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Biomedical subjects

M King

Publications and source records attributed to M King.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effects of methacholine and uridine 5'-triphosphate on tracheal mucus rheology in mice.

We compared the action of methacholine (MCh) and uridine 5'-triphosphate (UTP) with and without pretreatment with the chloride channel blocker 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) on the transepithelial potential difference (PD), the mucus collection rate (MCR), and tracheal mucus rheology using anesthetized C57BL/6 mice. The cystic fibrosis transmembrane conductance regulator (CFTR) blocker 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) was also used as a pretreatment for MCh. After collecting baseline mucus for 1.5 h, mucus secretion was stimulated by instilling 5 microl of 10(-2) M MCh or UTP around the upper trachea. There was a significant increase in PD after MCh or UTP stimulation (-21.3+/-2.0 mV MCh versus -14.1+/-1.6 mV control; -25.4+/-2.5 mV UTP versus -19.2+/-1.9 mV control). When UTP administration was preceded by DIDS, PD shifted from -15.2+/-2.9 to -12.0+/-2.2 mV. When MCh was preceded by DIDS or by NPPB, there was no change in PD. There was a significant decrease in mucus rigidity index, logG*, with MCh (2.54+/-0.09 versus 2.99+/-0.14 for control), similar to that previously reported in other species. With UTP, 14 of 16 mice responded in terms of PD becoming more negative, and of these, there was a significant difference in logG* after UTP administration (2.29 +/-0.10 versus 2.57+/-0.10 for control), whereas there was no change in logG* with DIDS administration before UTP. When DIDS administration preceded MCh, there was a diminished but still significant decrease in logG* from control, whereas there was no change in logG* when NPPB was preadministered. The control mucus collection rate was 0.19+/-0.09 mg/h, whereas after MCh stimulation, it increased to 2.83+/-0.78 mg/h. No significant difference was measured in the MCR after either UTP or DIDS+UTP stimulation. DIDS+MCh and NPPB+MCh both resulted in significant increases in MCR, but of a much smaller magnitude than that for MCh alone. We conclude that hypersecretion owing to UTP in C57BL/6 mice is less vigorous than with MCh, reflecting the limited population of Ca(2+)-dependent Cl(-) channels stimulated by UTP P(2) receptors. The action of MCh on tracheal mucus secretion in mice appears to involve both CFTR- and non-CFTR-dependent chloride channels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Prospective controlled study of psychiatric out-patient non-attendance. Characteristics and outcome.

BACKGROUND: Psychiatric clinics have high non-attendance rates and failure to attend may be a sign of deteriorating mental health. AIMS: To investigate why psychiatric out-patients fail to attend, and the outcome of attenders and non-attenders. METHOD: Prospective cohort study of randomly selected attenders and non-attenders at general adult psychiatric out-patient clinics. Subjects were interviewed at recruitment and severity of mental disorder and degree of social adjustment were measured. Six and 12 months later their engagement with the clinic and any psychiatric admissions were ascertained. RESULTS: Of the 365 patients included in the study, 30 were untraceable and 224 consented to participate. Follow-up patients were more psychiatrically unwell than new patients. For follow-up patients, non-attenders had lower social functioning and more severe mental disorder than those who attended. At 12-month follow-up patients who missed their appointment were more likely to have been admitted than those who attended. CONCLUSIONS: Those who miss psychiatric follow-up out-patient appointments are more unwell and more poorly socially functioning than those who attend. They have a greater chance of drop-out from clinic contact and subsequent admission.

Adolescent↗
PubMed2000

Patient-held shared care records for individuals with mental illness. Randomised controlled evaluation.

BACKGROUND: Few formalized shared care schemes exist within psychiatry and the evidence base for sharing psychiatric care is weak. AIMS: To evaluate the utility of patient-held shared care records for individuals with long-term mental illness. METHOD: Cluster-randomised controlled parallel-group 12-month trial involving 90 patients with long-term mental illness drawn from 28 general practices. RESULTS: Carrying a shared care record had no significant effect on mental state or satisfaction with psychiatric services. Compared with controls, patients in the shared care group were no more likely to be admitted (relative risk 1.2, 95% CI 0.86-1.67) and attend clinic (relative risk 0.96, 95% CI 0.67-1.36) over the study period. Uptake of the shared care scheme was low by patients and professionals alike. Subjects with psychotic illness were significantly less likely to use their records (relative risk 0.51, 95% CI 0.27-0.99). CONCLUSIONS: Patient-held records may not be helpful for patients with long-term mental illness.

Adolescent↗
PubMed2000

Tracheobronchial mucus viscoelasticity during environmental challenge in horses with recurrent airway obstruction.

