Exposure to extrinsic stressors, social defeat or bisphenol A, eliminates sex differences in DNA methyltransferase expression in the amygdala.

Chemical and psychological stressors can exert long lasting changes in brain function and behaviour. Changes in DNA methylation have been shown to be an important mechanism mediating long lasting changes in neural function and behaviour, especially for anxiety-like or stress responses. In the present study, we examined the effects of either a social or chemical stressor on DNA methyltransferase (DNMT) gene expression in the amygdala, an important brain region modulating stress responses and anxiety. In adult California mice (Peromyscus californicus) that were naïve to social defeat, females had higher levels of Dnmt1 expression in punch samples of the central amygdala (CeA) than males. In addition, mice that underwent social defeat stress showed reduced Dnmt1 and Dnmt3a expression in the CeA of females but not males. A second study using more anatomically specific punch samples replicated these effects for Dnmt1. Perinatal exposure (spanning from periconception through lactation) to bisphenol A or ethinyl oestradiol (oestrogens in birth control pills) also abolished sex differences in Dnmt1 expression in the CeA but not the basolateral amygdala. These findings identify a robust sex difference in Dnmt1 expression in the CeA that is sensitive to both psychological and chemical stressors. Future studies should aim to examine the impact of psychological and chemical stressors on DNA methylation in the CeA and also investigate whether Dnmt1 may have an underappreciated role in plasticity in behaviour.

Effect of elevated ambient temperature at parturition on duration of gestation, ruminal temperature, and endocrine function of fall-calving beef cows.

Fall-calving Angus cows were used to evaluate the effect of ambient temperature on duration of gestation. In Exp. 1, cows were AI and calved in August (n = 14) or October (n = 10). Cows grazed native prairie pasture in Oklahoma and had a BCS of 6.0 ± 0.5 (1 = emaciated, and 9 = obese) at parturition. Commencing 2 wk before the expected calving date, blood samples were taken from the coccygeal vein every 2 to 3 d until calving. Cows that calved in August tended to have shorter gestations (P = 0.07) compared with cows that calved in October. Maximum daily ambient temperature during the last 14 d of gestation was greater for August-calving cows (P < 0.001) compared with October cows. Concentrations of cortisol in plasma during the last 4 d of gestation were greater in cows that calved in August (P < 0.04) compared with cows that calved in October. In Exp. 2, cows were AI and calved in either mid-August (n = 7), late-August (n = 6), September (n = 6), or October (n = 8) to evaluate the effects of elevated ambient temperature on duration of gestation, ruminal temperature at parturition, and plasma cortisol, progesterone, and estradiol. Temperature boluses (SmartStock, LLC, Pawnee, OK) programmed to transmit temperature every hour were place in the rumen at 255 d of gestation. Cows grazed native prairie pasture in Oklahoma and had a BCS of 6.5 ± 0.4 at calving. Maximum ambient temperatures during d 263 to 273 of gestation were influenced by month of calving × day (P < 0.001). Duration of gestation was shorter for mid-August cows (P < 0.05) compared with October cows, but did not differ compared with late-August (P = 0.29) and September (P = 0.50) cows. Ruminal temperature during the 4 d before calving was not influenced by month of calving (P = 0.76). Ruminal temperature was decreased during the 24 h before parturition for cows in all months (P < 0.01) compared with 2 to 4 d before parturition. Concentrations of cortisol in plasma during d 271 to 276 of gestation were less (P < 0.05) for late-August compared with cows that calved during the other months. Concentrations of progesterone were greater during 7 d before parturition in October compared with cows that calved in September. Estradiol in plasma of cows during late gestation was not affected by month of calving (P = 0.76). Exposure of beef cows to elevated ambient temperature resulted in shorter gestations. Ruminal temperature in cows decreased ≥ 0.3°C the day before parturition.

Antigen-specific T lymphocyte proliferation decreases over time in advanced chronic hepatitis C.

