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Biomedical subjects

M King

Publications and source records attributed to M King.

At least 37 records · Page 2Linked to original sources

Differential actions and excitotoxicity of glutamate agonists on motoneurons in adult mouse cervical spinal cord slices.

Electrical activity was recorded from motoneurons in adult mouse cervical spinal cord (C4-8) slices. Motoneurons showed almost no response to ionophoretic application of N-methyl-D-aspartic acid (NMDA) in both control and Mg(2+)-free media, but very sensitive to kainate (KA) and amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). Bath perfusion of KA, AMPA or glucose/O(2) free Krebs-Ringer solution, but not bath perfusion of NMDA, caused membrane depolarization within 3 min and beading of the dendrite trees after more than 10 min perfusion. Our results indicate that adult motoneurons have few or no NMDA receptors.

Animals↗

Growth effects of systemic versus inhaled steroids in chronic lung disease.

AIM: To compare the effects of inhaled and systemic steroids on growth in very low birthweight (VLBW) infants with chronic lung disease (CLD). METHODS: Sixteen babies with CLD randomly received inhaled budesonide (100 microg four times daily for 10 days via Aerochamber) or systemic steroids (dexamethasone 0.5 mg/kg/day, reducing over nine days). Linear growth (lower leg length, LLL) was measured by knemometry twice weekly. RESULTS: The gestational age, birth weight, postnatal age, and LLL velocity (LLLvel) were similar between the two groups at the start of treatment. At the end of the treatment period, LLLvel was reduced in the dexamethasone group (mean -0.01 mm/day) but had increased in the budesonide group (mean 0.48 mm/day). Mean weight gain was non-significantly lower in the dexamethasone group (5.8 g/kg/day) compared to the budesonide group (mean 12.7 g/kg/day). CONCLUSION: Inhaled budesonide has less short term effects on growth than systemically administered dexamethasone.

Administration, Inhalation↗

Dose-finding and 24-h monitoring for efficacy and safety of aerosolized Nacystelyn in cystic fibrosis.

The aim of the present studies was to investigate the tolerability and activity of a novel mucolytic drug, Nacystelyn (NAL), for the treatment of cystic fibrosis (CF) lung disease. In study 1, involving 10 CF patients, the main objective was to determine the tolerability and potential efficacy of a range of single doses of NAL in comparison to a placebo, in order to establish an optimal dose for further testing. On five consecutive scheduled treatment days, patients inhaled either from two (4 mg) to eight puffs (16 mg) of a single dose of NAL from the range, administered in an open-label fashion, or 12 puffs of active NAL (24 mg) versus 12 puffs of placebo, administered in a randomized double-blind fashion. Pulmonary function data were unaffected and clinically-adverse effects were limited to wheezing in some patients that inhaled 12 puffs of either placebo or active drug. Subsequent rheological analysis of their sputum showed a dose-dependent decrease in sputum viscoelasticity, accompanied by a decrease in sputum solids content and an increase in chloride and sodium concentrations. In study 2, involving 12 CF patients, the clinical safety and mucolytic activity of a single dose of NAL was monitored over 24 h. On different scheduled treatment days, 7 days apart, patients inhaled a single dose of 12 puffs of active NAL (24 mg) or 12 puffs of placebo drug in a randomized, double-blind sequence, with sputum samples taken at intervals before and after inhalation. Mucus rigidity decreased following NAL inhalation, with the maximum effect observed at 4 h; the 1-, 2- and 4-h NAL rheology results were significantly different from placebo. No adverse effects were observed. The drug was well tolerated in both studies. Sputum results were predictive of improved clearability by ciliary and cough transport mechanisms.

Acetylcysteine↗

Practical method for evaluation of linearity and effective pathlength of on-capillary photometric detectors in capillary electrophoresis.

The optical characteristics of on-capillary photometric detectors for capillary electrophoresis were evaluated and five commercial detectors were compared. Plots of sensitivity (absorbance/concentration) versus absorbance obtained with a suitable testing solution yield both the linear range and the effective path length of the detector. The detector linearity is a crucial parameter when using absorbing electrolytes, such as for indirect photometric detection, and especially for highly absorbing electrolyte probe ions. The upper limits of the linear ranges (determined as 5% decline in sensitivity) for five commercial detectors ranged from 0.175 to 1.2 AU. The effective pathlength reflects the quality of the optical design of the detector and is equal to the capillary internal diameter only for a light beam passing exactly through the capillary centre, but becomes progressively shorter for imperfect optical designs. The determined effective pathlength for the five investigated detectors ranged from 49.7 to 64.6 microm for a 75 microm I.D. capillary.

Electrophoresis, Capillary↗

ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48-week results.

