“Gallstone Hip” and Other Sequelae of Retained Gallstones.

The fate of gallstones spilled during laparoscopic cholecystostomy has been thought to be relatively benign. Recent experience and a review of the recent literature shows that this is not always the case. We report three cases of complications of retained stones and analyse the literature with regard to types of complications, time to presentation, and recommendations for managing spilled gallstones. Retained gallstones have been shown to cause adhesions in the rat and inflammatory reactions in dogs with no evidence of absorption. The average time to presentation of complications arising from retained gallstones is 27.3 weeks. Complications include: Intraabdominal abscess formation with or without abdominal wall sinus tract formation, persisting abdominal wall sinus tracts from port site abscess, subhepatic inflammatory masses, cholelithoptysis, microabscesses and granuloma formation, liver abscess and “dumbell” shaped abscess with one side of the “dumbell” forming a subcutaneous abscess. We recommend the judicious use of retrieval devices during the extraction phase of the laparoscopic cholecystectomy, diligent removal of any spilled stones and awareness of delayed postoperative pain and tenderness as a harbinger of symptomatic retained gallstones. Documentation of intraoperative gallstone spillage, volume, type of gallstones, and effort to retrieve is recommended.     

Emerging Patterns in Adolescent Drug Use: The Belfast Youth Development Study 2000-2002

This paper reports the findings from the first 2 years of the Belfast Youth Development Study. The Belfast Youth Development Study is a 5-year longitudinal investigation of the onset and development of adolescent drug using behaviours, the findings of the first 2 years from the study in relation to drug use patterns among the young people participating in the research are reported here. The findings show that while the majority of young people have not yet used an illicit substance, the study has seen a substantial increase in the numbers using such substances between year 1 and year 2. Boys still make up the majority of drug users in this period but there has been a substantial increase in the number of girls using illicit drugs and, more generally, an increase in the frequency of use among all those using such substances during this period.     

Morphometric evaluation of hepatocellular proliferative lesions in the rat liver

Classification of rat hepatocellular proliferative lesions can vary between pathologists as the many qualitative histologic criteria have not been satisfactorily evaluated and ranked for prognostic value. Computer-assisted morphometry offers an objective method to evaluate certain cellular features. The Solt-Farber resistant hepatocyte model was used in this study to produce populations of rats with a full range of hepatocellular proliferative lesions. Cellular features within the lesions were then measured morphometrically and the data were analyzed by animal age and by subjective lesion diagnosis. The nuclear/cytoplasmic ratio followed by the cell area and nuclear area were found to be the most important parameters for separating microscopic foci and islands of cellular alteration, an early hyperplastic lesion, from other hepatocellular proliferative lesions. The coefficient of variation, as a relative measure of heterogeneity, increased in a linear manner for cell, nuclear and nucleolar areas as the animals aged and was significantly higher for cell and nuclear area in hepatocellular carcinoma compared to other hepatocellular proliferative lesions. Hepatocyte nodules (representing primarily late hyperplastic lesions) and persistent hepatocyte nodules (lesions with similarities to hepatocellular adenoma) could not be satisfactorily separated within the limits of this study. As these borderline lesions show a continuum of cytologic change, other features, such as architectural change, are necessary to satisfactorily classify them on a subjective basis. An alternative approach is to use discriminant functions derived from morphometric studies.     

In Vivo and In Vitro Models of Demyelinating Disease: Endogenous Factors Influencing Demyelinating Disease Caused by Mouse Hepatitis Virus in Rats and Mice

Intracerebral inoculation of JHM virus (JHMV), the neuropathic strain of mouse hepatitis virus, into Wistar Furth, Wistar Lewis, and Fischer 344 rats at various ages indicated that Wistar Furth rats are more susceptible to the virus than are the other strains. Fischer 344 and Wistar Lewis rats were more resistant to inoculation at 2 and 5 days of age and completely resistant by 10 days of age. In contrast, Wistar Furth rats which were very susceptible at both 2 and 5 days of age remained susceptible until 21 days of age. Intracerebral challenge of an F1 cross between Wistar Furth and Wistar Lewis rats at 10 days of age indicated that resistance to JHMV infection is dominant. Cyclophosphamide treatment 28 days after intracerebral inoculation exacerbated an inapparent infection, leading to paralysis in eight of nine and death in six of nine Wistar Furth test rats. In such immunosuppressed animals, grey- and white-matter lesions were noted throughout the central nervous system, in contrast to the purely demyelinating lesions noted previously. Since rats, unlike mice, were not susceptible to disease after intracerebral injection with the serorelated viscerotropic strain MHV-3, we wished to extend our understanding of the neurological disease process elicited by the two viruses in rodents. For this reason, various mouse strains, including some with recognized immunodeficiencies, were challenged by different routes of inoculation. Intraperitoneal infection of nude and beige mice with JHMV indicated that lack of natural killer cell functions does not markedly enhance the susceptibility to virus, whereas T-cell activity appears to be essential for resisting infection. JHMV and MHV-3 replication in peritoneal macrophages from highly resistant A/J mice was reduced in comparison with that noted in macrophages from susceptible C57BL6/J mice. An initial intraperitoneal inoculation of JHMV was able to protect C57BL6/J mice against fatal intracerebral challenge within 3 days, whereas A/J mice remained susceptible beyond day 3. The protective effect did not appear to result from increased levels of circulating interferon, preceded elevation in serum JHMV-neutralizing antibody titers, and persisted for at least several weeks after intraperitoneal inoculation. Based on the combined studies described here and on previous work by us and others, it appears that the factors influencing the outcome of coronavirus disease in rodents are age at inoculation, route of challenge, genetic constitution of the virus and host, and competence of the immune system, particularly cellular immunity involving T-cells.     

Epidemic pathogenic selection: an explanation for hereditary hemochromatosis?

Hereditary hemochromatosis (HH) is a disorder associated with progressive iron overload and deposition in multiple organs. It is the most common inherited single gene disorder in people of Northern and Western European descent. About 80% of individuals of European descent with HH are homozygous for a cysteine-to-tyrosine substitution (C282Y) in the gene now called HFE. The function of HFE protein, a major histocompatibility class I-like transmembrane protein, has not been fully elucidated. Three consequences of the C282Y mutation are lack of expression of HFE on the cellular surface, a lowered iron level in macrophages, and an increased rate of clearance of iron from the intestinal lumen. These changes could confer protection against certain pathogens early in life before iron overload occurs. Furthermore, the C282Y mutation might have been selected for during the European plagues caused by Yersinia spp. and other pathogens because of the conferred resistance to infection, i.e., by epidemic pathogenic selection.