Stimulant and hallucinogenic novel psychoactive substances; an update.

INTRODUCTION: The renewed interest in considering a range of stimulants, psychedelics and dissociatives as therapeutics emphasizes the need to draft an updated overview of these drugs' clinical and pharmacological issues. AREAS COVERED: The focus here was on: stimulants (e.g. amphetamines, methamphetamine, and pseudoephedrine; phenethylamines; synthetic cathinones; benzofurans; piperazines; aminoindanes; aminorex derivatives; phenmetrazine derivatives; phenidates); classical (e.g. ergolines; tryptamines; psychedelic phenethylamines), and atypical (e.g. PCP/ketamine-like dissociatives) psychedelics.Stimulant and psychedelics are associated with: a) increased central DA levels (psychedelic phenethylamines, synthetic cathinones and stimulants); b) 5-HT receptor subtypes' activation (psychedelic phenethylamines; recent tryptamine and lysergamide derivatives); and c) antagonist activity at NMDA receptors, (phencyclidine-like dissociatives). EXPERT OPINION: Clinicians should be regularly informed about the range of NPS and their medical, psychobiological and psychopathological risks both in the acute and long term. Future research should focus on an integrative model in which pro-drug websites' analyses are combined with advanced research approaches, including computational chemistry studies so that in vitro and in vivo preclinical studies of index novel psychoactives can be organized. The future of psychedelic research should focus on identifying robust study designs to convincingly assess the potential therapeutic benefits of psychedelics, molecules likely to present with limited dependence liability levels.

New/emerging psychoactive substances and associated psychopathological consequences.

BACKGROUND: The present paper provides an updated review of both the large number of new/novel/emerging psychoactive substances (NPS) and their associated psychopathological consequences. Focus was here given on identification of those NPS being commented in specialised online sources and the related short-/long-term psychopathological and medical ill-health effects. METHODS: NPS have been identified through an innovative crawling/navigating software, called the 'NPS.Finder®', created in order to facilitate the process of early recognition of NPS online. A range of information regarding NPS, including chemical and street names; chemical formula; three-dimensional image and anecdotally reported clinical/psychoactive effects, were here made available. RESULTS: Using the 'NPS.Finder®' approach, a few thousand NPS were here preliminarily identified, a number which is about 4-fold higher than those figures suggested by European and international drug agencies. NPS most commonly associated with the onset of psychopathological consequences included here synthetic cannabinoids/cannabimimetics; new synthetic opioids; ketamine-like dissociatives; novel stimulants; novel psychedelics and several prescription and over-the-counter medicines. CONCLUSIONS: The ever-increasing changes in terms of recreational psychotropics' availability represent a relatively new challenge for psychiatry, as the pharmacodynamics and pharmacokinetics of many NPS have not been thoroughly understood. Health/mental health professionals should be informed about the range of NPS; their intake modalities; their psychoactive sought-after effects; the idiosyncratic psychotropics' combinations and finally, their medical and psychopathological risks.

Peptide receptor radionuclide therapy for aggressive pituitary tumors: a monocentric experience.

In aggressive pituitary tumors (PT) showing local invasion or growth/recurrence despite multimodal conventional treatment, temozolomide (TMZ) is considered a further therapeutic option, while little data are available on peptide receptor radionuclide therapy (PRRT). We analyzed PRRT effectiveness, safety and long-term outcome in three patients with aggressive PT, also reviewing the current literature. Patient #1 (F, giant prolactinoma) received five cycles (total dose 37 GBq) of 111In-DTPA-octreotide over 23 months, after unsuccessful surgery and long-term dopamine-agonist treatment. Patient #2 (M, giant prolactinoma) underwent two cycles (12.6 GBq) of 177Lu-DOTATOC after multiple surgeries, radiosurgery and TMZ. In patient #3 (F, non-functioning PT), five cycles (29.8 GBq) of 177Lu-DOTATOC followed five surgeries, radiotherapy and TMZ. Eleven more cases of PRRT-treated aggressive PT emerged from literature. Patient #1 showed tumor shrinkage and visual/neurological amelioration over 8-year follow-up, while the other PTs continued to grow causing blindness and neuro-cognitive disorders (patient #2) or monolateral amaurosis (patient #3). No adverse effects were reported. Including the patients from literature, 4/13 presented tumor shrinkage and clinical/biochemical improvement after PRRT. Response did not correlate with patients' gender or age, neither with used radionuclide/peptide, but PRRT failure was significantly associated with previous TMZ treatment. Overall, adverse effects occurred only in two patients. PRRT was successful in 1/3 of patients with aggressive PT, and in 4/5 of those not previously treated with TMZ, representing a safe option after unsuccessful multimodal treatment. However, at present, considering the few data, PRRT should be considered only in an experimental setting.

