A retrospective epidemiological study on the association of bullous pemphigoid and neurological diseases

Bullous pemphigoid is a rare chronic recurrent dermatosis that is often reported in association with various neurological diseases. No investigation involving a large number of patients has ever been carried out to demonstrate such an association. This study was accomplished by analysing the discharge diagnosis of all hospitalized patients, both day-patients and inpatients, during a 5-year period (1995-2000) covering a total population group of 934,023 living in a region of Italy that has approximately 1,200,000 inhabitants. The results support the hypothesis of an association between bullous pemphigoid, multiple sclerosis and Parkinson's disease on a highly significant statistical basis. The aetiopathogenic mechanisms and the causes that induce the loss of immunological tolerance are not yet understood.     

Relationship between smoking and the clinical severity of psoriasis

OBJECTIVE: To evaluate the association between different components of smoking history and the clinical severity of psoriasis. DESIGN: A hospital-based cross-sectional study. SETTING: Inpatient wards of a hospital for skin diseases in Rome, Italy. PATIENTS: A total of 818 adults with psoriasis. MAIN OUTCOME MEASURE: The Psoriasis Area and Severity Index was used to assess the clinical severity of psoriasis between February 21, 2000, and February 19, 2002. RESULTS: After adjustment for potential confounders (sex, age, body mass index, psychological distress, family history of psoriasis, duration of psoriasis disease, and alcohol consumption), high intensity of smoking (>20 cigarettes daily) vs a lower level of consumption (< or =10 cigarettes daily) was associated with a more than 2-fold increased risk of clinically more severe psoriasis (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2-4.1). Cigarette-years, measured as the product of the intensity and duration (years) of smoking, significantly increased the risk of clinically more severe psoriasis after adjustment for confounding factors (OR,1.3; 95% CI, 1.0-1.6, for a 600-U increase in cigarette-years). Separate analyses for men and women showed that the effect of cigarette-years was stronger for women (OR, 1.8; 95% CI, 1.2-2.6, for a 400-U increase in cigarette-years) than for men (OR, 1.2; 95% CI, 0.9-1.6, for a 700-U increase in cigarette-years). CONCLUSION: Smoking is associated with the clinical severity of psoriasis and highlights the importance of smoking cessation in patients with psoriasis.     

Cerebral PET imaging and histological evidence of transglutaminase inhibitor cystamine induced neuroprotection in transgenic R6/2 mouse model of Huntington's disease

To investigate efficacy of cystamine induced neuroprotection, we conducted PET imaging studies of cerebral glucose metabolism with [(18)F]FDG (2-deoxy-2-[(18)F]fluoro-d-glucose) and striatal dopamine D2 receptor function with [(11)C]raclopride in R6/2 transgenic Huntington mice. In the control mice, exponentially decreasing glucose utilization was observed in the striatum N(str) [SUV]=(41.75+/-11.80)(58,str)*exp(-(0.041+/-0.007)*t [days]); cortex N(cort) [SUV]=24.14+/-3.66)(58,cort)*exp(-(0.043+/-0.007)*t [days]); and cerebellum N(cer) [SUV]=(34.97+/-10.58)(58,cer)*exp(-(0.037+/-0.008)*t [days]) as a function of age starting at 58 days. Given that the underlying degeneration rate in the cystamine treated mice is similar to that observed in control animals, the protection coefficient (beta) calculated from the equation N(t)=N(58)*exp(-(1-beta)*k*t) was 0.133+/-0.035 for the striatum; 0.122+/-0.028 for the cortex and 0.224+/-00.042 for the cerebellum with a dose of 100 mg/kg. The 50 mg/kg cystamine dose provided significant protection only for the striatum and only minor protection was obtained using lower doses. Striatal binding potential of [(11)C]raclopride was 1.059+/-0.030 in the control mice, and enhanced in the cystamine treated animals in a dose dependent manner up to 1.245+/-0.063 using the 100 mg/kg dose. Histological analysis confirmed cystamine induced neuroprotection of striatal and cortical neurons and Nissl staining revealed that formation of cellular inclusions was reversed in a dose dependent manner. Cerebral imaging and histological evidence support the use of cystamine as a neuroprotective agent for Huntington's disease (HD) pathology.     

