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Death due to asphyxia linked to antipsychotic drugs.

A 46-year-old man with schizophrenia, died in hospital. Autopsy revealed numerous facial injuries and the direct cause of death was apparently asphyxia as a large amount of coagulated blood was present in the lower part of the trachea and bronchi. The blood derived from a lacerated wound of the mouth. The question was raised as to why expectoration was impossible and a toxicological analysis was directed to the antipsychotic drugs allegedly prescribed by doctors at the hospital. Using gas chromatography and gas chromatography/mass spectrometry, four different antipsychotic drugs including chlorpromazine, levomepromazine, zotepine and haloperidol were identified in the whole blood and tissues with concentrations being 1.91, 0.75, 0.61 and 0.48 micrograms/g in the blood, respectively. These levels were toxic to the extent that he could not expectorate and blood accumulating in the airway led to asphyxia and death.

Antipsychotic Agents↗

[Is methicillin better than cloxacillin in serious infections caused by strong penicillinase-producing staphylococci (phage-type 94/96)?].

An intravenous drug addict was treated with cloxacillin for septicaemia with Staphylococcus aureus because of pneumonia and suspected endocarditis. After 51 days of treatment Staphylococcus aureus was still found in blood and expectorate despite continued treatment with intravenous cloxacillin 1 g three and later four times daily and oral rifampicin. The staphylococcal isolates were all of phage type 94/96. Investigations have shown that Staphylococci aurei of phage type 94/96 produce large amounts of penicillinase, and that methicillin is the most penicillinase-resistant of the penicillinase-resistant penicillins followed by dicloxacillin and cloxacillin. The penicillinase production of the patient's Staphylococcus aureus strain was 304-362 units per mg bacteria which is high compared to typical values of 50-200. After 50 days of cloxacillin treatment, the treatment was changed to methicillin 2 g four times daily. Within a week the staphylococci had disappeared from the expectorate, and were never again recovered from the blood. It is suggested that methicillin should have superior efficiency in serious infections with Staphylococcus aureus of phage type 94/96.

Cloxacillin↗

[Clinical-therapeutic considerations in a case of miliary tuberculosis in an indonesian girl].

The authors describe the case of widespread miliary tuberculosis, that arose in a ten year-old Indonesian girl of middle-class, who has been living in Italy from about three years. The girl was probably contaminated by a subject belonging to the same ethnic-social community, who was affected with tubercular disease. The diagnosis was effected on the ground of: clinical picture including continued-remitting fever, a loose cough, asthenia, anorexia, weight reduction, aching tumefaction on the left side of the neck; isolation of Mycobacterium tuberculosis from the expectoration, blood, urine, and a lymph node located on the left side of the neck; radiological picture that revealed a widespread miliary tuberculosis. In spite of polychemotherapy with isoniazid , rifampicin, pirazinamide, and streptomycin that was subsequently replaced by ethambutol, the course of the illness worsened and it was characterized with fever, cachexia, respiratory insufficiency and repeated episodes of pneumothorax. For such reasons on the ground of susceptibility to the antibiogram amikacin and ciprofloxacin, as well as glucocorticoids to limit the fibrousness, were added to the specific therapy that was already being out. For persisting of relapsing pneumothoraxes, the patient underwent a thoracoscopy and plerodesis with talcum powder. After four months of antitubercular therapy, the research of M. tuberculosis resulted negative in the expectoration, urine, bronchus-alveolar washing liquid and blood, in addition to improvement in general state of health with remission of fever was noticed.

Child↗

The use of Paxirasol in clinical practice.

Summarizing the observations of foreign and Hungarian investigators it may be concluded that: 1. Bromhexine is an expectorant of outstanding effect which has virtually no side-effects when used in therapeutic doses; by loosening the thick, sticky mucus in increases the effectivity of mucociliary clearance and hinders the infection of thick excretion sticking to the mucosa. 2. It promotes the diffusion of antibiotics into the lung tissue. 3. Considering the increasingly important aspects of "cost-benefit", the use of drug is also advantageous. 4. In addition to the traditional drug forms (tablet, injection, solution) new forms of the drug (inhalation aerosol, nasal spray) increase its indication field to a high degree. These allow to apply local expectorant-mucolytic therapies and to successfully treat the so-called sicca diseases (rhinitis sicca, pharyngitis sicca, etc.), which frequently occur in laryngological practice and was difficult to influence until present.

