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Biomedical subjects

W Pankow

Publications and source records attributed to W Pankow.

At least 19 recordsLinked to original sources

Influence of proportional assist ventilation on diaphragmatic activity in normal subjects.

In six awake healthy adults we studied the physiological effects of mechanical unloading of the respiratory muscles during increased ventilatory demand. We were interested in whether respiratory muscle activity is down regulated and if this is mainly a consequence of chemical factors, i.e. CO2-reduction, or non-chemical neuromuscular inhibition. With 33 mmHg inspiratory CO2 we induced modest hyperpnea of 24.4 +/- 3.9 L/min. Proportional assist ventilation (PAV) was applied with flow-related assist of 2.5 cm H2O/L/s and volume-related assist of 6 cm H2O/L. Respiratory muscle activity was measured by transdiaphragmatic pressure. Unloading caused a 57 percent reduction of the inspiratory transdiaphragmatic pressure-time product (p<0.05), while tidal volume, breathing frequency, and breathing pattern did not significantly change. These observations suggest that during increased ventilatory requirements, PAV results in down regulation of respiratory muscle activity and that this effect is mainly a consequence of neuromechanical inhibition.

Adult↗

[Patient-ventilator interaction during noninvasive pressure supported spontaneous respiration in patients with hypercapnic COPD].

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.

Aged↗

Differential frequencies of p16(INK4a) promoter hypermethylation, p53 mutation, and K-ras mutation in exfoliative material mark the development of lung cancer in symptomatic chronic smokers.

PURPOSE: The aim of this study was to investigate the frequency of three (epi)genetic alterations (p53 and K-ras mutations and p16(INK4a) promoter hypermethylation) in symptomatic chronic smokers compared with patients with lung cancer and to evaluate the use of exfoliative material for such analyses. PATIENTS AND METHODS: Fifty-one patients with histologically confirmed lung cancer and 25 chronic smokers (> 20 pack-years) were investigated for mutations in the K-ras (codon 12) and p53 (codons 248, 249, and 273) genes and for allelic hypermethylation of the p16(INK4a) gene. DNA was isolated from sputum and bilateral bronchial lavage, and brushings were taken at bronchoscopy. RESULTS: Forty-one genetic lesions were detected within exfoliative material from the group of 51 patients with lung cancer and 10 lesions in the chronic smoker group. K-ras mutations occurred exclusively in the lung cancer group, whereas p53 mutations and p16(INK4a) promoter hypermethylation were also found in chronic smokers. Three of eight chronic smokers who harbored an (epi)genetic alteration were subsequently diagnosed with lung cancer. Analysis of sputum yielded information equivalent to that of samples obtained during bronchoscopy. CONCLUSION: p16(INK4a) promoter hypermethylation and p53 mutations can occur in chronic smokers before any clinical evidence of neoplasia and may be indicative of an increased risk of developing lung cancer or of early disease. K-ras mutations occur exclusively in the presence of clinically detectable neoplastic transformation. Molecular analysis of sputum for such markers may provide an effective means of screening chronic smokers to enable earlier detection and therapeutic intervention of lung cancer.

Aged↗

Facilitated detection of oncogene mutations from exfoliated tissue material by a PNA-mediated 'enriched PCR' protocol.

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.

Bronchoalveolar Lavage Fluid↗

Arousal in patients with gastro-oesophageal reflux and sleep apnoea.

Nocturnal gastro-oesophageal reflux has been observed in patients with obstructive sleep apnoea (OSA). Negative intrathoracic pressure during apnoeas and arousal have been suggested as the underlying mechanisms. In order to evaluate this hypothesis, the coincidence and sequence in time of arousal, apnoea and reflux events were analysed. Fifteen patients with OSA or heavy snoring were studied by means of standard polysomnograpy with parallel recording of 24-h oesophageal pH. Reflux events during the day were present in all patients, five of whom had symptoms of reflux. In three of these and in five other patients, a total of 69 nocturnal reflux events were found. In 68 events, arousal was found with the reflux event. Only one reflux without arousal was found (sleep stage 2). Seventeen events occurred during wakefulness after sleep onset. The percentage of time with a pH of <4 during wakefulness after sleep onset was significantly higher than the percentage of time with a pH of <4 during total sleep time (p<0.05). In 37 of the 52 reflux events which occurred during sleep, either an apnoea or a hypopnoea was found prior to the event. The investigation of sequence in time did not prove a causal relation between respiratory events and reflux events. The results indicate that gastro-oesophageal reflux and obstructive sleep apnoea are two separate disorders, which both have a high prevalence in obese patients.

Adult↗

Expiratory flow limitation and intrinsic positive end-expiratory pressure in obesity.

Breathing at very low lung volumes might be affected by decreased expiratory airflow and air trapping. Our purpose was to detect expiratory flow limitation (EFL) and, as a consequence, intrinsic positive end-expiratory pressure (PEEPi) in grossly obese subjects (OS). Eight OS with a mean body mass index (BMI) of 44 +/- 5 kg/m2 and six age-matched normal-weight control subjects (CS) were studied in different body positions. Negative expiratory pressure (NEP) was used to determine EFL. In contrast to CS, EFL was found in two of eight OS in the upright position and in seven of eight OS in the supine position. Dynamic PEEPi and mean transdiaphragmatic pressure (mean Pdi) were measured in all six CS and in six of eight OS. In OS, PEEPi increased from 0.14 +/- 0.06 (SD) kPa in the upright position to 0.41 +/- 0.11 kPa in the supine position (P < 0.05) and decreased to 0.20 +/- 0.08 kPa in the right lateral position (P < 0.05, compared with supine), whereas, in CS, PEEPi was significantly smaller (<0.05 kPa) in each position. In OS, mean Pdi in each position was significantly larger compared with CS. Mean Pdi increased from 1.02 +/- 0.32 kPa in the upright position to 1.26 +/- 0.17 kPa in the supine position (not significant) and decreased to 1. 06 +/- 0.26 kPa in the right lateral position (P < 0.05, compared with supine), whereas there were no significant changes in CS. We conclude that in OS 1) tidal breathing can be affected by EFL and PEEPi; 2) EFL and PEEPi are promoted by the supine posture; and 3) the increased diaphragmatic load in the supine position is, in part, related to PEEPi.