To evaluate T cell immunity in advanced liver disease, antigen-specific lymphoproliferative (LP) responses were prospectively studied in the context of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Peripheral blood responses to hepatitis C virus (HCV), tetanus and Candida protein antigens were measured at baseline, month 12 (M12), M24, M36 and M48 in 186 patients randomized to either low-dose peginterferon-alfa-2a (PEG-IFN) only or observation. Liver histology was evaluated at baseline, M24 and M48. Patients with cirrhosis (Ishak 5-6) were less likely to have positive LP responses to HCV at baseline than patients with fibrosis (15%vs 29%, P = 0.03) and had lower levels of HCV c100 responses at baseline, M24 and M48 (P = 0.11, P = 0.05, P = 0.02, respectively). For 97 patients with complete longitudinal data, the frequency of positive LP responses to HCV, tetanus and Candida antigens declined over time (P < 0.003), and the slope of this decline was greater in the PEG-IFN treatment group than the observation group (P < 0.02). Lower levels of tetanus LP responses were associated with fibrosis progression and clinical outcomes (P = 0.009). Poorer CD4+ T cell proliferative function was associated with more advanced liver disease in chronic hepatitis C and may be further affected by long-term PEG-IFN treatment.

Monocyte infiltration and kidney allograft dysfunction during acute rejection.

Multiple cell types infiltrate acutely rejecting renal allografts. Typically, monocytes and T cells predominate. Although T cells are known to be required for acute rejection, the degree to which monocytes influence this process remains incompletely defined. Specifically, it has not been established to what degree monocytes impact the clinical phenotype of rejection or how their influence compares to that of T cells. We therefore investigated the relative impact of T cells and monocytes by correlating their presence as measured by immunohistochemical staining with the magnitude of the acute change in renal function at the time of biopsy in 78 consecutive patients with histological acute rejection. We found that functional impairment was strongly associated with the degree of overall cellular infiltration as scored using Banff criteria. However, when cell types were considered, monocyte infiltration was quantitatively associated with renal dysfunction while T-cell infiltration was not. Similarly, renal tubular stress, as indicated by HLA-DR expression, increased with monocyte but not T-cell infiltration. These data suggest that acute allograft dysfunction is most closely related to monocyte infiltration and that isolated T-cell infiltration has less acute functional impact. This relationship may be useful in assigning acute clinical relevance to biopsy findings.

The relationship of acute transfusion-associated hepatitis to the development of cirrhosis in the presence of alcohol abuse.

BACKGROUND: Although concomitant alcoholism is widely believed to enhance liver disease progression in persons with hepatitis C virus (HCV) infection, this relationship has not been well quantified. OBJECTIVE: To quantify the relationship of transfusion-associated HCV infection and history of heavy alcohol abuse to development of cirrhosis. DESIGN: Retrospective cohort study. SETTING: Liver clinics in university and government hospitals. PATIENTS: Extended follow-up of 1030 patients in prospective investigations of transfusion-associated viral hepatitis conducted in the United States between 1968 and 1980. MEASUREMENTS: Development of cirrhosis and history of heavy alcohol abuse were determined from review of interviews with patients or their proxies, medical records, death certificates, and autopsy and biopsy reports. Logistic regression was used to estimate the risk for cirrhosis associated with transfusion-associated HCV infection and history of heavy alcohol abuse. RESULTS: The absolute risk for cirrhosis was 17% among patients with transfusion-associated HCV; 3.2% among patients with transfusion-associated non-A, non-B, non-C hepatitis; and 2.8% among controls. Patients with transfusion-associated HCV were more likely than controls to develop cirrhosis (odds ratio, 7.8 [95% CI, 4.0 to 15.1]). A history of heavy alcohol abuse was associated with a fourfold increased risk for cirrhosis. Hepatitis C virus infection plus a history of heavy alcohol abuse led to a substantial increase in risk for cirrhosis (odds ratio, 31.1 [CI, 11.4 to 84.5]) compared with controls without such a history. CONCLUSIONS: Heavy alcohol abuse greatly exacerbates the risk for cirrhosis among patients with HCV infection. This finding emphasizes the need to counsel such patients about their drinking habits.

Multicenter comparison of magnetic resonance imaging and transcranial Doppler ultrasonography in the evaluation of the central nervous system in children with sickle cell disease.