The goal of this study was to compare the rheological properties of mucus from horses with recurrent airway obstruction (RAO) to that from healthy controls during environmental challenge by stabling in stalls with straw as bedding and hay as feed. We determined viscoelasticity (log G* dyn/cm2, at 10 radian/s) and calculated mucociliary clearability index (MCI) and cough clearability index (CCI), which are derivative parameters of G* and the ratio of viscosity and elasticity measured at 1 and 100 radian/s, respectively. We also investigated the solids content of mucus, and cytology of bronchoalveolar lavage fluid (BALF). Samples were obtained before (0 h) and 6, 24 and 48 h after environmental challenge. The central findings were rheological changes in airway mucus, which occurred over time in RAO-affected animals, but not in controls. Mucus rheology was similar in both groups at 0 and 6 h. In RAO-affected horses, mucus viscoelasticity, as measured by log G*, increased from 2.49 +/- 0.18 dyn/cm2 (mean +/- s.e.) at 0 h to 3.05 +/- 0.13 dyn/cm2 at 24 h after environmental challenge, and was accompanied by significant decreases in MCI and CCI. Percent solids of mucus did not differ significantly between the 2 groups, nor over time. Rheological values did not correlate with BALF cytology. We conclude that viscoelastic properties of tracheal mucus samples from RAO horses in remission do not differ from those of normal horses. However, environmental challenge causes clinical signs of small airway disease and a concurrent increase in mucus viscoelasticity only in RAO horses. Therefore, we infer that unfavourable changes in mucus rheology may contribute to stasis and accumulation of mucus in RAO horses in exacerbation, but not in clinical remission.

Airway Obstruction↗
PubMed2000

The influence of temperature and length of time of storage of frog mucus samples.

Frozen, stored mucus has been extensively used for transport studies but there is no clear evidence of the influence that the temperature and length of time of storage may have on the results. We stored frog mucus samples at -20 and -80 degrees C and analysed them on days zero, 2, 10, 30 and 90. At each temperature, a sample was thawed, studied and refrozen on each of the study days, at the same time that one sample was thawed only on the study day. Displacement in a simulated cough machine and on the frog palate, as well as contact angle measurements, were determined for the mucus samples on each study day. Mucus cytologic analyses on each of the study days were done with special regard to neutrophil counts and cell integrity. Friedman analysis of variance did not show any difference between the different periods of storage and the two temperatures for any of the parameters studied. The medians for the relative transport velocity on the frog palate varied between 0.88 and 1.03, for the contact angle between 21 and 28 degrees, and for the displacement in the simulated cough machine between 58 and 95 mm over the 90 days of the experiment. There were no cytologic alterations compatible with cell degeneration. We conclude that the storage of frog mucus either at -20 or -80 degrees C for periods up to 90 days does not lead to any significant differences in mucus transportability.

Animals↗
PubMed2000

Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy and usual general practitioner care in the management of depression as well as mixed anxiety and depression in primary care.

OBJECTIVES: The aim of this study was to determine both the clinical and cost-effectiveness of usual general practitioner (GP) care compared with two types of brief psychological therapy (non-directive counselling and cognitive-behaviour therapy) in the management of depression as well as mixed anxiety and depression in the primary care setting. DESIGN: The design was principally a pragmatic randomised controlled trial, but was accompanied by two additional allocation methods allowing patient preference: the option of a specific choice of treatment (preference allocation) and the option to be randomised between the psychological therapies only. Of the 464 patients allocated to the three treatments, 197 were randomised between the three treatments, 137 chose a specific treatment, and 130 were randomised between the psychological therapies only. The patients underwent follow-up assessments at 4 and 12 months. SETTING: The study was conducted in 24 general practices in Greater Manchester and London. SUBJECTS: A total of 464 eligible patients, aged 18 years and over, were referred by 73 GPs and allocated to one of the psychological therapies or usual GP care for depressive symptoms. INTERVENTIONS: The interventions consisted of brief psychological therapy (12 sessions maximum) or usual GP care. Non-directive counselling was provided by counsellors who were qualified for accreditation by the British Association for Counselling. Cognitive-behaviour therapy was provided by clinical psychologists who were qualified for accreditation by the British Association for Behavioural and Cognitive Psychotherapies. Usual GP care included discussions with patients and the prescription of medication, but GPs were asked to refrain from referring patients for psychological intervention for at least 4 months. Most therapy sessions took place on a weekly basis in the general practices. By the 12-month follow-up, GP care in some cases did include referral to mental healthcare specialists. MAIN OUTCOME MEASURES: The clinical outcomes included depressive symptoms, general psychiatric symptoms, social function and patient satisfaction. The economic outcomes included direct and indirect costs and quality of life. Assessments were carried out at baseline during face-to-face interviews as well as at 4 and 12 months in person or by post. RESULTS: At 4 months, both psychological therapies had reduced depressive symptoms to a significantly greater extent than usual GP care. Patients in the psychological therapy groups exhibited mean scores on the Beck Depression Inventory that were 4-5 points lower than the mean score of patients in the usual GP care group, a difference that was also clinically significant. These differences did not generalize to other measures of outcome. There was no significant difference in outcome between the two psychological therapies when they were compared directly using all 260 patients randomised to a psychological therapy by either randomised allocation method. At 12 months, the patients in all three groups had improved to the same extent. The lack of a significant difference between the treatment groups at this point resulted from greater improvement of the patients in the GP care group between the 4- and 12-month follow-ups. At 4 months, patients in both psychological therapy groups were more satisfied with their treatment than those in the usual GP care group. However, by 12 months, patients who had received non-directive counselling were more satisfied than those in either of the other two groups. There were few differences in the baseline characteristics of patients who were randomised or expressed a treatment preference, and no differences in outcome between these patients. Similar outcomes were found for patients who chose either psychological therapy. Again, there were no significant differences between the two groups at 4 or 12 months. Patients who chose counselling were more satisfied with treatment than those who chose c

