Learned irrelevance is disrupted in first-episode but not chronic schizophrenia patients

Learned irrelevance (LIrr) is a pre-exposure effect in which uncorrelated presentations of a conditioned stimulus (CS) and an unconditioned stimulus (US) retard subsequent CS-US association. LIrr is closely related to the phenomenon of latent inhibition (LI). LI refers to the retarding effects of inconsequential stimulus pre-exposure on subsequent conditioning to that stimulus, and is considered to reflect the organism's capacity to ignore irrelevant stimuli. LI is disrupted in schizophrenia patients, due to faster learning of the association between the preexposed CS and the US. A new within-subject target-recognition LIrr procedure was applied. The target was either cued by a priming signal or appeared at random, and priming signals were novel or preexposed cues. Schizophrenia patients were compared to age- and sex-matched control subjects. Normal subjects (n = 24) have shown robust LIrr, namely, faster cue-target associations of novel compared to preexposed cues. Schizophrenia patients at the early stages of their first episode (n = 7) showed LIrr disruption, namely, cue-target associations to preexposed cues were as fast as for novel cues. Chronic patients during an acute phase (n = 18) did not show LIrr as they failed to learn the cue-target association. In addition to the LIrr paradigm the same subjects were tested in a covert-orientation task. No differences were observed between the groups on this task. The possible advantages of the new LIrr paradigm are discussed.     

The prevalence of calcified carotid atheromas on the panoramic radiographs of patients with dilated cardiomyopathy

OBJECTIVE: Individuals with dilated cardiomyopathy (DCM) often die from heart failure without a transplant. Of those who do receive a transplant, a significant number suffer a perioperative stroke, although the cause is often in doubt. Our study attempts to determine whether the prevalence of calcified carotid artery atheromas, a known cause of stroke, is greater on the panoramic radiographs of individuals with DCM than it is among controls. STUDY DESIGN: Twenty-seven persons [mean age 62.3 years] enrolled in the UCLA Cardiac Transplantation Program were provided a panoramic radiograph. An age-matched, atherogenic risk-matched cohort of 54 patients free of DCM served as controls. The radiographs of patients in each group were examined for the presence of calcified carotid atheromas. RESULTS: Nine of the 27 patients with DCM had calcified atheromas, whereas only 2 of the 54 patients in the control group had such lesions. This difference was statistically significant (P<.001). CONCLUSIONS: Panoramic radiographs may be helpful in identifying some DCM patients with occult carotid artery atherosclerosis who may be at risk for a subsequent stroke.     

Antioxidant supplementation does not attenuate oxidative stress at high altitude

INTRODUCTION: Hypobaric hypoxia and heightened metabolic rate increase free radical production. PURPOSE: We tested the hypothesis that antioxidant supplementation would reduce oxidative stress associated with increased energy expenditure (negative energy balance) at high altitude (HA 4300 m). METHODS: For 12 d at sea level (SL), 18 active men were fed a weight-stabilizing diet. Testing included fasting blood and 24-h urine samples to assess antioxidant status [plasma alpha-tocopherol, beta-carotene, lipid hydroperoxides (LPO), and urinary 8-hydroxydeoxyguanosine (8-OHdG)] and a prolonged submaximal (55% Vo2peak) oxidative stress index test (OSI) to evaluate exercise-induced oxidative stress (plasma LPO, whole blood reduced and oxidized glutathione, glutathione peroxidase, and urinary 8-OHdG). Subjects were then matched and randomly assigned to either a placebo or antioxidant supplement group for a double-blinded trial. Supplementation (20,000 IU of beta-carotene, 400 IU alpha-tocopherol acetate, 500 mg ascorbic acid, 100 microg selenium, and 30 mg zinc, or placebo) was begun 3 wk prior to and throughout a 14-d HA intervention. At HA, subjects' daily energy intake and expenditure were adjusted to achieve a caloric deficit of approximately 1400 kcal. Fasting blood and 24-h urine samples were collected throughout HA and the OSI test was repeated on HA day 1 and day 13. RESULTS: Resting LPO concentrations increased and urinary 8-OHdG concentrations decreased over HA with no effect of supplementation. Prolonged submaximal exercise was not associated with increased concentrations of oxidative stress markers at SL or HA. CONCLUSIONS: Antioxidant supplementation did not significantly affect markers of oxidative stress associated with increased energy expenditure at HA.     

