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Biomedical subjects

M Naughton

Publications and source records attributed to M Naughton.

At least 19 recordsLinked to original sources

Questionnaires to assess urinary and anal incontinence: review and recommendations.

PURPOSE: We reviewed and provide recommendations about the most scientifically robust and appropriate questionnaires for evaluating symptoms and the quality of life impact of urinary and/or anal incontinence, and vaginal and pelvic floor problems. We also investigated the use of these questionnaires in randomized, controlled trials of treatment strategies. MATERIALS AND METHODS: The Symptom and Quality of Life Committee of the International Consultation on Incontinence performed a systematic review of questionnaires related to urinary and anal incontinence, and vaginal and pelvic floor problems, searching MEDLINE, The Cochrane Library and other electronic databases between 2001 and 2004. RESULTS: A total of 23 robust and relevant questionnaires could be recommended in clinical practice and research. The development of questionnaires to assess anal incontinence, and pelvic floor and vaginal problems has been limited with some promising measures but with none achieving the highest level of rigor. From 2001 to 2004 there were 150 published randomized trials of treatments for incontinence. Increasingly trials of incontinence are using recommended measures (38% of those for urinary incontinence and 22% of those for anal incontinence used the highest quality questionnaires in 2001 to 2004) but none of vaginal and pelvic floor problems used recommended questionnaires. CONCLUSIONS: With increasing acknowledgment of the value of patient based assessment much attention has been given to the development of questionnaires to assess symptoms and quality of life. Sufficient measures are now available for urinary incontinence, and researchers and clinicians are encouraged to use the 18 achieving the highest level of rigor and their validated translations. In contrast, the development of questionnaires for anal incontinence and pelvic/vaginal problems is in its infancy and further study in this area is needed. Randomized trials of treatments for incontinence should use only questionnaires achieving the highest level of scientific rigor.

Fecal Incontinence↗

Blood lead levels of primary school children in Dhaka, Bangladesh.

Dhaka, Bangladesh, has one of the highest air lead levels in the world. In February 2000, we evaluated children at five primary schools in Dhaka to determine blood lead (BPb) levels, sources of environmental exposure, and potential risk factors for lead poisoning. Selected schools represented a range of geographic and socioeconomic strata. A total of 779 students 4-12 years of age participated. The mean BPb level was 15.0 microg/dL (range 4.2-63.1 microg/dL). Most students (87.4%) had BPb levels above the Centers for Disease Control and Prevention's level of concern (10 microg/dL). Elevated BPb levels correlated with soil eating [odds ratio (OR) = 3.31; 95% confidence interval (CI), 1.30-8.39], low parental education (OR = 2.72; 95% CI, 1.97-3.75), living close to major roads (OR = 2.30; 95% CI, 1.23-4.29), and increasing age (OR = 1.11; 95% CI, 1.06-1.16). BPb levels measured were similar to those in other countries that use leaded gasoline. No other potential sources of lead exposure were consistently identified. Combustion of leaded gasoline is the main source of lead exposure in Dhaka, resulting in ubiquitous contamination of the environment. The increase in BPb levels with age, a finding contrary to observations in the United States and Australia, may be related to increased outdoor activities. The Bangladeshi government recently announced a plan to eliminate leaded gasoline. Baseline BPb surveys are critical to develop and evaluate intervention policies. Strategies to reduce BPb levels need to address variations in socioeconomic status, construction type and location of housing, and levels of hygiene.

Air Pollution↗

Scatter factor-hepatocyte growth factor elevation in the serum of patients with prostate cancer.

PURPOSE: Scatter factor (SF), also known as hepatocyte growth factor (HGF), has been shown to induce proliferation, scattering and invasiveness in human prostate cancer cell lines. In this study we determined the serum level of SF-HGF in men with metastatic prostate cancer compared to those with localized prostate cancer and without prostate cancer. MATERIALS AND METHODS: Serum samples were obtained from men with biopsy proved adenocarcinoma of the prostate and radiographic evidence of metastatic disease, those with biopsy proved adenocarcinoma of the prostate and clinically localized disease, and those with negative sextant prostate biopsies. Serum SF-HGF was determined using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Of the 108 men enrolled in our study 52 had negative sextant biopsies, 36 had clinically localized cancer and 20 had metastatic disease. The serum level in men with metastatic disease was significantly elevated (mean 2,117 pg./ml., range 820 to 6,403) compared to that in men with localized cancer and without prostate cancer (mean 974 pg./ml., range 437 to 2,132 and 700, range 272 to 1,875, respectively, p = 9.5 x 10(-15)). Logistic regression analysis demonstrated that the association of ln (SF-HGF) with prostate cancer persisted after controlling for patient age and ln (prostate specific antigen) (p = 3.1 x 10(-4)). CONCLUSIONS: Serum SF-HGF is increased in men with metastatic prostate cancer. SF-HGF levels are associated with metastatic prostate cancer independent of the prostate specific antigen level and patient age. These data imply that SF-HGF may be an important serum marker for prostate cancer.

