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Biomedical subjects

M Kenny

Publications and source records attributed to M Kenny.

At least 37 records · Page 2Linked to original sources
PubMed1987

Two novel endogenous digoxin-like immunoreactive substances isolated from human plasma ultrafiltrate.

Two digoxin-like immunoreactive substances (DLIS 1 and DLIS-2) were isolated from human plasma by ultrafiltration, alkaline solvent extraction, and HPLC. Both inhibit canine Na, K-ATPase and cross-react with anti-digoxin antibodies. Their UV spectra are similar, with absorption peaks at 190 and 220 nm. FAB mass spectral analysis of both compounds yield a single dominant (M+H)+ component at m/z 532 otherwise, the fragmentation patterns are slightly different. The spectral data are consistent with the postulate that these compounds are related. Their identity as the natriuretic hormone is being investigated.

Chromatography, High Pressure Liquid↗
PubMed1987

Effects of a circulating factor in patients with essential hypertension on intracellular free calcium in normal platelets.

Intracellular free (cytosolic) calcium has been reported to be increased in the platelets of patients with essential hypertension. We investigated the possibility that the high cytosolic calcium concentration may be caused by a circulating plasma factor, by incubating platelets from normotensive subjects with plasma ultrafiltrates from patients with essential hypertension. The cytosolic calcium concentration in normal platelets increased after incubation with plasma from patients with untreated hypertension (80 +/- 15 percent [+/- SEM]) or from patients in whom hypertension was well controlled by calcium-influx blockers (129 +/- 33 percent). In contrast, the cytosolic calcium concentration was unchanged after incubation with plasma from normotensive subjects. When platelets from the patients were incubated with plasma from the controls, cytosolic calcium in platelets decreased by more than 30 percent, into the normal range (P less than 0.01). These data demonstrate that plasma from patients with essential hypertension contains a substance that increases the cytosolic calcium concentration in platelets. Cytosolic calcium is a trigger for vascular smooth-muscle-cell contraction, and if the plasma factor acts on these cells as it acts on platelets, it may be responsible for the increased peripheral vascular resistance associated with hypertension.

Adult↗
PubMed1986

Study of the tolerance and diuretic properties of torasemide following oral or intravenous administration to healthy volunteers.

The tolerance and diuretic properties of torasemide after oral or intravenous administration to healthy volunteers were studied. Six groups, each of 6 subjects, were given single rising oral doses ranging from 10 to 100 mg; 8 subjects received ascending i.v. doses on alternate days, ranging from 2.5 to 80 mg. At the highest oral doses investigated (80 mg and 100 mg) a number of volunteers complained of cramps in the knees, calves and feet. These symptoms were generally of short duration. Similar effects were not encountered during the intravenous study. There were no significant changes in ECG. Some significant drug-related changes were encountered in the within-study biochemistry and haematology assessments. Torasemide proved to be a potent diuretic following oral administration at all the doses investigated and following intravenous administration at all doses except 2.5 mg. A linear relationship existed between the urine output and the logarithm of the dose, and both sodium and chloride excretion were linearly correlated with urine volume. The rate of potassium excretion was markedly lower than that of sodium and chloride and was linearly correlated with the logarithm of the urine volume. Torasemide was well tolerated from all perspectives studied. It showed a potent diuretic property, and was equally effective by the oral and intravenous routes.

Administration, Oral↗
PubMed1986

Interaction of antimicrobial agents with human peripheral blood leucocytes: uptake and intracellular localization of certain sulphonamides and trimethoprims.

The uptake of sulphamethoxazole, sulphadiazine, sulphamerazine, sulphanilamide, trimethoprim and brodimoprim by human peripheral blood leucocytes, has been investigated. High performance liquid chromatography (HPLC) was used to assay drug concentrations before and after incubation with leucocyte suspensions. Using radiolabelled material the intracellular localization of two of these compounds was also determined. The results indicated that all the investigated drugs were taken up by leucocytes. Differential studies demonstrated that mononuclear cells accumulated higher drug concentrations (0.13-0.55 microgram/10(7) cells), than resting neutrophils (0.02-0.26 microgram/10(7) cells) with the exception of sulphanilamide, which was taken up to a greater extent by neutrophils (0.75 microgram/10(7) cells). During neutrophil phagocytosis intracellular levels of all the drugs except brodimoprim increased from 3 to 130-fold as compared to resting neutrophils. The uptake of 14C-sulphanilamide and 14C-trimethoprim, in neutrophils and mononuclear blood cells, as assessed by measurement of the cell-associated radioactivity, correlated well with that determined by the HPLC procedure. In the intracellular localization studies 14C-sulphanilamide and 14C-trimethoprim exhibited similar distribution profiles. In neutrophils, 35-40% of radiolabelled drug was located in both the microsome and cytosol fractions whereas in peripheral blood mononuclear cells 40-60% was found in the cytosol and 10-20% in the microsome fraction. The results of this study suggest that, following activation, leucocytes may actively transport these drugs and release them locally at sites of infection. The ability of neutrophils to further concentrate the drugs during phagocytosis may result in reduced survival time of some ingested bacteria. These concepts may be important in designing treatment stratagems for intracellular pathogens.

