Menin molecular interactions: insights into normal functions and tumorigenesis.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease predisposed by heterozygous germline mutations in the MEN1 tumor suppressor gene. Biallelic loss of MEN1 resulting from small mutation and/or loss of heterozygosity occurs in a large tissue spectrum of MEN1 tumors or non-hereditary tumors. Mouse models of MEN1 underexpression or overexpression have also supported the tumor-suppressor effect of the MEN1 gene. Menin, the 610-amino-acid protein encoded by MEN1, is expressed ubiquitously and found predominantly in the nucleus. Sequence analyses do not reveal motifs of known function other than two nuclear localization sequences. Menin has been found to partner in vitro with a variety of proteins that comprise transcription factors, DNA processing factors, DNA repair proteins, and cytoskeletal proteins. The diverse functions of menin interactors suggest roles for menin in multiple biological pathways. Inactivation of menin switches its JunD partner from a downstream action of growth suppression to growth promotion. This is a plausible mechanism for menin tumorigenesis.

Practical issues and concepts in vagus nerve stimulation: a nursing review.

Estimates of epilepsy incidence among the U.S. population range between 0.5% and 1%. The most common type of seizure in adult patients is partial onset. Approximately 20% of these patients are refractory to antiepileptic drug therapy and experience intolerable side effects such as confusion, dizziness, weight gain, lethargy, and ataxia. The ketogenic diet appears to be beneficial for children but is not considered a standard option for adults. Epilepsy surgery can be an option for many and may offer control or a reduction in seizures. However, many patients are opposed to cranial surgery or may not tolerate the ketogenic diet. Recent advances in biomedical technology and perfection in surgical techniques have shown vagus nerve stimulation (VNS) using the Neuro Cybernetic Prosthesis (NCP) system is an effective new treatment option in reducing seizure frequency. On July 16, 1997, the U.S. Food and Drug Administration (FDA) approved the use of the NCP for vagus nerve stimulation, as an adjunctive treatment for refractory partial onset seizures in adults and adolescents over 12 years of age. Murphy et al. and Wheless have reported similar results in children younger than 12 years. VNS represents the first therapy using a medical device approved by the FDA for the treatment of refractory seizures. An estimated 10,000 patients have been implanted with the device.

Effect of orally administered nadolol on the intraocular pressure in normal volunteers.

Forty six normal volunteers were randomly assigned in double-blind fashion to once daily orally administered nadolol 10, 20, 40, or 80 mg for five days. Significant and dose related intraocular pressure (IOP) reductions (range 20-40%) were demonstrated both at three hours and 24 hours post dosing (p less than 0.001, all dosages). The reductions in IOP were dose related (p less than 0.05). One subject (in the 10 mg group) failed to show a significant intraocular pressure reduction. Significant reductions in blood pressure and heart rate also were recorded at all dose levels (with the exception of diastolic pressure in the 10 mg group), though considerably less in degree than IOP reductions. Two subjects (20 mg and 80 mg groups) experienced known side effects of beta blocker therapy necessitating termination of the drug, and four others experienced mild side effects but had no difficulty completing the study. The results have prompted further investigation of the usefulness of low doses of oral nadolol as therapy in chronic simple glaucoma patients.

Management of deep venous thrombosis and pulmonary embolism during pregnancy.

Despite venous stasis and a hypercoagulable state during pregnancy, the reported incidences of deep venous thrombosis and pulmonary embolism are remarkably low, about 1 in 2,000 and 1 in 10,000 cases, respectively. Mortality from antepartum thromboembolism has been reported in about 15 percent of untreated patients and less than 1 percent of treated patients. Adequate anticoagulant therapy significantly reduces maternal mortality and decreases postpartum morbidity. The proper anticoagulant agent for use during pregnancy has been widely debated. Coumarin compounds pass through the placenta and into the fetus. Hemorrhagic complications in the fetus are uncommon if prothrombin times are carefully controlled and if the drug is discontinued before delivery. However, coumarin during the first trimester has the teratogenic hazard of producing chondrodysplasia punctata. Heparin, in contrast, does not cross the placental barrier and is considered more effective treatment for deep venous thrombosis; however, long-term intravenous administration during pregnancy has been considered both impractical and possibly hazardous due to the risk of osteoporosis after 6 months of therapy. In our study, a combined regimen of intravenous and subcutaneous heparin was used successfully in four women with deep venous thrombosis. One patient who had recurrent embolization while on adequate intravenous heparin underwent vena caval clipping and had an uneventful Cesarian section at term with a normal infant. Another patient also underwent Caesarian section with a normal infant, while the other two women had normal vaginal deliveries at term. Miniheparin therapy was continued for 3 months postpartum, followed by long-term aspirin and Ascriptin therapy. Carefully controlled heparin therapy in a pregnant woman with deep venous thrombosis both safe and beneficial for mother and fetus.

Coagulopathy associated with peritoneovenous shunting.

Le Veen shunts successfully alleviated ascites in 19 of 24 patients (79 percent). Clinical clotting typical of disseminated intravenous coagulation occurred in nine of these patients (37 percent) and was fatal in seven (78 percent). Laboratory findings suggesting disseminated intravenous clotting were present in five other patients (21 percent) but were not associated with troublesome bleeding. Coagulopathy was reversed in 7 of 14 patients (50 percent), if the shunt was ligated and supportive measures were taken early in the postoperative course. Failure to recognize or take immediate action resulted in progressive disseminated intravenous clotting associated with a mortality of 50 percent (7 of 14 patients).