Exercise tolerance in obstructive sleep apnea-hypopnea (OSAH), before and after CPAP treatment: Effects of autonomic dysfunction improvement.

BACKGROUND: Obstructive sleep apnea hypopnea (OSAH) is associated with decreased exercise tolerance and autonomic abnormalities and represents a risk for cardiovascular diseases. The aim of the study was to evaluate the effects of CPAP on cardiovascular autonomic abnormalities and exercise performance in patients with OSAH without changes in lifestyle and body weight during treatment. METHODS: Twelve overweight subjects with OSAH underwent anthropometric measures, autonomic cardiovascular and incremental symptom-limited cardio-respiratory exercise tests before and after two months of treatment with CPAP. RESULTS: Lower frequency component of power spectrum of heart rate variability (59.5±24.2 msec2 vs 43.2±25.9 msec2; p<0.05) and improvements of maximal workload (99.3±13.5 vs 108.3±16.8%pred.; p<0.05) and peak oxygen consumption (95.3±7.6 vs 105.5±7.9%pred.; p<0.05) were observed in these patients after CPAP, being their BMI unchanged. CONCLUSIONS: CPAP-induced decrease of sympathetic hyperactivity is associated with better tolerance to the effort in OSAH patients that did not change their BMI and lifestyle, suggesting that OSAH limits per se the exercise capacity.

Pituitary apoplexy after laparoscopic surgery: a case report.

The occurrence of unprobable adverse events during laparoscopic surgery has increased over the years. Among them, pituitary apoplexy has been reported only twice. The increase in the abdominal pressure might play a role in the pituitary apoplexy, as well as hemodynamic instability, anticoagulant drugs and air-embolism due to insufflation of CO2 during pneumoperitoneum. We report a case of pituitary apoplexy during laparoscopic resection of sigmoid colon.

Hyperventilation and seizures in an adolescent female.

A 16 year-old girl was admitted after suffering from recurrent episodes of dyspnea and stridor, cyanosis, loss of contact, stiffening of all four limbs, clenching of the jaw and eye retroversion that lasted for a few seconds to a minute, followed by slow recovery of consciousness without any loss of sphincter control. These symptoms began at the age of 11 and worsened over time. Prolonged rate corrected QT intervals was observed with an ECG. Two cardio-respiratory monitorings were performed (one during daytime hours while the patient was awake, and one at night time while the patient slept). Daytime recordings showed 17 central apnoeas and 97 central hypopneas, with an apnea-hypopnea index (AHI) of 13.2 events/hour, that were associated with severe oxyhemoglobin desaturation. In contrast, night time recordings were normal (AHI=1.1 events/hour). The patient underwent diurnal monitoring of transcutaneous pCO2(PtcCO2), transcutaneous O2(PtcO2), SpO2 and end tidal CO2 (PETCO2), with simultaneous monitoring of regional cerebral oxymetry (rSO2) which showed values of PtcCO2 between 8 and 15 mmHg, suggesting several episodes of marked hyperventilation. Twenty-nine episodes of severe arterial desaturation (SpO2<50%) were registered, all after the same number of apnea events, with ascent of PtcO2 up to 28 mmHg at the end of apnea. During the final phase of apnea, the patient showed cyanosis, contact disturbance, grimaces, oral movements of rhyme, and, on three occasions, partial seizures. A mask was packaged and applied daytime to the face of the patient during episodes of hyperventilation to prevent, together with a psychiatric follow up, rapid falls of PaCO2 levels determining central apnoeas.