Chromatography, High Pressure Liquid↗
PubMed1986

Decreased calcium pump adenosine triphosphatase in red blood cells of hypertensive subjects.

Several operationally defined adenosine triphosphatase (ATPase) activities were determined in vitro in red blood cell lysates of normotensive or hypertensive humans: Mg2+-ATPase, Na+,K+-ATPase, and Ca2+ pump ATPase, the latter in the calmodulin-activated and basal states. Basal Ca2+ pump ATPase was defined as the Ca2+-activated ATPase resistant to 10(-4) M trifluoperazine. Subjects were part of a double-blind study in which treatment was divided into several phases: baseline (4 weeks), placebo or calcium (1 g elemental calcium/day, 8 weeks), placebo washout (4 weeks), placebo or calcium (1 g elemental calcium/day, 8 weeks). Irrespective of the phase of treatment, the basal Ca2+ pump ATPase activity in red blood cell lysates of 36 hypertensive subjects was significantly less than that in lysates from 18 normotensive subjects. Other ATPase activities did not differ significantly, although all ATPases tended to be decreased in hypertension. The data are consistent with previous reports of altered membrane Ca2+ binding and transport in hypertension, but the precise changes are not elucidated.

Adult↗
PubMed1986

Hypertension and a digoxin-like substance in the plasma of dialysis patients: possible marker for a natriuretic hormone.

Maintenance hemodialysis patients were randomly assigned to two groups based on the presence or absence of predialysis hypertension. Clinical profiles of the patients in the two groups were comparable except that there were more Blacks in the hypertensive group and that all the patients in this group received antihypertensive medications. Despite not taking any digitalis preparations, 10 of 12 hypertensives had measurable digoxin-like immunoreactive substance (DLIS) in their plasma. None of the 11 normotensives had detectable DLIS. Significantly higher (p less than 0.03) systemic vascular resistance was noted in hypertensives with DLIS compared to normotensives and hypertensives without DLIS. We propose that DLIS itself may be or may represent a marker for some vasopressive substance, possibly natriuretic hormone.

Adult↗
PubMed1985

Sudden death of a volunteer.

A volunteer participating in a study of eproxindine, a new antiarrhythmic agent, had a sudden cardiorespiratory arrest and died. Subsequently it became known that he had received a depot injection of flupenthixol on the day before his death; an interaction between these two drugs seems likely. This incident illustrates that it is impossible to guarantee absolute safety in volunteer studies if details of medical history are withheld.

Adult↗
PubMed1985

The DST in psychiatric outpatients with generalized anxiety disorder, panic disorder, or primary affective disorder.

The authors administered the dexamethasone suppression test (DST) to outpatients, who were free from psychoactive drugs for at least 10 days before the test, with primary affective disorder (N = 60), generalized anxiety disorder (N = 26), panic disorder (N = 22), and agoraphobia with panic attacks (N = 13). With a cortisol value of 5 micrograms/dl considered nonsuppression, there were no significant differences in dexamethasone nonsuppression rates among the diagnostic groups. Scores on the Hamilton Rating Scale for Depression and a melancholia subscale were significantly higher in the depressed group than in the anxiety disorder group. The findings raise questions concerning the specificity of the DST for primary affective disorder in relationship to anxiety disorders.

Adult↗
PubMed1984

Protein-primed replication of plasmids containing the terminus of the adenovirus genome. II. Purification and characterization of a host protein required for the replication of DNA templates devoid of the terminal protein.

A host protein, which is required for the replication of a plasmid DNA (pLA1), has been purified from extracts of uninfected HeLa nuclei. This plasmid DNA contains the origin of adenovirus DNA replication but lacks the 55,000-dalton terminal proteins. The purified host protein has been designated factor pL. Factor pL is essential for the initiation of DNA replication of EcoRI-digested pLA1 DNA, which proceeds via the formation of a covalent complex between the 80,000-dalton adenovirus coded preterminal protein and 5' dCMP. Factor pL has been purified approximately 120-fold to greater than 75% homogeneity. It is a heat labile and N-ethylmaleimide-sensitive protein with a native Mr = 39,000 (+/- 2,000). Initiation of DNA replication using EcoRI-digested pLA1 DNA as the template requires the 80,000-dalton preterminal protein and the 140,000-dalton adenovirus DNA polymerase, in addition to factor pL, and is stimulated as much as 10-fold by nuclear factor I ( Nagata , K., Guggenheimer , R. A., Enomoto , T., Lichy , J. H., and Hurwitz , J. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 6438-6442). Factor pL has no effect on in vitro DNA replication when adenovirus DNA covalently linked to the 55,000-dalton terminal protein is used as the template, however the replication of adenovirus DNA treated with Pronase, becomes totally dependent upon the addition of factor pL.

Adenoviridae↗
PubMed1984

Transcutaneous bilirubin monitoring of newborns.