Adult↗

Heart block in patients with obstructive sleep apnoea: pathogenetic factors and effects of treatment.

Heart block during sleep has been described in up to 10% of patients with obstructive sleep apnoea. The aim of this study was to determine the relationship between sleep stage, oxygen desaturation and apnoea-associated bradyarrhythmias as well as the effect of nasal continuous positive airway pressure (nCPAP)/nasal bi-level positive airway pressure (nBiPAP) therapy on these arrhythmias in patients without electrophysiological abnormalities. Sixteen patients (14 males and two females, mean age 49.6+/-10.4 yrs) with sleep apnoea and nocturnal heart block underwent polysomnography after exclusion of electrophysiological abnormalities of the sinus node function and atrioventricular (AV) conduction system by invasive electrophysiological evaluation. During sleep, 651 episodes of heart block were recorded, 572 (87.9%) occurred during rapid eye movement (REM) sleep and 79 (12.1%) during nonrapid eye movement (NREM) sleep stages 1 and 2. During REM sleep, the frequency of heart block was significantly higher than during NREM sleep: 0.69+/-0.99 versus 0.02+/-0.04 episodes of heart block x min(-1) of the respective sleep stage (p<0.001). During apnoeas or hypopnoeas, 609 bradyarrhythmias (93.5%) occurred with a desaturation of at least 4%. With nCPAP/ nBiPAP therapy, apnoea/hypopnoea index (AHI) decreased from 75.5+/-39.6 x h(-1) to 3.0+/-6.6 x h(-1) (p<0.01) and the number of arrhythmias from 651 to 72 (p<0.01). We conclude that: 1) 87.9% of apnoea-associated bradyarrhythmias occur during rapid eye movement sleep; 2) the vast majority of heart block episodes occur during a desaturation of at least 4% without a previously described threshold value of 72%; and 3) nasal continuous positive airway pressure or nasal bi-level positive airway pressure is the therapy of choice in patients with apnoea-associated bradyarrhythmias.

Adult↗

Frequent detection of ras and p53 mutations in brush cytology samples from lung cancer patients by a restriction fragment length polymorphism-based "enriched PCR" technique.

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.

Aged↗

Influence of sleep apnea on 24-hour blood pressure.

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.

Blood Pressure↗

[Effect of noninvasive ventilation on work of breathing in obesity].

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.

Adult↗

[Work of breathing in noninvasive proportional assist ventilation in patients with respiratory insufficiency].

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.

Aged↗

[An acute septic course of melioidosis after a stay in Thailand].

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.

Abscess↗

Influence of noninvasive positive pressure ventilation on inspiratory muscle activity in obese subjects.

Noninvasive positive pressure ventilation (NPPV) can improve ventilation in obese subjects during the postoperative period after abdominal surgery. Compared to nasal continuous positive airway pressure (nCPAP), NPPV was superior in correcting blood gas abnormalities both during the night-time and during the daytime in a subgroup of patients with the obesity hypoventilation syndrome (OHS). However, as it is unknown, if and to what extent NPPV can unload the respiratory muscles in the face of the increased impedance of the respiratory system in obesity, this is what was investigated. Eighteen obese subjects with a body mass index > or = 40 kg x m(-2) were investigated during the daytime, which included five healthy controls (simple obesity (SO)), seven patients with obstructive sleep apnoea (OSA) and six patients with the obesity hypoventilation syndrome (OHS). Assisted PPV was performed with bi-level positive airway pressure (BiPAP), applied via a face mask. Inspiratory positive airway pressure (IPAP) was set to 1.2 or 1.6 kPa and expiratory positive airway pressure (EPAP) was set to 0.5 kPa. Inspiratory muscle activity was measured as diaphragmatic pressure time product (PTPdi). Comparison of spontaneous breathing with BiPAP ventilation showed no significant difference in breathing pattern, although there was a tendency towards an increase in tidal volume (VT) in all three groups and a decrease in respiratory frequency (fR) in patients with OSA and OHS. End-tidal carbon dioxide (PET,CO2) with BiPAP was unchanged in SO and OSA, but was decreased in OHS. In contrast, inspiratory muscle activity was reduced by at least 40% in each group. This was indicated by a decrease in PTPdi with BiPAP 1.2/0.5 kPa from mean+/-SD 39+/-5 to 20+/-9 kPa x s (p<0.05) in SO, from 42+/-7 to 21+/-8 kPa x s (p<0.05) in OSA, and from 64+/-20 to 38+/-17 kPa x s (p<0.05) in OHS. With BiPAP 1.6/0.5 kPa, PTPdi was further reduced to 17+/-6 kPa x s in SO, and to 17+/-6 kPa x s in OSA, but not in OHS (40+/-22 kPa x s). We conclude that noninvasive assisted ventilation unloads the inspiratory muscles in patients with gross obesity.

Adult↗

Hypertension and obstructive sleep apnea. Ambulatory blood pressure monitoring before and with nCPAP-therapy.

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.

Adult↗

[Long-term analysis of respiration in sleep].

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.

Adult↗