The ancestral gene for transcribed, low-copy repeats in the Prader- Willi/Angelman region encodes a large protein implicated in protein trafficking, which is deficient in mice with neuromuscular and spermiogenic abnormalities

Transcribed, low-copy repeat elements are associated with the breakpoint regions of common deletions in Prader-Willi and Angelman syndromes. We report here the identification of the ancestral gene ( HERC2 ) and a family of duplicated, truncated copies that comprise these low-copy repeats. This gene encodes a highly conserved giant protein, HERC2, that is distantly related to p532 (HERC1), a guanine nucleotide exchange factor (GEF) implicated in vesicular trafficking. The mouse genome contains a single Herc2 locus, located in the jdf2 (juvenile development and fertility-2) interval of chromosome 7C. We have identified single nucleotide splice junction mutations in Herc2 in three independent N-ethyl-N-nitrosourea-induced jdf2 mutant alleles, each leading to exon skipping with premature termination of translation and/or deletion of conserved amino acids. Therefore, mutations in Herc2 lead to the neuromuscular secretory vesicle and sperm acrosome defects, other developmental abnormalities and juvenile lethality of jdf2 mice. Combined, these findings suggest that HERC2 is an important gene encoding a GEF involved in protein trafficking and degradation pathways in the cell.      

The use of single bipolar scalp derivation for the detection of ictal events during long‐term EEG monitoring

Aim. Epilepsy is difficult to diagnose using routine EEG recordings of short duration in patients who have low seizure frequency. Long‐term EEG may be useful but is impractical in an out‐of‐hospital setting. We investigated whether single‐channel scalp EEG placed behind the earlobe is suitable for seizure identification during prolonged EEG monitoring. Methods. Scalp EEG samples were selected from subjects over 15 years of age, and comprised two segments of either background followed by seizure or background followed by background. Bipolar EEG derivations in three directions (F8‐T8, C4‐T8 and T8‐P8) were evaluated for the presence of a seizure by two experienced reviewers. For each EEG segment containing a seizure, one pair of electrodes was oriented towards the suspected region of seizure onset, while two pairs of electrodes were oriented elsewhere. Results. The EEG data contained five frontally localized seizures, five parietal, five temporal, two occipital, and four primary or secondary generalized seizures. The sensitivity and specificity for recognition of seizures was 86% and 95% for Reviewer 1, and 79% and 99% for Reviewer 2, respectively. When identifying a seizure with the lead orientation towards the region of seizure onset, both reviewers identified 20 out of 21 seizures (95%). When the lead was not oriented towards the region of seizure onset, the reviewers identified 34 and 30 out of 42 ictal records correctly, respectively. Conclusions. These results suggest that it is possible to identify epileptic seizures by bipolar EEG derivation using only two scalp electrodes. Lead orientation towards the suspected region of seizure onset is important for optimal detection sensitivity.     

Endoscopies in Pediatric Small Intestinal Transplant Recipients: Five Years Experience

Objective : Intestinal transplantation has become an option as a treatment for permanent intestinal failure. Endoscopy is an essential tool in assessing the intestinal allograft after intestinal transplantation. The aim of this study was to analyze our experience using endoscopy in intestinal transplant recipients. Methods : This was a retrospective review of endoscopic and histological reports in 41 children who received an intestinal transplant between 1990 and 1995 at Children's Hospital of Pittsburgh. Results : A total of 1273 endoscopies was performed of which 760 were ileoscopies via allograft ileostomy, 273 were upper endoscopies, and 240 were colonoscopies. One hundred four rejection episodes were documented histologically in 32 patients, 6 days to >4 yr after transplantation. Most episodes were mild and easily treated with increased immunosuppression; however, severe rejection with mucosal exfoliation was seen in nine patients. Rejection sometimes involved only part of the allograft. Endoscopic appearance alone without biopsies was sensitive enough to diagnose only 63% of the rejection episodes. Epstein-Barr and cytomegalovirus infections occurred in 11 and eight patients, respectively, and involved both native bowel and allograft in some. Complications of endoscopy were few: one perforation, three episodes of bleeding, and three episodes of transient respiratory compromise. Conclusions : Endoscopy is an essential tool in the postoperative assessment of intestinal transplant recipients. Frequent surveillance ileoscopies with biopsies should be performed after transplantation. If patients clinically deteriorate with fever, diarrhea, bacteremia, or gastrointestinal bleeding and a clear cause is not elucidated by ileoscopy, an upper endoscopy with biopsies is indicated.     

The practice guideline 'Acne' (second revision) from the Dutch College of General Practitioners; a response from the perspective of dermatology

The second revised practice guideline 'Acne' from the Dutch College of General Practitioners contains adequate and scientifically well-supported recommendations for the management of patients with acne. There are some concerns about the initial treatment steps in these guidelines which only allow very slow progress to systemic therapy. This might, in some cases, lead to inadequate treatment of patients with more severe acne.     

Survival and prognostic factors of endometrial cancer patients in Iceland 1964–1985: Can attendance at population-based pap-smear screening affect survival?

