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Beta-secretase 1 (BACE1) is considered as the key enzyme in amyloid-β formation. Previous works suggest that high BACE1 activity may be present in brain, cerebrospinal fluid and serum of patients with late-onset Alzheimer's disease (LOAD) as well as mild cognitive impairment (MCI). Therefore, we evaluated whether serum BACE1 activity increases in MCI patients and is associated with the progression from MCI to dementia. BACE1 activity was measured in the serum of 259 MCI patients (162 amnestic-aMCI, 97 non-amnestic-naMCI) and 204 healthy Controls. After a median follow-up of 32 months (range: 10-153), 116 MCI progressed to dementia (87 aMCI and 29 naMCI). Serum BACE1 activity was higher in MCI compared with Controls (p

espanolLa necrosis grasa del recien nacido es una paniculitis lobulillar poco frecuente que se produce en las primeras semanas de vida. Se caracteriza por nodulos y placas eritemato-violaceos, indurados, asintomaticos y localizados en espalda, brazos, muslos, nalgas y mejillas. Es un trastorno benigno y autolimitado, que requiere el seguimiento de los pacientes por la posible aparicion de complicaciones, como hipercalcemia, hipocalcemia, trombocitopenia, hipertrigliceridemia, hipoglucemia y anemia, siendo las mismas poco frecuentes. Se presenta una serie de tres casos clinicos de necrosis grasa del recien nacido observados en este hospital con factores de riesgo para su desarrollo. EnglishSubcutaneous fat necrosis of the newborn is a rare lobular panniculitis, which occurs in the first weeks of life. It is characterized by erythematous-violaceous, asymptomatic, indurated, nodules and plaques, on the back, arms, thighs, buttocks and cheeks. It is a benign and self-limited disorder, which requires monitoring of patients due to the possible appearance of uncommon complications such as hypercalcemia, hypocalcemia, thrombocytopenia, hypertriglyceridemia, hypoglycemia and anemia being the same infrequent. A series of three clinical cases of fat necrosis of the newborn observed in our hospital, with risk factors for its development is presented.

Objectives To evaluate the possibility of predicting the risk of progression from mild cognitive impairment (MCI) to dementia using a combination of clinical/demographic parameters. Methods A total of 462 MCI elderly patients (follow-up: 33 months). Variable measured included cognitive functions, age, gender, MCI type, education, comorbidities, clinical chemistry, and functional status. Results Amnestic type (aMCI) represented 63% of the sample, non-amnestic (naMCI) 37%; 190 subjects progressed to dementia, 49% among aMCI, and 28% among naMCI. At Cox multivariate regression analysis, only MMSE (one point increase HR 0.84; 95% CI 0.79–0.90), aMCI (HR 2.35; 95% CI 1.39–3.98), and age (1 year increase HR 1.05; 95% CI 1.01–1.10) were independently associated with progression to dementia. A score was created based on these dichotomized variables (score 0–3): age (≥ or p 0.0001). Conclusions We have described a simple score, based on previously recognized predictors such as age, MMSE, and MCI type, which may be useful for an initial stratification of the risk of progression to dementia in patients affected by MCI. The score might help the clinicians to evaluate the need for more expansive/invasive examinations and for a closer follow-up in MCI patients.

Background Nicotine withdrawal syndrome is a major clinical problem. Animal models with sufficient predictive validity to support translation of pre-clinical findings to clinical research are lacking. Aims We evaluated the behavioural and neurochemical alterations in zebrafish induced by short- and long-term nicotine withdrawal. Methods Zebrafish were exposed to 1 mg/L nicotine for 2 weeks. Dependence was determined using behavioural analysis following mecamylamine-induced withdrawal, and brain nicotinic receptor binding studies. Separate groups of nicotine-exposed and control fish were assessed for anxiety-like behaviours, anhedonia and memory deficits following 2–60 days spontaneous withdrawal. Gene expression analysis using whole brain samples from nicotine-treated and control fish was performed at 7 and 60 days after the last drug exposure. Tyrosine hydroxylase (TH) immunoreactivity in pretectum was also analysed. Results Mecamylamine-precipitated withdrawal nicotine-exposed fish showed increased anxiety-like behaviour as evidenced by increased freezing and decreased exploration. 3H-Epibatidine labeled heteromeric nicotinic acethylcholine receptors (nAChR) significantly increased after 2 weeks of nicotine exposure while 125I-αBungarotoxin labeled homomeric nAChR remained unchanged. Spontaneous nicotine withdrawal elicited anxiety-like behaviour (increased bottom dwelling), reduced motivation in terms of no preference for the enriched side in a place preference test starting from Day 7 after withdrawal and a progressive decrease of memory attention (lowering discrimination index). Behavioural differences were associated with brain gene expression changes: nicotine withdrawn animals showed decreased expression of chrna 4 and chrna7 after 60 days, and of htr2a from 7 to 60 days.The expression of c-Fos was significantly increased at 7 days. Finally, Tyrosine hydroxylase (TH) immunoreactivity increased in dorsal parvocellular pretectal nucleus, but not in periventricular nucleus of posterior tuberculum nor in optic tectum, at 60 days after withdrawal. Conclusions Our findings show that nicotine withdrawal induced anxiety-like behaviour, cognitive alterations, gene expression changes and increase in pretectal TH expression, similar to those observed in humans and rodent models.

Objective: To assess quality of life and psychological differences between infertile women with endometriosis and without endometriosis. To investigate predictive role of perfectionism, mindful awareness and beliefs about parenthood to quality of life in a sample of women with fertility problems. Methods: 43 infertile women (22 with endometriosis; 21 without endometriosis) who recurred to Assisted Reproductive Treatments (ARTs) in the last 12 months took part to this cross-sectional study. Sociodemographic and clinical data were collected by means of a structured ad hoc questionnaire. Fertility Quality of Life, Fertility Problem Inventory – Need of parenthood subscale, Obsessive Beliefs Questionnaire – Perfectionism subscale, and Cognitive and Affective Mindfulness Scale – Revised were used to assess target outcomes. Results: Any difference in quality of life and psychological condition was found between infertile women with and without endometriosis. Importance given to parenthood (beta = −.60, p

