Transplacental isopropanol exposure: case report and review of metabolic principles.

Isopropanol, a known central nervous system depressant has been reported to cause toxicity via multiple routes including ingestion, inhalation and dermal exposure. We present a case of transplacental isopropanol exposure in a neonate. A woman reported polysubstance abuse in the 1 to 2 days before precipitously delivering a newborn infant. The neonate developed hypotension, hypotonia and seizure activity within the first few hours of life. Blood samples from the infant revealed toxic levels of isopropanol. Similar symptoms have been reported in infants with isopropanol toxicity from other routes of exposure.

RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist.

The 5-HT2C receptor is one of three closely related receptor subtypes in the 5-HT2 receptor family. 5-HT2A and 5-HT2B selective antagonists have been described. However, no 5-HT2C selective antagonists have yet been disclosed. As part of an effort to further explore the function of 5-HT2C receptors, we have developed a selective 5-HT2C receptor antagonist, RS-102221 (a benzenesulfonamide of 8-[5-(5-amino-2,4-dimethoxyphenyl) 5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione). This compound exhibited nanomolar affinity for human (pKi = 8.4) and rat (pKi = 8.5) 5-HT2C receptors. The compound also demonstrated nearly 100-fold selectivity for the 5-HT2C receptor as compared to the 5-HT2A and 5-HT2B receptors. RS-102221 acted as an antagonist in a cell-based microphysiometry functional assay (pA2 = 8.1) and had no detectable intrinsic efficacy. Consistent with its action as a 5-HT2C receptor antagonist, daily dosing with RS-102221 (2 mg/kg intraperitoneal) increased food-intake and weight-gain in rats. Surprisingly, RS-102221 failed to reverse the hypolocomotion induced by the 5-HT2 receptor agonist 1-(3-chlorophenyl)piperazine (m-CPP). It is concluded that RS-102221 is the first selective, high affinity 5-HT2C receptor antagonist to be described.

A double-blind comparative study of prophylactic antibiotic therapy in open heart surgery: penicillin G versus vancomycin.

A double-blind clinical study was carried out comparing the prophylactic effectivity of penicillin G with vancomycin in 113 adult patients undergoing open heart surgery. Eighty of these underwent valve replacement. A total of 14 of 52 penicillin-treated patients (26.9%) and 5 of 61 vancomycin-treated patients (8.2%) suffered from postoperative infection (0.005 less than p less than 0.02). Five patients in the penicillin group and none in the vancomycin group developed postoperative wound infection (0.01 less than p less than 0.02). No significant differences in blood culture and sepsis, tracheal culture and clinical respiratory tract infection, urine culture and clinical urinary tract infection, and colonization rate were found between the 2 groups. No cases of prosthetic valve endocarditis were diagnosed. Bacteriologic culture and resistance studies did not reveal significant changes concerning the resistance patterns; in particular, the emergence of a vancomycin-resistant strain of Staphylococcus albus was not seen. A decrease in the colonization rate with Staphylococcus albus from 53% in 1975 to 1977 to 34.6% and 31.1% in the penicillin and vancomycin groups, respectively, was found in the following 2 years.

Surgical treatment of bacterial endocarditis.

Valve replacement was performed during a 7-year period in 27 patients with acute or subacute infective endocarditis. Twenty-three patients had single valve affection--16 aortic and 7 mitral--and 4 patients had affection of both the aortic and mitral valves. Eight of the patients with aortic valve lesion had congenital aortic valve stenosis and 2 of the mitral patients had mitral prolapse. Two patients were operated upon only on the echocardiographic finding of valvular vegetations. The rest of the patients were operated because of cardiac insufficiency, intractable infection or peripheral embolization. Five patients died and 22 patients (82%) were discharged. One of these patients died in the follow-up period. The remaining 21 patients all belong to class I or II (NYHA) postoperatively. There were no cases of reinfection. Emphasis is placed on the use of echocardiography in detecting valvular vegetations, and the need to take the proper surgical action as a result of this finding, even in asymptomatic patients.

Results of surgical treatment of arterial embolism.

A report is given of the results obtained by surgical intervention in 260 patients with arterial embolism involving the extremities, in whom a total of 299 emboli devloped. Excellent results were obtained in 63.5% of the cases. It is emphasized that embolectomy is indicated in all cases, irrespective of the interval between onset of symptoms and surgery, unless gangrene of the limb is manifest. Furthermore, re-operation is is recommended on patients in whom fresh clots develop in the artery after an otherwise successful embolectomy. The mortality rate proved to be relatively high (28%) and the causes thereof are discussed.

Lung function and morphology after hemorrhagic shock, soft tissue trauma and regional ischemia in dogs.

Among 40 dogs submitted to 1 of 3 experimental shock procedures: hemorrhagic shock, soft tissue trauma or regional ischemia, 24 dogs fulfilled the criteria of irreversible shock, based on survival or characteristic hemodynamic and metabolic changes. The 24 dogs were studied by measurements of lung function and hemodynamics. During the shock period no impairment of lung function was observed. The pulmonary shunting ratio fell and pulmonary vascular resistance increased. The macroscopical aspect of the lungs did not differ from that of 10 control dogs. The microscopical examination of the lungs, performed after infusion fixation, revealed only a higher granulocyte infiltration in traumatic shock and more severe congestion in hemorrhagic shock.

Cardiopulmonary function during and after prolonged extracorporeal circulation with membrane oxygenators in dogs.

Prolonged veno-arterial partial extracorporeal circulation using membrane oxygenator was performed in 19 alert dogs. Investigations of alterations in the corpuscular elements of the blood during the perfusion showed 89 mg% as the highest value of free haemoglobin. A significant decrease in the platelet count during the first two hours of bypass to a value of about 100 000/mm3 was found. Measurements of lung and heart functions did not reveal any significant differences between the baseline values and those obtained after 24 hours' bypass and again after three months' observation. Microscopic examination of the lungs and hearts only showed moderate focal alveolar oedema in the dogs killed immediately after 24 hours' bypass. These alterations could be explained as a consequence of the extracorporeal circulation. No changes were found at the microscopic examination of the lungs and hearts three months later. By haemodilution technique, the dogs suffered from severe universal oedema after a few hours of bypass and the perfusion time in these experiments did not exceed 13 hours. The observation that 24 hours of partial veno-arterial bypass using membrane oxygenators in healthy dogs causes only minor changes in heart and lung function and in lung histology might explain the possibility of using such oxygenators in prolonged perfusions.

Cardioplegic cardiac arrest in aortic surgery.

Cardioplegia according to Bretschneider is able to protect the myocardium during long periods of cardiac arrest and a quiet relaxed heart has in many cases of congenital heart disease been of great surgical advantage. In the last 100 consecutive aortic valve replacements in cardioplegic arrest we have lost 6 patients and none of the deaths seems to be related to the method. In our hands it has been superior to coronary perfusion.

Hemorrhagic shock in dogs without major pulmonary changes.

Dogs were submitted to one of three hemorrhagic shock procedures: normovolemic shock, oligemic hypotension or posthemorrhagic hypotension. 13 animals fulfilled well-filled criteria of irreversible hemorrhagic shock, based on mortality, take-up volume and metabolic changes. Lung function was measured at regular intervals. Lungs were fixed by infusion fixation. The macroscopial aspect of the lungs was not different from that of six control dogs which were anesthetized for the same period. Minor microscopical changes were found, but the only histological parameter which was significantly different from the controls was accumulation of granulocytes. Gas exchange remained normal, ventilation was increased with an enlarged dead space and veno-arterial shunting was reduced. Pulmonary vascular resistance was not different from the control group.