Inspiratory capacity predicts mortality in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) severity is usually graded upon the FEV(1) reduction and FEV(1) has been considered the most important mortality predictor with age in COPD. Recent studies suggest other factors as more powerfully related to mortality than FEV(1) in COPD patients. AIM: To assess the impact of inspiratory capacity (IC) on mortality and morbidity in COPD patients during a 5-year follow-up period. METHODS: We recruited 222 patients with mild-to-moderate COPD from January 1995 to December 2001 with an average follow-up period of 60 months (range 30-114 months). Among different respiratory parameters measured in stable conditions FEV(1), FEV(1)/FVC%, IC and PaO(2), PaCO(2) and BMI were chosen and their relationships with all-cause and respiratory mortality and with morbidity were assessed. RESULTS: All these variables were associated with mortality at the univariate analysis. However, in a multivariate regression analysis (Cox proportional hazards model) for all-cause mortality age (year), IC (%pred.) and PaO(2) (mmHg) remained the only significant, independent predictors (HR=1.056, 95%CI: 1.023-1.091; HR=0.981, 95%CI: 0.965-0.998; HR=0.948, 95%CI: 0.919-0.979, respectively). According to the same analysis, IC (%pred.) and PaO(2) (mmHg) were significant independent predictors for respiratory mortality (HR=0.967, 95%CI: 0.938-0.997; HR=0.919, 95%CI: 0.873-0.969) together with FEV(1)/FVC% and BMI (kg/m(2)) (HR=0.967, 95%CI: 0.933-1.022; HR=0.891, 95%CI: 0.807-0.985, respectively). IC (%pred.), FEV(1)/FVC%, and PaO(2) (mmHg) were also significantly related to morbidity, as independent predictors of hospital admissions because of exacerbations (OR=0.980, 95%CI: 0.974-0.992; OR=0.943, 95%CI: 0.922-0.987; OR=0.971, 95%CI: 0.954-0.996, respectively). CONCLUSION: IC (%pred.) is a powerful functional predictor of all-cause and respiratory mortality and of exacerbation-related hospital admissions in COPD patients.

Expiratory flow limitation is associated with orthopnea and reversed by vasodilators and diuretics in left heart failure.

BACKGROUND: In patients with acute left heart failure (LHF), orthopnea has also been related to the occurrence or worsening of expiratory flow limitation (EFL) in the supine position. We wished to assess whether short-term treatment with vasodilators and diuretics was able to abolish supine EFL and whether this could help to control orthopnea in patients with acute LHF. METHODS: In nine nonobese (ie, mean [+/- SD] body mass index, 24 +/- 5 kg/m2), never-smoker patients (two men and seven women; mean age, 77 +/- 7 years) with acute LHF (mean ejection fraction, 43 +/- 15%), we assessed EFL by the negative expiratory pressure method and dyspnea by the Borg scale, with patients in both the seated and supine positions, before and after short-term treatment with vasodilators and diuretics until hospital discharge. Orthopnea was defined as a positive difference in the Borg score between measurements made with the patient in the supine and seated positions. Postural variations in the end-expiratory lung volume were inferred from changes in inspiratory capacity (IC) that were measured under the same circumstances. RESULTS: Before treatment, with the patient in the seated position the mean dyspnea score was 1.5 +/- 0.5, the mean IC was 1.49 +/- 0.38 L, seven patients were non-flow-limited, and two patients were flow-limited. During recumbency, the mean dyspnea score was 2.7 +/- 0.5 (p < 0.01 vs seated position values), the mean IC was 1.66 +/- 0.45 L, and seven patients exhibited EFL. After a mean duration of 17 +/- 8 days of treatment (range, 7 to 28 days), EFL was detected in two patients only in the supine position, IC increased both in the seated position (1.65 +/- 0.34 L; p < 0.01) and the supine position (1.81 +/- 0.41 L; p = 0.07) position, and, although only two patients denied orthopnea, the mean dyspnea score during recumbency actually decreased to 1.9 +/- 1.0 (p < 0.05). CONCLUSIONS: Our results indicate that short-term treatment with vasodilators and diuretics is able to control orthopnea and to remove supine EFL in most patients with acute LHF, suggesting a posture-related increase in bronchial obstruction as the main mechanism of EFL, which appears to play a role in the occurrence and severity of orthopnea in these circumstances.

Volume effect and exertional dyspnoea after bronchodilator in patients with COPD with and without expiratory flow limitation at rest.

