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Background: Noninvasive pressure support ventilation (NPSV) demands triggering with each breath. This study investigates the effects of NPSV via face mask on breathing pattern, ventilation and respiratory muscle loading in patients with hypercapnic stable COPD., Methods: 7 patients (age 66 +/- 9 years; FEV1 43 +/- 13% predicted; PaO2 52 +/- 19 mmHg; PaCO2 58 +/- 12 mmHg) were included. The physiologic variables were evaluated during spontaneous breathing and at the end of a 60 minutes period with NPSV. Inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) were adjusted to 12-14 cm H2O and 3 cm H2O, respectively. Respiratory muscle activity was measured as esophageal and transdiaphragmatic pressure time product (PTPes and PTPdi)., Results: Non-triggering was observed only occasionally. Compared to unsupported spontaneous breathing NPSV improved ventilation: PaCO2 was reduced from 58 +/- 11 mmHg to 50 +/- 14 mmHg (p +/- 0.05). Respiratory muscles were unloaded by 30% (p +/- 0.05). Breathing frequency and breathing pattern did not change., Conclusions: In patients with hypercapnic stable COPD NPSV effectively recognizes and supports breathing efforts. As a result ventilation is improved and respiratory muscles are unloaded.

An 'enriched polymerase chain reaction (PCR)' protocol has been established for the sensitive detection of oncogene mutations in body fluid samples from cancer patients. This two-step protocol combines an allele-specific PCR clamping step followed by a PCR-RFLP (restriction fragment length polymorphism) confirmatory step. The method thus resembles a nested PCR technique starting directly from genomic DNA material and, in no more than 54 PCR cycles, allows the sensitive detection of one mutant allele in 10(3) normal alleles. This protocol was tested on bronchial cytology samples and sputum taken from lung cancer patients and point mutations could be detected both in codon 12 of K-ras and in three codons (248, 249, and 273) of the p53 gene. Comparing this protocol with a different 'enriched PCR' method based on repetitive PCR-RFLP steps, a high concordance was noted between the two methods. Although the present protocol seems to be less sensitive by approximately one order of magnitude, it is much easier to perform and thus could be applied to the rapid but sensitive detection of allelic subfractions in a population of cells derived from exfoliative material., (Copyright 2000 John Wiley & Sons, Ltd.)

RFLP-mediated PCR has been successfully applied as a reliable tool in the detection of ras mutations in many cancers and provides a basis for "mutant-enriched PCR" protocols. We have, therefore, modified this technique to the sensitive detection of K-ras codon 12 and also p53 "hot spot" mutations, which, frequently in lung cancer, affect codons at the positions 157, 175, 245, 248, 249, and 273. With a high sensitivity of 1 mutant allele in 10(4) normal alleles, our enrichment assay allows the detection of oncogene alleles when only a few tumor cells are present within a normal cell population. Brush cytology material obtained from the tumor site of 20 patients with endoscopically apparent bronchial carcinoma was compared to macroscopically normal mucosa taken from the contralateral bronchus ("control" cytology). We found K-ras codon 12 mutations in 5 cases (25%) and p53 mutations in 13 cases (65%) in the tumor-derived cell material but, with the exception of two cases, not in cell material taken from the control cytology. Seventy-five % of the samples analyzed showed that at least one of the two oncogenes was affected. In several cases, two p53 lesions were detected concomitantly. The majority of the mutations could be reconfirmed by an alternative approach exploiting changes in the genomic RFLP pattern induced by these mutations and were also demonstrated in separate diagnostic biopsies taken. Thus, we conclude that the established enriched PCR protocol ensures a high sensitivity and preserved specificity for the diagnosis of oncogene lesions associated with lung cancer. Because conventional techniques normally yield a lower incidence of corresponding ras and p53 mutations, we think that both the high rate and the heterogeneity of p53 mutations found in some cases are, indeed, related to the increased sensitivity of this new enriched PCR technique.

