Search PubMed⌕ Search

Biomedical subjects

S Ismail

Publications and source records attributed to S Ismail.

At least 91 records · Page 5Linked to original sources

Changing concepts in the presentation, diagnosis and management of the Zollinger-Ellison syndrome.

Nine patients with the Zollinger-Ellison syndrome seen at a single referral centre between 1976 and 1981 are presented to highlight changes in the recognition, diagnosis and management of the condition. Less well recognized manifestations such as diarrhoea and features of the multiple endocrine neoplasia (MEN) type I syndrome are described, and the simplification of the pre-operative diagnosis by the use of both the serum gastrin estimation and the secretin provocation test considered. The problem of tumour localization is discussed with special reference to the newer techniques such as ultrasound, endoscopic retrograde cholangiopancreatography (ERCP) and CAT scanning, and the value of arteriography confirmed. The striking advances in management during the past few years are stressed with special reference to the role of the H2-receptor blocking drugs. Despite their profound inhibitory effect on both acid secretion and symptoms, all patients with the exception of those with proven metastases or the MEN type I syndrome underwent laparotomy to exclude a resectable lesion. If no resectable lesion was found truncal vagotomy was performed to facilitate acid secretory control post-operatively and H2-receptor blocking drugs continued in a dose necessary to maintain basal acid secretion under 5 mmol/hr.

Adolescent↗

Sgd 101/75: a sympathomimetic that can be used to identify a new subtype of alpha-adrenoceptor, the alpha 1s-adrenoceptor.

When Sgd 101/75 was compared with clonidine in a number of tests for CNS activity, Sgd 101/75 exhibited little activity in any test. Sgd 101/75 raised BP without affecting HR in several species of anaesthetised animals. The rise in BP was subject to tachyphylaxis, could be antagonised by alpha 1-adrenoceptor antagonists, and was obtainable in reserpinised animals. The vasopressor effect of NA was antagonised by Sgd 101/75. Thus Sgd 101/75 is a directly acting partial agonist for vascular alpha 1-adrenoceptors. On the coaxially stimulated guinea-pig ileum and field stimulated rat vas deferens, the twitch response to single pulse stimulation was reduced by NA or clonidine stimulating prejunctional alpha 2-adrenoceptors. Sgd 101/75 antagonised these inhibitory effects competitively (pA2 for antagonism of clonidine on the vas = 6.12). Sgd 101/75 acted as a specific partial agonist on the alpha 1-adrenoceptors of the guinea-pig taenia caecum that subserve relaxation of this tissue. Sgd 101/75 was a full agonist on the alpha 1-adrenoceptors of the rat anococcygeus in vitro. Phenoxybenzamine (300 pM for 30 min, followed by 20 washes over the next 30 min) reduced contractions of the anococcygeus to Sgd 101/75, but produced little inhibition of NA-induced contractions. In phenoxybenzamine-pretreated preparations, Sgd 101/75 (400 microM) did not antagonise NA (maximal effect and EC50 values not changed significantly), so it was concluded that Sgd 101/75 and NA interact with different alpha 1-adrenoceptor subtypes in this tissue. The subtype specifically activated by Sgd 101/75 was designated the alpha 1s-adrenoceptor. The mouse anococcygeus contained alpha 1s-adrenoceptors, whereas this receptor was absent from the rabbit anococcygeus.

Adrenergic alpha-Agonists↗

Pharmacological and toxicological studies of binodaline hydrochloride.

It has been shown, in extensive animal experiments, that 1-(omega-dimethylaminoethylmethyl)-amino-3-phenylindole hydrochloride (binodaline HCl, Sgd-Scha 1059), can be regarded as an antidepressant with novel characteristics. With anticholinergic and histamine-antagonistic effects almost completely lacking, the main effects of binodaline HCl are to increase noradrenergic influences and to produce CNS depression. The acute toxicity of binodaline HCl is comparatively low, and the good tolerance has been demonstrated in long-term studies in laboratory animals.

Animals↗

Pharmacological studies with beclobrate, a new hypolipidemic agent.

A new diphenylmethane derivative with potent hypolipidemic activity, ethyl-(+/-)-2-[[alpha-(p-chlorophenyl)-p-tolyl]-oxy]-2-methylbutyrate (Sgd 24774, beclobrate) has been investigated in animals. From a comparison of the ED25 values of beclobrate and clofibrate, the new drug is 11 times more potent with respect to its hypocholesterolemic activity and 36 times more hypotriglyceridemic in normally fed rats, and lowers fructose-induced hypertriglyceridemia in rats 20 times as effectively as does clofibrate. On a similar basis of comparison, the hepatomegalic effect of beclobrate in rats is 22 times that of clofibrate. High doses of beclobrate did not reveal any other peripheral or central effects in a wide range of pharmacological tests, indicating a high specificity of the action of the drug on blood lipids. On the basis of the results of interaction studies performed with beclobrate in animals, administration of the substance in man should be largely free from risk.

Animals↗

Response to the central and peripheral airways to cigarette smoking in human and rats.

