Role of Alcohol-induced Hypothermia in Mediating the Teratogenic Effects of Alcohol in C57BL/6 J Mice

The purpose of this study was to determine the role of alcohol-induced maternal hypothermia in the teratogenic actions of alcohol. C57BL/6J mice were administered an acute dose of alcohol (5.8 g/kg orally) or isocaloric sucrose on day 10 of gestation. One half of each group was placed for 6 hr in an incubator set at 32 degrees C and the other half was housed in the incubator at room temperature (22 degrees C). As expected, acute prenatal alcohol exposure at this time of gestation was associated with decreased birth weight and an increase in limb and kidney malformations. The significant alcohol x environmental temperature interaction on these dependent variables indicated that the teratogenic insult was not attenuated, but was in fact even greater for the 32 degrees C/alcohol group. An absence of a main effect of environmental temperature indicated that the 32 degrees C environment, per se, was not teratogenic. Thus, maternal hypothermia is probably not an etiological factor in animal models of fetal alcohol syndrome. Moreover, antagonism of alcohol-induced maternal hypothermia exacerbates the teratogenic actions of alcohol observed at room temperature.     

Evidence of Increased Class I MHC Expression on Human Peripheral Blood Lymphocytes during Acute Ethanol Intoxication

Certain ethanol-related diseases in humans have been linked to disorders of immunity. Although humoral and cellular immunity have been studied, the precise mechanisms whereby ethanol use leads to tissue damage remain unknown. In order to explore the hypothesis that ethanol may lead to alteration in expression of tissue Class I major histocompatibility antigen causing an autoimmune phenomenon, a population of acutely ethanol-intoxicated patients was studied. Measurement of Class I major histocompatibility antigen on peripheral blood lymphocytes in this population showed a highly significant (p less than 0.01) increase over controls. The role that this increased antigenicity may play in the evolution of clinical disease is discussed.     

Transferrin Phenotype and Level of Carbohydrate-deficient Transferrin in Healthy Individuals

Elevated concentrations of carbohydrate-deficient components of transferrin (CDT) in serum may be used as a sensitive and specific marker of regular, high alcohol consumption. When determined by a new, simplified assay, CDT values are nearly normally distributed in low- or non-alcohol-consuming control populations. The importance of transferrin phenotype for this normal variation was analyzed in 100 healthy, European men and women with no or negligible alcohol intake. No significant relation was found between phenotype and CDT value in this population. The three rare B-variants found had low CDT levels, and one subject, examined outside the study, with a rare D-variant indicated that D-variants may result in false-positive CDT values. Moreover, women tended to have somewhat higher values than men, in whom CDT levels were weakly correlated with age. Other as yet undefined biological factors are clearly responsible for the major part of the normal variation of CDT values in nonalcoholic individuals.     

Active oxygen species generated by monocytes and polymorphonuclear cells in Crohn's disease

Chemiluminescence (CL) analysis of monocytes and polymorphonuclear cells (PMNs) was performed on 13 patients with Crohn's disease (CD) and 10 healthy volunteers. The percentages of monocyte populations in mononuclear cells obtained from the patients with CD were greater than those from the healthy volunteers, but the numbers of PMNs were not different between the two groups. The peak level of phorbol myristate acetate (PMA)-induced CL activity generated by diluted whole blood from the patients with CD was more significantly elevated than that from the healthy volunteers, whereas the peak levels of opsonized zymosan-induced CL activity did not differ between the two groups. In monocytes, the peak levels of both PMA- and opsonized zymosan-induced CL activity were significantly higher in the patients with CD than in the healthy volunteers. CL in PMNs, however, showed no significant difference between CD and controls. It is suggested that monocytes of CD have a large capacity to generate active oxygen species. The present study suggests that excessive active oxygen species released by monocytes and perhaps macrophages may play an important role in formation of the intestinal lesions in CD.This work was supported by the Grant of Tokuteishitsukan from the Japanese Ministry of Welfare and Health.     

Maternal-Fetal Immune Relationship: Another Point of View

Placental transfer of maternal IgG is known to be an active process resulting in a concentration on the fetal side of the circulation--at the apparent expense of that in the mother--at full term. However, when this apparent decrease in maternal IgG is related to the actual hemodilution occurring in parallel, the total inventory of the mother's IgG appears to be constant throughout pregnancy. Therefore, conclusions regarding the variations in IgG concentrations cannot be drawn without simultaneous information about plasma volume fluctuations.     

