Behavioral treatment of angina-like chest pain in patients with hyperventilation syndrome

The hyperventilation syndrome is present in as many as 50% of patients with non-cardiac chest pain. This study evaluated a behavioral treatment of this disorder in three adult females. They had long histories of chest pain and were documented to be free of coronary artery disease. Each subject met the DSM-III-R diagnostic criteria for an anxiety disorder. Following treatment, all subjects showed a marked decrease in the frequency and intensity of chest pain episodes and in the frequency of shortness of breath episodes. Two subjects maintained their progress at one-year follow-up. The results lend support to the efficacy of controlled breathing and relaxation training for the treatment of hyperventilation-related chest pain and to the inclusion of a hyperventilation provocation test in the diagnosis of the syndrome as well as its role in changing cognitions regarding cardiac status. Also discussed is the rationale for treating hyperventilation related chest pain in a medical care setting.     

Interactive effects of ozone and formaldehyde on the nasal respiratory lining epithelium in rats

The combined effects on the nasal epithelium of mixtures of ozone and formaldehyde at cytotoxic and noncytotoxic concentrations were examined. Male Wistar rats were exposed by inhalation during 22 h/d for 3 consecutive days to 0.3, 1.0, or 3.0 ppm formaldehyde, or to 0.2, 0.4, or 0.8 ppm ozone, or to mixtures of 0.4 ppm ozone and 0.3, 1.0, or 3.0 ppm formaldehyde, or to 1.0 ppm formaldehyde and 0.2, 0.4, or 0.8 ppm ozone, or they were sham-exposed to clean air. The noses were examined for pathological changes at six standard cross levels by light microscopy and for epithelial cell proliferation by counting [3H-methyl]thymidine-labeled cells at cross levels II and III. Ozone at 0.4 ppm or 0.8 ppm or formaldehyde at 3 ppm enhanced cell proliferation at cross level II at all locations, except for the epithelium of the septum, which was not affected by ozone. At cross level III ozone alone did not induce cell proliferation, but formaldehyde at 0.3 and 1 ppm tended to reduce cell proliferation while at 3 ppm proliferation was slightly stimulated. The combined exposure to 0.4 ppm ozone and 0.3 ppm formaldehyde induced less cell proliferation at cross levels II and III when compared with that of 0.4 ppm ozone alone. Less cell proliferation was also seen at cross level II when animals were exposed to 0.4 or 0.8 ppm ozone in combination with 1 ppm formaldehyde than when exposed to these ozone concentrations alone. A more than additive increase in cell proliferation was found at cross level II after exposure to 0.4 ppm ozone in combination with 3 ppm formaldehyde, and at cross level III in animals exposed to 0.4 ppm ozone and 1 or 3 ppm formaldehyde. Treatment-related histopathological nasal changes, such as disarrangement, loss of cilia, and hyper/metaplasia of the epithelium were seen at 0.2, 0.4, and 0.8 ppm ozone and at 3 ppm formaldehyde. Simultaneous exposure to both materials did not noticeably affect type, degree, and size of the microscopic nasal lesions.     

Subacute (4-week) inhalation toxicity study of formaldehyde in male rats: 8-hour intermittent versus 8-hour continuous exposures

Male Wistar rats were exposed for 4 weeks, 5 days a week, to 0 (controls), 5 or 10 ppm formaldehyde continuously (8 hours a day), or to 10 or 20 ppm formaldehyde interruptedly (eight 30 min exposure periods separated by 30 min non-exposure periods). Histopathology and cell proliferation studies indicated that under the conditions of exposure used, concentration rather than the total dose of formaldehyde determined the severity of the cytotoxic effects on the nasal epithelium.     

Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents

The conditioned taste aversion (CTA) is routinely used to assess the aversive consequences of anorexic agents, including potential pharmacological therapies for obesity. In a typical CTA paradigm, rats briefly sampling a novel tastant (e.g., saccharin) are acutely administered with toxin (e.g., lithium chloride, LiCl). After as few as one taste-toxin pairing, rats will reliably avoid the novel tastant. This paradigm is frequently used for the assessment of possible aversive consequences of drugs that are candidates for pharmacological therapies. The degree to which the drug supports development of a CTA is interpreted as an index of its aversive properties. Difficulties with previous work include the inability to assess affects on food intake and CTA simultaneously, particularly during chronic drug administration. We report here two novel CTA paradigms for the assessment of appetitive and aversive consequences of anorexic agents, simultaneously. In the first experiment, animals receive an intraoral infusion of a novel and highly palatable tastant immediately prior to administration of increasing doses of LiCl. In the second experiment, rats were implanted intraperitoneally with osmotic minipumps that chronically delivered a low dose of LiCl for 7 days. LiCl did not affect short or long term food intake in either experiment. However, LiCl did support the development of a CTA in both paradigms. These results suggest that both the appetitive and aversive consequences of anorexic agents can be assessed simultaneously during either acute or chronic drug administration.     

