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Biomedical subjects

M Kendall

Publications and source records attributed to M Kendall.

At least 37 records · Page 2Linked to original sources
PubMed1991

Quality of life in cardiovascular diseases. Emphasis on beta-blocker treatment.

In this article, the issues involved in the measurements of quality of life in clinical trials of cardiovascular drugs are discussed with emphasis on beta-blocker treatment. The extensive documentation available for beta-blockers makes it possible to evaluate different aspects of this class of drugs. Generally, beta-blockers have been shown to be safe with a low frequency of serious side effects. However, results of different studies have shown that this class of drugs affects various aspects of well-being and psychomotor tests both negatively and positively. Adverse effects often associated with beta-blockers are the subjective symptoms that are considered to be related to the central nervous system. Today there is increasing evidence that these can be quantitatively as well as qualitatively reduced by using beta-blockers in a low dose and avoiding high plasma peak concentrations. Considering effects on well-being and psychomotor tests, there seems to be no clinical difference between hydrophilic and lipophilic beta-blockers, when administered in comparable therapeutic dosages, whereas beta 1-selective blockers in clinically relevant doses seem to produce fewer and less severe adverse effects than nonselective blockers. Compared with other classes of cardiovascular drugs, there is no clear evidence of differences in well-being between selective beta-blockers and angiotensin converting enzyme inhibitors or calcium antagonists.

Adrenergic beta-Antagonists↗
PubMed1990

DNA specificity of the Cre recombinase resides in the 25 kDa carboxyl domain of the protein.

The Cre protein of bacteriophage P1 is a 38.5 kDa site-specific recombinase that belongs to the Int family of recombination proteins. Cre acts by binding specifically to a 34 base-pair sequence, lox, where it carries out recombination. A limited chymotryptic digest of Cre resulted in two fragments of sizes 25 and 13.5 kDa, respectively. The sequence of the amino terminus of the purified 25 kDa peptide demonstrates that this peptide represents the carboxyl-terminal portion of the Cre protein. A truncated version of the cre gene was constructed which produces only the 25 kDa peptide. The 25 kDa peptide is capable of specific binding to the lox site, but binds at lower affinity than does wild-type Cre. Footprinting with Fe-EDTA indicates that the 25 kDa peptide protects the inverted repeats of the lox site but shows only partial protection of the spacer region. This is in contrast to the footprint obtained with wild-type Cre which protects the entire spacer region.

Amino Acid Sequence↗
PubMed1990

Is metoprolol CR/ZOK more selective than conventional metoprolol and atenolol?

An alternative, simple method to assess beta 1-selectivity is to establish the impact of the beta blocker on beta 2-stimulated increases in plasma glucose and decreases in plasma potassium during an intravenous infusion of terbutaline. In the present study the effects of metoprolol CR/ZOK 100 mg, conventional metoprolol 100 mg, atenolol 100 mg, and placebo on these biochemical changes have been compared. In 12 healthy volunteers, terbutaline infusion of 6 micrograms/kg was administered intravenously over 1 hour. Three and a half hours before the infusion they were given a single dose of each of the four treatments in random order, single-blind. The maximum increase in plasma above baseline occurred at the end of a 60-minute terbutaline infusion. All three-beta blockers decreased the peak plasma glucose level achieved compared with placebo (P less than .01) but this reduction was significantly less with metoprolol CR/ZOK pretreatment than with atenolol (P less than .05). Similar results were seen for the AUC values for the curves obtained from the increments over the 60 minutes of the infusion and the subsequent 120 minutes after the infusion. In addition, both the AUC values and the maximum fall in potassium were significantly reduced by all treatments (P less than .05). The metoprolol CR/ZOK preparation produced significantly less effect than atenolol with respect to both AUC (P less than .05) and maximum fall (P less than .01) and significantly less effect than conventional metoprolol tablets in maximum fall (P less than .01). In conclusion, the metoprolol CR/ZOK formulation produces lower plasma concentrations and results in less effect on potassium and glucose compared to conventional metoprolol and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Pharmacokinetics of felodipine in patients with liver disease.

