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Biomedical subjects

P Keane

Publications and source records attributed to P Keane.

At least 37 records · Page 2Linked to original sources

Plasma sodium-potassium ATPase inhibition activity in low- and normal-renin hypertension.

Thirty-seven subjects with low- and normal-renin hypertension (plasma renin activity less than 0.45 ng/L/sec on a 100 mmol Na diet) were studied on a 10 and 100 mmol sodium diet (100 mmol K and 25 mmol Ca) to examine the effect of varied sodium intake on plasma Na,K-ATPase inhibitory activity (NKAIA) (% inhibition). On the 10 mmol Na diet, plasma NKAIA correlated with mean arterial pressure (MAP) (r = 0.384, P = .019). On the 100 mmol Na diet, plasma NKAIA correlated with daily urinary sodium excretion (r = 0.384, P = .019). With the increase in sodium intake, the mean change in MAP was 0.5 +/- 7.8 mm Hg (range -12.7 to 16.3) and the mean change in plasma NKAIA was -4.2 +/- 11.2% inhibition (range -37.5 to 16). The change in MAP was correlated to the change in plasma NKAIA (r = 0.384, P = .019). Plasma NKAIA is related to mean arterial pressure or urinary sodium excretion depending on the dietary sodium intake, and is related to sodium-induced changes in MAP in low and normal renin hypertensive patients.

Adult↗

Age and other determinants of survival after in-hospital cardiopulmonary resuscitation.

A retrospective review of 274 patients who received in-hospital cardiopulmonary resuscitation was performed to determine whether age is independently associated with survival to discharge. Eighty-two (29.9 per cent) of the 274 patients were resuscitated initially, but only 25 (9.1 per cent) were discharged alive. Survival to discharge was significantly poorer in patients aged greater than or equal to 70 years (6/175; 3.4 per cent) than in patients less than 70 years old (19/99; 19.2 per cent) (p less than 0.001). Severity of illness, assessed by the number of diagnoses and a multifactorial morbidity index, did not differ between the two age groups. The best results were obtained with witnessed arrests, ventricular arrhythmias and resuscitation lasting less than 5 minutes; however, elderly patients were less likely to be resuscitated in all circumstances. Age (r = -0.31, p less than 0.001) and the morbidity index (r = -0.18, p less than 0.05) were independently associated with survival by multivariate analysis. These results indicate that advanced age is an important independent determinant of survival after resuscitation. This should be taken into consideration when making in-hospital resuscitation decisions.

Adolescent↗

Post-cannulation radial artery aneurysm--a rare complication.

The following case report describes an expanding aneurysmal dilatation of the radial artery which developed 17 days following cannulation. Possible causes of this complication are: abnormal state of the vessel wall, multiple attempts at cannulation, and haematoma or infection at cannulation site. Other major and minor sequelae following arterial cannulation are reviewed.

Aged↗

Three-monthly GnRH agonist (buserelin) for prostatic cancer.

A new slow release formulation of buserelin given as a 3-monthly depot injection has been evaluated in 4 patients with advanced prostatic cancer previously maintained on shorter acting depots. Treatment was maintained for a mean period of 21 months. Steady state urinary buserelin concentrations were reached by the beginning of the third treatment week and maintained until the end of the third treatment month. Serum testosterone remained suppressed in the castrate range for the duration of the study. Seven previously untreated patients were entered into treatment. Serum testosterone was suppressed into the castrate range between the seventh and fourteenth days after implantation. This preparation offers an advantage for the patient and clinician over existing methods of GnRH analogue administration and will now enter further clinical trial.

Buserelin↗

Cerebral-activating (EEG) properties of two inverse agonists and of an antagonist at the benzodiazepine receptor in the rat.

