Evaluation of the efficacy of dimercapto chelating agents for the treatment of systemic organic arsenic poisoning in rabbits

1 The standard drug for the treatment of arsenic poisoning is BAL (dimercaprol). BAL possesses marked side-effects and a low safety ratio, drawbacks which new BAL analogues, DMPS and DMSA, do not possess. 2 The efficacy of three chelating agents, BAL, DMPS and DMSA, has been evaluated as a treatment for systemic organic arsenic poisoning, induced by intravenous dichloro(2-chlorovinyl)arsine (lewisite) administration to rabbits. Equimolar dosing schedules were used based upon realistic doses for the most toxic agent, BAL. 3 It was concluded that all three dimercapto chelating agents provided significant protection against the lethal systemic effects of lewisite, and, under the test conditions reported here, there was no significant difference between them in therapeutic efficacy. 4 The cause of mortality following intravenous lewisite in treated and untreated rabbits was pulmonary damage. 5 It is considered that DMPS and DMSA are worthy of further study as replacements for BAL in the treatment of systemic poisoning by lewisite.     

Stent placement for benign pancreatic diseases: correlation between ERCP findings and clinical response.

OBJECTIVE. We performed a study to determine if the appearance of the pancreatic duct on ERCP before and after placement of pancreatic duct stents correlates with the therapeutic response in patients treated for impaired pancreatic drainage. MATERIALS AND METHODS. Findings in 29 consecutive patients with a variety of benign pancreatic diseases in whom pancreatic stents were placed and subsequently removed within a 3-year period were reviewed retrospectively. Early (1-5 days) and late (1-3 months) clinical outcomes after stent placement were assessed. These findings were correlated with a blinded interpretation of ERCP findings (Cambridge criteria were used) before and after stent placement. RESULTS. ERCP findings before stent placement were normal in 10 patients. At the end of stent therapy, ERCP showed changes associated with chronic pancreatitis in all 10; five had focal narrowing at the tip of the stent. Subsequent ERCP studies in five of these 10 patients showed that ductal changes induced by stents diminished after stent removal. Of the 19 patients with abnormal findings on ERCP at the time of stent placement, ERCP at the end of stent therapy showed some improvement in seven patients, no change in eight, and deterioration in four. Changes seen on ERCP had no statistically significant correlation with clinical outcome (p = .36). CONCLUSION. Our findings show that pancreatic duct stents can induce abnormalities on ERCP indicative of chronic pancreatitis. However, diminution of these abnormalities after stent removal in some patients suggests that these changes may be due to edema rather than to fibrosis. Ductal changes seen on ERCP are not a useful guide for determining the degree of response to pancreatic stents.     

K-ras activation and ras p21 expression in latent prostatic carcinoma in Japanese men.

Twenty-three clinically silent prostatic carcinomas discovered in Japanese men at autopsy were surveyed for ras proto-oncogene mutations by mutation-specific oligonucleotide probe hybridization after polymerase chain reaction (PCR) amplification from a section of formalin-fixed, paraffin-embedded tissue. Six of the 22 that were satisfactory amplified contained activating point mutations in codon 12 of K-ras, a significantly higher frequency than has been reported in patients with clinically advanced disease in the United States. Of the six cases with activating point mutations in codon 12 of K-ras, one had a GGT----GAT transition, four had GGT----GTT transversions, and one had both GGT----GAT and GGT----GTT mutations. Sections from the same tissues were immunohistochemically stained with an anti-ras p21 antibody. Carcinoma cells stained for ras p21 to some degree in 13 cases. Immunohistochemically detectable expression of p21 was always focal and was not necessarily associated with K-ras mutation. K-ras oncogene activation in prostatic carcinoma appears to merit additional study as a significant event in the pathogenesis of this neoplasm.     

Prostaglandins in experimental syphilis: treponemes stimulate adherent spleen cells to secrete prostaglandin E2, and indomethacin upregulates immune functions.

Incubation of microorganisms with macrophages enhances the production of prostaglandin E2 (PGE2). Previous research had indicated that macrophages from syphilitic rabbits suppressed spleen cell synthesis of interleukin-2 (IL-2); this suppressive activity was reversed by indomethacin. Experiments were designed to further characterize the involvement of prostaglandins in immune processing. When Treponema pallidum was incubated with unfractionated spleen preparations, PGE2 production was accelerated, and within 24 h, pharmacologic concentrations of the prostaglandin were detected. When cytochalasin B was used to block phagocytosis, decreased levels of PGE2 were apparent. Commercial preparations of PGE2, in the range generated by macrophage-treponeme interaction, inhibited concanavalin A-induced IL-2 secretion by splenic cells. T. pallidum stimulated IL-1 production by adherent cells, and indomethacin markedly enhanced this effect. In vivo, indomethacin upregulated immune function. Two groups of rabbits were infected, and one was given daily injections of indomethacin for 18 days. Both groups were treated with penicillin to terminate infections. One week later, rabbits were challenged with viable organisms to determine their immune status. The indomethacin-treated group was more resistant to reinfection. In further research, indomethacin enhanced the immunogenicity of vaccine preparations containing heat-killed T. pallidum. Results are discussed in terms of the role of PGE2 as it impinges on immune functions involving macrophage activation (IL-1 production) and T lymphocyte activation (IL-2 production).     

Brain and tissue levels of mercury after chronic methylmercury exposure in the monkey

Estimated half-lives of mercury following methylmercury exposure in humans are 52-93 d for whole body and 49-164 d for blood. In its most recent 1980 review, the World Health Organization concluded that there was no evidence to suggest that brain half-life differed from whole-body half-life. In the present study, female monkeys (Macaca fascicularis) were dosed for at least 1.7 yr with 10, 25, or 50 micrograms/kg.d of mercury as methylmercuric chloride. Dosing was discontinued, and blood half-life was determined to be about 14 d. Approximately 230 d after cessation of dosing, monkeys were sacrificed and organ and regional brain total mercury levels determined. One monkey that died while still being dosed had brain mercury levels three times higher than levels in blood. Theoretical calculations were performed assuming steady-state brain:blood ratios of 3, 5, or 10. Brain mercury levels were at least three orders of magnitude higher than those predicted by assuming the half-life in brain to be the same as that in blood. Estimated half-lives in brain were between 56 (brain:blood ratio of 3) and 38 (brain:blood ratio of 10) d. In addition, there was a dose-dependent difference in half-lives for some brain regions. These data clearly indicate that brain half-life is considerably longer than blood half-life in the monkey under conditions of chronic dosing.     

Models of adult day care: findings from a national survey

We examined a nationally representative sample of 60 adult day care centers to describe the state of this evolving care modality after a decade's growth. Results indicate that day care centers can be categorized into three models of care, each of which serves a distinctive subpopulation. Model appropriateness was tested with analysis of variance of differences in participant characteristics. Services, staffing, costs, and other program features are contrasted among the three models.     

Basic surgical techniques and variations of endoscopic sinus surgery

This article gives complete information on the care of the endoscopic sinus surgery patient. Indications and preoperative evaluations necessary for endoscopic sinus surgery are described. The technique of functional endoscopic sinus surgery is covered in detail. Postoperative care and complications are also described. Various procedures for patients with extensive or unusual disease are discussed.