Pulmonary Langerhans Cell Histiocytosis and Diabetes Insipidus in a Young Smoker.

Langerhans cell histiocytosis is characterized by the abnormal nodular proliferation of histiocytes in various organ systems. Pulmonary involvement seen in young adults is nearly always seen in the context of past or current cigarette smoking. Although it tends to be a single-system disease, extrapulmonary manifestations involving the skin, bone, and hypothalamic-pituitary-axis are possible. High resolution CT (HRCT) of the thorax findings includes centrilobular nodules and cysts that are bizarre in shape, variable in size, and thin-walled. Often the diagnosis can be made based on the appropriate clinical presentation and typical imaging findings. Treatment includes smoking cessation and the potential use of glucocorticoids or cytotoxic agents depending on the severity of disease and multisystem involvement.

Lost in translation? How adults living with Cystic Fibrosis understand treatment recommendations from their healthcare providers, and the impact on adherence to therapy.

OBJECTIVE: This study builds on the limited research documenting Cystic Fibrosis (CF) patients' understanding of treatment recommendations and how this may impact adherence to therapy. METHODS: We surveyed adults with CF and their healthcare professional (HCP) to capture treatment recommendations provided by the HCP, and patients' knowledge, and frequency of performance, of these recommendations. We classified CF participants' understanding of treatment recommendations (correct/incorrect) as compared to the actual recommendations made by the HCP. We computed CF participants' adherence in relation to HCP treatment recommendations and to their own understanding of treatment recommendations (adherent/non-adherent). RESULTS: Complete HCP and patient data were available for 42 participants. The recommended treatment frequency was correctly understood by 0%-87.8% of CF participants. Adherence to HCP treatment recommendations ranged from 0 to 68.3% (mean 45.4%±21.5), and rates were low (<33%) for acapella, percussion/postural drainage, tobramycin nebulization and insulin. Participants' adherence was greater when calculated in relation to participants' understanding of treatment recommendations (62.4%±25.1) than when calculated in relation to actual HCP treatment recommendations (45.4%±21.5%) (p=0.009). CONCLUSION AND PRACTICE IMPLICATIONS: Adults with CF misunderstand treatment recommendations; this likely affects treatment adherence. Interventions to ensure HCPs use effective communication strategies are needed.

A new stability indicating HPLC method for related substances in zolmitriptan.

A sensitive, precise, specific, linear and stability indicating isocratic HPLC method was developed for the analysis of related substances in zolmitriptan. The potential known related substances are (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (impurity I) and (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one (impurity II). The method can be used for the detection and quantification of known and unknown impurities and degradants in the drug substance zolmitriptan during routine analysis and also for stability studies in view of its capability to separate degradation products.

Influence of lung volume reduction surgery (LVRS) on health related quality of life in patients with chronic obstructive pulmonary disease.

BACKGROUND: The clinical value of LVRS has been questioned in the absence of trials comparing it with pulmonary rehabilitation, the prevailing standard of care in COPD. Patients with heterogeneous emphysema are more likely to benefit from volume reduction than those with homogeneous disease. Disease specific quality of life is a responsive interpretable outcome that enables health professionals to identify the magnitude of the effect of an intervention across several domains. METHODS: Non-smoking patients aged <75 years with severe COPD (FEV(1) <40% predicted, FEV(1)/FVC <0.7), hyperinflation, and evidence of heterogeneity were randomised to surgical or control groups after pulmonary rehabilitation and monitored at 3 month intervals for 12 months with no crossover between the groups. The primary outcome was disease specific quality of life as measured by the Chronic Respiratory Questionnaire (CRQ). Treatment failure was defined as death or functional decline (fall of 1 unit in any two domains of the CRQ). Secondary outcomes included pulmonary function and exercise capacity. RESULTS: LVRS resulted in significant between group differences in each domain of the CRQ at 12 months (change of 0.5 represents a small but important difference): dyspnoea 1.9 (95% confidence interval (CI) 1.3 to 2.6; p<0.0001); emotional function 1.5 (95% CI 0.9 to 2.1; p<0.0001); fatigue 2.0 (95% CI 1.4 to 2.6; p<0.0001); mastery 1.8 (95% CI 1.2 to 2.5; p<0.0001). In the control group one of 27 patients died and 16 experienced functional decline over 12 months. In the surgical group four of 28 patients died and three experienced functional decline (hazard ratio = 3.1 (95% CI 1.3 to 7.6; p=0.01). Between group improvements (p<0.05) in lung volumes, flow rates, and exercise were sustained at 12 months (RV -47% predicted (95% CI -71 to -23; p=0.0002); FEV(1) 0.3 l (95% CI 0.1 to 0. 5; p=0.0003); submaximal exercise 7.3 min (95% CI 3.9 to 10.8; p<0.0001); 6 minute walk 66 metres (95% CI 32 to 101; p=0.0002). CONCLUSIONS: In COPD patients with heterogeneous emphysema, LVRS resulted in important benefits in disease specific quality of life compared with medical management, which were sustained at 12 months after treatment.

Behavior of uptake of moisture by drugs and excipients under accelerated conditions of temperature and humidity in the absence and the presence of light. 1. Pure anti-tuberculosis drugs and their combinations.

An investigation was carried out to determine the behavior of moisture gain by four anti-tuberculosis drugs, viz. rifampicin, isoniazid, pyrazinamide and ethambutol, when exposed in pure form and in combinations to accelerated conditions of 40 degrees C and 75% RH, in the absence and the presence of light. Weight gain was seen only in those samples that contained ethambutol, and this behavior was observed both in dark and lighted chambers. There was a decrease in moisture uptake with an increase in the number of drugs in the mixture. Another observation was a higher weight gain by the mixture of ethambutol and isoniazid in a dark chamber, than either pure ethambutol or drug combinations containing ethambutol. The most interesting finding was an overall acceleration of weight gain in the presence of light as compared with dark conditions, which is a hitherto unknown phenomenon.

