Variceal hemorrhage and cystic fibrosis: outcomes and implications for liver transplantation.

Autopsy and imaging studies show that liver involvement is common in cystic fibrosis. However, complications of chronic liver disease including portal hypertension and variceal bleeding are infrequently encountered, and the degree to which variceal hemorrhage affects prognosis in cystic fibrosis is unclear. This uncertainty has lead to debate as to whether liver transplantation is indicated in these patients. We describe a case series of 18 patients and compare their survival with a control group of cystic fibrosis patients without liver disease. The median age at first bleed was 20.0 years (range 9.7-30.9). The median survival after first bleed was 8.4 years, compared to 13.0 years in the control group (P = 0.15). A total of 14 patients have died, 9 from respiratory disease with no discernable contribution from their liver disease. Liver disease contributed to 4 deaths. Only 1 patient suffered a fatal hemorrhage, which may have been either variceal or bronchial in origin. Long-term survival is a frequent occurrence in patients with cystic fibrosis who suffer variceal hemorrhage, and age at death is comparable to the general cystic fibrosis population. In conclusion, this suggests that liver transplantation is not indicated in these patients without additional features of liver decompensation.     

Old and homeless: a review and survey of older adults who use shelters in an urban setting.

OBJECTIVES: Research on the mental health and service needs of homeless seniors has been scant. This paper reviews the available literature and presents findings of a Toronto survey in an effort to describe the demographics of homeless seniors, their level of impairment, and their mental and physical health needs. METHODS: We searched the Medline, AgeLine, and PsycINFO databases, using the following key words: elderly homeless, elderly hostel users, and urban geriatrics. To better describe the service needs of the elderly homeless, we obtained demographic data from the Community and Neighbourhood Services Department and distributed a survey questionnaire to 11 Toronto hostel directors. The questionnaire elicited data relating to reasons for shelter use, problem behaviours, and mental health needs of those over age 65 years. RESULTS: Although seniors represent a small percentage of the homeless population, their numbers are growing. The available literature suggests a high prevalence of psychiatric disorders and cognitive impairment in this population, with a greater proportion of older women than men having severe mental illness. Further, our survey suggests that the service needs of elderly hostel users in Toronto differ from those of their younger counterparts. CONCLUSION: The homeless elderly are the most vulnerable of this impoverished population. Although more research is needed to define their mental and physical health needs and ways of meeting them, their characteristics appear to be unique. Geriatric psychiatrists could play a significant role in evaluating and treating this population more comprehensively.     

IGF-I signalling in bone growth: inhibitory actions of dexamethasone and IL-1beta.

OBJECTIVE: To determine if glucocorticoids and proinflammatory cytokines inhibit bone growth through a common mechanism involving impaired IGF-I signalling. DESIGN: IGF-I (100 ng/ml), dexamethasone (dex) (10(-6)M) and IL-1beta (10 ng/ml) with inhibitors of the PI3K (LY294002) and Erk 1/2 (PD98059 and UO126) IGF-I pathways (all 10 microM) were studied using the ATDC5 chondrocyte cell line and murine fetal metatarsal cultures. RESULTS: IGF-I stimulated ATDC5 chondrocyte proliferation (322%; P < 0.001 versus control). Addition of PD or LY individually to IGF-I supplemented ATDC5 cultures partially reduced proliferation by 32% (P < 0.001), and 66% (P < 0.001), respectively. PD and LY in combination blocked all IGF-I stimulated ATDC5 proliferation. LY significantly reversed IGF-I stimulatory effects on metatarsal growth (P < 0.001), whereas PD and UO treatment had no effect. IGF-I induced ATDC5 proliferation was further decreased when Dex (24%; P < 0.01) or IL-1beta (33%; P < 0.001) were added to PD but not LY cultures. Metatarsal growth inhibition by LY was unaltered by Dex or IL-1beta addition. CONCLUSIONS: Both the PI3K and Erk 1/2 pathways contributed independently to IGF-I mediated ATDC5 proliferation. However in metatarsal cultures, the Erk 1/2 pathway was not required for IGF-I stimulated growth. Dex and IL-1beta may primarily inhibit IGF-I induced bone growth through the PI3K pathway.     

A comparison of research general practices and their patients with other practices--a cross-sectional survey in Trent.

BACKGROUND: When interpreting results of studies undertaken by research networks we need to know how representative volunteer practices and their registered patients are of the total population of practices and patients in their locality. AIM: To compare the following in research and non-research general practices in one region: practice and population demography, morbidity and mortality, selected performance indicators, and health outcomes. DESIGN OF STUDY: Cross-sectional survey. SETTING: Sixty-six Trent Focus Collaborative Research Network general practices and 749 other general practices in Trent, United Kingdom. METHOD: Practice characteristics and GP contract data were obtained from the NHS Executive, Quarry House, Leeds. The Trent Regional NHS Hospital Admission Database was searched to identify all relevant admissions to hospital from all practices between 1 April 1993 and 31 March 1997. Ward-linked data on cancer were obtained from the Trent Cancer Registry. RESULTS: Of the 815 general practices in Trent Region in the study period, 66 (8%) were in the Trent Focus network. They were more likely to be involved in training GPs and to have a female partner. They tended to be larger, with fewer single-handed doctors and younger GPs. Network practices prescribed a higher proportion of generics (median % prescribed/practice = 70%, versus 51%, Mann-Whitney U = 1615, P<0.0001). There were no clinically important differences between hospital admission rates between the two groups or waiting times for surgical procedures. There was no difference in the incidence of cancer and standardised mortality ratios related to the electoral wards of the GP surgery. CONCLUSION: Although there were differences in practice structure and some aspects of performance, we found no important differences in the demography of registered patients, nor in morbidity, mortality, or access to or use of secondary care.     

