Synthesis,physical properties and microbiological activities of more water soluble silver sulfadiazine derivatives

In this study the preparation of five hydrophilic derivatives of sulfadiazine is reported. The common structural element in the compounds is the 2-sulfonamidopyrimidine moiety. Three of these compounds are suitable for the preparation of a photostable 1∶1 silver compound. These silver compounds are five to ten times more water soluble than silver sulfadiazine. TheIr,¹H- and¹³C-Nmr data point to a similar co-ordination of silver in these compounds as with silver sulfadiazine. The microbiological activity of these silver compounds againstSt. aureus is slightly lower.     

Sequential changes in plasma renin activity and plasma catecholamines in mildly hypertensive patients during acute,furosemide-induced body-fluid loss

Summary To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension. Furosemide induced a prompt and long-lasting increase in renin, with PRA more than doubled at all times. The increase in PRA within the first 30 min paralleled the peak increases in urinary water and sodium flow rates, and significant decreases in plasma volume and central venous pressure. There was no change in plasma catecholamine concentrations. Plasma noradrenaline was increased significantly at 60 min and adrenaline at 90 min, once furosemide had induced a marked loss of body-fluid and 65% decrease in central venous pressure. Both catecholamines remained elevated until the end of the study, whereas urinary water and sodium flow rates had returned to their pre-treatment values by 150 min. Mean blood pressure was essentially unchanged throughout the study, whereas heart rate increased significantly after 90 min. The findings suggest that in mildly hypertensive patients adrenergic mechanisms are not involved in the initial renin response to furosemide, but they come into play later, probably as a result of reflex sympathetic activation triggered by marked volume depletion.     

A device to select the optimal time to replace the pacemaker activated by a lithium-iodine battery: results of 8 years of experience

The discharge curve of lithium-iodine batteries does not havefeatures which make the clinical decision to replace the pacemakereasy. The output voltage fall corresponding to the end of theirlife is evidenced by variations of the output variables (frequencyand/or length of pulse) and the time of elective replacementtime (ER) is arbitrarily established by the manufacturer, ERmay be too early or too late in relation to the threshold valueof myocardial stimulation. Furthermore, the variables indicatingend of life may be changed by troubles in the circuit components,irrespective of the state of battery. A device to detect theoptimal time for replacement (OR) of pacemaker was studied in1692 subjects with implanted LEM VVl electro-stimulators. Thisdevice consists of a resistance of 110 connected in serieswith the catheter through a magnetic switch, which is activatedby placing a magnet over the skin. The transient connectionof the resistor reduces the output voltage by an amount dependingon the resistive load between the electrodes. In a follow-up of 35 000 months the OR device revealed a verygood reliability. Pacemaker replacement, established when stimulation becomesineffective during the application of the magnet or when thespike amplitude in the standard oscilloscope rapidly declined,was necessary in 77 patients (six of them were excluded dueto a circuit blackout). The OR device was useful in 53 patients(74.6%) with a chronic myocardial threshold of more than 2.5V, useless in 18 patients with a myocardial threshold lowerthan 2.5 V; to obviate this limitation a new OR device is describedfeigning a temporary increment of battery impedance. The employmentof the OR device rather than using ER enabled the patients togain 1333 months of stimulation. The gain of pacing varied froma few months to 3 years, with an average of 18.7 months.     

Preliminary experiences with "real-time" intraoperative ultrasonography associated to the laser and the ultrasonic aspirator in neurosurgery

Twelve cerebral lesions were operated upon with various laser sources (carbon dioxide, neodymium-yttrium-argon-garnet, and argon) and with an ultrasonic aspirator utilizing the intraoperative "real-time" ultrasonography. With the last method, the tumor was imaged just as well through the intact dura mater as on the brain surface itself, allowing a precise localization of deep intracranial lesions. A sharp selectivity on the healthy tissues is, in this way, achievable to reach the tumor, which is successively removed with the laser and ultrasonic aspirator checking the surgical maneuvers on the visual control of the ultrasonograph.     

Long-term treatment with Pilogel/β-blocker in glaucoma patients

In a multicentre clinical trial thirteen patients with primary open angle glaucoma or ocular hypertension were followed during at least six months while selfinstilling Pilogel (once daily) and topical -blocker (twice daily). After six months of combination therapy there was an average decrease in intra-ocular pressure (IOP) of 33.6% 9.5 hours after Pilogel administration and an IOP decrease of 23.4% 22.5 hours after Pilogel administration. With topical -blocker alone, an average IOP decrease of 15% was measured. Throughout the study we observed in six patients (46.1%) a superficial punctate keratitis which mostly spontaneously cleared. We did not see any serious side-effects after six months of combination therapy.     