Objective: To study the influence of obstructive sleep apnea (OSA) on 24-h BP., Setting: Sleep laboratory of the Medical Department, Neukölln Hospital, Berlin, Germany., Methods: In 93 subjects, noninvasive 24-h BP monitoring was performed with BP recordings made at 15-min intervals. Apnea severity was evaluated by means of a portable device that allows calculation of an oxygen desaturation index (ODI). A normal 24-h BP profile (dipping) was defined by a night/day BP ratio of 0.9., Results: ODI was related to systolic and diastolic daytime (p<0.001) and nighttime BP (p<0.001) as well as systolic and diastolic BP night/day ratios (p<0.001). Multiple regression analysis showed that age and ODI were independently related to daytime BP. When subjects were grouped according to apnea severity, daytime BP increased as ODI increased: 127/80+/-10/11 mm Hg in habitual snorers (ODI 0 to 5), 135/87+/-15/9 mm Hg in mild OSA (ODI 6 to 30), and 140/90+/-13/10 mm Hg in severe OSA (ODI >30) (p values <0.05 for comparisons of OSA groups with habitual snorers). Compared to subjects with mild OSA or habitual snorers, BP night/day ratios were greater in patients with severe OSA (p values <0.05). Accordingly, hypertension and nondipping increased as ODI increased., Conclusion: OSA is associated with hypertension independent of the confounding factors of age and obesity. Nondipping is related to apnea severity. These alterations might contribute to the increased mortality in patients with severe OSA.

Background: Noninvasive ventilation with nose- or face-masks has been increasingly used in the past. The objective of mechanical ventilation is in addition to improve gas exchange to reduce breathing work. While improvement on breathing work has been shown mainly on normal-weight patients with different respiratory diseases, there is no existing data about the effect of noninvasive ventilation on the breathing work of patients with massive obesity., Patients and Methods: Assisted mask-ventilation with bilevel positive airway pressure (BiPAP) was carried out on 5 overweight control subjects (overweight controls), 7 overweight patients with obstructive sleep apnea (OSA), 6 patients with obesitas-hypoventilation syndrome (OHS), and 7 overweight patients with chronic obstructive lung disease (COLD). Inspiratory pressure assist (IPAP) was set to 12 or 16 cm H2O, exspiratory pressure (EPAP) was set to 5 cm H2O. All, subjects were massive overweight (body mass index [BMI] 42.2 +/- 5.8; range 31.8 to 55.4 kg/m2). Respiratory muscle activity was measured as esophageal pressure change (delta Pes) and transdiaphragmatic pressure change (delta Pdi) and calculated as pressure time integral., Results: With noninvasive ventilation respiratory muscle activity was significantly (p < 0.05) reduced in all groups at least 40% compared to baseline values during spontaneous respiration., Conclusions: Noninvasive ventilation via face masks can efficiently reduce work of breathing in subjects with massive obesity.

Background: The aim of the present study was to evaluate if Proportional Assist Ventilation (PAV), when applied noninvasively via face mask, can reduce ventilatory effort in patients with respiratory failure. We present preliminary results of an ongoing study., Patients and Methods: In 5 patients with respiratory failure due to different underlying disorders (pulmonary fibrosis, bilateral diaphragm paralysis, COPD) we compared the transdiaphragmal pressure-time integral. PTdi (integral off Pdi dt) after 15 minutes of noninvasive PAV to the baseline values without ventilatory support., Results and Conclusion: Four patients showed reduction of PTdi to various extend. One patient who presented low diaphragmal activity at baseline due to diaphragmal paralysis showed a slight increase in PTdi during ventilation. Mean PTdi decreased by 26.7%. PaCO2 in the 5 patients showed no significant change after 15 minutes of ventilation, thus indicating that with noninvasive PAV patients can maintain constant ventilation with reduced effort.

History and Clinical Findings: Two weeks after returning from a trip to Thailand a 79-year-old man developed a higher fever, pain in the right flank and progressive clouding of consciousness. She had meningism on admission., Investigations: There was a marked leukocytosis (WBC count 17,700/microliter) and raised C-reactive protein (6.5 mg/dl). Cerebrospinal fluid was clear, containing 119 cells/mm3 and elevated protein (90 mg/dl). Abdominal sonography demonstrated segmental pyelonephritis, and blood culture grew Pseudomonas pseudomallei., Treatment and Course: On the basis of sensitivity tests imipenem was chosen as the antibiotic and was given for 6 weeks. Because of an inadequate response and a right renal abscess a right nephrectomy was performed. After marked improvement the septicaemia recurred one week after antibiotic treatment had been discontinued, and the patient died., Conclusion: Efficacious treatment of melioidosis (a glanders-like disease) presupposes diagnosis of the causative microorganism and testing of its antibiotic sensitivity. As Pseud. pseudomallei may encapsulate and persist intracellularly, the selection of antibiotic and the duration of treatment are crucial.