Adenocarcinoma↗

Characterization of D-fenfluramine-induced hypothermia: evidence for multiple sites of action.

The effects of D-fenfluramine on core body temperature has been largely investigated under conditions of either high or low ambient temperature, whereas little research has focused on this response under normal environmental conditions. Moreover, there has been neglect in research on the mechanisms underlying changes in body temperature. In this study, we demonstrate that D-fenfluramine (5 and 10 mg/kg) induces a sustained decrease in body temperature in the rat under normal ambient temperatures. Pre-treatment with the selective serotonin reuptake inhibitor sertraline (5 mg/kg), the full 5-HT(1A) receptor antagonist 4-fluoro-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-2-pyridinyl benzamide], WAY 100635 (0.15 mg/kg) and the 5-HT(2C) receptor antagonist benzofuran-2-carboxamidine, RO 43-0440 (2.5 mg/kg) blocked D-fenfluramine-induced hypothermia. Depletion of 5-hydroxytryptamine (5-HT) stores following treatment with the serotonergic neurotoxin parachlorophenylalanine reversed the initial hypothermic effects of D-fenfluramine but not the later effects, as D120 min post-challenge) in animals pre-treated with parachlorophenylalanine. Such findings are consistent with a requirement for D-fenfluramine uptake into 5-HT neurons followed by release of 5-HT from intracellular stores and stimulation of post-synaptic 5-HT receptors to reduce body temperature. The hypothermic response to D-fenfluramine was potentiated by ketanserin pre-treatment 30 min post-challenge but then antagonized at later time intervals. Pre-treatment with the dopamine, D(2) antagonist, haloperidol (1 mg/kg) and sulpiride (30 mg/kg) had a similar effect in blocking the hypothermia as WAY 100635, suggesting a role for dopamine D(2) receptors in the response. Pre-treatment with the alpha(2)-adrenoceptor antagonist yohimbine failed to block the hypothermic response. These results suggest multiple sites of action mediating D-fenfluramine-induced hypothermia and may be the result of a combined effect of D-fenfluramine and its active metabolite norfenfluramine affecting not only the release of 5-HT but also stimulation of post-synaptic receptors.

Adrenergic alpha-Antagonists↗

Tularemia--an unusual cause of a solitary pulmonary nodule in the post-transplant setting.

We report a case of tularemia presenting as a solitary pulmonary nodule following syngeneic PBSC transplant. Seven months after undergoing a syngeneic PBSC transplant for AML, our patient presented with fever without localizing signs. Chest X-ray revealed a solitary pulmonary nodule. Culture of a CT guided needle aspiration revealed Francisella tularensis. The patient was successfully treated with ciprofloxacin. His fever resolved and clearance of the nodule was documented on a CT scan 2 months after diagnosis and initiation of treatment. To our knowledge, this is the only reported case of tularemia occurring in the post-transplant setting. The possible relationship between transplant-induced immune dysfunction and the occurrence of this rare infection is discussed.

Anti-Infective Agents↗

Trust amalgamation. A partnership challenge.

Structure and role clarity should be an early priority A rigorous and fair appointments process is required Short term performance will be affected Communicate all the time The 'must be dones' still have to be done The trust has not reached its first birthday

Communication↗

Acute liver failure caused by isoniazid in a child receiving carbamazepine.

We report a case of a 10-year-old boy, being treated for seizures with carbamazepine, who developed acute liver failure within four days of initiation of therapy for suspected tuberculosis with isoniazid, rifampin, pyrazinamide, and ethambutol. Isoniazid-induced liver disease was diagnosed. The likely role of carbamazepine and rifampin in potentiating the hepatotoxicity of isoniazid, and the importance of early recognition of isoniazid-induced liver disease, are discussed.

Anticonvulsants↗

Assessing health-related quality of life in HIV disease: key measurement issues.

The reliable and valid assessment of health-related quality of life (HRQoL) in human immunodeficiency virus (HIV) clinical research presents both familiar and unique challenges. Consistent with HRQoL research in general, measures of HRQoL in HIV disease must meet a set of standard psychometric properties, produce interpretable results, and be responsive to relatively small treatment effects. Furthermore, as clinical research for a range of diseases and conditions becomes increasingly global, HRQoL investigators are confronted with the formidable task of developing measures that are applicable across a range of cultures and languages within and across national boundaries. In this paper, we present a model of HRQoL to be applied across disease and conditions, with a discussion of the key measurement issues. We then briefly consider the natural history and treatment aspects of HIV that are relevant to HRQoL research. In the final sections of the paper, we describe the elements needed in an 'ideal' HRQoL/HIV instrument and propose a method for evaluating the degree to which current HRQoL measures address the challenges posed by HIV clinical research.

