REINVESTING HOSPITAL WASTE – A MASTER PLAN FOR DEVELOPMENT OF PATIENTS

It is a general observation that hospital stay is dull and boring. It is mainly because the patients remain unoccupied. Their time is wasted. It is more so in service hospitals where apparently trivial cases are admitted for prolonged periods. A development programme for the patients by reinvesting their own wasted seconds may generate revolutionary progress in patient care.KEY WORDS: Managing patients'' time, Patients development programme     

Pharmacodynamic and Pharmacokinetic Studies in Rats of S-8-(2-Furyl)- and R-8-Phenyl-2-(di-n-Propylamino)Tetralin,Two Novel 5-HT1A Receptor Agonists In-vitro with Different Properties In-vivo

R- and S-8-(2-Furyl)- and R- and S-8-phenyl-2-(di-n-propylamino)tetralins (R- and S-LY-55 and R- and S-LY-49, respectively), novel enantiopure dipropylaminotetralins, have been screened as 5-HT_1A receptor ligands. All had nanomolar affinities for 5-HT_1A receptors and fully inhibited forskolin-stimulated adenylyl cyclase in-vitro (i.e. the four compounds appeared to be 5-HT_1A agonists). It was also found that the enantiomers of LY-55 behaved as typical 5-HT_1A receptor agonists in rats in-vivo by inducing a typical behavioural 5-HT syndrome, hypothermia and a decrease in 5-HT synthesis and turnover, indicating effects both on postsynaptic 5-HT_1A receptors and somatodendritic 5-HT_1A autoreceptors. In contrast, R- and S-LY-49 did not cause any 5-HT_1A receptor-related effects in-vivo except for a partial inhibition of 5-HT synthesis after high doses. The 5-HT_1A receptor antagonist WAY-100635 was shown to attenuate the R-LY-49-induced inhibition of 5-HT synthesis, indicating the compound to be a weak agonist at somatodendritic 5-HT_1A autoreceptors. R-LY-49 at a high dose and with a long pre-treatment time interval inhibited the hypothermic and behavioural effects, but not the inhibition of 5-HT synthesis induced by the 5-HT_1A receptor agonist R-8-hydroxy-(dipropylamino)tetralin (R-8-OH-DPAT). Taken together, these findings seem to indicate, that R-LY-49 is a weak partial agonist at 5-HT_1A receptors. A comparative pharmacokinetic study showed that the enantiomers of LY-55 entered the brain rapidly after subcutaneous administration and reached peak brain tissue/plasma concentration ratios within 15–30 min of injection, whereas the brain concentrations of R-LY-49 increased slowly, reaching a relatively low peak brain tissue/plasma concentration ratio 90 min after injection despite their similar lipophilicity. The differences between the pharmacological activity of the two compounds in-vivo seem to be explained by their different abilities to cross the blood-brain barrier, and a weak agonistic activity of R-LY-49 on 5-HT_1A receptors, both pre- and postsynaptically, compared with S-LY-55. Further studies are, however, needed for a deeper understanding of these differences.     

Acute antiischaemic properties of high dosages of intravenous diltiazem in humans in relation to its coronary and systemic haemodynamic effects

The antiischaemic properties of intravenous diltiazem in recommendedtherapeutic doses are disputed. In 17 patients with coronaryartery disease the systemic and coronary haemodynamic effectsof diltiazem were assessed during a high-dose infusion (0.4mg kg^-1 per 5 min. followed by 0.4 mg kg^-1 per 10 min). In addition,its potential antiischaemic properties were investigated duringidentical pacing stress tests. 30 minutes before (P₁) and immediatelyafter diltiazem administration (P₂). Diltiazem reduced leftventricular systolic pressure from 133±5 to 116±5mmHg (P<0.005, ±SEM). persisting until after P₂. Itdecreased systemic and coronary resistance by 32% (P<0.001)and 29% (P<0.005), respectively, with a sustained increasein cardiac output from 5.9±0.4 to 7.3±0.61 min^-1(P<0.01), but a brief 20% rise in coronary flow (P<0.05),after the bolus infusion only. Heart rate, contractility, leftventricular filling pressure and myocardial O₂ consumption remainedunchanged. Despite high plasma levels (673±81 µgl^–1)diltiazem was well tolerated. During identical maximal pacingrates diltiazem considerably reduced myocardial O₂ demand (doubleproduct: 16.3±0.8 (P₂) vs 21.1±1.1 (P₁), P<0.005),due to an 18% decrease in left ventricular systolic pressure,resulting in diminished coronary flow and myocardial O₂ consumptionduring P₂ (14% and 15%, respectively, P<0.05 vs P₁). Diltiazemalso significantly reduced pacing-induced ischaemia, indicatedby normalization of myocardial lactate extraction (1±8%(P₂) vs –41±12% (P₁), P<0.05), and left ventricularfilling pressure (13±2 (P₂ vs 27±3 mmHg (P₁),P<0.01). less ST-segment depression (0.12±0.01 (P₂)vs 0.24±0.02 mV (P₁), P<0.01) and improved contractility(V_max 59±5 (P₂) vs 48±3 s^-1 (P₁), P<0.05).Angina was absent or less in 15 patients during pacing afterdiltiazem. Thus, diltiazem, in high dosages, induces continuingsystemic but short lasting coronary vasodilation, improves pumpfunction without negative chronotropic and inotropic effectsand has pronounced antiischaemic properties, predominantly dueto diminished myocardial O₂ demand.     

