Bone marrow transplantation for adults with acute leukaemia and 11q23 chromosomal abnormalities

Adults with acute leukaemia and abnormalities of chromosome 11q23 have a poor prognosis when treated with conventional chemotherapy. To determine whether more intensive therapy can improve outcome for patients with this karyotypic finding, a retrospective analysis of all patients with acute leukaemia and 11q23 abnormalities treated at our centre was performed. 12 patients were treated with conventional chemotherapy alone (CC); 20 patients received high-dose chemo/radiotherapy (HDCT) with autologous (seven patients) or allogeneic (13 patients) bone marrow transplantation (BMT). The treatment-related mortality was 25% [95% Confidence Interval (CI) 7-69%] for the CC group and 46% (CI 25-73%) for the BMT group (P = 0.69). Cumulative risk of leukaemia progression was 89% (CI 61-100%) in the CC patients and 38% (CI 12-69%) in the BMT patients (P = 0.001). The 2-year event-free survival for patients treated with CC was 8% (CI 0-31%) and for patients receiving HDCT and BMT was 34% (CI 14-54%) (P = 0.03). These results confirm that conventional chemotherapy is rarely curative for adults with acute leukaemia and 11q23 abnormalities but that HDCT with BMT can result in long-term survival in a significant proportion of patients.     

Daily variation of CNS gene expression in nocturnal vs. diurnal rodents and in the developing rat brain

To identify risk factors associated with an increased risk for ipsilateral breast tumor recurrence following breast-conserving surgery, a cohort of 759 women with T1-T2 tumors were studied. The majority of the patients (88%) had received postoperative radiation therapy to the breast. Median follow-up time was 10 (range: 6-17) years. There was a 1-1.5% yearly increase in ipsilateral breast tumor recurrences. For women < 50 ys the cumulative recurrence rate at 10 years was 18% and for women > or = 50 ys, 9%. Node positive women had a cumulative breast recurrence rate of 25% versus 10% for node negative women. Ten years postoperatively, irradiated patients had a cumulative recurrence rate of 11% versus 26% when no irradiation was given. The beneficial effect of radiotherapy was substantial during the first four postoperative years. The relative risk for an ipsilateral breast tumor recurrence during this period was 4.5 times higher than for non-irradiated patients. However, the protective effect of radiotherapy decreased with time. After ten years the relative risk of ipsilateral breast tumor recurrence was the same among irradiated and non-irradiated patients although the number of events during this period was low. Univariate analysis showed that seven factors were significantly associated with an increased risk of ipsilateral breast tumor recurrence, namely age < 50 ys, increasing tumor size, uncertain microscopic margins, axillary lymph node metastases, no postoperative tamoxifen treatment, premenopausal status, and no postoperative radiotherapy. Three factors remained independently significant after multivariate analysis: age < 50 ys, no postoperative radiation therapy, and positive lymph nodes. In conclusion, radiotherapy reduced the breast recurrence rate, but the effect decreased with time. Node-negative women > or = 50 were a low risk-group for ipsilateral breast tumor recurrence, with a cumulative risk at 10 years of 9% without radiation therapy and 5% with breast irradiation.     

Lowering the burden of suffering from child psychiatric disorder: trade-offs among clinical, targeted, and universal interventions

OBJECTIVE: To examine the trade-offs among clinical, targeted, and universal interventions aimed at lowering the burden of suffering from child psychiatric disorders. METHOD: Data from clinical and research studies were organized to show the advantages and disadvantages of the three strategies. RESULTS: Important trade-offs exist among these three approaches. The strategy to reduce the burden of suffering from child psychiatric disorder should consist of a number of concurrent steps. First, effective universal programs should be in place. Targeted programs should follow for those not helped sufficiently by the universal programs. Finally, for those unaffected by the targeted programs, clinical services should be available. CONCLUSION: An optimal mix of universal, targeted, and clinical programs is needed. The nature of the combination will change as knowledge accumulates, and there will always be trade-offs among these three. Acad.     

Role of CYP2A5 and 2G1 in acetaminophen metabolism and toxicity in the olfactory mucosa of the Cyp1a2(-/-) mouse

