CASE-REPORT Dysregulation of gene expression in a patient with depressive disorder after transient ischemic attack confirmed by a neurophysiological neuromarker.

The aim of this study was to evaluate dysregulation of gene expression associated with the cellular stress response in a patient with a post-"warning stroke" depressive disorder confirmed by the presence of a neurophysiological neuromarker through the use of quantitative EEG and event-related potentials. The patient was tested for seven genes associated with the stress reaction: HSPA1A, HSPB1, IL6, IL10, CRP, and HSF-1 along with NF-κB, compared to gene expression in health controls. A 54-year-old patient with a past history of schizophrenia (at the age of 20), and of transient ischemic attack (at the age of 53) and depressive disorder confirmed by functional, cognitive, emotional, and affectional diagnostics underwent additional testing for expression of the genes associated with stress response. The expression of genes coding for heat shock protein (HSPA1A, HSPB1), interleukins (IL6, IL10), and C-reactive protein was tested along with factors that regulate their expression. The results of the tests conducted on this patient were compared with 42 healthy control subjects. Diagnostic testing revealed upregulation in expression of these genes, presenting as increased expression of the target genes and of the regulatory genes. A post-"warning stroke" depressive disorder appears to be associated with overexpression of the genes coding for HSP and interleukins. Further research on larger groups of people may provide grounds for treatment modification.

[Respiratory response to inspiratory resistive load changes in patients with obstructive sleep apnea syndrome]. / Odpowiedz oddechowa na zmiane oporu wdechowego u chorych na obturacyjny bezdech senny.

Patients with OSA have many episodes of increased airway resistance because of repeated collapses of upper airways during night. The aim of this work was to evaluate respiratory response during chemical stimulation without and with added inspiratory resistive load (10 cmH2O/L/sec). The studies were performed during quiet breathing with air and during hypercapnic and hypoxic rebreathing tests without and with inspiratory resistive loading in 23 obese (BMI = 34.4 +/- 4.3 kg/m2) patients with OSA and in 10 healthy subjects with similar weight (BMI = 32.4 +/- 4.3 kg/m2). The measurements of respiratory responses (ventilation, mouth occlusion pressure) were performed with the use of computerized equipment. During quiet breathing in response to added load an increase of P0.1 in controls and in OSA patients was observed. During hypercapnic stimulation the ventilatory response with additional load decreased in patients as well as in controls. The slope of mouth occlusion pressure response increased significantly in controls (from 4.40 to 6.83 cmH2O/kPa, p < 0.001) and slightly weaker in OSA patients (from 4.21 to 5.43 cmH2O/kPa, p < 0.05). Although the difference between the slopes was not significant, we found that the absolute increase of P0.1 measured at point 8 kPa of PEtCO2 during loaded breathing was significantly smaller in OSA patients in comparison to controls. (2.1 vs. 10.3 cm H2O; p < 0.001). During hypoxic stimulation occlusion pressure responses were similar in both examined groups. In conclusion we postulate that OSA patients have impaired respiratory compensation of additional inspiratory load, what was demonstrated during hypercapnic rebreathing test.

Respiratory responses to chemical stimulation in patients with obstructive sleep apnoea.

Chemical control of breathing in obstructive sleep apnoea (OSA) patients has been studied by many authors. The results of previous studies, especially those dealing with hypoxic drive, are discordant. Respiratory responses were studied during hypercapnic and hypoxic stimulation in a group of 37 normocapnic patients with OSA during wakefulness. The diagnosis of OSA was established by standard polysomnography. These patients had increased apnoea/hypopnoea index (AHI; 51 +/- 22 (mean +/- SD)), obesity (body mass index (BMI) 32.4 +/- 5.6 kg.m-2) and normal lung function tests. The control group consisted of 14 healthy obese subjects (BMI 31.2 +/- 3.3 kg.m-2). Respiratory responses (ventilatory and mouth occlusion pressure (P0.1)) during hypercapnic and hypoxic rebreathing tests were measured with the use of computerized equipment. Respiratory responses during hypercapnic stimulation were similar to those in the control group (change in (delta) minute ventilation (V'E)/delta carbon dioxide tension (PCO2) 23.5 +/- 14.8 versus 22.3 +/- 10.0 L.min-1.kPa-1, delta P0.1/delta PCO2 4.6 +/- 3.6 versus 4.2 +/- 2.6 cmH2O.kPa-1). During isocapnic hypoxic stimulation in OSA patients the mean ventilatory response was higher than in the control group (delta V'E/delta arterial oxygen saturation (Sa,O2) 2.6 +/- 1.7 versus 1.7 +/- 0.7 L.min-1.%-1) but this difference was not statistically significant. Nevertheless, it was found that 13 (35%) OSA patients had increased ventilatory responses. The mean P0.1 response in OSA patients was higher but did not differ significantly from those in the control group (delta P0.1/delta Sa,O2) 0.43 +/- 0.38 versus 0.35 +/- 0.12 cmH2O.%-1). The results demonstrated that respiratory responses to chemical stimulation in awake normocapnic patients with obstructive sleep apnoea were in the normal range, similar to those in control obese subjects. During hypoxic stimulation some of them had increased ventilatory (35%) and mouth occlusion pressure (16%) responses.