Combined BRAFV600E analysis and 99mTc-MIBI scintigraphy can be a useful diagnostic tool in differentiated thyroid cancer patients with incomplete bio-chemical response to first radioiodine therapy (RAIT): a pilot investigation.

PURPOSE: The aim of the present study was to evaluate the possible diagnostic role of the combined performance of BRAF mutation analysis and MIBI scintigraphy in papillary thyroid cancer (PTC) patients with incomplete bio-chemical response to first radioiodine therapy (RAIT) performed for thyroid remnant ablation. METHODS: The records of 15 PTC patients with bio-chemical incomplete response to first RAIT were retrospectively analyzed. BRAFV600E analysis on primary tumor samples was obtained in all cases along with neck ultrasonography and 99mTc-MIBI scintigraphy of the neck-thorax regions at first follow-up. All patients then underwent RAIT with high radioiodine activities. A post-therapy whole-body scan (pT-WBS) was acquired 5-7 days after RAIT. RESULTS: Abnormal radioiodine uptake was found in 10 out of the 15 patients (67%, 131I+ve), while in the remaining 33%, no abnormal radioiodine uptake was detected (5/15, 131I-ve). Abnormal tracer uptake was found in 6 out of 10 131I+ve patients at 99mTc-MIBI scintigraphy (MIBI+ve). BRAFV600E mutation was not found in the majority of 131I+ve patients (9 out of 10 BRAFV600E-ve). On the contrary, in the 5 131I-ve patients, 99mTc-MIBI scintigraphy did not show any abnormal tracer uptake (MIBI-ve), while BRAFV600E mutation was present (BRAFV600E+ve). Thus, in our series, the association between MIBI-ve scintigraphy and BRAF+ve mutation was a useful diagnostic tool in predicting negative pT-WBS outcome. CONCLUSION: Albeit obtained in a small retrospective series, our results suggest that the combination of BRAFV600E+ve mutation and MIBI-ve scintigraphy may be considered a negative prognostic clue, which predicts the absence of radioiodine uptake at pT-WBS in DTC patients with incomplete bio-chemical response to first RAIT.

Sentinel node biopsy after neoadjuvant treatment in breast cancer: Five-year follow-up of patients with clinically node-negative or node-positive disease before treatment.

PURPOSE: It is controversial whether sentinel node biopsy (SNB) without axillary dissection (AD) should be performed in cN1/2 breast cancer patients who become cN0 after neoadjuvant treatment, since the false negative rate (FNR) may be unacceptably high. We assessed outcomes to address this issue. METHODS: We retrospectively assessed 396 cT1-4, cN0/1/2 patients, who became or remained cN0 after neoadjuvant treatment and underwent SNB with at least one sentinel node (SN) found, and AD not performed if the SN was negative. RESULTS: After a median follow-up of 61 months (interquartile range 38-82), five-year overall survival was 90.7% (95% CI, 87.7-93.7) in the whole cohort, 93.3% (95% CI, 90.0-96.6) in those initially cN0, and 86.3% (95% CI, 80.6-92.1) in those initially cN1/2 (P = 0.12). Axillary failure occurred in only 1 (0.7%) initially cN1/2 patient who became cN0. In initially cN0 patients, and also initially cN1/2 patients who responded well to neoadjuvant treatment (ypT0/ypTx), SN-negativity was a significant predictor of good outcome, consistent with the known prognostic significance of axillary status, and suggesting that SN status accurately reflected axillary status. By contrast, in initially cN1/2 patients found to be ypT1/2/3, SN status (and whether or not AD was performed) had no influence on survival. CONCLUSIONS: These findings suggest that SNB is acceptable in cN1/2 patients who become cN0 after neoadjuvant therapy.