Acetaminophen (AP) is a widely-used analgesic agent that has been linked to human liver and kidney disease with prolonged or high-dose usage. In rodents, the target organs that are affected include liver, kidney, and the olfactory mucosa. AP toxicity requires cytochrome P450(CYP)-mediated metabolic activation, and the isozymes CYP1A2, 2E1, and 3A are known to activate AP in the human. In the present study, we determined that olfactory mucosal toxicity of AP was not different between the Cyp1a2(+/+) wild-type and the Cyp1a2(-/-) knockout mouse, whereas the hepatic toxicity of AP was significantly diminished in Cyp1a2(-/-) mice. Western blots of olfactory mucosa revealed that CYP2E1 and CYP3A levels are similar between untreated Cyp1a2(+/+) and Cyp1a2(-/-) mice. Diallyl sulfide (DAS), a known inhibitor of CYP2E1 and of CYP2A10/2A11 (the rabbit orthologue of mouse CYP2A5), completely eliminated olfactory toxicity of AP in both the Cyp1a2(-/-) and wild-type mouse olfactory mucosa. We found that heterologously expressed mouse CYP2A5 and CYP2G1 enzymes (known to be present in olfactory mucosa) form 3-hydroxyacetaminophen (3-OH-AP) and 3-(glutathion-S-yl)acetaminophen (GS-AP); CYP2A5 is considerably more active than 2G1. Addition of GSH caused increases in GS-AP proportional to decreases in 3-OH-AP, suggesting that these two metabolites arise from a common precursor or are formed by way of competing pathways. We also found that both CYP2A5 and CYP2G1 are inhibitable by DAS in vitro. These studies provide strong evidence that, in addition to CYP2E1, CYP2A5 and 2G1 are important in AP bioactivation in the mouse olfactory mucosa and that CYP1A2 appears to be of minor importance for AP olfactory toxicity.     

Migraine--diagnosis, differential diagnosis and therapy

Migraine is caused by intermittent brain dysfunction. Attacks result in severe unilateral headache with nausea, vomiting, photophobia, phonophobia and general weakness. The prevalence of migraine is 12 to 20% in women and 8 to 12% in man. Treatment of an acute attack is done by antiemetics in combination with analgesics. Severe migraine attacks are treated with ergotamine or sumatriptan. Parenteral treatment is performed most efficiently and safely with i.v. ASA. Frequent and severe attacks require prophylaxis. Drugs of first choice are metoprolol, propranolol, flunarizine and cyclandelate. Substances of second choice are valproic acid, DHE, pizotifen, methysergide and magnesium. Homeopathic remedies are not superior to placebo. Nonpharmacological treatment consists of sport therapy and muscle relaxation techniques.     

Purification, characterization and complete amino acid sequence of nuclease C1 from Cunninghamella echinulata var. echinulata

The authors hypothesized that children's perceptions of their parents' job insecurity mediate the effects of parental job insecurity and layoffs on children's work beliefs and work attitudes. Male and female undergraduate students (N = 134; M age = 18.9 years), as well as their mothers (M age = 47.0 years) and fathers (M age = 49.1 years), participated voluntarily. With structural equation modeling as implemented by LISREL VIII, support for the proposed model was obtained, whereas no support was obtained for a competing model. Moreover, identification with fathers moderated the influence of perceived paternal job insecurity on children's humanistic work beliefs, but no comparable effect emerged for mothers.     

Echocardographic features of papillary fibroelastoma and their consequences and management

Clone CL Brener is the reference organism used in the Trypanosoma cruzi Genome Project. Some biological parameters of CL Brener were determined: (a) the doubling time of epimastigote forms cultured in liver infusion-tryptose (LIT) medium at 28 degrees C is 58 +/- 13 hr; (b) differentiation of epimastigotes to metacyclic trypomastigotes is obtained by incubation in LIT-20% Grace's medium; (c) trypomastigotes infect mammalian cultured cells and perform the complete intracellular cycle at 33 and 37 degrees C; (d) blood forms are highly infective to mice; (e) blood forms are susceptible to nifurtimox and benznidazole. The molecular typing of CL Brener has been determined: (a) isoenzymatic profiles are characteristic of zymodeme ZB; (b) PCR amplification of a 24S alpha ribosomal RNA sequence indicates it belongs to T. cruzi lineage 1; (c) schizodeme, randomly amplified polymorphic DNA (RAPD) and DNA fingerprinting analyses were performed.     

A case of bilateral ulnar nerve palsy in a patient with traumatic brain injury and heterotopic ossification

Heterotopic ossification after head injury may occur in the elbow joint. Rarely does this lead to entrapment of the ulnar nerve. We describe the case of a 20-year-old patient who developed heterotopic ossification 6 weeks after a traumatic brain injury. She subsequently developed bilateral ulnar nerve palsy which was confirmed by electrodiagnostic studies and treated by transposition of the ulnar nerve.     

Trade-off associated with selection for increased ability to resist parasitoid attack in Drosophila melanogaster

Costs of resistance are widely assumed to be important in the evolution of parasite and pathogen defence in animals, but they have been demonstrated experimentally on very few occasions. Endoparasitoids are insects whose larvae develop inside the bodies of other insects where they defend themselves from attack by their hosts' immune systems (especially cellular encapsulation). Working with Drosophila melanogaster and its endoparasitoid Leptopilina boulardi, we selected for increased resistance in four replicate populations of flies. The percentage of flies surviving attack increased from about 0.5% to between 40% and 50% in five generations, revealing substantial additive genetic variation in resistance in the field population from which our culture was established. In comparison with four control lines, flies from selected lines suffered from lower larval survival under conditions of moderate to severe intraspecific competition.