A multicenter, double-blind, randomized comparison of oral ondansetron 8 mg b.i.d., 24 mg q.d., and 32 mg q.d. in the prevention of nausea and vomiting associated with highly emetogenic chemotherapy

The objectives of this study were to compare the efficacy and safety of orally administered ondansetron 8 mg b.i.d., 24 mg q.d., and 32 mg q.d. in the prevention of nausea and vomiting associated with high-dose cisplatin-based chemotherapy (cisplatin > or = 50 mg/m2). This was a randomized, parallel-group, double-blind study conducted in North America. It was planned that all patients would receive one of the following orally administered ondansetron treatments 30 min before starting cisplatin dosing (administered over < or = 3 h): 8 mg b.i.d. with 8 h between doses (124 patients), 24 mg q.d. (116 patients), and 32 mg q.d. (117 patients). Use of prophylactic corticosteroids was not permitted. During the 24-h study period, the highest complete response rate (no emesis, rescue antiemetic therapy, or withdrawal) occurred in patients who received ondansetron 24 mg q.d.: 76/115 or 66%, as against 68/124 (55%) after ondansetron 8 mg b.i.d. and 64/117 (55%) after ondansetron 32 mg q.d. Complete control of nausea (no nausea, no rescue, no withdrawal) occurred in more patients in the ondansetron 24 mg q.d. group (64/114, 56%) than in the ondansetron 8 mg b.i.d. group (43/121, 36%) or in the ondansetron 32 mg group (55/117, 50%). These results demonstrate that following highly emetogenic cisplatin-based chemotherapy (> or =2 50 mg/m2), oral ondansetron 24 mg q.d. is more effective than 8 mg b.i.d. for overall control of nausea, and at least as effective if not more effective in the control of acute vomiting than 8 mg b.i.d. or 32 mg q.d. Ondansetron 24 mg q.d. was well tolerated, and no new or unexpected adverse events were identified.     

Nedocromil sodium. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of reversible obstructive airways disease

Nedocromil sodium is a sodium cromoglycate-like drug which inhibits activation and mediator release from inflammatory cells such as eosinophils, neutrophils, macrophages, monocytes, mast cells and platelets. Non-comparative and placebo-controlled therapeutic studies in adult patients of up to 52 weeks duration have demonstrated the tolerability and efficacy of nedocromil 4 mg twice or 4 times daily in the management of reversible obstructive airways disease producing significant improvements in asthma symptom scores and pulmonary function tests. When added to existing therapy, nedocromil sodium permits reductions of 20 to 70% in concomitant bronchodilator use and appears to have a moderate steroid sparing effect in patients receiving inhaled corticosteroids. To date no controlled studies have been published comparing nedocromil sodium with sodium cromoglycate and other established therapies in adult reversible obstructive airways disease or asthma, which limits the overall conclusions which can be drawn about the position of nedocromil sodium relative to other treatments. However, preliminary clinical data suggest that although nedocromil sodium cannot substitute completely for bronchodilators or inhaled corticosteroids, with its additive and dose-sparing effects and the convenience of a twice daily dosage it is a promising prophylactic adjunctive agent for the management of reversible obstructive airways disease.     

Pneumothorax preceding pulmonary blastoma in a child

Serial plain radiographic, ultrasound and CT findings of an unusual case of pulmonary blastoma are described with a review of the literature.     

Retrospective Study on Efficacy of Intermaxillary Fixation Screws

Background

We evaluated the efficacy of intermaxillary fixation (IMF) screws in the treatment of mandibular fractures.

Methods

Two hundred patients with mandibular fractures, treated by IMF using these screws, were evaluated by pre and postoperative panoramic radiographs. Clinical testing was carried out for vitality and abnormal mobility of teeth adjacent to the site of screw insertions. Other factors such as possible iatrogenic dental injuries, loss, breakage or screw cover by oral mucosa and postoperative occlusion were also studied.

Result

The most important complication noticed was iatrogenic damage to dental roots.

Conclusion

Use of intraoral cortical bone screws for IMF is a valid alternative to arch bars in the treatment of mandibular fractures. Iatrogenic injury to dental roots is the commonest problem which can be minimized by an experienced surgeon.Key Words: Intermaxillary fixation, Bone screws, Mandibular fractures, Iatrogenic injury     

A multiplex immunoassay demonstrates reductions in gingival crevicular fluid cytokines following initial periodontal therapy

