DNA copy number changes in lung adenocarcinoma in younger patients.

We performed a comparative genomic hybridization study on 25 lung adenocarcinoma samples from younger patients (<41 y of age) and compared the results with a previous comparative genomic hybridization analysis of lung adenocarcinoma samples from older patients (50-81 y of age). Twenty of the 25 tumor samples from younger patients had DNA copy number changes. Gains, losses, and high-level amplifications were seen more frequently in the specimens from the younger group. The most striking difference between the two groups was the high frequency of gains and/or high-level amplifications in the long arm of chromosome 20 in the samples from the younger patients (14/25, 56%) compared with that in the samples from the older patients (2/24, 8%, P <.001). Gains in the long arm of chromosome 22 and of the chromosomal band 11q13 were also detected significantly more often in the younger group. No correlation was found between DNA copy number changes and clinical parameters. Our results suggest that amplification of genes in the long arm of chromosome 20 may be important in the tumorigenesis of lung adenocarcinoma in young adults. Several candidate genes have already been described in the long arm of chromosome 20, particularly in breast cancer.     

The use of fine-needle aspiration biopsy in detection of acute rejection in children after liver transplantation

Diagnosis of acute rejection after liver transplantation is based mainly on clinical signs and the liver core biopsy findings. In this study we retrospectively analyzed our data on the routine use of fine-needle aspiration biopsy (FNAB) after 63 pediatric liver transplantations. A total of 824 FNABs was taken during the postoperative hospitalization, with a mean of 13 biopsies per patient. Forty-nine acute rejection episodes were diagnosed and treated after 39 transplantations (62%). The FNAB analysis detected rejections often before clinical signs. At the time of rejection diagnosis, fever was present in 38% of the patients, and serum bilirubin and alanine aminotransferase were elevated in only 19% and 13%, respectively. The rejections responded well to oral methylprednisolone, and lymphoglobulins were needed in only two episodes (4%). The results indicate that FNAB is a safe and sensitive method for the diagnosis and follow up of acute cellular rejection in pediatric liver recipients.     

Endocrinology: Normal serum uric acid concentrations in women with polycystic ovary syndrome

Recently, an inverse correlation between serum uric acid concentrationsand insulin sensitivity has been described in subjects withvarying degrees of metabolic syndrome, suggesting that measurementof serum uric acid may provide a simple marker of insulin resistance.Several biochemical and clinical features of polycystic ovarysyndrome (PCOS) resemble those of metabolic syndrome: womenwith PCOS are often obese; they are also at increased risk forthe development of coronary artery disease, hypertension anddiabetes mellitus. The objective of the present study was toanalyse the usefulness of serum uric acid measurement in screeningfor the metabolic syndrome in women with PCOS. For that purposeserum concentrations of uric acid, insulin and triglycerideswere measured in 38 women with PCOS and 20 weight-matched controlwomen with regular menstrual cycles. No differences were foundin the uric acid concentrations between the PCOS and controlgroups. The mean concentrations of triglycerides and fastinginsulin were higher in the women with PCOS than in the healthycontrols. Serum uric acid concentrations were inversely relatedto serum hormone-binding globulin (SHBG) concentrations, andpositively with body mass index (BMI), insulin concentrationsand testosterone:SHBG ratio in the PCOS group. Our results suggestthat measurement of serum uric acid does not provide new meansfor identification of metabolic syndrome in patients with PCOS.     

The persistence of teacher-reported behavioral problems among children aged 8 to 12

 This investigation assessed psychiatric symptoms in children reported by teachers at two points of time, and the persistence of symptom groups over an interval of four years. 1128 children born in 1981 (mean age 8.5 yr in Study 1 and 12.5 yr in Study 2) were studied, using the Rutter Scale B2 questionnaires in both studies. The frequencies of teacher-reported problems generally decreased over an interval of four years. Hyperkinetic symptoms were the most prevalent at both occasions. Gender differences were seen in both studies, boys outnumbering girls on most items. Symptoms were classified into five groups representing hyperactivity, internalizing and externalizing behaviour, relationship difficulties, and habits. The correlations of these different groups in Study 1 with those in Study 2 were moderate. Among deviant girls, correlations were high or moderate for externalizing, hyperactivity and internalizing behavior between the two studies. For deviant boys, high correlations between the studies were found for hyperactivity and habits. Externalizing behavior was also highly correlated with relationship difficulties among deviant boys. Two symptom groups (hyperactivity and relationship difficulties) and low performance level in Study 1 increased the probability of being deviant in Study 2 among boys, and four interactional terms (hyperactivity by relationship difficulties, hyperactivity by performance level, internalizing by performance level, and externalizing by relationship difficulties) also had an effect. Among girls, the probability of being deviant in Study 2 was increased if they were hyperactive or had relationship difficulties in Study 1. Furthermore, one interactional term (hyperactivity by performance level) had an impact on deviance among girls. Accepted: 22 January 1998     

