Prevalence of vitamin K and vitamin D deficiency in patients with hepatobiliary and pancreatic disorders

Little is known about the role of fat-soluble vitamins K and D in liver function and bone metabolism in biliary and pancreatic diseases associated with cholestasis and/or fat malabsorption. The aim of this study was to determine vitamin K of bone, vitamin D and parathyroid hormone status in patients with biliary and pancreatic disorders. In 90 consecutive patients (mean ± SD age, 65.5 ± 17.7 years; 45 females) undergoing endoscopic retrograde cholangiopancreatography (68 with choledocholithiasis, 14 with other benign condition, and 8 with cholangiopancreatic cancers) fasting concentrations of carboxylated (cOC) and undercarboxylated osteocalcin (ucOC), 25-hydroxyvitamin D, calcium, phosphorus, magnesium, prothrombin time, liver function tests, lipase, and creatinine were measured. Vitamin D deficiency (25-hydroxyvitamin D <50 nmol/L) was found in 45.6% of patients and elevated parathyroid hormone levels in 27.8%. The ratio ucOC/cOC (index of vitamin K deficiency) was above 20% in 50.6% of patients, above 30% in 31%, and above 50% in 18.4%. Hyperbilirubinemia was a significant independent predictor of low cOC (odds ratio [OR], 11.6; 95% confidence interval [CI], 1.9-59.4; P = .07). The ratio ucOC/cOC positively correlated with alanine aminotransferase levels (r = 0.410; P < .001). Elevated γ-glutamyltransferase (>180 U/L) and international normalized ratio (>1.1) levels were significant independent predictors of ucOC/cOC greater than 30% after adjustment for other covariants (OR, 5.5; 95% CI, 1.2-25.2; P = .027, and OR, 3.1; 95% CI, 1.1-8.8; P = .036, respectively). This study demonstrates that vitamin K and vitamin D deficiencies are common in patients undergoing endoscopic retrograde cholangiopancreatography. Liver dysfunction is associated with and predictive of vitamin K deficiency of bone and decreased production of osteocalcin, indicating the need for appropriate supplementation.     

The clinical outcome of small (<20 mm) arterially enhancing nodules on MRI in the cirrhotic liver

OBJECTIVES: To evaluate the outcome of arterially enhancing nodules (AENs) measuring <20 mm detected on MRI in patients with cirrhosis. METHODS: Prospective analysis of 54 patients with a total of 161 AENs <20 mm on MRI. Inclusion criteria included a minimum of 12 months of MRI follow-up or histological evaluation of the AEN. Key exclusions were patients with an AEN >20 mm or prior diagnosis of HCC. Two radiologists blinded to the clinical and pathological data reviewed serial MRIs and classified the AENs as no longer visible, stable, increasing, or decreasing in size. RESULTS: A total of 161 AENs were identified and were followed by serial MRI for a mean of 24 months. Eighty (50%) AENs were no longer visible on repeat imaging, 42 (26%) remained stable, 1 of which was diagnosed as HCC on short-term follow-up, 8 (5%) increased in size and were subsequently diagnosed as HCC, and 24 (15%) decreased in size. In addition, 7 AENs (4%) were diagnosed on biopsy immediately following the initial MRI. Overall MR characteristics diagnostic of HCC were growth > or =2 mm and peripheral rim enhancement on initial MRI. CONCLUSIONS: The majority (90%) of AENs <20 mm in cirrhosis are benign. The presence of rim enhancement or interval growth of an AEN are suggestive of HCC.     

Reduced eye gaze explains "fear blindness" in childhood psychopathic traits

ObjectiveDamage to the amygdala produces deficits in the ability to recognize fear due to attentional neglect of other people's eyes. Interestingly, children with high psychopathic traits also show problems recognizing fear; however, the reasons for this are not known. This study tested whether psychopathic traits are associated with reduced attention to the eye region of other people's faces.MethodAdolescent males (N = 100; age mean 12.4 years, SD 2.2) were stratified by psychopathic traits and assessed using a Tobii eye tracker to measure primacy, number, and duration of fixations to the eye and mouth regions of emotional faces presented via the UNSW Facial Emotion Task.ResultsHigh psychopathic traits predicted poor fear recognition (1.21 versus 1.35; p < .05) and lower number (1.85 versus 2.51; p < .001) and duration (375 versus 620 ms; p < .001) of eye fixations, and fewer first foci to the eye region (1.01 versus 2.01; p < .001). There were no differences in gaze indices to the mouth region. All indices of gaze to the eye region correlated positively with accurate recognition of fear for the high psychopathy group, especially the number of times that subjects looked at the eyes first (r = .50; p < .01).ConclusionsAttention to other people's eyes is reduced in young people with high psychopathic traits, thus accounting for their problems with fear recognition, and is consistent with amygdala dysfunction failing to promote attention to emotional salience in the environment.     

Abeta-globulomers are formed independently of the fibril pathway

Soluble A beta-oligomers are currently discussed as the major causative species for the development of Alzheimer's disease (AD). Consequently, the beta-amyloid cascade hypothesis was extended by A beta-oligomers and their central neuropathogenic role in AD. However, the molecular structure of A beta-oligomers and their relation to amyloid fibril formation remains elusive. Previously we demonstrated that incubation of A beta(1-42) with SDS or fatty acids induces the formation of a homogeneous globular A beta-oligomer termed A beta-globulomer. In this study we investigated the role of A beta-globulomers in the aggregation pathway of A beta-peptide. We used in vitro assays such as thioflavin-T binding and aggregation inhibitors like Congo red to reveal that A beta-peptide in its A beta-globulomer conformation is a structural entity which is independent from amyloid fibril formation. In addition, cellular Alzheimer's-like plaque forming assays show the resistance of A beta-globulomers to deposition as amyloid plaques. We hypothesize that a conformational switch of A beta is decisive for either fibril formation or alternatively and independently A beta-globulomer formation.     

