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Dose-dependent uricosuric effect of ambroxol.

Ambroxol is known to promote bronchial secretion and is used as an expectorant. Previous studies had suggested that high doses of ambroxol could reduce the plasma uric acid concentration. The present study was undertaken to confirm this finding, to determine its dose-response relationship and to identify the underlying mechanism of action. Using a placebo-controlled, double-blind parallel group design, 48 healthy male volunteers were randomly allocated to receive placebo b.d. and ambroxol 125 mg b.d., 250 mg b.d. or 500 mg b.d. (12 subjects per group). The subjects were hospitalised during a dietary run-in period of 3 days (Days -3 to -1) and a treatment period of 5 days (Days 1 to 5). On Day -1 (baseline) and Days 1 to 5, all urine was collected and blood samples were taken for the analysis of uric acid, creatinine, xanthine and ambroxol. The measurements were repeated four days after treatment had closed. Steady state plasma concentrations of ambroxol (trough levels) were reached after 2 or 3 days and were linearly related to dose. Ambroxol induced a significant, dose-dependent, reduction in plasma uric acid (250 mg b.d. about 20%; and at 500 mg b.d. about 30%). The diurnally fluctuating uric acid clearance was dose dependently increased and there was no notable effect on creatinine clearance. Plasma hypoxanthine levels were not affected by ambroxol. No severe adverse events were reported and no drug induced changes in the clinical laboratory values were observed. It is concluded that ambroxol has an uricosuric action following oral administration of higher doses (250 mg-500 mg b.d.) and it is well tolerated.

Adult↗

Clinical studies in workers engaged in maintenance of watermark moulds in a paper mill.

Thirty subjects engaged in maintenance and repair of moulds used for producing watermarks on paper were studied, along with 27 control subjects from the same paper mill. The workers were simultaneously exposed to copper, chromium, zinc, xylol, and fumes of sulphuric acid in the course of their work. The study subjects were investigated for clinical, occupational, radiological haematological and psychological details. The aforementioned combined exposure was found to be responsible for a high prevalence of symptoms pertaining to the respiratory system and higher nervous functions. Breathlessness (26.7%), expectoration (10.0%) and emphysema (10.0%) were significantly higher among the exposed subjects. The exposed subjects also showed lowered visuomotor coordination and delayed reaction to light and sound stimuli.

Adult↗

Is mis-swallowing or smoking a cause of respiratory symptoms in patients with gastroesophageal reflux disease?

Respiratory symptoms were studied in 119 patients operated on for fundoplication and crural repair because of gastroesophageal reflux disease (GERD). The effect of antireflux surgery and of smoking habits on their respiratory symptoms was evaluated. A questionnaire was completed before and after surgery in connection with esophageal investigations. Chronic bronchitis was present in 20% of the patients, 38% of whom were smokers. In the rest of the patients, 18% were smokers. Cough was reported by 34% and expectoration by 21%. After surgery the number of patients with cough and chronic bronchitis was reduced significantly in nonsmokers and to some extent in smokers. It is believed that fundoplication with distal anchoring of the longitudinal esophageal muscle will improve pharyngoesophageal function and thereby decrease aspiration and respiratory symptoms due to mis-swallowing.

Adolescent↗

Iodine-induced hypothyroidism and goiter following lipiodolTM lymphography.

Hypothyroid goiter is a rare but well recognized complication following long term administration of iodine containing expectorants and disinfectants in children. Only few reports exist on iodine-induced hypothyroidism after a single injection of the iodized radiopaque dye Lipiodol. A 15-year-old boy with previously normal thyroid function is described who developed hypothyroid goiter within six weeks following bipedal lymphography. Urinary iodine excretion was extremely elevated up to 18 mg/day while serum concentrations of total thyroxine were below the euthyroid range and thyrotropin levels were elevated. After oral L-thyroxine treatment the goiter disappeared. Thyroid function remained normal when treatment was discontinued after five months although iodine excretion was still 50 times higher (2.5 mg/day) than in normal age matched children. The observed alterations of the thyroid gland were caused by a long lasting Wolff-Chaikoff effect with a delayed adaptation to high iodide concentrations.

