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Biomedical subjects

J Docherty

Publications and source records attributed to J Docherty.

At least 19 recordsLinked to original sources
PubMed1999

Deficiency in myocardial NO biosignalling after cardioplegic arrest: mechanisms and contribution to post-storage mechanical dysfunction.

1 In order to understand mechanisms that limit the safe ischaemic time of donor hearts, this study evaluated NO/cyclic GMP biosignalling in the recovery of function after cardioplegia and hypothermic storage. 2 Hearts removed from anaesthetized rats were either perfused in working mode (Fresh) or arrested (St. Thomas' II cardioplegia) and stored at 3 degrees C for 8 h (CPL) prior to working mode perfusion. LV work and indices of the production of NO (Ca2+-dependent and Ca2+-independent NOS), cyclic GMP (soluble guanylyl cyclase (sGC) and GTP) and superoxide (xanthine oxidase (XO) and xanthine dehydrogenase (XDH)) were measured. 3 Relative to Fresh hearts, CPL hearts were deficient in cyclic GMP and had poor function. Correction of cyclic GMP deficiency (SNP, 200 microM) improved LV work and LV compliance. SNP effects were prevented by inhibition of sGC (ODQ, 3 microM), and potentiated by inhibition of cyclic GMP-dependent phosphodiesterase (zaprinast, 20 microM). SNP (200 microM) had no effect on function of Fresh hearts. 4 NOS activities (pH = 7.2) were similar in CPL and Fresh hearts, but at end-ischaemic pH (6.3), Ca2+-dependent NOS activity was reduced. The sensitivity of sGC to SNP was greater, and activities of XO and XDH were higher, in CPL than in Fresh hearts. 5 The deficiency in NO biosignalling in CPL hearts may arise due to acidosis-induced inhibition of NOS activity, reduced availability of GTP and/or enhanced inactivation of NO by superoxide. These findings provide rationales for novel strategies to prevent the deficiency in NO biosignalling and so improve the function of the transplanted heart.

Adenosine Triphosphate↗
PubMed1998

Spectral analysis of intercycle heart fluctuations in the diethyl-ether-anaesthetized or pithed rat treated with prazosin, dl-propranolol, endothelin-1, alpha-r atriopeptin and ACE-inhibitors.

1. Frequency-domain spectral analysis of stationary ECG R-R intervals was made by fast Fourier transformation (FFT) in conditions of monitored arterial blood pressure and respiratory activity in diethyl-ether-anaesthetized and pithed adult rats. This technique yields a number of parameters which allow quantitative evaluation of the non-random distribution of the mean values obtained in time-domain studies. The frequency-analysis method enables the overall heart rate variability to be broken down into its various constituents, which are differently affected by physiological loading and capable of selective reactivity to pharmacological agents. 2. The low-frequency spectral component obtained by breaking down the total spectral density power, i.e. the appropriate variability signal (band width < 0.15 Hz) and a higher-frequency band corresponding to spontaneous (0.80-1.60 Hz) or artificially imposed (0.75 Hz) respiratory activity were estimated and their integrated areas evaluated as absolute powers or normalized fractional values. 3. The power of the high-frequency spectral component increased in all animal preparations under treatment with prazosin, dl-propranolol, endothelin-1 and the angiotensin converting enzyme (ACE) inhibitors captopril, lisinopril, quinapril and ramipril. The power of the low-frequency band increased under alpha-r atriopeptin and ACE inhibitors in the pithed preparations only, and decreased in the anaesthetized animals. 4. The new power spectrum features and trends detected indicate that these time-independent, model-dependent cardiovascular and respiratory markers are subject to some form of complex peptidergic control. 5. The relative roles of the various factors operating in the genesis of these short-term changes in spectral power in the low- and high-frequency bands cannot be interpreted as indicating a reciprocal push-pull relationship between sympathetic and parasympathetic control. 6. The study findings, however, can be interpreted as providing evidence of a different and to some extent alternative form of integrative cardiovascular control persisting in the pithed rats (i.e. in the 'peripheral', CNS-destroyed preparations). 7. New areas of theoretical and applied research are being developed in the (auto)classification of (iso)receptors and drug analogues through exploration of multiple physiological and pharmacokinetic parameters in the frequency-domain. Furthermore, model-independent frequency-domain methods not requiring stationary data will afford scope for even more significant developments by separating the overlapping dynamic processes from a whole series of correlated effects.

Animals↗
PubMed1998

A new method of developing expert consensus practice guidelines.

To improve the quality of medical care while reducing costs, it is necessary to standardize best practice habits at the most crucial clinical decision points. Because many pertinent questions encountered in everyday practice are not well answered by the available research, expert consensus is a valuable bridge between clinical research and clinical practice. Previous methods of developing expert consensus have been limited by their relative lack of quantification, specificity, representativeness, and implementation. This article describes a new method of developing, documenting, and disseminating expert consensus guidelines that meets these concerns. This method has already been applied to four disorders in psychiatry and could be equally useful for other medical conditions. Leading clinical researchers studying a given disorder complete a survey soliciting their opinions on its most important disease management questions that are not covered well by definitive research. The survey response rates among the experts for the four different psychiatric disorders have each exceeded 85%. The views of the clinical researchers are validated by surveying separately a large group of practicing clinicians to ensure that the guideline recommendations are widely generalizable. All of the suggestions made in the guideline are derived from, and referenced to, the experts' survey responses using criteria that were established a priori for defining first-, second-, and third-line choices. Analysis of survey results suggests that this method of quantifying expert responses achieves a high level of reliability and reproducibility. This survey method is probably the best available means for standardizing practice for decisions points not well covered by research.

