Expression analysis of alpha-NAC and ANX2 in juvenile myelomonocytic leukemia using SMART polymerase chain reaction and "virtual Northern" hybridization

Juvenile myelomonocytic leukemia (JMML) is a malignant hematopoietic disease of early childhood with both myeloproliferative and myelodysplastic features. We had previously identified the genes for the alpha-chain of the nascent polypeptide-associated complex (NACA) and annexin II (ANX2) as potentially involved in the pathophysiology of JMML. Now we used SMART cDNA synthesis and subsequent "virtual Northern" blot to analyze differential expression of NACA and ANX2 genes in various hematologic cell lines and compared the data to those obtained by standard Northern analyses. The results show that SMART cDNA reproduces the expression profile found in mRNA. Dilution experiments showed that analyses using as little as 0.5 ng of total RNA led to reliable results. After validating the technique, we used virtual Northern blots to analyze expression of NACA and ANX2 in progenitor cultures of nine children with JMML and five healthy individuals. We found no consistent pattern of differential expression between patients and healthy donors. We conclude that aberrant regulation of NACA or ANX2 does not play a relevant role in JMML pathogenesis.     

Effects of ethnicity on treatment attendance,stimulant response/dose,and 14-month outcome in ADHD

From the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder--a randomized clinical trial of 579 children ages 7-9 years receiving 14 months of medication management, behavioral treatment, combination, or community care--the authors matched each African American and Latino participant with randomly selected Caucasian participants of same sex, treatment group, and site. Although Caucasian children were significantly less symptomatic than African American and Latino children on some ratings, response to treatment did not differ significantly by ethnicity after controlling for public assistance. Ethnic minority families cooperated with and benefited significantly from combination (multimodal) treatment (d = 0.36, compared with medication). This incremental gain withstood statistical control for mother's education, single-parent status, and public assistance. Treatment for lower socioeconomic status minority children, especially if comorbid, should combine medication and behavioral treatment.     

A comparison of clinical variables that predict adverse outcome in term infants with severe respiratory failure randomised to a policy of extracorporeal membrane oxygenation or to conventional neonatal intensive care

OBJECTIVE: To identify clinical variables predicting adverse outcome in a group of infants with severe respiratory failure who were randomized either to referral for extra-corporeal membrane oxygenation (ECMO) or to conventional neonatal intensive care within the United Kingdom. METHODS: Adverse outcome was defined by death or disability by four years of age. Receiver operator characteristic (ROC) plots were constructed for variables with continuous data and relative risk (RR) with 95% confidence intervals (CI) calculated for binominal data. RESULTS: Of variables measurable at trial entry, congenital diaphragmatic hernia and lower birthweight was also associated with increased mortality and morbidity. Seizures or supplementary oxygen at discharge were markers of disease course, which predicted a poorer outcome amongst survivors. These variables behaved similarly in the two trial groups. Those infants in the ECMO group with an episode of sepsis, established full sucking feeds after 14 days of age or a hospital stay over 30 days were at increased risk of disability. CONCLUSIONS: This study has identified clinical variables that predict adverse outcome for term infants with severe respiratory failure. The results may assist clinicians caring for these babies, when counseling their families and in the development of guidelines for neonatal ECMO.     

The group II metabotropic glutamate receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0.]hexane-4,6-dicarboxylate (LY379268) and clozapine reverse phencyclidine-induced behaviors in monoamine-depleted rats

Recent studies have indicated that the selective group II metabotropic glutamate (mGlu) receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0.]hexane-4,6-dicarboxylate (LY379268) shares common biochemical and pharmacological effects with the atypical antipsychotic clozapine. The present study aimed to further investigate these similarities (or differences) in monoamine-depleted animals by using the phencyclidine (PCP) model. Animals were pretreated 24 h before PCP administration with (i.p.) vehicle, alpha-methyl-DL-p-tyrosine methyl ester (alpha-MPT; 400 mg/kg), or DL-p-chlorophenyl-alanine methyl ester (PCPA; 300 mg/kg) injections. alpha-MPT and PCPA pretreatment significantly and selectively reduced catecholamine (dopamine and norepinepherine) or 5-hydroxytryptamine (5-HT, serotonin) and 5-hydroxyindoleacetic acid levels, respectively, in whole brain tissue. Both LY379268 and clozapine (s.c.) blocked PCP-evoked ambulatory activity and fine movements in control, alpha-MPT-, and PCPA-treated animals. In contrast, the typical antipsychotic haloperidol (s.c.) attenuated PCP behaviors in control and PCPA-pretreated animals, but was without effect in subjects pretreated with alpha-MPT. The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate-selective antagonist (3S,4aR,6R,8aR)-6-[2-(1(2)OH-tetrazole-6-yl)ethyl]decahydroisoquinoline-3-carboxylic acid (LY293558) attenuated locomotor activity in alpha-MPT-treated animals only, whereas the 5-HT(2A/2C)-selective antagonist ketanserin was effective at reducing ambulations and fine movements in control and alpha-MPT-treated animals. Taken together, these data indicate an important role for glutamatergic and serotonergic mechanisms for PCP-evoked behaviors in catecholamine-depleted animals and suggest that like clozapine, LY379268 is more effective than typical antipsychotics in these models. This study further supports the potential use of group II mGlu agonists as novel therapeutic agents in the treatment of schizophrenia.     