BACKGROUND: A study was undertaken to investigate whether bronchodilators are associated with less breathlessness at rest and during light exercise in patients with moderate to severe chronic obstructive pulmonary disease (COPD) with resting tidal expiratory flow limitation (EFL; flow limited (FL)) compared with those without EFL (non-flow limited (NFL)). METHODS: Twenty subjects (13 men) of mean (SD) age 65 (8) years (range 43-77) suffering from COPD with forced expiratory volume in 1 second (FEV(1)) 47 (18)% predicted were studied before and after inhalation of salbutamol (400 microg). Routine pulmonary function tests were performed in the seated position at rest. EFL was assessed by the negative expiratory pressure (NEP) method and changes in end expiratory lung volume (EELV) were inferred from variations in inspiratory capacity (IC). Dyspnoea was measured using the Borg scale at rest and at the end of a 6 minute steady state exercise test at 33% of the maximal predicted workload. RESULTS: EFL occurred in 11 patients. Following salbutamol IC did not change in NFL patients but increased by 24% (95% CI 15 to 33) in FL patients (p<0.001). Maximal inspiratory pressure (PImax) improved at EELV from 45 (95% CI 26 to 63) to 55 (95% CI 31 to 79) cm H(2)O (p<0.05) in FL patients after salbutamol but remained unchanged in NFL patients. The workload performed during exercise amounted to 34 (95% CI 27 to 41) and 31 (95% CI 21 to 40) watts (NS) for patients without and with EFL, respectively. After salbutamol, dyspnoea did not change either at rest or during exercise in the NFL patients, but decreased from 0.3 (95% CI -0.1 to 0.8) to 0.1 (95% CI -0.1 to 0.4) at rest (NS) and from 3.7 (95% CI 1.7 to 5.7) to 2.6 (95% CI 1.1 to 4.0) at the end of exercise (p<0.01) in FL patients. CONCLUSIONS: Patients with COPD with EFL may experience less breathlessness after a bronchodilator, at least during light exercise, than those without EFL. This beneficial effect, which is closely related to an increase in IC at rest, occurs even in the absence of a significant improvement in FEV(1) and is associated with a greater PImax.

Alpha-1-antitrypsin deficiency and nephropathy.

Glomerulonephritis occurring in association with alpha(1)-antitrypsin deficiency has been sporadically reported in the literature but it is assumed to be a rare and poorly investigated disease. The complete pathologic pattern of glomerular lesions has not yet been established. The aim of our work was to investigate the correlation between the extent of antiprotease deficiency and the expression of nephropathy evaluated in two groups of patients (47 heterozygotic subjects with the PiMZ phenotype and 12 homozygotic subjects with the PiZZ phenotype) by a noninvasive approach with urinalyses and proteinuria measurement. No statistical differences between proteinuria in the two groups were observed suggesting that nephropathy is not a direct and single expression of the protein deficiency.

Exhaled nitric oxide in patients with PiZZ phenotype-related alpha1-anti-trypsin deficiency.

There is no report of exhaled NO (eNO) in subjects with different phenotypes of alpha1-anti-trypsin (AAT) deficiency. Exhaled nitric oxide was evaluated by means of single-breath chemiluminescence analysis (fractional exhaled concentration at the plateau level [plFE(NO)]) in 40 patients with AAT deficiency. Patients were divided according to the protease inhibitor (Pi) phenotype: PiMZ/MS, n = 25; PiSZ n = 6; PiZZ, n = 9. Nineteen healthy subjects served as controls. Levels of eNO in PiZZ patients were also compared with those of subjects, without AAT deficiency (PiMM), matched for diagnosis, sex, age, smoking habit and forced expiratory volume in 1 sec (FEV1). In AAT deficiency subjects airway hyper-responsiveness to methacholine (PD20 FEV1) was also assessed. plFE(NO) was significantly lower in the PiZZ group (4.5+/-1.4 ppb) than in matched PiMM subjects (8.2+/-3.8 ppb), in healthy controls (9.3+/-2.8 ppb) and in patients of other phenotypes. Dynamic lung volumes and DL(CO) were significantly lower in PiZZ than in other AAT-deficient patients. Bronchial hyper-responsiveness was not different among AAT phenotypes. These results suggest that eNO may be significantly reduced in PiZZ as compared to healthy control subjects and to AAT subjects with other phenotypes, independent of the level of airway obstruction. Whether, at least potentially, eNO may be considered as an early marker of lung involvement in AAT deficiency must be confirmed with studies on larger number of subjects.

