Postherpetic neuralgia: From preclinical models to the clinic

Postherpetic neuralgia (PHN), a common complication of herpes zoster, which results from reactivation of varicella zoster virus, is a challenging neuropathic pain syndrome. The incidence and severity of herpes zoster and PHN increases with immune impairment or age and may become a greater burden both in terms of health economics and individual suffering. A clearer understanding of the underlying mechanisms of this disease and translation of preclinical outcomes to the clinic may lead to more efficacious treatment options. Here we give an overview of recent findings from preclinical models and clinical research on PHN.     

Heterogeneity of 5-fluorouracil radiosensitivity modulation in cultured mammalian cell lines.

There is ample evidence that 5-fluorouracil (5-FU) improves both local control and survival of a variety of gastrointestinal tumors when added to radiotherapy. However, the modulation of radiosensitivity by 5-FU is incompletely understood and some reports are apparently contradictory. Therefore, we have reevaluated the modulation of radiosensitivity by 5-FU in a variety of mammalian cells. HT-29 and WiDr (human colon adenocarcinoma), DU-145 (human prostate adenocarcinoma), V-79 (Chinese hamster lung fibroblast), and HeLa cell lines were maintained in exponential growth as monolayer cultures. Cell survival following treatment with drug and/or radiation was determined by colony formation assay. Radiation was delivered either alone; midway through a 1 hr exposure to 7-25 micrograms/ml 5-FU (pulse); or following initiation of 0.1-1.5 micrograms/ml 5-FU present throughout the entire incubation for assay of colony forming ability (continuous exposure). These 5-FU levels were selected to approximate those achieved in vivo in humans. The results indicate that mammalian cell lines may vary substantially insofar as modulation of their radiosensitivity by 5-FU is concerned. Radiosensitization, defined by reduction in D0, was observed for continuous exposure only in V-79, WiDr, and HT-29 cell lines, was observed for both pulse exposure and continuous exposure in DU-145, and was not present in HeLa cells. Radioenhancement, defined by reduction in n, was observed in V-79, WiDr, and HT-29 but not in the other cell lines. This effect, characterized by reduction in the shoulder portion of the curve, is naturally accompanied by a decrease of Dq. This indicates that mammalian cell lines may have different responses to radiosensitivity modulation by 5-FU. Though the cell lines may exhibit radiosensitivity by either alterations in the slope or shoulder of the cell survival curve, the mechanisms responsible for both the heterogeneity as well as the radiosensitization itself are completely unknown at this time. Insight into the mechanisms for both the heterogeneity and the radiosensitization will be important areas for further investigation.     

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.      

Determinants of acquisition of MR imaging units in an era of prospective payment

A survey was undertaken to examine the impact of Medicare's Prospective Payment System (PPS) and other recent changes in the health care environment on providers' decisions regarding acquisition of high-cost technologic equipment. The survey group included 199 hospitals and freestanding imaging centers known to have acquired magnetic resonance (MR) imaging units, as well as a random sample of 400 hospitals whose acquisition decisions were unknown to the authors. Fifty-eight percent of the known adopters and 61% of the randomly selected hospitals responded to the survey. Nonadopters' decisions were dominated by economic considerations, including the high cost of MR imagers and concerns about Medicare's reimbursement policies. Competition and a desire to provide the highest quality of care are counterbalancing the retardant effects of PPS, however, and are stimulating widespread diffusion of MR imagers.     

The site of protein loss in Sch?nlein-Henoch purpura.

Schönlein-Henoch purpura may be complicated by hypoproteinaemia, which in most patients is due to the development of nephrotic syndrome. However, in some proteinuria is insignificant and enteric protein loss has been suggested as the cause. A case with supportive evidence for this is reported.