Sequence specificity of mutation induced by the anti-tumor drug cisplatin in the CHO aprt gene

Cis-diammine dichloroplatinum (cisplatin) is an effective anticancerdrug which forms adducts with DNA, in both bacterial and mammaliancells. It is suspected of producing tumors as well. To determinethe molecular nature of geneti alterations induced by cisplatin,we cloned and sequenced cisplatin-induced mutants in the adeninephosphoribosyl-transferase (aprt) gene of Cinese hamster ovary(CHO) cells. Mutation by cisplatin appears to be targeted asthe sites of mutation are consistent with the known bindingspecificity of cisplatin. Many mutations occur at or proximalto the sequence 5'-AGG-3' and 5'-GAG-3' and include transversions,transitions, frameshifts and short deletions and duplications.Several double changes were also observed. No major rearrangementswere recovered in our collection. At several locations, a numberof mutants were found to be clustered within a small targetregion, but unlike traditional hotspots, tese represent diversechanges occurring in a localized region of a few base pairs.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

“Avoidable mortality” as an index of health care outcome: Results from the european community atlas of “Avoidable death”

The history of the European Community Atlas of “Avoidable Death” is given. Data from the second Atlas are presented. For all causes of death except asthma there was a decrease in mortality in the period 1980–1984 with respect to 1974–1978. Taking the EC as a whole as the standard (100) population the standardised mortality ratio (SMR) in Ireland in the period 1980-1984 for tuberculosis was 160, for asthma 180 and maternal mortality 58. Ireland had the highest mortality for tuberculosis in both time periods. Asthma mortality increased in all countries except Scotland between 1974–1978 and 1980–1984. Ireland had one of the highest declines in maternal mortality over the two time periods. Within Ireland tuberculosis mortality was highest in the Mid-Western Health Board and lowest in the North-Western Health Board. Asthma mortality was highest in the Western Health Board and lowest in the Mid-Western Health Board. Maternal mortality was highest in the Midland Health board and lowest in the Southern Health Board.     

Presurgical electroencephalographic patterns and outcome from anterior temporal lobectomy.

We reviewed data from 48 patients after anterior temporal lobe resection for medically intractable epilepsy. All had ictal electro-encephalographic (EEG) evidence of unilateral temporal lobe onset. Depth electrodes were used in 19 patients. Successful surgical outcome correlated significantly with factors that suggested a temporal lobe focus, particularly in the interictal scalp EEG. The most successful outcome occurred in patients with well-localized unilateral interictal temporal spikes (100% improved). The group with well-localized bilateral temporal spikes also did well (76% improved). Patients with extratemporal spread of the interictal spike on scalp EEG, either unilaterally or bilaterally, did less well. Only one third improved, despite extensive extracranial and intracranial monitoring, when indicated. The interictal scalp EEG may be the only EEG necessary for the presurgical evaluation of selected patients with intractable temporal lobe epilepsy.     

Thrombus causing fatal left ventricular outflow tract obstruction in a heart transplant patient

A 60 year male, orthotopic heart transplant recipient developed a fatal left ventricular outflow obstruction secondary to thrombus at 38 months post transplant. Although he had episodes of mild to moderate rejection at 2 and 16 months post transplant, subsequent biopsies were negative and annual cardiac catheterizations showed mild left ventricular hypokinesis and normal coronary arteries. This case represents a catastrophic complication of transplant rejection and illustrates the problems with identifying rejection using current diagnostic methods.     

Perioperative effects of oral ketorolac and acetaminophen in children undergoing bilateral myringotomy

Prophylactic administration of analgesics before surgery can decrease the intraoperative anaesthetic requirement and decrease pain during the early postoperative period. In a double-blind, placebo-controlled study involving 90 healthy ASA physical status I or II children undergoing bilateral myringotomy, we compared the postoperative analgesic effects of oral acetaminophen and ketorolac, when administered 30 min before induction of anaesthesia. Patients were randomized to receive saline (0.1 ml.kg-1), acetaminophen (10 mg.kg-1) or ketorolac (1 mg.kg-1) diluted in cherry syrup to a total volume of 5 ml. Anaesthesia was induced and maintained with halothane and nitrous oxide via a face mask. Postoperative pain was assessed by a blinded observer using an objective pain scale. The three study groups were similar with respect to demographic data, duration of anaesthesia and surgery, induction behaviour, oxygen saturation, incidence of postoperative emesis and, recovery times. The ketorolac group had lower postoperative pain scores and required less frequent analgesic therapy in the early postoperative period compared with the acetaminophen and placebo groups. In contrast, there were no differences in pain scores or analgesic requirements between the acetaminophen and the placebo groups. We conclude that the preoperative administration of oral ketorolac, but not acetaminophen, provided better postoperative pain control than placebo in children undergoing bilateral myringotomy.