High prevalence of latent tuberculosis infection in autoimmune disorders such as psoriasis and in chronic respiratory diseases, including lung cancer.

The early diagnosis and treatment of individuals harboring M. tuberculosis is key to ensuring the effectiveness of health programs aimed at the elimination of tuberculosis (TB). Monitoring for TB also has other important health care implications for the related immune pathology caused by the chronic inflammatory response to M. tuberculosis. Moreover, the recent introduction of biologic therapies for the treatment of several immune-mediated inflammatory diseases has shown unexpected high frequencies of reactivation of latent TB. The present cross-sectional study is aimed at estimating the prevalence of latent tuberculosis infection (LTBI) in different groups of subjects, either undergoing a routine program of screening for TB or a clinical monitoring of autoimmune or lung disorders, by analyzing their immune response in vitro to a pool of different M. tuberculosis antigens through an IFN-gamma-release assay (IGRA). We consecutively tested 1,644 subjects including health care workers (931), healthy immigrants from different countries (93), patients with a diagnosis of psoriasis (405), patients with lung inflammatory disease (60) or lung neoplasia (32) and a group of HIV-1 infected Italian subjects (120). The prevalence of IGRAs positive responses among health care workers was 8.9 percent. In comparison, significantly higher frequencies were found in healthy immigrant subjects (33.3%), similar to those found in inflammatory broncho-pneumopathies (34.5%) or lung cancer (29.6%). Interestingly, an unexpected high prevalence was also found in patients affected by psoriasis (18.0%), while HIV-infected subjects had values comparable to those of health care workers (10.8%). An age cut-off was determined and applied for each group by receiver operating characteristic (ROC) curves in order to perform the statistical analysis among age-comparable groups. Multivariate analysis showed that the age and clinical conditions such as having a diagnosis of psoriasis or a lung inflammatory disease were independent risk factors for developing an IGRA positive response. This study highlights an unprecedented high prevalence of IGRA positive responses among patients affected by psoriasis and emphasizes the need for a preliminary assessment of LTBI before the administration of any biologic therapy based on cytokine antagonists such as anti-TNF-alpha. Moreover, screening for LTBI should be routinely performed in the presence of a chronic pulmonary disease.

Folie à deux: double case-report of shared delusions with a fatal outcome.

BACKGROUND: Treatment of shared delusional disorder (folie à deux) often involves separation and use of antipsychotic medication, with uncertain outcomes and potential risks. METHODS: We report on two highly interdependent and chronically psychotic sisters with shared systematic delusion, followed by psychiatrists over several years. RESULTS: The dominant patient was diagnosed with schizoaffective disorder and her non-dominant sister with paranoid schizophrenia. Both received antipsychotics and supportive therapy as outpatients and allowed to continue conjoint therapy with individual psychiatrists-therapists. They returned for follow-up visits for 20 months, when the dominant decided to continue treatment alone, as her sister gradually improved symptomatically and functionally. After separation, the dominant became increasingly anxious. She impulsively ingested an overdose of the non-dominant sister's medicines and died of cardiac arrest, despite her sister's efforts to seek medical assistance. The surviving non-dominant sister developed anxiety and increasing agitation requiring psychiatric hospitalization and increased pharmacotherapy. She improved gradually, but continued to be dysfunctional and required placement in a psychiatric inpatient unit for several months, eventually doing better in a community-based rehabilitative program with regular psychiatric follow-up. CONCLUSIONS: Combined treatment of patients with folie à deux may encourage continuous pathological interactions, but separation may increase risk of adverse outcomes.

