Comparative dermal carcinogenesis of shale and petroleum-derived distillates

Ten test materials derived from petroleum or hydrotreated shale oils were applied 3 times/week for up to 105 weeks to the shaved skin of 25 male and 25 female C3H/HeN mice per group. Mineral oil and benzo(a) pyrene (0.15%) were control materials. Clinical observations were recorded during the study. At death, histopathologic examination was conducted on skin, internal organs and any gross lesions. Exposures to some materials were ended midway in the study due to severe irritation. Chronic toxicity of all materials was limited to inflammatory and degenerative skin changes. Significant increases over control incidence of skin tumors (squamous cell carcinoma and fibrosarcoma) occurred with both petroleum and shale-derived naphtha (21%, 50%), Jet A (26%, 28%), JP-4 (26%, 50%), and crude oils (84%, 54%). Severely hydrotreated shale oil and petroleum and shale-derived diesel distillates were not considered tumorigenic. Results indicate that toxicity of comparable petroleum and shale-derived fractions was qualitatively similar and confirm earlier findings that hydrotreating reduces or eliminates carcinogenicity of raw shale oil.     

Report of the Canadian Hypertension Society Consensus Conference: 2. Nonpharmacologic management and prevention of hypertensive disorders in pregnancy

OBJECTIVE: To provide Canadian physicians with comprehensive, evidence-based guidelines for the nonpharmacologic management and prevention of gestational hypertension and pre-existing hypertension during pregnancy. OPTIONS: Lifestyle modifications, dietary or nutrient interventions, plasma volume expansion and use of prostaglandin precursors or inhibitors. OUTCOMES: In gestational hypertension, prevention of complications and death related to either its occurrence (primary or secondary prevention) or its severity (tertiary prevention). In pre-existing hypertension, prevention of superimposed gestational hypertension and intrauterine growth retardation. EVIDENCE: Articles retrieved from the pregnancy and childbirth module of the Cochrane Database of Systematic Reviews; pertinent articles published from 1966 to 1996, retrieved through a MEDLINE search; and review of original randomized trials from 1942 to 1996. If evidence was unavailable, consensus was reached by the members of the consensus panel set up by the Canadian Hypertension Society. VALUES: High priority was given to prevention of adverse maternal and neonatal outcomes in pregnancies with established hypertension and in those at high risk of gestational hypertension through the provision of effective nonpharmacologic management. BENEFITS, HARMS AND COSTS: Reduction in rate of long-term hospital admissions among women with gestational hypertension, with establishment of safe home-care blood pressure monitoring and appropriate rest. Targeting prophylactic interventions in selected high-risk groups may avoid ineffective use in the general population. Cost was not considered. RECOMMENDATION: Nonpharmacologic management should be considered for pregnant women with a systolic blood pressure of 140-150 mm Hg or a diastolic pressure of 90-99 mm Hg, or both, measured in a clinical setting. A short-term hospital stay may be required for diagnosis and for ruling out severe gestational hypertension (preeclampsia). In the latter case, the only effective treatment is delivery. Palliative management, dependent on blood pressure, gestational age and presence of associated maternal and fetal risk factors, includes close supervision, limitation of activities and some bed rest. A normal diet without salt restriction is advised. Promising preventive interventions that may reduce the incidence of gestational hypertension, especially with proteinuria, include calcium supplementation (2 g/d), fish oil supplementation and low-dose acetylsalicylic acid therapy, particularly in women at high risk for early-onset gestational hypertension. Pre-existing hypertension should be managed the same way as before pregnancy. However, additional concerns are the effects on fetal well-being and the worsening of hypertension during the second half of pregnancy. There is, as yet, no treatment that will prevent exacerbation of the condition. VALIDATION: The guidelines share the principles in consensus reports from the US and Australia on the nonpharmacologic management of hypertension in pregnancy.     

Malakoplakia and colorectal adenocarcinoma.

We report a case of malakoplakia in association with colonic adenocarcinoma. Tumour-associated malakoplakia in the gastrointestinal tract is a rare finding, generally confined to the colon. It may be locally aggressive, with invasion of pericolic tissues, but is always located adjacent to the tumour. This contrasts with the often more diffuse, multifocal distribution of colonic malakoplakia in association with other pathologies.     

A double-blind, multicentre, placebo-controlled study of tiludronate in Paget's disease of bone.

A multicentre, randomised, placebo-controlled, dose-ranging study was conducted to investigate the therapeutic activity and sustained efficacy of tiludronate (200 mg, 400 mg and 600 mg once daily) taken orally for 12 weeks in patients with Paget''s disease. Serum alkaline phosphatase concentrations were compared with baseline at weeks 12 and 24; treatment success was defined as a 50% reduction compared with baseline. Changes in the hydroxyproline: creatinine ratio were also measured. Pain was assessed using the Huskisson Visual Analogue Scale and by questionnaire. Patients completing at least 11 weeks of treatment were followed-up 18 months later by postal questionnaire. Significantly greater numbers of patients in the tiludronate groups successfully responded to treatment compared with the placebo group. A dose-response was observed; the percentage of patients responding to treatment being 31% (200 mg), 52% (400 mg) and 82% (600 mg) at week 12 and 45% (200 mg), 70% (400 mg) and 82% (600 mg) at week 24. Tiludronate treatment also significantly reduced hydroxyproline: creatinine ratios compared with placebo, again showing a dose response. Dose-related gastrointestinal symptoms were the commonest adverse events, occurring in 2.4%, 11.0%, 5.5% and 18.9% of patients receiving placebo and tiludronate 200, 400 and 600 mg daily, respectively. The response to oral tiludronate was sustained for more than 18 months in some patients and there was evidence of a reduction in the longer term complications of the disease. These results show that oral tiludronate is an effective, well-tolerated treatment for Paget''s disease; the 400 mg once daily dose appears to offer the optimum balance of efficacy and tolerance.