A comparison of adolescent- and adult-onset first-episode, non-affective psychosis: 2-year follow-up

This study aimed to compare 2-year outcome among individuals with early-onset (EO; <18?years) versus adult-onset (AO) first-episode, non-affective psychosis. We compared clinical and treatment characteristics of 43 EO and 189 AO patients 2 years after their inclusion in a clinical epidemiologic population-based cohort study of first-episode psychosis. Outcome variables included symptom severity, remission status, drug abuse, treatment utilization, cognition and social functioning. At baseline, EO patients were more symptomatically compromised. However, these initial baseline differences were no longer significant at the 2-year follow-up. This study challenges the findings of a larger and older literature base consisting primarily of non-comparative studies concluding that teenage onset indicates a poor outcome. Our results indicate that adolescent-onset and adult-onset psychosis have similar prognostic trajectories, although both may predict a qualitatively different course from childhood-onset psychosis.     

Glycosylation of immunoglobulin light chains associated with amyloidosis.

AL amyloidosis is a fatal disease caused by deposition of immunoglobulin light chains in a fibrillarforin (AL) in various organs. By searching the Kabat database of immunoglobulin sequences using the KabatMan software, we have shown that there is a preponderance of the consensus glycosylation sequon (AsnXxxSer/Thr) in the framework regions of amyloid light chains. We have characterised by computer graphics simulations, NMR spectroscopy and carbohydrate biochemistry the structure and conformation of the oligosaccharide from amyloid protein AL MS (lamba1) and from the amyloid associated Bence Jones protein of patient MH (kappa1). These proteins have glycosylation in the hypervariable complementarity-determining region versus framework region, respectively. Both contained a 2-6 sialylated core fucosylated biantennary chain mostly with bisecting GIcNAc. Together our results suggest that light chain glycosylation may be one of several modifications which may render the protein more prone to amyloid formation.     

Severe craniofacial malformations and deglutition dysfunction in a brother and sister: New syndrome?

We report seemingly unique craniofacial malformations and deglutition dysfunction in a sib pair. The boy had right maxillomandibular alveolar synechae, ankylosis of right temporomandibular joint, hypoplasia of the zygomatico-maxillary region, nasal deviation to the left, choanal stenosis, and exophthalmos due to shallow orbita. His ears were apparently low-set with prominent lobules. He had severe gastroesophageal reflux and increasing respiratory problems and died at age 11 months. Psychomotor development was normal. His 10-year-old sister had similar craniofacial malformations and a cleft soft palate. She also had a severe deglutition dysfunction and developed a thoracolumbar kyphoscoliosis. Psychomotor development was normal. The parents were healthy and non-consanguineous. The malformations in the sibs do not fit any reported craniofacial malformation syndrome and may represent a previously unrecognized monogenic disorder. This may be an autosomal recessive or dominant trait with gonadal mosaicism in one of the parents. Am. J. Med. Genet. 78:260–262, 1998. © 1998 Wiley-Liss, Inc.     

NMR spectroscopy study of the effect of 3-nitropropionic acid on glutamate metabolism in cultured astrocytes

3-Nitropropionic acid (3-NPA) is a selective and irreversible inhibitor of succinate dehydrogenase. The effect of this compound on the metabolism of [U-¹³C]glutamate was studied in astrocytes using ¹³C nuclear magnetic resonance spectroscopy. The appearance of [1,2,3-¹³C]glutamate in cell extracts and [1,2,3-¹³C]glutamine and [U-¹³C]lactate in cell media demonstrated the metabolism of labeled glutamate via the tricarboxylic acid cycle. Such labeling was observed in the control situation and also in cells treated with 3 mM 3-NPA. In the cells treated with 3 mM 3-NPA, however, the labeling was significantly reduced, and with 10 mM 3-NPA no such labeling was observed. Labeled aspartate was observed in untreated cells only. Labeled succinate was not detectable under control conditions, but increased dose dependently in the presence of 3-NPA. Glutamate uptake and conversion of [U-¹³C]glutamate to U-¹³C]glutamine was largely unaffected by 3-NPA, and ATP content was unchanged. In a previous study using cerebellar neurons, tricarboxylic acid cycle metabolism was blocked with 3 mM 3-NPA. The present results show that astrocyte metabolism is more adaptable to blockade of the tricarboxylic acid cycle by 3-NPA than neuronal metabolism. J. Neurosci. Res. 47:650–654, 1997. © 1997 Wiley-Liss, Inc.     

Valproate: past,present, and future

Preclinical studies have been carried out during the past four decades to investigate the different mechanisms of action of valproate (VPA). The mechanisms of VPA which seem to be of clinical importance include increased GABAergic activity, reduction in excitatory neurotransmission, and modification of monoamines. These mechanisms are discussed in relation to the various clinical uses of the drug. VPA is widely used as an antiepileptic drug with a broad spectrum of activity. In patients, VPA possesses efficacy in the treatment of various epileptic seizures such as absence, myoclonic, and generalized tonic-clonic seizures. It is also effective in the treatment of partial seizures with or without secondary generalization and acutely in status epilepticus. The pharmacokinetic aspects of VPA and the frequent drug interactions between VPA and other drugs are discussed. The available methods for the determination of VPA in body fluids are briefly evaluated. At present, investigations and clinical trials are carried out and evaluated to explore the new indications for VPA in other conditions such as in psychiatric disorders, migraine and neuropathic pain. Furthermore, the toxicity of VPA, both regarding commonly occurring side effects and potential idiosyncratic reactions are described. Derivatives of VPA with improved efficacy and tolerability are in development.     

Fatigue is not associated with vitamin D deficiency in inflammatory bowel disease patients

AIM To investigate if vitamin D deficiency is associated with fatigue in patients with inflammatory bowel disease(IBD).METHODS IBD patients were recruited from nine hospitals in the southeastern and western regions of Norway to participate in a multicenter cross-sectional study lasting from March 2013 to April 2014. Data were collected by interviews, from medical records and laboratory tests. The Fatigue Questionnaire(FQ) was used to measure fatigue. Linear and logistic regression models were applied to explore the possible association between vitamin D deficiency and total fatigue scores and chronic fatigue, respectively. The analyses were adjusted for age, gender, disease activity, depressive symptoms and sleep disturbance.RESULTS In total, 405 patients were included in the analyses, of which 227(56%) had Crohn's disease(CD) and 178(44%) had ulcerative colitis(UC). Vitamin D deficiency( 50 nmol/L) was present in half(203/405) of the patients. Chronic fatigue was reported by 116(29%) of all included patients with substantial fatigue reported by 194(48%). Vitamin D levels were neither associated with total fatigue nor with chronic fatigue. Higher total fatigue scores and chronic fatigue were both associated with increased disease activity scores in patients with UC and CD, but not with increased CRP or fecal calprotectin. In UC patients, female gender was associated with fatigue in the univariate analysis, but no such difference was found when adjusted for elevated disease activity scores. Sleep disturbance and more depressive symptoms were associated with total fatigue scores in both UC and CD patients, but with chronic fatigue only in CD patients.CONCLUSION In this study, no significant association between fatigue and vitamin D deficiency in IBD patients was revealed.