HIV-1 gp120-dependent induction of apoptosis in antigen-specific human T cell clones is characterized by ''tissue'' transglutaminase expression and prevented by cyclosporin A

Inhalation is the method of choice for delivering therapeutic agents to the lung. The advent of metered-dose inhalers (MDIs) has made inhalation easier, less expensive and more efficient. However, 20-50% of patients are unable to use MDIs correctly. The main problems are: 1) impact of aerosol particles in the mouth (responsible for side-effects); 2) poor co-ordination between firing the MDI and breathing; 3) and too fast an inspiration. Various spacer devices have been designed to overcome these problems. These are: large volume devices, which reduce the oral impact and select the respirable particles; devices equipped with a one-way valve that reduces co-ordination problems; indication of too rapid an inspiration by a high-flow mark. The introduction of these devices has resulted in an improved bronchial/oral deposition rate and a reduced incidence of side-effects. Training and education of patients is fundamental in ensuring the correct use of inhalers.     

Valproate reduces intake of alcoholic beverage among rats

SETTING: University of Malaya Medical Centre, Kuala Lumpur, Malaysia. OBJECTIVE: To assess the awareness of the ozone layer and the acceptance of the new non-chlorofluorocarbon (CFC) propellant hydrofluoroalkane 134a salbutamol pressurised metered dose inhaler (MDI) Airomir among asthmatic patients. DESIGN: A total of 113 consecutive asthmatic patients aged 12 years and above from the out- and in-patient services of the hospital were interviewed using a questionnaire. RESULTS: Sixty-five per cent of the patients were aware of the existence of the ozone layer, 23% that CFCs play a role in ozone depletion, and only 10% that current MDIs contained CFCs. All the patients felt that pressurised MDIs should be made CFC-free after they had considered the role of CFCs in the destruction of the ozone layer. Eighty-one per cent of 94 patients who preferred the Airomir inhaler over a multi-dose dry powder inhaler for administering bronchodilator medications were willing to switch to the new inhaler once it became available on the market. CONCLUSION: Awareness of the damaging effect of CFCs on the ozone layer among asthmatic patients would encourage them to change to an ozone-friendly, CFC-free pressurised MDI.     

Nonaccidental endosulfan intoxication: a case report with toxicokinetic calculations and tissue concentrations

Compatibility of propellants, excipients, and solvents with the components of the valve greatly influences performance of metered-dose inhalers (MDIs). Ozone-friendly hydrofluoroalkane propellant 134a has potential for use as a chlorofluorocarbon (CFC) replacement. No suitable replacement for propellant 11 and 114 has yet been found and the problems arising from this may be overcome by use of ethanol as a solvent. In this study, compatibility of MDI valve elastomers Dowty Nitrile 0117, White Buna, and Type 674 (B) with P134a placebo formulations having different concentrations of ethanol was investigated. The results indicate that formulations containing no ethanol adversely affected the functioning of the valves. Higher concentrations of ethanol improved valve performance, but showed increased leakage. Physical characteristics of the valve elastomers evaluated by determining swelling caused after exposure to the P134a placebo formulations exhibited increased swelling with increasing concentrations of ethanol in the formulation.     

Exudative pleural effusion and pleural leukocytoclastic vasculitis in limited scleroderma

Chlorofluorocarbons (CFCs) damage stratospheric ozone permitting enhanced levels of ultraviolet B radiation to reach the Earth's surface. As a result, production of CFCs is now banned under the Montreal Protocol with the exception of their temporary continued use in pressurized metered dose inhalers used to treat those with airway disorders. Replacement propellants have now been identified and shown to be safe and a major exercise is under way to reformulate the commonly used aerosolized medicines with the new propellants. The new products are now undergoing clinical trials and the first reformulated beta-agonist and corticosteroid inhalers have reached the marketplace. The majority of the current products will have been changed over to the new types over the next 3 yrs, and each country will adapt a transition strategy to oversee this process. The politicians, the environmentalists, the pharmaceutical industry and the regulatory authorities have fulfilled their part in this changeover, and respiratory interested health professionals now need to address what this means for them and their patients so that there may be a seamless transition for the millions of people who use inhaled medicines worldwide.     