Culture↗

IFN-gamma up-regulates expression of the complement components C3 and C4 by stabilization of mRNA.

We investigated the mechanisms underlying the regulation of complement genes C3 and C4 by IFN-gamma. IFN-gamma (500 U/ml, 24 h incubation) increased steady state mRNA levels for both C3 and C4 in three different cell types (Hep G2, U937, and primary fibroblasts). The response to IFN-gamma in Hep G2 cells was time and dose dependent. At all doses of IFN-gamma and at all incubation times, the transcription rate for these two genes, determined by nuclear run-on assays, was reduced (0.3 +/- 0.1; unstimulated rate = 1.00). The t1/2 of mRNA for C3 and C4 in unstimulated cells was 1.8 +/- 0.3 and 2.2 +/- 0.2 h, respectively. After high-dose IFN-gamma stimulation, both C3 and C4 mRNA levels remained at 100% with respect to baseline at 5 h, but after 12 h, levels fell to 13 +/- 2% (C3) and 8 +/- 3% (C4) of baseline values, giving a half-life for these mRNA species of between 5 and 12 h. IFN-gamma stimulation increased C3 and C4 protein synthesis measured at 24 h. We suggest that it is the increase in mRNA stability that is the major effector mechanism by which IFN-gamma regulates C3 and C4 gene expression.

Cell Line↗

Assessment of personality functioning in the transition from adolescent to adult life: preliminary findings.

BACKGROUND: The Adolescent to Adult Personality Functioning Assessment (ADAPFA) a modification of the Adult Personality Functioning Assessment (APFA) is described. It may be used to assess specific and general social dysfunction in the transition from childhood to adult life. METHOD: Two raters independently rated 38 audiotaped interviews to test the interrater reliability of the instrument. The relationship between dysfunction in specific domains and overall psychosocial dysfunction was examined. RESULTS: Interrater reliabilities for the total ADAPFA score and for the majority of the domains were high. Agreement on type of dysfunction and on categorical ratings indicating the presence of personality disorder were good. CONCLUSION: The ADAPFA is a useful measure of interpersonal and social role performance in the transition between adolescent and adult life.

Adolescent↗

Is the construction of an ileoanal pouch associated with the development of arthritis?

The construction of an ileoanal pouch in patients who have undergone total colectomy for ulcerative colitis is claimed to be associated with the development of arthritis. The pattern and prevalence of reported musculoskeletal symptoms in the 15 patients with ileoanal pouches attending our hospital was not significantly different to a control group of 60 patients with an ileostomy for inflammatory bowel disease. There was no clinical or serological evidence of arthritis in the eight patients from the study group reporting symptoms. We conclude that the majority of symptoms occurring following pouch construction are not attributable to an inflammatory arthropathy.

Adolescent↗

Idiopathic recurrent non-suppurative focal myositis: a report of two cases.

We describe two patients with acute recurrent focal myositis affecting discrete muscle groups. Sepsis was initially suspected in both cases and excluded only after surgical intervention. Spontaneous remissions occurred and extensive investigations have not demonstrated a precipitating cause.

Acute Disease↗

Role of hyperventilation in the pathogenesis of central sleep apneas in patients with congestive heart failure.

Periodic breathing with central apneas during sleep is typically triggered by hypocapnia resulting from hyperventilation. We therefore hypothesized that hypocapnia would be an important determinant of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with congestive heart failure (CHF). To test this hypothesis, 24 male patients with CHF underwent overnight polysomnography during which transcutaneous PCO2 (PtcCO2) was measured. Lung to ear circulation time (LECT), derived from an ear oximeter as an estimate of circulatory delay, and CSR-CSA cycle length were determined. Patients were divided into a CSR-CSA group (n = 12, mean +/- SEM of 49.2 +/- 6.3 central apneas and hypopneas per h sleep) and a control group without CSR-CSA (n = 12, 4.9 +/- 0.8 central apneas and hypopneas per h sleep). There were no significant differences in left ventricular ejection fraction, awake PaO2, mean nocturnal SaO2, or LECT between the two groups. In contrast, the awake PaCO2 and mean sleep PtcCO2 were significantly lower in the CSR-CSA group than in the control group (33.0 +/- 1.2 versus 37.5 +/- 1.0 mm Hg, p < 0.01, and 33.2 +/- 1.2 versus 42.5 +/- 1.2 mm Hg, p < 0.0001, respectively). Neither group had significant awake or sleep-related hypoxemia. In addition, CSR-CSA cycle length correlated with LECT (r = 0.939, p < 0.001). We conclude that (1) hypocapnia is an important determinant of CSR-CSA in CHF and (2) circulatory delay plays an important role in determining CSR-CSA cycle length.

Adult↗