A comparison of two theoretically driven treatments for verb inflection deficits in aphasia

Errors in the production of verb inflections, especially tense inflections, are pervasive in agrammatic Broca's aphasia (*The boy eat). The neurolinguistic underpinnings of these errors are debated. One group of theories attributes verb inflection errors to disruptions in encoding the verb's morphophonological form, resulting from either a general phonological deficit or a morphological affixation impairment. A second group of theories attribute verb inflection errors to disruptions that arise during sentence formulation, either for syntactic reasons or due to impairments in making fine semantic distinctions between inflectional variants of a verb (+PAST-->ate, hugged; +FUTURE-->will eat, will hug). These morphophonological and morphosemantic accounts were evaluated by comparing the efficacy of two treatment protocols that exclusively targeted either morphophonological operations or morphosemantic distinctions. Using a single participant design, it was found that aphasic individuals who received morphosemantic treatment showed significant improvement in accurate production of trained and untrained verb inflections in sentence contexts. In contrast, individuals who received morphophonological treatment failed to show improvements in accuracy of sentence production, although the number and diversity of inflected verbs increased. The differential outcomes suggest that morphosemantic impairments contribute to verb inflection deficits in agrammatic aphasia to a greater extent than morphophonological impairments, at least in this group of participants.     

Non-surgical management of acoustic neuromas.

Watchful waiting is one of the options available in the management of acoustic neuromas and this article deals with 13 patients who were so managed. Non-operative management was advised because of age, poor general health, small size of tumour, only hearing ear, or in patients unwilling to undergo surgery for various reasons. This group was followed up at 6-12-monthly intervals and the follow-up period ranged from 1 to 18 years (mean 5.3 years). Ten patients had small tumours and only in 2 of these was increase in tumour size demonstrated on follow-up CT scan. In one this increase was later followed by regression. Two patients required partial removal of tumour because of increasing symptoms after 3 and 7 years of follow-up; one of them died on the twelfth post-operative day. There appears to be a small group of patients for whom delay is worth while rather than to subject all patients with acoustic neuroma to surgery from which full recovery cannot be guaranteed.     

Independent mediation of unconditioned motor behavior by striatal D1 and D2 receptors in rats depleted of dopamine as neonates

The effects of systemic administration of DA receptor antagonists suggest that unconditioned motor behavior in rats depleted of DA as neonates continues to be dependent upon dopaminergic transmission, yet the specific contribution of D₁ and D₂ receptors to these behaviors has been altered. The purpose of the present study was to determine whether these depletion-induced receptor changes are occurring at the level of striatal DA terminals and their targets. The ability of bilateral intrastriatal injections (0.5 µl) of DA receptor antagonists to induce motoric deficits was determined in adult rats treated with vehicle or 6-OHDA (100 µg, intraventricular) on postnatal day 3. Administration of the D₁-like antagonist SCH 23390 (0.5–2.0 µg) or the D₂-like antagonist clebopride (1.0–4.0 µg) induced dose-dependent akinesia, catalepsy, and somatosensory neglect in vehicle-treated controls. In contrast, neither antagonist produced deficits in rats depleted of forebrain DA as neonates. However,combined administration of SCH 23390+clebopride induced similar akinesia, catalepsy, and somatosensory neglect in both controls and DA depleted animals. Animals depleted of DA were more sensitive than controls to the low doses of this combined D₁+D₂ antagonism. These results demonstrate that activation of striatal DA receptors remains necessary for unconditioned motor behavior in rats depleted of DA as neonates. However, the specific contributions of D₁- and D₂-like receptors to these behaviors differ between intact animals and those depleted of DA as neonates. The ability of endogenous DA acting at either D₁ or D₂ receptors to support spontaneous motor behavior in rats depleted of DA as neonates may contribute to their relative sparing from parkinsonian deficits.     

Gabapentin can improve postural stability and quality of life in primary orthostatic tremor.

Primary orthostatic tremor (OT) is characterized by leg tremor and instability on standing. High frequency (13-18 Hz) tremor bursting is present in leg muscles during stance, and posturography has shown greater than normal sway. We report on an open-label add-on study of gabapentin in 6 patients with OT. Six patients were studied with surface electromyography, force platform posturography, and a modified Parkinson's disease questionnaire (PDQ-39) quality of life (QOL) scale before and during treatment with gabapentin 300 mg t.d.s. If on other medications for OT, these were continued unchanged. Of the 6 patients, 4 reported a subjective benefit of 50 to 75% with gabapentin, 3 of whom showed reduced tremor amplitude and postural sway of up to 70%. Dynamic balance improved in all 3 patients who completed the protocol. QOL data from 5 patients showed improvement in all cases. No adverse effects were noted. Gabapentin may improve tremor, stability, and QOL in patients with OT, and symptomatic response correlated with a reduction in tremor amplitude and postural sway. The findings confirm previous reports of symptomatic benefit with gabapentin and provide justification for larger controlled clinical trials. Further work is required to establish the optimal dosage and to validate the methods used to quantify the response to treatment.