Simplified insertion of a transpyloric feeding tube

Placement of a transpyloric feeding tube is a common procedure done through a previous gastrostomy site. Conventional fluoroscopic and endoscopic methods can be tedious because of the difficulty in cannulating the pylorus. Described here is a simplified method to place a transpyloric feeding tube under fluoroscopy.     

mRNA silencing in erythroid differentiation: hnRNP K and hnRNP E1 regulate 15-lipoxygenase translation from the 3' end

Although LOX mRNA accumulates early during differentiation, a differentiation control element in its 3' untranslated region confers translational silencing until late stage erythropoiesis. We have purified two proteins from rabbit reticulocytes that specifically mediate LOX silencing and identified them as hnRNPs K and E1. Transfection of hnRNP K and hnRNP E1 into HeLa cells specifically silenced the translation of reporter mRNAs bearing a differentiation control element in their 3' untranslated region. Silenced LOX mRNA in rabbit reticulocytes specifically coimmunoprecipitated with hnRNP K. In a reconstituted cell-free translation system, addition of recombinant hnRNP K and hnRNP E1 recapitulates this regulation via a specific inhibition of 80S ribosome assembly on LOX mRNA. Both proteins can control cap-dependent and internal ribosome entry site-mediated translation by binding to differentiation control elements. Our data suggest a specific cytoplasmic function for hnRNPs as translational regulatory proteins.     

Concert of lamentations

OBJECTIVE: To determine the risk of suicide in patients attending an accident and emergency (A&E) department with deliberate self harm. METHODS: Information was obtained on suicides and open verdicts from the coroner's office and cross checked with computerised records in the A&E department. RESULTS: There was a trend to suicide among younger socially isolated males and older females. CONCLUSIONS: There is a significant association between suicide and a previous attendance at A&E with deliberate self harm. Appropriate assessment of these patients is an efficient way of managing self harm.     

1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis

OBJECTIVES: To test the hypothesis that irrecoverable neurological deficit in multiple sclerosis is associated with axonal loss. METHODS: 1H magnetic resonance spectroscopy (MRS) was carried out in a group of patients with clinically definite multiple sclerosis (n=31). Using this technique, the apparent concentration of NA ([NA] the sum of N-acetyl aspartate (NAA), a neuronal marker, and N-acetylaspartylglutamate has been compared in four groups of patients with multiple sclerosis classified as relapsing-remitting, secondary progressive, primary progressive, benign, and a control group. RESULTS: In the patients with relapsing-remitting disease (n=9) there was a highly significant reduction of apparent NA (median 8.73 mM, range 6.86 mM-10.74 mM, P=0.0008) from an area of high signal compared with the control group (median 11.97 mM, range 10.55 mM-14.5 mM). In the patients with secondary progressive disease (n=10), there was again a highly significant reduction of apparent NA (median 7.82 mM, range 3.5 mM-10.3 mM, P=0.0003) from an area of high signal compared with the control group. In the patients with primary progressive disease (n=6) there was once again a highly significant reduction of apparent NA (median 8.83 mM, range 6.95 mM-9.89 mM, P<0.002) from an area of high signal compared with the control group. In the patients with benign disease, however, there was no significant difference in the apparent NA (median 10.5 mM, range 8.53 mM-12.8 mM, P>0.05) from an area of high signal compared with the control group. In the patients with benign disease (n=5) there was also no significant difference in the apparent NA (median 10.74 mM, range 8.58 mM-13.4 mM, P>0.3) from an area of normal appearing white matter compared with the control group. In the patients with primary progressive disease, however, there was a significant reduction of apparent NA from an area of normal appearing white matter (median 8.78 mM, range 8.7 mM-12.38 mM, P< 0.025) compared with the control group. There was a significant inverse correlation between [NA] from lesions in the patients with multiple sclerosis and disability as measured on the Kurtzke expanded disability scale score (r= -0.364, 0.05>P>0.02). CONCLUSION: These findings support the hypothesis that axonal loss is important in the development of disability in multiple sclerosis. They also provide evidence for axonal loss in normal appearing white matter in patients with primary progressive disease.     

Effect of vitamin D deficiency on lipid composition and calcium transport in basolateral membrane vesicles from chick intestine

Vitamin D deficiency affects the lipid composition and Ca2+ uptake of intestinal basolateral membranes from chick intestine. The increased cholesterol content causes an increase in the molar ratio cholesterol/phospholipid. Phospholipid classes remain unchanged, but the percentages of arachidonic acid from the from the major phospholipid fractions are increased. After 24 hours of oral administration of 2,000 IU of cholecalciferol to vitamin D-deficient chicks, the cholesterol values do not change, but the amount of arachidonic acid returns to normal values. Ca2+ uptake driven by ATP is diminished in vesicles from intestinal basolateral membranes of vitamin D-deficient chicks. Cholecalciferol treatment returns these values to the controls which might be due mainly to the increased number of Ca2+ pump units. In conclusion, changes in lipid composition and in Ca2+ pump caused by vitamin D deficiency seems to play a role in the decrease of vesicular Ca2+ transport. A single dose of cholecalciferol restores only partially the lipid-protein changes produced by vitamin D deficiency.     