PURPOSE: To compare the results of standardized magnetic resonance imaging (MRI) of the brain and transcranial Doppler (TCD) ultrasonography of cerebral arteries in school-aged children with sickle cell disease to determine the correlation between these two different neurodiagnostic tests. PATIENTS AND METHODS: Data were analyzed from 78 children with sickle cell disease (mean age 11 yrs) who participated in both the Cooperative Study of Sickle Cell Disease (CSSCD) and the Stroke Prevention Trial in Sickle Cell Anemia (STOP). Patients who had experienced an overt stroke were excluded. MRI findings were classified as normal or "silent infarct." Results of TCD were classified as normal, conditional, or abnormal, based on the time-averaged maximum mean flow velocity in the proximal middle cerebral and distal internal carotid arteries. RESULTS: Of 61 patients who had a normal MRI examination, 11 (18%) had either conditional (5 patients) or abnormal (6 patients) TCD results. Among 17 patients in whom silent infarction was seen on MRI, only 5 (29%) had a conditional (1 patient) or abnormal (4 patients) TCD velocity. Thus, discordant results were seen in 23 patients: 12 in which the TCD result was normal and the MRI abnormal; 11 in which the TCD velocity was elevated and the MRI normal. CONCLUSIONS: Abnormal TCD and MRI examinations reveal different aspects of the pathophysiology of central nervous system (CNS) injury in sickle cell disease and are often discordant. Although TCD abnormality is predictive of overt stroke, the lack of concordance between TCD and MRI findings suggests a need to develop more sensitive and specific indicators of early CNS pathology, such as neuropsychometric testing and positron-emission tomography (PET) scans, and to obtain more information about microvascular pathologic processes that may affect CNS function.

Results of the National Cooperative Inner-City Asthma Study (NCICAS) environmental intervention to reduce cockroach allergen exposure in inner-city homes.

BACKGROUND: Cockroach allergen is important in asthma. Practical methods to reduce exposure are needed. OBJECTIVE: We sought to evaluate the effectiveness of house cleaning and professional extermination on lowering cockroach antigen levels in inner-city dwellings. METHODS: As part of the National Cooperative Inner-City Asthma Study intervention, 265 of 331 families with asthmatic children who had positive skin test responses to cockroach allergen consented to a professional home extermination with 2 applications of a cockroach insecticide (Abamectin, Avert) combined with directed education on cockroach allergen removal. On a random subset of 48 homes undergoing cockroach extermination in the intervention group, Bla g 1 was measured in settled dust from the kitchen, bedroom, and TV/living room. The first sample was collected 1 week before extermination, with additional samples after the exterminations at approximately 2, 6, and 12 months after the first sample. Self-reported problems with cockroaches were collected at baseline and after 12 months of follow-up in both the intervention and control group. RESULTS: The geometric mean kitchen level of Bla g 1 decreased at 2 months (33.6 U/g) relative to preextermination levels (68.7 U/g, P <.05). The percent of kitchens with over 8 U/g of Bla g 1 followed a similar pattern, but only the decrease from preextermination to 6-month levels was significant (86.8% vs 64.3%, P <.05). By the 12-month visit, the allergen burden had returned to or exceeded baseline levels. Except for an increase in the bedroom at 2 months (8.9 U/g vs 11.1 U/g, P <.05), no other significant change was seen. Only about 50% of the families followed the cleaning instructions; no greater effect was found in these homes. Self-reported problems with cockroaches showed no difference between the intervention and control group after 1 year of follow-up. CONCLUSIONS: Despite a significant, but short-lived, decrease the cockroach allergen burden remained well above levels previously found to be clinically significant.

Self-reported adherence, management behavior, and barriers to care after an emergency department visit by inner city children with asthma.

OBJECTIVE: The inability to adhere to a prescribed therapeutic program for the treatment of a chronic disease may be responsible in part for continued disease activity. This problem may be more of an issue in the treatment of asthma, a common, potentially lethal chronic condition in which the lack of symptoms may be interpreted as remission. Adherence was one of the key areas of interest for the National Cooperative Inner-City Asthma Study. The focus of this study was to identify those issues reported by families that could adversely affect their adherence to an asthma care program. The identification of barriers to adherence could then form the basis of a successful intervention program. This study describes barriers to adherence, asthma management behavior, and self-reported adherence. METHODS: Patients presenting during an acute attack of asthma at an emergency department (ED) were recruited for this study. The medical record of the ED encounter was abstracted and compared with information that was obtained during a baseline interview 3 to 5 weeks later. During the baseline interview, parents were asked about health care behaviors related to adherence. RESULTS: There were 344 children 4 to 9 years of age living in inner city census tracts in the study. Four areas of adherence (medicine use, appointment-keeping, emergency actions, and asthma attack prevention) were investigated. The parental report of medications prescribed at the ED and the information on the abstracted ED report agreed 94.9% of the time for the beta-agonists, 86.8% for steroids, and 69.4% for cromolyn. Among respondents, 85.4% of parents reported that they are able to follow the ED recommendations almost all of the time; side effects of medicines were a concern for 81.1% of caretakers who were adherent and for 89.5% of caretakers who were nonadherent. Doubts regarding the usefulness of medications occurred in 34.4% of those considered adherent and 54.2% who admitted nonadherence. Medications were forgotten some of the time by 45.2% of the children, and 52.8% tried to get out of taking medicine. Appointments for follow-up care were kept by 69% of those given an appointment in the ED, by an estimated 60.0% of those who were told specifically to call for an appointment, and by an estimated 25.2% of those who were neither given an appointment nor told specifically to make one. Only one third of parents report that they were able to keep the child away from known asthma triggers nearly all of the time. Approximately half avoided allergens; however, only 37.5% reported avoidance of cigarette smoke. The use of preventive medicines occurred in 23.5%. Using a medicine and taking the child to a physician were reported as the first or second action during an acute attack of asthma by 72.1% of respondents. CONCLUSIONS: Adherence to an asthma-management program involves a number of areas: medication, appointment-keeping, prevention, and applying an emergency plan of action. Barriers to adherence may exist in one or all four of these areas, leading to ineffective control of asthma. Recommendations are made for improving the patient-physician partnership to improve adherence.

