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Biomedical subjects

K Witte

Publications and source records attributed to K Witte.

At least 109 records · Page 6Linked to original sources
PubMed1991

Rhythms in second messenger mechanisms.

In this chapter circadian rhythms in the beta-adrenoceptor/adenylate cyclase/phosphodiesterase system are presented and discussed. Daily variation in total number and affinity of beta-adrenoceptors in rat forebrain and rat heart ventricles seem to be of minor importance in the circadian regulation of the cAMP concentration in these tissues. Pronounced and significant circadian rhythms in cAMP formation by the adenylate cyclase and cAMP degradation by the phosphodiesterases could be demonstrated in either rat forebrain or heart ventricles. Also the accessibility of cardiac adenylate cyclase to different stimuli was circadian-phase-dependent. Furthermore, data are presented which indicate that the catalytic unit of the adenylate cyclase must undergo qualitative changes with age.

Adenylyl Cyclases↗
PubMed1991

Nicardipine sustained release in hypertension.

1. A novel formulation of nicardipine (25% standard, 75% sustained release--SR) was evaluated in mild hypertension in a double-blind, randomized, placebo-controlled comparison with standard nicardipine (STD), using clinic measurements (Hawksley) augmented by home recorded blood pressures (Copal UA 251). 2. At 2 h after dosing (peak effect) both STD nicardipine (30 mg three times daily) and SR nicardipine (60 mg twice daily) for 28 days produced a highly significant reduction in sitting and standing blood pressure. The mean sitting blood pressure was reduced by 20/16 mm Hg (STD) and by 25/18 mm Hg (SR) compared with placebo. 3. Predose (8-11 h after last dose of STD, 12-15 h after last dose of SR) the reductions in sitting blood pressure relative to placebo were 11/6 mm Hg (STD) and 14/7 mm Hg (SR). 4. Home recordings confirmed the hypotensive effect of both formulations. Both exhibited a distinct 'peak dose' effect between 1-3 h after dosing. The effect of the SR formulation was sustained throughout the 12 h dosing interval. 5. Of the 60 patients entering the study, one died of unexplained staphylococcal septicaema, two were withdrawn for non drug-related reasons and 14 (32%) were withdrawn because of adverse effects on active therapy (headaches, facial flushing, leg oedema, chest pain, dizziness). 6. In the 43 patients who completed the study adverse symptoms were reported more frequently while they were on the two active formulations of nicardipine compared with placebo. Most of these reactions were again of vasodilator origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

PHARMFIT--a nonlinear fitting program for pharmacology.

A new program is presented for nonlinear fitting of data from pharmacological and chronobiological investigations. It contains functions for calculating data from ligand-binding studies and competition experiments, for the analysis of dose-response curves, for pharmacokinetic calculations, and for cosine analysis of harmonic and overlapping rhythms. In addition, it is possible to implement general equations by the user. The program allows data exchange with most spreadsheet, database, and graphics presentation programs, and accepts data from two widely used ambulatory 24-h blood-pressure monitoring systems. The fitting procedure uses the Marquardt-Levenberg algorithm. It calculates the weighted or the unweighted fit together with a great variety of statistics for estimation of goodness of fit. A graphics module permits graphical presentation of the fitted curve. Moreover, fitting of data to different models can be compared for the most likely fit and model discrimination statistics for improvement of further experiments are provided. To demonstrate the chronobiological application of the fitting program PHARMFIT, the analysis of telemetric heart rate data from rats is presented.

Binding Sites↗
PubMed1990

An evaluation of the A&D UA-751 semi-automated cuff-oscillometric sphygmomanometer.

We compared blood pressure recordings made with the A&D UA-751 semi-automated cuff-oscillometric sphygmomanometer (A&D Co. Ltd, Tokyo, Japan) and with a conventional Hawksley random-zero mercury sphygmomanometer (Hawksley and Sons Ltd, Lancing, UK). Simultaneous single-arm recordings were obtained in duplicate with both devices in 200 subjects having blood pressure in the ranges 92-221/51-121 mmHg. The measurements obtained by three observers using the Hawksley sphygmomanometer were compared with recordings from two A&D UA-751 devices. In most cases, there was an acceptable level of agreement between the results, according to the criteria suggested by the Association for the Advancement of Medical Instrumentation (range of differences systolic: mean - 0.9 to 1.4 mmHg, s.d. 4.6-9.8 mmHg; diastolic: mean - 0.6 to 1.3 mmHg, s.d. 2.9-5.1 mmHg), although there were sizeable discrepancies in individual subjects. Thus the A&D UA-751 device appears to be an acceptable alternative to a conventional sphygmomanometer; it should be suitable for routine clinical and limited research use, including intermittent home blood pressure recording.