Adolescent↗

Oxalosis associated with an aspergillus niger fungus ball. Report of a case.

During a seventeen day period an A. niger fungus ball evolved within a healed tuberculous cavity of a patient. Symptoms were a cough with a chocolate brown expectoration and dyspnea. The patient died and necropsy was performed. Crystals of calcium oxalate were deposited in the cavity lining and in the adjacent tissue of the lung. Fibrosis, mononuclear infiltration and intraalveolar purulent exudate were seen in these tissues. Some small vessels presented recent thrombosis and deposition of calcium oxalate. The bronchus connected with the cavity presented a disrupted epithelial layer, edema, polymorphonuclear infiltration and birefringent crystals. Scattered areas of tubular atrophy, glomerular sclerosis and lymphoid infiltration were seen in the cortex of the kidney. Oxalate crystals were also seen within the renal tubuli.

Aspergillosis↗

Over-the-counter sales of drugs in Sweden 1976-1983.

The over-the-counter (OTC) sales of drugs were estimated by subtraction of sales on prescription and to hospitals from total drug sales in Sweden during the period 1976-1983. Increased sales of antitussives and decreased sales of expectorants characterized cough remedies. Making topical nasal decongestants available as OTC drugs immediately resulted in a large and increasing volume of OTC sales. Among analgesics, sales of acetaminophen and acetylsalisylic acid + caffeine combinations increased, while those of other groups decreased. Drugs for disorders of the alimentary tract were second to analgesics in the numbers of packs sold; amongst them antacids and laxatives dominated. Laxative sales decreased due to decreased sales of stimulant preparations. Vitamin C and multivitamin preparations dominated OTC vitamin sales. The sales of topical corticosteroids, only available as OTC drugs during the last quarter of 1983, were substantial. The OTC drug sales statistics reflect patterns of self-medication and may be used to monitor this important part of health care.

Humans↗

Effect of sublingual isosorbide dinitrate on sputum volume and viscoelasticity in chronic obstructive lung disease.

The effect of isosorbide dinitrate (ISDN) on sputum volume and sputum viscoelasticity in 12 patients with chronic obstructive lung diseases (COLD) was investigated by the double-blind randomized cross-over method with matched placebo. Each patient was given either sublingual ISDN 5 mg or placebo at 9 a.m. and sputum was collected for 3 h before and after 9 a.m. The dynamic viscoelasticity of the sputum was measured using a coaxial cylinder rheometer at an angular frequency of 0.1 rad/s. ISDN significantly increased sputum volume, and it caused a significant decrease in dynamic viscosity and in dynamic elasticity compared to placebo. The findings suggest that ISDN might be useful as an expectorant in the treatment of COLD when abundant and viscous sputum is present.

Adult↗

[The detection of guaiacol glyceryl ether, a content of many sedatives and hypnotics in the Federal Republic of Germany].

Guaiacol Glyceryl Ether (GGE) is well known as an expectorant in a large number of cough syrups etc. More recently it was used in surgery because of its activity as a muscle relaxant and its additive effect on narcotics. Today many of the sedatives and hypnotics in the BRD, which are available without prescription, contain GGE in doses of 50 mg to 250 mg partially combined with other sedative acting substances. With regard to the abuse of sedatives and hypnotics GGE therefore will be more important in future. The analytical data of GGE (for details see key words), extraction behavior and identification of TLC combined with quantitative determination by HPLC are described.

Chromatography, Gas↗

Effects of antireflux therapies on salivary function in normal humans.

