Deletion of the Ink4-locus (the p16ink4a, p14ARF and p15ink4b genes) predicts relapse in children with ALL treated according to the Nordic protocols NOPHO-86 and NOPHO-92.

Inactivation of the Ink4 gene locus locus on 9p comprising the tumour suppressor gene p16ink4a and its neighbours p14ARF and p15ink4b is common in childhood acute lymphoblastic leukaemia (ALL), but the prognostic significance is controversial. DNA from 230 patients was retrospectively analysed by Southern blotting, single strand conformation polymorphism (SSCP) and sequencing techniques. The results were correlated with clinical characteristics and outcome. One hundred and ninety-four fully analysed patients, similarly treated using the Nordic NOPHO-86 or the current NOPHO-92 protocols, were included in the outcome analysis. Deletions approached a minimally deleted region between the p16ink4a and p15ink4b genes, making the p14ARF gene the most commonly deleted coding sequence. Bi-allelic deletion was associated with high white blood cell count (WBC) (P < 0.001), T cell phenotype (P < 0.001) and mediastinal mass (P < 0.001). Patients with Ink4 locus bi-allelic deletions had an inferior pEFS (P < 0.01) and multivariate analysis indicated that bi-allelic deletion of the p16ink4a and the p14ARF genes was an independent prognostic risk factor (P < 0.05). Sub-group analysis revealed a pronounced impact of deletion status for high-risk patients, ie with high WBC. Deletion-status and clinical risk criteria (WBC) could thus be combined to further differentiate risk within the high-risk group. The analysis of the Ink4 locus adds independent prognostic information in childhood ALL treated by Nordic protocols and may help in selection of patients for alternative treatment.     

Abordaje conservador del embarazo ectópico cervical

Cervical pregnancy is a rare form of ectopic pregnancy with a high risk of hemorrhage. Early diagnosis is an important prognostic factor for survival and preserved fertility in these patients. We present the case of a patient diagnosed with cervical ectopic pregnancy in her seventh week of gestation. The therapeutic management was conservative and involved the combination of systemic and intra-amniotic methotrexate Because of the lower associated morbidity and mortality and the possibility of maintaining the patient’s fertility, conservative treatment is a viable therapeutic approach in cases such as that presented herein.     

Renal artery calcified aneurysm in a female patient with solitary kidney, rare pathology

Renal artery aneurysm are uncommon. The true prevalence of renal aneurysms in the general population is unknown (less than 0.4%). Because of more widespread use of Angiography and CT as well as improved imaging techniques, they are diagnosed more frecuently. Fibromuscular dysplasia and arteriosclerotic occlusion of the renal artery are believed to be the most frecuent causes. In general, there are no pathognomonic signs and symptoms of renal aneurysm. Nonspecific complaints include flank pain, hematuria, hypertension and hypotension (suspect rupture of aneurysm). We report a case of a woman with a renal artery calcified aneurysm in a solitary kidney.     

Laryngeal papillomatosis - first recognition in Germany as an occupational disease in an operating room nurse

BACKGROUND: The CO (2)-Laser is an established and well-proven tool in the excision and vaporisation of laryngeal papillomatosis. Actually there exists only one report of an iatrogenous infection with the Human Papillomavirs (HPV) in a gynecological laser surgeon. CASE REPORT: A 28-year-old gynecological operating room nurse, who assisted repeatedly in electrosurgical and lasersurgical excisions of anogenital condylomas, developed a recurrent and histologically proven laryngeal papillomatosis. The expert opinion of a virological institute confirmed a high probability of correlation between the occupational exposition and the laryngeal papillomatosis so that it was accepted as occupational disease. INFECTIVITY OF LASER PLUME: HPV-DNA has been repeatedly detected in laser-plume after excision of papillomas and condylomas. As of the present an exact proof that these particles are infectious has not been brought forward. CONCLUSION: When following the recommended protective measures the potential risk of infection is estimated as very low for surgeons and nurses. The risk of exposition seems to be higher in gynecological interventions than in ENT because of the much larger tissue masses and because laser plume escapes easier into the room air when applying an open approach.     

