Prevalence of simple nodular goiter and Hashimoto's thyroiditis in current, previous, and never smokers in a geographical area with mild iodine deficiency.

Simple nodular goiter and Hashimoto's thyroiditis are 2 frequent nonmalignant thyroid diseases. Tobacco smoking has detrimental effects on the endocrine system and in particular on thyroid function and morphology. The objective of this cross-sectional study, involving 1800 Caucasian adults from a geographical area with mild iodine deficiency, was to evaluate the relationship between tobacco smoking, smoking cessation, and the prevalence of simple nodular goiter and Hashimoto's thyroiditis. Thyroid status was evaluated by ultrasonic exploration of the neck, measurement of FT3, FT4, TSH, antibodies against thyroid peroxidase and thyroglobulin, and urinary iodine excretion. The fine-needle aspiration biopsy of significant nodules was also performed. Smoking habits were evaluated by a specific questionnaire and the calculation of number of pack years. Both current and previous smokers showed an increased risk of simple nodular goiter compared to never smokers after adjustment for potential confounders and known goitrogen factors. Interestingly, the simple nodular goiter risk was similar for never smokers and for previous smokers declaring a time since cessation of smoking for more than 69 months. Smoking habit was not associated to an increased risk of Hashimoto's thyroiditis.Smoking appears to be an independent risk factor for simple nodular goiter but not for Hashimoto's thyroiditis in an area with mild iodine deficiency. A prolonged withdrawal of smoking dramatically reduces the risk of simple nodular goiter occurrence.

Potassium-rich diet and risk of stroke: updated meta-analysis.

Recently a few prospective population studies provided additional and heterogeneous information concerning the reported statistical associations between potassium (K) intake and stroke risk. Therefore, we updated our previous meta-analysis of K intake and risk of cerebrovascular events. Three studies were added to the previous analysis, and the results of the comparison between the event rate in the two extreme categories of K intake were used. Pooled analysis of 14 cohorts (overall 333,250 participants and 10,659 events) showed an inverse and significant association between K intake and risk of stroke (Relative Risk: 0.80; 95% CI: 0.72-0.90). Our results indicated a favorable effect of higher K intake on risk of stroke. These results confirm the appropriateness of worldwide recommendations for a population increased consumption of potassium-rich foods to prevent cardiovascular disease.

Excess dietary sodium and inadequate potassium intake in Italy: results of the MINISAL study.

OBJECTIVE: As excess sodium and inadequate potassium intake are causally related to hypertension and cardiovascular disease, the MINISAL-GIRCSI Program aimed to provide reliable estimates of dietary sodium and potassium intake in representative samples of the Italian population. DESIGN AND METHODS: Random samples of adult population were collected from 12 Italian regions, including 1168 men and 1112 women aged 35-79 yrs. Electrolyte intake was estimated from 24 hour urine collections and creatinine was measured to estimate the accuracy of the collection. Anthropometric indices were measured with standardised procedures. RESULTS: The average sodium excretion was 189 mmol (or 10.9 g of salt/day) among men and 147 mmol (or 8.5 g) among women (range 27-472 and 36-471 mmol, respectively). Ninety-seven % of men and 87% of women had a consumption higher than the WHO recommended target of 5g/day. The 24 h average potassium excretion was 63 and 55 mmol, respectively (range 17-171 and 20-126 mmol), 96% of men and 99% of women having an intake lower than 100 mmol/day (European and American guideline recommendation). The mean sodium/potassium ratio was 3.1 and 2.8 respectively, i.e. over threefold greater than the desirable level of 0.85. The highest sodium intake was observed in Southern regions. Sodium and potassium excretion were both progressively higher the higher the BMI (p < 0.0001). CONCLUSIONS: These MINISAL preliminary results indicate that in all the Italian regions thus far surveyed dietary sodium intake was largely higher and potassium intake lower than the recommended intakes. They also highlight the critical association between overweight and excess salt intake.

High-circulating leptin levels are associated with greater risk of hypertension in men independently of body mass and insulin resistance: results of an eight-year follow-up study.