[Chemical control of breathing in patients with obstructive sleep apnea]. / Chemiczna regulacja oddychania u chorych na obturacyjny bezdech senny.

The authors have studied chemical control of breathing in 37 normocapnic patients with OSA. These patients had increased apnea-hypopnea index (AHI = 51 +/- 22), obesity (BMI = 32.4 +/- 5.6 kg/m2) and normal lung function tests. Control group consisted of 20 healthy subjects with normal weight (BMI = 23.1 +/- 2.4 kg/m2). Respiratory responses (ventilatory and P0.1) to hypercapnic and hypoxic stimulation during rebreathing tests were measured with computerized methods. The obtained results in OSA patients were compared with the data of the control group. The results exceeding mean values of the control group above 1.64 SD were recognized as hyperreactive responses. The majority e.g. 26 patients (OSA-N) had normal respiratory responses during hypercapnic stimulation. delta V/delta PCO2 = 16.8 +/- 4.5 L/min/kPa, P0.1/delta PCO2 = 3.5 +/- 2.4 cm H2O/kPa/. In remaining 11 patients (OSA-H) respiratory responses were significantly increased delta V/delta PCO2 = 39.1 +/- 18.8 L/min/kPa, P0.1/delta PCO2 = 8.6 +/- 3.9 cm H20/kPa). During isocapnic hypoxic stimulation majority e.g. 25 patients (OSA-H) had significantly increased respiratory responses delta V/delta SaO2 = 3.28 +/- 1.63 L/min/%, delta P0.1/delta SaO2 = 0.54 +/- 0.43 cm H2O/%/. In remaining 12 patients (OSA-N) respiratory responses were within normal limits delta V/SaO2 = 1.2 +/- 0.28 L/min/%, delta P0.1/ delta SaO2 = 0.21 +/- 0.07 cm H2O/%/. The above results indicated, that majority OSA patients (67.5%) had increased ventilatory and P0.1 responses to hypoxic stimulation. Among them also 11 patients had increased respiratory responses to hypercapnia. It seems, that increased respiratory responses to hypoxic stimulus in OSA patients are symptoms of protective reaction to hypoxaemia occurring during repetitive sleep apnoea and reveals increased neuro-muscular output.

[Pattern of breathing and obstruction pressure in patients with airway obstruction after inhalation of bronchodilators]. / Wzorzec oddychania i cisnienie okluzji u chorych z obturacja dróg oddechowych po inhalacji leku rozszerzajacego oskrzela.

The neuromuscular drive is increased in patients with an airway obstruction. The aim of the study was to estimate an influence of beta-agonist on breathing pattern and mouth occlusion pressure (P0.1) in patients with reversible and nonreversible airway obstruction. Ventilatory function tests, pattern of breathing analysis, mouth occlusion pressure (P0.1) and inspiratory impedance (P0.1/Vt/Ti) were measured in 23 obstructive patients and 20 healthy subjects. In all patients these measurements were repeated 20 minutes after bronchodilator inhalation (0.2 mg fenoterol). During quiet room-air breathing in patients we observed increased Vt, Vt/Ti comparing with healthy persons. The time of inspiration (Ti) and total time (Ttot) were shortened in comparison to our control group. P0.1 and inspiratory impedance were significantly increased (P0.1 3.6 +/- 1.6 vs 1.6 +/- 0.3 cm H2O, p < 0.01 and P0.1/Vt/Ti 6.6 +/- 2.3 vs 3.8 +/- 1.0 cm H2O/L/s). Measurements performed after bronchodilator inhalation revealed decrease of P0.1 and P0.1/Vt/ Ti in patients responsive to beta-agonist (delta FEVI > 15%). In unresponsive patients (delta FEVI < or = 15%) such decrease in neuromuscular respiratory drive was not observed. We conclude that diminishing of increased neuromuscular respiratory drive in patients with reversible obstruction is a consequence of airway resistance decreasing. It seems to be an additional, advantageous for a patient, effect of bronchodilator inhalation.