COURSE OF RENAL FUNCTION IN IgA GLOMERULONEPHRITIS IN CHILDREN AND ADOLESCENTS

ABSTRACT. The pathophysiology of IgA GN was investigated in different stages of the disease. Seventeen patients who were between 3.5 and 16.5 years of age at the onset were included in the study. Clearance studies were performed repeatedly in 6 patients (in 5 of them over a period extending from the onset to 5-9.5 years) and only once in 9 patients (10-23 years after the onset). Two patients (one with uremia) were only evaluated clinically. C_In, C_PAH and U_NaV were studied during hydropenia (HP) and 3% isotonic saline volume expansion (VE). Shortly after the onset C_In, C_PAH and U_NaV were depressed. Renal function was essentially normal 1 and 2 years after the onset in spite of signs of active disease. A supernormal GFR was found in 7 patients after they had had the condition between 5 and 17 years. After a duration of IgA GN for >9 years 3 of 12 patients had developed hypertension and uremia and 2 had hypertension or labile BP. Three of 10 patients had a normal GFR and BP, but had increased natriuresis during VE. Only 2 of 10 patients were normotensive and had normal renal function. Disturbancies in the renal function are thus frequent in all stages of IgA GN and the changes seem to be related to the duration of the disease. Exaggerated natriuresis may indicate progressive disease.     

Lingual Infarction and Sudden Blindness Due to Giant Cell Arteritis

ABSTRACT. A 72-year-old woman suffered from giant cell arteritis (GCA) which developed into lingual infarction and monocular blindness. Temporary obscuration of vision and lingual symptoms such as increasing malaise, pain and intermittent claudication may precede the catastrophic results of arteritis. Emphasis is laid on early recognition and treatment of GCA.     

Propafenone versus Disopyramide for Treatment of Chronic Symptomatic Ventricular Arrhythmias

ABSTRACT The efficacy and safety of propafenone, 150 mg four times daily, were compared with those of disopyramide, 100 mg four times daily, in a randomized single-blind, cross-over study in 38 patients with symptomatic premature ventricular complexes (PVCs). The 24-hour ambulatory ECG, employed for assessing antiarrhythmic efficacy, was analyzed blindly. The median reduction in the number of PVCs was higher with propafenone than with disopyramide (91.4% vs. 63.5%, respectively, p<0.01). A reduction of at least 80% was achieved by propafenone in 22 (59%) and by disopyramide in 16 patients (43%) (NS). Ventricular tachycardias (VTs) were abolished by propafenone in eight out of 11, and by disopyramide in five out of nine patients with VTs (NS) A possible proarrhythmic effect was seen in three patients during disopyramide and in one patient during propafenone treatment. Micturition disturbances (p<0.001) and a dry mouth (p<0.01) were more commonly associated with disopyramide than with propafenone. In conclusion, in the given dosages, propafenone was superior to disopyramide in suppressing PVCs and had fewer side-effects.     

Diabetes Mellitus and Intermittent Claudication: Relation between Peripheral Vascular Complications and Location of the Occlusive Atherosclerosis in the Legs

ABSTRACT. Forty-seven diabetic patients with intermittent claudication without rest pain or gangrene at the initial examination were followed up over a six-year period. They were compared with 224 non-diabetic patients with intermittent claudication. The cumulative proportions of patients with gangrene were 31 % in the diabetic group and 5% in the control group (p < 0.001). The corresponding figures for rest pain and/or gangrene were 40 and 18%, respectively (p < 0.001). The frequency of aorto-iliac and multiple stenoses was higher among diabetic patients who developed peripheral vascular complications (rest pain, gangrene) than in the control group. The frequency of multiple stenoses was also higher in the former subgroup than in diabetics without such complications. In conclusion, the degree of involvement of the large vessels in occlusive arterial disease influences the risk of development of peripheral vascular complications in diabetic patients with intermittent claudication.