Saliva has received recent attention because of its potential role in esophageal clearance and neutralization of refluxed gastric contents. Gastric antisecretory drugs or promotility drugs used to treat reflux have not been studied for their ability to affect salivary function. We conducted a double-blind randomized study of four antisecretory drugs, two promotility drugs, and placebo (PL) on 12 healthy volunteers on seven different days. Following a 6-hr fast, accumulated saliva was expectorated at least once per minute. The initial 10-min sample was discarded and a baseline 20-min sample collected. One of the following was given per os: PL, pirenzepine (PIR), 50 mg; propantheline (PRO), 30 mg; cimetidine (CIM), 300 mg; ranitidine (RAN), 150 mg; bethanechol (BET), 25 mg; or metoclopramide (MET), 10 mg. Saliva was collected for 60 min. Saliva was then stimulated (STIM) by sucking a peppermint lozenge for 30 min. Specimens were collected under oil, kept on ice, and analyzed within 30 min. Saliva flow in milliliters per minute and capacity for acid neutralization (CAN) in microequivalents acid per milliliter saliva were analyzed on all samples. The known effect of PRO to inhibit both basal saliva flow and STIM flow and CAN was seen. In contrast, the selective antimuscarinic PIR did not significantly decrease saliva flow or CAN. CIM, RAN, and MET did not significantly effect salivary function, but both CIM and RAN showed a tendency to increase CAN. Oral BET had no detectable effect on salivary function.

Adult↗

Relationship between swallow rate and salivary flow.

Recent studies indicate that swallow-induced, primary peristalsis is a major determinant of normal esophageal acid clearance. However, factors that regulate the rate of spontaneous swallowing in normal subjects are incompletely understood. We postulated that the rate of salivary flow influences the rate of spontaneous swallows. To test this hypothesis, we did a total of 60 studies measuring salivary flow or the rate of spontaneous swallowing in 10 healthy volunteers, age 10-30 years. Saliva was collected by expectoration. Swallow rate was recorded by a small, transnasal catheter stationed in the pharynx and also, in some circumstances, by cervical electrodes. On separate sessions, we evaluated the effect of five test manipulations on salivary flow and swallowing rate, respectively. The test manipulations consisted of: (1) pharyngeal intubation, (2) sucking of a dummy lozenge, (3) sucking of a peppermint lozenge, (4) bethanechol injection (5 mg subcutaneously), and atropine administration (12 micrograms/kg intravenously). Pharyngeal intubation caused a small, but significant increase in the rate of salivation and spontaneous swallows. Sucking of a peppermint lozenge caused a sixfold increase in salivary flow while nearly doubling the swallowing rate whereas the dummy lozenge caused only a modest increase in salivary flow and swallowing. Cholinergic stimulation by bethanechol elicited a substantial increase in salivary flow and swallowing rate. In contrast, atropine caused a significant decrease in both salivary flow and swallowing. We conclude that in awake, normal subjects the rate of spontaneous swallows is influenced directly by salivary flow. Because oral lozenges substantially increase both swallowing rate and salivary flow, such agents merit investigation as a potentially useful ancillary treatment for the relief of heartburn.

Adolescent↗

Sham feeding. Cephalic-vagal influences on gastric myoelectric activity.

The effects of sham feeding on gastric motility of human subjects have not previously been studied. The amplitude of 3-cpm electrogastrogram (EGG) waves increases after the ingestion of food. We hypothesized that sham feeding would stimulate a similar, but briefer gastric myoelectric response. Healthy human subjects chewed and expectorated a hot dog on a roll and later ate a second hot dog. EGGs were continuously recorded before, during, and after sham feeding and eating. The results of experiment I (N = 27) showed that the hand-scored amplitude of the 3-cpm waves increased significantly (P less than 0.01) during sham feeding. Two minutes after sham feeding, the mean amplitude of 3-cpm EGG waves returned to baseline level. The increase in EGG amplitude during eating was also significant (P less than 0.01), and remained increased for approximately 30 min after ingestion. The procedure used in experiment II (N = 20) was similar to experiment I, but EGGs were computer analyzed and power, ie, spectral intensities, at 3 cpm were obtained. The increase in power at 3 cpm during sham feeding and during eating was significant (P less than 0.05 and P less than 0.02, respectively). Similar to experiment I, the duration of increase in power at 3 cpm was brief during sham feeding compared to the postprandial increase. Four vagotomized subjects failed to show an increase in power at 3 cpm in response to sham feeding. We conclude: (1) The cephalic-vagal stimulation of sham feeding increases briefly the amplitude and power of 3-cpm gastric myoelectric activity in healthy subjects but not vagotomized patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Legionella pneumophila pneumonia masked by simultaneous demonstration of further non-specific pneumonia pathogens].

