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.     

Geriatric heart failure, depression, and nursing home admission: an observational study using propensity score analysis.

OBJECTIVE: Heart failure (HF) and depression are both common in older adults, and the presence of depression is known to worsen HF outcomes. For community-dwelling older adults, admission to a nursing home (NH) is associated with loss of independent living and poor outcomes. The objective of this study was to examine the effect of depression on NH admission for older adults with HF. METHODS: Using the 2001-2003 National Hospital Discharge Survey datasets, the authors identified all community-dwelling older adults who were discharged alive with a primary discharge diagnosis of HF. The authors then identified those with a secondary diagnosis of depression. Using a multivariable logistic regression model, the authors then determined probability or propensity to have depression for each patient. The authors used propensity scores for depression to match all 680 depressed patients with 2,040 nondepressed patients. Finally, the authors estimated the association between depression and NH admission using bivariate and multivariable logistic regression analyses. RESULTS: Patients had a mean (+/- standard deviation) age of 79 (+/- 8) years, 72% were women, and 9% were blacks. Compared with 17% nondepressed patients, 25% depressed patients were discharged to a NH. Depression was associated with 50% increased risk of NH admission (unadjusted relative risk [RR]: 1.50; 95% confidence interval [CI]: 1.28-1.74). The association became somewhat stronger after multivariable adjustment for various demographic and care covariates (adjusted RR: 1.60; 95% CI: 1.35-1.68). CONCLUSION: In ambulatory older adults hospitalized with HF, a secondary diagnosis of depression was associated with a significant increased risk of NH admission.     

A computer and video display based system for training eccentric viewing in macular degeneration with an absolute central scotoma

A new approach designed to establish the most suitable area for eccentric viewing and to teach and train patients with severe age-related macular degeneration (AMD) to use the eccentric viewing technique is described. Using a computer and video display based system, as well as software written specifically for this purpose, we investigated and trained ten consecutive patients with AMD. The patients were 80.1 ± 5.6 years old, on average. All of them had an absolute central scotoma. Mean visual acuity was 0.035 ± 0.016. After 30 min of testing, instruction and reading on the screen, followed by 2.6 ± 0.69 one-hour training sessions, on average, with the low vision therapist, reading newspaper and book texts with the aid of hyperoculars or aplanatic systems and a very short reading distance, the patients achieved a reading speed of 58.9 ± 19.7 words/min, significantly (p<0.001) higher than the initial speed when reading on the screen, 11.5 ± 4.5 words/min.     

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.     

Challenges in the Diagnosis of the Right Patient for Testosterone Replacement Therapy

Diagnosis of testosterone deficiency is important to identify patients who might benefit from testosterone replacement therapy. Unfortunately, the diagnosis of hypogonadism may be a challenge for many practicing physicians, including endocrinologists and urologists. Signs and symptoms, such as sexual dysfunction, change in body composition, lethargy, and mood changes, are nonspecific and the available questionnaires are generally not useful in clinical practice. The diagnosis of testosterone deficiency is ultimately based on measurement of serum testosterone levels. However, marked variations in the reference ranges of serum testosterone levels among laboratories pose a challenge for physicians when interpreting the results. In addition, initial laboratory assessments usually determine total testosterone levels. About 1–2% of total testosterone is free and a further 30–50% is bound with low affinity to albumin; only these two components are bioavailable to the target tissues. In general, assuming the normal reference range for serum total testosterone in adult men is 300–1000 ng/dl (10–35 nmol/l), levels of < 250 ng/dl (8.7 nmol/l) suggest the patient is likely to be hypogonadal, whereas levels of > 350 ng/dl (12.7 nmol/l) suggest the symptoms may not be due to androgen deficiency. Values between 250 to 350 ng/dl warrant a repeat morning serum testosterone determination with assessment of free or bioavailable testosterone. In men with symptoms suggestive of androgen deficiency and borderline serum testosterone levels, where there are no contraindications to androgen therapy, a short therapeutic trial of testosterone may be justified.     

Computer-assisted LISS plate osteosynthesis of proximal tibia fractures: feasibility study and first clinical results.

Fluoroscopy is the most common tool for the intraoperative control of long-bone fracture reduction. Limitations of this technology include high radiation exposure for the patient and the surgical team, limited visual field, distorted images, and cumbersome verification of image updating. Fluoroscopy-based navigation systems partially address these limitations by allowing fluoroscopic images to be used for real-time surgical localization and instrument tracking. Existing fluoroscopy-based navigation systems are still limited as far as the virtual representation of true surgical reality is concerned. This article, for the first time, presents a reality-enhanced virtual fluoroscopy with radiation-free updates of in situ surgical fluoroscopic images to control metaphyseal fracture reduction. A virtual fluoroscopy is created using the projection properties of the fluoroscope; it allows the display of detailed three-dimensional (3D) geometric models of surgical tools and implants superimposed on the X-ray images. Starting from multiple registered fluoroscopy images, a virtual 3D cylinder model for each principal bone fragment is constructed. This spatial cylinder model not only supplies a 3D image of the fracture, but also allows effective fragment projection recovery from the fluoroscopic images and enables radiation-free updates of in situ surgical fluoroscopic images by non-linear interpolation and warping algorithms. Initial clinical experience was gained during four tibia fracture fixations that were treated by LISS (Less Invasive Stabilization System) osteosynthesis. In the cases operated on, after primary image acquisition, the image intensifier was replaced by the virtual reality system. In all cases, the procedure including fracture reduction and LISS osteosynthesis was performed entirely in virtual reality. A significant disadvantage was the unfamiliar operation of this prototype software and the need for an additional operator for the navigation system.