OBJECTIVE: To evaluate the safety and antiviral activity of different dose levels of the HIV protease inhibitor ABT-378 combined with low-dose ritonavir, plus stavudine and lamivudine in antiretroviral-naive individuals. DESIGN: Prospective, randomized, double-blind, multicenter. METHODS: Eligible patients with plasma HIV-1 RNA > 5000 copies/ml received ABT-378 200 or 400 mg with ritonavir 100 mg every 12 h; after 3 weeks stavudine 40 mg and lamivudine 150 mg every 12 h were added (group I, n = 32). A second group initiated treatment with ABT-378 400 mg and ritonavir 100 or 200 mg plus stavudine and lamivudine every 12 h (group II, n = 68). RESULTS: Mean baseline HIV-1 RNA was 4.9 log10 copies/ml in both groups and CD4 cell count was 398 x 10(6)/l and 310 x 10(6)/l in Groups I and II respectively. In the intent-to-treat (ITT; missing value = failure) analysis at 48 weeks, HIV-1 RNA was < 400 copies/ml for 91% (< 50 copies/ml, 75%) and 82% (< 50 copies/ml, 79%) of patients in groups I and II respectively. Mean steady-state ABT-378 trough concentrations exceeded the wild-type HIV-1 EC50 (effective concentration to inhibit 50%) by 50-100-fold. The most common adverse events were abnormal stools, diarrhea and nausea. No patient discontinued before 48 weeks because of treatment-related toxicity or virologic rebound. CONCLUSIONS: ABT-378 is a potent, well-tolerated protease inhibitor. The activity and durable suppression of HIV-1 observed in this study is probably attributable to the observed tolerability profile and the achievement of high ABT-378 plasma concentrations.

Adult↗

Sexual dysfunction after treatment for testicular cancer: a systematic review.

OBJECTIVES: We aimed to assess the nature and risk of sexual dysfunction in men after treatment for testicular cancer. METHOD: Systematic review of sexual dysfunction in men treated for testicular cancer. The odds ratio or proportions of subjects with reduced sexual drive, erectile dysfunction or orgasmic/ejaculatory dysfunction was calculated. RESULTS: A detailed review of 79 of the 227 citations was conducted. The highest level of evidence found, were controlled studies. Six controlled studies examined sexual function in 709 patients after they had received treatment. Seven uncontrolled studies examined sexual function in 337 subjects before and after treatment for testicular cancer. Most studies were limited by low response rates, use of unvalidated questionnaires and inclusion of a variety of treatment modalities. Few assessed psychological function and none examined its possible interaction with sexual dysfunction. Meta-analysis of the controlled studies indicated significantly reduced or absent orgasm (OR=4.62, 95% CI=2.47-8.63) together with erectile (OR=2.47, 95% CI=1.54-3.96) and ejaculatory dysfunction (OR=28.57, 95% CI=1.75-464.78) up to 2 years after treatment. Effects on sexual function were less consistent in the uncontrolled studies. CONCLUSIONS: The controlled studies indicate that sexual dysfunction persists for up to 2 years after treatment. However, better evidence is needed in studies that control for the impact of the testicular cancer, the treatment modality and psychological reactions to both.

Clinical Trials as Topic↗

A comparison of three measures: the time trade-off technique, global health-related quality of life and the SF-36 in dialysis patients.

We investigated the correlation between descriptive and valuational measures of health-related quality of life (HRQL) and assessed determinants affecting these measures. Our suspicion was that there is little similarity in the content of descriptive and valuational measures of HRQL. We thus conducted a cross-sectional observational study of 56 hemodialysis patients. All underwent structured interviews. Dependent variables were patients utilities [time trade-off (TTO)], global rating of HRQL and generic HRQL (SF-36). Independent variables were socioeconomic details, disease severity, comorbidity, symptoms, depression, social support, and laboratory data. The correlation between TTO and global HRQL was -0.33 (P = .0178) and between TTO and the SF-36 physical and mental summary scores -0.16 (P = .2383) and -0.20 (P = .1443), respectively. The regression models for the SF-36 physical and mental summary scores explained 75% and 64% of the variance, and for global HRQL 29% of the variance. The independent variables had no effect on the TTO. This confirmed our suspicion that a qualitative difference exists between TTO and descriptive quality of life tools. The TTO content could not be explained by the variables that entail the content of HRQL instruments.

Adult↗

The royal free interview for spiritual and religious beliefs: development and validation of a self-report version.