Administration, Inhalation↗

[II. multidisciplinary analysis of chronic excretors of Mycobacterium tuberculosis bacilli].

For the most patients with pulmonary tuberculosis, treatment are successful and the chemotherapy can be finished within a year. Few patients, though receiving standard anti-tuberculous chemotherapy, expectorate tubercle bacilli continuously for more than a year. They are named "chronic excretors of mycobacterium tuberculosis bacilli" or "intractable tuberculosis patients". Being suspected that this phenomenon is produced by many factors, it is necessary to correspond suitably to these patients for eradication of tuberculosis. This symposium was organized to search for some factors on the bacterium and on the host, which caused patients to be the chronic excretors or intractable patients. We hope that our discussion may contribute to take the appropriate measures for such hard diseases. The main results are summarized as follows. 1) Dr. TSUCHIYA conducted a epidemiologic study by questionaire method to 33 Japanese national sanatoriums. The total number of tuberculosis patients admitted to these hospitals on a optimal day from September to October 1994 were 1,295. Numbers of patients who had expectorated bacilli continuously for more than 12 months were 85 (6.6%). The male/female ratio was about 3, their average age was 64. They had a tendency of thin-physique and most of them had past histories of tuberculosis, being the refractory cases. The average clinico-epidemiologic conditions of the patients came before our eyes. 2) Dr. OGATA analysed the results of drug sensitivity tests of mycobacterium tuberculosis bacilli from 2,630 pulmonary tuberculosis patients which contained 179 chronic excretors. The only 2.2% of bacilli from the chronic excretors were sensitive to RFP (50 gamma). The 99.4% of bacilli showed to be resistant to INH (0.1 gamma). The 39.1% of bacilli were sensitive to streptomycin (20 gamma). To EB (2.5 gamma) 34.1% of bacilli were sensitive. However, the ratio of chronic excretors in tuberculosis patients was not increased in these 17 years, and for many cases of these chronic excretors, they are all inexperienced in PZA, multi-sensitive-drug chemotherapy including PZA and OFLX were useful. Some of them underwent lobectomy combined for effective chemotherapy. The chronic excretors are likely to be affected multidrug-resistant bacilli, and it is important for such cases to treat intensively with several kinds of sensitive drugs. 3) Dr. FUJIWARA studied Interleukin-10 (IL-10) producing function of monocytes stimulated by Mycobacterium tuberculosis (M-TB). The IL-10 usually down-regulates a number of different macrophage functions, including microbicidal activity against intracellular bacteria such as Mycobacterium species. They found that the mean IL-10 production by peripheral blood mononuclear cells (PBMC) obtained from a healthy tuberculin-reactor stimulated with multidrug-resistant M-TB was greater than that with drug-sensitive M-TB. The IL-10 producing cells were monocytes, not T-lymphocytes. They moreover found that PBMC from intractable tuberculosis patients secreted greater amounts of IL-10 than those of healthy subjects. These data may give a hint for development of new immunotherapeutic methods for multi-drug-resistant tuberculosis patients. 4) Dr. HARA analysed clinical courses of 580 consecutive cases of bacilli positive pulmonary tuberculosis admitted in his hospital from a point of underlying diseases. All of dead 24 cases had some underlying diseases; diabetes mellitus 3, chronic liver diseases 4, others 17 (malignant neoplasms, central nerve vascular diseases, malnutritional condition, etc). (ABSTRACT TRUNCATED)

Chronic Disease↗

[Epidemiologic study of the actual investigation of chronic excretors of Mycobacterium tuberculosis bacilli].