A socioeconomic assessment of human exposure to ozone in the South Coast Air Basin of California

The purpose of this study is to assess by age, race, ethnicity, and income the effects of air pollution control measures and population growth on human exposure to ozone in the South Coast Air Basin of California (SoCAB). A methodology to study human exposure to air pollutants from a socioeconomic perspective has been developed. Specifically, the Regional Human Exposure model (REHEX-II) has been applied to estimate historical (1980-1982) and recent (1990-1992) human exposure to ozone. The model accounts for time spent in different microenvironments for different age groups and incorporates long-term air quality data with high spatial resolution. The simulation results, expressed as per capita hours of exposure to ozone above various concentration thresholds, are associated with population race, ethnicity, and per capita income. The results indicate that ozone exposure differences by race and ethnicity have diminished over time. However, the study suggests that on average, low income areas may be experiencing higher ozone exposure than high income areas, suggesting that environmental health risks (e.g., respiratory diseases) may be systematically higher for low income groups in the SoCAB.     

The role of powered instrumentation in the surgical treatment of allergic fungal sinusitis

Allergic fungal sinusitis is a chronic disorder that is being more frequently recognized by otolaryngologists. It is a recurrent illness characterized by frequent exacerbations, and requires aggressive medical and surgical treatment. When surgical therapy is employed, it is necessary to ensure adequate debridement and removal of edematous tissue. We have been using powered dissection as our primary method in sinus surgery over the past three year. We have treated 11 patients with allergic fungal sinusitis, and find powered instrumentation to be very effective in removing the polypoid tissue from the nose and sinuses, and in providing a clear surgical field. The procedure can be performed safely with minimal trauma to normal tissue. We believe that the use of powered dissection greatly enhances the comprehensive treatment of allergic fungal sinusitis.     

Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices

STUDY OBJECTIVES: To compare lung deposition of fenoterol or flunisolide administered from a novel, multidose inhalation device delivering liquid droplets (RESPIMAT; Boehringer Ingelheim Ltd; Bracknell, UK) or from conventional metered-dose inhalers (MDIs) with and without spacers. DESIGN: Two randomized, three-way crossover studies. SETTING: Clinical research laboratory. PARTICIPANTS: Healthy, nonsmoking volunteers. INTERVENTIONS: In one study, radiolabeled aerosols of fenoterol from the RESPIMAT device and from a conventional MDI with or without an Aerochamber spacer (Trudell Medical; London, Ontario Canada). In the second study, radiolabeled aerosols of flunisolide from a RESPIMAT device, from a RESPIMAT device modified by inclusion of a baffle/impactor in the mouthpiece, and from a conventional MDI with an Inhacort spacer (Boehringer Ingelheim; Ingelheim, Germany). MEASUREMENTS AND RESULTS: Assessment of the deposition of fenoterol or flunisolide in the lung and oropharynx using gamma scintigraphy. Safety was assessed based on reported adverse effects and spirometry (FEV1, FVC, and peak expiratory flow rate) to detect any paradoxical bronchoconstriction. The RESPIMAT device delivered significantly more fenoterol to the lungs than either an MDI alone or an MDI with Aerochamber (39.2% vs 11.0% and 9.9% of metered dose, respectively; p<0.01). Oropharyngeal deposition of fenoterol from the new device was lower than that from the MDI (37.1% vs 71.7%, respectively; p<0.01). The RESPIMAT device deposited significantly more flunisolide in the lungs compared with MDI plus spacer (44.6% vs 26.4%, respectively; p<0.01), while resulting in similar oropharyngeal deposition (26.2% vs 31.2%, respectively). Introduction of a baffle into the RESPIMAT system reduced lung deposition of flunisolide to 29.5%, and oropharyngeal deposition to 7.8% (p<0.01). CONCLUSION: The RESPIMAT device may prove to be an effective alternative to MDIs for the administration of inhaled bronchodilators and corticosteroids. The high lung deposition and low oropharyngeal deposition may lead to improved efficacy and tolerability of inhaled medications, especially corticosteroids.     

