Gefitinib and celecoxib in advanced metastatic gastrointestinal tumors: a pilot feasibility study

Background

This pilot, open-label study examined the safety and tolerability (primary objective) and efficacy (secondary objective) of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, in patients with advanced or refractory gastrointestinal (GI) tumors of epithelial origin.

Methods

Patients were administered gefitinib (250 mg/day) plus celecoxib (400 mg twice daily). In the event of toxicity, dose interruptions were permitted and a single celecoxib dose reduction was allowed.

Results

Thirty patients (median age 60 years) with primary colorectal (25 patients), pancreatic (3 patients), esophageal (1 patient), or gall bladder (1 patient) tumors were recruited, 29 of whom had received prior chemotherapy. Adverse events (AEs) were generally mild and consisted mainly of acne, diarrhea, and nausea. Few severe AEs were noted. There were no withdrawals or deaths due to AEs. Dose reductions for celecoxib were reported for five patients, in three cases due to toxicity. Stable disease was confirmed in 12 patients (40%), with progressive disease in 18 patients (60%).

Conclusions

After study completion, safety issues relating to the long-term use of COX-2 inhibitors have been raised. However, in this pilot study, the combination of gefitinib and celecoxib was generally well tolerated in patients with advanced GI cancer.     

Non-ST elevation myocardial infarction (NSTEMI) in three hospital settings in South Africa: does geography influence management and outcome? A retrospective cohort study

Background

Guidelines advise early angiography in non-ST elevation myocardial infarction (NSTEMI) to ensure an optimal outcome. Resource limitations in secondary hospitals in the Western Cape dictate a local guideline to treat NSTEMIs medically with out-patient assessment for angiography, unless mandatory indications for early angiography occur.

Methods

A retrospective cohort study assessed NSTEMIs at Tygerberg Hospital (TBH), Karl Bremer Hospital (KBH) and Worcester Hospital (WH) over one year. Two cohorts were analysed, secondary hospitals (KBH and WH; SH) and secondary service within a tertiary hospital (TBH). Where differences were found, sub-analysis compared WH and KBH.

Results

TBH and SH were similar at baseline and in clinical presentation. Cases at TBH were more likely to receive in-patient angiography (94 vs 51%, p < 0.0001), and had a lower in-patient mortality rate (6 vs 23%, p = 0.0326). There was no difference between KBH and WH in sub-analysis.

Conclusion

This study confirmed that the management and mortality of NSTEMIs in the public health sector in the Western Cape, South Africa is not influenced by geography, but rather by the level of service available in the hospital of first presentation.     

Central nervous system disease in acquired immunodeficiency syndrome: prospective correlation using CT, MR imaging, and pathologic studies

A prospective study compared the abilities of high-resolution computed tomography (HRCT) and magnetic resonance (MR) imaging in detection and evaluation of central nervous system disease in neurologically symptomatic patients with acquired immunodeficiency syndrome (AIDS). Eighteen CT scans and 19 MR images in 14 patients were compared. HRCT images with contrast material enhancement were superior to unenhanced 0.35-T MR images for differentiating a lesion from surrounding edema, discriminating between lesions in close proximity, locating lesions for biopsy, judging lesion activity, detecting small cortical lesions with minimal edema, and spatial resolution. MR imaging was superior to CT scanning in evaluation of white-matter lesions and detection of small lesions surrounded by edema. MR imaging exhibited higher contrast resolution and greater sensitivity. Complementary uses of MR and CT imaging are suggested.     

Atherosclerotic rabbit aortas: expandable intraluminal grafting

Balloon-expandable intraluminal grafts that ranged in diameter from 2 to 4 mm were placed in the atherosclerotic abdominal aortas of 24 rabbits. The animals were killed 1, 3, 8, or 24 weeks after placement of the graft. All grafts retained patency without altering the luminal diameter. The small degree of neointimal thickening covering the graft's inner surface was not detectable on conventional in vivo arteriograms. Aortic atherosclerotic plaque external to the graft was markedly compressed 1 week after graft placement. The plaque regained full thickness 24 weeks after grafting when the plaque expanded outside the graft as a result of relaxation or atrophy of the surrounding arterial media.     

Impact of MR imaging on clinical diagnosis and management: a prospective study

The clinical value of magnetic resonance (MR) imaging was prospectively evaluated in 189 patients referred for examination of the brain or spine. Comparison of the attending physician's diagnosis, proposed treatment, and estimated prognosis before and after MR imaging indicated a substantial effect of the additional information provided by this study. A suspected diagnosis was refined or changed in 16% of all patients, and the physician's level of confidence in the diagnosis changed in over half of the cases in which the diagnosis was unchanged. In two-thirds of all cases the physician indicated that the treatment or estimated prognosis was altered.     

棉酚对加入S9的哺乳类细胞染色体畸变的影响

棉酚在S9mix存在下,並不引起地鼠某些细胞染色体断裂也不引起多倍体增加,说明该药並不在染色体水平上引起遗传损伤,但对哺乳类培养细胞存在着毒性。如进一步证实其安全性。可作为男性避孕药推广应用。