The effects of tobacco smoke on the central nd peripheral airways were assessed in humans and rats by direct and indirect methods. In both species tobacco smoke affected the central and peripheral airways. In humans there were apparent decreases in the 1-second forced expiratory volume, peak expiratory flow rate and significant increases in closing volume and closing capacity (P less than 0.001). In rats significant changes were seen in specific airway resistance from the 6th week of exposure onwards. Similarly, airway luminal diameter decreased markedly in tobacco-exposed animals to subthreshold concentrations of acetylcholine (10(-8) M). This decrease was also exposure time dependent. The increased responsiveness of the respiratory system has been attributed to inter alia: (1) increased vagal activity; (2) increased mucus production leading to decreased airway lumen; (3) mucosal swelling due to changed ionic constellation; (4) disturbance of the lungs' defense mechanism; (5) imbalance in and easy accessibility to the adrenoceptors.

Adult↗

Bronchomotor tone in protein-energy malnutrition.

The study examined the reactivity of the tracheobronchial tree of rats maintained on low protein and tryptophan-deficient diets. It was found that: (1) Rats maintained on 5% protein or tryptophan-deficient diets showed little or no weight gain. A 15% protein diet was adequate for normal growth of female rats, but not of male rats. (2) Airways of malnourished rats showed significant bronchoconstriction when treated to an acetylcholine (AcCh) concentration of 10(-11) M. The threshold concentration of AcCh for normal rats was 10(-5) M. Airways of malnourished rats were also more sensitive to cold. (3) Rehabilitation of the malnourished rats attenuated the response to AcCh. Recovery, however, was not complete. (4) Prior application of phentolamine and atropine markedly reduced the sensitivity of the airways of malnourished rats to AcCh. The results seem to indicate that alpha-adrenoceptors and the vagus nerve may be involved in the observed increased reactivity of airways of malnourished rats.

Acetylcholine↗

Tracheobronchial function in health and disease. Effect of mucolytic substances.

The effect of mucolytic and expectorant substances on ciliary beat frequency, mucus transport velocity and mucus production, was investigated in normal and bronchitic rats. The results showed that: (i) N-acetylcysteine and S-carboxymethylcysteine were mildly cilioexcitatory at low and ciliodepressive at higher concentrations in both normal and bronchitic rats. A similar pattern was seen in mucus transport velocity. (ii) Bisolvon enhanced all aspects of mucociliary activity in both groups of animals. Sobrepin was less effective than Bisolvon and more effective than Tachoquilin. (iii) Geleomyrtol, Ozothin and prostaglandin E1 were all cilioexcitatory in rats with bronchitis. Mucus transport velocity was similarly stimulated by both Geleomyrtol and Ozothin. (iv) Ammonium chloride and potassium iodide enhanced mucociliary activity in normal and bronchitic rats. (v) All substances stimulated mucus production, however, the most potent was prostaglandin E1. The mechanisms for increased mucociliary activity involve inter alia the probable cleaving of disulfide bridges, decreased mucosal swelling, altered rheological characteristics and stimulation of adenylate cyclase.

Animals↗

Direct determination of luminal diameter changes in intrapulmonary airways.

A method is described for the direct measurement of changes in luminal diameter at all levels of the airway. Using this method it was found that (i) abrupt bronchiolar collapse occurred in the preterminal and terminal bronchioles once the luminal diameter was reduced to a critical level: (ii) decreased temperatures resulted in airway narrowing which was reversed by increasing the temperature to above 25 degrees C; as a rule, airway narrowing followed a cranial to caudal direction, and higher concentration of a drug being required to close the peripheral airways; (iii) bronchodilators except Carbuterol had no effect on resting bronchial tone or on acetylcholine-induced constriction in the absence of alpha-adrenoceptor blockade; (iv) at 35 degrees C rhythmic waves (frequency 6--20/min) were observed; these waves travelled from the periphery in a cranial direction.

Action Potentials↗

Lactate dehydrogenase and transaminase activities in the cerebrospinal fluid of protein-energy malnourished children.

The present study is aiming to assess whether there are variations in the activities of the enzymes glutamic-oxalacetic transaminase (GOT) and lactate dehydrogenase (LDH) in the cerebrospinal fluid (CSF) of children suffering from protein-energy malnutrition (PEM). In this respect, serum and CSF activities of GOT and LDH were assayed in thirteen cases suffering from kwashiorkor and ten normal cases serving as controls. Increased activities of both enzymes in sera and CSF of PEM children compared with normals were observed. The significance of these variations was discussed.

Child↗

Studies of tryptophan metabolism in protein-energy malnutrition (PEM).

Studies on tryptophan metabolism in PEM were performed. In this respect, the basal excretion of tryptophan and some of its metabolites, namely, kynurenine, 3 OH-anthranilic, anthramilic, indol-3-acetic, 5 OH-indol acetic and xanthurenic acids were determined. The response of these metabolites to oral tryptophan load, singly and in combination, with pyridoxine, were performed in kwashiorkor cases compared to normal controls. The study revealed that kynurenine leads to niacine pathway is hindered, Indole-3-acetic acid levels are lower and respond poorly to tryptophan loading in PEM. Increased levels of 5 OH-indol acetic were found in kwashiorkor compared to marasmus, although lower response to tryptophan was noted. Xanthurenic acid excretion is much higher in PEM and poorly responds to tryptophan load either singly or in combination with pyridoxine. These errors of tryptophan metabolism in PEM are suggested to be due to defects in the enzyme systems involved rather than to vitamin B6 deficiency.

Child, Preschool↗