Sodium-phosphate cotransporters, nephrolithiasis and bone demineralization

PURPOSE OF REVIEW: We discuss how recent findings obtained in disorders of phosphate metabolism in humans and in animal models have provided insights into the pathogenesis of renal stone formation and bone demineralization. RECENT FINDINGS: Mice that are null for the sodium-phosphate cotransporter (NPT)2a gene (NPT2a(-/-) mice) exhibit hypophosphataemia, increased urinary phosphate excretion, hypercalciuria and nephrolithiasis, but no bone demineralization. Mice null for the sodium-hydrogen exchanger regulatory factor (NHERF)1 (NHERF1(-/-) mice) also exhibit hypophosphataemia and increased renal phosphate excretion with decreased renal NPT2a expression, but they present with a severe sex-dependent bone demineralization. Heterozygous loss-of-function mutations in the NPT2a gene in humans induce hypophosphataemia, increased urinary phosphate excretion, hypercalciuria, nephrolithiasis in males (to date) and bone demineralization of variable severity in both sexes. Patients and experimental animals with increased circulating levels of fibroblast growth factor 23 present with hypophosphataemia, increased urinary phosphate excretion, inappropriate calcitriol synthesis and rickets/osteomalacia, but no nephrolithiasis except when treated. Low-phosphate diet in spontaneously hypercalciuric rats and disruption of the 1-alpha-hydroxylase gene in NPT2a mice prevent renal stone formation. SUMMARY: Increased urinary phosphate excretion is a risk factor for renal calcium stone formation when it is associated with hypercalciuria. As yet undefined interplay between NPT2a, NHERF1 and possibly other cotransporters or associated proteins in bone cells may account for the diversity of bone phenotypes observed in disorders of phosphate metabolism with impaired renal phosphate reabsorption. The pathogenesis of both renal stone and bone demineralization appear to be affected by species, sex and mutation type, among other factors.     

Therapeutic options in the treatment of tinea capitis

Tinea capitis is primarily a disease of pre-adolescent children. In North America and the UK, Trichophyton tonsurans is responsible for > 90% of cases. Microsporum canis is the predominant pathogen in certain parts of Europe. The standard of care for the treatment of tinea capitis is oral griseofulvin and so far, it remains the only medication approved by the US FDA for this condition. The newer oral antifungal agents, such as terbinafine, itraconazole and fluconazole, appear to be effective, safe and have the advantage of a shorter treatment duration. Although a significant number of clinical trials and reports have documented experience with terbinafine and itraconazole for the treatment of tinea capitis, it should be noted that only a few trials have been conducted utilising fluconazole. Both 2% ketoconazole and 1% selenium sulfide shampoos have been shown to reduce surface colony counts of dermatophytes in infected individuals, and these agents are often recommended for adjuvant therapy. This article reviews data currently available on various therapeutic alternatives for the treatment of tinea capitis and summarises all relevant clinical trials that have thus far investigated the use of these drugs for tinea capitis in the paediatric population.     

Gemcitabine-related radiation recall preferentially involves internal tissue and organs

Radiation recall refers to inflammatory reactions triggered by cytotoxic agents and develops in previously irradiated areas. Most reactions develop cutaneously. The most common chemotherapeutic agents implicated are anthracyclines and taxanes. Gemcitabine, a nucleotide analog, recently was implicated in several cases. The authors performed a literature search using PubMed and the search terms "gemcitabine" and "radiation recall" to find prior cases of radiation recall attributed to gemcitabine. These cases were compared with those attributed to anthracyclines and taxanes. The literature search found 12 cases of radiation recall caused by gemcitabine. The authors also determined that their case of myositis developing in the rectus abdominus muscle of a patient with pancreatic adenocarcinoma was the manifestation of radiation recall, thereby bringing the number of patients who developed radiation recall to gemcitabine and were discussed in the current study to 13. Approximately 70% of the cases manifested as inflammation of internal organs or tissues and 30% manifested as a dermatitis or mucositis. This finding differs from other common agents, in which 63% of the radiation recall events are reported to manifest as a dermatitis. Compared with anthracyclines and taxanes, the interval from the completion of radiation therapy to the initiation of chemotherapy is less for gemcitabine (median time of 56 days for gemcitabine, compared with 218 days for the taxanes and 646 days for doxorubicin). The majority of radiation recall reactions attributed to gemcitabine are reported to affect internal tissue or organs. In contrast, other common agents for the most part trigger cutaneous inflammation. The development of internal tissue inflammation is reportedly correlated with a shorter interval from the time of completion of radiation therapy to the initiation of chemotherapy.     

Delirium in palliative care

Delirium is highly prevalent in cancer patients with advanced disease. Frequently a preterminal event, the condition is a sign of significant physiologic disturbance, typically involving multiple medical etiologies including infection, organ failure, adverse medication effects, and in rare situations, paraneoplastic syndromes. Unfortunately, delirium is frequently unrecognized or misdiagnosed and, therefore, inappropriately treated or untreated in terminally ill patients. The clinical features of delirium are numerous and encompass a variety of neuropsychiatric symptoms common to other psychiatric disorders. Three clinical subtypes of delirium, based on arousal disturbance and psychomotor behavior, have been described: hyperactive, hypoactive, and mixed. The differential diagnosis for delirium includes depression, mania, psychosis, and dementia. Numerous instruments have been developed to aid the clinician in rapidly screening for the disorder. Standard management requires an investigation of the etiologies, correction of the contributing factors, and management of symptoms. Symptomatic and supportive therapies, including numerous pharmacologic approaches, are important, but several aspects of the use of neuroleptics and other agents in the management of delirium in the dying patient remain controversial.