A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Nosocomial infections are a major cause of morbidity and mortality in premature infants. As a rule, their low serum gamma globulin levels at birth subsequently decline to hypogammaglobulinemic values; hence, prophylactic administration of intravenous immune globulin may reduce the rate of hospital-acquired infections. METHODS: In this prospective, multicenter, two-phase controlled trial, 2416 infants were stratified according to birth weight (501 to 1000 g and 1001 to 1500 g) and randomly assigned to an intravenous immune globulin group (n = 1204) or a control group (n = 1212). Control infants were given placebo infusions during phase 1 of the study (n = 623) but were not given any infusions during phase 2 (n = 589). Infants weighing 501 to 1000 g at birth were given 900 mg of immune globulin per kilogram of body weight, and infants weighing 1001 to 1500 g at birth were given a dose of 700 mg per kilogram. The immune globulin infusions were repeated every 14 days until the infants weighed 1800 g, were transferred to another center, died, or were sent home from the hospital. RESULTS: Nosocomial infections of the blood, meninges, or urinary tract occurred in 439 of the 2416 infants (18.2 percent): 208 (17.3 percent) in the immune globulin group and 231 (19.1 percent) in the control group (relative risk, 0.91; 95 percent confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5 percent of the immune globulin recipients and 17.2 percent of the controls. During phase 1 the rate of nosocomial infections was 13.4 percent in the immune globulin group and 17.8 percent in the control group; the respective rates during phase 2 were 21.0 percent and 20.4 percent. The predominant organisms included gram-positive cocci (53.0 percent), gram-negative bacilli (22.4 percent), and candida species (16.0 percent). Adverse reactions were rarely observed during the infusions. Immune globulin therapy had no effect on respiratory distress syndrome, bronchopulmonary dysplasia, intracranial hemorrhage, the duration of hospitalization, or mortality. The incidence of necrotizing enterocolitis was 12.0 percent in the immune globulin group and 9.5 percent in the control group. CONCLUSIONS: Prophylactic use of intravenous immune globulin failed to reduce the incidence of hospital-acquired infections in very-low-birth-weight infants.

A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome. National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: To compare the efficacy of two surfactants, Exosurf Neonatal (Burroughs Wellcome Co.) and Survanta (Ross Laboratories), for the treatment of neonatal respiratory distress syndrome. DESIGN: Multicenter randomized trial. SETTING: Eleven tertiary care university neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. PATIENTS: Newborn infants (n = 617) weighing 501 to 1500 gm with respiratory distress syndrome who were receiving assisted ventilation with 30% oxygen or more within 6 hours of birth were enrolled between January 1991 and January 1992. INTERVENTIONS: Infants were randomly assigned to receive up to four intratracheal doses of either Exosurf Neonatal (n = 309) or Survanta (n = 308). MAIN OUTCOME MEASURES: The occurrence of death or bronchopulmonary dysplasia 28 days after birth and the average fraction of inspired oxygen (FIO2) and mean airway pressure (MAP) during the first 72 hours after treatment. RESULTS: Death or bronchopulmonary dysplasia occurred in 67% of the infants in the Exosurf group and 62% of those in the Survanta group (adjusted relative risk, 1.07; 95% confidence interval, 0.96 to 1.20). During the 72 hours after the first surfactant dose, the average FIO2 (+/- SEM) was 0.50 +/- 0.01 for Exosurf and 0.42 +/- 0.01 for Survanta (difference, 0.08; 95% confidence interval, 0.05 to 0.11); the average MAP (+/- SEM) was 7.64 +/- 0.21 cm H2O for Exosurf and 6.93 +/- 0.21 cm H2O for Survanta (difference, 0.71 cm H2O; 95% confidence interval, 0.13 to 1.29 cm H2O). There was no difference between the groups in the incidence of other neonatal morbidities or in the duration of hospitalization, assisted ventilation, or supplemental oxygen administration. CONCLUSION: We found no difference between treatment groups in the incidence of death or bronchopulmonary dysplasia, although we did observe a difference in the initial response to treatment as measured by FIO2 and MAP.

Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group.

BACKGROUND: Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known. METHODS: We traced patients with transfusion-related non-A, non-B hepatitis who had been identified in five major prospective studies conducted in the United States between 1967 and 1980. We matched each patient with two control subjects (identified as the first and second controls) who received transfusions but who did not have hepatitis. The mortality rates in the three groups were determined with use of data from the National Death Index and Social Security Death Tapes. Cause-specific mortality was determined by reviewing death certificates. RESULTS: Vital status was established for over 94 percent of the 568 patients who had had non-A, non-B hepatitis and the two control groups (526 first controls and 458 second controls). After an average follow-up of 18 years, the estimate by life-table analysis of mortality from all causes was 51 percent for those with transfusion-associated non-A, non-B hepatitis, as compared with 52 percent for the first controls and 50 percent for the second controls. The survival curves for the three groups were virtually the same. Mortality related to liver disease was 3.3, 1.1, and 2.0 percent, respectively, among the three groups (P = 0.033 for the comparison of the group with non-A, non-B hepatitis with the combined control group). Seventy-one percent of the deaths related to liver disease occurred among patients with chronic alcoholism. CONCLUSIONS: In this long-term follow-up study, there was no increase in mortality from all causes after transfusion-associated non-A, non-B hepatitis, although there was a small but statistically significant increase in the number of deaths related to liver disease.

Inheritance of proliferative breast disease in breast cancer kindreds.

Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer.

Evidence against the reported linkage of the cutaneous melanoma-dysplastic nevus syndrome locus to chromosome Ip36.

The reported linkage between cutaneous melanoma and the dysplastic nevus syndrome (CM/DNS) to markers located on the distal portion of the short arm of chromosome 1 was examined in three Utah kindreds ascertained for multiple cases of melanoma. Family members in these kindreds were genotyped for the two markers reported to be most closely linked in the Bale study, PND and D1S47. Both melanoma alone and a combined melanoma/DNS phenotype were analyzed; no evidence for linkage was found. By multipoint linkage analysis the CM/DNS locus was excluded from an area of 55 cM containing the PND-D1S47 region. Diagnostic or genetic heterogeneity are alternate explanations for the discrepancy between our observations and those of Bale et al.

A genetic map of human chromosome 17p.

A genetic linkage map was constructed with 18 loci from the short arm and pericentric region of chromosome 17 typed on the CEPH reference families. The genetic map includes three markers extracted from the CEPH public database. Nine loci could be ordered using a threshold of odds of at least 1000:1 against alternative orders during the map construction process. With a reduced tolerance of 100:1, a total of 13 loci could be placed on the map spanning a distance of approximately 60 cM in females and 46 cM in males. There were statistically significant differences between the male and the female genetic maps. The order inferred from the genetic data was consistent with the physical localizations of these probes obtained from somatic cell hybrids and tumor deletion studies. This map should be useful for genetic fine mapping of 17p loci.

Airways obstruction and the risk for lung cancer.

The presence of airways obstruction identify in middle-aged male smokers at increased risk for lung cancer. This hypothesis was tested in a sample of patients with moderate to severe obstruction from the Intermittent Positive Pressure Breathing Trial and a sample of patients with no obstruction to moderate obstruction from the Johns Hopkins Lung Project, all of whom were followed for the development of lung cancer. On follow-up, the risk of developing lung cancer was found to be associated with entry values for age, smoking, and ventilatory status by linear, proportional hazard, and log-linear adjustment techniques. Among cigarette smokers, the presence of airways obstruction was more of an indicator for the subsequent development of lung cancer than was age or the level of smoking. The risk for lung cancer also increased in proportion to the degree of airways obstruction. These data suggest that smokers with ventilatory obstruction are at greater risk for lung cancer than are smokers without obstruction.

Bronchodilator response in chronic obstructive pulmonary disease.