Background: The analysis of early patterns of lung disease among preterm infants may help to identify predictors of pulmonary deterioration. Objectives: To analyze FIO2 requirement in the first 14 days of life among preterm infants and to find predictors of bronchopulmonary dysplasia (BPD). Methods: Retrospective cohort study. Setting: 3 Italian level III NICUs. Population: infants born between 240/7 and 276/7 weeks' gestational age (GA) who survived to 14 days. A consecutive sample of 588 infants was analyzed. Daily mode FIO2 in the first 2 weeks of life were analyzed according to the criteria defined by Laughon et al. [Pediatrics 2009;123:1124-1131], who found 3 early respiratory patterns: consistently low FIO2 (LowFIO2), pulmonary deterioration (PD), and early persistent pulmonary deterioration (EPPD). Factors associated with pulmonary deterioration were studied by univariate and multivariate analysis. Results: Forty percent of infants had low FIO2, 18% had pulmonary deterioation, 21% had early persistent pulmonary deterioration, and 21% had a previously unreported pattern (pulmonary improvement, PI). The prevalence of BPD was 7% in the LowFIO2 group, 28% in the PI group, 44% in the PD group, and 62% in the EPPD group (p = 0.000). Infants with lung deterioration were more frequently males (OR = 2.019, CI: 1.319-3.090, p = 0.001), had lower GA (OR = 0.945, CI: 0.915-0.975, p = 0.000), higher incidence of severe respiratory distress syndrome (OR = 2.956, CI: 1.430-6.112, p = 0.003), and lack of postnatal caffeine (OR = 0.167, CI: 0.052-0.541, p = 0.003). Conclusions: We report 4 distinct patterns of early respiratory disease associated with significantly different prevalence of BPD and discuss risk factors for lung deterioration.

Impulse control disorders and compulsive medication intake may occur in a minority of patients with Parkinson's disease (PD). We hypothesize that genetic polymorphisms associated with addiction in the general population may increase the risk for addictive behaviors also in PD.Sixteen polymorphisms in candidate genes belonging to five neurotransmitter systems (dopaminergic, catecholaminergic, serotonergic, glutamatergic, opioidergic) and the BDNF were screened in 154 PD patients with addictive behaviors and 288 PD control subjects. Multivariate analysis investigated clinical and genetic predictors of outcome (remission vs. persistence/relapse) after 1 year and at the last follow-up (5.1 ± 2.5 years).Addictive behaviors were associated with tryptophan hydroxylase type 2 (TPH2) and dopamine transporter gene variants. A subsequent analysis within the group of cases showed a robust association between TPH2 genotype and the severity of addictive behaviors, which survived Bonferroni correction for multiple testing. At multivariate analysis, TPH2 genotype resulted the strongest predictor of no remission at the last follow-up (OR[95%CI], 7.4[3.27-16.78] and 13.2[3.89-44.98] in heterozygous and homozygous carriers, respectively, p 0.001). The extent of medication dose reduction was not a predictor. TPH2 haplotype analysis confirmed the association with more severe symptoms and lower remission rates in the short- and the long-term (p 0.005 for all analyses).The serotonergic system is likely to be involved in the pathophysiology of addictive behaviors in PD, modulating the severity of symptoms and the rate of remission at follow-up. If confirmed in larger independent cohorts, TPH2 genotype may become a useful biomarker for the identification of at-risk individuals.

Risk factors for levodopa-induced dyskinesias (LIDs) in Parkinson’s disease (PD) include young age at onset, disease progression and individual dose of levodopa.1 Nevertheless, established risk factors do not fully explain the marked individual variability in the time elapsing between levodopa initiation and the onset of LIDs, and genetic predisposition is likely to play a critical role. To identify the genetic determinants modulating the time at onset of LIDs, we investigated 10 polymorphisms previously associated with LIDs in PD. Among these variants, we selected those additionally associated with addictive disorders, based on the recent hypothesis that pathophysiological mechanisms underlying LIDs share similarities with non-motor hyper-dopaminergic states, such as addictive disorders (including impulse control disorders).2 Clinical records of consecutive outpatients diagnosed with PD, attending our clinic from April 2009 to April 2011 and contributing to the ‘Parkinson Institute Biobank’, were retrospectively reviewed. We included only patients who were free of LIDs at baseline and who developed LIDs during the follow-up (to maximise the accuracy in recording the date of onset of LIDs and to overcome the limitation due to the retrospective study design). Patients were visited at least twice/year by the same neurologist. The onset of LIDs was defined as the first-ever report by the neurologist (off-state dystonia excluded).(e-1) We compared demographic and clinical variables with those of an independent cohort of 1002 PD patients followed during the same period, fulfilling similar inclusion/exclusion criteria but whose genetic data were not available (see online …

Background The aim of this study was the detection of risk factors for lacunar strokes with visible lesions on computed tomography (CT) scan, considering in particular clinical characteristics, echocardiographic parameters, and carotid–femoral pulse wave velocity (PWV, a marker of large-artery stiffness). Lacunar strokes with very small or nonvisible lesions may have different risk factors. Methods We examined 106 patients (mean age 66.9 ± 12.3 years, 60 men), including 55 patients with clinically lacunar stroke associated with deep ischemic lesions of .3-1.5 cm on brain CT scan, and 51 control patients with cortical ischemic stroke, with lesions of 2.5-10.0 cm. Results In multiple logistic regression, with respect to cortical strokes, the following variables were independently associated with lacunar strokes: tricuspid regurgitation velocity (inverse relationship, odds ratio [OR] .13, 95% confidence interval [CI] .04-.43, P = .0007, cutoff at 228 cm/s), mean systolic blood pressure (SBP) (OR 3.98, 95% CI 2.78-7.79, P = .008, cutoff at 145 mmHg), ever-smoker status (OR 2.68, 95% CI 1.06-6.80, P = .04), and atrial fibrillation (inverse relationship, OR .11, 95% CI .01-1.00, P = .0496). In univariate analysis, the patients with lacunar stroke also had a lower prevalence of mitral regurgitation. There were no differences between the 2 groups in relation to diabetes, cholesterol, left ventricular mass and dimensions, and PWV. Conclusions The patients with lacunar strokes with visible cerebral lesions on CT scan, compared with the patients with cortical infarct, had a lower tricuspid regurgitation velocity, a higher mean SBP, a greater prevalence of ever-smokers, and a lower prevalence of atrial fibrillation.

Background: Data for time trends in the prevalence of occupational asthma (OA) and rhinitis (OR) are not known. Objective: To investigate the prevalence and incidence of OA and OR over time. Methods: We chose to review studies on the prevalence and incidence of OA and OR due to laboratory animals (LA) as a marker of changing OA and OR patterns over time and analysed 15 cross-sectional and 4 longitudinal studies published from 1980 to 2006. Results: The estimated prevalence of OA, defined as work-related chest symptoms (WRCS), declined from 8.2% in 1976 to 4.2% in 2001 (P < 0.005). When defined by WRCS and positive skin prick test (SPT) to LA, the estimated prevalence of OA was 6.7% in 1977 and 2.9% in 1999 (P < 0.02). The prevalence of OR, defined by WRNS or WRNS and SPT to LA, was not related to study date but was inversely associated with mean exposure duration. In four longitudinal studies no clear trend emerged over time. Conclusions: This review suggests a trend toward a progressive decline in the prevalence of occupational asthma due to laboratory animals, which may be due to the reduction of exposure since the early 1980s. A further reduction of exposure is needed to prevent the onset of occupational rhinitis.

