Study objective: Childhood exposure to environmental tobacco smoke (ETS) adversely affects dynamic spirometric indexes as a result of combined early life (including in utero) and current exposure to parental smoking. The aim of our study was to investigate the effect of ETS on lung function and to identify the most sensitive functional parameter for evaluating lung damage.Design: Cross-sectional survey.Setting: Health survey on secondary school children.Subjects: Eighty adolescents boys (mean age +/- SD, 16 +/- 1 years) classified in three groups: 21 smokers, 30 nonsmokers, and 29 passive smokers.Measurements: Standardized questionnaire on the smoking habits of the subjects and their parents; assay of urinary cotinine level and measurement of the cotinine/creatine ratio (CCR); and lung function tests, including measurements of lung volumes, spirometric dynamic parameters, and the single-breath diffusing capacity of the lung for carbon monoxide (DLco).Results: Passive smokers presented a higher residual volume than nonsmokers, and a lower maximal expiratory flow at 25% of FVC (MEF25) and DLco. Passive smokers whose mothers had smoked during pregnancy had significantly lower MEF25 percentage, DLco, carbon monoxide transfer coefficient, and diffusion capacity of the alveolar-capillary membrane (Dm) values than did passive smokers whose mothers had given up smoking during pregnancy. Nevertheless, the MEF25, and Dm values of subjects with mothers who had given up smoking during pregnancy were lower than those observed in nonsmokers (p < 0.05), suggesting a negative effect of passive smoking independent of the mother's smoking habit during pregnancy. A statistically significant, negative correlation was found between CCR and DLco in smokers (r = - 0.63, p < 0.01) and in passive smokers (r = - 0.91, p < 0.001), but not in nonsmokers (r = 0.26, p = not significant), suggesting a dose-effect relationship.Conclusions: Current exposure to ETS in healthy male adolescents is associated with lung function impairment independently of the effects of maternal smoking during pregnancy. More information may be obtained from determining static lung volumes and DLco.

OBJECTIVEIn the dynamic organization of sleep, cyclic alternating pattern (CAP) expresses a condition of instability of the level of vigilance that manifests the brain's fatigue in preserving and regulating the macrostructure of sleep. We evaluated the presence of CAP in patients with fibromyalgia (FM) compared to healthy controls.METHODSForty-five patients with FM (42 women) were studied and compared with 38 healthy subjects (36 women) matched for age, sex, and body mass index. Entry criteria were diagnosis of FM according to 1990 American College of Rheumatology criteria; willingness to participate in the study; and having no other diagnosis of autoimmune, neoplastic, or other possible causes of secondary diffuse musculoskeletal pain. Patients in the study underwent polysomnography recordings and a sleep questionnaire. Hypersomnolence was evaluated according to the Epworth Sleepiness Scale.RESULTSFM patients had less sleep efficiency (sleep time/time in bed) than controls (79 +/- 10 vs 89 +/- 6; p < 0.01), a higher proportion of stage 1 non-rapid eye movement (non-REM) sleep (20 +/- 5 vs 12 +/- 5; p < 0.001), and twice as many arousals per hour of sleep (9.7 +/- 3.3 vs 4.1 +/- 1.9; p < 0.01). The CAP rate (total CAP time/non-REM sleep time) was significantly increased in FM patients compared to controls (68 +/- 6% vs 45 +/- 11%; p < 0.001). CAP rate seemed to correlate with the severity of clinical symptoms in FM patients (tender points index; p < 0.01) and with less efficiency of sleep (p < 0.01).CONCLUSIONThe increase of CAP rate indicates a worse quality of sleep in patients with FM. These data are strongly correlated to the severity of symptoms.

