Chromosome mapping of multiple loci affecting the genetic predisposition to rat liver carcinogenesis

Previous studies on (BNxF344)F1 (BFF1) rat model of genetic predisposition to hepatocarcinogenesis led to the identification, in BFF1xF344 backcross progeny, of two hepatocarcinogenesis susceptibility (Hcs) and three resistance (Hcr) loci affecting the progression of neoplastic liver nodules. To evaluate the presence of other hepatocarcinogenesis-related loci in the BFF1 genome, nodule induction by resistant hepatocyte model in 116 male BFF2 rats 32 weeks after initiation with diethylnitrosamine was subjected to quantitative trait loci analysis. The rats were typed with 179 genetic markers, and linkage analysis identified three loci on chromosomes 1, 16, and 6, in significant linkage with nodule mean volume (V), volume fraction, and number, respectively, and two loci on chromosomes 4 and 8 in suggestive linkage with V. These loci were differently positioned with respect to Hcs and Hcr loci mapped previously in backcross rats. On the basis of phenotypic and allele distribution patterns of BFF2 rats, loci on chromosomes 1 and 16 were identified as Hcs3 and Hcs4, and loci on chromosomes 4, 8, and 6 as Hcr4, Hcr5, and Hcr6. Additive interactions occurred between Hcs3 and Hcs4, and Hcr4 and a locus on chromosome 3 with less than suggestive linkage with V. All of the loci were in chromosomal regions syntenic to mouse and/or human chromosomal segments showing allelic gain or loss in hepatocellular carcinomas. These data indicate that inheritance of predisposition to rat liver tumor is characterized by the interplay of several genetic factors and suggest some possible mechanisms of polygenic control of human liver cancer.     

Use of lipid-lowering drugs and blood pressure control in patients with arterial hypertension

A large proportion of patients have both hypertension and hypercholesterolemia, two of the most important risk factors for cardiovascular diseases. Statins are the most widely used drugs for the treatment of plasma lipid abnormalities and have been reported to interact with elevated blood pressure. A reduction in blood pressure associated with the use of these agents has been reported in patients with untreated hypertension and in patients treated with antihypertensive drugs, particularly angiotensin-converting enzyme inhibitors and calcium channel blockers. This effect on blood pressure control has also been observed in diabetic patients. The mechanism responsible for the hypotensive effect seems to be largely independent of the effect of statins on plasma cholesterol, and probably is related to the interaction of the medications with endothelial function or angiotensin II receptors. The capacity of statins to improve blood pressure control may represent a useful tool for improvement in the prevention of cardiovascular diseases.     

Cell cycle deregulation in liver lesions of rats with and without genetic predisposition to hepatocarcinogenesis

Preneoplastic and neoplastic hepatocytes undergo c-Myc up-regulation and overgrowth in rats genetically susceptible to hepatocarcinogenesis, but not in resistant rats. Because c-Myc regulates the pRb-E2F pathway, we evaluated cell cycle gene expression in neoplastic nodules and hepatocellular carcinomas (HCCs), induced by initiation/selection (IS) protocols 40 and 70 weeks after diethylnitrosamine treatment, in susceptible Fisher 344 (F344) rats, and resistant Wistar and Brown Norway (BN) rats. No interstrain differences in gene expression occurred in normal liver. Overexpression of c-myc, Cyclins D1, E, and A, and E2F1 genes, at messenger RNA (mRNA) and protein levels, rise in Cyclin D1-CDK4, Cyclin E-CDK2, and E2F1-DP1 complexes, and pRb hyperphosphorylation occurred in nodules and HCCs of F344 rats. Expression of Cdk4, Cdk2, p16(INK4A), and p27(KIP1) did not change. In nodules and/or HCCs of Wistar and BN rats, low or no increases in c-myc, Cyclins D1, E, and A, and E2F1 expression, and Cyclin-CDKs complex formation were associated with p16(INK4A) overexpression and pRb hypophosphorylation. In conclusion, these results suggest deregulation of G1 and S phases in liver lesions of susceptible rats and block of G1-S transition in lesions of resistant strains, which explains their low progression capacity.     

Esophago-pharyngeal diverticulum: a case report

The Authors report a case of Zenker's diverticulum seen and treated at the University Department of Surgical Sciences of the University of Foggia. The treatment of this condition is invariably surgical and consists in a diverticulectomy combined with a lengthwise extramucosal myotomy. This latter technical adjunct, however, would not appear to be accepted by all Authors. Other techniques have been proposed for the treatment of this condition, but no confirmation of their efficacy exists in the literature. Mortality fluctuates in the various case series, from 0.45% to 8.1%, and the morbidity varies from 5.3% to 40%. The risk of postoperative complications is always present, but can be reduced if the patient undergoes a thorough preoperative investigation.     