Summary Rheumatoid arthritis (RA) may promote endothelial dysfunction. This phenomenon requires further investigation, especially in collagen-induced arthritis (CIA), as it is considered the experimental model most similar to RA. The objectives of this study were to identify CIA-induced changes in noradrenaline (NE) and acetylcholine (ACh) responses in mice aortas that may suggest endothelial dysfunction in these animals. Moreover, we characterize CIA-induced modifications in inducible nitric oxide synthase (iNOS) expression in the aortas and cardiac and renal tissues taken from these mice that may be related to possible endothelial dysfunction. Male DBA/1J mice were immunized with 100 μg of emulsified bovine collagen type II (CII) plus complete Freund's adjuvant. Twenty-one days later, these animals received a boost of an additional 100 μg plus incomplete Freund's adjuvant. Fifteen days after the onset of the disease, aortic rings from CIA and control mice were challenged with NE and ACh in an organ bath. In these animals, iNOS was detected through immunohistochemical analysis of aorta, heart and kidneys. Plasma nitrite concentration was determined using the Griess reaction. CIA did not change NE or ACh responses in mice aorta but apparently increased the iNOS expression not only in aorta, but also in cardiac and renal microcirculation. In parallel, CIA reduced nitrite plasma concentration. In mice, CIA appears to increase the presence of iNOS in aorta, as well as in heart and in kidney microcirculation. This iNOS increase occurs apparently in parallel to a reduction of the bioavailability of NO. This phenomenon does not appear to change NE or ACh responses in aorta.

Study objective To evaluate the effect of treatment with beclomethasone dipropionate (500 μg bid) and salmeterol (50 μg bid) on lung function and respiratory symptoms in 20 subjects with occupational asthma (OA) still exposed to the work environment cause of their disease. Methods At enrollment and every 6 months for 3 years, respiratory symptom score (from 0 [no symptoms] to 2 [moderate-to-severe symptoms]), spirometry, methacholine challenge, peak expiratory flow (PEF) variability, and the use of rescue salbutamol were evaluated. During the 3 years of follow-up, 10 subjects were excluded from the study because they retired or changed jobs. Measurements and results Symptoms of work-related asthma started 12.6 ± 13.1 years (mean ± SD) before diagnosis. At baseline, mean FEV 1 was 80.2% of predicted values and provocative dose of methacholine causing a 20% fall in FEV 1 (PD 20 ) was 1,001 ± 1,275 μg; the workers received 2.1 ± 2.4 puffs of salbutamol per day. After 3 years, no significant differences in any of the morbidity outcomes (FEV 1 , PD 20 , PEF variability, use of rescue salbutamol, respiratory symptom score) were found as compared with baseline or run-in values. Conclusions Regular treatment with inhaled corticosteroids and long-acting bronchodilators seems to prevent respiratory deterioration over a 3-year period in workers with mild-to-moderate persistent OA who were still exposed at work to the environmental cause of their disease.

Summary Background Larvae of insects and worms, used as live fish bait (LFB), are a common source of allergy in anglers and occupationally exposed workers, but the prevalence and predictors have not yet been investigated. Objective This study assessed the prevalence and associated factors of occupational allergy in workers exposed to LFB. Methods We assessed the prevalence of sensitization to LFB and work-related symptoms (WRS) in 76 workers occupationally exposed to it. All workers completed a case history questionnaire and underwent skin prick tests (SPT) for common aeroallergens and bluebottle (Calliphora vomitoria), bee moth (Galleria mellonella), mealworm (Tenebrio molitor), and gusano rojo (Cilecomadia moorei). Specific IgE were tested in 64 subjects. Two-thirds of the workers had a high level of LFB exposure. Results Sensitization to LFB was found in 24 workers (31.6%). Seven subjects (9.2%) reported WRS (asthma in 3, rhinoconjunctivitis in 5, and contact urticaria in 1), and 5 were positive for SPT and serum IgE to one or more LFB extracts. One was also exposed to LFB while fishing. Sensitization to LFB extracts and WRS were strongly associated (Odds Ratio = 6.6, P

The aim of this study was to evaluate the influence of the two-step hepatocyte isolation procedure on primary cultured trout (Oncorhynchus mykiss) hepatocytes over time. We characterised the possible changes of a variety of some cellular parameters within the first 24-48 h after seeding. We followed the time dependent changes of these parameters during subsequent culture times in order to see if the cells maintained a differentiated status. Scanning electron microscopy revealed bleb formation and 20% cell damage in freshly isolated hepatocytes. During subsequent culture times the bleb dimension appear to be reduced. Heat shock proteins 70 and 50 (HSP70, HSP50) were induced by hepatocyte isolation. During the first 4 h of culture, the hepatocytes showed a variation in mitochondrial activity, an increase in free radical species (ROS), and a decrease in both glutathione (GSH) content and catalase (CAT) activity; the generation of free radicals led to an increase in the formation of 8-hydroxydeoxyguanosine (8-OHdG) in the DNA. The cells showed detectable ethoxyresorufin-O-deethylase activity after 4 h of culture, which had rapidly increased by the 24th hour. After 24 h, mitochondrial and CAT activity, free radical production, and the content of GSH and 8-OHdG returned to their original levels. P450 activity was retained for at least 48 h after seeding. Our data show that trout hepatocytes suffer significant cell injury as a result of the isolation procedure, but primary cultured cells metabolically recover from this stress after a few hours: they are capable of repairing their damaged surfaces, recovering their antioxidant defences and retaining their ability to repair DNA. Our results also confirm that trout hepatocytes in a primary culture maintain their in vivo-like metabolic activities for 3-8 days.

A multicenter study was carried out in 10 Italian Headache Centers to investigate the prevalence of psychosocial stress and psychiatric disorders listed by the IHS classification as the “most likely causative factors” of tension-type headache (TTH). Two hundred and seventeen TTH adult outpatients consecutively recruited underwent a structured psychiatric interview (CIDI-c). The assessment of psychosocial stress events was carried out using an ad hoc questionnaire. The psychiatric disorders that we included in the three psychiatric items of the fourth digit of the IHS classification were depressive disorders for the item depression, anxiety disorders for the item anxiety, and somatoform disorders for the item headache as a delusion or an idea. Diagnoses were made according to DSM-III-R criteria. At least one psychosocial stress event or a psychiatric disorder was detected in 84.8% of the patients. Prevalence of psychiatric comorbidity was 52.5% for anxiety, 36.4% for depression, and 21.7% for headache as a delusion or an idea. Psychosocial stress was found in 29.5% of the patients and did not differ between patients with and without psychiatric comorbidity. Generalized anxiety disorder (83.3%) and dysthymia (45.6%) were the most frequent disorders within their respective psychiatric group. The high prevalence of psychiatric disorders observed in this wide sample of patients emphasizes the need for a systematic investigation of psychiatric comorbidity aimed at a more comprehensive and appropriate clinical management of TTH patients.

