Captopril protects against myocardial injury induced by magnesium deficiency.

We have previously reported that antioxidant drug intervention protects against magnesium deficiency-induced myocardial lesions. In the present study, Golden Syrian male hamsters were fed either a magnesium-deficient diet or a magnesium-supplemented diet. Animals from each group received sulfhydryl-containing angiotensin converting enzyme inhibitors: captopril, epi-captopril (a stereoisomer of captopril), and zofenopril* (arginine blend of zofenopril containing a free SH group); another group of animals received the non-sulfhydryl-containing angiotensin converting enzyme inhibitor enalaprilat. The animals were killed after 14 days, and their hearts were isolated for morphological and morphometric analyses. Hematoxylin and eosin-stained sections were examined by a computer image analysis system for a morphometric determination of the severity of myocardial injury. Captopril reduced both the density of lesions, from 0.32 to 0.08 lesions/(mm2) (p less than 0.01), and the area fraction of lesions, from 7.42 x 10(-4) to 2.03 x 10(-4) lesion area/(mm2) (p less than 0.01), as well as the degree of inflammatory infiltration around the blood vessels. Epi-captopril and zofenopril* were virtually equipotent to captopril, but enalaprilat afforded only slight (nonsignificant) protection. These results indicate that a significant component of the protective effect of captopril in this model was attributable to its sulfhydryl moiety, rather than solely due to the inhibition of the angiotensin converting enzyme. These data further support our previous findings of possible free radical participation in cardiomyopathy due to magnesium deficiency.

Short-term effects of naltrexone in 155 heroin ex-addicts.

The narcotic antagonist naltrexone was administered for periods of up to 8 months to a total of 155 patients at a dose of 40-200 mg per day. The antagonistic effect of naltrexone was tested by injections of heroin. Eighty milligrams of natrexone was effective for 48hr. The antagonistic effect decreased at 72 hr after the administration of 120-200 mg of naltrexone. Laboratory tests indicated no signs of toxicity. Naltrexone may elicit an increase in blood pressure and opigastric pain. Neither of these side effects appear clinically important. No signs of dependence on naltrexone were detected. These results suggest that naltrexone may be useful for clinical treatment of opiate dependence.

Research training in psychiatry.

The authors examined data on 13 requests for federal support for psychiatric research investigation that were evaluated as part of the NIMH review of psychiatric education grants in fiscal year 1975. Thirteen factors were found to be associated with quality of psychiatric research training, and the interaction and importance of these factors are illustrated in summaries of 5 programs. The ideal program is described as one in which there is a clearly stated concept, content that is broad and relevant enough to interest trainees in psychiatry, a continuing evaluation process, and superior research that can be documented. Adequate depth and breadth in terms of faculty and facilities are also essential. The authors believe that all psychiatrists should be encouraged to integrate scientific observation into their professional work and to evaluate systematically the effectiveness of their clinical interventions.

Effects of an ACTH short chain neuropeptide in man.

The authors studied the effect of an ACTH 4-9 analogue (the shortest behaviorally active fragment of the ACTH neuropeptide) on mood in normal aging volunteers. These mood changes, described as a sense of well-being, energy, and drive, are consistent with an arousal-stimulant mechanism of action of the compound. No effect of the compound was found on attention or memory. Because of its apparent safety and the lack of adverse effects, the authors suggest that this short chain neuropeptide be further explored in older individuals for its mood-elevating and potential antidepressant properties.

Medical student education in psychiatry.

The authors interpret data obtained from 99 medical schools which submitted grant applications for support of either undergraduate psychiatric education programs or human behavior programs. They tentatively conclude that high-quality programs for teaching medical students psychiatry are characterized by a well-rounded faculty, a psychodynamic orientation, a greater commitment to medical student education than to resident training, varied teaching methods, enthusiastic student response, and systematic evaluation that produces change in subsequent years.

Chronic hashish use and mental disorder.

The authors compared 47 long-term users of hashish with a control group of 40 subjects matched for age, ethnic origin, education, etc., in order to determine whether they differed significantly on psychiatric, physical health, and demographic variables. There was a significantly higher incidence of personality disorders, unemployment, and prison sentences in the group of chronic users. However, in contrast to the findings of other researchers, the hashish users did not have organic psychoses, nor did they differ from control subjects in neurologic signs or EEG and echo encephalogram patterns.

l-Alpha-acetylmethadol (LAAM): prognostic considerations.

