Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study.

BACKGROUND: The upper normal limit (ULN) of serum alanine-aminotrasferase (ALT) normal range was recently challenged, because patients diagnosed with liver diseases may have 'normal' or near-'normal' ALT levels, and because possible modulators are often ignored in determining normal range. AIM: To estimate the ULN for serum ALT and to identify factors modulating it. SUBJECTS AND METHODS: We reviewed medical records of subjects aged 15-90, who underwent standard panels of laboratory tests, including serum ALT, over 6 months at a central laboratory. Three groups were defined: Group 1, comprised total study population (N=272 273). Group 2 (N=87 020) comprised total study population, excluding those receiving potentially hepatotoxic drugs, or diagnosed with liver disease, or had any abnormal laboratory test results other than for triglycerides, cholesterol, glucose, or HbA1c. Group 3 (N=17 496) the 'healthy' population, from whose ALT values we established the new ULN, comprised Group 2 subjects with normal triglycerides, cholesterol, glucose, and HbA1c levels. RESULTS: The 95th percentile ALT values, corresponding to the ULN, in groups 1, 2, and 3 were 50.1, 40, and 37.5 U/l, respectively. 6.2% (16 943/273 273) of subjects whose ALT was below ULN listed by the test manufacturer (52 U/l), had ALT level above our new ULN. Linear and logistic-regression analyses showed that ALT levels were significantly modified by gender, age, glucose, cholesterol, triglycerides, and overweight/obesity diagnosis. Significant interaction was found between gender, glucose and cholesterol levels. CONCLUSIONS: In this first large-scale study of 'healthy' population, serum ALT ULN was far lower than currently accepted value. Age and gender may be considered when determining the ULN for ALT.     

Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain

AIM: To characterize the antinociceptive action of the novel melatonin receptor(MT) agonists, Neu-P11 and Neu-P12 in animal models of visceral pain. METHODS: Visceral pain was induced by intracolonic(ic) application of mustard oil or capsaicin solution or by intraperitoneal(ip) administration of acetic acid. Neu-P11, Neu-P12, or melatonin were given ip or orally and their effects on pain-induced behavioral responses were evaluated. To identify the receptors involved, thenon-selective MT1/MT2 receptor antagonist luzindole, the MT2 receptor antagonist 4-P-PDOT, or the μ-opioid receptor antagonist naloxone were injected ip or intracerebroventricularly(icv) prior to the induction of pain. RESULTS: Orally and ip administered melatonin, Neu-P11, and Neu-P12 reduced pain responses in a dose-dependent manner. Neu-P12 was more effective and displayed longer duration of action compared to melatonin. The antinociceptive effects of Neu-P11 or Neu-P12 were antagonized by ip or icv. administered naloxone. Intracerebroventricularly, but not ip administration of luzindole or 4-P-PDOT blocked the antinociceptive actions of Neu-P11 or Neu-P12. CONCLUSION: Neu-P12 produced the most potent and long-lasting antinociceptive effect. Further development of Neu-P12 for future treatment of abdominal pain seems promising.     

Admission Norton scale scores (ANSS) and postoperative complications following hip fracture surgery in the elderly

We sought to determine if low ANSS, usually associated with high pressure ulcer risk, are also associated with postoperative complications and in-hospital mortality following hip fracture surgery in the elderly. This was a retrospective cross-sectional study conducted in a tertiary medical center. The medical charts of consecutive elderly (≥ 65 years) patients admitted for hip fracture surgery were studied for the following measurements: ANSS, demographic data, co-morbidities, postoperative complications, the need for revision procedures, and in-hospital mortality. Except for pressure ulcers, postoperative complications included: acute coronary syndrome, acute renal failure, confusion, pneumonia, urinary tract infection, venous thromboembolism, and wound infection. The final cohort included 269 patients: 198 (73.6%) females and 71 (26.4%) males. Mean age for the entire cohort was 82.8 ± 0.4 years. Most patients underwent an internal fixation (n=146; 54.3%) or hemiarthroplasty (n=92; 34.2%). Overall, 110 (40.9%) patients had low (<15) ANSS. Patients with low ANSS had significantly more postoperative complications relative to patients with high ANSS (0.77 ± 0.09 vs. 0.23 ± 0.04; p<0.0001). Among all postoperative complications, urinary tract infection was independently associated with low ANSS (p<0.0001). ANSS were independently associated with postoperative complications (p<0.0001), the need for revision procedures (p=0.019), and in-hospital mortality (p=0.016). We conclude that the Norton scoring system may be used for predicting postoperative complications and in-hospital mortality following hip fracture surgery in the elderly.     

Safety and efficacy of long-term low-dose clozapine aftercare treatment in a patient with learning difficulties who suffered from neuroleptic malignant syndrome

INTRODUCTION : Antipsychotic medication continues to be an essential component in the treatment of schizophrenia. Neuroleptic malignant syndrome (NMS) is one of the most serious complications of neuroleptic treatment and the optimal therapeutic aftercare regimen for patients is unclear. Also, it is not clear if low-dose neuroleptic maintenance in such patients is safe and efficient enough over time. METHOD : We present a case of a 56-year-old woman suffering from schizoaffective disorder, who was successfully treated with a low dosage of clozapine for 6.5 years following a NMS episode. RESULT : To the best of our knowledge this is the first report of such a long-term beneficial use of low-dose clozapine in a patient who previously underwent such a serious complication. CONCLUSION : Large-scale studies are needed to substantiate this observation. (Int J Psych Clin Pract 2002; 6: 121-123)     

Food Allergy: Temporal Trends and Determinants

This review summarizes studies discussing temporal trends in the prevalence of food allergy as well as potential factors associated with the development of food allergy. In addition, we will address the potential hypotheses accounting for the apparent increase in food allergy prevalence. Studies suggest increased prevalence of food allergy. However, relatively little is known about its pathogenesis. This review aims to assess temporal trends in the prevalence of food allergy and discuss potential genetic, environmental, and demographic determinants. The search strategy examined the medical literature database MEDLINE (using PubMed) for the time period of January 1, 2002 to January 31, 2012. In recent decades, the prevalence of food allergy in general has increased by 0.60 % [95 % confidence interval (CI), 0.59 %-0.61 %] and the prevalence of peanut allergy by 0.027 % (95 % CI, 0.026 %-0.028 %), but it has now likely stabilized in developed countries. Genes, the environment, and demographic characteristics play a role in the pathogenesis of food allergy. Numerous environmental and demographic factors as well as gene-environment interactions may account for this increase in prevalence, but further studies are required to tease out their relative contribution.