In order to assess the effects of inverse benzodiazepine agonists and antagonists on brain function, computerized EEG (CEEG) analysis was performed in rats following the i.p. administration of SR 95195 (7-phenyl-3-methyl-1,2,4 triazolo-[4,3-b]pyridazine) and CGS 8216 (2-phenylpyrazolo-[4,3c]-quinoline-3-[5H]-one) two benzodiazepine receptor inverse agonists (BRIAGs) and of flumazepil (Ro 15-1788), a benzodiazepine receptor antagonist (BRANT). The EEG effects of SR 95195 (3, 10, 30 and 60 mg/kg), CGS 8216 (10 and 30 mg/kg) and flumazepil (3, 10, 30 and 60 mg/kg) were compared to those of the psychostimulant drugs DL-amphetamine (0.1, 0.3 and 1 mg/kg), and caffeine (10 and 30 mg/kg) and those of aniracetam (100 and 300 mg/kg), a nootropic pyrrolidone derivative. The CEEG profiles of SR 95195, CGS 8216 and flumazepil were mainly characterized by a power increase in the 20-32 Hz frequency range and by a power reduction in the 8-16 Hz range. These effects were quite similar to those of the psychostimulants DL-amphetamine and caffeine as well as to those of the nootropic aniracetam. Other psychotropic drugs with CNS-depressant properties, namely diazepam (10 mg/kg p.o.), pentobarbital (30 mg/kg p.o.), chlorpromazine (10 mg/kg i.p.) and imipramine (10 mg/kg i.p.) induced quite different EEG power modifications. These results show that BRIAGs and BRANTs possess a marked intrinsic activity at the central level and suggest that this activity is CNS-activating in nature.

Animals↗

Change in glycoconjugate for the binding site of the lectin Ulex europeus 1 following malignant transformation of prostatic epithelium.

Immunoperoxidase techniques were used to detect Ulex europeus (UEA1) binding sites on benign and malignant prostatic epithelium. Formalin-fixed, paraffin-embedded (FFPE) and cryostat sections were compared. In benign epithelium, less than 10% of cells on FFPE sections but between 50 and 90% of cells on cryostat sections expressed UEA1 binding sites. In malignant epithelium, more than 90% of cells bound UEA1, irrespective of whether FFPE or cryostat sections were used. Lipid solvents are required for FFPE (but not cryostat) processing and may cause glycolipid extraction. Glycoproteins are not affected. These results suggest that the UEA1 binding site is predominantly glycolipid-based in benign prostatic epithelium but, following malignant transformation, becomes predominantly glycoprotein-based.

Aged↗

Atrial natriuretic peptide production in association with nonimmune fetal hydrops.

The presence and elevation of atrial natriuretic peptide in fetuses has not previously been demonstrated. This study of right atrial pacing in fetal lambs demonstrated a threefold to fourfold increase in atrial natriuretic peptide during the production of fetal hydrops. Its rate of return to a normal level paralleled the clearance of fetal hydrops. Its possible role in fetal cardiovascular hemodynamics is discussed.

Animals↗

Dual-precipitation method evaluated for determination of high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol concentrations.

We evaluated a dual-precipitation method for determining cholesterol in high-density lipoprotein (HDL) and its subfractions HDL2 and HDL3. After total HDL was isolated by precipitation of very-low-density (VLDL) and low-density (LDL) lipoproteins with polyethylene glycol (Mr 8000), HDL2 was isolated from total HDL by precipitation with dextran sulfate (Mr 15,000), leaving HDL3 in the supernate. Concentration of total HDL cholesterol after precipitation of VLDL and LDL with PEG showed significant proportional and constant biases of -3.8% and 0.04 mmol/L, respectively, when compared with a phosphotungstic acid-based comparison method, although results by the two methods were correlated highly (r = 0.99, P less than 0.001). HDL2 and HDL3 cholesterol concentrations measured with the present technique were not different from those obtained by density-gradient ultracentrifugation or by combined precipitation-ultracentrifugation.

Centrifugation, Density Gradient↗

Effects of age, gender and female sex hormones upon contractility of the human gallbladder in vitro.