The authors studied the responses of 28 adult male volunteers who were openly changed from methadone to l-alpha-acetylmethadol (LAAM) maintenance. They found that patients who had been receiving middle-range doses (50-70 mg) of methadone required a significantly lower mean increase in LAAM than patients who had been receiving either high or low methadone doses and that the patients who accepted LAAM differed significantly from those who did not in MMPI 2-point-code ratings and mean social adjustment scale scores. These findings may provide prognostic indicators for response to LAAM, a possible alternative to methadone.

Propranolol preserves ultrastructure in adult cardiocytes exposed to anoxia/reoxygenation: a morphometric analysis.

The protective effect of d,l-propranolol was studied using freshly isolated canine ventricular cardiocytes (1.5 x 10(6)/mL) exposed to 30 min anoxia (95% N2/5% CO2) and 0, 3, 20, and 45 min of reoxygenation (95% O2/5% CO2). In addition to preventing lipid peroxide formation, propranolol maintained cellular viability, and minimized ultrastructural alterations. In the absence of propranolol, the outer mitochondria become swollen and rounded up within the first few minutes of reoxygenation. The perinuclear mitochondrial area increased only slightly. We observed that the cellular injury process proceeded differentially from the exterior to the interior, with a mitochondrial area increase and outer membrane rupture. Sarcolemmal damage was also observed with prevalent blebbing and membrane loss. The Z-lines became wider and more diffuse with reoxygenation. Injury to the nuclear double membrane was observed. Incubation with propranolol showed significant protection during postanoxia reoxygenation. In contrast, the more water soluble beta-blocker atenolol only exhibited slight protection. In addition, d-propranolol (the non beta-blocking isomer) and the antioxidant enzymes, SOD and catalase, showed significant protection. These data support previous findings concerning the antioxidant properties of propranolol which appear to be independent of beta-receptor blockade.

Protective effects of sulfhydryl-containing angiotensin converting enzyme inhibitors against free radical injury in endothelial cells.

The effects of SH-containing (captopril, epi-captopril, and the free-SH form of zofenopril) and non-SH-containing (enalaprilat and lisinopril) angiotension converting enzyme (ACE) inhibitors on free radical injury in cultured endothelial cells were studied. When cultured endothelial cells were exposed to a superoxide and hydroxyl radical generating system (dihydroxyfumarate + Fe3(+)-ADP) for 30 min, lipid peroxidation [malondialdehyde (MDA) formation] occurred, and cellular viability (trypan blue exclusion) decreased to 41%; concomitantly, plasma membrane blebbing, assessed by scanning electron microscopy, occurred in 65% of the cells. Preincubation of the cells with each of the SH-agents before free radical addition resulted in an equipotent concentration-dependent (10-200 microM) inhibition (15-60%) of MDA formation; both losses in cellular viability and percent blebbed cells were reduced significantly (P less than 0.05) by concentrations as low as 10 microM of each SH-agent. However, neither of the non-SH agents up to 200 microM produced any major effect. When the effects on hydroxyl radical formation in the system were assessed by ESR spin-trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), concentrations of 10 and 50 microM of the SH-agents reduced the intensity of the DMPO-OH adducts 20 and 50% respectively. Similar results were observed when the hydroxyl radical was generated from the Fenton-reagents (Fe2+ + H2O2), suggesting direct hydroxyl radical scavenging. Thus, these results demonstrate that the SH-containing ACE agents are capable of protecting the endothelial cells against free radical induced lipid peroxidation and cell injury; the mechanism may be due to direct hydroxyl radical scavenging.

Infections in breast implants.

Infection following breast implants is an uncommon event. This is somewhat surprising, since the human breast is not a sterile anatomical structure. The flora found in the breast are derived from the nipple ducts and closely resemble those of normal skin. These organisms, predominantly S. epidermidis, may in some cases be responsible for firmness secondary to capsular contracture. Treatment of the periprosthetic infection usually involves implant removal, but salvage by systemic antibiotics is sometimes possible. Atypical mycobacteria are very rarely the cause of infection, but can be extremely difficult to eradicate when involved. Toxic shock syndrome has been reported to occur following breast implants and is a life-threatening problem requiring immediate removal of the implant. It may be significant that in some cases with effusion and infection occurring many months or years after implant placement, there has been a preceding event such as a laryngitis or flu-like illness. This suggests the possibility of a bacteremia being involved in the causation of the infection. If this were the case, then these patients should be handled in a fashion similar to those with prosthetic heart valves. Accordingly, in our own practice, we advise that penicillin "V" be given beforehand when a patient with breast implants is to have any dental procedure. It must be stressed that there is no statistical or scientific proof at the present time that this is of any value. In conclusion, when dealing with these large foreign bodies, absolute sterility is essential, and excellent surgical technique to obviate hematoma and the occurrence of tissue ischemia is mandatory. Evidence of severe infection necessitates implant removal, but in less severe cases a trial of intravenous antibiotics is permissible. Having removed an implant, further insertion should be deferred, preferably for 6 months. If the new implant can be placed in a different plane, that is, submuscular, this is desirable. Exposed implants can be salvaged but this requires considerable judgment and one should be prepared for re-exposure or frank infection.