Disparity in total hip replacement affecting Hispanic Medicare beneficiaries

OBJECTIVE: To compare the utilization of total hip replacement (THR) between Hispanic persons and non-Hispanic persons in a sample with health insurance. RESEARCH DESIGN: Case-control study using Medicare claims data. PATIENTS: The cases were Medicare beneficiaries from Arizona, Illinois, New Mexico, or Texas who underwent a primary THR. The controls were Medicare beneficiaries who did not receive a THR, matched by age, sex, and county of residence. MEASURES: Beneficiary surnames and the race indicator in Medicare records were used to classify beneficiaries' probability of being Hispanic. Conditional logistic regression was used to estimate the odds of receiving of THR, adjusting for Medicaid eligibility. RESULTS: Six thousand four hundred thirty-seven recipients of a primary THR were matched to 12,874 controls. According to the Medicare race indicator, 1% of recipients of THR and 3.3% of controls were Hispanic (P < or =0.001). The odds of THR decreased as the probability of Hispanic ethnicity increased, from an odds ratio (OR) of 1.00 among beneficiaries with non-Hispanic surnames, to an OR of 0.36 among those with heavily Hispanic surnames (95% CI, 0.31, 0.43). Poverty, as reflected by eligibility for Medicaid, did not modify the low odds of THR among Hispanic persons (OR, 0.25 among Medicaid-eligible Hispanic persons; 95% CI, 0.19, 0.33; and OR, 0.30 among Hispanic persons not Medicaid eligible; 95% CI, 0.24, 0.38). CONCLUSION: Hispanic persons with Medicare receive THR at lower rates than do non-Hispanic persons. Because Medicare covers THR, our findings suggest that under utilization of THR by Hispanic persons cannot be attributed to lack of health insurance alone.     

Human internal mammary artery organ culture model of coronary stenting: a novel investigation of smooth muscle cell response to drug-eluting stents

Local drug delivery by coronary stents is of current research interest. Organ culture of human vascular tissue is a model of intimal hyperplasia. We report an ex vivo organ culture model of stented vessels. This allows stent-artery interactions to be studied in living tissue. The recognized anti-restenosis agent paclitaxel was chosen to test the organ culture model. Mammary artery specimens were cultured 'closed' (i.e. without opening them flat) for 72 h. Phosphocholine-coated stents, half of them loaded with the anti-restenosis drug paclitaxel, were implanted. The absorption and elution characteristics of paclitaxel were established. Artery tissue remained viable at 72 h when cultured closed, despite stent implantation. Specimens developed smooth muscle cell proliferation. The stents absorbed up to 127+/-29 microg of paclitaxel, with a biphasic elution curve. A mean of 13% of the absorbed paclitaxel remained after a 24 h perfusion. In mammary artery, these paclitaxel stents reduced or abolished smooth muscle cell proliferation compared with controls. This model allows the effects of stenting on human arterial tissue to be studied for at least 72 h, long enough to demonstrate effects on smooth muscle cell proliferation. Phosphocholine-coated stents absorb adequate doses of paclitaxel, which is eluted gradually, inhibiting muscle cell proliferation. Such an organ culture model of stented mammary artery will provide useful data in addition to that from animal or cell culture models of drug-eluting stents.     

Information needs and information-seeking behaviors of men with prostate cancer and their partners: a review of the literature

A critical review of the literature was carried out in the United Kingdom to identify the information needs and information-seeking behaviors of men with prostate cancer and their partners. Relevant papers published between 1990 and 2000 were reviewed and despite having several methodologic limitations, a number of conclusions can still be drawn from this review. First, men with prostate cancer have distinct information needs and information-seeking behaviors throughout their cancer journeys. Although there is considerable variation in the amount and type of information that men require, the majority of men with prostate cancer are satisfied with the information they receive. Second, although partners of men with prostate cancer have needs for information, these needs are often unmet. Partners undergo an information-seeking pattern that is comparable with, if not more active than, patients' information-seeking behaviors. These findings have a number of implications for cancer nursing practice and research, which are discussed in the article.