Impact of early angiographic evaluation on the frequency of emergency reoperations after coronary bypass surgery.

BACKGROUND AND AIMS: early graft failure following coronary bypass surgery results in elevated morbidity and mortality. This study focused on the impact of angiographic graft evaluation. MATERIAL AND METHODS: of 5251 coronary artery bypass grafting (CABG) patients, 36 with postoperative persistent ischaemia underwent early angiography (23) or emergency resternotomy (13) 2000-2007 (Angiography era). Of the 23 patients, who underwent angiography, five were subsequently reoperated. Of 8807 CABG patients, 76 underwent postoperative emergency resternotomy 1988-1999 (Pre-angiography era) and served as controls. RESULTS: the angiography era patients were older (64.0 years vs. 58.2 years, P = 0.002) and the proportion of female patients (22% vs. 43%, P = 0.029) was smaller. The rate of emergency reoperations decreased (0.86% vs 0.34%, P < 0.001) during the Angiography era and graft repairs (P = 0.013) or additional grafts (P = 0.006) were less frequent, although occluded anastomoses were observed more often (P = 0.043). In 5 Angiography era patients graft complications were corrected with percutaneous coronary intervention. ICU stay (5.72 + 0.98 days vs. 5.53 + 0.68 days) and hospital stay (12.2 + 1.54 days vs. 13.1 + 1.63 days) did not differ between the groups, but the rate of myocardial infarction (63.8% vs. 92.1%, P < 0.001) and in-hospital death (22.2% vs. 46.1%, P = 0.015) decreased. CONCLUSION: after the introduction of early postoperative angiographic evaluation of CABG patients the rate of emergency reoperations and related morbidity and mortality decreased.

Ischemic intestinal injury during cardiopulmonary bypass does not show an association with neutrophil activation: a porcine study.

BACKGROUND: Neutrophil activation and tissue sequestration are crucial events in intestinal ischemia-reperfusion injury, but their role in the gut wall after clinical cardiopulmonary bypass (CPB) remains unclear. We tested whether local post-CPB inflammatory response in the gut wall would be associated with intestinal mucosal perfusion. METHODS: Twenty pigs underwent 60 min of aortic clamping and 75 min of normothermic perfusion. Intestinal biopsies were taken after 120 min of reperfusion. Based on ileal myeloperoxidase activity (MPO), the animals were divided into 2 groups, CPB-induced increase in MPO (MPO+) versus no such increase (MPO-), for comparison of the parameters that measure gut mucosal perfusion. Ileal p(CO)((2)) and intramucosal pH were determined, and arterial gases were analyzed. Additionally, several hemodynamic parameters and blood thrombin-antithrombin complexes (TAT) were measured. RESULTS: Myocyte degeneration, endothelial activation and vasculitis were more pronounced in the MPO+ group (p < 0.05), while the MPO- group showed significantly increased pi(CO)((2)) and lower mucosal pH values during reperfusion. Hemodynamics and TAT levels did not differ between the groups. CONCLUSION: Tissue sequestration of neutrophils was poorly associated with perturbed mucosal perfusion after CPB. Mechanisms of gut wall injury after a low-flow/reperfusion setting can differ from those in reperfusion injury after total ischemia.

Serum cytokines and bioumoral immunological characterization of psoriatic patients in long term etanercept treatment.

