VASCULAR CONNECTIVE TISSUE CHANGES IN EXPERIMENTAL PORTACAVAL ANASTOMOSIS

Hepatic vascular changes are generally associated to fibrotic lesions of the liver but their role in the development and extension of fibrosis is not well known. By performing a portacaval anastomosis in rats, a proliferation of hepatic vessels was attained progressively, comparable to proliferations seen in cirrhosis and schistosomiasis. Such a modification of the hepatic vasculature was accompanied by changes in the connective matrix of the liver, mainly related to the vascular walls. Moreover, sinusoidal capillarization was detected at the electron microscopical level whereas no alterations could be seen neither in the distribution nor in the quality of the connective matrix proteins with Immunofluorescence technique. The only modification detected by light microscopy, at this zone, was the shrinked aspect of reticulin fibers which could be related to the important liver atrophy provoked by the anastomosis. It can be assumed that in liver pathology, selective changes occur in the connective matrix components depending on the type of injury. Necrotic and inflammatory processes lead mainly to the deposition of interstitial collagens and associated proteins, related to a diffuse stroma reaction resultant from activation of specific cell populations whereas in portacaval anastomosis, a selective increase of vascular connective matrix (mainly basement membrane components) occurs as a direct consequence of vessel proliferation.     

Regulatory aspects of drug dissolution from a European perspective.

The need for an early identification of formulation and manufacturing factors that are important for setting satisfactory specification limits for the dissolution rate of an active substance from a dosage form is emphasized. A discriminatory dissolution test has to be developed based on experiences from early drug development, bioavailability/bioequivalence studies and clinical trials. References are given to guidelines of the EU-system and to the monographs and chapters of the European Pharmacopoeia, which have to be considered. The dissolution test is expected to be an appropriate tool for checking that the manufacture of dosage forms is consistent and successful and that each dosage unit of a batch will have pharmaceutical qualities that correspond to those on which the safety and efficacy documentation of a product is based.     

Separation discrimination with embedded targets

Previous research has shown that separation discrimination thresholds are independent of the internal spatial scale (local spatial frequency) of the targets whose separation is being judged. The experiments reported here tested the generality of this conclusion for separation discrimination of targets that were embedded in an array of identical objects, where crowding could enhance the importance of the scale at which the individual target locations are encoded. No effect of the local spatial scale of the targets was found under these conditions.     

Cytogenetic analysis of tissues from patients with familial paragangliomas of the head and neck

Background. Paragangliomas of the head and neck are slow-growing tumors that originate from neural crest cells. Between 7% and 9% of these tumors have a familial occurrence. The suspected gene for familial paragangliomas (FP) is transmitted with an autosomal dominant mode of inheritance with incomplete penetrance, and appears to exhibit genomic imprinting. It has been demonstrated by family studies that individuals who inherit the gene(s) from their father will develop the disease. Through linkage analysis, the gene(s) for FP has been postulated to be located on the long arm of chromosome 11. The discovery of many different genes has been elucidated through the cytogenetic analysis of affected individuals who carry specific chromosome aberrations. This project was designed to look for chromosome abnormalities in several second-generation family members to further assist in the localization of the gene(s) for FP. Methods. This study involved the cytogenetic evaluation of lymphocytes, fibroblasts, and tumor cells of several second-generation family members from a three-generation family with FP of the head and neck to look for chromosome abnormalities generally, and for abnormalities of chromosome 11 specifically. Standard cytogenetic techniques were used for lymphocyte and fibroblast cultures. Tumor cells were cultured in a collagen matrix with F12 medium supplemented with 3% L-glutamine and 10% fetal calf serum. Results. There were no detectable abnormalities of chromosome 11 in any of the cells. However, nonrandom abnormalities of chromosomes 5 and 7 were seen in some of the tumor cells of one FP patient. To our knowledge, this is the first article which demonstrated the ability to successfully culture FP of the head and neck. © 1995 Jons Wiley & Sons, Inc.     

Users' subjective evaluation of electronic vision enhancement systems

The aims of this study were (1) to elicit the users' responses to four electronic head-mounted devices (Jordy, Flipperport, Maxport and NuVision) and (2) to correlate users' opinion with performance. Ten patients with early onset macular disease (EOMD) and 10 with age-related macular disease (AMD) used these electronic vision enhancement systems (EVESs) for a variety of visual tasks. A questionnaire designed in-house and a modified VF-14 were used to evaluate the responses. Following initial experience of the devices in the laboratory, every patient took home two of the four devices for 1 week each. Responses were re-evaluated after this period of home loan. No single EVES stood out as the strong preference for all aspects evaluated. In the laboratory-based appraisal, Flipperport typically received the best overall ratings and highest score for image quality and ability to magnify, but after home loan there was no significant difference between devices. Comfort of device, although important, was not predictive of rating once magnification had been taken into account. For actual performance, a threshold effect was seen whereby ratings increased as reading speed improved up to 60 words per minute. Newly diagnosed patients responded most positively to EVESs, but otherwise users' opinion could not be predicted by age, gender, diagnosis or previous CCTV experience. User feedback is essential in our quest to understand the benefits and shortcoming of EVESs. Such information should help guide both prescribing and future development of low vision devices.     

Diagnosing osteoporosis by using dental panoramic radiographs: the OSTEODENT project.

OBJECTIVES: Measurement of cortical thickness and subjective assessment of cortical porosity on panoramic radiographs are methods previously reported for diagnosing osteoporosis. The aims of this study were to determine the relative efficacy of the mandibular cortical index and cortical width in detecting osteoporosis, both alone and in combination, and to determine the optimal cortical width threshold for referral for additional osteoporosis investigation. STUDY DESIGN: Six hundred seventy-one postmenopausal women 45 to 70 years of age were recruited for this study. They received dual energy x-ray absorptiometry (DXA) scans of the left hip and lumbar spine (L1 to L4), and dental panoramic radiographic examinations of the teeth and jaws. Three observers separately assessed the mandibular cortical width and porosity in the mental foramen region of the mandible. Cortical width was corrected for magnification errors. Chi-squared automatic interaction detection analysis (CHAID) software was used (SPSS AnswerTree, version 3.1, SPSS Inc., Chicago, IL). RESULTS: Chi-squared automatic interaction detection analysis showed that the cortical porosity was a poorer predictor of osteoporosis than mandibular cortical width. For the 3 observers, a mandibular cortical width of <3 mm provided diagnostic odds ratios of 6.51, 6.09, and 8.04. The test is therefore only recommended in triage screening of individuals by using radiographs made for purposes other than osteoporosis. CONCLUSION: When evaluating panoramic radiographs, only those patients with the thinnest mandibular cortices (i.e., <3 mm) should be referred for further osteoporosis investigation.     

Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle

Human Molecular Genetics     

Department of law and ethics

The January 7, 1988 issue of The New England Journal of Medicine has two interesting articles concerning what might generally be termed euthanasia. The article titled Initiating and Withdrawing Life Support represents a consensus among members of the Stanford University Medical Center Committee on Ethics. Its main authors have written a fine example of applied ethics (1).