Nine patients (6 males, 3 females) with biopsy-proven liver cirrhosis participated in an open, cross-over, three centre study of the effect of impaired liver function on the pharmacokinetics of felodipine. Two of the nine patients had undergone porto-caval anastomosis. Each patient was given 0.75 mg i.v. and 10 mg p.o. on separate occasions. The results of this study have been compared with published data from younger subjects and elderly hypertensive patients. The mean peak plasma concentration normalized to a dose of 10 mg (Cmax 46 nmol/l) was twice as high in the cirrhotic patients as in the healthy subjects, but the bioavailability, f, (17.0%) was comparable. Subjects with a porto-caval shunt did not have higher f than the mean for the group. The volume of distribution at steady-state, Vss, was significantly lower than in the healthy subjects. Protein binding was significantly lower in the patients with cirrhosis: 99.46% compared to 99.64% in the healthy subjects. The weight-corrected clearance was 1/3 of the value in healthy subjects. No correlation between systemic availability and oral clearance was found, so it is proposed that felodipine is metabolized both in the liver and also in the gut wall. The results suggest that at least the starting dose should be reduced in patients with severe liver disease.

Adult↗
PubMed1988

The effects of flosequinan and nifedipine on glucose tolerance in healthy volunteers.

The influence of flosequinan and nifedipine on glucose tolerance has been investigated in a placebo-controlled four-way crossover study in 12 healthy volunteers. There was no statistical difference between the glucose tolerance curves after placebo, a single dose of flosequinan, chronic treatment with flosequinan or nifedipine at steady state. Headache was more frequent in volunteers on flosequinan than after either nifedipine or placebo.

Adult↗
PubMed1988

Motor-evoked potentials of tongue musculature in dogs.

Transcranial brain stimulation by either electrical or noninvasive magnetic stimulation has produced motor responses of limb musculature. However, recordings from muscles innervated by cranial nerves have not previously been reported. A right-sided craniotomy was performed in 18 dogs. An electric stimulus was delivered to the motor cortex via surface electrodes and evoked EMG responses were recorded from the tongue musculature to determine conduction time. Magnetic stimulation of the motor cortex yielded EMG latencies similar to those obtained by electrical direct cortical stimulation, thus demonstrating the potential of magnetic stimulation in intraoperative and outpatient clinical evaluation of hypoglossal nerve disorders. For the first time, it appears possible to noninvasively stimulate the cranial nerves proximal to the point of injury and to evaluate more central conduction pathways.

Action Potentials↗
PubMed1988

Motor-evoked potentials of facial musculature in dogs.

Motor responses of limb musculature have been elicited by transcranial brain stimulation using electrical and magnetic stimulation. Recording from muscles innervated by cranial nerves has not previously been reported. A unilateral hemispheric craniotomy was performed in 24 dogs. An electric stimulus was delivered directly to the exposed motor cortex via surface electrodes. Evoked electromyographic responses to motor cortex stimulation were recorded from the contralateral orbicularis oculi and orbicularis oris muscles. Preliminary investigation into the use of magnetic stimulation of the motor cortex is compared to direct electrical cortical stimulation. This study demonstrates the potential for magnetic stimulation in the intraoperative and outpatient clinical evaluation of facial nerve disorders. It appears possible, for the first time using magnetic stimulation, to noninvasively stimulate these nerves proximal to the point of injury and to evaluate more central conduction pathways.

Animals↗
PubMed1987

A mutational analysis of the bacteriophage P1 recombinase Cre.

Bacteriophage P1 encodes a 38,600 Mr site-specific recombinase, Cre, that is responsible for reciprocal recombination between sites on the P1 DNA called loxP. Using in vitro mutagenesis 67 cre mutants representing a total of 37 unique changes have been characterized. The mutations result in a wide variety of phenotypes as judged by the varying ability of each mutant Cre protein to excise a lacZ gene located between two loxP sites in vivo. Although the mutations are found throughout the entire cre gene, almost half are located near the carboxyl terminus of the protein, suggesting a region critical for recombinase function. DNA binding assays using partially purified mutant proteins indicate that mutations in two widely separated regions of the protein each result in loss of heparin-resistant complexes between Cre and a loxP site. These results suggest that Cre may contain two separate domains, both of which are involved in binding to loxP.

Amino Acid Sequence↗
PubMed1984

The role of the prostacyclin-thromboxane system in cerebral vasospasm following induced subarachnoid hemorrhage in the rabbit.