Soft-tissue sarcomas of the head and neck.

We reviewed the charts of 352 patients at the Mayo Clinic who were diagnosed and treated for primary soft-tissue sarcomas of the head and neck from 1962 to 1982. The age at diagnosis ranged from 6 weeks to 91 years; 28 percent were pediatric patients. Regional or distant metastases were present at the time of primary diagnosis in 8 percent of patients. Nonorbital rhabdomyosarcoma was the most common tumor type (17 percent), and neuroblastoma was the rarest (2 percent). In children, rhabdomyosarcomas were proportionally more common, as was overall involvement of the orbit. Surgical excision was the sole method of tumor control in 49 percent of patients; excision with adjuvant radiotherapy or chemotherapy was used in 33 percent. In those with localized disease, overall survival was 81 percent at 2 years, 68 percent at 5 years, and 60 percent at 10 years postoperatively. Patients with angiosarcoma and nonorbital rhabdomyosarcoma experienced the poorest survival rates.

Maintenance of psychosocial attitudes in medical students.

Attitudes of medical students towards the psychosocial aspects of illness is of serious concern to medical educators. It is thought that medical students are overwhelmingly disease-oriented and not sufficiently sensitive to the role of the psychological, emotional, sociological and economic factors in the etiology and management of illness. In the present study the ATSIM (Attitudes Towards Social Issues in Medicine) was presented to third year medical students and compared with their responses obtained 2 years previously when they were first year students. The data suggest that third year medical students have positive attitudes towards certain psychosocial issues (the importance of social factors as determinants of health or illness, the role of preventive medicine in maintaining health, the role of physician-patient interactions in patient care). These attitudes were positive during the students' first year and have been maintained during the course of medical school. These finding are contrary to previous studies which indicate a deterioration in attitudes during the course of medical school.

Computer-analyzed EEG (CEEG) and dynamic brain mapping in AIDS and HIV related syndrome: a pilot study.

In a group of HIV positive young male patients without any significant neuropsychiatric signs, computer-analyzed EEG (CEEG) and Dynamic Brain Mapping evaluations were conducted. These patients, who only had micro-neuropsychiatric symptoms, demonstrated CEEG profiles that more closely resemble those of patients diagnosed as suffering from mild dementia than age-related normals from our CEEG data base. The CEEGs of patients diagnosed as having Acquired Immune Deficiency Syndrome (AIDS), compared to patients with HIV positive, showed greater similarity in CEEG patterns to severely demented patients than to normal control groups. The findings of this pilot study suggest that CEEG may be useful for early determination of the Central Nervous System's (CNS) involvement with the AIDS virus and monitoring the progress of the illness.

Angioleiomyomas of the extremities: report of a case and review of the Mayo Clinic experience.

Angioleiomyomas are rare smooth-muscle tumors that occur anywhere in the body. We present the case of a 46-year-old woman with a 3-year history of a painless angioleiomyoma in the right-hand fourth web space with the typical histologic features of tortuous vascular channels and thick muscular walls. In the 39 cases of angioleiomyoma of an extremity treated at the Mayo Clinic, we found a male-to-female ratio of 1:2.2, a mean age of 52 years, and pain as the presenting symptom in 67 percent of the patients. The lesions usually were less than 1 cm in diameter, and they decreased significantly in size with increasing patient age. Simple excision was curative. Angioleiomyoma should be considered in all patients with nodular lesions of an extremity.

Magnesium-deficient myocardium demonstrates an increased susceptibility to an in vivo oxidative stress.

Previous studies in our laboratory have indicated free radical participation in magnesium deficiency cardiomyopathy. In this study, we examined the capacity of the magnesium-deficient animals to withstand an in vivo oxidative stress. Syrian hamsters were placed on either magnesium-deficient diet or a magnesium-supplemented control diet. Animals from each group also received vitamin E. After 14 days some of animals were given the catecholamine isoprenaline; 2 days later the animals were killed. The severity of the isoprenaline-induced injury was assessed by a morphometric analysis. The isoprenaline-induced injury was dramatically increased in the magnesium-deficient animals. The addition of vitamin E reduced the severity of the injury by 81% in these animals, indicating that the injury process was primarily due to an oxidative mechanism. These data show that magnesium deficiency increases the susceptibility of the cardiovascular system to oxidative stress.