This study aimed to evaluate the prevalence of dyspnoea and its predictors in studies on several working male groups in British Columbia (BC), Canada (cedar sawmill, grain elevator, pulpmill, and aluminum smelter workers), and Tuscany (T), Italy, (shoe and furniture makers, millers, bakers, and pharmaceutical workers). We performed cross-sectional health studies (interviews and pulmonary function tests) for 2498 BC and 1474 T workers exposed to air contaminants, and 1110 BC and 243 T controls. Similar questionnaires and the same definitions were used in BC and in T. Pulmonary function tests were also performed. The participation rates were >92% in BC workers and >82% in T workers. The overall prevalence of moderate dyspnoea was not different in exposed BC and T workers in comparison with controls. Slight dyspnoea was significantly more frequent in BC workers, but not in T workers, with respect to controls. After adjusting for age, body mass index (BMI), smoking, current asthma, and chronic bronchitis, forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were found to be significantly associated with slight and moderate dyspnoea in BC workers, and slight dyspnoea in T workers. Isolated dyspnoea is associated with reduction in FEV 1 and FVC in working populations, after adjusting for potentially confounding variables.

Nitroglycerine is known to induce a headache attack in cluster headache patients, which is indistinguishable from a spontaneous attack. It has recently been suggested that a release of calcitonin gene-related peptide (CGRP) from peripheral terminals of trigeminal nociceptive neurons, which supply cephalic blood vessels, underlies symptoms of cluster headache. The aim of this study was to investigate whether the provocative action of nitroglycerine in cluster headache is due, at least in part, to activation of the trigeminovascular system. Nineteen subjects suffering from episodic cluster headache participated in the study. Eleven of them were in an active period, whilst the others were in remission at the time of the study. CGRP-like immunoreactivity (CGRP-LI) was measured in blood samples from the extracerebral circulation before and after the sublingual administration of nitroglycerine. Baseline CGRP-LI plasma levels were higher (P < 0.05) in the patients who were in an active period. Only in these patients did nitroglycerine induce an attack, which was preceded by a latent period with a mean duration of 27 +/- 3 min. When compared with the baseline, a significant (P < 0.01) increase in plasma CGRP-LI was detected at the peak of the provoked attack; no such increase was detected during the latent period, or at the onset of the attack. The results of this study suggests that the provocative action of nitroglycerine in cluster headache is due, at least in part, to activation of the trigeminovascular system. This mechanism seems to be slow and unrelated to the well-known rapidly occurring vasodilator effects of the drug. Finally, activation of the trigeminovascular system only occurs in those patients already in an active cluster headache period who also have high basal CGRP-LI plasma levels. This suggests that a hyperactivity of trigeminal nociceptive fibres could make the trigeminovascular system of these patients sensitive to the triggering action of nitroglycerine.

The aim of this study was to evaluate the diagnostic accuracy of transvaginal sonography vs. hysteroscopy in the preoperative staging of endometrial carcinoma, in order to establish the most appropriate surgical therapy. Transvaginal sonography and hysteroscopy were used preoperatively in 67 women with histologically proven endometrial carcinoma. Deep myometrial invasion (> 50%) was present at post-operative pathology in 26/67 (39%) women and spread to the cervix occurred in 1 l/67 (14%) women. Transvaginal sonographic examination was initially directed at assessing myometrial invasion, which was correctly predicted in 52/67 (78%) women. Transvaginal sonography demonstrated a sensitivity of 88% (23/26) and a specificity of 71% (29/41) for deep invasion, with a positive predictive d p value (PPV) of 66% (23/35) and a negative predictive value (NPV) of 91% (29/32). The accuracy of transvaginal sonography in detecting cervical involvement was 82% (55/67), and that of hysteroscopy was 72% (48/67): transvaginal sonography was slightly less sensitive (54% vs. 64%), but more specific (87% vs. 73%) than hysteroscopy. When cervical invasion was present, the PPVs of transvaginal sonography and hysteroscopy were 46% (6/13) and 32% (7/22), respectively, while the NPV was 91% for both techniques (49/54; 41/45). Our data show that the accuracy of transvaginal sonography was comparable with that of hysteroscopy in detecting cervical involvement. Therefore, in the majority of cases, when both techniques showed that disease was limited, the appropriately limited type of surgery would be performed. Conversely, detection of a myometrial invasion of B 50% or an extension to the cervix would lead to an unnecessarily extensive operation if this was the sole criterion used for making the decision. Copyright © 1996 International Society of Ultrasound in Obstetrics and Gynecology

Aim of the study was to compare urinary galactosyl-hydroxylysine (GHyl), deoxypyridinoline (D-Pyr) and pyridinoline (Pyr) before and after 5 to 9 months of hormone replacement therapy (HRT) in postmenopausal women. The urinary markers were measured by HPLC in the second void of fasting samples and were expressed as ratio to creatinine. GHyl was also expressed as a ratio to glucosylgalactolysyl-hydroxylysine (GGHyl). After short-term hormone replacement therapy, urinary D-Pyr fell significantly, but Pyr and GHyl, also when expressed as a ratio to GGHyl, remained unmodified. We conclude that GHyl and Pyr are not useful markers in monitoring the bone response to HRT in postmenopausal women.

