Current and future therapies for HCV infection: what should the end point for treatment be?

Based upon all of the available data relating to the natural history, chemical course, and response to therapy of HCV, the following recommendations are made: 1) The primary end point for HCV therapy should be HCV clearance from all tissue sites, eg plasma, liver and others 2) Therapy should be provided for patients with early infections as they have the best chance of achieving a virologic response 3) Therapy should be offered to patients with cirrhotic disease, as prevention of hepatic decompensation and degeneration to hepatic cancer is possible 4) End stage decompensated disease should be treated, particularly if liver transplantation is being considered, in an effort to either eliminate or ameliorate disease recurrence 5) Combination therapies are preferable to monotherapy as they enhance the likelihood of a therapeutic response. Some of these include agents that reduce the frequency of IFN-induced untoward events (NSAIDs) 6) The approach to HCV infection should be to view it as an infectious disease. In this way, multi-agent therapy could be used to prevent the emergence of drug resistant mutants as well as to obtain earlier clearance of the infection than is possible with monotherapy.     

Granulocytic sarcoma (chloroma) initially seen as acute mastoiditis

Granulocytic sarcoma (chloroma) is a localized tumefaction of immature granulocytes that is typically seen in association with myelogenous leukemia. The primitive cell population seen in biopsy material may be misinterpreted as histiocytic lymphoma or other sarcoma unless additional studies are performed. We saw a 36-year-old woman with promyelocytic leukemia in remission who had the signs and symptoms of an acute coalescent mastoiditis. Histologic examination of the surgical specimen, however, demonstrated a granulocytic sarcoma. Our case exemplifies some of the difficulties that may be encountered in the diagnosis of granulocytic sarcoma and illustrates the point that symptoms of an inflammatory process in a patient with a diagnosis of leukemia must be regarded with a degree of suspicion.     

Exposure assessment to preformed environmental N-nitroso compounds from the point of view of our own studies

The largest human exposure to N-nitrosamines is in the industrial section. Leather tanners are exposed to N-nitrosodimethylamine at levels up to 47 microgram/m3, corresponding to 440 microgram/person/day. Workers in the curing area of tire factories are exposed to N-nitrosomorpholine at levels up to 27 microgram/m3, corresponding to a intake of 250 microgram/person/day. These industrial exposures are considerably greater than exposure via foodstuffs, beer, cosmetics, cutting fluids and herbicides.     

The DNA extruded by rat spleen cells in culture

1. Part of the DNA extruded by cultured rat spleen cells occurs in the form of a low density lipid complex. 2. The present work indicates that this complex is also associated with protein but not with RNA and its elementary properties have been studied. 3. For example, it is destroyed by freezing and thawing or by deoxycholate treatment and small quantities of copper salts added to the medium may either inhibit or stimulate its release depending on the conditions.     

Fossils, molecules and embryos: new perspectives on the Cambrian explosion

The Cambrian explosion is named for the geologically sudden appearance of numerous metazoan body plans (many of living phyla) between about 530 and 520 million years ago, only 1.7% of the duration of the fossil record of animals. Earlier indications of metazoans are found in the Neoproterozic; minute trails suggesting bilaterian activity date from about 600 million years ago. Larger and more elaborate fossil burrows appear near 543 million years ago, the beginning of the Cambrian Period. Evidence of metazoan activity in both trace and body fossils then increased during the 13 million years leading to the explosion. All living phyla may have originated by the end of the explosion. Molecular divergences among lineages leading to phyla record speciation events that have been earlier than the origins of the new body plans, which can arise many tens of millions of years after an initial branching. Various attempts to date those branchings by using molecular clocks have disagreed widely. While the timing of the evolution of the developmental systems of living metazoan body plans is still uncertain, the distribution of Hox and other developmental control genes among metazoans indicates that an extensive patterning system was in place prior to the Cambrian. However, it is likely that much genomic repatterning occurred during the Early Cambrian, involving both key control genes and regulators within their downstream cascades, as novel body plans evolved.     

Management of upper urinary tract calculi with ureteroscopic techniques

Frequent loss of heterozygosity on chromosome 8p in a variety of human malignancies, including head and neck cancers, has suggested the presence of a tumor suppressor gene (or genes) associated with the pathogenesis of these cancers. To test the role of genetic alterations at 8p23 in oral carcinogenesis, we studied 51 squamous cell carcinomas of the head and neck and 29 oral squamous cell carcinoma cell lines for allelic loss using 7 microsatellite markers spanning approximately 5 cM of chromosome band 8p23. Twenty-three of 51 tumors (45%) and 23 of 29 cell lines (79%) showed allelic loss at 1 or more loci. Three cell lines showed homozygous deletion of loci within a 3 cM region defined by the markers D8S1781 and D8S262. Our results suggest that a tumor suppressor gene (or genes) is located in 8p23 and is associated with the development and/or progression of oral carcinomas.     

Posttraumatic elbow arthritis and arthroplasty

Elbow contractures without significant articular injury can be treated with soft-tissue procedures, such as joint capsular releases, resection of heterotropic ossification, and joint debridement. Elbows with significant intra-articular injuries or posttraumatic arthritis require some form of joint reconstruction, such as a distraction arthroplasty, interposition arthroplasty, or implant replacement arthroplasty. With a better understanding of the surgical indications for elbow arthroplasty, improvements in surgical technique, improvements in elbow implants, and increased surgical experience, the results of implant arthroplasty for the posttraumatic elbow continue to improve.