BACKGROUND: We previously reported a significant association between plasma leptin (LPT) concentration and blood pressure (BP), which was partly independent of serum insulin levels and insulin resistance. The aims of this study were to detect whether serum LPT levels predict the development of hypertension (HPT) in the 8-yr follow-up investigation of a sample of an adult male population (the Olivetti Heart Study), and to evaluate the role of body mass index (BMI) and insulin resistance in this putative association. PATIENTS AND METHODS: The study population was made up of 489 untreated normotensive subjects examined in 1994-1995 (age: 50.1 +/- 6.7 yr; BMI: 26.3 +/- 2.8 kg/m(2); BP: 120 +/- 10/78 +/- 6 mm Hg; and homeostatic model assessment index: 2.1 +/- 1.6). RESULTS: The HPT incidence over 8 yr was 35%. The participants with incident HPT had similar age but higher BMI (P < 0.001), serum LPT (P < 0.001), and BP (P < 0.01) at baseline. One sd positive difference in baseline serum LPT log was associated at univariate analysis with a 49% higher rate of HPT [95% confidence interval (CI) 22-83; P < 0.001]). In three different models of multivariable logistical regression analysis, LPT was respectively associated with a 41% greater risk to develop HPT (95% CI 15-74; P < 0.001) upon adjustment for age and baseline BP, with a 48% (95% CI 20-81) greater risk when adding the homeostatic assessment model index to the model, and with 33% greater risk (95% CI 6-67; P < 0.02) upon adjustment for BMI. CONCLUSIONS: In this sample of originally normotensive men, circulating LPT level was a significant predictor of the risk to develop HPT over 8 yr, independently of BMI and insulin resistance.

Indications for flexible fiberoptic bronchoscopy and its safety in the very elderly.

AIM: To evaluate the indications and the safety of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL), protected specimen brushing (PSB), endobronchial biopsy (EBB), and transbronchial biopsy (TBB) in a population of very elderly patients. METHODS: We performed a retrospective study of all adult patients, aged 50 years or older, who underwent FOB in the Bronchology Unit of the University of Parma Hospital between 1 January, 2003 and 31 April, 2005. Bronchoscopy records of 436 consecutive patients, including 191 patients, 75 yrs of age and older ("very elderly"; = > 75 yrs), were reviewed. RESULTS: Patients aged < 75 years and aged =/> 75 years were no different with regard to gender, BMI, baseline FEV1/FVC ratio, baseline SaO2, and blood pressure. The primary indication in patients aged < 75 years, was to assist in the diagnosis of a pulmonary mass of unknown aetiology (33%) and to remove secretions in the very elderly patients (31%). Indications for FOB and sampling procedures in the two groups were similar. Approximately 30% of patients in each group required supplemental oxygen during the procedure and fever occurred in 9.2% and 10.3% of patients, respectively. Hypertension and bleeding were relatively rare and did not occur more often in the very elderly. CONCLUSIONS: Indication for FOB did not vary with age and adverse events in both groups were uncommon and generally not severe.

Effect of sputum induction on spirometric measurements and arterial oxygen saturation in asthmatic patients, smokers, and healthy subjects.

BACKGROUND: Sputum production induced by inhalation of hypertonic saline solution has been proposed as a technique to collect secretions and inflammatory cells from the airways of subjects with bronchial asthma or with a history of smoking. The aim of this study was to determine the effect of a sputum induction procedure on spirometric results and arterial oxygen saturation (SaO(2)) in asthmatic patients, smokers, and healthy subjects. METHODS: We recruited 14 subjects suffering from asthma (11 men and 3 women; age range, 18 to 49 years), 14 subjects with a history of smoking (5 men and 9 women; age range, 23 to 64 years), and 9 healthy volunteers (7 men and 2 women; age range, 28 to 54 years). To obtain a sample of induced sputum, all subjects inhaled a mist of 3% hypertonic saline solution nebulized for 5 min and repeated the cycle no more than four times. Asthmatic patients were pretreated with 200 microg salbutamol (inhaled). During sputum induction, the transcutaneous SaO(2) was continuously measured and baseline, fall, and the differences between baseline and fall SaO(2) were recorded. Additionally, we measured the duration of mild desaturation (change in SaO(2), < 4%) and of marked desaturation (change in SaO(2), > 5%) in each subject. Finally, baseline FEV(1) and changes in FEV(1) as a percentage of baseline values were recorded in all subjects. RESULTS: We found that baseline and fall SaO(2) values for the three groups were similar. However, in each group a significant mean change in SaO(2) was evident during sputum production (asthmatic patients, 6.0%; smokers, 5.3%; healthy subjects, 6.0%). Moreover, the mean durations of mild desaturation were 7 min, 21 s in asthma patients; 8 min, 24 s in smokers; and 7 min, 16 s in healthy subjects. Similarly, the durations of marked desaturation were 1 min, 25 s in asthmatic patients, 1 min, 19 s in smokers, and 1 min, 21 s in healthy subjects. The mean (+/- SD) fall in FEV(1) was not statistically different among the three groups (asthmatic patients, 1.36 +/- 5.6%; smokers, 7.58 +/- 11.76%; and healthy subjects, 0.05 +/- 9.6%). However, one smoker did experience excessive bronchoconstriction (fall in FEV(1), > 20%). CONCLUSIONS: This study demonstrated a significant and comparable fall in SaO(2) during sputum induction by inhalation of hypertonic saline solution in asthmatic patients, smokers, and healthy subjects. The results suggest that subjects who are hypoxemic before sputum induction require SaO(2) monitoring during the procedure.