Geographical distribution of the male/female ratio of cardiovascular mortality in Spain

Objectives: To describe the geographic distribution of the male/female ratio (MFR) of mortality from ischaemic heart disease (IHD) and cerebrovascular disease (CVD) in 1991-1995 in Spain, and to examine wether the differences between men and women in exposure to cardiovascular risk factors could explain such distribution.Methods: Mortality data come from National Vital Statistics. Age-adjusted mortality rates for the period 1991-1995 were calculated for IHD and CVD using the direct method, in population aged 40 to 79 years. Data on tobacco and alcohol consumption, hypertension, hypercholesterolemia, diabetes, obesity, sedentariness, and health services use come from the 1993 Spanish National Health Survey, and socioeconomic data from the 1991 Population Census. Data were analyzed by correlation and Poisson regression methods.Results: MFR of mortality from IHD and CVD are higher in the provinces of the north of Spain, and are correlated negatively with mortality from IHD and CVD. This negative association is stronger for mortality in women than in men. Among the risk factors examined, only MFR of alcohol consumption showed a significant (p < 0.05) association with MFR of mortality from IHD and CVD. MFR of alcohol consumption explains 23 and 14% of the provincial variation in MFR of mortality from IHD and CVD, respectively, and showed a U shaped relationship with MFR of mortality for both diseases.Conclusions: Provinces in the north of Spain, which register the lowest cardiovascular mortality, show the highest MFR of IHD and CVD mortality, because of the lower mortality in women than in men. As derived from the dose-response relationship between MFR of IHD and CVD mortality and the MFR of alcohol consumption, a higher alcohol consumption in men could contribute to a higher MFR of cardiovascular mortality in some Spanish provinces.     

A new family with hereditary choreo-acanthocytosis

We describe a new family with hereditary choreo-acanthocytosis. Two members of this family were affected; neither of them suffered from anaemia or signs of haemolysis. The acanthocytes showed an impaired deformability with an increase in whole blood viscosity. The composition of the plasma and erythrocyte membrane lipids was normal, as was the fatty acid composition of the erythrocyte ghost membranes. The only alteration found was a decrease in the fluidity of the erythrocytic membrane.     

Dietary factors and prostatic cancer

In order to learn about the influence of dietary factors and obesity on prostatic cancer in our environment, a case-control study was performed. The group of cases consisted of 90 men histologically diagnosed with prostatic cancer in the 'La Paz' hospital (Madrid) during the 4-year period of 1983-1987. The controls were 180 men selected to obtain a random sample of males from the same hospital, stratified according to age and date of admission as compared with the prostatic cancer patients. The results of the study revealed that a diet rich in animal fats as well as high in meat consumption increased the risk of prostatic cancer. Low ingestion of vitamin A or vitamin C and obesity were unassociated to the disease.     

Cerebrospinal fluid biomarkers in human genetic transmissible spongiform encephalopathies

The 14-3-3 protein test has been shown to support the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) when associated with an adequate clinical context, and a high differential potential for the diagnosis of sporadic CJD has been attributed to other cerebrospinal fluid (CSF) proteins such as tau protein, S100b and neuron specific enolase (NSE). So far there has been only limited information available about biochemical markers in genetic transmissible spongiform encephalopathies (gTSE), although they represent 10–15% of human TSEs. In this study, we analyzed CSF of 174 patients with gTSEs for 14-3-3 (n = 166), tau protein (n = 78), S100b (n = 46) and NSE (n = 50). Levels of brain-derived proteins in CSF varied in different forms of gTSE. Biomarkers were found positive in the majority of gCJD (81%) and insert gTSE (69%), while they were negative in most cases of fatal familial insomnia (13%) and Gerstmann-Sträussler-Scheinker syndrome (10%). Disease duration and codon 129 genotype influence the findings in a different way than in sporadic CJD.     

Diagnostic, prognostic and pathogenic value of the direct immunofluorescence test in cutaneous leukocytoclastic vasculitis

BACKGROUND: No precise studies have been performed on cutaneous leukocytoclastic vasculitis (LV) to establish whether it is better to obtain a skin biopsy from lesional or from perilesional skin for direct immunofluorescence (DIF). There is no agreement on the immunoglobulins most frequently detected and the value of DIF for the classification of cutaneous vasculitis. METHODS: A prospective study of DIF in lesional and perilesional skin was performed in 50 leukocytoclastic vasculitis patients and 15 nonvasculitis patients. RESULTS: We detected a higher level of positivity in involved skin than in uninvolved skin for IgG, IgA, IgM, C3 and fibrinogen but not for C1q. In vasculitic patients, IgA was the immunoglobulin most frequently detected in lesional (82%) and perilesional skin (68%), followed by IgM (56 and 34%, respectively) and IgG (20 and 8%, respectively). Only IgA deposits were associated with the diagnosis of vasculitis, with a sensitivity of 82% in lesional and 68% in perilesional skin, and with a specificity of 73 and 66.7%, respectively. The presence of IgA in lesional skin was associated with renal involvement but there was no association with severity. The presence of IgG or IgM, or the absence of IgA in perilesional skin was related to the presence of cryoglobulins. The absence of IgA in lesional and perilesional skin was also related to hepatitis C virus infection. CONCLUSIONS: DIF findings in involved skin are more closely related to the diagnosis of vasculitis and can give more information about overall renal involvement than findings in uninvolved skin. However, findings in uninvolved skin are more closely related to the pathogenic factors that trigger the development of vasculitis.