[Hospital discharge report of patients with chronic obstructive pulmonary disease]. / La relazione di dimissione ospedaliera del paziente con broncopneumopatia cronica ostruttiva.

Chronic obstructive pulmonary disease usually doesn't require hospital admission. However, the course of the disease is characterized by frequent exacerbations that often require hospital admission, representing a good chance to define all aspects of chronic obstructive pulmonary disease and improve the management of the patient. When the patient is discharged from the hospital, an essential Report should specify the reasons of admission, the symptoms (e.g.: cough, sputum production and dyspnoea) and the findings of physical examination, the results of the main laboratory and radiological tests performed (pulmonary function tests are essential to define the severity of degree of airway obstruction and useful for its longitudinal assessment), the treatment administered, the final diagnosis, the suggested therapy, the follow-up appointments and the recommendations (nutrition, psychological support, muscle reconditioning) of a possible rehabilitation program.

[Alpha 1-antitrypsin deficiency: the Brescia clinical study]. / Il deficit di alpha 1-antitripsina: lo studio clinico di Brescia.

In a longitudinal clinical study, two hundred subjects have been evaluated in order to identify alpha 1-antitrypsin deficiency patients. According to their serum alpha 1-antitrypsin levels, they have been divided into three groups: 25 patients with severe deficiency (with both pathological alleles--ZZ, SZ or Z and rare deficiency allele--and, if clinically suggested, to be treated with augmentation therapy), 92 patients with intermediate deficiency (with one pathological allele, to be followed up in order to evaluate the risk to develop deficiency related disease) and 63 healthy subjects (normal alleles MM). They performed lung function test (including cardiopulmonary exercise test and methacholine bronchial challenge) chest X-ray and high resolution computed tomography, blood tests. Severe deficiency patients also performed perfusional lung scan to detect early disorders of blood flow, evaluation of arterial blood gases and liver echotomography. Expiratory flow limitation, the prevalence of vascular disease, the amount of urine elastin products and correlations between the amount of nitric oxide exhaled and bronchial hyperresponsiveness have been also investigated. The study showed that in Brescia county the deficiency is more common than expected and that evaluation of liver and vessels might be as useful as lung function tests. In addition, beneficial effect on local system has been observed. The longitudinal study might permit to detect early organ damage and to eliminate additive risk factors.

[Severe alpha 1-antitrypsin deficiency: cross sectional clinical study]. / Grave deficit di alpha 1-antitripsina: studio clinico trasversale.

The aim of this study was to investigate a group of severe alpha 1-antitrypsin deficient subjects. Of the 20 subjects detected, 7 were classified as Index Cases (discovered because they were symptomatic and had pulmonary emphysema or liver disease), while 13 were classified as Non-Index Cases (asymptomatic and discovered because they were relatives of Index Cases or because of the absence of alpha 1 band in serum electrophoresis). They underwent pulmonary function tests, determination of arterial blood gases, lung high resolution computed tomography and lung perfusion scan. All Index Cases were with the ZZ phenotype, indicating a major risk of developing related pulmonary emphysema or liver disease; most Index Cases (71%) were ex-smokers, while among the Non-Index Cases, 46% were smokers or ex-smokers, suggesting that smoking might be the main cofactor in the development of emphysema. Index Cases were older (statistical significance) and mostly male as compared with Non-Index Cases. A statistical significance was observed between the two groups for several lung function parameters (forced expiratory volume in one second, Tiffenau index, residual volume, diffusing capacity of the lung for carbon monoxide, arterial oxygen tension) as a result of a pathological impairment in Index Cases. This underdiagnosed condition merits more attention in order to prevent its complications and to get a better understanding about its diagnosis and management.

Ventricular arrhythmias in normotensive subjects and in mild hypertensive patients.