Of 1,295 patients with tuberculosis who were admitted in 33 Japanese national sanatoriums from September to October, 1994, actual investigation of patients with persistent expectorate tubercle bacilli continuously for more than 12 months was carried out by questionnaire. From the result, numbers of patients who had persistently expectorated bacteria were 85 (6.6% of inpatient). The rate of male and female was 3:1, and mean age was 63.5 years old. Many slim type patients (less than 90% of the standard body weight) were observed at the rate of 55.8%. The rate of the inpatient whose admission period was for more than 10 years were found in 22%. The past history of the tuberculosis and surgical therapy were existent at the rate of 83.3% and 18.8% respectively. The chief complications such as diabetes mellitus (12.4%), pyothorax (10.1%), alcoholism (10.1%) and hepatic dysfunction (6.7%) were observed at the respective rate. As chest X-ray findings on admission, severe cases with cavity of I or II 3 by the classification of the Japanese society for tuberculosis were found in 32.2%, and many cases with much amount persistently excreted bacteria such as more than number 7 of Gaffky scale (24.7%) or 3+ by culture (55.8%) were detected by sputum-test on admission. From the result drug-resistance, resistance of the main drugs early found from initial medication, and high degree resistance of isonicotinic acid hydrazide (INH; 80%), rifampicin (RFP; 94.4%), ethambutol (EB; 85.6%) and streptomycin (SM; 76.4%) was found. As intractable causes which were indicated by doctor in charge, drug-resistance, drug allergy, disorder of life, unfavorable medication-compliance and unsuitable treatment were considered.

Adult↗

Comparison of the use of a child and an adult dentifrice by a sample of preschool children.

The purpose of this study was to compare the use of a child dentifrice (CD) and an adult dentifrice (AD) by a convenience sample of preschool-aged children. Fifty participants, ages 31 to 60 months, were recruited from a dental school clinic and an area day care center. All were healthy, free of developmental delays, and capable of applying dentifrice to a toothbrush. The study employed a crossover design in which the children each brushed their teeth twice, once with each type of dentifrice. The order of dentifrice use was assigned randomly, and the two brushings were separated by at least 1 week. The following were recorded: 1) the amount of dentifrice applied, 2) the time spent brushing, and 3) whether the child expectorated and/or rinsed after brushing. The mean weight of CD the children used (0.689 g, 0.43 SD) was significantly greater than that of AD (0.509 g, 0.41 SD, P = 0.02, Wilcoxon's signed rank test). The mean time spent brushing with CD (83.56 sec, 85.4 SD) was significantly greater than for AD (57.48 sec, 39.0 SD, P = 0.01). A "risk factor" (dentifrice weight x usage time) was derived to estimate the relative fluoride exposure of each child. The mean risk factor for CD (58.54, 64.8 SD) was significantly greater than that for AD (27.43, 25.0 SD, P < 0.001). Most children did not expectorate or rinse after brushing. Most parents selected drawings on a questionnaire that indicated that their child routinely used 0.25-0.5 g of dentifrice per brushing, which underestimated the amount they used in the study. The results of this study indicated that young children may be exposed to more fluoride for a longer period of time with CD.

Cariostatic Agents↗

Methods of examining induced sputum: do differences matter?

Analysis of induced sputum has been proposed as a direct, relatively noninvasive method for the evaluation of airway inflammation in diseases such as asthma or chronic obstructive pulmonary disease (COPD). An important question in the validation of this technique concerns the potential influence of differences in the methods of examining sputum. Up to the present time, two basic techniques for processing sputum have been described. The first approach consists of selecting all viscid portions from the expectorated sample, whereas the second approach processes the whole expectorate, containing sputum plus saliva. Both processing techniques have been shown to provide valid and reliable data on the composition of the cellular and soluble fraction of induced sputum. From the data currently available, it would therefore appear that the usefulness of induced sputum as a method for assessing airway inflammation is not influenced by differences in the methods currently used for examining sputum.

Humans↗

[Diagnosis of pulmonary tuberculosis by the amplicor test for Mycobacterium tuberculosis in induced sputum].