Induced sputum in patients with newly diagnosed sarcoidosis: comparison with bronchial wash and BAL.

OBJECTIVES: Sarcoidosis is characterized by a diffuse alveolar inflammatory process, although bronchial airways are often involved. This study compares the cellular profiles of induced sputum (IS), bronchial washing (BW), and BAL in newly diagnosed sarcoidosis patients to those in control subjects, and examines whether inflammatory cell counts from IS are correlated with inflammatory cell counts from BW and BAL in sarcoidosis patients. PATIENTS AND MEASUREMENTS: We recruited 15 untreated patients with stage I and II pulmonary sarcoidosis and 12 healthy volunteers. Sputum was induced with hypertonic saline solution in all individuals. Bronchoscopy was performed on a different occasion in all patients and in five control subjects. RESULTS: Mean lymphocyte counts in IS, BW, and BAL fluid from sarcoidosis patients were significantly higher than in control subjects (9.4% vs 3.8%, p < 0.05; 12.6% vs 3.9%, p < 0.05; 24.1% vs 2.6%, p < 0.05, respectively). Moreover, total cell count and percentage of epithelial cells in IS were significantly higher in sarcoidosis patients than in control subjects (p < 0.01 and p < 0.05, respectively). In sarcoidosis patients, comparison between different samples showed significantly higher percentages of macrophages in BW and BAL than in IS (p < 0.05 and p < 0.01, respectively), whereas the percentage of neutrophils was higher in IS compared with BW and BAL (p < 0.01 and p < 0.001, respectively). Finally, the percentage of lymphocytes in IS was significantly lower than that in BAL (p < 0.05) but not that in BW. CONCLUSIONS: We demonstrated that, compared with IS in healthy control subjects, IS in untreated pulmonary sarcoidosis patients contains more total cells, lymphocytes, and epithelial cells. Although the relative proportion of inflammatory cells in the three samples differed, lymphocyte counts in IS were high. This finding suggests that IS could be used as a valuable alternative to more conventional invasive techniques in clinical assessment of pulmonary sarcoidosis patients.

Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man.

Human anti-pig antibodies were obtained by perfusing pig hearts (n = 4) and kidneys (n = 8) with human AB or O plasma followed by elution with 3 M NaSCN. The antibodies were screened against a panel of 132 synthetic carbohydrates conjugated to bovine serum albumin using an enzyme-linked immunoassay. An anti-immunoglobulin antibody was also used to detect immunoglobulin deposits on pig tissues. Four carbohydrate molecules with a terminal alpha-galactose residue bound all but one of the human anti-pig kidney antibodies and most of the anti-pig heart antibodies. These were: (i) alpha Gal(1-->3)beta Gal(1-->4)beta GlcNac (linear B type 2); (ii) alpha Gal(1-->3)beta Gal(1-->4)beta Glc (linear B type 6); (iii) alpha Gal(1-->3)beta Gal(B disaccharide); and (iv) alpha Gal(alpha-D-galactose). Immunoglobulin deposition was documented post-plasma perfusion in all pig hearts and particularly strongly in all pig kidneys. These results suggest that human anti-pig antibodies are mainly directed against alpha-galactosyl structures. Extracorporeal immunoadsorption of human plasma through columns of the specific synthetic carbohydrate(s) might lead to depletion of anti-pig antibodies and allow discordant xenografting in man. Alternatively, the infusion of the specific carbohydrate(s) for a period of several days might result in neutralization of the anti-pig antibodies and allow accommodation to take place.

Excision of pulmonary and renal aspergillomas. Its use in treating chronic granulomatous disease of childhood.

Renal and pulmonary Aspergillus granulomas in two 6-year-old boys with chronic granulomatous disease were treated by nephrectomy and lobectomy as well as intravenous amphotericin B and granulocyte transfusion. After lobectomy two smaller pulmonary aspergillomas resolved with medical therapy. The second child's condition improved after nephrectomy, but he died with disseminated Aspergillus infection. This experience suggests that surgical excision of localized Aspergillus granulomas in conjunction with specific antimicrobial therapy provides temporary clinical improvement and may prevent further blood-borne dissemination of the fungus.