Pathogenesis of some neurological immune ultrastructural and morphometrical observations on rat thymus

Numerous studies on neuro-immuno-modulation indicate that the thymus is involved in many neurological diseases, including experimental allergic encephalomyelitis (EAE). Twenty Lewis rats were induced for EAE. At X, XII, XX and XXX days post-inoculation the animals were killed, and the thymus was recovered and harvested. Specimens of thymus were submitted to morphological light microscopy analysis (1% toluidine blue) and ultra-structural analysis (transmission electron microscopy). Significant morphometric data were collected by examining the images quantitatively and by statistically analysing the values. Our results show that the microenvironment of the thymus is severally involved in acute EAE. Thymocytes and reticular epithelial cells show many changes which are closely related to the pathogenesis of EAE. In particular we observed: (1) inside the cell an increase in intra-cytoplasmic vacuoles, and changes in the thickness of the nuclear membrane, mitochondria, rough endoplasmic reticulum, cellular inter-digitations and cellular electron-density; (2) outside the cell an increase in pericellular translucent halo, intercellular spaces, intercellular contacts and apoptotic and necrotic figures. The evidence of a thymic role in MS may suggest the intriguing therapeutic concept of thymectomy in the management of this neurological disease.     

Early developmental exposure to BDE 99 or Aroclor 1254 affects neurobehavioural profile: interference from the administration route

Among the most persistent and bio-accumulative environmental pollutants are the polybrominated diphenyl ethers (PBDEs), a class of chemicals widely used as flame retardants in plastics and textile coating, and the polychlorinated biphenyls (PCBs), previously used as coolants and lubricants in electrical equipment. Monitoring programs revealed high levels of both these classes of compounds in human breast milk, raising concerns for their potential noxious effects on infants. The aim of the present study was to investigate the neurotoxic effects of 2,2',4,4',5-penta BDE (BDE 99: 18mg/kg/day) or Aroclor 1254 (A1254, a PCB mixture: 10mg/kg/day) administration, from gestational day (GD) 6 to postnatal day (PND) 21, on neurobehavioral development in the CD-1 Swiss mouse. In addition, we investigated whether the administration route affects the emergence or the magnitude of the toxic effects of BDE 99 or A1254. In particular, we compared self-administration, consisting in letting the mouse drink spontaneously the compound dissolved in oil from a syringe, with gavage, consisting in force-feeding a substance by a tube inserted in the mouth and then into the stomach, a procedure reported to be stress-inducing. Both compounds induced hyperactivity, though BDE 99 affected activity profile only during adolescence and A1254 mainly at adulthood. Levels of total circulating thyroxine were decreased by both BDE 99 and A1254 administration, though only in the latter group the decrease was statistically significant. These findings suggest a different neurotoxic action exerted by PBDEs and PCBs. An effect of the administration route, independent from the compound administered, was found on thigmotactic behavior and gavage administration affected pup body weight gain only in the A1254 group, suggesting that the stress induced by gavage procedure may either affect results per se or modulate the detrimental action of selected compounds.     

Plasma concentrations of anxiolytic neuroactive steroids in men with panic disorder

Plasma concentrations of neuroactive steroids in men with panic disorder (PD) were measured to evaluate their relations to psychopathology both before and during treatment. Participants comprised 13 men with PD and 10 normal controls. Patients were evaluated while drug-free as well as after 1 and 2 months of paroxetine therapy. Psychopathology was assessed by the State-Trait Anxiety Inventory (STAI), the Panic-Associated Symptom Scale, and the Fear Questionnaire total score. Plasma concentrations of steroids were measured by radioimmunoassay. The plasma concentrations of progesterone and dehydroepiandrosterone were greater in drug-free patients than in controls, whereas those of allopregnanolone and tetrahydrodeoxycorticosterone did not differ between the two groups. Paroxetine treatment for 2 months significantly increased the plasma concentration of allopregnanolone but did not affect those of the other steroids. At 2 months of therapy, allopregnanolone concentrations in patients were significantly greater than those in controls. The plasma concentrations of progesterone and tetrahydrodeoxycorticosterone correlated with the STAI state score in patients before treatment. Our data suggest that neuroactive steroids may play a role in PD in men.     