Whole chromosome 17 loss in ovarian cancer

Chromosomal deletions, associated with the loss of normal function of tumour suppressor genes, have been identified in a variety of both familial and sporadic human cancers. Although the molecular pathology of ovarian cancer is not understood, several studies have reported deletions in chromosome 17 in ovarian tumours. We have used 13 restriction site polymorphic, microsatellite, and variable number tandem repeat markers to make a detailed analysis of chromosome 17 deletions in 12 benign and 19 malignant ovarian tumours. Two benign and 11 malignant tumours were informative for at least one marker on each arm of the chromosome. Loss of heterozygosity (LOH) was detected in both arms (by all informative markers) in 5 malignant tumours from four women (three with the disease at FIGO stage la). In a further bilateral ovarian tumour a partial LOH affecting 17q22-q25 was present in one ovary only. By contrast to a number of previous studies, none of the 19 malignant and 12 benign tumours showed ERBB2 (17q12ndash;22) amplification. The data presented show that the loss of a whole copy of chromosome 17 is a frequent and relatively early event in the development of some ovarian cancers. This suggests the possible involvement of multiple chromosome 17 loci in the pathogenesis of ovarian cancer. Equally plausible is that the loss of a whole chromosome copy could be the product of chromosomal instabilities induced by loss of the normal allele of tumour suppressors, such as TP53, located on this chromosome. © 1993 Wiley-Liss, Inc.     

Role of oxidative stress,angiogenesis and chemo-attractant cytokines in the pathogenesis of ischaemic protection induced by remote ischaemic conditioning: Study of a human model of ischaemia-reperfusion induced vascular injury

Aims

We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.

The latex allergen hev B 5 is an antigen with repetitive murine B-cell epitopes

BACKGROUND: Hev b 5 is a potent latex allergen. In this study, we characterize the linear B-cell epitopes for three monoclonal antibodies (mAbs) to Hev b 5. METHODS: The mAbs included 2 IgG1 (6A10, 3G3) and 1 IgG2b (6F6) isotypes. We used SPOTscan analysis with overlapping octapeptides to identify the binding regions for the antibodies and then methionine substitution analysis to further define the critical amino acids (aa) in each epitope. Site-directed mutagenesis was used to selectively eliminate the IgG binding for each epitope and single and multiple mutations were expressed as recombinant GST fusion proteins. Antibody recognition of the mutant proteins was determined by inhibition ELISA. RESULTS: All three mAbs recognized the same aa sequence by SPOTs analysis with slight variations, and this epitope was repeated 3 times in the Hev b 5 sequence; APETEK (63-68), PAEGEK (120-125), and PAEEEK (126-131). Sequential methionine substitution by SPOTsalogue identified K68, E122, and K131 as critical aa in each epitope to change by site-directed mutagenesis. Inhibition ELISA with the mutant proteins indicated that epitope 126-131 was the dominant epitope, but mutation of epitope 120-125 was also required to eliminate mAb reactivity to Hev b 5. The antibodies did not appear to recognize the epitope 63-68 in the recombinant fusion protein. CONCLUSIONS: We identified an immunodominant B-cell epitope in Hev b 5 that is repeated 3 times within the sequence, making Hev b 5 multivalent. Well-characterized monoclonals recognizing repeated epitopes would be a good choice for immunodetection of Hev b 5 in glove extracts where individual epitopes could get altered by the manufacturing process.     

Tetrasomy 9p: Tissue-limited idic(9p) in a child with mild manifestations and a normal CVS result. Report and review

Supernumerary isochromosomes resulting in autosomal tetrasomy are rare and have been described only for 12p, 18p, and 9p. Nineteen previous cases of tetrasomy 9p have been reported, and in 6 cases, tissue-specific mosaicism was implied with the i(9p) cell line present exclusively or predominantly in blood. We report on an infant who had apparently normal chromosomes (46,XY) on CVS. He was referred for genetic evaluation because of mild developmental delay and minor anomalies. In 75% of blood cells he had an extra isodicentric 9p chromosome (pter→q12→pter). The interpretation of tetrasomy 9p was confirmed by elevated GALT activity. No tetrasomy 9p cells were seen in 100 skin fibroblasts. This case demonstrates the tissue specific mosaicism in tetrasomy 9p which rendered the anomaly undetectable by CVS. It also demonstrates the mild end of the clinical spectrum associated with tetrasomy 9p. © 1993 Wiley-Liss, Inc.