Efficacy and safety of salmeterol in childhood asthma

In children with asthma, twice daily administration of salmeterol 25 micrograms, salmeterol 50 micrograms and salbutamol 200 micrograms were compared in two, 3-month, double-blind, parallel group studies, one using metered dose inhalers (MDIs), the other using dry powder inhalers (Diskhaler, DPIs). Both studies were continued for a further 9 months during which time exacerbation rates, lung function at the clinic and adverse events were monitored. Similarities in design and methodology of the two studies justified a combined analysis. Eight hundred and forty-seven asthmatic children aged between 4 and 16 (mean 10.1) years, requiring inhaled beta 2-agonist treatment were randomised to treatment. After a 2 week run-in when all bronchodilator therapy was withdrawn, 279 patients received salmeterol 25 micrograms bd, 290 patients salmeterol 50 micrograms bd and 278 patients salbutamol 200 micrograms bd. After 3 months' treatment the change from baseline in daily morning and evening peak expiratory flow (PEF) was significantly greater with salmeterol 50 micrograms bd than with salbutamol 200 micrograms bd (P < 0.001). Salmeterol 50 micrograms bd was also significantly better than salmeterol 25 micrograms bd at improving mean morning PEF (P = 0.017) but both treatments had a similar effect on evening PEF. Analysis of variance showed an interaction between baseline PEF less than 100% predicted normal value and treatment outcome. Analysis of this sub-set of patients with lower lung function revealed similar results to the total population although the improvements in PEF from baseline were greater. Data from both studies, showed that the improvement in lung function was maintained throughout 12 months' treatment. Patients receiving salmeterol 50 micrograms bd had significantly more symptom-free nights (P < 0.01) and a higher percentage of rescue bronchodilator-free days (P = 0.01). The incidence of asthma exacerbations was evenly distributed between the three treatment groups and there was no evidence of any change in the rate of occurrence of exacerbations over the 12 month period. Adverse events were no different across treatment groups or across age groups and were primarily related to the patients' disease state. CONCLUSION: Salmeterol 50 micrograms bd is the appropriate dose for the treatment of children with mild to moderate asthma.     

Studies on the biological effects of ozone: 4. Cytokine production and glutathione levels in human erythrocytes

We have investigated the effect of various concentrations of ozone on human blood aiming to correlate the production of cytokines with depletion of reduced glutathione and hemolysis. As erythrocytes constitute the bulk of blood cells and represent the main target of ozone they have been taken as a useful marker of its oxidative activity. It appears that a transient exposure (30 sec) of blood of up to 78 micrograms ozone per ml of blood does not depress the production of cytokines even though there is a slight increase of hemolysis and a small decrease of intracellular reduced glutathione. In contrast either a constant (up to 30 sec) exposure to an ozone flux or a high ozone concentration (108 micrograms/ml) markedly decreases reduced glutathione levels and depresses cytokine production.     

Work-family conflict, gender, and health-related outcomes: a study of employed parents in two community samples

Female sifaka mate selectively with one or more resident and/or non-resident males during the breeding season. Various adaptive explanations have been advanced to explain why female primates mate with multiple males including that 1) females seek to confuse paternity and thereby forestall male infanticide and/or ensure male infant care or 2) females seek to ensure fertilization. Assessing the power of fertilization insurance to explain mating patterns in females requires information on the temporal relationship between mating and ovarian hormones. The hormonal correlates of reproduction and mating in free-ranging Propithecus verreauxi were investigated using excreted steroids as indices of reproductive state. Solid-phase extraction and radioimmunoassay techniques were used to measure unconjugated estradiol (E(2)) and progesterone (P(4)) in 485 desiccated fecal samples collected from five female sifaka before and during the breeding season at Beza Mahafaly, Madagascar. Results suggest that behavioral estrus was characterized by 10 to 15-day elevations in E(2); hormonal activity was observed to be similar to pseudo-estrus reported for other lemur species; apparent conception was associated with sustained P4 elevations beginning 1 to 3 days post-estrus with gestational phase elevations of E2 beginning 42 to 45 days post-conception; and mating with multiple partners appeared not to be a prerequisite to fertilization, as conception resulted from both monoandrous and polyandrous matings. These preliminary data suggest that fertilization insurance is not adequate to explain polyandrous mating in sifaka at Beza Mahafaly.     