Age, gender and female sex hormones are thought to influence contractility of the gallbladder. Surgically removed gallbladders with gallstones and mild chronic cholecystitis from three groups of patients (males and premenopausal and postmenopausal females) were studied. Strips were incubated in Krebs solution, in Krebs containing 0.2 per cent ethanol-propylene glycol solvent (solvent controls) or in Krebs solution containing progesterone (0.1, 1.0 and 10.0 micromolar) or 17-beta-estradiol (0.1 and 1.0 micromolar). Concentration response curves were obtained for acetylcholine and octapeptide of cholecystokinin and the maximum contraction and median effective dose values were recorded. Steroid receptor levels in the wall of the gallbladder were also estimated. In gallbladders from males, the sensitivity to acetylcholine increased significantly with age. However, in gallbladders from premenopausal women, there was a significant decrease in sensitivity to acetylcholine and cholecystokinin with age. Progesterone (1 and 10 micromolar) reduced the spontaneous rhythmic contractions of the strips by 35 +/- 8 and 65 +/- 8 per cent, respectively, and also reduced the maximum contraction of gallbladders from postmenopausal females to acetylcholine. Estradiol-17 beta had no effect upon the contractility of the gallbladder. The results of additional studies showed that the human gallbladder is estrogen and progesterone receptor negative. The sensitivity of the gallbladder to neurohormonal stimulation varies with age and gender. These results indicate that short term exposure to female sex hormones has an inhibitory effect upon gallbladder contractility. The inhibitory effects of short term exposure to progesterone seen in this study are probably nonspecific in nature.

Acetylcholine↗

EEG effects of i.v. infusion of pentylenetetrazol in rats: a model for screening and classifying antiepileptic compounds.

In order to validate a new animal model predictive of the profile of antiepileptic drugs, we studied the antagonism by standard antiepileptics of the EEG modifications induced by low-speed IV infusion of pentylenetetrazol (PTZ) in rats. The activity of the drugs was measured by their effects on temporal characteristics of the PTZ-induced EEG paroxysms. Most compounds had moderate to potent anti-PTZ effects, as shown by the changes in the EEG temporal parameters. However, these effects depended on the drugs and doses. Cluster analysis showed that drugs and doses which evoked similar changes were closely related and were included in separate clusters with respect to one another. In particular, the present results showed that benzodiazepines and antiepileptics cluster differently in their effects. Thus, this model could be a useful tool for assessing new antiepileptic drugs.

Animals↗

The role of the carbohydrate moiety in the biologic properties of fibrinogen.

The carbohydrate moiety of some glycoproteins influences their secretion and functional properties. We have examined the importance of the oligosaccharide chains of fibrinogen in this regard. Fibrinogen was labeled de novo by the addition to rabbit hepatocyte monolayer cultures of either 3H-amino-acids or [2-3H] mannose, in the presence or absence of tunicamycin, a potent inhibitor of glycosylation. Inhibition of glycosylation, which ranged from 75 to 80%, was determined by incorporation of [2-3H]mannose as quantitated by gel filtration. Synthesis and secretion of fibrinogen were quantitated by 3H-amino-acid incorporation, using anti-fibrinogen immunoaffinity column chromatography of medium and cell homogenates. Tunicamycin did not appreciably inhibit fibrinogen synthesis, as compared to a 30-40% inhibition of overall protein synthesis, determined by incorporation of 3H-amino-acids into trichloroacetic acid-precipitable material. There was no evidence that secretion of fibrinogen was impaired. Fibrinogen from medium was copurified by adding cold plasma fibrinogen as carrier. Nonglycosylated fibrinogen was found to be functional as demonstrated by incorporation of radioactivity into clots of the copurified material at a rate identical to that of glycosylated fibrinogen. When clotted in the presence of Ca2+ and Factor XIII, cross-linking of glycosylated and nonglycosylated fibrin was demonstrable on fluorography of sodium dodecyl sulfate-polyacrylamide gels, showing disappearance of gamma-chain and appearance of gamma-gamma-dimers.