Systemically administered D-glucose conjugates of 7-chlorokynurenic acid are centrally available and exert anticonvulsant activity in rodents.

We have synthesized D-glucose or D-galactose esters of 7-chlorokynurenic acid (7ClKynA) as prodrugs to facilitate the transport of 7ClKynA across the blood-brain barrier. Intraperitoneal (i.p.) administration of either 7ClKynA-D-glucopyranos-6'-ylester (7ClKynA/Glu6) or 7ClKynA-D-glucopyranos-3'-yl ester (7ClKynA/Glu3) was protective against seizures induced by N-methyl-D-aspartate (NMDA) in mice, with the former drug showing the highest anticonvulsive activity. Systemic injection of equal amounts of 7ClKynA-D-galactopyranos-6'-yl ester (7ClKynA/Gal6) or free 7ClKynA did not protect against NMDA seizures. Microdialysis in freely moving rats showed the presence of significant amounts of 7ClKynA/Glu6, as well as of 7ClKynA or KynA, in cortical perfusates after i.p. injections of 7ClKynA/Glu6. In contrast, only small amounts of 7ClKynA or KynA were detected after i.p. injection of unconjugated 7ClKynA. Prodrug metabolism has also been examined in mouse cortical cultures containing both neurons and astrocytes. 7ClKynA/Glu6 and 7ClKynA/Gal6 were rapidly metabolized into 7ClKynA and KynA, whereas 7ClKynA/Glu3 was metabolized with a slower kinetics. As a result of its conversion into 7ClKynA and KynA, 7ClKynA/Glu6 protected cortical neurons against NMDA toxicity. We conclude that sugar conjugates of 7ClKynA (and perhaps of other excitatory amino acid receptor antagonists) are prodrugs of potential interest in the experimental therapy of epilepsy and acute or chronic neurodegenerative disorders.

Patterns of drug use among young men in Piedmont (Italy).

Increasing alarm is shown regarding patterns of polydrug use among young people, particularly regarding recreational drugs. Prevalence of recreational drug usage in Europe is not clearly defined, varying for ecstasy, from 0.2% (Finland, 1995) to 9.2% (UK, 1995) and suggesting a tendency to increase in the last years. The aim of this study is to present patterns of polydrug use among a sample of the general population of young males in Piedmont (Northern Italy), focusing particularly on ecstasy consumption. A cross sectional study was carried out between September and November 1998 on a continuous sample of 3274 18-year-old conscripts. A self-administered anonymous questionnaire on socio-demographic characteristics and substances use was submitted during routine tests. Results showed that the overall lifetime prevalence of drug use is 36.6%; prevalence of polydrug use is 30% and the more frequently associated drugs are LSD, cocaine, inhalants and ecstasy. One hundred and forty five (4.6%) subjects reported having taken ecstasy at least once in their life; 20 of the 145 (13.8%) suffered from negative effects and three (2%) presented to a hospital or to a physician. The risk of ever taking ecstasy is inversely related to father's education, with a trend that is quite similar to that of heroin consumption but that is different from the trend for cannabis. In conclusion the four major results of this study are: (i) a prevalence of drug consumption similar to other European estimates, with a clear tendency to polydrug use; (ii) for ecstasy, a very high association rate with other substances; (iii) the moderately high prevalence of self-reported symptoms, and (iv) a social distribution of use similar to the one observed for heroin. This last consideration suggests that a high level of attention and further research should be addressed to the natural history of ecstasy use.

Relationship between outcome measures of six-minute walk test and baseline lung function in patients with interstitial lung disease.