The problems of radon therapy: its benefits and risks]

Local administration of drugs by means of aerosol device is widely used in the treatment of asthma. Nevertheless, the effectiveness of this method depends on an adequate inhalation technique (IT), which available evidence has shown to be rather problematic. The aim of this study was to assess IT in out-patients with bronchial asthma who frequently use aerosol therapy with Pressurized Metered dose inhalers (MDI), pressurized inhalers with spacer (MDI-S) and the Astra-Draco Turbuhaler system (TH). A sample of 150 adults with asthma were evaluated. These patients had been followed up for than two years and they often used one of the devices mentioned above. The IT has broken down into several steps for each procedure. Percentages of patients with one error in the IT were 50%, 44% and 42% for MDI, MDI-S and TH procedures, respectively. 18%, 20% and 14% of patients committed three errors in the IT, respectively. Differences detected were not significant. Seven patients committed errors in every step of the IT. In conclusion, the level of errors found in our study is high, similar to that cited in the existing literature. It is also roughly equivalent for the three devices tested. We believe that the proper teaching monitoring of IT skills is highly important in the treatment of bronchial asthma.     

Comparison of systemic and mucosal priming for mucosal immune responses to a bacterial protein antigen given with or coupled to cholera toxin (CT) B subunit, and effects of pre-existing anti-CT immunity

The advantages of the laparoscopic mode of access for hysterectomy include shorter recovery time and less pain and scarring. The laparoscopic component of the hysterectomy is usually combined with a vaginal component. The relative proportions of the procedure, performed laparoscopically and vaginally, vary considerably between surgeons. The main problem associated with the laparoscopic approach is to ensure adequate hemostasis while avoiding damage to the urinary tract. A variety of differing techniques have been developed in attempts to ensure the safe and efficient removal of the uterus laparoscopically.     

The nicotine inhaler in smoking cessation

BACKGROUND: Nicotine replacement therapy has been shown to improve success rates in smoking cessation treatment. However, the available products cause adverse effects, which prevent some smokers from using them. A new method of delivering nicotine via inhaler supplies nicotine orally through inhalation from a plastic tube. This mode of delivering nicotine resembles smoking, as it includes handling and active inhalation. OBJECTIVES: To assess the efficacy and safety of the nicotine inhaler as an aid in smoking cessation. METHODS: A 1-year, randomized, double-blind, placebo-controlled study was conducted in a smoking cessation clinic. Two hundred forty-seven smokers who smoked at least 10 cigarettes per day and who had previously made a serious attempt to stop smoking using nicotine chewing gum were recruited through advertisements. Randomization to treatment or control conditions were made at the first group session, with 123 participants receiving nicotine inhalers and 124 receiving placebo inhalers. The inhalers were distributed at the second session and participants were allowed to use the inhalers for 6 months. MAIN OUTCOME MEASURE: Biochemically verified continuous abstinence from smoking after 2 and 6 weeks and at 3, 6, and 12 months. RESULTS: Significantly more participants who had used the nicotine inhalers were continuously abstinent compared with those who had used the placebo inhalers. The respective success rates after 12 months were 28% and 18% (P = .046). At 6 months, 20 participants (16%) in the nicotine group were still using the inhaler, compared with 4 (3%) in the control group (P < .001). CONCLUSION: The nicotine inhaler was an effective smoking cessation aid that produced a few mild and transient adverse effects.     

Esophageal approach in rythmology. Diagnostic and therapeutic applications

Congestive heart failure is a major public health problem in developed countries. There have been significant advances in the management of this condition over the last few decades. However, many patients are still not receiving adequate therapy. Optimal management requires appropriate investigation, education, counselling, medical treatment and planned follow-up. This review outlines the recommended approach for optimal management of patients with heart failure.     

HACCP approach to ensure the safety and quality of food packaging

EC Directive 93/43/EEC of 14 June 1993 on the hygiene of foodstuffs has been implemented in the Netherlands through the Food and Commodity Act (Warenwet) of 14 December 1995. This Directive requires food companies to identify steps in their activities that are critical to ensuring food safety, and to ensure that adequate safety procedures are identified, implemented, maintained and reviewed based on the principles of the Hazard Analysis Critical Control Point (HACCP) system. HACCP is a tool used to assess hazards, estimate risks and establish specific control measures that emphasize prevention and control rather than reliance on end-product testing. Increasing public awareness of food safety, together with the introduction of this new legislation, has led producers and retailers of food to demand higher standards from their suppliers. Suppliers of raw materials, ingredients and also food packaging will be expected to bring their standards of hygiene in line with the expectations of the food industry. Food producers will need to obtain the guarantee from their suppliers that the packaging does not negatively influence their products. HACCP is a method that can also be applied to ensure the safety and other quality aspects of all kinds of food packaging materials such as films, foils, trays, cups, boxes and tubs made of paper, cardboard, polymers, metal and other materials (single use or disposable packagings as well as re-usable and recycled packagings). At the Netherlands Organization for Applied Scientific Research (TNO), the quality and safety aspects of re-use of food packaging, and refillable bottles in particular, have been the subject of extensive investigations in the project 'Quality monitoring of synthetic refillable bottles'. In this paper the set-up of the project and the Codes of Practice for refillable bottles are described. Moreover, the applicability of HACCP to food packagings and an example of a HACCP study for refillable PET bottles will be discussed.     

