New multi protein patterns differentiate liver fibrosis stages and hepatocellular carcinoma in chronic hepatitis C serum samples

~~New multi protein patterns differentiate liver fibrosis stages and hepatocellular carcinoma in chronic hepatitis C serum samples@Thomas Gbel$Klinik für Gastroenterologie,Hepatologie und Infektiologie,Heinrich-Heine-UniversitatDusseldorf,Moorenstr.e,D…     

Divergent effects of human lymphokine derived oligopeptides on PMNLs function of young and aged healthy subjects

The effects of low molecular weight lymphokine-derived oligopeptides (LK-OPs) on PMNLs effector functions and receptor mediated biochemical events were studied in the case of healthy young and aged subjects. In the case of young subjects the low mol. wt. LK-OPs stimulated the Fc gamma receptor-mediated effector functions of PMNLs, whereas an inhibition was observed in PMNLs of the elderly (extracellular cytotoxicity and intracellular killing). The underlying biochemical events, induced by low mol. wt. LK-OPs stimulation, were also investigated. In PMNLs of young subjects the oxidative metabolism was stimulated (enhanced O2 consumption, O2 and H2O2 production) by low mol. wt. LK-OPs, while in elderly subjects it was inhibited. The cyclic nucleotides regulating the Fc gamma receptor mediated effector functions and the oxygen radicals formation showed an altered dynamic response under low mol. wt. LK-OPs stimulation with aging i.e. the cGMP level could not be changed at all. Our results suggest that low mol. wt. LK-OPs induced inhibition of Fc gamma receptor mediated effector functions with aging could be partly explained by an altered post receptorial coupling switch and as a consequence the lymphokines could not play their role of immunomodulators further impairing the altered immune response with aging.     

Histopathology of smokeless tobacco lesions in professional baseball players. Associations with different types of tobacco.

We examined 142 biopsy specimens of smokeless tobacco-associated oral mucosal lesions from 133 professional baseball players. Four types of epithelial change were observed in the specimens: hyperparakeratosis, hyperorthokeratosis, pale surface staining, and basal cell hyperplasia. These types of epithelial change were associated with the type of smokeless tobacco used (snuff or chewing tobacco) but not with the duration (years) or amount (hours per day) of use. The thickness of hyperkeratosis in a specimen correlated directly with the amount of smokeless tobacco use. The use of snuff was more frequently associated with development of oral mucosal lesions than was the use of chewing tobacco, and snuff appeared to cause a greater variety and severity of epithelial change than did chewing tobacco.     

Tricuspid Atresia Associated with Truncus Arteriosus versus Aortopulmonary Window: Combining Fetal and Postnatal Echocardiography to Make the Diagnosis

The coincident occurrence of tricuspid atresia and aortopulmonary window (APW) is exceedingly rare, with one previous case reported in the literature. We present a patient with tricuspid atresia, pulmonary atresia, and APW. Postnatal echocardiograms demonstrated no visible pulmonary valve, and additional defects including a bicuspid aortic valve, right aortic arch and anomalous coronary arteries raised suspicion for tricuspid atresia with persistent truncus arteriosus. However, fetal echocardiography and direct visualization of the anatomy confirmed the alternate diagnosis. The patient underwent successful palliation consisting of APW repair, atrial septectomy and a 3.5 mm modified Blalock–Taussig shunt, followed by a bidirectional cavopulmonary connection.     

Dopaminergic regulation of dopamine D3 and D3nf receptor mRNA expression

Dopamine D3 receptors have the highest dopamine affinity of all dopamine receptors, and may thereby regulate dopamine signaling mediated by volume transmission. Changes in D3 receptor isoform expression may alter D3 receptor function, however, little is known regarding coordination of D3 isoform expression in response to perturbations in dopaminergic stimulation. To determine the effects of dopamine receptor stimulation and blockade on D3 receptor alternative splicing, we determined D3 and D3nf isoform mRNA expression following treatment with the D3 receptor antagonist NGB 2904, and the indirect dopamine agonist amphetamine. Expression of tyrosine hydroxylase (TH) mRNA, the rate‐limiting enzyme in dopamine synthesis, was also determined. The D3/D3nf mRNA expression ratio was increased in ventral striatum, prefrontal cortex, and hippocampus 6 h following D3 antagonist NGB 2904 treatment, and remained persistently elevated at 24 h in hippocampus and substantia nigra/ventral tegmentum. D3 mRNA decreased 65% and D3nf mRNA expression decreased 71% in prefrontal cortex 24 h following amphetamine treatment, however, these changes did not reach statistical significance. TH mRNA expression was unaffected by D3 antagonist NGB 2904, but was elevated by amphetamine in ventral striatum, hippocampus, and prefrontal cortex. These findings provide evidence for an adaptive response to altered D3 receptor stimulation involving changes in D3 receptor alternative splicing. Additionally, these data suggest D3 autoreceptor regulation of dopamine synthesis does not involve regulation of TH mRNA expression. Finally, the observation of regulated TH mRNA expression in dopamine terminal fields provides experimental support for the model of local control of mRNA expression in adaptation to synaptic activity. Synapse, 2010. © 2010 Wiley‐Liss, Inc.     

Trends in anthropometric measurements among Mescalero Apache Indian preschool children. 1968 through 1988.