Objective: In this study, we would like to show that anterior rhinometry measurement of nasal resistance would be a simple and useful test to identify severe obstructive sleep apnea (OSA) in a population of children affected by adenotonsillar hypertrophy. Methods: Seventy-three consecutive children (44 males; mean age 5.4±1.2 years) with adenotonsillar hypertrophy, who complained sleep-disordered breathing, were studied. All the parents completed a questionnaire concerning the children's sleeping habits and sleep complaints before consultation; each child underwent a general paediatric examination and an evaluation of craniofacial features and upper airway patency. In all 73 children polysomnography was performed and anterior rhinometry nasal patency was measured. Results: The diagnosis of OSA was confirmed in 44/73 patients (60%). Total nasal resistance showed a significant direct correlation with apnea hypopnea index, arousal index, snoring time, percentage of sleep time spent at SaO2<90% and a significant inverse correlation with total sleep time, sleep efficiency and the mean of SaO2% during sleep. Total nasal resistance was significantly related to snoring, mouth breathing and daytime sleepiness. The receiver operator characteristics (ROC) curve indicates that in the range of age of our sample a nasal resistance value of 0.59 Pa/cm3/s has a sensitivity of 91% and specificity of 96% for identifying the children with adenotonsillar hypertrophy affected by OSA. Conclusions: Our study shows that in children with adenotonsillar hypertrophy nasal resistance seems to be risk factor for OSA. The anterior rhinometry appears as a useful tool in routine evaluation of sleep-disordered breathing in these patients.

Background: Nocturnal oxygen desaturations (NOD), especially during REM sleep, have been described in patients with COPD. However, the role of NOD in the evolution of COPD to chronic respiratory failure has not been well studied. Objective: The aim of our study was to evaluate whether NOD is a risk factor for the development of chronic respiratory failure in COPD patients. Methods: We studied 34 consecutive COPD patients with a stable daytime PaO2 >60 mm Hg over a period of 42 months. We classified patients as desaturators (NOD) when episodic desaturations were found mainly during REM sleep, independently of baseline SaO2 values. Results: At enrolment 19 patients (55.8%) had NOD. Over the follow-up period, 10 patients (29.4%) were included in a long-term oxygen therapy (LTOT) programme (9 were desaturators). The LTOT was initiated a median time of 22 ± 6.8 months after enrolment. Patients who were subsequently prescribed LTOT had lower values of FEV1 at enrolment, with a higher degree of NOD and PaCO2. Stable respiratory failure developed earlier in patients with NOD: the two enrolment curves for LTOT differed significantly (log-rank test 2.56, p = 0.005). PaCO2, NOD and FEV1 were statistically significantly associated, both in univariate and multivariate Cox proportional hazards analyses, with an increased risk of entering a LTOT programme. Conclusions: We conclude that NOD may represent an independent risk factor for the development of chronic respiratory failure in COPD patients with daytime PaO2 >60 mm Hg. A larger study is needed to confirm the role of NOD in the natural history of COPD and subsequently to identify the most appropriate therapeutic approach.

The aim of this study was to analyze the role of ACE gene insertion/deletion (I/D) and PC-1 gene K121Q polymorphisms in the changes of glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and blood pressure (BP) levels in a cohort of normoalbuminuric Type 1 diabetic patients. This is a 10.2+/-2.0-year prospective study of 30 normotensive normoalbuminuric Type 1 diabetic patients. UAER (immunoturbidimetry), GFR ((51)Cr-EDTA single injection technique), GHb (ion exchange chromatography), and BP levels were measured at baseline and at 1.7+/-0.6-year intervals. The presence of ACE gene I/D and PC-1 gene K121Q polymorphisms was determined by polymerase chain reaction (PCR) and restriction enzyme techniques. Three patients developed diabetic nephropathy (DN), all carriers of allele D. The presence of allele D was the only predictor (R(2)=.15, F=4.92, P=.035) of the observed GFR decline (-0.29+/-0.34 ml/min/month, P<.05). UAER increased during the study (log UAER=0.0275+/-0.042 microg/min/month, P=.002) and was associated with baseline UAER levels only (R(2)=.17, F=5.72, P=.024). A significant increase (P<.05) in cases of hypertension and retinopathy were observed in ID/DD (n=19) and not in II patients (n=11). Patients with the KQ/QQ genotype (n=8) presented a significant increase (P=.045) in new cases of retinopathy. In conclusion, the presence of the ACE gene D allele in this sample of normoalbuminuric normotensive Type 1 diabetic patients was associated with a higher proportion of microvascular complications and hypertension.

