WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer

Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of...     

The National Summit on Preconception Care: A Summary of Concepts and Recommendations

The Centers for Disease Control and Prevention (CDC) and 35 partner organizations have engaged in developing an agenda for Preconception Health. A summit was held in June 2005 to discuss the current state of knowledge regarding preconception care and convene a select panel to develop recommendations and action steps for improving the health of women, children, and families through advances in clinical care, public health, and community action. A Select Panel on Preconception Care, convened by CDC, deliberated critical related issues and created refined definition of preconception care. The panel also developed a strategic plan with goals, recommendations, and action steps for improving preconception health. The recommendations and action steps are specific to the implementation of health behavior, access, consumer demand, research, and surveillance activities for monitoring and improving the health of women, children and families. The outcome of the deliberations is the CDC publication of detailed recommendations and action steps in the Morbidity and Mortality Weekly Report series, Recommendations and Reports.

     

Adherence to continuous positive airway pressure treatment in patients with Alzheimer's disease and obstructive sleep apnea.

OBJECTIVE: This analysis examined whether patients with Alzheimer disease (AD) tolerate continuous positive airway pressure (CPAP). METHOD: Thirty patients with AD were randomized to CPAP or sham CPAP and completed sleep, depression, and quality-of-life questionnaires. Participants could choose to continue treatment after the trial. RESULTS: Patients wore CPAP for 4.8 hours per night. More depressive symptoms were associated with worse adherence (rS=-0.37; N=30, p<0.04). Patients who continued using CPAP had fewer depressive symptoms (t [19]=2.45, p=0.02) and better adherence (t [19]=2.32, p=0.03) during the trial. CONCLUSION: Patients with AD with obstructive sleep apnea can tolerate CPAP. Adherence and long-term use may be more difficult among those patients with more depressive symptoms.     

Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data.

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing doxorubicin and human immunoglobulin as an actively/passively targeting moiety was used in four patients with generalized breast cancer resistant to standard cytotoxic chemotherapy. The dose and time schedule were deduced from a Phase I clinical trial in which doxorubicin bound to HPMA copolymer carrier (PK1) was tested. It was confirmed that the Dox-HPMA-HuIg conjugate is stable and doxorubicin remains in the peripheral blood with a small amount also in the urine, mostly in its polymer-bound form. More than 116 biochemical, immunological and hematological parameters were determined for blood samples taken from patients 24 h, 48 h, 72 h and 1 to 11 weeks after treatment. Depending on the patient, some parameters decreased permanently or temporarily to the normal level (CRP, C3, CA 72-4, beta(2)-microglobulin, ferritin, CEA, CA 125, CD4, CD8, CE19, CD16(+)56(+), leu, ery) and some moved markedly towards physiological values (AST, ALT, ALP, GMT, CA 15-3, NSE, AFP). While the number of peripheral blood reticulocytes was significantly decreased after treatment with the classical free drug, their number was not affected or was even elevated after treatment with Dox-HPMA-HuIg. Increased absolute numbers of CD16(+)56(+) and CD4(+) cells in the peripheral blood and activation of NK and LAK cells in all patients support data obtained in experimental animals, pointing to a dual, i.e. cytostatic and immunomobilizing character of Dox-HPMA conjugates containing a targeting immunoglobulin moiety.     

Continuous Preperitoneal Infusion of Ropivacaine Provides Effective Analgesia and Accelerates Recovery after Colorectal Surgery: A Randomized, Double-blind, Placebo-controlled Study

Background: Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial.

Methods: After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia.

Results: Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed.     

Effects of MK-801 and Phenytoin on Flurothyl-Induced Seizures During Development

Summary We determined the effects of the N-methyl-Daspartate (NMDA) receptor blocker MK-801 (0.05, 0.1, and 0.5 mg/kg intraperitoneally, i.p.) and phenytoin (PHT, 5, 10, and 20 mg/kg i.p.) on flurothyl-induced clonic and tonic-clonic seizures in 9-, 1 5, 30-, and 60-day-old male rats. Both agents had seizure-, age-, and dose-specific effects. The highest dose of MK-801 was anticonvulsant against clonic flurothyl-induced seizures only in 9- and 60-day-old rats, but suppressed tonic-clonic seizures in all ages. The lowest dose of MK-801 (0.05 mg/kg) produced significant anticonvulsant effects only in 15 day old rats. PHT did not have any effect on clonic seizures throughout development. Both doses of PHT (10 and 20 mg/kg) were anticonvulsant against tonic-clonic seizures in adult rats but not in any other age group. The results indicate that NMDA receptors play an important role in tonic-clonic flurothyl-induced seizures throughout development (especially in 15-day-old rats) and that the anticonvulsant effects of PHT may vary at different stages of brain development.     

Age-Specific Effects of Baclofen on Pentylenetetrazol-Induced Seizures in Developing Rats

Summary: Purpose : To determine whether seizures have age-specific features, we studied the role of γ-aminobutyric acid, (GABAB) transmission in rats of various ages (9, 15, 30, and 60 postnatal days). Methods: We used a GABA, receptor agonist baclofen (2 or 5 mg/kg intraperitoneally, i.p.) and a GABA_B receptor antagonist CGP 35348 (100 or 600 mg/kg i.p.) in the pentylenetetrazol (PTZ)-induced model of clonic and tonic-clonic seizures (100 mg/kg subcutaneously, s.c.).
Results : Whereas baclofen was anticonvulsant and CGP 35348 proconvulsant in most animals, there were distinct age-related differences in the effectiveness of these drugs and the antagonist had some anticonvulsant activity in adults. Furthermore, the two drugs acting at GABA_B receptors had a different profile of action in clonic seizures as compared with tonic-clonic seizures.
Conclusions : The differences in the age-specific action of the GABA_B agonist and antagonist suggest that different GABA_B receptor subsets may mediate the drug effects. The results indicate that putative antiepileptic drugs (AEDs) must be tested during development because it may not be possible to extrapolate age-specific anticonvulsant effects from studies in adult animals.     

Recent advances in understanding the pathogenesis of polyglutamine diseases: involvement of molecular chaperones and ubiquitin-proteasome pathway

Polyglutamine diseases consist of a group of familial neurodegenerative disorders caused by expression of proteins containing expanded polyglutamine stretch. Over the past several years, tremendous progress has been made in identifying the molecular mechanisms by which the expanded polyglutamine tract leads to neuronal dysfunction and neurodegeneration. A common feature of most polyglutamine disorders is the occurrence of ubiquitin-positive neuronal intranuclear inclusions. The appearance of ubiquitinated aggregates implies an underline incapability of the cellular chaperones and proteasome machinery that normally functions to prevent the accumulation of misfolded proteins. Here we review the recent studies that have revealed a critical role for molecular chaperones and ubiquitin-proteasome pathway in the pathogenesis of polyglutamine diseases.