Qualitätskontrolle audiologischer Befunde einer universitären phoniatrisch/pädaudiologischen Einrichtung

AIM: An investigation was made to reveal whether suspicion of occupational hearing loss can be satisfactorily determined by an otolaryngologist or workplace audiological measurement. These were compared with a formal audiometrical assessment at a university clinic. METHODS AND RESULTS: A retrospective study was made of 95 cases of noise induced hearing loss. A total of 78 individuals were investigated by an otolaryngologist and 70 by workplace audiometry. Using workplace audiometry, 27% of the tests showed a reduction in working capacity of at least 20%. In only five of these was a specialist opinion sought within a year. In 50%, this took longer than 5 years. A comparison of audiometric data from expert opinion revealed that there was conformity in only 47% with workplace audiometry and 48% with otolaryngologist testing. In some cases (27% workplace and 33% ENT practice), the measured hearing loss and calculation of disability exceeded that determined by the experts. CONCLUSIONS: The results of workplace audiometry demonstrated that hearing loss was frequently reported only after the workers had received a disability of at least 20%. Possible reasons for discrepancies in audiological testing might be the exaggeration of hearing loss by the worker, insufficient recovery time after noise exposure, or inexperienced audiologists. Our data show that audiometric testing in workplace audiometry, as well as in ENT practice, often reveal a higher disability rating compared to formal audiological (university) assessment, even if these discrepancies do not reach statistical significance.     

Einflussfaktoren auf die Rehabilitation der Innenohrschwerhörigkeit mit Hörgeräten

BACKGROUND: A large proportion of older as well as younger patients do not use their hearing aids. Of the younger hearing impaired population, this occurs in the majority of those who do not benefit sufficiently from their hearing aids and, consequently, they face difficulties in their working and social life. SCIENTIFIC QUESTION: Our aim was to evaluate whether a classical hearing aid adjustment is of sufficient predictive value to determine whether adequate rehabilitation in everyday and professional life will occur. METHODS AND RESULTS: A questionnaire was returned by 197 adult hearing impaired patients. Only 108 were using their hearing aids all the time; 57 rarely and 32 never. The main reason for this low rehabilitation rate proved to be inadequate amplification. At the workplace, insufficient speech discrimination came into play. Another important factor was dysacusis induced by specific noise signals. There was an intolerable acoustic feedback in 40% which could not be sufficiently alleviated. Taking these results into account, only about a third of patients were sufficiently rehabilitated. CONCLUSIONS: Proof of effectiveness in a typical audiological testing situation is an important but not a fully reliable predictor for effectiveness in everyday life. Even when hearing aids are shown to be effective with such testing, their application in particular everyday or work situations may be insufficient of even impossible.     

Malignant cervical teratoma: report of a case in a newborn

Malignant cervical teratoma (MCT) usually appears in newborns as an enlarging mass of the neck that causes respiratory distress, requiring prompt airway control. We report a case of MCT in an infant electively delivered at 32 weeks to prevent airway impairment. At first, the preoperative diagnosis was hygroma of the neck, and a surgical excision was performed when the newborn was 9 days old. Diagnosis was benign extragonadic immature teratoma, but it was changed in MCT when cervical metastases appeared and the alpha-fetoprotein (AFP) level increased. Subsequent surgical procedures and chemotherapy were necessary. The child has been free from disease and healthy for 7 years since the last surgery. The preoperative diagnosis of MCT is difficult because of its rarity and non-specific clinical findings. Surgical excision is required for an adequate cure and airway repair; a long-term follow-up is mandatory to promptly treat any recurrence.     

Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia. It is characterized by beta-amyloid (A beta) plaques, neurofibrillary tangles and the degeneration of specifically vulnerable brain neurons. We observed high expression of the cholesterol 25-hydroxylase (CH25H) gene in specifically vulnerable brain regions of AD patients. CH25H maps to a region within 10q23 that has been previously linked to sporadic AD. Sequencing of the 5' region of CH25H revealed three common haplotypes, CH25Hchi2, CH25Hchi3 and CH25Hchi4; CSF levels of the cholesterol precursor lathosterol were higher in carriers of the CH25Hchi4 haplotype. In 1,282 patients with AD and 1,312 healthy control subjects from five independent populations, a common variation in the vicinity of CH25H was significantly associated with the risk for sporadic AD (p = 0.006). Quantitative neuropathology of brains from elderly non-demented subjects showed brain A beta deposits in carriers of CH25Hchi4 and CH25Hchi3 haplotypes, whereas no A beta deposits were present in CH25Hchi2 carriers. Together, these results are compatible with a role of CH25Hchi4 as a putative susceptibility factor for sporadic AD; they may explain part of the linkage of chromosome 10 markers with sporadic AD, and they suggest the possibility that CH25H polymorphisms are associated with different rates of brain A beta deposition.     

A follow-up study of patients with Zollinger-Ellison syndrome in the period 1966-2002: effects of surgical and medical treatments on long-term survival

AIM: To evaluate the clinical history of a series of patients with Zollinger-Ellison syndrome (ZES) in the period 1966 to 2002, before and after the introduction of the current antisecretive H2 receptor antagonists and proton pump inhibitors into clinical practice. PATIENTS AND METHODS: The study involved 18 ZES patients (9 males; mean age, 43 years; range, 12-70 years), 8 with Type 1 multiple endocrine neoplasia (MEN-1), diagnosed on the basis of standard criteria. We considered the type, number and effectiveness of surgical interventions before and after appropriate treatment, the localization of the gastrinoma, the presence of associated diseases, the causes of death, and the duration of survival. RESULTS: Total gastrectomy (but not antrectomy and vagotomy) and full compliance to antisecretory treatment reduced the number of operations from 29 to 9. One patient was cured (5.5%), whereas relapsing gastrinomas occurred in 4 patients and associated diseases or complications in ten. Death was related to ZES in 5 patients and to other causes in 4. CONCLUSIONS: Curing gastrinoma or appropriately inhibiting gastric acid hypersecretion in ZES patients prevent death and favors long-term survival, regardless of gastrin levels and the size or number of tumors.