Thunell DH, Tymkiw KD, Johnson GK, Joly S, Burnell KK, Cavanaugh JE, Brogden KA, Guthmiller JM. A multiplex immunoassay demonstrates reductions in gingival crevicular fluid cytokines following initial periodontal therapy. J Periodont Res 2009; doi: 10.1111/j.1600‐0765.2009.01204.x. © 2009 John Wiley & Sons A/S Background and Objective: Cytokines and chemokines play an important role in the pathogenesis of periodontal diseases. The objective of this study was to quantitatively assess the effect of initial periodontal therapy on gingival crevicular fluid levels of a comprehensive panel of cytokines and chemokines, including several less extensively studied mediators. Material and Methods: Clinical examinations were performed and gingival crevicular fluid samples obtained from six subjects with generalized severe chronic periodontitis prior to initial periodontal therapy and at re‐evaluation (6–8 weeks). Four diseased and two healthy sites were sampled in each subject. Twenty‐two gingival crevicular fluid mediators were examined using a multiplex antibody capture and detection platform. Statistical analyses were performed by fitting mixed effects linear models to log‐transformed gingival crevicular fluid values. Results: Gingival crevicular fluid interleukin (IL)‐1α and IL‐1β were the only cytokines to differ in initially diseased vs. initially healthy sites. Following initial therapy, 13 of the 16 detectable cytokines and chemokines decreased significantly in diseased sites, including IL‐1α, IL‐1β, IL‐2, IL‐3, IL‐6, IL‐7, IL‐8, IL‐12 (p40), CCL5/regulated on activation, normally T cell expressed and secreted (RANTES), eotaxin, macrophage chemotactic protein‐1, macrophage inflammatory protein‐1α and interferon‐γ. At healthy sites, only three of the 16 mediators were significantly altered following therapy. Conclusion: This is the first study, to our knowledge, to evaluate such an extensive panel of gingival crevicular fluid mediators within the same sample prior to and following initial therapy. The results confirm that periodontal therapy effectively reduces pro‐inflammatory cytokines and chemokines, including less well‐described mediators that may be important in initiation and progression of periodontitis. The multiplex assay will prove useful for future gingival crevicular fluid studies.     

Flutamide. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in advanced prostatic cancer

Flutamide is a non-steroidal antiandrogenic drug devoid of hormonal agonist activity. Flutamide appears to be a specific antiandrogen only at androgen-dependent accessory genital organs. Its pharmacological activity is due substantially to the principal metabolite, 2-hydroxyflutamide. In comparative trials involving small numbers of patients with previously untreated advanced prostatic cancer, flutamide 750mg daily is comparable with stilboestrol 1 or 3mg daily and with estramustine 560 or 840mg daily. Treatment of newly diagnosed advanced prostatic cancer with flutamide plus a luteinising hormone releasing hormone (LHRH) agonist has produced very promising results, and appears to prolong survival relative to that achieved with leuprolide alone. However, these results require confirmation in suitably designed prospective studies. In previously treated patients refractory to castration, flutamide 750mg daily appears comparable in efficacy to estramustine phosphate 600 mg/m2 daily. Apart from a high incidence (34 to 100%) of gynaecomastia flutamide monotherapy is usually well tolerated, and has the advantage of preserving libido and sexual potency in at least 80% of patients. Gynaecomastia is infrequent, however, when flutamide is used in conjunction with surgical castration or an LHRH agonist. Thus, flutamide is a suitable alternative to other systemic treatment in patients with advanced prostatic cancer who wish to preserve sexual potency. In combination with an LHRH agonist flutamide may become a first-line agent for previously untreated patients with cancer of the prostate.     

Evaluation of antihyperglycemic activity of methanolic Tecomaria capensis Thunb. (Bignoniaceae) leaves extract in alloxan induced hyperglycemic rats

ObjectiveTo evaluate the antihyperglycemic activity of Tecomaria capensis (T. capensis) Thunb. (Bignoniaceae) methanolic leaves extract (TCLE) using blood glucose level in normal fasted rats, glucose tolerance test and alloxan induced hyperglycemia models.MethodsTCLE (100, 300, 1 000 and 2 000 mg/kg body wt.) was given to rats orally to observe acute toxicity, and observed for 14 d. TCLE 200 and 400 mg/kg, and glibenclamide 0.6 mg/kg were given orally in all models.ResultsResults demonstrated that the no mortality was reported even after 14 d. This indicates that the methanol extract is safe up to a single dose of 2 000 mg/kg body weight. TCLE (200 and 400 mg/kg p.o.) exhibited remarkable blood glucose lowering effect in blood glucose level in normal fasted rats, glucose tolerance and alloxan induced hyperglycemia model. Cholesterol and triglyceride also decreased in alloxan induced hyperglycemia model.ConclusionsThe results of this study exhibites that methanol extract of T. capensis possesses antihypergycemic activity and it may prove to be effective for the treatment of hyperglycemia.     

Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer.

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.