Background: The occupational uses of latex gloves may be associated with asthma. Hypersensitivity to latex has been shown to be IgE-mediated. The asthmatic reaction to latex is usually early; however, the natural history of latex asthma is still unknown. Objective: The purposes of this study were to investigate asthmatic responses induced by natural rubber latex and to assess the long-term respiratory consequences of latex-induced asthma after removal from exposure. Methods: This report describes the clinical and immunologic study of six nurses with work-related respiratory and skin disorders induced by the use of latex gloves. To determine whether the symptoms induced by latex gloves were IgE-mediated, we assessed latex IgE antibody levels by skin prick tests (SPTs) and RASTs with latex extracts. To confirm work-related latex reactions, we assessed respiratory symptoms, skin reactions, and FEV 1 after a glove exposure test and an inhalation provocation test with latex gloves. All subjects were followed up for 7 months to 7 years after the first observation. Results: All subjects had positive SPT and RAST responses to latex extracts, positive double prick test responses to latex gloves, and negative SPT responses to cornstarch and common allergens. Ten atopic and 10 nonatopic control subjects had negative SPT responses to latex and cornstarch extracts and negative double prick test responses to latex gloves. In three subjects latex allergy was associated with allergy to fruit (banana and chestnut). After the glove exposure test, four of six subjects had contact urticaria, all had rhinoconjunctivitis, and two had a late asthmatic response. The inhalation provocation test was performed on four subjects: all had rhinoconjunctivitis, two had urticaria and late asthmatic response, and one had laryngeal edema. A late asthmatic response was recorded in four subjects. Three subjects continued to have chronic asthma, and four subjects had increased nonspecific bronchial responsiveness 7 months to 7 years after being assigned to duties not involving latex gloves. Conclusions: This study of six nurses shows that latex is a potential cause of occupational asthma, rhinoconjunctivitis, and urticaria-angioedema. Latex seems to include antigens that elicit IgE-mediated hypersensitivity and may cause a late asthmatic reaction. Occupational asthma caused by latex may lead to permanent respiratory disability, even after removal from exposure. (J ALLERGY CLIN IMMUNOL 1995;96;457-64.)

A cross-sectional study was conducted to investigate seroprevalence of canine leptospirosis in urban Harare and five selected rural communities in Zimbabwe and to assess public awareness of the disease. Sera from randomly selected dogs were tested for antibodies to the serovars Canicola, Grippotyphosa, Icterohaemorrhagiae and Pomona of Leptospira interrogans using an enzyme-linked immunosorbent assay. Clinical chemistry was performed on all seropositive and selected seronegative sera to screen for hepatic and renal insufficiency. A questionnairebased survey was conducted in Harare to assess dog owners’ awareness of leptospirosis and other zoonoses. Overall, 15.6% of sera samples tested (39 out of 250; 95% confidence interval [CI]: 11.0% – 20.2%) were positive for leptospiral antibodies. A significantly higher (p < 0.05) seroprevalence was recorded in urban dogs than in rural dogs (25% vs. 11.2%). No significant difference in seroprevalence was observed amongst dogs from different rural communities or between sexes of dogs. There was a significant association between seropositivity and hepatic and/or renal insufficiency (p < 0.01), with dogs having hepatic and/or renal insufficiency being approximately twice as likely to be seropositive (relative risk = 1.96; 95% CI: 1.3–3.0). Of the dog owners, 78.8% (119/151) were aware of zoonoses. Except for rabies (92.4%), awareness of leptospirosis (5.0%) and other zoonoses amongst these owners was low. This study showed that leptospirosis was present and represented a risk to dogs from urban Harare and the selected rural communities in Zimbabwe. Availing training programmes for dog owners would be beneficial in improving disease control and reducing the public health risk of pet zoonoses. Council for Assisting Refugee Academics (CARA), the AWARE Trust of Zimbabwe and the University of Zimbabwe Research Board Grant no. RB/103/11

A follow-up study of 128 subjects with red cedar asthma was conducted to evaluate the clinical and socioeconomic impact of the disease in determining the working status of the subjects after the diagnosis was made. The results suggest that the severity of asthma is not the main determinant of working status. Comparing the data at diagnosis and at follow-up examination, we found that the persistence of exposure resulted in a deterioration in the asthma despite the use of more medications. Subjects who were working were younger and had a larger number of dependents than the subjects who were not working at the time of the follow-up examination. We conclude that the socioeconomic factors are important in determining the working status of subjects with red cedar asthma. To prevent severe impairment and disability, there should be more economic incentives for these subjects to choose other jobs.

A microfluorometric DNA study was conducted on isolated cells from 64 fragments of ovarian epithelial tumors. Data analysis considered the DNA content of the main stemline and the prevalence of cells in the different compartments of the DNA ploidy histogram in relation to the mitotic activity index and the histologic architecture. Main stemlines were found remarkably stable in different parts of the same tumor. Peridiploid (1.8c to 2.2c) stemlines were found both in well-differentiated and in poorly differentiated tumors. However, low aneuploid (2.2c to 3.0c) stemlines were mostly found in nonsolid tumors and high ploidy (3.2 to 5.04 c) stemlines were prevalent in solid tumors. A comparative analysis between DNA ploidy parameters and mitotic activity was useful to evaluate the expanding modalities of neoplastic cell populations. This analysis revealed that several tumors accumulate an excessive amount of heteroploid cells and others an excessive amount of G2 cells. Yet, most neoplastic cell populations vary from slow to rapidly growing patterns without relevant abnormalities in their ploidy graphic profiles. No relationship was found between stemline ploidy and histologic architecture compared with expanding modalities. These findings indicate that multifaced criteria combining features such as main ploidy, graphic profile, mitotic rate, and histologic architecture measured on one or more microsamples of the same tumor may help to objectively estimate the aggressiveness reached by the neoplastic cells at the time of clinical presentation.

Partsch G, Matucci-Cerinic M, Marabini S, Jantsch S, Pignone A and Cagnoni M. Collagenase Synthesis of Rheumatoid Arthritis Synoviocytes: Dose-dependent Stimulation by Substance P and Capsaicin. Scand J Rheumatol 1991; 20: 98-103.The synthesis and release of collagenase in the presence of the neuropeptide substance P (SP) and capsaicin, were investigated in vitro using identical synoviocyte cultures from patients with rheumatoid arthritis (RA). On average 10−12 M SP augmented statistically significantly the collagenase production by approximately a factor of five. An increase in the concentrations up to 10−6 M SP resulted in a decreased collagenase synthesis, which, however, was still above the level of that of the untreated synoviocytes. Capsaicin, a homovanillic acid derivative that acts as a releaser of SP from primary afferent neurons, caused a strong stimulation of collagenase production and release at 10−8 and 10−6 M (about 7 times the amount of the control). With increasing concentrations up to 10−...