The polymerase chain reaction (PCR) technique was compared with the conventional smear and culture method for the detection and identification of Mycobacterium tuberculosis in 25 induced sputa samples. Sputum induction was performed with an ultrasonic nebulizer using 3% hypertonic saline in 27 previously untreated patients suspected of active pulmonary tuberculosis clue to chest X-ray findings, but who were unable to spontaneously expectorate sputum. All patients received anti-tuberculosis drugs for at least 6 months after sputum induction. Two patients could not expectorate sputum after hypertonic saline inhalation. Microscopy failed to detect positive acid-fast bacilli in 25 induced sputa samples. Induced sputa were both PCR- and culture-positive for 10 patients, PCR-positive and culture-negative for 4 patients, and PCR-negative and culture-positive for 2 patients. These results suggest that the PCR method is useful in diagnosing tuberculosis in induced sputum, and that the results of PCR and culture Procedures can complement each other.

Adolescent↗

Chronic obstructive airway diseases. Current concepts in diagnosis and comprehensive care.

Physicians and paramedical personnel often find the early diagnosis and differentiation of obstructive airway diseases to be a challenging problem. The history and physical examination are often not enough to allow the physician to detect either the presence of, or determine the type of, disease present. Patterns of pulmonary function abnormality to determine the presence of obstructive or restrictive defects are discussed. Guidelines useful in the differentiation of obstructive airway diseases are presented. Once a patient with COAD is assessed, the physician needs to outline a therapeutic program after establishing goals with the patient. These goals include (1) improved ability for the patient to achieve relief from symptoms and (2) improved capacity to carry out the activities of daily living. The therapeutic modalities available for the comprehensive care of patients with COAD are discussed. These include general factors such as patient and family education, avoidance of smoking and other inhaled irritants, avoidance of infection, a minimum stress environment, high fluid intake, and proper nutrition. The appropriate use of the medications most commonly employed in the teatment of these patients, eg, bronchodilators, expectorants, antimicrobials, corticosteroids, cromolyn, digitalis, and diuretics, are individually discussed. The use of such respiratory therapy techniques as aerosol therapy, intermittent positive pressure breathing, and oxygen therapy are considered. Application of the specialty of rehabilitation medicine to patients with obstructive airway disease is described. This includes physical therapy with breathing retraining, clapping and postural drainage, and exercise reconditioning, occupational therapy with attention to energy conservation in activities of daily living, psychological considerations, and vocational rehabilitation. Definite benefits that can be demonstrated if the physician employs this type of systematic respiratory care program include a decrease in the frequency and duration of hospital admissions, socioeconomic gains from reduced hospitalizations, a reduction in anxiety, depression and somatic concern, the return of patients to positions of employment and the establishment of a better quality of life. Persistence in making sure the patient continues in a systematic program, including both pharmacological and nonpharmacological modalities, may be the means of assuring maintenance or even improvement in his health. The day-to-day treatment for the majority of patients should remain in the hands of the primary physician. However, community resources must be established to allow the primary physician to provide these patients with adequate comprehensive respiratory care. Development of three levels of care (the primary physician, community respiratory rehabilitation units, and the regional respiratory center) should make superior respiratory care available to every patient with obstructive airway disease.

Adrenal Cortex Hormones↗

Airway inflammation after treatment with aerosolized deoxyribonuclease in cystic fibrosis.