Blood Pressure Determination↗
PubMed1990

Bench and ambulatory field evaluation of the A & D TM-2420 automated sphygmomanometer.

Adequate evaluation of automated sphygmomanometers, in terms of safety, accuracy, mechanical reliability, patient acceptability and ability to record ambulatory blood pressure is essential before these devices are used in clinical practice and in clinical trials. We have evaluated the accuracy and performance of the A & D TM-2420 automated sphygmomanometer, an auscultatory device designed for ambulatory blood pressure recording. Four devices were tested for accuracy by simultaneous comparison against two experienced observers using standard mercury column sphygmomanometers. Two of these devices developed faults that precluded complete evaluation. One of the remaining devices met and one failed to meet the somewhat liberal criteria for accuracy recommended by the American Association for the Advancement of Medical Instrumentation, the current standard for evaluation (mean difference of less than or equal to 5 mmHg and standard deviation of differences less than or equal to 8 mmHg). The mean differences (standard deviation of differences) between observers for simultaneous triplicate observations of systolic/diastolic pressure in 50 subjects, including 35 hypertensives, were 0.8 (3.0)/-0.6 (2.4) mmHg. In comparison, the differences between each device and each observer were: device 11, observer 1, -6.4 (5.4)/-6.3 (9.9); device 11, observer 2, -5.6 (4.7)/-7.0 (10.4); device 12, observer 1, -4.9 (5.2)/-4.0 (7.5); device 12, observer 2, -4.1 (4.9)/- -4.5 (7.7) mmHg. Ambulatory trials were carried out with a further 10 devices. Of these, seven developed faults requiring their return to the supplier. Numerous additional problems were encountered with microphones, cuffs, leads and connections, the processing unit, error algorithms and data-handling software. The device was not capable of making truly ambulatory recordings. We do not confirm the previously favourable, but limited, evaluation of this device. We stress the vital importance of subjecting a number of devices to benchtesting for accuracy, and the need to undertake extensive 'field' testing before any devices can be considered suitable for ambulatory recording. Exercise testing under laboratory conditions is not an adequate substitue for true ambulatory evaluation.

Algorithms↗
PubMed1989

Circadian rhythm of the in vitro stimulation of adenylate cyclase in rat heart tissue.

Adenylate cyclase activity in rat heart ventricles displayed a circadian rhythm with a maximum around 8:00 h and a minimum around 20:00 h. In vitro stimulation with 0.1 mM of isoprenaline, Gpp(NH)p or forskolin increased the 24-h-mean basal adenylate cyclase activity by 1.7-, 2.7- and 10.7-fold, respectively. The magnitude of the drug-induced stimulation varied significantly with the time of day. However, the drugs did not affect the timing of the circadian maximum or the amplitude (as % of 24-h-mean) of the basal rhythm. The data are the first to show that the response to the in vitro stimulation of the cardiac adenylate cyclase also displays a pronounced circadian rhythm.

Adenylyl Cyclases↗
PubMed1989

Evaluation of a long acting formulation of nicardipine in hypertension by clinic and home recorded blood pressures and Doppler aortovelography.

1. A novel formulation of nicardipine (50% standard (short acting), 50% sustained release) was evaluated in mild hypertension in a double-blind, randomized, placebo-controlled study, using clinic measurements (Hawksley) augmented by home recorded blood pressures (Copal UA 251). 2. Nicardipine 60 mg twice daily for 28 days produced a highly significant reduction in sitting blood pressure compared with placebo both pre dose (mean difference 17/8 mm Hg) and 2 h post dose (mean difference 34/26 mm Hg). 3. Home recordings confirmed the hypotensive effect and also revealed a consistent 'peak' effect between 2-4 h after dosing (mean difference 32/22) mm Hg). 4. Doppler aortovelography at 2 h post-dose showed a significant increase in in stroke and minute distance (linear analogues of stroke volume and cardiac output respectively) compared with placebo. The increase in stroke distance was linearly related to change in plasma concentration of nicardipine. 5. Of the 14 patients enrolled in the study, nine experienced troublesome adverse effects on nicardipine (headaches, facial flushing, palpitations, ankle oedema) and two of these were unable to complete the study as a result. 6. This formulation of nicardipine, in the fixed dosage used in this study, is characterized by an effective antihypertensive action but also by an unacceptable adverse effect profile, presumably due to an excess of its 'short acting' component.