BACKGROUND: Spiritual beliefs are rarely considered in psychological or medical publications. We recently published the psychometric properties of an interview designed to measure religious and spiritual belief. In this study, we aimed to develop this instrument further as a self-report questionnaire and to make it more comprehensive by including measurement of spiritual experiences in addition to faith or intellectual assent. METHODS: Based on extensive discussion with colleagues, advice from users of the interview and comments from respondents, a self-report format was designed. We then evaluated the final format of the questionnaire in terms of (1) patterns of response and demographic predictors of beliefs; (2) test-retest reliability and internal consistency; (3) criterion and internal validity; and (4) the nature of spiritual experiences and their relationship to beliefs and strength of beliefs. RESULTS: Two hundred and ninety-seven people took part in the validity and reliability tests of the questionnaire. Criterion validity, predictive validity, internal consistency and test-retest reliability were acceptably high. The instrument consistently differentiated between people with high and low spiritual beliefs. CONCLUSIONS: This instrument is brief and simple to complete. We would recommend that measures of religious and/or spiritual belief like this be more widely applied in health services research as they evaluate aspects of people's lives that go somewhat further than health status or quality of life.

Adult↗

'Transgressing venues': 'health' studies, cultural studies and the media.

This paper looks at how the strategies of media and cultural studies can be applied to the health studies field. This relationship, however, has been met with resistance due to a number of status debates. We argue the importance of fostering links between these 'disciplines' namely because the definition of what constitutes 'health' has been broadened and is inscribed in most forms of popular media. Using the example of the 'health and lifestyle' debate, we argue that the media informs cultural understandings about requirements for living and is therefore a crucial area of analysis for health studies (and cultural/media studies) students. We are also concerned with analysing how the media contributes to the construction and regulation of 'healthy' subjects making links with public health discourses and current debates in the field of media and health.

Anecdotes as Topic↗

Transport of opioids from the brain to the periphery by P-glycoprotein: peripheral actions of central drugs.

Many peptides and transmitters found within the brain also have peripheral sites of action. We now demonstrate that the brain releases functionally active neurotransmitters/neuromodulators directly from the brain into the blood through a saturable P-glycoprotein (Pgp) transport system. Downregulating Pgp1 expression with antisense reduced the brain-to-blood transport of morphine, beta-endorphin and other opioids. Lowering Pgp expression significantly enhanced systemic morphine analgesia and prevented tolerance, but diminished the analgesic activity of centrally administered morphine, implying that supraspinal analgesia resulted from a combination of central and peripheral mechanisms activated by morphine transported from the brain to the blood. Similarly, mice with a disruption of the Mdr1a gene were more sensitive to systemic morphine and less sensitive to morphine given centrally. This ability of the Pgp transport system to pump functionally active compounds from the brain to periphery defines a potentially important mechanism for the central nervous system to modulate peripheral systems.

ATP Binding Cassette Transporter, Subfamily B↗

The KBG syndrome, characteristic dental findings: a case report.

Short stature and developmental delay may be observed in many genetic conditions and well-defined syndromes. A 7-year-old girl presented with the non-specific findings of subtle dysmorphism, short stature and developmental delay. Although a genetic syndrome was suspected, a definitive diagnosis was not made until the dental findings of KBG syndrome were recognised, namely grossly enlarged maxillary permanent central incisors and hypodontia.

Abnormalities, Multiple↗

Spontaneous regression of metastatic malignant melanoma of the parotid gland and neck lymph nodes: a case report and a review of the literature.

We report the case history of a patient with complete spontaneous regression of metastatic cutaneous melanoma with parotid and neck lymph node metastases. Complete spontaneous regression of metastatic melanoma is very rare, with an estimated incidence of 0.22%-0.27%. We review the literature on this subject. Elucidation of the process of spontaneous regression may offer the possibility of improved methods of treating and preventing cancer.

Adult↗

Evaluating the use of benzodiazepines following recent bereavement.

BACKGROUND: There is no evidence to support current advice not to use benzodiazepines after bereavement. AIMS: To determine the role of benzodiazepines in the management of bereavement. METHOD: We conducted a randomised, double-blind, placebo-controlled evaluation of the use of diazepam after recent bereavement. Participants were randomised to either 2 mg diazepam or identically packaged placebo up to three times daily. The primary outcome measure was the Bereavement Phenomenology Questionnaire. RESULTS: Thirty subjects were randomised. No evidence was found of an effect of benzodiazepines on the course of the first 6 months of bereavement (estimated mean difference of combined follow-up assessments=0.3 in favour of placebo; 95% Cl - 6.2 to +6.7). CONCLUSION: We found no evidence of a positive or negative effect of benzodiazepines on the course of bereavement.

Aged↗

Legal pitfalls of psychiatric research.