We completed polysomnography and complementary measurement of the oesophageal pressure and airflow in 6 subjects (2 volunteers, 4 patients with sleep-related breathing disorder). The evaluation of the physiological parameters of the breathing over the whole night showed a strong correlation between the pressure-time product and the work of breathing. Our results revealed distinct differences between the parameters of the breathing mechanics in volunteers versus in patients. The continuous long-term analysis of respiration during sleep may contribute to reveal further pathological mechanisms of the respiratory system.

We studied 24-h blood pressure (BP) in 17 hypertensive patients with polysomnographic verified moderate to severe obstructive sleep apnea (OSA) before, after 1-3 days and after 4-6 months of treatment with nasal continuous positive airway pressure (nCPAP). BP was recorded using an ambulatory blood pressure monitoring (ABPM) device with oscillometric measurement method (SpaceLabs 90207) over a period of 24 h with intervals of 15 min in daytime and nighttime. Hypertension was defined as mean BP in the daytime period > 135/85 mm Hg; OSA was diagnosed when a full night polysomnography indicated an apnea hypopnea index (AHI) > 10/h. Hypertensive systolic/diastolic daytime BP values decreased significantly from 144.8/94.4 mm Hg at baseline to 138.9/89.4 mm Hg after short-term, and to 136.4/86.9 mm Hg after long-term nCPAP-therapy. Nighttime BP values, too, were reduced significantly from 137.6/87.1 mm Hg at baseline to 129.9/82.3 mm Hg after short-term, and to 128.6/ 79.8 mm Hg after long-term therapy. In addition to these data the heart rate fell significantly from 82.5 b/min to 74.8 b/min after 4-6 months in daytime, and from 70.9 b/min to 63.6 b/min in nighttime. The beneficial effect on diurnal and nocturnal hypertension in patients with nCPAP-therapy of OSA suggests a causal relationship between systemic hypertension and obstructive sleep apnea.

Investigations were carried out to test the efficacy of a two dose treatment with ivermectin or doramectin on reactivated larvae of Toxocara canis in bitches to prevent prenatal and galactogenic infections of their pups. Thirty pregnant bitches were treated by subcutaneous injection of ivermectin or doramectin on day 40 and 50 post conception (p.c.) each with a dose of 1 mg/kg body weight. The efficacy of the treatments was determined by faecal examinations and by comparing the number of infected pups and the onset of patency in each group of pups. 1. Patient infections with T. canis were seen in pups from untreated bitches from day 21 after birth and all pups were coproscopically positive one week later. To prevent severe clinical symptoms all pups in this group were treated with anthelmintics on day 42 after birth. 2. Pups from ivermectin treated bitches occasionally exhibited patent infections from day 28 after birth onwards; pups from doramectin group exhibited infections from day 56 after birth. The number of patently infected pups in both groups increased till 70 days after birth, probably because of postnatal infections. 3. 28 days after parturition, T. canis infections became patent in all untreated bitches. Single bitches in the ivermectin and doramectin groups developed patent infections after day 49 after parturition. All coproscopically positive bitches had patently infected pups in their litters. 4. The contamination of the environment with eggs of T. canis was calculated from the results of the faecal examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate the influence of cigarette smoking on alveolar macrophages (AM) we compared morphologic and immunocytochemic characteristics of bronchoalveolar lavage cells collected from 10 smokers and 8 nonsmokers. AM were studied using single cell fluorescence photometry. AM of smokers were larger in size (p < 0.001), showed stronger autofluorescence (p < 0.001), and expressed fewer HLA-DR antigens (p < 0.001) compared with AM of nonsmokers. AM of smokers were more heterogeneous in respect to cell size, autofluorescence, and HLA-DR antigen expression. HLA-DR antigen density on AM of smokers was independent of cell size and autofluorescence. This suggests that tobacco smoke reduces HLA-DR antigen expression in AM of different maturational states and that this defective expression of HLA class II antigens is not dependent on the amount of phagocytosed autofluorescent tobacco particles.

Radiological investigation of the vertebral column in two patients with low-back pain (53-year-old woman and a 52-year-old man) revealed unusually marked osteoporosis and sintering fractures of the 3rd, and 1st and 4th lumbar vertebrae, respectively. Biochemical tests failed to provide any evidence about metabolic or endocrinological abnormality. Iliac crest biopsy showed mastocytosis. There were no skin changes in either patient. Additional examinations excluded involvement of any internal organs. Despite treatment with calcium, sodium fluoride, vitamin D3 and calcitonin in the woman, and aspirin and chromoglycinic acid in the man the osteoporosis has slowly progressed during the last 7 and 5 years, but the disease has remained limited to the skeletal system. In a case of unusually marked osteoporosis, mastocytosis should be included in the differential diagnosis even in the absence of urticaria pigmentosa.