Using skin jaundice measurements as an index of infant bilirubin status is subject to a number of uncertainties as described by many investigators. They are illustrated by the experience with a commercial device described here. In view of the widespread need for a quantitative measurement that can replace the visual inspections and subjective evaluations of jaundice being routinely used in clinical settings, such jaundice meters are likely to gain increasing acceptance. We expect future research to include more studies on: (1) reflectance spectra or multiple wavelength measurements for SBI; (2) quality control needed for SBI determinations; (3) the relative significance of physiological factors that influence tissue bilirubin deposits; and (4) the comparative significance of blood versus tissue bilirubin concentrations as true indicators of potential nervous tissue damage.

Bilirubin↗
PubMed1983

Platelet uptake of serotonin following repeated administration of 3-cyano-imipramine to healthy volunteers.

In a double blind, placebo-controlled study the effects of daily oral administration of 3-cyano-imipramine on the 3H-serotonin uptake capacity of platelets were investigated in healthy volunteers. The initial dose was 1 mg, rising to 3 mg daily for 7 days. A rapid and profound inhibition of 3H-serotonin uptake was observed in platelets isolated from the treated subjects. During repeated administration, uptake was reduced to less than 10% of pre-drug values. Five days after the final dose uptake had only partially recovered, to 53% of pre-drug values. A similar inhibition profile was observed when serum from the treated subjects was incubated with normal platelets and 3H-serotonin. The results establish 3-cyano-imipramine as a potent inhibitor of platelet serotonin uptake in humans.

Adolescent↗
PubMed1983

Absence of central effects in man of the benzodiazepine antagonist Ro 15-1788.

The benzodiazepines are typified by a profile of side effects which includes drowsiness, ataxia and incoordination. Ro 15-1788, an imidazodiazepine derivative, exhibits marked antagonism of the behavioural and biochemical effects of the benzodiazepines in animals and man. It is devoid of any behavioural activity in animals, except at very high doses. In the present study the effects of single rising oral doses of Ro 15-1788 on cognitive, psychomotor and subjective function in man have been assessed using a battery of psychometric tests designed to identify the sedative action of the benzodiazepines. At all doses up to 600 mg, Ro 15-1788 demonstrated none of the classical behavioural effects of the benzodiazepines.

Adult↗
PubMed1983

Effects of a single oral dose of 3-cyano-imipramine on serotonin uptake and content of platelets in healthy volunteers.

Changes in platelet serotonin uptake and content were investigated following administration of a single oral dose of 3-cyano-imipramine to healthy volunteers. The uptake of 3H-serotonin by platelets harvested from these subjects was almost completely inhibited 4 h after dose administration. This inhibition continued for at least 24 h. Plasma taken from the subjects inhibited the uptake of 3H-serotonin by platelets isolated from non-treated subjects. A small but significant reduction in platelet serotonin content was observed 3.75 h after dosing and was still evident after 24 h.

Administration, Oral↗
PubMed1983

The effect of PK5078, a new serotonin uptake inhibitor, on serotonin levels and uptake in human platelets, following administration to healthy volunteers.

PK 5078 is a recently developed compound which inhibits specifically the neuronal reuptake of serotonin and enhance its release. PK 5078 was administered to healthy male volunteers in single and multiple oral doses and the effects on platelet serotonin uptake and content were examined. A significant dose-related inhibition of 3H-serotonin uptake by platelets was observed following single oral doses of PK 5078 (25-150 mg), with maximal inhibition at 75 mg. This was evident 2 h after dosing and was still marked after 10 h. Plasma collected from the subjects after dosing also had a considerable dose-related effect on the uptake of 3H-serotonin by untreated platelets. No significant alteration in platelet serotonin content was observed after single doses of PK 5078. When PK 5078 (50 mg) was administered twice daily for 9 days there was a rapid and sustained reduction in 3H-serotonin uptake by platelets, which returned to pretreatment levels 2 days after discontinuation of the drug. A similar response was observed when plasma from these subjects was incubated with untreated platelets. The rate of depletion of endogenous platelet serotonin was much slower with minimum levels being attained on the morning after the final dose. The recovery following withdrawal was also slow with serotonin levels approaching pre-dose values 14 days after the final dose of PK 5078.

Adolescent↗
PubMed1983

Ro 15-1788 antagonizes the effects of diazepam in man without affecting its bioavailability.

In a double-blind, placebo-controlled three-way cross over study, the efficacy of Ro 15-1788 200 mg, a new benzodiazepine antagonist, in blocking the amnesic, cognitive, psychomotor and subjective effects of diazepam 20 mg, was investigated in a group of six healthy male volunteers. The amnesic effects of diazepam were markedly attenuated by the combined administration of Ro 15-1788. The psychomotor and subjective effects of diazepam by mouth were most pronounced 2.5 h after administration. Concurrent oral administration of Ro 15-1788 completely prevented these effects at 2.5 h. Plasma diazepam concentrations observed after administration of the combination of diazepam and the antagonist did not differ from those observed following diazepam alone.

Adolescent↗