Plasminogen activator inhibitor (PAI-1) antigen and fibrin/ogen degradation products (FbDP, FgDP) were measured before and 8 days after gynaecological surgery in 50 patients randomly submitted to prophylaxis with low molecular weight heparin (Alfa LMW1-OP 2123, Alfa Wassermann, Bologna, Italy; LMWH group) or standard calcium heparin (CH group). All patients were screened for deep venous thrombosis by the 125I Fibrinogen uptake test. In the CH group, but not in LMWH group, postoperative PAI-1 levels were significantly higher (p

These studies of cluster headache (CH) focus on two key features of pain transmission: a) sensory nerves when stimulated, as well as the expected afferent transmission, also display an efferent function which affects capillaries, glands, and smooth muscle (of the iris in CH); substance P (SP) and allied transmitters such as Vasoactive Intestinal Peptide (VIP) and Calcitonin Gene-Related Peptide (CGRP) are the main agonists of this dual afferent-efferent function; b) impaired pain transmission (deafferentation-like condition) provokes a rostral spread of neuronal irritability and automatic firing ("quasi epileptic foci") producing a clinical predilection for pain with the generation of "spontaneous" pains along the sensory pathways. The substrates studied in the present experiments are the iris, salivary glands, and nasal mucosa. 1) Iris: the conjunctival instillation of SP induces isocoric miosis both in CH sufferers and in normals, thus excluding gross SP receptoral dysfunction of the iris muscle in CH. Electrical stimulation of extraocular (infratrochlear) endings of the first branch of the trigeminal nerve provokes a miosis, which is significantly less in the symptomatic eye than in the contralateral one. This miosis is ascribed to a retrograde release of SP, induced by electrical stimulation of the trigeminal ophthalmic branch. The relatively poor miosis in the painful eye could correlate with a deficient release of SP from the sensory terminals in the iris. 2) Salivary glands: an increase of substance P-like immunoreactivity is found in the saliva taken from the asymptomatic side, but not from the painful side during a cluster headache attack, thus showing at this level also an asymmetry as previously shown in other head structures. 3) Nasal mucosa: intranasal application of capsaicin, a powerful releaser of SP from sensory terminals, evokes an immediate burning pain in the ipsilateral nasal, ocular, and temporal areas, as well as lacrimation and rhinorrhea. A gradual decrease (tachyphylaxis) of these phenomena is consistently observed after few days of daily nasal administration of capsaicin. When this treatment is applied to CH patients, a rapid decrease in the number and intensity of attacks, and even disappearance of symptoms accompanies the decline of the capsaicin-induced manifestations. Local (nasal) capsaicin, in spite of evoking immediately the same vegetative (rhinorrhea, lacrimation, conjunctival congestion) and in part nociceptive (transient nasal, ocular, temporal burning) phenomena of CH, never has been able to provoke delayed spontaneous-CH like attacks. Such delayed provoked attacks, one of the most pregnant phenomena in CH investigations, are almost constantly evoked by systemic stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Cigarette smoking is a known risk factor for many chronic illnesses such as coronary heart and chronic obstructive pulmonary diseases. Smoking is often described as a risk factor for occupational asthma even though its effect on the development of asthma is still under debate and the links between smoking and occupational asthma, occupational rhinitis or occupational sensitization are elusive, controversial and contradictory. This review describes these relationships in a wide range of occupations, from laboratory, farm, brewery and hospital workers, to bakers, printers, cleaners, fish processors and others as observed in cross-sectional, cohort, and case-control studies published over the past thirty-five years i.e. from 1970 to 2005. Surprisingly, the data show there is little to support the view that the risk of occupational asthma is increased in workers who are smokers. However, evidence emerges of an increased risk of occupational sensitization in smoking workers exposed to several high and low molecular weight agents. This in-depth review confirms the relationship between smoking and occupational asthma is complex and contradictory. It deserves more attention and further studies, which need to be conducted without being influenced by selection bias or by the justifiable prejudice against smoking.

Asthma education programs result in clinical improvement. However, most studies involved programs of up to 1 year of follow-up, and their efficacy in improving quality of life (QoL) is still controversial. The aim of this study was to evaluate the effectiveness of a program of patient education in asthmatics over 2 years. Thirty-seven asthmatic patients were randomly allocated to group A (usual treatment) and 32 to group B (usual treatment plus patient education program). The effectiveness of the education program was evaluated by comparing morbidity outcomes at baseline and 12 and 24 months afterwards. At baseline, no intergroup difference emerged in age, sex, smoking, asthma severity, atopy, FEV1, symptom-free days, use of rescue salbutamol, and QoL. One year later, group B subjects had an improvement in the overall QoL (from 5.8 +/- 0.8 to 6.1 +/- 0.7, p < 0.005), and in "Activities" (from 5.3 +/- 0.9 to 5.7 +/- 0.8, p < 0.05) and "Environment" (from 6.4 +/- 1.0 to 6.8 +/- 0.4, p < 0.05) domains. Two years later the "Activities" domain score increased in group B (from 5.3 +/- 0.9 to 5.7 +/- 1.1, p < 0.05). QoL did not vary in group A. The education program was ineffective in all other parameters at both follow-up time-points. In group A, a significant increase in medication expenses and a significant decrease in rescue salbutamol use was found 1 and 2 years after baseline, respectively. In conclusion, this education program improved QoL for 1 year, but the improvement was not sustained in the 2nd year.

Asthma educational programs have been shown to reduce the use of emergency room, frequency of severe asthma attacks and hospitalization. However, its effectiveness in other morbidity parameters and on quality of life has yet to be fully understood. This prospective randomized control trial evaluated the effectiveness of a patient education program in 77 asthmatics according to “Teach Your Patients About Asthma: A Clinician's Guide”(1992). Forty asthmatic patients were randomly allocated to Group A (usual treatment) and 37 to Group B (usual treatment plus a patient education program). The effectiveness of the educational program was evaluated by comparing morbidity outcomes at baseline and 3 months after initial evaluation. At enrolment, the two groups were not different with regard to age, sex, smoking, asthma severity, atopy, FEV1, symptom-free days, use of rescue salbutamol and quality of life. Three months later, subjects in Group B showed a significant improvement in the overall quality of life (p

Background. The severity of occupational asthma (OA) at the time of diagnosis is not known. In this study we aimed to evaluate some features of the disease at the time of diagnosis, particularly looking at severity and treatment before diagnosis. Methods: Medical records of subjects (n = 197) who had received a diagnosis of OA in six specialized centres of Northern and Central Italy in the period 1992–97 were reviewed. The severity of the disease at the time of diagnosis was determined on the basis of symptoms, peak expiratory flow (PEF, percentage predicted), forced expiratory volume in one second (FEV1, percentage predicted), and PEF variability, following the criteria of the National Institutes of Health and World Health Organizaton (NIH/WHO) guidelines on asthma. Medications used in the month before diagnosis were recorded. Results: The most common etiological agents were isocyanates (41.6%), flours (19.8%), woods (9.7%) and natural rubber latex (7.6%). The level of asthma severity (AS) was mild intermittent in 23.9% patients, mild persistent in 28.9%, moderate in 41.6%, and severe in 5.6%. Asthma severity was positively associated with current or previous smoking (P

Objective. To study the antiinflammatory effect of different doses of intraarticular somatostatin in experimental arthritis in rabbits. Methods. Chronic arthritis was induced by a single injection of fibrin into the knee joint of rabbits previously sensitized to this antigen. The effects of sequential intraarticular injections of somatostatin into the rabbit knee, at doses of 500, 750, and 1,000 μg, were monitored by measuringknee joint circumferences and hematologic parameters. The measurements were compared with those obtained following use of triamcinolone acetonide and placebo. At the end of the experiments, the knee joints were examined histologically. Results. Somatostatin treatment induced a statistically significant and dose-related reduction of knee joint swelling. This effect was shorter than that produced by triamcinolone acetonide; however, the antiinflammatory activity elicited by successive doses of triamcinolone acetonide declined both in extent and duration, while the effects of somatostatin remained unchanged at each successive treatment. Histopatho-logic observations showed that both somatostatin and triamcinolone acetonide reduced the inflammatory signs in the joint structures, although triamcinolone acetonide appeared to be more effective. Conclusion. These findings suggest that somatostatin exerts an antiinflammatory effect in this model of experimental arthritis and may represent a valid and safer alternative to corticosteroids for intraarticular therapy of arthritis.