OBJECTIVE:To analyze the role of autonomic function and other possible factors associated with a blunted fall in nocturnal blood pressure. RESEARCH DESIGN AND METHODS:A total of 39 normotensive normnoalbuminuric type 1 diabetic patients were studied. Glomerular filtration rate (51Cr-EDTA technique), extracellular volume (51Cr-EDTA distribution volume), and urinary albumin excretion rate (UAER) (by radioimmunoassay) were measured. The subjects' 24-h ambulatory blood pressure and a 24-h electrocardiogram were recorded simultaneously Heart rate variability was calculated in the time domain for 24 h, in the frequency domain at night, at rest in the supine position, and during tilt. Patients were classified according to diastolic blood pressure (dBP) night/day ratio as dipper patients (< or =0.9) and nondipper patients (>0.9). RESULTS:Nondipper patients presented a higher low-frequency (LF) component (a sympathetic index) and higher LF/high-frequency (HF) ratio during sleep than dipper patients (0.29 +/- 0.12 vs. 0.19 +/- 0.10 normalized units [n.u.], P = 0.008; and 0.98 +/- 0.53 vs. 0.55 +/- 0.45 n.u., P = 0.007, respectively). At rest, the LF component in nondipper patients (0.38 +/- 0.13 n.u.) was higher than in dipper patients (0.27 +/- 0.12 n.u., P = 0.04). After the tilt, nondipper patients did not show an increase in the LF component (P = 0.32), but in dipper patients, the increase was significant (P = 0.001). In both groups, tilting promoted a decrease in the HF component (a parasympathetic index). In a stepwise multiple linear regression analysis, the LF component during sleep and the UAER accounted for 24% of the variability in the dBP night/day ratio. CONCLUSIONS:The predominance of sympathetic activity and increased levels of UAER, although within the normal range, are associated with a blunted fall in nocturnal dBP in normoalbuminuric normotensive type 1 diabetic patients.

OBJECTIVE:To analyze the changes in glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and blood pressure (BP) levels in a cohort of normoalbuminuric and normotensive type 1 diabetic patients.RESEARCH DESIGN AND METHODS:This is an 8.4+/-2.1-year prospective study of 33 normotensive normoalbuminuric (24-h UAER <20 microg/min) type 1 diabetic patients. UAER (radioimmunoassay), GFR (51Cr-EDTA single-injection technique), and GHb (ion-exchange chromatography) were measured at baseline and at 1- to 2-year intervals.RESULTS:The GFR decreased (137.6+/-16.5 to 116.4+/-21.3 ml x min(-1) x 1.73 m(-2) P < 0.05) during the follow-up period. GFR reduction (-0.20+/-0.29 ml x min(-1) x month(-1); P < 0.05) was associated with baseline GFR and mean GHb (R2 = 0.30; beta = 0.072; F = 6.54; P = 0.004). UAER was higher at the end of the study (3.7-7.1 microg/min; P = 0.017). Microalbuminuria was observed in two patients, while macroalbuminuria was observed in one. No changes in UAER were observed when these three patients were excluded from the analysis. Mean blood pressure (MBP) increased during the study (85.8+/-9.7 to 99.6+/-11.6 mmHg; P < 0.001). MBP at the end of the study was associated with age and GFR at baseline (R2 = 0.39; beta = 0.074; F = 9.64; P = 0.001).CONCLUSIONS:In this cohort of normoalbuminuric normotensive type 1 diabetic patients, GFR decreased and BP levels increased during the follow-up period. The predictors for the GFR change were baseline GFR level and metabolic control. For end-of-study MBP, the predictor was baseline GFR level.

