Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.     

Theoretical QSAR study on carcinogenic potency of N-nitrosamines

A mechanistic QSAR study on N-nitrosamines (NA) was performed with the aid of the semiempirical MINDO/3 method. Both the chemical reactivity and the transport in biological medium were taken into account. The parent NA molecules and their first reaction intermediates in the metabolic activation pathway were examined for possible determinants of the relative carcinogenic potency. The correlations found support the previous suggestions concerning the metabolic C alpha radical hydroxylation of NA. The role of transport properties in the early stage of NA biotransformation was also demonstrated.     

Pulmonary valve insertion during reoperation for tetralogy of Fallot

Our experience with pulmonary valve insertion during reoperation for residual lesions after initial open repair of tetralogy of Fallot in 15 patients is reported. Preoperatively, 14 patients were in moderate to severe congestive heart failure, and all 15 had decreased right ventricular (RV) function at cardiac catheterization. All 15 patients had pulmonary insufficiency but not as an isolated finding. The most common residual lesions encountered were ventricular septal defect in 9, tricuspid insufficiency in 11, and peripheral pulmonary arterial stenosis in 6. Tissue valves were inserted in all patients. Mean peak RV-left ventricular pressure ratio measured in the operating room decreased from 0.61 +/- 0.10 (+/- the standard deviation) to 0.47 +/- 0.17 (p less than 0.05). There were no operative deaths. At follow-up (mean, 33 months), all but 1 patient were in New York Heart Association Class I or II. Pulmonary valve insertion should be considered during reoperation for tetralogy of Fallot when pulmonary insufficiency and RV failure are present.     

Operative treatment of median cervical cysts

Median cervical cysts are congenital anomalies arising from remaining thyroglossal duct epithelium. A major problem in the surgical treatment of these cysts is the high frequency of recurrence. Embryonic considerations indicate an important causal role for the hyoid bone in these recurrences. We studied the relationship between operative techniques and the number of recurrences in 36 patients treated in our hospital. Fourteen patients sent from other hospitals had a recurrent fistula; in thirteen cases the hyoid bone was still in place. All patients who had the central part of the hyoid bone excised were cured. In 14 patients without adequate excisions of the hyoid bone we found four recurrences. To prevent recurrence a total excision of thyroglossal duct epithelium is necessary.     

The value of sonography in the diagnosis and follow-up of patients with blunt renal trauma

Eighty-eight patients with blunt renal trauma were examined sonographically. Rupture of the kidney was diagnosed in 41 patients and contusion of the kidney in 45. The correlation between operative findings, sonography and urography showed positive sonographic findings to be correct in all patients with rupture of the kidney. In 4 patients with normal sonograms, the diagnosis of a contusion was based on the urographic results. Three patients underwent angiography. An intimal lesion was seen in 2 and a tear of the renal artery in 1. The results of our investigation suggest that sonography should be applied in the first place in the evaluation of blunt renal trauma. It is the investigation of choice during follow-up after surgical as well as conservative therapy.     

Significance of lung contusion in mortality following polytrauma. Possibilities for therapeutic influence

Multiple trauma is often associated with blunt thoracic injuries. Especially lung contusion can result in respiratory insufficiency and therefore a higher mortality rate. In our prospective study comparing 8 multiple trauma patients with and without associated lung contusion, we found that respiratory function was already significantly disturbed (decrease of paO2/FiO2 and increase of AaDO2, a rise in extravascular lung water (EVLW) both early after trauma and also with a second peak following the 4th day. This group (LK) developed significantly more cases of respiratory distress (ARDS). The disturbance of respiratory function seen initially was interpreted as a consequence of the direct mechanical impact, leading to the formation of interstitial fluid and hematoma. The frequent development of ARDS in the LK-group probably results from a pronounced activation of cellular and humoral mechanisms and therefore an enforced injury of the pulmonary capillary bed. A significant increase of pulmonary infections or the development of sepsis was not seen in the LK-group and is probably not responsible for the higher ARDS-rate in this group.     

Effect of diffusion chamber pore size on differentiation and proliferation of periosteal cells. An experimental study

The influence of the pore size of Nucleopore diffusion-chamber filters on the rate of proliferation and differentiation of periosteal cells in muscle was studied in 44 growing rabbits. Periosteal grafts were placed in chambers (16-19 in each experimental group) sealed with filters with a pore size of 0.4, 0.6, 0.8, 1.0, or 2.0 micron. Each chamber was implanted into the paraspinal muscle of the rabbit, where it remained for 16 weeks. The osteochondrogenic activity of the graft grew linearly when the pore size increased from 0.4 to 1.0 micron. In the chambers with a pore size of 2.0 micron, both bone and cartilage were found in only one chamber. Bone and cartilage were not found outside any of the chambers. The present results showed that the pore size of the filters significantly affected the ability of the periosteal graft to form bone and cartilage.     

The effects of bulk versus particulate polymethylmethacrylate on bone

Twenty-one mature New Zealand white female rabbits were allocated into three groups of seven rabbits. Group I received a bolus of doughy Simplex polymethylmethacrylate (PMMA) cement injected into the proximal tibia through a drill hole. Group II received a preformed, cooled, bulk PMMA pellet. Group III had particulate PMMA powder implanted. The operated, but nonimplanted, left tibiae served as controls. Animals were killed after four months. Histologically, both Group I and Group II demonstrated a thin, fibrous tissue membrane at the implant interface. Particulate PMMA (Group III) stimulated a much thicker, florid, foreign body reaction composed of histiocytes and giant cells. The foreign body response to particulate acrylic cement was similar to that seen in failed cemented joint replacement arthroplasty in humans.