Recombinant human deoxyribonuclease (rhDNase) has been shown to reduce sputum viscoelasticity and to improve lung function in patients with cystic fibrosis (CF). The aim of this study was to determine whether airway inflammation would decrease after administration of rhDNase. Twenty patients with CF and chronic suppurative lung disease inhaled 2.5 mg of rhDNase daily for 1 month. Before and after the 1-month trial, lung function was measured and sputum was obtained, either after spontaneous expectoration or after sputum induction with hypertonic saline. Sputum total cell and differential counts were measured using techniques previously described. The mean age of the patients was 16.8 years (range, 6.7-27.5). After 1 month of rhDNase, mean FEV1 increased from a baseline of 62.3% predicted to 70.8% (P= 0.02, paired t test); and FVC increased from 74.4% to 83.9% predicted (P=0.007). No significant differences were found in sputum cytology before or after rhDNase (median total cell counts 16.0 x 10(6)/ml vs. 19.3 x 10(6)/ml, P=0.68). Thirteen patients had a 10% or greater increase in FEV1 after rhDNase (responders). Initial lung function was less in responders than in nonresponders (53.5% vs. 78.6%, P=0.007). There was no significant change in total cell count and neutrophil count after rhDNase in either responders or nonresponders. We conclude that airway inflammation, as measured by total cell counts in sputum, was a prominent feature in cystic fibrosis, and neutrophils were the dominant inflammatory cells. Although the administration of rhDNase resulted in significant improvements in FEV1, there was no evidence of accompanying changes in airway inflammation.

Administration, Inhalation↗

Identification of components in iodinated glycerol.

Iodinated glycerol (CAS no. 5634-39-9), therapeutically used as an expectorant and source of organically bound iodine, was analyzed to determine the purity and composition of the chemical samples used in carcinogenicity and toxicity studies. The manufactured product is described by the patent and chemical literature as a mixture of two isomeric iodopropylideneglycerols (structures 1 and 2). The results of our studies, however, indicate that the two principal components of the product were 3-iodo-1,2-propanediol (IPD) and glycerol (GLY). Analyses from GC-MS (full scan electron impact) and carbon-13 nuclear magnetic resonance spectrometry provided conclusive identification of these components. The quantification of IPD and GLY in one of two samples of commercial product using GC-flame ionization detection indicated concentrations of 33 and 17%, respectively (Sample A). Similar concentrations were determined for a second sample from the same source (Sample B), which was a gratis sample procured approximately nine years after Sample A. Numerous minor components were also observed in these two samples. These components were tentatively identified as condensation products of glycerol and iodine-containing analogues. The iodopropylideneglycerol compounds, described in the patent, were not observed in either of the two samples.

Carbon Isotopes↗

Evaluation of antitussive agents in man.

Methodology to evaluate the efficacy of antitussive drugs rely largely on subjective methods and cough counts. There are few studies in cough due to natural disease especially using objective techniques. This paper presents data from a series of randomized, double blind, placebo controlled clinical trials in cough due to both chronic bronchopulmonary disease and acute upper respiratory tract infections. In these studies, cough was quantified using a standardized and validated computerized system for the acquisition and multidimensional analysis of the cough sound. Key objective parameters like cough counts, intensity, latency and total effort expended were studied. Guaiphenesin and bromhexine showed significant expectorant effects in patients with productive cough due to chronic bronchopulmonary disease. Differences were observed in speed of action, and objective and subjective measures, that probably indicate differences in drug action. More recently, three studies evaluated the antitussive drug dextromethorphan in non-productive cough due to uncomplicated upper respiratory tract infections. Reproducible cough suppressant effects were demonstrated after a single 30 mg dose using objective measures of cough counts, latency and total effort. These results establish the sensitivity and robustness of the cough quantitation methodology in the objective evaluation of cough treatments.

Acute Disease↗

Depressant effects of ambroxol on lipopolysaccharide- or fMLP-stimulated free radical production and granule enzyme release by alveolar macrophages.

In order to explore the depressant action of ambroxol, a bronchial expectorant, on the activated alveolar macrophage responses, its effect on lipopolysaccharide (LPS)- or N-formyl-methionyl-leucyl-phenylalanine (fMLP)- stimulated free radical production and granule enzyme release by rat lung alveolar macrophages was investigated. Ambroxol attenuated the 100 ng/ml LPS- or 1 microM fMLP-stimulated superoxide, H(2)O(2)and nitric oxide production and releases of acid phosphatase and lysozyme by alveolar macrophages. Ambroxol attenuated phorbol myristate acetate-stimulated superoxide and nitric oxide production that was inhibited by 100 nM staurosporine. N,N-dimethylsphingosine (DMS, 4.5 and 9 microM) alone stimulated superoxide production by macrophages, while 45 microM of the compound did not show a stimulatory effect. However, DMS decreased nitric oxide production in a dose-dependent manner. Ambroxol did not alter the DMS effect on free radical production that was affected by 10 microM genistein. A preincubation of macrophages with ambroxol (10 and 100 microM), staurosporine and genistein attenuated the elevation of [Ca(2+)](i)caused by LPS. The results suggest that ambroxol exerts a depressant effect on LPS- or fMLP-stimulated free radical production and granule enzyme release by rat alveolar macrophages, which may be attributed to its inhibitory action on the activation process, protein kinase C, but its action on protein tyrosine kinase is not suggested.