Effects of the enantiomers of disopyramide and its major metabolite on the electrophysiological characteristics of the guinea-pig papillary muscle

Summary Disopyramide, a Class la antiarrhythmic drug, is clinically used as a racemic mixture; R(–)disopyramide and S(+)disopyramide. The major metabolite in man is desisopropyldisopyramide: R(–)desisopropyl-disopyramide and S(+)desisopropyldisopyramide. The effects of the four compounds were compared on the electrophysiological characteristics of the guinea-pig papillary muscle using the standard microelectrode technique. At an external K⁺ concentration of 5.4 mmol/l and a stimulation frequency of 1 Hz, S(+)disopyramide (20 mol/l) increased action potential duration (APD) by more than 18%, while it was diminished by 6% in the presence of R(–)disopyramide. Resting membrane potential amounted to –87.1 ± 0.5 mV (n = 14) and –85.6 ± 1.2 mV (n = 10), respectively. Also a small but significant difference in effect on the maximal rate of depolarization was observed, R(–)disopyramide being more potent, related with a slower recovery of the maximal rate of depolarization.The enantiomers of the metabolite appeared to be three times less potent than those of the parent drug in their effect on the maximal rate of depolarization. The characteristics of the enantiomers of the metabolite correlated with those of the parent drug: also the R(–)-enantiomer was more potent in decreasing the maximal rate of depolarization and caused more shortening of the action potential than the S(+)enantiomer.Time constants for onset and recovery of/from rate dependent block of the maximal rate of depolarization were dependent upon the external K⁺ concentration, both for the enantiomers of the parent drug and those of the metabolite. Onset slowed down while recovery accelerated when external K⁺ was increased. Time constants were lower for the metabolite.When stimulation interval was shortened, the effect on the maximal rate of depolarisation increased. Only for the metabolite statistical significant stereoselective differences were observed at all stimulation intervals. The effects on the action potential duration were dependent upon stimulation interval; for all enantiomers the action potential duration tended to be relatively (% of control) higher at short stimulation intervals than at large stimulation intervals. The effect on the maximal rate of depolarization was also voltage dependent, but no significant differences were observed between the enantiomers, for the parent drug as well as for the metabolite. Send offprint requests to N. Verbeke at the above address     

Rectal Mucosa Damage in Rabbits After Subchronical Application of Suppository Bases

The effect of suppository bases on rabbit rectal mucosa was investigated using six triglyceride bases, polyethylene glycol, and a triglyceride base combined with monoglycerides or fatty acids and methyl esters of those acids. Rectal irritation was evaluated and scored according to defined pathological features. Pure triglycerides and a triglyceride to which a nonionic surfactant was added caused severe mucosal damage with ulceration and inflammation. Hyperemia was characteristic for irritation by polyethylene glycol suppositories. Mucosal damage by a pure triglyceride combined with monoglycerides or fatty acids and methyl esters of those acids was similar but statistically less pronounced than with all other bases.     

Risk factors for cancer of the tongue in Uruguay

From 1987 to 1989, a hospital-based case-control study of cancer of the tongue was conducted in Montevideo, Uruguay, as part of a large study to investigate a number of risk factors for cancer of the oral cavity, pharynx, and larynx. The study involved interviews with 57 cases and 353 controls and was restricted to men. Relative risks (RR) associated with tobacco smoking, alcohol drinking, and selected dietary items were obtained by unconditional logistic-regression analysis. Users of black tobacco had a RR fourfold higher than users of blond tobacco, and heavy drinkers of alcohol had a RR of 11.6. Infrequent consumption of vegetables was associated with a significant RR of 5.3, and heavy drinkers of the local infusion "mate" had a RR of 2.5. It was concluded that black tobacco smoking and alcohol drinking were the strongest risk factors for cancer of the tongue in Uruguay. Their effects combine according to a multiplicative model. Also, infrequent vegetable intake and mate ingestion contribute to the risk of cancer of the tongue.     

Plasma insulin-like growth factor-I determinations in patients with cystic fibrosis: Influence of the nutritional and liver status

Insulin-like growth factor-1 (Igf1), a useful and early marker of undernutrition in inflammatory diseases, is dependent on the calorie and protein content of the diet. In 31 children and adolescents with cystic fibrosis (CF), a chronic inflammatory disease, the influence of the degree of liver dysfunction and the protein and calorie content of the diet on the circulating Igf1 was evaluated. No significant difference in the median plasma Igf1 concentration, measured by RIA, between the CF children (0.80 U/ml) and a for age and puberty matched control group (0.61 U/ml) was found. Expressing the Igf1 concentration as a percentage of normal for age, gave for the CF patients with liver involvement a lower level (median: 76%) than in those without (median: 101%). No correlation existed between the circulating Igf1 levels and the body height SDS, the body weight index and the calorie or protein intake of the patients.     

Assessment of quality of life in the elderly assisted at home through a Tele-Check service

This study evaluates the effects of a Tele-check/Tele-emergency service on the quality of life in the elderly. Through telephone interviews a questionnaire has been repeatedly administered to explore various psychological, somatic, and social aspects in a random sample of 574 subjects aged 65 years and over (mean = 76.8 years). The findings suggest that the elderly helped by the service (in its control functioning) make less demands on health facilities (GPs visits, number of days in hospital) as compared to controls. Implications are presented and discussed.