Methanol as a Marker of Alcohol Abuse

Serum methanol levels were studied in 16 skid-row alcoholics, 16 alcoholics entering a detoxification unit, 193 drunken drivers, and 50 social drinkers, all of whom had a blood-ethanol concentration exceeding 5 mmol/liter at the time of sampling. Highest mean serum methanol level was found in alcoholics entering detoxification (636 +/- 68 mumol/liter, p less than 0.001 as compared to social drinkers), followed by skid-row alcoholics (567 +/- 105 mumol/liter, p less than 0.001), drunken drivers (231 +/- 11 mumol/liter, p less than 0.001) and social drinkers (127 +/- 10 mumol/liter). During 2 days heavy drinking mean serum methanol concentration in 10 nonalcoholic volunteers increased from 177 +/- 15 mumol/liter 1 h after the beginning of drinking to 322 +/- 29 mumol/liter 42 h after the beginning of drinking (p less than 0.001). In 70 of the drunken drivers urinary methanol concentration was determined as well and a fairly good correlation (r = +0.56, p less than 0.001) between serum and urinary methanol levels were found. Our results suggest that methanol determined either from serum or urine can be used as a biological marker of alcohol abuse.     

CMV infection, diagnosis and antiviral strategies after liver transplantation

Cytomegalovirus (CMV) is a significant pathogen complicating the post-transplant course of organ recipients. In liver transplant patients, the febrile clinical illness caused by CMV may be associated with end-organ disease, such as hepatitis or infection of the gastrointestinal tract. In addition to direct effects, CMV may have indirect effects including the risk of other infections or graft rejection. Recently, major advances in the management of CMV infection have been achieved through the development of new diagnostic techniques and antiviral strategies to prevent CMV disease. Quantitative nucleic acid testing to monitor viral load is now commonly used to diagnose and guide the treatment of CMV infections. The standardization of the testing, however, needs to be improved. There are two main strategies to prevent CMV disease after liver transplantation: prophylaxis and pre-emptive therapy. Both strategies are effective, but also have disadvantages. The disadvantages of prophylaxis include prolonged drug exposure, the development of resistance and, most of all, the development of delayed and late-onset CMV disease. On the other hand, the pre-emptive strategy is based on frequent laboratory monitoring of viral loads, and some patients may develop symptomatic infection before the diagnosis of CMV. This overview summarizes the current status of CMV in liver transplantation.     

Identification of reactive synthetic gliadin peptides specific for coeliac disease.

Gluten intolerance (coeliac disease) is characterised by the development of a small intestinal lesion following exposure to the gliadin fraction after consumption of wheat and related cereals. Cellular immune mechanisms are thought to be responsible for gliadin toxicity, but the toxic sequence/s within gliadin have not been clearly established. A panel of synthetic gliadin peptides was tested using peripheral blood mononuclear cells from coeliac patients and two assays for cell-mediated immunity. Using the indirect leucocyte migration inhibition factor and the macrophage procoagulant activity assays, gliadin peptides which were located in the aminoterminal or the proline-rich domain of the alpha/beta gliadin molecule were coeliac-active. Peptides predicted by T cell algorithms or on the basis of homology to adenovirus Ad12 Elb protein and which were located in the proline-poor gliadin domains were inactive. Protein sequence studies which indicate significant homology in the proline-poor gliadin domains with a number of non-coeliac-toxic seed proteins also supported the hypothesis that the proline-rich domains may be more important in the pathogenesis of coeliac disease.