Regulation of eicosanoid synthesis by whole fetal rat brainex vivo

Intact cerebral hemispheres from 20-d-old rat fetuses incubated at 37°C in Dulbecco’s Modified Eagle Medium (DMEM) synthesize and release a number of arachidonic acid derived metabolites, such as thromboxane B₂ (TxB₂), 6-keto prostaglandin F1α (6k-PGF1α), and prostaglandin E₂ (PGE₂) eicosanoids. Synthesis is time-dependent and is stimulated upon addition of the calcium ionophore A23187(10 μM). Ionophore stimulation is prevented by EDTA/EGTA (5 mM each) ion chelators, dextran-70 (5%), and indomethacin (10 μM), a potent cyclooxygenase inhibitor. Ca²⁺ (2 mM) enhances ionophoremediated formation of TxB₂, 6K-PGF1α, and PGE₂ by 2.5-, 2.9-, and 4.2-fold, respectively; Mg²⁺ blocks ionophore stimulation. Freezing and thawing enhances release of eicosanoids to a level nearly the same as that obtained in the presence of A23187, indicating a common mode of action.     

Phase II trial of fazarabine (arabinofuranosyl-5-azacytidine) in patients with advanced pancreatic adenocarcinoma

We conducted a phase II evaluation of fazarabine 1.75–2.0 mg/m²hr over 72 hours every 28 days in 14 previously untreated patients with advanced adenocarcinoma of the pancreas. The intial dose was 1.75 mg/m²/hr in 10 patients, and 2.0 mg/m²hr in 4 patients. The dose was escalated in 8 patients, including all 4 who started at the higher dose level. Toxicity was unexpectedly mild. The median WBC nadir was 4.4 (range: 2.4–15.8)×10³/l, the median absolute neutrophil nadir was 3.2 (range: 0.9–13.0)×10³/l, and the median platelet count was 134.0 (range: 48.0–291.0)×10³/l. Gastrointestinal toxicity was generally mild. No major responses were seen, excluding, with 95% confidence, a response rate in excess of 20%.     

Phase II trial of edatrexate in patients with advanced pancreatic adenocarcinoma

We conducted a phase II evaluation of edatrexate in 17 previously untreated patients with advanced adenocarcinoma of the pancreas; 14 patients had at least one month of therapy. The initial dose was 80 mg/m²iv. Treatment was administered weekly for 5 weeks, then every other week. Toxicity was generally mild. The median WBC nadir was 5.4 (range 0.6–7.4)×10³/l, and the median platelet nadir was 164.0 (range 62.0–341.0)×10³/l. One patient died with sepsis and gastrointestinal bleeding associated with pancytopenia. Five patients had a mild rash. Nausea occurred in 6 patients, including 3 who had vomiting. In addition, 11 patients complained of vague malaise which seemed to begin within 24–48 hours after administration of edatrexate, and lasted for 2 to 3 days, resolving within 6 days of drug administration. Median survival was 85 days. Although 5 patients had stable disease, including one with relief of pain, no major responses were seen, excluding, with 95% confidence, a response rate in excess of 20%.     

Phase II trial of VP16-213 in non-small cell lung cancer (NSCLC)

Summary Fifty-one patients with non-small cell lung cancer (NSCLC) were treated, during a phase II trial, with 4 demethylepipodophyllotoxin--d-ethylidene glucoside (VP16-213). Forty-nine were evaluable for response, and of these two (4%) had partial responses lasting 5 and 6 months. Prior treatment with chemotherapy may have adversely affected response rate; none of the 24 previously treated patients had a major response. Myelosuppression was the dose limiting toxicity. Anorexia, nausea and vomiting, partial alopecia, and chills plus hypotension during drug infusion were the other toxic effects. We conclude that VP16-213 has only minimal activity as a single agent in NSCLC.Supported in part by NIH Grant No. CA-05826 and CA-09027, and by NCI Contract NO-1-CM 972744Demethylepipodophyllotoxin--d-Ethylidene Glucoside (NSC141540) was supplied by the Drug Evaluation Branch of the National Cancer Institute     

Management of sleep bruxism in adults: a qualitative systematic literature review

This paper updates the bruxism management review published by Lobbezoo et al. in 2008 (J Oral Rehabil 2008; 35: 509–23). The review focuses on the most recent literature on management of sleep bruxism (SB) in adults, as diagnosed with polysomnography (PSG) with audio–video (AV) recordings, or with any other approach measuring the sleep‐time masticatory muscles' activity, viz., PSG without AV recordings or electromyography (EMG) recorded with portable devices. Fourteen (N = 14) papers were included in the review, of which 12 were randomised controlled trials (RCTs) and 2 were uncontrolled before–after studies. Structured reading of the included articles showed a high variability of topics, designs and findings. On average, the risk of bias for RCTs was low‐to‐unclear, whilst the before–after studies had several methodological limitations. The studies’ results suggest that (i) almost every type of oral appliance (OA) (seven papers) is somehow effective to reduce SB activity, with a potentially higher decrease for devices providing large extent of mandibular advancement; (ii) all tested pharmacological approaches [i.e. botulinum toxin (two papers), clonazepam (one paper) and clonidine (one paper)] may reduce SB with respect to placebo; (iii) the potential benefit of biofeedback (BF) and cognitive–behavioural (CB) approaches to SB management is not fully supported (two papers); and (iv) the only investigation providing an electrical stimulus to the masseter muscle supports its effectiveness to reduce SB. It can be concluded that there is not enough evidence to define a standard of reference approach for SB treatment, except for the use of OA. Future studies on the indications for SB treatment are recommended.     

Occupation as a potential contributing factor for temporomandibular disorders,bruxism, and cervical muscle pain: a controlled comparative study

The aim of the study was to compare the prevalence of cervical muscle pain (CMP) and myogenic temporomandibular disorders (MFP) among female dentists, high‐tech workers, and a group of subjects employed in other occupations; to investigate the associations among CMP, MFP, and bruxism in those groups; and to evaluate the influence of work‐related stress on MFP and CMP. Evaluation was based on clinical examinations of MFP and CMP and self‐reported questionnaires concerning pain and stress. The diagnosis of sleep bruxism was adapted using the validated diagnostic criteria of the American Academy of Sleep Medicine (International Classification of Sleep Disorders (ICSD‐2), 2005, Westchester, IL), whilst the diagnosis of awake bruxism was made on the basis of a questionnaire. The odds of a subject with MFP experiencing concurrent CMP or bruxism (sleep and/or awake) ranged from 2.603 to 3.077. These results suggest that high‐tech workers and dentists are at greater risk for developing temporomandibular disorders (TMDs) and CMP when compared with general occupation workers, as defined in this study. Furthermore, the associations shown here between TMDs and CMP highlight the importance of palpating neck musculature as part of any routine examination of TMD.