Effects of short-term moderate exercise training on sexual function in male patients with chronic stable heart failure

BACKGROUND: Patients with chronic heart failure (CHF) have sexual dysfunction that impairs quality of life. Recent trials have demonstrated that exercise training (ET) improves quality of life (QOL) of CHF patients, but it is not established whether this benefit may be associated with an improvement in sexual dysfunction. OBJECTIVE: To determine whether ET can improve sexual dysfunction in patients with CHF. METHODS: We prospectively studied 59 male patients (57+/-9 years) with stable CHF in sinus rhythm and without prostatic disease. Patients were randomized into two groups. A group (T, n = 30) underwent supervised cycle ergometer ET at 60% of peak VO2, three times a week, 60 min each session, for 8 weeks. A group (NT, n = 29) was not exercised. Medications were not changed during the study. On study entry and at 8 weeks all patients underwent a symptom-limited cardiopulmonary exercise testing, brachial artery endothelium-dependent (ED) and endothelium-independent (EI) vasomotor responses, QOL and sexual activity profile assessment (SAP) by questionnaire. RESULTS: At 8 weeks, no changes were observed in control patients. In trained patients, however, peak VO2 improved by 18% (P < 0.005) and was correlated with QOL (r = 0.80; P < 0.001). Flow-mediated dilation improved in trained patients (from 2.29+/-1.13% to 5.04+/-1.7%, P = 0.0001), while EI dilation (after 0.3 mg sublingual NTG) did not. In group T, all three domains (i.e. Domain 1=relationship with the partner; Domain 2 = quality of penile erection; Domain 3 = personal wellness) were significantly improved from baseline (total score patients: from 3.49+/-3.4 to 6.17+/-3.2, P < 0.001; partners: from 2.47+/-2.7 to 4.87+/-2.5, P < 0.001). Pre-post training change in SAP total score was correlated with changes in coronary risk profile (r = -0.49; P = 0.01), peak VO2 (r = 0.67; P < 0.001) and QOL (r = 0.73; P = 0.01). Multivariate analysis selected the improvement in ED-vasomotor response as the strongest independent predictor of SAP improvement (r = 0.63, P < 0.001). CONCLUSIONS: In stable CHF, cycle ergometer ET significantly improves brachial artery endothelial dysfunction, suggesting a systemic effect of leg exercise. This benefit was correlated with improvements in sexual activity.     

Microalbuminuria, renal function and development of sustained hypertension: a longitudinal study in the early stage of hypertension

OBJECTIVE: Microalbuminuria (MA) is a marker of adverse outcome in hypertension. The aim of this study was to investigate the association of MA with cardiovascular risk factors and glomerular hyperfiltration in the early stage of hypertension and to assess its predictive value for the development of sustained hypertension requiring antihypertensive treatment. DESIGN AND PARTICIPANTS: We studied 1041 young stage 1 hypertensive subjects. Study variables were 24-h ambulatory blood pressure and heart rate, anthropometric measures, metabolic variables, creatinine clearance and lifestyle factors analyzed as a function of ascending urinary albumin measured from 24-h collections. Subjects were followed until they developed sustained hypertension and were eligible for antihypertensive medication according to current guidelines. SETTING: Seventeen outpatient clinics in Italy. RESULTS: Eighty-five percent of the subjects were normoalbuminuric, 9% had borderline MA, and 6% had overt MA. No between-group differences were found for age, body mass index, heart rate, lifestyle factors and biochemistry in both genders. Creatinine clearance was greater in the subjects with overt MA and borderline MA than in the normoalbuminuric subjects (P = 0.003 and 0.011, respectively). In a two-way ANCOVA, microalbuminuric subjects both with hyperfiltration (P < 0.001) and with normal filtration (P = 0.04) had higher 24-h systolic blood pressure than subjects with normoalbuminuria and normal filtration. In a Cox analysis, neither MA nor hyperfiltration were significant predictors of development of sustained hypertension. CONCLUSION: MA is not associated with an adverse metabolic risk profile in the early stage of hypertension. MA is associated with greater hemodynamic load and with glomerular hyperfiltration in this clinical setting, but does not help in predicting those subjects destined to develop sustained hypertension requiring antihypertensive therapy.