Distribution of major and minor alkaloids in tobacco, mainstream and sidestream smoke of popular Indian smoking products.

Various Indian smoking products--cigarette, bidi, chutta and a brand of US cigarette--were analysed by gas chromatography-flame ionization detection (GC-FID) for the levels of nicotine and minor tobacco alkaloids in tobacco, mainstream smoke (MS) and sidestream smoke (SS) employing modified smoking standards, namely two puffs/min. The analysis clearly demonstrated relatively higher levels of nicotine and minor tobacco alkaloids in tobacco from bidi (37.7 mg/g) and chutta (34.5 mg/g) when compared with Indian and US cigarettes (14-16 mg/g) studied. Relatively lower levels (SS/MS) of nicotine in SS from bidi and chutta compared with Indian/US cigarettes, suggest that the contribution of nicotine in SS from a single bidi/chutta to environmental tobacco smoke (ETS) is very much less than that of a single Indian/US cigarette. Reduced levels of nicotine in SS of bidi/chutta result in relatively higher deliveries of nicotine in MS as reflected by higher MS/SS values. The observed differences are likely to be due to difference in tobacco processing, burning rate/temperature and design of the smoking product.

Chemical analysis of smoke of Indian cigarettes, bidis and other indigenous forms of smoking--levels of steam-volatile phenol, hydrogen cyanide and benzo(a)pyrene.

Levels of steam-volatile phenol, hydrogen cyanide and benzo(a)pyrene in various types of tobacco smoking products marketed in the country have been determined for the first time. Steam-volatile phenol levels in six popular brands of Indian cigarettes varied from 118 to 226 micrograms, and in six popular brands of bidis, from 129 to 273 micrograms. Cheroot and cigarillos yielded 400 micrograms and 333 micrograms steam-volatile phenol respectively. The hydrogen cyanide levels in the mainstream smoke of five popular brands of Indian cigarettes varied from 366 to 638 micrograms and in the mainstream smoke of four popular brands of bidis from 688 to 904 micrograms. Cheroot and cigarillos yielded 588 micrograms and 1119 micrograms hydrogen cyanide respectively. The values of benzo(a)pyrene content in Indian cigarettes varied from 85 to 114 ng and in bidis from 108 to 144 ng. Herbal bidi and cheroot had 1315 ng and 2519 ng benzo(a)pyrene respectively. Cigarettes were smoked as per international standard smoking conditions and the levels of noxious agent were found to be higher than in currently marketed western cigarettes. However, these levels in all the indigenous products including bidis cannot be directly compared with those of cigarettes as they were smoked under modified conditions.

Total particulate matter and nicotine in Indian bidis and cigarettes: a comparative study of standard machine estimates and exposure levels in smokers in Bombay.

Standard emission levels of total particulate matter (TPM) and nicotine in bidi and cigarette smoke were compared with exposure levels based on smoking behaviour of smokers in Bombay. Bombay cigarette smokers are getting much higher amount of carcinogenic dry TPM (28 to 79%) and nicotine (31 to 104%), compared to standard machine estimates. In the case of regular bidi (60 mm) harmful ingredients like dry TPM decreased from 11 to 15 percent and nicotine increased from 11 to 22 percent, whereas long bidi (80 mm) delivered higher amount of dry TPM (14 to 22%) and nicotine (33 to 37%) in smokers in Bombay compared to standard machine estimates.

Carcinogenic tobacco-specific nitrosamines in Indian tobacco products.

Various Indian tobacco products--cigarette, bidi, chutta and their smoke, chewing tobacco and snuff (used for inhalation as well as a dentifrice) were analysed for their content of tobacco-specific nitrosamines (N'-nitrosonornicotine, 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone and N'-nitrosoanatabine) by means of a gas chromatograph interfaced with a thermal energy analyser. These tobacco-specific nitrosamines were detected at microgram/g levels in all products investigated and in ng quantities in tobacco smoke. The highest concentrations were in chutta tobacco and snuff used for inhalation. The use of these Indian tobacco products may lead to high exposure to the potentially carcinogenic tobacco-specific nitrosamines.

Carcinogenicity of Indian bidi and cigarette smoke condensate in Swiss albino mice.

The carcinogenicity of Indian bidi and cigarette smoke condensate given by gavage was studied in Swiss mice. Bidi smoke condensate induced liver haemangiomas in four animals, forestomach papilloma in one animal and carcinomas in two animals, in one of them was in the oesophagus and in the other in the forestomach. At the same dose level cigarette smoke condensate failed to produce any tumour. Similarly, none of the untreated and solvent-treated control mice developed tumour. Chemical analysis of the smoke concensate of bidis and cigarettes showed that condensate from bidis had a higher benzo[a]pyrene level than was observed in cigarette smoke condensate, when compared on the basis of the mass (mg) burnt.

Mutagenicity of smoke condensate of bidi--an indigenous cigarette of India.

The possible mutagenicity of bidi smoke condensate (BSC), an indigenous form of an Indian cigarette has been studied using three short-term test systems. It was seen that BSC caused frame-shift mutations in Salmonella typhimurium strains TA 98 and TA 1538 and required metabolic activation. In the mammalian test systems, BSC induced 8 azaguanine resistant mutations in V79 Chinese hamster cells in the presence of S9 mixture and induced elevated frequencies of micronucleated erythrocytes in the bone marrow of Swiss mice.