We measured response to 250 micrograms isoproterenol in 985 patients with COPD who were carefully studied and followed closely for nearly 3 yr. Response was quantitated in relative (% increase in FEV1) and absolute (change in FEV1 as a % predicted normal) terms. Patients were told to abstain from bronchodilator for 6 h before testing, and responses were larger in those who said they had done this. Responses were not related to blood theophylline concentrations. In patients who had abstained for 6 h, response averaged 15% of the baseline FEV1 or 5% of the predicted normal FEV1. Relative response was inversely proportional to baseline FEV1, whereas absolute response was directly related to baseline FEV1. Responses were positively related to symptomatic wheezing and exercise capacity, and negatively to smoking history, but these features accounted for little of the observed variation in response. Patients with large relative and absolute responses demonstrated increased variability of FEV1 with time and a decreased annual rate of decline of FEV1. There was little change in response with time, and the change observed could probably be explained by a gradual decrease in FEV1. However, time-related interindividual and intraindividual variations of response were large and impossible to separate from random variations of FEV1.

Quality of life and its predictors in patients with mild hypoxemia and chronic obstructive pulmonary disease.

Measures of quality of life were obtained on 985 patients with mild hypoxemia and chronic obstructive pulmonary disease (COPD). A subsample of 100 patients were also given extensive neuropsychological and personality tests. Mildly hypoxemic COPD patients showed impairment in quality-of-life activities. They showed less impairment in physical function, compared with previous studies on COPD patients with hypoxemia, but about equal impairment in psychosocial function and dysphoric mood. Nonrelated health changes in life do not seem to account for these findings. Degree of self-reported tension-anxiety was the single greatest predictor of both physical and psychosocial measures of quality of life. Level of exercise completed, forced expiratory volume in 1 s, and neuropsychological status were significantly related to physical limitations, but not psychosocial functioning. The Pao2 was not significantly related to quality-of-life measures in this patient group.

Primary pulmonary artery sarcoma diagnosed noninvasively by two-dimensional echocardiography.

A 21-year-old white male was evaluated in our echocardiographic laboratory for presumed mitral valvular bacterial endocarditis. Electrocardiographic, physical, and initial two-dimensional echocardiographic findings suggested a left-to-right shunt at the atrial septal level. However, injection of contrast saline solution failed to demonstrate signs of an atrial septal defect. Continuation of the echocardiographic study led to the diagnosis of an unsuspected primary sarcoma of the pulmonary trunk, which was rapidly confirmed by computerized axial tomography. Therapeutic interventions were undertaken. This case highlights the usefulness of two-dimensional echocardiography.

Glutathionuria: gamma-glutamyl transpeptidase deficiency.

A mentally retarded young woman with severe behaviour problems was found to excrete large amounts of glutathione due to a generalized gamma-glutamyl transpeptidase deficiency. As in the only other case described in detail, plasma levels and renal reabsorption of the amino acids were normal. In the parents' urine, plasma and leukocytes, enzyme activity was normal but in their cultured fibroblasts it was below the minimum for the control range. An autosomal recessive mode of inheritance is suggested. The implications of these findings for possible role of the gamma-glutamyl cycle in amino acid transport are briefly discussed.

Hepatic disease in asymptomatic parenteral narcotic drug abusers: a Veterans Administration collaborative study.

The Veterans Administration is currently conducting a collaborative study in three hospital-based drug treatment clinics to evaluate asymptomatic parenteral drug addicts for evidence of hepatic disease. Preliminary data are presented on 347 patients who have completed at least three months of follow-up evaluation. On admission, abnormal serum transaminase values were demonstrated in one half, HBs Ag in 7 per cent, and anti-HBs in 59 per cent. The frequency of these findings increased during the follow-up evaluation, only 19 (5.5 per cent) remaining entirely free of one or more of these abnormalities. Definable hepatologic disease (acute or chronic hepatitis, alcoholic hepatitis) developed in 46 per cent of the patients. However, among 60 of them subjected to liver biopsy, a poor correlation was noted between the clinical and histologic diagnoses. In particular, routine liver function and immunologic tests did not discriminate between histologically detected chronic active and chronic persistent hepatitis. However, HBs Ag was present significantly more frequently in those with chronic active hepatitis. Wide variability of histologic diagnoses was seen among patients subjected to more than one biopsy, apparent progression and regression of the lesion being noted. This demonstrates the hazard of attempting to assign a prognosis to the disease on the basis of a single liver biopsy specimen, and suggests that repeated biopsies should be mandatory for the evaluation of chronic liver disease in drug addicts.