The purpose of this study is to evaluate blood cytokines and immunological parameters in psoriatic patients during long-term treatment with Etanercept. Forty-five subjects of both sexes affected by psoriasis with or without arthritis entered the study and were treated with Etanercept according to international standard protocols. Biochemical blood analysis was carried out at baseline and during follow-up every second month. In particular, the following parameters were kept under control: antinuclear antibodies, anti-nDNA antibodies, anti-histone antibodies, blood cell count, circulating lymphocyte subtypes (CD3, CD4, CD8, CD16, CD19) and IgE. Cytokine profiles (IL-1-alpha, IL-1-beta, IL-6, IL-8, IL-10, IL-12, INF, TNF-alpha) were also evaluated in blood samples during the treatment up to 1 year of follow-up. A significant decrease in PASI score (p < 0.01) and in several cytokine levels was observed, particularly in IL-1, IL-6, IFN-gamma (p < 0.01) and to a lesser extent in TNF-alpha (p < 0.05). No statistically significant changes were recorded after 1 year of follow-up in blood immunological parameters, in particular in ANA titre, CD4/CD8 ratio, IgE levels, CD16, CD19 and eosinophils count. In conclusion, long-term treatment with Etanercept leads not only to a significant improvement in PASI score, but also to significant changes (reduction) in several proinflammatory and modulatory cytokines involved in the pathogenesis of the disease; on the other hand, there are no effects on immunological or bioumoral parameters showing that etanercept modulates rather than suppresses the physiological responses during psoriasis treatment.

An evaluation of mitral valve procedures using the European system for cardiac operative risk evaluation.

BACKGROUND AND AIMS: This study was undertaken in order to evaluate the usefulness of the Euroscore in the choice and outcome of mitral valve procedures undertaken at the Helsinki University Central Hospital. MATERIAL AND METHODS: Data from 378 patients was collected. predicted mortalities were calculated for all patients using the European System for Cardiac Operative Risk Evaluation and different mitral valve procedures were compared with 30-day mortality, length of hospital care and rate of post-operative complications. RESULTS: The mortality rate in the mitral valve repair (MVP) group decreased gradually from 5.9% (in 1999) to 2.2% (2003). The variation of annual mortality was higher in the mitral valve replacement (MVR) group. The predicted mortality given by Euroscore increased over the years in both groups. The mortality in the MVR group was nearly four times higher than in the MVP group. the length of both intensive and overall hospital stay decreased in patients with MVP procedures. Post-operative survival was 89% in the MVP patients and 74% in mvr patients after three years. DISCUSSION: The results of mitral valve operations have improved. This is observed as decreased mortality rates and lengths of hospital care in the MVP group, although the predicted mortality rate was increased.

Antithrombin reduces pulmonary hypertension during reperfusion after cardiopulmonary bypass in a pig.

BACKGROUND: Antithrombin (AT) may alleviate many cardiopulmonary bypass (CPB) and ischemia-reperfusion (I/R)-related adverse effects. Using a porcine model of clinical cardiac surgery on CPB, we tested the effects of supplementary AT on myocardial and lung I/R injury. METHODS: Twenty pigs undergoing 60-min aortic clamping and 75-min normothermic perfusion were randomized in a blinded setting to receive an intravenous (i.v.) bolus of AT (250 IU/kg) (AT group, n = 10) or placebo (n = 10) 15 min before aortic declamping. An additional group of five animals received 500 IU/kg AT in an open-label setting (AT+). Thrombin-antithrombin complexes (TAT), activated clotting times (ACT), AT and myeloperoxidase (MPO) activities, troponin T, and several hemodynamic parameters were measured before CPB and after weaning from CPB up to 120 min after aortic declamping. After 120 min of reperfusion, myocardial and lung biopsies were taken for histological examination. RESULTS: AT effectively inhibited coagulation as assessed by ACT. In the AT and AT+ groups only, cardiac output (CO) and stroke volume (SV) showed a trend of post-ischemic recovery during the first 15 min after CPB. AT-attenuated reperfusion induced an increase in pulmonary arterial diastolic pressure (PAPD) but did not have significant effects on systemic or pulmonary vascular resistance. The effects of AT on SV, CO, and PAPD were fortified in the AT+ group. AT did not show effects on inflammatory changes in either myocardial or pulmonary tissue specimens. AT did not reduce post-ischemic troponin T release. CONCLUSION: Supplementary AT, in doses with significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of histological inflammatory changes or post-ischemic troponin T release. Instead, however, AT-attenuated reperfusion induced an increase in pulmonary pressure after CPB. Mechanisms and clinical implications of these effects remain to be explored.

