12-O-tetradecanoyl phorbol 13-acetate, macrophages displayed a biphasic pHi change: a marginal acidification followed by an alkalinization. The latter results from activation of Na+/H+ exchange, since it is Na+-dependent and prevented by amiloride. When the antiport is inhibited, the full magnitude of the initial acidification can be appreciated. This acidification is independent of the nature of the ionic composition of the medium and probably reflects accumulation of protons generated during the metabolic burst. Under physiological conditions, these protons are rapidly extruded by the Na+/H+ antiport.

Animals↗

Evaluation of the turbine pocket spirometer.

A compact electronic spirometer, the turbine pocket spirometer, which measures the FEV1, forced vital capacity (FVC), and peak expiratory flow (PEF) in a single expiration, was compared with the Vitalograph and the Wright peak flow meter in 99 subjects (FEV1 range 0.40-5.50 litres; FVC 0.58-6.48 l; PEF 40-650 l min-1). The mean differences between the machines were small--0.05 l for FEV1, 0.05 l for FVC, and 11.6 l min-1 for PEF, with the limits of agreement at +/- 0.25 l, +/- 0.48 l, and +/- 52.2 l min-1 respectively. The wide limits of agreement for the PEF comparison were probably because of the difference in the technique of blowing: a fast, long blow was used for the pocket spirometer and a short, sharp one for the Wright peak flow meter. The FEV1 and FVC showed a proportional bias of around 4-5% in favour of the Vitalograph. The repeatability coefficient for the pocket spirometer FEV1 was 0.18 l, for FVC 0.22 l, and for PEF 31 l min-1. These compared well with the repeatability coefficients of the Vitalograph and the Wright peak flow meter, which gave values of 0.18 l, 0.28 l, and 27 l min-1 respectively. At flow rates of over 600 l min-1 the resistance of the pocket spirometer marginally exceeded the American Thoracic Society recommendations. The machine is easy to operate and portable, and less expensive than the Vitalograph and Wright peak flow meter combined. It can be recommended for general use.

Evaluation Studies as Topic↗

An investigation of operating theatre staff exposed to humidifier fever antigens.

Sixty staff working in a hospital operating theatre, where a case of humidifier fever had been identified, were studied together with 49 subjects working in other parts of the hospital. They each had a blood test for serology, a skin test, and a chest radiograph and completed a questionnaire. The theatre staff also had pulmonary function tests. The theatre humidifier was found to contain several organisms including amoebae and antigens cross-reacting highly with those implicated in previous outbreaks of humidifier fever. Of the 60 exposed subjects, 25 had developed antibodies, nine had probable symptoms of humidifier fever, and six possible symptoms. There was a strong association between symptoms and antibodies (p = 6 x 10(-5) by Fisher's exact test). The development of antibodies was also related to duration of exposure in the theatre (p less than 0.01 by X2 test for trend) and inversely to smoking (p = 0.0073 by Fisher's exact test) but not to history of atopy. Because of the presence of antigens and because certain biocides added were ineffective in controlling antigenic build-up the humidifier was switched off. Eight months later specific IgG levels in the theatre staff sera, estimated by an enzyme-linked immunosorbent assay technique, had fallen on average by 25%. Inhalation challenge with humidifier water was performed in eight subjects. Four subjects reacted to the challenge, including both those with antibodies and previous symptoms.

Air Conditioning↗

Physiological patterns in early morning asthma.

Sixteen asthmatic patients who regularly showed early morning falls in peak expiratory flow rate of more than 25% were studied at 06.00 hours and 14.00 hours. At 06.00 hours considerable deterioration in static lung volumes and airways resistance occurred which was typical of an attack of acute asthma. Blood gas analysis showed less variation, with mild hypoxia and a wide alveolar-arterial oxygen tension gradient throughout the study. Diurnal variation was also seen in the response of maximal mid expiratory flow rates to the inhalation of helium/oxygen mixture in seven patients, but another seven were consistently non-responders. The overall pattern of results suggests that the calibre of both large and small airways decreased at night but improvement was more complete in large airways during the day. Despite these findings patients had few symptoms at 06.00 hours when most of them showed marked reversibility after inhaling aerosol salbutamol. This phenomenon might account for the sudden nature of some asthma deaths as these often occur in the early morning. If this is the case, the minority of patients whose early morning decline in lung function was not immediately reversible would appear to be at greatest risk.

Adult↗