Adult↗
PubMed1999

Safe motherhood.

Explore the source record for details and available documents.

Family Planning Services↗
PubMed1999

Antagonism of heroin and morphine self-administration in rats by the morphine-6beta-glucuronide antagonist 3-O-methylnaltrexone.

In mice, 3-O-methylnaltrexone blocks the analgesic actions of morphine-6beta-glucuronide and heroin at doses which are inactive against morphine. We found a similar selectivity in rats. 3-O-Methylnaltrexone antagonized the analgesic actions of 6-acetylmorphine in Sprague-Dawley rats and heroin in Wistar rats at doses that were inactive against morphine. Inclusion of a fixed dose of 3-O-methylnaltrexone significantly shifted the analgesic dose-response curves for 6-acetylmorphine and heroin without altering the morphine dose-response curves. In a self-administration model, 3-O-methylnaltrexone treatment significantly increased both heroin and morphine intake during the first hour, suggestive of an antagonist effect. This effect at doses of 3-O-methylnaltrexone which were inactive against morphine analgesia implied a role for the morphine-6beta-glucuronide opioid receptor in the reinforcing properties of heroin and morphine.

Animals↗
PubMed1999

Lifetime prevalence, characteristics, and associated problems of non-consensual sex in men: cross sectional survey.

OBJECTIVE: To identify the lifetime prevalence of non-consensual sexual experiences in men, the relationship between such experiences as a child and as an adult, associated psychological and behavioural problems, and help received. DESIGN: Cross sectional survey. SETTING: England. SUBJECTS: 2474 men (mean age 46 years) attending one of 18 general practices. MAIN OUTCOME MEASURES: Experiences of non-consensual and consensual sex before and after the age of 16 years-that is, as a child and adult respectively-psychological problems experienced for more than 2 weeks at any one time, use of alcohol (CAGE questionnaire), self harm, and help received. RESULTS: 2474 of 3142 men (79%) agreed to participate; 71/2468 (standardised rate 2.89%, 95% confidence interval 2.21% to 3.56%) reported non-consensual sexual experiences as adults, 128/2423 (5.35%, 4.39% to 6.31%) reported non-consensual sexual experiences as children, and 185/2406 (7.66%, 6.54% to 8.77%) reported consensual sexual experiences as children that are illegal under English law. Independent predictors of non-consensual sex as adults were reporting male sexual partners (odds ratio 6.0, 2.6 to 13.5), non-consensual sex in childhood (4.2, 2.1 to 8.6), age (0.98, 0.96 to 0.99), and sex of interviewer (2.0, 1.2 to 3.5). Non-consensual sexual experiences were associated with a greater prevalence of psychological problems, alcohol misuse, and self harm. These sexual experiences were also significant predictors of help received from mental health professionals. CONCLUSION: Almost 3% of men in England report non-consensual sexual experiences as adults. Medical professionals need to be aware of the range of psychological difficulties in men who have had such experiences. They also need to be aware of the relationship between sexual experiences in childhood and adulthood in men.

Adolescent↗
PubMed1999

A conserved motif in the yeast nucleolar protein Nop2p contains an essential cysteine residue.

Nop2p is an essential nucleolar protein in Saccharomyces cerevisiae that is involved in large ribosomal subunit assembly. It has substantial homology with human p120, the proliferation-associated nucleolar antigen that is overexpressed in many human cancers. A motif containing an invariant Pro-Cys dipeptide is found in Nop2p, p120 and the bacterial Fmu proteins. A total of nine conserved residues, including Pro423 and Cys424, were individually altered in Nop2p by site-directed mutagenesis. Nop2p function was abolished by conversion of Cys424 into either alanine or serine. All of the other Nop2p mutations tested sustained yeast viability, including glycine replacement of Pro423 and the conversion of a second conserved cysteine into alanine. The crucial role of Cys424 in Nop2p is intriguing, due to the critical roles that cysteine residues adjacent to a proline have in a number of nucleotide-modifying enzymes.

Amino Acid Sequence↗