We evaluated the prevalence of asthma and its predictors in studies of several male working groups: 619 cedar sawmill, 724 grain elevator, 399 pulpmill, 798 aluminum smelter, and 1,127 unexposed workers. These workers had taken part in health studies for assessment of chronic respiratory effects of various workplace exposures between 1979 and 1982. The American Thoracic Society Adult Questionnaire (ATS-DLD-78) was used for these studies. Allergy skin tests were also performed. The participation rates were > 80%. The overall prevalance of physician-diagnosed asthma was 4.6%, and current asthma 3%. The prevalence of asthma after employment in the current industry, as a surrogate for work-related asthma, was 3.9 times higher in cedar sawmill workers, 2.2 times higher in pulpmill and aluminum smelter workers, and 1.7 times higher in grain elevator workers compared with unexposed workers. Atopy and a positive parental history of asthma, but not smoking, were important risk factors for asthma before the onset of first employment. Also, for asthma after employment in the current industry, atopy and a positive parental history of asthma were important risk factors. Smoking was associated with a significant reduction in the risk for asthma after employment in the current industry. Within specific work groups, the prevalence of atopy was significantly higher among pulpmill workers with asthma after employment in current industry than those without asthma. Conversely, cedar sawmill workers who had asthma after employment in the current industry were nonatopic and nonsmokers.

Preliminary studies have shown that repeated nasal applications of capsaicin prevented the occurrence of cluster headache attacks. The present study was designed to verify the difference in efficacy of treatment with nasal capsaicin, depending on the side of application. Fifty-two patients affected by episodic form were divided into 2 groups, one receiving the treatment on the same side where the attacks occurred (ipsilateral side), the other on the controlateral side. Eighteen patients with a chronic form alternately received both ipsilateral and controlateral treatments. Seventy percent of the episodic patients, treated on the ipsilateral side, showed a marked amelioration whereas no improvement was noted in the patients treated on the contralateral side. The efficacy of ipsilateral treatment was emphasized by the results obtained in chronic patients. However, in these patients, the maximum period of amelioration lasted no more than 40 days. The difference between the effects of the 2 treatments (contralateral and ipsilateral) was statistically significant in both episodic and chronic sufferers. The efficacy of repeated nasal applications of capsaicin in cluster headache is congruent with previous reports on the therapeutic effect of capsaicin in other pain syndromes (post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia) and supports the use of the drug to produce a selective analgesia.

Coronary subclavian steal syndrome is a possible sequel in patients who have undergone myocardial revascularization with an internal mammary artery. We report a case of this syndrome in a 67-years-old man. In 1990 he underwent a quadruple bypass: aorta-obtuse margin, aorta-right coronary (two sequential), internal artery mammary-descending coronary artery. Three months later he started to have angina pectoris. In April 1992 an aortic arch angiography and a coronary angiography were performed. The examination showed an occlusion of the left subclavian artery at its origin. The artery was opacified countercurrently by the left vertebral artery but the left mammary artery was not opacified. Left coronary angiography showed a very severe disease of left anterior descending coronary artery and retrograde flow through the anastomosis in the left mammary artery. The patient underwent a left common carotid-subclavian artery bypass operation using a 6 mm vascutex graft. Eighteen months later the patient is doing well without angina pectoris and with very little alteration of the perfusion in the left frontal lobe observed by SPECT neuroimaging with a lipophilic tracer (99mTc-HMPAO). We think that the coronary-subclavian steal syndrome can be treated successfully with low risk by means of common carotid-subclavian artery bypass.

The expression of epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) was compared with the presence of "squamous differentiation" (SD) visualized in various histotypes of endometrial carcinoma by using a panel of monoclonal antibodies. The results of the current study demonstrate that EGFr and TGF-alpha are present in routinely processed endometrial carcinoma. The highest positive EGFr and TGF-alpha expression was seen in the group of adenocarcinomas with SD. The more intense EGFr and TGF-alpha immunoreactivity was observed in "squamous" foci both in adenoacanthomas (AA) and in adenosquamous carcinomas (AS). These EGFr- and TGF-alpha-positive squamous areas prevalently displayed a "stratification-related" cytokeratin (CK) immunoprofile characterized by the expression of CKs 1, 4, 5, 10, 13, 14, and 16. No correlation was found between EGFr- and TGF-alpha-positive status and depth of myometrial invasion or surgical stage. These results clearly demonstrate that EGFr and TGF-alpha expression is related remarkably to endometrial carcinoma with "squamous" areas both morphologically and immunophenotypically. This specific association leads us to suggest that EGFr and TGF-alpha expression in endometrial carcinoma may be prevalently involved in the equilibrium of cell differentiation of the "squamous" foci commonly observed in this group of neoplasias.

The circannual secretion of melatonin in 14 Swedish and 15 Italian patients suffering from episodic cluster headache was compared with 14 Swedish and 15 Italian healthy controls matched for sex and age. Overnight samples of urine were collected once a month from 8 to 14 months and kept at -20° C until analysed with RIA. The melatonin concentrations in nocturnal urine were permanently low in cluster headache and there was no consistent change of the melatonin concentration in relation to cluster periods occurring during the study. There was no definitive circannual or infraannual rhythmicity of melatonin in patients or controls. Multiple analysis of variance with repeated measurements showed a significant effect of disease ( p < 0.05), but not of time. Sex, geographical location, age, and smoking also had significant effects ( p < 0.001) on the melatonin concentrations. Lower melatonin levels in cluster headache patients than in controls may in part be related to a larger number of smokers in the patient group. The relation between tobacco use and melatonin should be further studied.