Vasopressin, when added to norepinephrine, was not associated with increased predicted mortality after cardiac surgery.

BACKGROUND AND AIMS: Arginin vasopressin (AVP) is a potent vasoconstrictor which has been used in vasodilatory shock when therapy with catecholamines and fluids has failed. In this study we evaluated the association of AVP with organ failure and mortality in cardiac surgical patients suffering from vasodilatory shock refractory to norepinephrine (NE) treatment. MATERIAL AND METHODS: Cardiac surgical patients who received AVP in addition to NE (N=33, AVP-group) and 33 control patients (NE group) who were treated with an equal dose of NE compared with AVP patients when AVP infusion started. Data on preoperative risk factors according to EuroSCORE and predicted mortality calculated by logistic EuroSCORE were collected preoperatively. Data on hemodynamics, organ dysfunctions, length of intensive care unit stay and mortality were collected. RESULTS: EuroSCORE did not differ between the groups, AVP:10.4 +/- 3.9 vs. NE 8.9 +/- 4.0. Observed 30 day mortality was lower than predicted in both groups, AVP: 7 (21.7%) vs. predicted mortality 25.9% and NE: 2 (6.1%) vs. 16.0%, respectively. There were more renal complications (36.4% vs. 9.1%, p = 0.008) and infections (30.3% vs. 3.0%, p = 0.003) in patients receiving AVP. Cardiovascular complications did not differ between the groups. CONCLUSIONS: In this prospectively observed cohort of cardiac surgical patients, AVP did not increase mortality predicted by Euroscore. Anyhow renal and infection complications were common.

Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery.

BACKGROUND: Pre-existing chronic renal failure is a significant risk factor for acute renal failure (ARF) after cardiac surgery. N-acetylcysteine (NAC) has been shown to prevent contrast media-induced ARF. Our objective was to evaluate whether i.v. NAC has renoprotective effects in patients with mild renal failure undergoing cardiac surgery. METHODS: In this prospective, randomized, double-blind study, 80 patients with mild to moderate renal failure undergoing elective heart surgery with cardiopulmonary bypass were recruited. All received either i.v. NAC (n=38) or placebo (n=39) at induction of anaesthesia and then up to 20 h. Urine N-acetyl-beta-D-glucosaminidase (NAG) and urine creatinine ratio, plasma creatinine, and serum cystatin C levels indicated renal function. RESULTS: Levels of urinary NAG/creatinine ratio, plasma creatinine and serum cystatin C did not significantly differ between NAC and placebo groups during five postoperative days. Urine NAG/creatinine ratio increased over 30% in 100% of patients in the NAC group vs 92.3% in the placebo group (P=0.081). Plasma creatinine increased by 25% from baseline or over 44 mumol litre(-1) in 42.1% in NAC group vs 48.7% in placebo group (P=0.560). Serum cystatin C exceeded 1.4 mg litre(-1) in 78.9% in NAC group vs 61.5% in placebo group (P=0.096). CONCLUSIONS: Prophylactic treatment with i.v. N-acetylcysteine had no renoprotective effect in patients with pre-existing renal failure undergoing cardiac surgery.

Sentinel lymph node biopsy for localised ductal carcinoma in situ?