Acid Phosphatase↗

The effect of erdosteine and its active metabolite on reactive oxygen species production by inflammatory cells.

OBJECTIVE: We examined the effect of erdosteine (KW-9144), an expectorant, and related compounds on inflammatory cell-derived reactive oxygen species which are involved in airway inflammation. METHODS: Neutrophils were isolated from peritoneal lavages of casein-injected rats and from peripheral blood of healthy human donors. Eosinophils were isolated from peritoneal lavages of horse serum-injected guinea pigs. These cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and the production of reactive oxygen species was measured with luminol-dependent chemiluminescence (LDCL). RESULTS: M1, an active metabolite of erdosteine, significantly inhibited PMA-induced LDCL of the all cell populations with treatment before stimulation. The effects of S-carboxymethylcysteine (S-CMC), ambroxol and N-acetylcysteine (NAC) on the LDCL response were weaker than those of M1. Furthermore, PMA-induced LDCL was decreased by posttreatment with M1. CONCLUSION: These results suggest that M (an active metabolite of erdosteine) may exert an antiinflammatory effect by scavenging inflammatory cells-derived reactive oxygen species.

Animals↗

Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver.

Drug-induced liver toxicity is a common cause of liver injury. This study was designed to elucidate whether high dose vancomycin (VCM) induces oxidative stress in liver and to investigate the protective effects of erdosteine, an expectorant agent. Twenty-two young Wistar rats were divided into three groups as follows: control group, VCM, and VCM plus erdosteine. VCM was administered intraperitoneally in the dosage of 200 mg/kg twice daily for 7 days. Erdosteine was administered orally administered once a day at a dose of 10 mg/kg body weight. The activities of antioxidant enzymes such as superoxide dismutase and catalase as well as the concentration of malondialdehyde, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the liver. VCM administration increased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities. Erdosteine co-administration with VCM injections caused significantly decreased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities in liver tissue when compared with VCM alone. It can be concluded that erdosteine may prevent VCM-induced oxidative changes in liver by reducing reactive oxygen species.

Animals↗

Therapeutic approaches to mucus hypersecretion.

Mucolytic and related agents have been in use since prehistoric times. Although widely prescribed and used extensively in over-the-counter preparations, their efficacy and mechanisms of action remain in doubt. These agents belong to several distinct chemical classes. Mucolytic agents such as N-acetyl-cysteine are thiols with a free-sulfhydryl group. They are assumed to break disulfide bonds between gel-forming mucins and thus reduce mucus viscosity. Mucokinetic agents are thiols with a blocked sulfhydryl group. Expectorants such as guaifenesin increase mucus secretion. They may act as irritants to gastric vagal receptors, and recruit efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. Cough may be provoked. This combination may flush tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or the work of breathing. The roles of anticholinergic agents, DNase, and other drugs are also discussed with regard to their roles in reducing mucus production in rhinitis and other airway diseases.

Animals↗

Tracheal phenol red secretion, a new method for screening mucosecretolytic compounds.

A simple method for screening drugs that influence tracheobronchial secretion has been described. After i.p. application of a phenol red solution, part of the dye is secreted into the tracheal lumen. This basal secretion is increased by both parasympathomimetics and sympathomimetics. In addition, expectorants are also capable of increasing tracheal phenol red output. Therefore this method is suitable for the study of drugs that may be capable of influencing tracheobronchial secretion.

2-Hydroxyphenethylamine↗