BACKGROUND: The increasing complexity of psychiatric research, including recent attempts to evaluate mental health legislation, suggests legal advice may be valuable in a wide range of research contexts. AIMS: We aim to illustrate both the legal pitfalls of research in psychiatry and the potential for solutions if the methods are carefully chosen. METHOD: Two examples of research are subject to legal analysis, one involving advance directives, the other the random discharge of compulsory out-patients. RESULTS: This analysis illustrates that participation in research may expose clinicians to additional forms of liability, but the legal risks can be minimised through changes in the methods or additional safeguards. CONCLUSIONS: Collaboration between academic law and psychiatry can enrich research agendas and avoid serious legal pitfalls. We argue that sound legal advice should be sought at the planning stage of research in psychiatry, but the fear of liability should not lead to overly defensive research practices. The aim should be to strike the right balance between avoiding unacceptable exposure to liability and stifling innovative research.

Advance Directives↗

Straight talking: an investigation of the attitudes and practice of psychoanalysts and psychotherapists in relation to gays and lesbians.

BACKGROUND: Early psychodynamic writing on same-gender sexual preference contributed to its pathologisation and an interest in treatment directed at changing sexual orientation. AIMS: To establish the therapeutic approaches taken by contemporary psychotherapists and psychoanalysts to gay and lesbian clients/patients. METHOD: A random sample of individuals listed as working with adults in the British Confederation of Psychotherapists' register were sent postal questionnaires. RESULTS: Data are available from 274 (69%) of 395 questionnaires. Only one of 218 respondents said that he/she was homosexual. One-third said that gay and lesbian patients did have a right to a gay or lesbian therapist. A total of 179 (82% of 218) respondents described work with gay and lesbian clients/patients, and in the majority of cases sexual orientation was an important aspect of the work. CONCLUSIONS: Gays and lesbians seeking psychoanalysis or psychotherapy in the National Health Service or outside it for personal and/or training purposes will be unlikely to find a gay or lesbian therapist if they want one. The British Confederation of Psychotherapists' practitioners take on gay and lesbian clients/patients, although many do not see these social identities as relevant to the therapeutic process. Evidence from this study indicates that such clients/patients may encounter overt or covert bias, including the pathologisation of homosexuality per se.

Attitude of Health Personnel↗

The diabetes health care of Aboriginal people in South Australia (Part 1).

Although type 2 diabetes is a recognised health priority in South Australia, Aboriginal people with diabetes do not utilise the mainstream diabetes health services on a regular basis for health care. This means that Aboriginal clients have the potential to develop diabetes-related problems and, furthermore, are not in a position to make informed decisions about health care issues. This lack of client empowerment is contrary to the goals of contemporary diabetes health care and, as a result, Aboriginal clients suffer the consequences of ineffective management with a compromised lifestyle. To identify how this situation might be improved, a qualitative study funded by Diabetes Australia was undertaken in South Australia. The overall goal was, firstly, to identify the reasons why Aboriginal people with diabetes do not attend mainstream health agencies on a regular basis and secondly, if possible, to improve attendance. Thus, Aboriginal health professionals (n = 43) were recruited from the 8 statistical divisions of South Australia and interviewed about Aboriginal diabetes health care issues. In Part 1 of this series, the research findings indicated the beliefs and attitudes held by clients about diabetes, their lack of knowledge about management issues, their responses to diabetes, the effects of diabetes on their lifestyle and the strategies that diabetes health professionals used to help their clients deal with diabetes health issues. In Part 2 the research findings indicated the importance of the Aboriginal health worker to the successful diabetes management of Aboriginal clients, the constraints that affect the delivery of diabetes health care and the recommendations made by health professionals to improve the standard of diabetes health services.

Australia↗

The diabetes health care of Aboriginal people in South Australia (Part 2).

Although type 2 diabetes is a recognised health priority in South Australia, Aboriginal people with diabetes do not utilise the mainstream diabetes health services on a regular basis for health care. This means that Aboriginal clients have the potential to develop diabetes-related problems and, furthermore, are not in a position to make informed decisions about health care issues. This lack of client empowerment is contrary to the goals of contemporary diabetes health care and, as a result, Aboriginal clients suffer the consequences of ineffective management with a compromised lifestyle. To identify how this situation might be improved, a qualitative study funded by Diabetes Australia was undertaken in South Australia. The overall goal was, firstly, to identify the reasons why Aboriginal people with diabetes do not attend mainstream health agencies on a regular basis and secondly, if possible, to improve attendance. Thus, Aboriginal health professionals (n = 43) were recruited from the 8 statistical divisions of South Australia and interviewed about Aboriginal diabetes health care issues. In Part 1 of this series, the research findings indicated the beliefs and attitudes held by clients about diabetes, their lack of knowledge about management issues, their responses to diabetes, the effects of diabetes on their lifestyle and the strategies that diabetes health professionals used to help their clients deal with diabetes health issues. In Part 2 the research findings indicated the importance of the Aboriginal health worker to the successful diabetes management of Aboriginal clients, the constraints that affect the delivery of diabetes health care and the recommendations made by health professionals to improve the standard of diabetes health services.

Australia↗