After histological review of all cases registered during the period 1964–1985 at the Cancer Registry, 260 cases with endometrial carcinoma were eligible for analyses of survival rates and prognostic factors, as well as the association of Pap-smear screening attendance with these factors and survival. The total age-adjusted 5- and 10-year relative survival rates were 76% and 75%, respectively. The prognostic factors were tested by univariate analysis and simultaneously by a multivariate analysis using the Cox proportional hazards model. Factors that independently gave a less favorable prognosis were non-attendance at screening, older age at diagnosis, deep myometrial invasion, advancing stages and tumor grading, radiotherapy only, extra-genital symptoms and histology types of serous, clear cell and undifferentiated tumors (histologic type 3). Tested simultaneously with the Cox proportional hazards model, parameters that maintained a less favourable prognosis were grade 3, stage III-IV, deep myometrial invasion, older age, radiotherapy only and extra-genital symptoms. In addition, screening attendance showed significant interaction with age. In stages III and IV only grade 3 maintained a significantly less favorable prognosis. We conclude that our results indicate that attendance at Pap-smear screening (taking Pap smears and screening for genital symptoms) has a favorable prognostic value, especially among women under the age of 62. Int. J. Cancer (Pred. Oncol) 79:166–174, 1998.© 1998 Wiley-Liss, Inc.     

Human papillomavirus (HPV) in an Icelandic population: The role of HPV DNA testing based on hybrid capture and PCR assays among women with screen-detected abnormal pap smears

This study was based on 358 cases with abnormal smears referred for colposcopy and HPV DNA testing. We analysed: 1) the frequency of different grades of cyto- and histopathologic findings; 2) the frequency and relative amount of HPV DNA with the hybrid capture assay (HCA) in swabs, and the frequency of HPV with PCR in swabs (-S) and biopsies (-B); and 3) the frequency of HPV types according to the grade of the cyto- and histopathologic findings. Of all cases, 95% were positive with all HPV tests combined. The HCA (HPV: 16, 18, 31, 33, 35, 45, 51, 52 and 56) and the PCR-S and PCR-B (HPV: 16, 18, 31, 33 and 35) tests for high-risk HPV exhibited sensitivities of 57%, 56% and 48%, respectively. The high-grade smears and the high-risk PCR-S HPV had about 80% sensitivity for histologic high-grade lesions compared with around 70% for HCA and the PCR-B. Combining the high-grade smears and the high-risk HPV increased the sensitivity to 93–96%. Among the cervical intraepithelial neoplasia I (CIN I) and the atypical squamous cells of undetermined significance (ASCUS) smears the sensitivity of high-risk HPV for high-grade histologic lesions was 63% for the HCA and 79% for the PCR-S. No correlation was found between the relative amount of HPV DNA detected by HCA and the grade of cyto- and histological lesions. We conclude that the results strongly indicate that HCA is less sensitive than PCR in the diagnosis of high-risk HPV, that swabs are more sensitive than biopsies as a sampling method, that high-risk HPV and high-grade smears are complementary for the diagnosis of high-grade histologic lesions and that the present role of HPV testing in screening could be limited to identifing women with low-grade smears and koilocytotic or low-grade colposcopic biopsies that are at risk of concealing or developing high-grade histologic lesions. Int. J. Cancer 72:446–452, 1997. © 1997 Wiley-Liss, Inc.     

Medical treatment and secondary prevention of coronary heart disease in general practice in Iceland

Objective - To evaluate the implementation of secondary prevention and treatment of coronary heart disease (CHD) in general practice in Iceland. Settings - Two health care centers adjacent to Reykjavik with a total of 25766 inhabitants. Patients - All patients (533) with CHD living in the study area were sent an invitation letter and a request for informed consent. Those who chose to participate answered a questionnaire about CHD risk factors and their current treatment, and their medical records were reviewed. The patients were divided into four groups on the basis of their history: I. Coronary artery bypass surgery (CABG), II. Percutaneous transluminal coronary angioplasty (PTCA), III. Myocardial infarction (MI), IV. Angina pectoris (AP). If a patient fulfilled the criteria for more than one diagnostic group the CABG group had the highest priority followed by PTCA, MI and finally AP. Main outcome measures - Blood pressure, smoking habits, BMI, exercise profile, cholesterol levels and drug therapy. Results - Of 533 patients with CHD, 402 (75%) participated in the study, 15% were managed exclusively by their family physician and 23% by both cardiologists and family physicians. Obesity was relatively common, with nearly 60% being overweight (BMI > 25). Average cholesterol in the total group was 6.2 mmol/L (95% CI 6.07 to 6.34). Blood pressure had been recorded in 92% of the patients, and mean systolic and diastolic blood pressures were 143 and 82 mmHg, respectively. While 15% were current smokers, 56% were ex-smokers. A total of 113 patients (28%) were being treated with cholesterol-lowering drug therapy at the time of the study. Respective treatment ratios in the four subgroups were 47% in group I, 42% in II, 25% in III and 13% in group IV. Aspirin was taken by 284 patients (71%), beta blockers by 52% and calcium channel blockers by 36%. More than twice as many women than men were treated with nitrates, 57% versus 27%. Conclusions - The results indicate that there are numerous possibilities for improvements in secondary prevention and medical management of coronary heart disease in Iceland. Particular emphasis should be placed on smoking cessation, life-style modification with exercise and diet recommendations to lower BMI and lipid-lowering therapy.