BACKGROUND AND AIM OF THE WORK: In patients with interstitial lung disease (ILD), the six-minute walk test (6MWT) has been rarely used, and up till now, the relationship between outcome measures of the test and baseline lung function has not yet been examined. Therefore, we assessed walk distance, oxygen desaturation, and breathlessness perception during 6MWT, and their relationships to baseline lung function in patients with ILD. METHODS: Forty ILD patients with history of breathlessness during physical exertion performed a 6MWT following a standard protocol. Breathlessness perception during walk was assessed by visual analogue scale (VAS, in mm). RESULTS: The mean walk distance was 487 meters (range 271-689). Mean baseline oxygen saturation (Base SpO2, %) was 94% and was reduced during walk, either as mean oxygen saturation (Mean SpO2, 89%, p < 0.001) or as mean fall in oxygen saturation during walk (Fall SpO2, 5%). Furthermore, VAS significantly increased after walk (5 mm to 44 mm, p < 0.001). A close relationship of TLco and TLC to walk distance and Fall SpO2 was found (r = 0.45 and 0.42 and r = -0.75 and -0.64, respectively; p < 0.001, each). On the basis of regression equations by stepwise multiple regression analysis, walk distance was predicted by age and FVC (r2 = 0.50), Mean SpO2 by TLco and Base SpO2 (r2 = 0.80), and Fall SpO2 only by TLco (r2 = 0.57). Breathlessness perception was not reliably predicted by any assessed variables. CONCLUSIONS: We confirmed that 6MWT provides a global evaluation of sub-maximal exercise capacity in ILD patients. We also found that walk distance and oxygen desaturation, but not breathlessness perception during walk, are strictly related to baseline lung function.

Intrathecal baclofen suppresses central pain in patients with spinal lesions. A pilot study.

OBJECTIVE: To assess the efficacy of acute intrathecal (i.t.) baclofen on chronic, dysesthetic, and spasm-related pain (SRP) among patients with spinal spasticity [i.e., multiple sclerosis (MS), spinal cord injury (SCI), transverse myelitis (TMy)]. DESIGN: Double-blind, randomized, and placebo (vehicle) controlled trials (n = 7), and nonrandomized, nonblinded trials (n = 2). SETTING: In-patient program at Samaritan Rehabilitation Institute, Phoenix, Arizona, U.S.A. PATIENTS: MS (n = 4), spinal cord compression (n = 1), and TMy (n = 2) in the double-blind trial, and SCI (n = 2) in the nonblinded trial; all had chronic spinal lesions and function-limiting spasticity refractory to oral medications, including baclofen (p.o.). INTERVENTIONS: i.t. baclofen (50 micrograms) in 1 ml preservative-free normal saline into the L1-2 interspace. OUTCOME MEASURES: Electromyographic (EMG) activity; intravesical and intraurethral pressures; Ashworth Scale and tendon response values; visual analog scales for describing dysesthetic pain intensity; and threshold/EMG relationships after controlled pinch as an indication of nociceptive pain. RESULTS: i.t. baclofen (a) caused marked reduction of segmental reflexes before suppression of intersegmental reflexes; (b) significantly suppressed dysesthetic pain and SRP with temporal dissociation; and (3) did not influence pinch-induced and musculoskeletal (low back) pain. CONCLUSIONS: The suppressive action of i.t. baclofen on spontaneous and evoked (allodynia) dysesthetic pain suggests that a dysfunctional spinal gamma-aminobutyric acidB receptor system, including functional supersensitivity, is associated with the phenomenon of central pain among patients with spinal lesions. Temporal dissociation regarding the action on dysesthetic pain and SRP suggests that disparate central mechanisms subserve the two clinical states.

Synthesis, pharmacokinetics and anticonvulsant activity of 7-chlorokynurenic acid prodrugs.

7-Chlorokynurenic acid 1 is a potent glycine-N-methyl-D-aspartate (NMDA) receptor antagonist, but it shows weak activity after systemic administration. In order to overcome the Blood-brain barrier (BBB), we synthetized three new esters 2-4 of 1 obtained by chemical conjugation with essential nutrients such as glucose and galactose, that are actively transported across the BBB. These compounds were assayed to evaluate their in vitro chemical and enzymatic hydrolysis. In addition the prodrugs 2-4 were tested for their ability to protect mice against NMDA-induced seizures after systemic administration. All the prodrugs 2-4 appeared moderately stable in pH 7.4 buffered solution and were susceptible to in vitro enzymatic hydrolysis. Intraperitoneal administration of either esters 2 or 4 was highly protective against seizures induced by NMDA in mice, with the latter prodrug showing the highest anticonvulsive activity. In addition, ester 4 undergoes a time-dependent extracellular hydrolysis into 1 when applied to mixed cultures of mouse cortical cells, a model that reproduces in vitro the cellular milieu encountered by the prodrugs once they penetrate the brain parenchyma.

Acute acalculous cholecystitis associated with common hepatic duct obstruction: a variant of Mirizzi's syndrome.

A variation of Mirizzi's syndrome is described in which common hepatic duct obstruction occurs due to extrinsic compression by an acutely inflamed acalculous gallbladder abutting the common hepatic duct. This case suggests that extrinsic compression and inflammation in the absence of stones can result in complete obstruction of extrahepatic biliary flow.