Molecular variants of the ATM gene in Hodgkin's disease in children

Ataxia telangiectasia is an autosomal recessive disease with a striking predisposition of lymphoid malignancies. ATM mutations have been reported in adult sporadic lymphoma and leukaemia. The aim of this study was to investigate the possible involvement of the ATM gene in the carcinogenesis of Hodgkin disease in children. Tumours were obtained from 23 patients and were subjected to mutation screening and loss of heterozygosity analysis. Eight base substitutions were identified in seven patients. Of them, Y54Y, a silent change, was observed in two patients and a known polymorphism, D1853N, in three patients. Of the other two patients, one harboured a combined genotype P604S/F1463C, identified previously in two patients with Hodgkin lymphoma, and the other a novel missense mutation, V595A. The alterations were present in the germ line, and both had a more aggressive disease. In all, 100 matched normal ethnic controls were screened for these mutations and P604S/F1463C was identified in one healthy control. Loss of heterozygosity was identified in four patients and in three of them it was located centromeric to the ATM gene, and, in one, it spanned a large region, indicating the involvement of other tumour-suppressor genes in this disease. Missense variants of the ATM gene are a rare event in childhood Hodgkin disease.     

Acetazolamide-enhanced neuroSPECT scan reveals functional impairment after minimal traumatic brain injury not otherwise discernible

A patient suffering from aggressive personality changes and cognitive impairment following head trauma, without neurological or anatomical imaging findings, underwent neuroSPECT scans with and without acetazolamide injection, both before treatment and during treatment with valproate. Acetazolamide injection induced increased prefrontal perfusion not evident at baseline. Valproate treatment was associated with increased prefrontal perfusion concomitant with clinical improvement and abolished response to acetazolamide challenge.     

Coronary calcification compared in patients with acute versus in those with chronic coronary events by using dual-sector spiral CT

PURPOSE: To compare underlying calcific atherosclerotic lesions in acute versus chronic coronary events in patients with hypertension by using dual-sector spiral computed tomography (CT). MATERIALS AND METHODS: Eight hundred eighty-four calcific lesions were analyzed in a cohort of 50 patients (39 men, 11 women; age range, 55-79 years; mean age, 66 years +/- 6 [SD]) with hypertension who sustained a coronary event during 3-year follow-up. All underwent dual-sector spiral CT within 12 months before the event. Twenty-nine patients had an acute event (acute group): acute myocardial infarction, 20; unstable angina pectoris, six; acute ischemia, two; sudden death, one. Twenty-one patients had chronic manifestations of obstructive coronary disease (chronic group): severe stable angina, five; angiographically identified disease, 12; disease requiring angioplasty, two; and disease requiring bypass surgery, two. To examine differences between the two study groups, the chi(2) or Fisher exact test was applied to categorical parameters and the two-sample t test or Wilcoxon rank sum test to quantitative parameters. RESULTS: High prevalence of coronary calcium (total coronary calcium score [TCS] >0) was observed in both groups: 93% (27 of 29) in the acute and 95% (20 of 21) in the chronic group. There were 518 lesions in the chronic and 366 in the acute group, with a median number of 35 and nine lesions per patient, respectively (P <.001). The median TCS was 906 for the chronic and 63 for the acute group (P <.01). CONCLUSION: A mild degree of calcification characterizes patients with acute coronary events, while diffuse high-attenuation calcific plaques are associated with chronic coronary events.     

Patient and family physician preferences for care and communication in the eventuality of anthrax terrorism

BACKGROUND: The threat of bioterrorism consequent to the September 11, 2001 attack in the USA generated suggestions for improved medical response mainly through hospital preparedness. OBJECTIVES: The aim of the present study was to investigate the impact of this period of tension on patients' first choice for care and for receiving relevant information, and on primary care doctors' feelings of responsibility in the eventuality of an anthrax attack. METHODS: During October 11-31, 2001, 500 patients from 30 clinics throughout Israel were asked to complete a questionnaire on their awareness of the anthrax threat, measures taken to prepare for it, and preferred sources of care and information. Their 30 physicians, and an additional 20, completed a questionnaire on knowledge about anthrax and anthrax-related patient behaviours and clinic visits. RESULTS: The outstanding finding was the low rate (30%) of patients who chose the hospital emergency department as their first choice for care or information if they were worried about an anthrax attack or the media communicated that an attack was in progress. The other two-thirds preferred their family doctor or the health authorities. Most of the physicians (89%) felt it was their responsibility to treat anthrax-infected patients and that they should therefore be supplied with appropriate guidelines. CONCLUSION: This study suggests that in Israel, a country with a high degree of awareness of civil defence aspects, both patients and primary care doctors believe that family physicians should have a major role in the case of bioterrorist attacks. This must be seriously considered during formulation of relevant health services programmes.     

Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity

The cytokine interleukin-1 (IL-1) is produced by peripheral immune cells as well as glia and neurons within the brain; it plays a major role in immune to brain communication and in modulation of neural, neuroendocrine, and behavioral systems during illness. Although previous studies demonstrated that excess levels of IL-1 impaired memory processes and neural plasticity, it has been suggested that physiological levels of IL-1 are involved in hippocampal-dependent memory and long-term potentiation (LTP). To examine this hypothesis, we studied IL-1 receptor type I knockout (IL-1rKO) mice in several paradigms of memory function and hippocampal plasticity. In the spatial version of the water maze test, IL-1rKO mice displayed significantly longer latency to reach a hidden platform, compared with wild-type controls. Furthermore, IL-1rKO exhibited diminished contextual fear conditioning. In contrast, IL-1rKO mice were similar to control animals in hippocampal-independent memory tasks; i.e., their performance in the visually guided task of the water maze and the auditory-cued fear conditioning was normal. Electrophysiologically, anesthetized IL-1rKO mice exhibited enhanced paired-pulse inhibition in response to perforant path stimulation and no LTP in the dentate gyrus. In vitro, decreased paired-pulse responses, as well as a complete absence of LTP, were observed in the CA1 region of hippocampal slices taken from IL-1rKO mice compared with WT controls. These results suggest that IL-1 contributes to the regulation of memory processes as well as short- and long-term plasticity within the hippocampus. These findings have important implications to several conditions in humans, which are associated with long-term defects in IL-1 signaling, such as mutations in the IL-1 receptor accessory protein-like gene, which are involved in a frequent form of X-linked mental retardation.     

High frequency of loss of heterozygosity for 1p35-p36 (D1S247) in Wilms tumor

We analyzed the loss of heterozygosity (LOH) for 1p in 18 Wilms tumors using a panel of 11 polymorphic markers. Loss of heterozygosity was identified in 56% of the tumors. The smallest region of overlap was defined for marker D1S247, underlying the 1p35-1p36.1 locus. This is the highest LOH frequency for 1p, or for the well-defined 11p13 and 11p15.5 loci. Based on the fact that tumors of all stages, with both favorable and unfavorable histology, exhibited LOH, we suggest that the 1p35-1p36.1 locus is involved in the etiology of Wilms tumor.     

Is uterine papillary serous adenocarcinoma a manifestation of the hereditary breast-ovarian cancer syndrome?

BACKGROUND: Uterine papillary serous carcinoma (UPSC) shares common pathologic, genetic, and clinical features with other serous cancers of müllerian origin. The most common histologic type of ovarian tumor associated with BRCA mutations is papillary serous. Because of these histologic similarities, we postulated that, in some cases, UPSC may be a manifestation of a field defect in BRCA1 carriers, which also includes ovarian carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. METHODS: Fifty-six living patients with UPSC were contacted through their treating physicians and agreed to a family history interview and to provide a blood specimen for BRCA testing. The protein truncation test was used to detect mutations in exons 10 and 11 of BRCA1 and in exon 11 of BRCA2. The presence of four common mutations was assessed by PCR-based specific assays. RESULTS: A high proportion of patients had a past history of breast cancer (11%) or a first-degree relative with breast cancer (29%). Four patients were from families with site-specific hereditary breast cancer. However, there was no clear example of the hereditary breast-ovarian cancer syndrome, and none of the 56 patients was found to carry a BRCA1 or BRCA2 mutation. CONCLUSIONS: BRCA mutations do not appear to predispose to UPSC and this type of cancer does not appear to be a manifestation of the classical hereditary breast-ovarian cancer syndrome. The observed association between UPSC and breast cancer may be due to the presence of mutations in other cancer predisposing genes.