Reactions to Alcohol in Sons of Alcoholics and Controls

This paper synthesizes some major findings coming from our laboratory over the last decade. The data focuses on our search for mechanisms that might contribute to the elevated risk for alcoholism in sons of alcoholic fathers. Consistent results corroborated by several additional groups indicate that the higher risk sons of alcoholics demonstrate less intense reactions to ethanol as measured by their subjective self-reports, measures of body sway, changes in several hormones after drinking, and the intensity or persistence of ethanol-related changes on two electrophysiological measures. The potential implications of these results as they might relate to an enhanced vulnerability to alcoholism, and some possible future research directions, are discussed.     

Effect of OPC-8212 (2(1H)-quinolinone), a new inotropic agent, on myocardial energy metabolism in patients with coronary heart disease

We examined the effects of a new inotrope, OPC-8212 (OPC: 2(1H)-quinolinone), on coronary sinus flow (CSF), myocardial oxygen consumption, myocardial lactate extraction ratio (LER), cardiac index (CI) and pulmonary arterial diastolic pressure (PADP) in eleven patients with prior myocardial infarction. Measurements were taken before (control) and 8 hours after administration of OPC (480 mg, p.o.). A cardiac function curve was obtained in each stage with rapid intravenous administration of 500 ml of saline (loaded state) after baseline measurements. There was a significant increase in the cardiac index and decrease in the pulmonary arterial diastolic pressure in the loaded state after OPC. Thus the ventricular function curve was shifted to the left and showed a steep incline, indicating an increased inotropic state. On the other hand, myocardial oxygen consumption and myocardial lactate extraction ratio were unchanged. Thus we concluded that OPC improved cardiac performance without increasing myocardial oxygen consumption.     

Sexually transmitted diseases in abused children and adolescents

The prevalence of abnormal physical signs (e.g., bleeding, scars, or bruises) and genital infections, notably Chlamydia Trachomatis, Neisseria Gonorrhea, and Herpes Simplex Genitalis was studied in 219 female children with validated sexual abuse. They were compared to 113 nonabused female children. The average abused child was 8.3 years old, with 69% having been abused on multiple occasions. Most offenders were family members (65%) or a close family friend (22%). Stranger-perpetrated sexual assault, in the sample, was low (9.1%). Few children had severe vaginal tears, though 56% showed signs of subtle anatomical injury to their genitalia. No similar anatomical abnormalities were present in nonabused children. Among the sexually abused children and adolescents, 35% were colonized with a pathogen or a potential pathogen, compared to a prevalence rate of 18.5% in non-abused children. The proportion of abused children colonized with Ureaplasma Urealyticum and Mycoplasma Hominis was not significantly different from that found in nonabused children. At present, Neisseria gonorrhea and Chlamydia Trachomatis remain the only conclusive markers for sexual abuse. It is recommended that routine cultures of the pharyngeal, rectal, and vaginal areas be taken in all cases of suspected child sexual abuse, regardless of clinical findings.     

Response of lower esophageal contractility to changing concentrations of halothane or isoflurane: A multicenter study

A multiple-center study was performed to determine the relationship between lower esophageal contractility, clinical signs, and anesthetic concentration as expressed by minimum alveolar concentration (MAC). One hundred four American Society of Anesthesiologists Class I through III patients were exposed to isoflurane (with and without nitrous oxide) or halothane in concentrations of 0.5, 1.0, and 1.5 MAC. Heart rate and systolic blood pressure were continuously monitored. Both the amplitude and frequency of spontaneous and provoked lower esophageal contractions were measured in situ by using a 24-F probe equipped with provoking and measuring balloons. Combined results demonstrated statistically significant correlations (P<0.001) between lower esophageal contractility and MAC. Spontaneous lower esophageal contractions decreased from 1.10±0.12 (SEM) contractions per minute (0.5 MAC) to 0.42±0.05 (1 MAC) to 0.18±0.05 (1.5 MAC). Provoked lower esophageal contractility values decreased from 45±4 mm Hg (0.5 MAC) to 29±3 (1 MAC) to 19±2 (1.5 MAC). Heart rate changes did not correlate with MAC, and systolic blood pressure correlated in only one of three centers. Intracenter and intercenter analyses failed to demonstrate a significant relationship between lower esophageal contractility and heart rate or systolic blood pressure. No intracenter differences in either amplitude or frequency of lower esophageal contractions were observed, despite differences in volatile agents, induction techniques and agents, patient populations, and duration of anesthesia. Our studies indicate that lower esophageal contractility may be an indicator of anesthetic depth as reflected by MAC, but further studies are needed to quantify the effects of surgical stimulus, intravenous anesthetics, vasodilators, anticholinergics, calcium channel blockers, beta-adrenergic agonists, and the presence of a nasogastric tube.