Twenty-five normotensive subjects (14 men, 11 women) aged from 25 to 60 years (mean 36) and 30 untreated patients with mild hypertension (stages 1 and 2, JNC V) without target organ damage (16 men, 14 women), aged 26-59 years (mean 35.8) underwent continuous 24-hour ECG Holter monitoring with a Fukuda Denshi SM-40 ambulatory recorder and SCM-400 ECG analyzer. During 24-hour ambulatory ECG recording, mean heart rate was slightly but not significantly higher in hypertensive patients (73.3 +/- 10 beats per minute [bpm]) in comparison with normotensive subjects (71.2 +/- 12 bpm). The prevalence of premature atrial contractions was similar in the two groups. Total ventricular arrhythmias were more prevalent in the group of mild hypertensive patients (P < 0.05), who also had a higher prevalence in complex forms of ectopy (r = 0.81 for bigeminy; r = 0.83 for trigeminy; r = 0.83 for couplets). Holter recordings did not show abnormalities of ST-T wave or episodes of silent ischemia.

New cycloalkylpyrazoles as potential cyclooxygenase inhibitors.

In this study some cycloalkyl-3-(N-substituted carbamoyl)-1-phenylpyrazoles have been synthesized in order to screen their capability to inhibit human cyclooxygenase. The synthetic pathway is based on the well known property of nitrilimines to undergo 1,3-dipolar cycloaddition reactions. The structures of all the synthesized compounds have been elucidated by means of both analytical and spectroscopic methods.

Ambulatory-determined 24-hour blood pressure in mild hypertensives and in normotensives.

Noninvasive ambulatory twenty-four-hour blood pressure (BP) monitoring was carried out in 30 normotensive subjects (16 women, 14 men), aged twenty-five to sixty years (mean thirty-eight) and in 29 mild essential hypertensive patients without target organ damage (14 women, 15 men), aged twenty-three to sixty-one years (mean thirty-nine). Hypertensive patients were not treated, and they discontinued any antihypertensive treatment at least four weeks before the study. During the daytime period (6 AM-10 PM) BP was monitored every fifteen minutes, and during the night (10 PM-6 AM), every thirty minutes. Obviously, mean twenty-four-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in hypertensive patients (P < 0.001). There was a persistent correlation in the group of mild hypertensives between successive BP hourly mean readings (r ranged from 0.61 to 0.93 for SBP and from 0.45 to 0.82 for DBP). In normotensive subjects these correlations failed in particular periods: 8 AM-9 AM, r = 0.30 for SBP and 0.45 for DBP; 1 PM-3 PM, r = 0.17-0.49 for SBP and 0.28-0.37 for DBP; 9 PM to midnight, r = 0.21-0.57 for SBP and 0.23-0.38 for DBP.

Kaposi's disease and sarcoidosis.

A human immunodeficiency virus (HIV) antibody-negative 65 year old woman was treated with corticosteroids for 7 yrs because of bilateral uveitis. One year after the beginning of corticosteroid treatment, erythematous skin lesions appeared on the legs. Eight years after the diagnosis of uveitis, gastric and bronchial biopsies revealed noncaseating epithelioid cell granulomas, whilst a cutaneous biopsy showed Kaposi's disease. Sarcoidosis-associated alteration of immune regulation and corticosteroid therapy may have promoted the development of disease.

Deficiency of two red-cell flavin enzymes in a population in Sardinia: was glutathione reductase deficiency specifically selected for by malaria?

In two areas in Italy where malaria was endemic--in the Po delta and Maremma on the west coast--we have found a high prevalence of an inherited flavin-deficient red cell in the normal population, suggesting selection by malaria. This study in Sardinia enabled a direct comparison of red-cell activities of FAD-dependent glutathione reductase (EGR) and FMN-dependent pyridoxine phosphate (PNP) oxidase in an ethnically homogeneous population, between two coastal villages where malaria was endemic from 300 B.C. and two mountain villages with no history of malaria. Both enzyme activities were significantly lower on the coast, and it did not seem that this could be explained by possible small differences in dietary riboflavin. As was thought to be the case in Ferrara and Grosseto, it is probable that a genetically controlled flavin-deficient red cell was selected for by malaria. Low EGR apoenzyme activity was more common on the coast, usually explaining the accompanying low basic EGR activity, and may also have been selected for by malaria. This adds to evidence from others that the mechanism of defence of a flavin-deficient red cell against malaria may be through EGR deficiency. It could also play a part in the protection given by heterozygous beta-thalassemia. The multifactorial protection of the population against malaria is discussed.