Subarachnoid hemorrhage (SAH) was induced in 50 rabbits by injecting 1.25 cc/kg of autologous, well heparinized, fresh arterial blood into the cisterna magna, followed by suspending the animals in a head-down position at 30 degrees for 15 minutes. The animals were evenly divided into five groups: a control group, or groups receiving post-SAH prostacyclin (PGI2), carbacyclin, thromboxane A2 (TXA2) synthetase inhibitor (OKY-1581), or nutralipid. Radiographic vertebrobasilar arterial spasm was demonstrated on the 3rd day post-SAH in the control animals. This was decreased in the prostacyclin and the carbacyclin groups and was absent in the OKY-1581 and the nutralipid groups. Cerebral blood flow (CBF) measurements on the 4th day post-SAH using the xenon-133 technique failed to reveal any significant difference between the prostacyclin, the carbacyclin, and the control groups, but flows in the nutralipid and the OKY-1581 groups were significantly higher. There was a good correlation between the clinical status and the CBF. Intracytoplasmic vacuolation and detachment of the vascular endothelium, seen ultrastructurally, may account for the impaired synthesis of prostacyclin. Exogenous prostacyclin and carbacyclin decreased vasospasm but failed to improve cerebral perfusion. OKY-1581 blocked the synthesis of the potent vasoconstrictor, TXA2, which is not only formed during platelet aggregation but also induces platelet aggregation. Nutralipid contains linolenic acid, a precursor of eicosapentaenoic acid (EPA), which is more potent in inhibiting platelet aggregation and in blocking TXA2 production. The various fatty acid constituents of nutralipid bind to albumin and thereby shorten the half-life of TXA2.

Acrylates↗
PubMed1982

Sensitivity to heat and water loss at rest and during exercise in asthmatic patients.

We investigated the respiratory heat and water loss in 24 asthmatic patients who performed bicycle exercise while inspiring air conditioned to varying temperatures and water contents. Measurements of peak expiratory flow and forced expiratory volume in 1 s were made at rest, during and after exercise to determine changes in airways resistance. Respiratory heat and water loss were measured using rapid thermistors and a mass spectrometer to measure inspired and expired temperature and water vapour pressure. Exercise-induced asthma (EIA) was enhanced as the inspired water content of the air was reduced. However, there was a wide variation in sensitivity to the loss of heat and water between individual patients. This variability could not be accounted for by differences in body size. When patients inspired air conditioned to body temperature and fully saturated with water vapour, EIA was significantly reduced; however, half the patients still had an attack of asthma following exercise which had induced no significant loss of heat or water. It is suggested that the bronchoconstriction induced by water loss from the airways during exercise may be due to a change in osmolarity in the respiratory tract fluid.

Adolescent↗
PubMed1979

Metoprolol with and without chlorthalidone in hypertension.

After a control period on a placebo, 45 patients with mild to moderate hypertension were treated with metoprolol, 100 mg twice daily alone and in free combination with chlorthalidone 50 mg daily using a double-blind crossover technique. The beta-blocker alone induced a significant fall in blood pressure; the diastolic pressure was reduced to 100 mg Hg or less in 37 of the 45 patients and to 95 mm Hg or less in 19 patients. The addition of chlorthalidone enhanced the antihypertensive effect so that in 33 patients diastolic pressure fell to 95 mm Hg or less. The drugs were well tolerated even by a small number of patients with chronic bronchitis and diabetes mellitus. None of the patients developed cardiac failure. Adding a diuretic caused a small reduction in serum potassium concentrations, and the relevance of this observation is discussed.

Adult↗
PubMed1976

Escherichia coli O 27 in adult diarrhoea.

Escherichia coli O 27 H 7 was found in 16 stool samples submitted during a Caribbean cruise (Cruise Z) by 29 patients reporting with diarrhoea. A retrospective search revealed E. coli O 27 H 7 in 11 of 20 and 2 of 14 stool cultures from patients on two previous cruises (Y and X respectively) and in a culture from fresh cream (Cruise Y). The repeated occurrence of E. coli O 27 H 7 in the absence of any other apparent cause suggested that this serotype may have been responsible for the diarrhoea. The results of pathogenicity tests suggested that this strain elaborated heat-stable (ST) enterotoxin. The possibility that food may have been the vector is discussed.

Adult↗
PubMed1972

The effect of two methods of cooking and cooling on Clostridium welchii and other bacteria in meat.

A comparison was made of beef cooked in conventional and moist air (Rapidaire) ovens. In both large (ca. 4.5 kg.) and small (ca. 2.7 kg.) joints, spores of Clostridium welchii survived after cooking but vegetative cells, Escherichia coli, and Staphylococcus aureus, did not, regardless of the type of oven used.Cooling at room temperature after cooking permitted growth of Cl. welchii. Although some multiplication also occurred in the centre of large roasts cooled under refrigeration, the viable counts were considered too low to constitute a potential health risk.

Animals↗