The pathogenesis of obesity hypoventilation is incompletely understood. We investigated 505 patients with sleep apnoea in respect of determinants that correlate with chronic hypercapnia. 14 patients (2.8 per cent) exhibited daytime hypercapnia (PCO2 greater than or equal to 45 mmHg). Compared with the entire group of patients, these patients showed heavier overweight (p less than 0.001) and their nightly respiratory dysregulation defined by the apnoea index was more severe (p less than 0.001). If these patients were compared with 14 normocapnic controls matched for apnoea index, weight and age, there was no difference in respect of lung function data. We conclude that overweight and the severity of sleep apnoea are determinants that predispose to chronic alveolar hypoventilation.

The expression of HLA class II genes is essential to the antigen-presenting function of monocytes and macrophages. With a new cytofluorometric method of single-cell analysis we investigated the density of HLA-DR antigen expression on alveolar macrophages (AM) of smokers. Although all AM of nonsmokers (100 +/- 1%) expressed HLA-DR antigens, only 79 +/- 12% of AM from smokers showed positive findings (p less than 0.001). Furthermore, the antigen density of those cells expressing this antigen was significantly reduced in smokers (p less than 0.001). The defective expression of class II genes on AM of smokers might contribute to the impaired antigen-presenting function found by some previous investigators.

Hypertrophic pulmonary osteoarthropathy (HPO) is characterised by clubbed, or drumstick, fingers and a painful periostitis of the extremities, and occurs most frequently as paraneoplastic symptom in association with bronchial carcinoma. Much rarer are inflammatory pulmonary changes such as lung abscesses. Curative treatment of the underlying disease will always also alleviate the pain in the extremities. This article reports on a case of a bronchial carcinoma masked by a pulmonary abscess. Despite the treatment of the abscess the patient developed the typical pattern of signs and symptoms of hypertrophic pulmonary osteoarthropathy for the bronchial carcinoma which was identified only later and which had been masked by the abscess. Persistence of hypertrophic pulmonary osteoarthropathy in case of a successfully treated pulmonary abscess should, therefore, always be regarded as a possible pointer towards an undetected bronchial carcinoma.

An immunofluorescence method for assaying membrane-bound antigens on individual alveolar macrophages (AM) collected by bronchoalveolar lavage (BAL) is described. Cells were labelled with FITC-conjugated anti-HLA-DR antibodies in a single (direct) step. Quantification of the fluorescence was performed by computer-assisted cytophotometry. Alveolar macrophages, especially when obtained from cigarette smokers, exhibited an autofluorescence which interfered with the measurement of specific fluorescence. The specific fluorescence was calculated by determination of total fluorescence in the wave-length optimal for FITC and the non-specific fluorescence in a different wavelength during a second measurement. Specificity and reproducibility testing confirmed the reliability of the method.

The quantitation of cell surface antigens on alveolar macrophages (AM) using flow-cytometry is complicated by strong autofluorescence and wide variation of cell- size and autofluorescence. Therefore a microscope-fluorometric method was developed which allows simultaneous assessment of fluorescence of fluorochrome-labelled monoclonal antibodies and size in individual cells. Autofluorescence of smokers AM was found to be variable and considerably stronger than autofluorescence of nonsmokers AM. By means of a multi step determination of autofluorescence and specific fluorescence using different filter combinations of the microscope fluorometer density of membrane bound HLADR-antigens could be efficiently determined also in strongly autofluorescent smoker AM.

At the a two-year apprenticeship, a young female hairdresser developed rhinoconjunctivitis and bronchial asthma, induced by a hair bleach containing the substance persulphate. On each occasion, her symptoms occurred in the form of an immediate reaction. The causative role of the bleach was demonstrated with the aid of an inhalation challenge test. In addition, the prick test produced a positive reaction vis-a-vis persulphate. The long latency period and the positive prick test might militate in favour of an allergic pathomechanism.

Salivary glands of various stages of the last larval instar of Chironomus tentans were quantitatively analyzed with respect to the expansion of their Balbiani rings (B1, B2, B3) by a fast green staining procedure as well as to the rate of synthesis of their secretory proteins (S1, S2, S3) by a scintillation counting procedure of electrophoretic fractions. The extent of expansion of B1, B2 and B3 correlates positively with the rate of synthesis of S3, S2 and S1, respectively. With B1 and S3 these parameters undergo a parallel and developmentally specific change being rather depressed in intermolt, and particularly in diapausing animals.