Blood Pressure↗
PubMed1987

Single doses of enalapril and atenolol in hypertensive patients treated with bendrofluazide.

Enalapril in single doses of 5 and 10 mg and atenolol in a single dose of 50 mg were given to 16 hypertensive patients on long-term treatment with bendrofluazide, 5 mg daily, in a double-blind randomized crossover placebo controlled study. Both doses of enalapril and atenolol produced similar effects on blood pressure. The mean maximal reduction in blood pressure from baseline with all three active treatments was approximately 32/18 mmHg both supine and standing and occurred on average at 6 h after tablet ingestion. Both supine and standing heart rate fell significantly after atenolol, but no significant change occurred after enalapril. This study establishes that 5 mg enalapril is the maximal starting dose that need be used in hypertensive patients already on diuretic treatment. Even this dose may be hazardous in some patients. The study also serves to emphasize that such combination-therapy studies should be carried out at an early stage in drug development, prior to widespread prescription to patients, in order to avoid unnecessary overdosage with new agents.

Adult↗
PubMed1987

Atenolol or propranolol in hypertensive patients poorly controlled on captopril and frusemide.

Eighteen patients whose clinic blood pressure (BP) remained over 95 mmHg despite treatment with captopril 50 mg twice daily plus frusemide 40 mg twice daily were randomised in a crossover study to four weeks' treatment with once daily atenolol 100 mg, slow release propranolol 160 mg or placebo. The reduction in BP on atenolol was superior to that on both propranolol and placebo. The mean supine BP 24 hours post dosing were 177/110 mmHg (placebo), 173/109 mmHg (propranolol) and 164/100 mmHg (atenolol). The corresponding mean heart rates were 77 bpm (placebo), 63 bpm (propranolol) and 62 bpm (propranolol) and 62 bpm (atenolol). The difference in hypotensive efficacy between atenolol and propranolol is not readily explained but our study shows that atenolol has a clinically useful supplementary effect on BP. Refractory hypertension remains an important clinical problem and further studies are required to establish the optimum combination of drugs that should be used with captopril in order to achieve 'target' BP in patients with moderate to severe hypertension.

Aged↗
PubMed1980

Audit of an oral anticoagulant teaching program.

Quality assurance criteria for a pharmacist-conducted oral anticoagulant teaching program were studied. The teaching program involved the presentation of descriptive diagrams accompanied by a reinforcing explanation given by a pharmacist. Topics discussed included clotting, warfarin therapy, diet and drug interactions. An audit, consisting of a pretest and posttest, was developed to measure patient knowledge as a measurement of the program's effectiveness. Forty ambulatory patients participated in the study over a three-month period. Before instruction, only five patients were adequately knowledgeable about all of the information components. After instruction, this number increased to 20 patients, and all 40 patients had a better knowledge of each topic. The audit revealed that the program's standards were not completely appropriate and that other methods of program delivery must be evaluated and implemented.

Anticoagulants↗
PubMedDate not supplied

Addressing cultural orientations in fear appeals: promoting AIDS-protective behaviors among Mexican immigrant and African American adolescents and American and Taiwanese college students.

Fear appeals threatening the individual have been shown to be powerful persuasive devices in the cultures where they have been studied. However, most fear appeal research has been conducted with members of individualist cultures. Individualist cultures place self-needs above group concerns, while collectivist cultures place group needs above self-concerns. Little is known about the effectiveness of fear appeals (or other persuasive strategies) in collectivist cultures. Two studies assessed the effectiveness of AIDS-prevention fear appeals threatening the self versus fear appeals threatening the group (i.e., family) on members of individualist and collectivist cultures. The first study focuses on African American and Mexican immigrant junior high school youth. The second study focuses on U.S. and Taiwanese college undergraduates. The results indicated that fear appeals should address cultural orientation (i.e., individualist versus collectivist orientation) to achieve maximum effectiveness. The results also indicate that one cannot assume cultural orientation based on ethnicity.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Understanding barriers to preventive health actions for occupational noise-induced hearing loss.

A theoretically based formative evaluation was conducted with coal miners in the Appalachian Mountains who were at high risk for noise-induced hearing loss (NIHL). The results of four focus groups indicate that despite high levels of knowledge, strong perceived severity of negative consequences, and strong perceived susceptibility to hearing loss, two main categories of barriers (environmental and individual) keep coal miners from using their hearing protection devices (HPD). Further analysis suggests that the environmental factors, rather than individual variables, more strongly influence decisions against protective actions. Recommendations and practical implications are offered.

Adult↗