OBJECTIVE To analyze the blood pressure patterns in normoalbuminuric IDDM patients with glomerular hyperfiltration. RESEARCH DESIGN AND METHODS A controlled cross-sectional study of 38 normotensive normoalbuminuric (urinary albumin excretion rate <20 μg/min) IDDM patients (18 hyperfiltering [glomerular filtration rate >134 ml · min−1 · 1.73 m−2] and 20 normofiltering) and 20 normal individuals matched for age, sex, and BMI was performed. The 24-h ambulatory blood pressure was monitored using an auscultatory technique (Pressurometer IV, Del Mar Avionics), the glomerular filtration rate was measured by 51Cr-labeled EDTA method, extracellular volume by the distribution volume of 51Cr-labeled EDTA, and the 24-h urinary albumin excretion rate by radioimmunoassay. RESULTS Mean nocturnal diastolic blood pressure was higher in hyperfiltering IDDM patients (70.4 ± mmHg), when compared with the control group (65.1 ± 5.3 mmHg, P = 0.04). Diastolic blood pressure night:day ratio was higher in hyperfiltering IDDM patients (92.0 ± 8.6%), when compared with normofiltering IDDM patients (85.9 ± 4.8%) and control subjects (87.0 ± 6.8%, P = 0.02). In IDDM patients, the glomerular filtration rate significantly correlated with the diastolic blood pressure night:day ratio (r = 0.5, P = 0.002), extracellular volume (r = 0.04, P = 0.002), and HbA1 (r = 0.3, P = 0.03). In stepwise multiple regression analysis, factors associated with glomerular filtration rate were diastolic blood pressure night:day ratio, extracellular volume, and HbA1 (adjusted r2 = 0.27, P = 0.003). CONCLUSIONS Glomerular hyperfiltration is associated with higher nocturnal diastolic blood pressure and with a blunted nocturnal decrease in diastolic blood pressure levels in normotensive and normoalbuminuric IDDM patients.

Alterations of oxidants and antioxidants now appear to be pivotal in the development of bronchial hyperresponsiveness and bronchial asthma, To evaluate the potential protective role of the antioxidant reduced glutathione (GSH) administered by ultrasonic nebulizer on metacholine-induced bronchoconstriction, we designed a double-blind, randomized study enrolling 18 subjects,vith mild asthma and previous bronchoconstriction after a methacholine challenge; we did not find a statistically significant decrease in bronchoconstriction after premedication with inhaled GSH, Further investigation under different experimental conditions is warranted because our information about the mode of action and pharmacokinetics of GSH is still incomplete and sometimes the data are conflicting.

The aim of this study was to evaluate gallbladder dynamics in insulin-dependent diabetic patients with and without autonomic neuropathy. Gallbladder dynamics was studied by a scintigraphic method after a test meal in 26 insulin-dependent diabetic patients and 10 normal individuals. The presence and severity of autonomic neuropathy were defined according to the number of abnormal cardiovascular reflex tests: absent (no abnormal test), mild (1-3 abnormal tests), and severe (4-5 abnormal tests). The time from the moment when the patient started to take the test meal to the beginning of gallbladder emptying was longer (P = 0.01) in diabetic patients with mild (N = 11, 12.1 +/- 7.6 min) and severe neuropathy (N = 8, 11.0 +/- 10.6 min) than diabetic patients without autonomic neuropathy (N = 7, 3.9 +/- 4.4 min) and controls (N = 10, 4.8 +/- 4.2 min). The ejection rate was higher (P = 0.02) in the group with severe autonomic neuropathy (N = 8, 5.1 +/- 3.3%/min) than diabetic patients with mild (N = 11, 2.0 +/- 1.0%/min) or without autonomic neuropathy (N = 7, 1.8 +/- 0.8%/min) and controls (N = 10, 2.6 +/- 1%/min). Thirty-two percent of the diabetic patients with autonomic neuropathy presented increased perspiration, nausea and urgency to defecate after the ingestion of the test meal. A significant positive correlation of ejection rate with the presence of these symptoms (biserial point correlation test = 0.67, P < 0.01) was also observed. These data suggest that insulin-dependent diabetic patients with autonomic neuropathy present abnormalities of gallbladder emptying that could be related to specific gastrointestinal symptoms.