Patient satisfaction with the Diskhaler and the Diskus inhaler, a new multidose power delivery system for the treatment of asthma

To evaluate patient satisfaction with two breath-actuated powder inhalers (Diskhaler and Diskus), investigators asked patients to complete questionnaires as part of a randomized, double-masked, double-dummy, placebo-controlled study of fluticasone propionate powder (500 mg twice daily) in the treatment of chronic persistent asthma. At baseline, patients rated the importance of various inhaler attributes (i.e., ease of use, ease of loading with medication, ease of holding and operating, ease of cleaning, and ease of telling how many doses of medication are left). After 2 weeks of placebo and 6 and 12 weeks of active therapy, patients rated the inhalers on these same attributes. They also rated their general satisfaction with the inhalers and how comfortable they were using them. After 12 weeks, patients also rated the durability and convenience of carrying each device and were asked to indicate which they preferred. Data were available from 213 patients. All seven inhaler attributes measured were considered important by the majority of patients (71% to 91%), contributing to the validity of the patient-rated performance assessments. After 12 weeks of use, 57% to 88% of patients expressed a high level of satisfaction with the performance of the Diskhaler on all attributes; a high level of overall satisfaction (72%) and comfort (79%) was reported with this inhaler. Patients rated the performance of the Diskus inhaler very favorably, with 76% to 96% expressing a high level of satisfaction on all attributes; a high level of overall satisfaction (87%) and comfort (85%) was reported with this inhaler. At end point, 61.4% preferred the Diskus inhaler, 25.4% preferred the Diskhaler inhaler, and 13.2% expressed no preference. These breath-actuated powder inhalers may be acceptable alternatives to traditional metered-dose inhalers for the treatment of patients with asthma.     

Aerosol therapy

Aerosol therapy plays a major role in the diagnosis and treatment of various lung diseases. The aim of inhalation therapy is to deposit a reproducible and adequate dose of a specific drug to the airways, in order to achieve a high, local, clinical effect while avoiding serious systemic side effects. To achieve this goal, it is therefore important to have an efficient inhalation device to deliver different medications. However, the currently available therapeutic inhalation devices (nebuliser, pressurised metered-dose inhaler and dry powder inhaler) are not very efficient in aerosol delivery and have several disadvantages. Inhalation devices can be assessed by in vitro studies, filter studies and radiolabelled deposition studies. Several radiolabelled deposition studies have shown that nebulisers and pressurised metered-dose inhalers are not very efficient in aerosol delivery. In children, before 1997, only 0.5% to 15% of the total nebulised or actuated dose from a nebuliser or pressurised metered-dose inhaler actually reached the lungs. These numbers were somewhat improved in adults, 30% of the total nebulised or actuated dose reaching the airways. Aerosol therapy with dry powder inhalers was the most efficient before 1997, 30% of the total dose being deposited in the lungs of adults and children. In 1997, new developments in pressurised metered-dose inhalers much improved their efficiency in aerosol delivery. Lung deposition can be increased by up to 60% with use of a non-electrostatic holding chamber and/or a pressurised metered-dose inhaler with a hydrofluoroalkane propellant possessing superior aerosol characteristics. Several studies comparing the clinical efficiency of different inhalation devices have shown that the choice of an optimal inhalation device is crucial. In addition to the aerosol characteristics, ventilation parameters and airway morphology have an important bearing on deposition patterns. These parameters may be greatly influenced by the patient's acceptance of a specific inhalation device and therefore determine the choice of the device used. It is important for the clinical impact to develop more efficient inhalation devices, which need to be assessed for use in different age groups. These devices should be cheap, easy to use, portable, usable with all medications and environmentally safe.