Intraductal carcinoma of the breast (DCIS), by definition, cannot give axillary metastases. Axillary dissection is therefore not indicated. The role of the sentinel lymph node (SLN) biopsy in the management of DCIS has not yet been established. A 6-13% risk of SLN involvement is reported in Literature. The aim of the present study is to assess the role of SLN biopsy in patients with pure DCIS and attempt to identify guidelines for routine practice in managing such patients. From March 1996 to December 2003, 508 consecutive patients with pure DCIS of the breast underwent SLN biopsy at the European Institute of Oncology in Milan. Clinical and pathological data were prospectively collected. In all cases of previous surgery or stereotactic biopsy performed elsewhere all pathological slides were reviewed. Cases with microinvasion were excluded from this investigation. Lymphatic mapping was performed using a radiocolloid technique. Most of the patients underwent conservative surgery and removal of the SLN which was sent for conclusive histology. SLN metastases were detected in 9 out of 508 (1.8%) patients. In five patients only micrometastasis (<2 mm) was detected. Eight patients underwent complete axillary dissection. In none of these patients did we find additional positive axillary lymph nodes. In conclusion, due to the low prevalence of metastatic involvement (1.8%), SLNB should not be considered a standard procedure in the treatment of all patients with DCIS. In pure non-comedo DCIS completely excised by radical surgery with free margins of resection SLNB should be avoided since not only it is unnecessary but could also jeopardize a successive re-SLNB in case of invasive recurrence. A very extensive and accurate histological examination of the tumour in DCIS is compulsory to exclude micro-invasive foci and, finally, to decrease the prevalence of unexpected SLN metastases. SLNB should be considered in case of DCIS where there exists a strong doubt of invasion at the definitive histology, such as large solid tumours or diffuse or pluricentric microcalcifications undergoing mastectomy. Moreover, if the trend is statistically confirmed with a wider population, large comedo-DCIS, presenting superior risk of SLNs metastasis, could be scheduled for SLNB. If the SLN is micrometastatic complete axillary dissection is not unavoidable.

Development of axillary surgery in breast cancer.

Axillary surgery is a critical part of the treatment of breast carcinoma: its importance is related to the staging of disease, prescription of adjuvant therapy and prognosis. For years, complete axillary dissection has remained the standard approach to breast cancer lymphatic staging; its value is still high, but the development of sentinel-node biopsy has significantly changed the indication of the procedure. We discuss the evolution of axillary surgery in breast cancer.

Evaluation of recombinant antigen-based assays for diagnosis of bullous autoimmune diseases.

The diagnosis of autoimmune bullous diseases is based on clinical observation and on the presence of autoantibodies directed to molecules involved in the adhesion systems of the skin. Immunofluorescence assays are the currently accepted method for detection of autoantibodies; such assays depend greatly on the skill of operators and are difficult to standardize. Recombinant desmoglein-1 (Dsg1), Dsg3, and BP180 peptides, the main autoantigens in pemphigus or bullous pemphigoid, have been used to develop new quantitative enzyme immunoassays (EIA) for the detection of specific antibodies. The present study was undertaken to evaluate the sensitivity and specificity of these immunoassays and to determine the correlation between the results and the clinical aspects of diseases. Serum samples from patients with pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, or mucous membrane pemphigoid, from healthy individuals, and from patients with unrelated autoimmune conditions were tested. Anti-desmoglein reactivity was detected in all the patients with pemphigus and in none of the controls. Patients with the more benign form of cutaneous disease had anti-Dsg1 antibodies, while patients with deeper cutaneous lesions or with mucosal involvement had anti-Dsg3 reactivity also, or exclusively. The BP180-based assay was positive for 66.6% of patients with bullous pemphigoid and for none of the patients with mucous membrane pemphigoid, and no reactivity was detected in the control sera. In conclusion, the anti-Dsg1 and anti-Dsg3 assays are useful in the diagnosis of pemphigus and provide information on the clinical phenotype of the disease. However, the sensitivity of EIA for detection of autoantibodies in bullous pemphigoid should be improved by the use of additional antigens or epitopes.

Possible role of nitric oxide in the biology of breast carcinoma: review of the available literature.

Nitric oxide was studied to investigate its possible involvement in the promotion of breast carcinoma: both the development of the primary tumour and the process of metastasis seem to be influenced by the presence and the amount of nitric oxide. We review the available literature on this topic, which seems to suggest an influence of nitric oxide on the cancer cell biology in breast carcinoma, but the argument is still controversial. More studies are needed to clarify the sequence of events and the real impact of nitric oxide on the behaviour of the disease.