For difficult asthma, treatment is aimed at improving airway obstruction and minimizing adverse effects of systemic corticosteroids. The combination of troleandomycin (TAO) with methylprednisolone (MP) reportedly has a beneficial steroid-sparing effect on difficult asthma.To test the steroid-sparing effect of TAO, 14 subjects with severe corticosteroid-dependent asthma were studied before and during treatment with MP and TAO.Treatment with MP and TAO resulted in a clear reduction in respiratory symptoms, asthmatic attacks, corticosteroid and hospitalization requirements, improvement in pulmonary function tests, and a remarkable decrease in peak expiratory flow rate circadian variability when compared with the period before TAO treatment (with corticosteroids). Treatment with MP and TAO was fairly well tolerated. Only a reduction (-5.2%, p0.01) in bone mineral content and an increase in plasma glucose levels (from 81.7 to 94.3 mg/dl, p0.05) were found, in comparison with pre-TAO values. One subject discontinued MP-TAO treatment because of a mild but persistent increase in serum alanine aminotransferase. In an evaluation of the clinical and pulmonary function test results, eight of the 14 subjects were responders and six were nonresponders. During follow-up three subjects discontinued TAO and consequently had an asthmatic attack after 4, 7, or 15 days, respectively.This study confirms that treatment with MP and TAO has a beneficial effect in a subgroup of severely steroid-dependent asthma patients.

The need for a postoperative treatment of patients with highly aggressive endometrial cancer necessitates more specific and accurate prognostic indicators.In a prospective study, 88 samples from 72 endometrial tumors were subjected to microfluorometric single-cell DNA analysis to assess the DNA content of the main stemline and the ploidy distribution histogram. The histologic grade of differentiation, architecture, and mitotic index (MI) also were evaluated as biologic characteristics of neoplastic cells.The main stemline was peridiploid in 44 of 72 cases, peritetraploid in 4 of 72, and aneuploid in 24 of 72. High ploidy levels (3 c) were associated strictly with papillary and solid architecture, high MI, and undifferentiated grade. Multiple analyses of different sites showed stable ploidy values in 11 of 13 cases; 2 solid tumors changed from showing peridiploidy to peritetraploidy in one of the three sites examined. The number of S-phase and greater than G2 cells (heteroploid index) was compared with MI and showed six tumors with histogram irregularities probably resulting from intratumor genetic instability. Survival information was available for 65 patients with a mean observation period of 50 months. A single parameter, high ploidy level (3 c), was the most important determinant of survival at all stages; its prognostic value was fundamental in patients with Stage I disease, in whom DNA content showed higher independent significance (P0.001) than the other histologic and clinical factors considered.These studies suggest that DNA content is a biologic characteristic firmly associated with tumor aggressiveness; DNA analysis could offer early and objective evidence of an intrinsic highly malignant phenotype.

The pathogenetic mechanisms of occupational asthma (OA) due to low-molecular-weight compounds have been poorly defined, and further studies are required to clarify the role of immunologic mechanisms in OA. Until now cellular mechanisms have been less investigated than humoral ones. We have evaluated interleukin-1 (IL-1) and tumor necrosis factor (TNF) production by peripheral blood monocytes (PBM), and peripheral T-cell subpopulations in 22 subjects with possible OA before and after specific bronchoprovocation test (SBPT). After SBPT, three subjects had an immediate reaction, seven a late reaction, and two a dual reaction. Ten subjects had no asthmatic reaction to SBPT. Spontaneous release of IL-1 from PBM did not change significantly after SBPT. TNF activity was increased 48 h after SBPT in immediate reactions, and 72 h after SBPT in late-dual reactions. These results suggest that exposure to occupational agents may induce activation of PBM with increased spontaneous release of cytokines, such as TNF.

To differentiate histologically partial hydatidiform moles (PM) and complete hydatidiform moles (CM) may be difficult. Cytogenetic studies have shown that PMs often had a triploid karyotype while CMs were always diploid. We assessed the DNA content of 31 paraffin-embedded cases of trophoblastic disease with flow cytometry. Twenty-four cases were histologically diagnosed as PM, 3 cases as CM; the others as hydropic abortion (2 cases), choriocarcinoma (1 case), and persistent trophoblastic disease (1 case). Four normal term placentas were used as diploidy controls. In 9 cases the results of the cytogenetic analysis were available. All placental specimens included also maternal tissue as an internal control. Eight of the 24 histologically diagnosed PMs were triploid; there was agreement in 8 cases out of 9 (90%) between the flow cytometric analysis and the karyotypic determination of ploidy. All normal controls as well as the hydropic abortion, the CM and the persistent trophoblastic disease were diploid. Abnormal content of DNA (DI = 1.3) was observed in the choriocarcinoma. Our results show that flow cytometric analysis of DNA content is a reliable and fast method of diagnosing PM on paraffin-embedded material.

Vasopressin plasma concentrations have been measured in two groups of subjects, 13 moderate essential hypertensive patients without target organ damage and eight control normotensive subjects, before and after the assumption of the upright position, and intravenous infusions of hypotonic saline (0.45% NaCl, 0.25 ml kg-1 min-1 for 1 h) and hypertonic saline (100 mmol NaCl in 50 ml). Plasma vasopressin in recumbent baseline conditions was not significantly different in the two groups. Upright posture and hypertonic challenge augmented, while hypotonic saline reduced plasma vasopressin levels, which were not significantly different between the two groups. Plasma renin activity increased in the upright position, was reduced by administration of hypotonic saline and unaffected by hypertonic saline, with no differences between the hypertensives and normotensives. After hypertonic saline, urinary flow rate and urinary sodium excretion in the hypertensive group increased to values significantly (p less than 0.05) higher than in normotensive subjects. In conclusion our study excludes significant alteration of vasopressin regulation in moderate uncomplicated hypertension. In hypertensives although the response of vasopressin to an osmotic load is preserved, the data suggest that the renal handling of the osmotic load may be altered.

The effects of capsaicin, the ingredient of hot pepper, on rheumatoid arthritis synoviocytes have been studied. Capsaicin was shown to have a direct action on the metabolism of synovial cells. Thus at 10(-6) mol/l and at higher doses DNA synthesis was restored to the control level. Capsaicin at both doses induced an increase in the synthesis of collagenase and at the lower concentration (10(-8) mol/l) only of prostaglandins. These results indicate that the different effects of capsaicin on cellular proliferation and on metabolic activities are dependent on dose. The responses seen in rheumatoid arthritis synoviocytes in vitro might not be mediated by tachykinins if the synovial tissue is still able to produce neuropeptides in the absence of neuronal afferents. These results suggest that capsaicin, in addition to its direct action on the afferent nervous fibres and the consequent release of tachykinins, may also have a direct action on the cells. The mechanisms by which capsaicin stimulates DNA synthesis and production of collagenase and prostaglandin E2, in a manner dependent on dose, remain to be determined.