Frequency of delta F508 mutation in Venezuelan patients with cystic fibrosis

Cystic Fibrosis (CF) is the most common and severe autosomal recessive disease in Caucasian populations, with an incidence of 1 in 2500 live births. It is characterized by a generalized disturbance in exocrine glands and it is caused by over one thousand mutations at the cystic fibrosis conductance regulator gene (CFTR) mapped at 7q31. AF508 is the most frequent mutation worldwide and it consists in a deletion of the codon that encodes fenilalanine at the 508 protein's position. The aim of this study was to determine the frequency of the delta F508 mutation in Venezuelan patients with CF using the Polymerase Chain Reaction (PCR). We studied thirty patients of twenty eight families who were diagnosed with CF based on their clinical features and sweat chloride level > 60 mEq/l in two determinations. Detection of the mutation was performed from the amplification of a 98 pair of bases (pb) CF gene segment which contains the codon that encodes fenilalanine in the 508 position by PCR. This PCR product is absent in those who have the mutation. The delta F508 allelic frequency was 26.79%, distributed in six homozygous and seven compound heterozygote delta F508/X. The reminder mutations (no delta F508) represent 73.21%. The delta F508 frequency in our sample is less than the reported in European countries. On the other hand, a delta F508 frequency highly heterogeneous has been observed in Latin-American countries. This variation results from mixed populations with a different genetic background influenced by external migration and CF molecular alterations, which exists in the analyzed populations. In this study, the delta F508 mutation comes mainly from grandparents (79.41%) who were born in Mediterranean countries and Colombia, while the no delta F508 mutations come from grandparents who were born in Venezuela (79.27%) and Colombia (17.07%).     

Effect of cigarette smoke on autoimmunity in murine and human systemic lupus erythematosus.

Several studies have found that smoking cigarettes is a risk factor for systemic lupus erythematosus (SLE). To examine this issue in a mouse model, we subjected pre-autoimmune MRL-lpr/lpr mice for 4 weeks to cigarette smoke to provide standardized smoke effluents equivalent to moderate or to heavy smoking habits for people. The spontaneous production of IgG anti-chromatin but not IgM anti-chromatin, anti-denatured DNA, or rheumatoid factor antibodies was lower in mice exposed to 250 mg/m3 particulates from mainstream smoke, and this suppression of autoimmunity was sustained for 8 weeks (p < 0.02). In contrast to control mice anti-chromatin activity in smoke-exposed mice began to increase in 16-week-old mice, reaching levels at 6 months that were two- to three-fold higher than controls for IgG (p < 0.03) and 10-fold higher for IgM (p < 0.001). There was no significant effect on total IgG or IgM. In newly diagnosed SLE patients, smoking was negatively correlated with IgG anti-DNA antibodies (p < 0.03). However, of nine patients who discontinued smoking prior to diagnosis, eight had elevated IgG anti-DNA compared to 29/79 never smokers and 9/31 smokers (p < 0.01 compared to former smokers). Inhaled cigarette smoke appears to have a long-lasting immunosuppressive effect on T-cell-dependent autoimmune responses, although autoantibodies increase to supra-elevated levels after the suppressive effect has abated.     

Early versus late parenteral nutrition in ICU patients: cost analysis of the EPaNIC trial

ABSTRACT: INTRODUCTION: The EPaNIC randomized controlled multicentre trial showed that postponing initiation of parenteral nutrition (PN) in ICU-patients to beyond the first week (Late-PN) enhanced recovery, as compared with Early-PN. This was mediated by fewer infections, accelerated recovery from organ failure and reduced duration of hospitalization. Now, the trial's preplanned cost analysis (N = 4640) from the Belgian healthcare payers' perspective is reported. METHODS: Cost data were retrieved from individual patient invoices. Undiscounted total healthcare costs were calculated for the index hospital stay. A cost tree based on acquisition of new infections and on prolonged length-of-stay was constructed. Contribution of 8 cost categories to total hospitalization costs was analyzed. The origin of drug costs was clarified in detail through the Anatomical Therapeutic Chemical (ATC) classification system. The potential impact of Early-PN on total hospitalization costs in other healthcare systems was explored in a sensitivity analysis. RESULTS: ICU-patients developing new infection (24.4%) were responsible for 42.7% of total costs, while ICU-patients staying beyond one week (24.3%) accounted for 43.3% of total costs. Pharmacy-related costs represented 30% of total hospitalization costs and were increased by Early-PN (+608.00 EUR/patient, p = 0.01). Notably, costs for ATC-J (anti-infective agents) (+227.00 EUR/patient, p = 0.02) and ATC-B (comprising PN) (+220.00 EUR/patient, p = 0.006) drugs were increased by Early-PN. Sensitivity analysis revealed a mean total cost increase of 1,210.00 EUR/patient (p = 0.02) by Early-PN, when incorporating the full PN costs. CONCLUSIONS: The increased costs by Early-PN were mainly pharmacy-related and explained by higher expenditures for PN and anti-infective agents. The use of Early-PN in critically ill patients can thus not be recommended for both clinical (no benefit) and cost-related reasons. TRIAL REGISTRATION: ClinicalTrials.gov NCT00512122.