Novel and selective partial agonists of 5-HT3 receptors. 2. Synthesis and biological evaluation of piperazinopyridopyrrolopyrazines, piperazinopyrroloquinoxalines, and piperazinopyridopyrroloquinoxalines

In continuation of our previous work on piperazinopyrrolothienopyrazine derivatives, three series of piperazinopyridopyrrolopyrazines, piperazinopyrroloquinoxalines, and piperazinopyridopyrroloquinoxalines were prepared and evaluated as 5-HT3 receptor ligands. The chemical modifications performed within these new series led to structure-activity relationships regarding both high affinity and selectivity for the 5-HT3 receptors that are in agreement with those established previously for the pyrrolothienopyrazine series. The best compound (8a) obtained in these new series is in the picomolar range of affinity for 5-HT3 receptors with a selectivity higher than 10(6). Four of the high-affinity 5-HT3 ligands (8a, 15a,b, and 16d) were selected in both the pyridopyrrolopyrazine and the pyrroloquinoxaline series and were characterized in vitro and in vivo as agonists or partial agonists. Compound 8a was also evaluated in the light/dark test where it showed potential anxiolytic-like activity at very low doses per os.     

Radiotherapeutic management of cervical carcinoma that complicates pregnancy

BACKGROUND: Data regarding radiation therapy for pregnant patients with cervical carcinoma are limited. The goal of this study was to assess the effects of pregnancy on tumor control, survival, and morbidity associated with radiation therapy administered to pregnant patients. METHODS: The authors performed a retrospective case-control analysis of 26 women with cervical carcinoma who were diagnosed during pregnancy and treated primarily with radiation therapy. These cases were matched with 26 controls based on age, histology, stage, treatment, and year of treatment. RESULTS: Patients were treated with external beam radiation (mean dose, 46.7 gray [Gy]) and intracavitary radiation (mean dose, 56.5 Gy to Point A). Two patients with Stage IA2 squamous cell carcinoma treated in the third trimester had a planned delay in treatment of 3 weeks, and both infants had an uncomplicated neonatal course. Seven pregnant patients (2 Stage IB1, 5 Stage IB2) underwent radiation after radical hysterectomy was aborted due to positive regional lymph nodes. Three patients diagnosed during the first trimester were treated with radiation with the fetus in situ, and all had spontaneous abortions 20-24 days after the start of radiation (mean dose, 34 Gy). In all these cases, radiation was interrupted for only 3 days or less. There were no statistically significant differences in recurrence rates or survival between the pregnant group and the controls. Short term toxicity was comparable in pregnant and nonpregnant patients and easily controlled. Long term complications were more common in controls (12% in pregnant patients, 27% in controls), but this difference was not statistically significant. Most complications were likely related to radiation techniques (particularly the predominance of cobalt-60). CONCLUSIONS: Planned delay in treatment should be offered to pregnant patients with early stage squamous cell carcinoma in the late second and early third trimester. Patients diagnosed in the first or second trimester who are not good candidates for planned delay in treatment should be given radiation therapy immediately. It may be necessary to reconsider planned radical hysterectomy for pregnant women with Stage IB2 disease due to the high rate of lymph node positivity found on exploration. For patients with advanced disease, radiation therapy appears to be a safe and effective modality.     

A 6.1 kb 5' upstream region of the mouse tryptophan hydroxylase gene directs expression of E. coli lacZ to major serotonergic brain regions and pineal gland in transgenic mice

Tryptophan hydroxylase (TPH) catalyzes the first step of serotonin biosynthesis in serotonergic neurons and neuroendocrine cells. Serotonin influences diverse vital physiological functions and is thought to play an important role in several human psychiatric disorders. To localize DNA element(s) important for serotonergic tissue-specific expression of TPH, 6.1 kb of the 5' flanking region of the mouse TPH gene was fused to the coding region of the E. coli lacZ gene, and expression of the resulting fusion gene was analyzed in transgenic mice. The 6.1 kb of 5' flanking sequence was able to direct the expression of a lacZ reporter gene to serotonergic tissues in six lines of transgenic mice. A high level of lacZ expression in transgenic mice carrying the fusion gene was detected in the pineal gland as well as a moderate level of lacZ expression in serotonergic brain regions such as the median and dorsal raphe nuclei, the nuclei raphe magnus and raphe pallidus. In contrast, a smaller 5' flanking sequence of 1.1 kb directed no detectable serotonergic tissue-specific lacZ expression in five lines of transgenic mice. These results presented in this paper suggest first that DNA elements critical to serotonergic tissue-specific expression reside between -6.1 kb and -1.1 kb of 5' flanking region of the mouse TPH gene, but second that this region confers a restricted tissue-specific expression.