OBJECTIVE--To determine if there were trends in underweight, short stature, and obesity among 1- through 5-year-old Mescalero (NM) Apache Indian children from 1968 through 1988. DESIGN--Cross-sectional review of hospital clinic charts for five cohorts. SETTING--General pediatric outpatient clinic at the Mescalero Indian Health Service Hospital. PARTICIPANTS--Sixty-nine patients aged 1 through 5 years in 1968, 1973, 1978, 1983, or 1988 for whom weight and height were recorded during a well-child visit that occurred in the respective year. SELECTION PROCEDURES--Approximately half the charts were screened for eligibility through systematic sampling for all years except 1988; for 1988 all available charts were screened for eligibility for the study. INTERVENTIONS--None. MEASUREMENTS AND RESULTS--We found trends of decreasing prevalence of both underweight (defined as weight-for-height below the fifth percentile) and short stature (defined as height-for-age below the fifth percentile) based on the Centers for Disease Control/World Health Organization growth reference. We found no secular trends in obesity (weight-for-height above the 95th percentile), although the prevalences throughout the 21-year period were as much as two to four times higher than expected when compared with the Centers for Disease Control/World Health Organization reference. There has been an upward shift in both weight-for-height and height-for-age distributions since 1968, indicating that Mescalero children today are, on average, heavier and taller. CONCLUSIONS--Underweight and short stature decreased among Mescalero preschool children from 1968 through 1988, suggesting nutritional improvements. However, given the current high prevalence of obesity, it is recommended that surveillance of nutritional status be continued and appropriate interventions be developed to treat and prevent obesity in this population.     

High frequency oscillation in newborn infants with respiratory failure

Objective: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV).
Methodology Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation.
Results Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights <1500g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight >1500g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing <1500g who received HFOV in the first week of life developed periventricular haemorrhage.
Conclusion The initial results of HFOV for severe respiratory failure were encouraging although a learning curve was encountered with its introduction.     

Blunt renal trauma: biomechanics and origination of renal lesions

OBJECTIVES: Computer-assisted simulation of trauma is supposed to improve protective systems in traffic and risky leisure activities. In case of blunt renal injury biomechanical data being concerned with kidneys as a whole are extremely sparse. To enable three-dimensional simulations this study should supply important data of the renal biomechanics and elucidate the relationship between force distribution and origination of renal lesions. MATERIALS & METHODS: The present study investigated 66 isolated uninjured porcine kidneys using a drop impactor. Changes in deformation, brake force of power, deceleration and intrapelvic pressure are depicted while varying energy application between 1.4 and 14.2J. Lesions were detected by cross-dissecting the organs into slices. RESULTS: The measured values reflect a high correlation between load energy or brake force of power and deformation. Except the intrapelvic pressure all biomechanical parameters rise under increasing energy load. Comparing the different parameters over time a simultaneous concurrence of maximum brake force of power, deceleration and intrarenal pressure can be shown, the peak of deformation was reached belatedly. CONCLUSIONS: The paths of biomechanical curves prove a viscoelastic behaviour of the kidney. In contrast to the literature the region principally bearing the load seems to be the collision zone between renal pelvis and cortex where first lesions appear. This is mainly caused by the fluid filled pelvis, an incompressible support, that is supposed to change its shape after exceeding energy application of about 4J.     

Content Uniformity and Dose Uniformity: Current Approaches,Statistical Analyses,and Presentation of an Alternative Approach,with Special Reference to Oral Inhalation and Nasal Drug Products

This article reviews current and proposed approaches to content uniformity testing. In addition, the article proposes an approach that allows regulatory agencies and compendia to clearly state allowable consumer risk. Further, the article suggests that producers be allowed to control producer risk through selection of numbers of units and testing tiers. The approach facilitates risk communication to practitioners and patients/consumers, which is impeded with current approaches, and reduces regulatory and compendial burden.     

Recovery of upper-extremity strength in complete and incomplete tetraplegia: a multicenter study

OBJECTIVE: To examine upper-extremity motor recovery of subjects with tetraplegia with both complete and incomplete injuries, to predict which patients and at what time they would recover a motor level. DESIGN: Prospective, multicenter clinical study of upper-extremity motor recovery in subjects with acute traumatic spinal cord injury. SETTING: Three regional spinal cord injury centers. SUBJECTS: One hundred sixty-seven individuals with acute traumatic tetraplegia (144 males [86%], and 23 females [14%]) between the ages of 15 and 75 years (mean age, 35.5 yrs). METHODS: Subjects were examined and classified using sequential manual muscle tests performed on admission, 72 hours, 1, 2, and 3 weeks, and 1, 2, 3, 6, 12, 18, and 24 months postinjury. C5 biceps, C6 extensor carpi radialis, C7 triceps, and C8 flexor digitorum profundus were evaluated using a 0-5 scale. Analyses of the right motor levels used a series of logistic regression models, and for multiple measurements on each subject, models were estimated using generalized estimating equations. RESULTS: The analysis for recovery of the biceps for the C4 group showed 70% of complete compared with 90% of incomplete injuries recovered (p < .001); of the extensor carpi radialis in the C5 group, 75% complete and 90% incomplete recovered (p < .002); and of the triceps in the C6 group, 85% of complete and 90% of incomplete injuries recovered (p < .16). CONCLUSION: Predicting future potential for upper-extremity motor recovery and for independence in self-care in groups of patients at a specific motor level is possible within the first week of injury.