We are presenting a case of Legionella type I pneumonia, accidentally diagnosed by selective culture with simultaneous identification of pneumococci, meningococci and Hemophilus influenzae in the general sputum culture. A 35-year-old patient had been hospitalized with the typical signs of Legionnaires' disease (severe pneumonia with symptoms of cardiac, hepatic, renal, and cerebral involvement), following several days of prodromi. The routine sputum bacteriology according to DGHM standards first revealed pneumococci, meningococci and H. influenzae in significant numbers. Later, the special culture medium named after Edelstein (BMPA alpha-medium), routinely inoculated in our laboratory, grew Legionella pneumophila type I. Legionella type I-specific serum antibodies in IIFT confirmed the diagnosis of Legionnaires' disease. After therapy with amoxicillin plus clavulanic acid and cefoxitin, the temperature declined and laboratory as well as radiologic findings returned to normal. Without the culture of L. pneumophila from expectorated sputum, the diagnosis of Legionnaires' disease would not have been found.

Adult↗

Respiratory cryptosporidiosis: case series and review of the literature.

Five case of intestinal cryptosporidiosis with pulmonary involvement in patients with AIDS are reported. The diagnosis was based on the recognition of acid-fast oocysts in sputum or aspirated bronchial material and stool specimens. Coughing and excess secretions were present in all cases. Four patients had other associated pulmonary pathogens: two Mycobacterium tuberculosis, one Mycobacterium fortuitum and one Cytomegalovirus + Pneumocystis carinii; all of them had a previous (three cases) or simultaneous (one case) diagnosis of intestinal cryptosporidiosis, presenting with diarrhoea and vomiting. In the fifth patient Cryptosporidium was the only pulmonary pathogen found in a bronchial aspirate, and the onset of diarrhoea was 1 month after respiratory detection. Fifty-seven cases of respiratory cryptosporidiosis have been reported since 1980. In 17 of them, no other pathogen was found. Diarrhoea was present in 77% of the patients, cough in 77%, dyspnea in 58%, expectoration in 54%, fever in 45%, thoracic pain in 33%.

Acquired Immunodeficiency Syndrome↗

Detection of Pneumocystis carinii with direct fluorescence antibody and calcofluor white stain.

Direct fluorescence monoclonal antibody stain (DFA) was compared prospectively, with calcofluor white (CFW) stain for the diagnosis of Pneumocystis carinii in 163 respiratory specimens from 97 patients. The patient population included persons with HIV infection (58%), bone marrow transplant recipients (10%), immunosuppressed patients owing to chemotherapy (21%) and others (11%). Nineteen specimens including 12 sputa, six bronchoalveolar lavage fluids (BALs) and one induced sputum were positive by DFA. In contrast, only six sputa, and five BALs were positive by CFW. All specimens positive by CFW were also positive by DFA. Of 86 sputa that were negative by either method 29 were followed by more invasive sample collections. Three specimens were followed by induced sputum collection, 18 by BAL, six by lung biopsy, and two by pleural fluid aspiration. All the subsequent induced sputa, pleural fluids, and lung biopsies were negative by both methods. However, four of 18 subsequent BALs (22%) were positive by both methods, provided at least two CFW stained slides were examined per specimen. Except for expectorated sputum, it is concluded that CFW is a rapid and inexpensive test to detect P. carinii in most respiratory specimens.

AIDS-Related Opportunistic Infections↗

Bacteria-induced IgE-mediated histamine release: examination of patients with chronic bronchitis (CB) during acute exacerbations.