OBJECTIVE:To compare the effect of a normal protein diet (test diet) in which chicken and fish were substituted for red meat with a low-protein diet (LPD) on glomerular filtration rate (GFR) in normoalbuminuric insulin-dependent-diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS:A crossover randomized clinical trial was performed in 15 normoalbuminuric IDDM patients, 9 normofiltering, and 6 hyperfiltering patients. They followed three diets for a 3-week period each: a usual diet (UD), an LPD (0.5 g.kg-1.day-1 of proteins, 7% calories as protein, 33% as fat, and 60% as carbohydrates), and a normoproteic isocaloric test diet in which white meat (chicken and fish) was substituted for red meat of the UD. At the end of each diet, a clinical evaluation and measurements of GFR (51Cr-ethylenediaminetetraacetate (EDTA) single injection technique), urinary albumin excretion (UAE), and plasma amino acids were performed. Dietary compliance was assessed by a 24-h urinary urea and weekly interviews with the dietitian. RESULTS:In all diabetic patients, GFR after the LPD (114.9 +/- 16.5 ml.min-1 x 1.73 m-2) and after the test diet (122.7 +/- 16.7 ml.min-1 x 1.73 m-2) was significantly lower than after the UD (132.0 +/- 27.7 ml.min-1 x 1.73 m-2) (P = 0.001). Similar results were found in the hyperfiltering group: after UD = 161.1 +/- 15.4 ml.min-1 x 1.73 m-2, after LPD = 129.8 +/- 9.0 ml.min-1 x 1.73 m-2, and after the test diet = 136.5 +/- 3.1 ml.min-1 x 1.73 m-2, (P < 0.001). In the normofiltering group, no significant changes in GFR were observed after the three diets. Metabolic control, nutritional indexes, blood pressure (BP), and UAE did not change after the three diets in all patients. CONCLUSIONS:A normoproteic diet with chicken and fish as the only meat protein source decreases the GFR in the hyperfiltering normoalbuminuric IDDM patients. The GFR reduction after this diet is similar to that observed after an LPD.

time of initial diagnosis (2). This neuropathy is deemed to be secondary to deposition of metabolic by-products of hyperglycemia, i.e., sorbitol in neurilemmal sheaths, and is often reversed on achieving and maintaining optimal metabolic control. We report on 2 men with severe disabling sensory motor polyneuropathy at the time of diagnosis of diabetes mellitus. They lacked recovery on attainment and maintenance of optimal metabolic control for 12 mo, but had a total remission after testosterone replacement therapy within 6 mo after documentation of associated hypergonadotropic hypogonadism. The 2 men, ages 54 and 56 yr, were referred to a diabetes clinic because of progressive muscle weakness and wasting involving the lower extremities with a greater distal distribution including bilateral foot drop, severe disabling hyperasthesiae, dysanthesiae, and parasthesiae involving both hands and feet. They were unable to perform routine activities of daily living without assistance and were wheelchair bound. These manifestations began 6 -8 mo before diagnosis of diabetes mellitus and did not abate despite administration of phenytoin (300 mg/day), carbamazepine (800 mg/day), or application of capsaicin cream (0.075%), as well as maintenance of metabolic control as reflected by fasting plasma glucose <140 mg/dl and HbAlc <9.0% on quarterly determinations during the last year. Amytriptilline was not used because of the presence of orthostasis. Both subjects also had undergone extensive neuromuscular testing, including CAT scans of the head and lumbosacral spine, nerve conduction studies and electromyography, cerebrospinal fluid examination, as well as biopsies of the sural nerve and of gluteus and gastrocnemius muscles, confirming the presence of polyneuropathy and neurogenic muscle atrophy. Aggressive work-up also was conducted for each subject to exclude occult malignancy as a cause of inability to regain the lost weight (12.0 and 15.0 Kg) despite maintaining optimal metabolic control. On inquiry, patients related history of impotence for 18 mo, which was thought to be secondary to diabetic autonomic neuropathy because orthostasis also was detected. At this time, a thorough endocrine evaluation was performed. Serum cortisol and thyroid function tests were within normal ranges. However, serum testosterone levels were 150-180 ng/dl and 195-240 ng/dl, all values being subnormal (<300 ng/dl) with marked elevations of folliclestimulating hormone and leutinizing hormone (>25.0 mlU/ml) on several occasions. Therefore, fortnightly intramuscular administration of depot testosterone (200 mg) was initiated. During the next 6 mo, both subjects regained body weight, muscle mass, and strength, and also recovered from bilateral foot drops. Orthostasis and sensory abnormalities also abated with a return of sexual function. Finally, both returned to their occupations on a fulltime basis. We believe that initial lack of remission of severe sensory motor polyneuropathy and cachexia after optimal metabolic control of diabetes mellitus may be attributed to associated hypogonadism. We suggest that a thorough evaluation of sexual dysfunction be performed at the onset of diabetes rather than deeming it to be secondary to autonomic neuropathy because appropriate therapy with sex hormones appears distinctly beneficial in remitting severe polyneuropathy, including muscle wasting.