Animals↗

Variations in urinary levels of free 6 beta-hydroxycortisol, cortisol, and estrogens in late pregnancy.

The urinary excretion of 6 beta-hydroxycortisol (6 beta-OHF), free cortisol, and estriol was studied at 4-hourly intervals in 9 subjects between the 36th and 38th week of pregnancy. The ratio of 6 beta-OHF to creatinine showed a significant diurnal rhythm with a 40% fall from a peak at 06.00-10.00 h to a trough at 22.00-02.00 h. There was a significant positive correlation between the excretion of 6 beta-OHF and free cortisol. Estrogen excretion showed no diurnal variation. No increase was observed in the 6 beta-OHF:creatinine ratio in early morning urine samples from 5 subjects followed daily prior to the onset of spontaneous labour at term. Normal nonpregnant females were also found to excrete significant quantities of 6 beta-OHF. These findings suggest that the clinical significance of 6 beta-OHF levels measured in a single void sample of urine has to be reassessed in the face of such a marked diurnal variation.

Circadian Rhythm↗

Urinary cAMP and calcium excretion in the fasting state and their response to oral calcium loading in patients with calcium urolithiasis.

Fifty-two patients with idiopathic calcareous urolithiasis (ICU) were studied with an oral calcium loading test. Twenty-one subjects were normo-calciuric with no other detectable abnormalities (NDA). Of 31 patients with hypercalciuria, 16 had elevated fasting urinary calcium excretion (UCaE) (HFC), and 15 had normal UCaE (NFC). The fasting UCaE was significantly higher and the theoretical renal threshold for phosphate (TmPO4) was significantly lower in ICU patients as compared to 19 control individuals. The mean post oral calcium loading (Post Ca) UCaE rose significantly in hypercalciuric patients compared with control subjects; however, only 18/31 (58 per cent) had values above the normal range. There was no correlation between the fasting UCaE and either the immunoreactive parathyroid hormone (iPTH) or nephrogenous cAMP (ncAMP) in ICU patients. The fasting ncAMP was normal in all subjects with ICU and 7 of 52 subjects had elevated fasting iPTH values. When ranked according to the fasting UCaE value, ICU patients formed a continuum in which the NDA and HFC groups represented the extremes. It is concluded that the responses to oral Ca loading serve no useful role in the identification of an individual ICU patient either in terms of the pathogenetic subgroup or in the differentiation from normal controls.

Administration, Oral↗

[Is the benzodiazepine binding site a receptor?].

The benzodiazepines bind to high affinity sites on neuronal membranes in the central nervous system. These sites form part of a multimolecular postsynaptic complex which also includes the GABA receptor and its ionophore. The benzodiazepine binding sites appear to present a certain heterogeneity which may correspond to a diversity of functions. A good correlation exists between the pharmacological potencies of the various benzodiazepines and their affinities for the receptor in vitro, but the relationship is less clear when binding is studied in vivo. Nevertheless, high affinity benzodiazepine binding remains an essential tool for the pharmacologist in search of more specific drugs.

Animals↗

Who receives the aftercare? Utilization of services by discharged in-patients.

A prospective one-year follow-up of 216 in-patients showed that utilization of aftercare was significantly associated with certain clinical and social factors in the year after discharge from hospital. Rural domicile, a diagnosis of schizophrenia, long dependence on services, and ease of access to care comprised an aftercare dependency syndrome with substantial predictive power. Alcoholic and personality disordered patients were light users of services. Staff-patient relationships and attitudes of staff and patients to the need for aftercare were important. Depot neuroleptics were associated with high levels of aftercare for patients with chronic schizophrenia. The findings reveal the steady silting up of a new area service for the adult mentally ill by patients with a combination of social disadvantage and severe chronic psychosis. Family doctors played very little part in the delivery of aftercare. Some implications of the findings for the future development of community-based psychiatric services are discussed.

Adolescent↗