Twelve patients hospitalized with acute exacerbations of chronic bronchitis (CB) and infected in the lower respiratory tract with H. influenzae (HI) or Streptococcus pneumoniae (SP) were examined. Bacteria, isolated from the expectorate caused an IgE-mediated histamine release from the patient's own blood leukocytes, indicating that all were sensitized to their own bacteria. Sensitization was only observed in some of the patients when tested with a standard panel of HI or SP obtained from other patients, indicating the importance of using the patient relevant bacterial antigenic determinants. No sensitization was found in twelve controls. The patients showed cellular hyperreactivity to HI and SP, i.e. the releasability was higher than in the control group. The cellular hyperreactivity was not dependent on sensitization since it was also found against the non-infecting species. Both sensitization and cellular hyperreactivity may contribute to the aggravation of the disease.

Aged↗

A follow-up study of pulmonary function in patients with primary Sjögren's syndrome.

Twenty-seven patients (25 women, 2 men) with primary Sjögren's syndrome, previously reported to have reduced pulmonary diffusing capacities were reexamined in a 7-year follow-up in order to evaluate longitudinal alterations in pulmonary function. Primary Sjögren's syndrome was diagnosed according to the Copenhagen criteria. The present examination revealed normal and unchanged values for vital capacity, forced expiratory volume in 1 s, maximal expiratory flow at 50% of expired vital capacity (MEF50), and diffusing capacity per liter alveolar volume. Total diffusing capacity (P less than 0.01) and MEF75 (P less than 0.05), were, however, significantly reduced compared with the predicted values, indicating pulmonary involvement primarily affecting the small airways. The longitudinal examination, furthermore, showed increasing values for total diffusing capacity (P less than 0.02), diffusing capacity per liter alveolar volume (P less than 0.001), and MEF75 (P less than 0.02), suggesting an improvement in lung status in the course of time. No correlation was found between MEF75 and diffusing capacities, nor between alterations in pulmonary function and complaints of dyspnoea, tiredness, cough, expectoration, tobacco smoking, or medical treatment with bromhexine, glucocorticosteroids, essential fatty acids, or nonsteroid antiinflammatory drugs.

Adult↗

Treatment of acute pulmonary failure by CPAP via face mask: when can intubation be avoided?

Continuous positive airway pressure (CPAP) is used frequently to improve gas exchange in acute pulmonary failure. We investigated clinical and respiratory variables in 98 patients presenting with two or more of the classical criteria for endotracheal intubation and mechanical ventilation. CPAP applied by a face mask was efficient in 60 cases. Posttraumatic and postoperative pulmonary problems responded better to this therapy than lung dysfunction secondary to left heart failure, sepsis or pneumonia. Abundant expectorations, discoordination of respiratory movements and an increase in arterial carbon dioxide were frequently associated with failure of CPAP by mask and the necessity of endotracheal intubation and mechanical ventilation.

Acute Disease↗

The value of sputum cytology.

OBJECTIVE: To assess the value of cytologic examination of expectorated sputum in the diagnosis and management of patients with suspected lung cancer. DESIGN: Retrospective chart review. SETTING: Inpatient wards, tertiary care university hospital. MEASUREMENTS AND MAIN RESULTS: The charts of 357 patients were reviewed. Two hundred eighty-eight of the 357 patients had had initial sputum cytologic examination prior to other diagnostic procedures, of which 41 (15%) had positive cytologic results. Thirty-six of the 41 were confirmed histologically or shown to have metastatic spread by noninvasive tests. Of the 222 patients with negative or unsatisfactory sputum tests, 97 went on to bronchoscopy and 35 had needle-aspiration biopsies. In the population of patients whose chest x-rays were highly suggestive of primary or metastatic lung cancer, the positive rate for cytologic examination was 38/94 (40%). There was no false-positive test in this study. Of the 50 patients with positive cytologic results, five (10%) had diseases that were of a different cell type; two of these five (40%) had diseases that involved small-cell cancer. There was an unsatisfactory delay in obtaining these samples for analysis. CONCLUSIONS: Sputum cytology was found to be too insensitive and insufficiently accurate to be included in the routine workup of a patient suspected of having lung cancer. The results of the test did not influence further diagnostic procedures. This test should, therefore, be reserved for patients considered on initial assessment to be too sick for further investigations and treatment.

Humans↗