Bias↗
PubMed1997

Spectral analysis of intercycle heart fluctuations in Xenopus laevis, conscious or spinalized, treated with calcium channel blockers. Part I.

1. In this study, electrocardiographic second lead tracings were recorded and analyzed online and offline in the conscious and spinalized Xenopus laevis under control conditions and after treatment with at least two effective doses of racemic diltiazem, nifedipine and racemic verapamil hydrochlorides. 2. Heart rates (HR) and intercycle heart rate power spectra (IHRPS) were calculated in the various experimental conditions. 3. Dose-dependent bradycardia was found in most cases, which was associated with dose-related increases in the overall dynamic range of the largest peak of HR variability (increased IHRPS), this being particularly marked at the higher nifedipine dose. The frequency position of the largest peak was unchanged in the spinalized preparation, as well as in the various treatments. 4. These findings may contribute toward a more complete pharmacodynamic definition of calcium channel blockers in their current therapeutic use.

Animals↗
PubMed1997

Spectral analysis of intercycle heart fluctuations in the diethyl-ether-anaesthetized or pithed rat treated with l-hyoscyamine.

1. Within the context of neural regulation of the activity of sinus node pacemaker cells, the study of heart rate variability, as explored in the frequency domain by spectral analysis, was proposed about 15 years ago as a quantitative tool for the evaluation of short-term autonomic cardiovascular control. It has since been postulated that the two main oscillations observed, one at low and the other at high frequency, may respectively be markers of sympathetic vs. vagal efferent cardiac activity, and that the low- and high-frequency signals may reflect a reciprocal or 'push-pull' relationship between sympathetic and parasympathetic control. 2. In our power spectra assessment, ECG R-R intervals were submitted to fast Fourier transformation analysis in order to study the mechanisms underlying the control of heart beats in rats. Data were acquired in conditions of steady arterial blood pressure and cardiac and respiratory activity (spontaneous or artificially stimulated) in diethyl-ether-anaesthetized and pithed rats, as well as in a group of control rats, all in the presence and absence of l-hyoscyamine. 3. With increasing doses of the parasympathetic antagonist, the fractal dimension of the time-series structure remained stable in most cases. The low-frequency spectral component narrowed with increasing drug doses and the high-frequency band underwent either no, or only very slight, changes. 4. In these rodent assays, the low- and high-frequency signals cannot be interpreted as a push-pull relationship between sympathetic and parasympathetic control.

Anesthetics, Inhalation↗
PubMed1993

The case for a services-based approach to payment for mental illness under national health care reform.

In this position paper drafted by the committee on psychopathology of the Group for the Advancement of Psychiatry, the authors discuss merits and disadvantages of three different approaches to equitable coverage of mental illness: coverage for selected psychiatric diagnoses, coverage based on severity of impairment, and coverage of services. They believe that coverage of selected disorders has political appeal but is discriminatory and arbitrary; it is also impractical because clinicians may overdiagnose conditions covered by insurance and underdiagnose excluded conditions. Coverage based on severity of impairment, or disability, has similar limitations. The authors believe services should be the principal basis for coverage, as under general medical insurance. The approach is nondiscriminatory, and costs can be controlled through such means as managed care, changes in the payment system, or benefit design.

Community Mental Health Services↗
PubMed1992

Total quality management within the NHS.

Total quality management is a system which enables managers to analyse and develop their services within a common framework. It incorporates the needs and preferences of service users in the setting and improvement of quality standards, within resource constraints.

Humans↗
PubMed1987

Ageing and alpha 1 adrenoceptors in the iris.

This study was undertaken to determine if the age related decrease in pupil size is attributable to altered sympathetic adrenoceptor responsiveness. Log dose response curves using the selective alpha 1 agonist phenylephrine and antagonist thymoxamine showed that there is no difference in alpha 1 adrenoceptor sensitivity in the elderly and the young. Therefore age related miosis is not caused by an alteration in alpha 1 receptors with age.

Adult↗
PubMed1982

Recurrence of depression after discontinuation of long-term amitriptyline treatment.

In this study 10 of 17 patients receiving long-term amitriptyline treatment (average duration: 3.7 years, average dose: 138 mg) had their medication tapered and discontinued under double-blind conditions. Eight became depressed within 3 to 15 weeks. None of the 7 control subjects became depressed during the 6 months of the study. Those who became depressed also showed psychomotor retardation and sleep disturbance. Relief of longstanding anticholinergic side effects followed medication discontinuation. Some patients whose amitryptyline was discontinued experienced a mild withdrawal syndrome within the first 2 weeks, consisting of irritability, dream and sleep disturbance, and restlessness during the first few weeks.

Adult↗
PubMed1976

The use of 5-(125I)iodo-2'-deoxyuridine for monitoring DNA synthesis in organ culture.

5-[125I]iodo-2'-deoxyuridine (125IUdR) has been shown to be effective in monitoring DNA synthesis in murine tumour and human benign prostatic hyperplasia explants maintained in organ culture for 2 days, thus making possible the rapid screening of antitumour drugs. Uptake was linear for at least 24 hours in the case of the murine tumour and for 6 hours in the case of the prostate. Hydroxyurea almost completely blocked uptake by the murine tumour at doses above 10(-4) mole. Fluorodeoxyuridine (10(-6) mole) markedly increased the uptake of 125IUdR into the human prostate explants. Fixation of the murine tumour explants in alcoholic Bouin after culture did not alter the radioactive uptake and so routine histological examination of the tissue can be carried out after counting, which is a major advantage over [3H]thymidine.

Adenocarcinoma↗