Effect of acute and chronic vitamin D administration on systemic renin angiotensin system in essential hypertensives and controls.

AIM: To investigate the systemic renin-angiotensin system (RAS) in essential hypertensives (EH) and controls (C) after short- and long-term vitamin D receptor activation. DESIGN: Ten consecutive EH (under controlled low-salt diet) and 10 C underwent calcitriol administration (0.25 µg bid) for 1 week (Group A). Eighteen consecutive EH under angiotensin II receptor antagonist therapy received a single oral dose of 300,000 IU of cholecalciferol and were followed up for 8 weeks (Group B). METHODS: In basal conditions and at the end of the study (1 week in Group A and 8 weeks in Group B), plasma renin activity (PRA), plasma active renin, aldosterone, and angiotensin II were evaluated, as well as blood pressure, plasma 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and PTH. RESULTS: In Group A, plasma 25(OH)D levels in EH and C were below the normal range, although lower levels were found in the former. No association between basal plasma 25(OH)D or 1,25(OH)2D levels and blood pressure values or RAS components was observed either in the whole group or in the two subgroups. Calcitriol administration did not affect any RAS parameter either in EH or in C. In Group B, cholecalciferol significantly increased 25(OH)D and 1,25(OH)2D levels without interfering with the angiotensin II receptor antagonist-induced increase in RAS components. No correlation was found between plasma 25(OH)D or 1,25(OH)2D levels and blood pressure values or RAS parameters before and after cholecalciferol administration. CONCLUSIONS: The present data suggest that, in our experimental conditions, vitamin D receptor activation is unable to influence systemic RAS activity.

Cardiovascular changes in patients with primary aldosteronism after surgical or medical treatment.

BACKGROUND: Data on the cardiovascular middle-term follow-up of patients with primary aldosteronism (PA) are scanty. AIM: To detect the cardiovascular effects of surgery in patients with aldosterone (ALD)-producing adenoma (APA) and of pharmacotherapy in those with bilateral adrenal hyperplasia (BAH), a prospective study involving 60 consecutive patients with PA was performed. MATERIAL/ METHODS: Clinical, biochemical, and cardiovascular assessment was obtained before and after (31.5±4.4 months) surgery or proper medical treatment (32.1±5.0 months) in 19 and 41 patients, respectively. RESULTS: As expected, plasma ALD normalized in all operated patients, while in the other group it did not change. Systolic and diastolic blood pressure decreased (p<0.001) after both treatments. However, absolute and percentage reduction was significantly more pronounced (p<0.01) in operated than in non-operated patients. Left ventricular (LV) mass showed significant reduction after surgery (LV mass g/m(2), p<0.0007; LV mass g/m(2.7), p<0.01), but no change after medical treatment, so that the differences between absolute and percentage values at follow- up were statistically significant (p<0.01) between groups. Basal LV mass/m(2.7) was positively associated with age (p<0.009), body mass index (p<0.0008), drug number (p<0.03), and ALD/plasma renin activity ratio (p<0.01). Allocating the patients according to plasma ALD and cardiac parameters, patients who presented ALD reduction during the study also had a decrement in cardiac mass (p<0.04). CONCLUSIONS: Our data indicate that in patients with PA the removal of ALD excess by surgery in APA is effective in reducing blood pressure and in improving cardiac parameters, while anti-hypertensive therapy in BAH shows less positive impact on cardiovascular system.

Breast surgeons updating on the thresholds of COVID-19 era: results of a multicenter collaborative study evaluating the role of online videos and multimedia sources on breast surgeons education and training.

OBJECTIVE: Current trends show a rise of attention given to breast cancer patients' quality of life and the surgical reconstructive result. Along with this trend, surgical training quality and efficacy are gaining importance and innovative training methods such as online videos shared on social media portals, are becoming main updating tools. In hazardous times like COVID-19 pandemic nowadays, online communication becomes of vital importance and adaptation and innovation are fundamental to keep research and education alive. The authors aimed to investigate the role of video and multimedia sources on the daily activity and surgical training of a representative group of surgeons specifically dedicated to oncologic, oncoplastic and reconstructive breast surgeries. MATERIALS AND METHODS: A survey was produced and administered to 20 major Italian Breast Centers. Collected data were analyzed with Fisher's Exact Test. RESULTS: From October 2019 to March 2020, a total of 320 surveys were collected. Among the responders, there were 188 trainees (intern medical doctors and residents) and 110 faculty, 72% of them belonged to a plastic surgery environment, while 28% to general surgery environment. Almost all respondents have ever watched videos concerning breast surgery. CONCLUSIONS: The results of the study show how breast surgeons rely on videos and web platforms, mostly YouTube, when searching for training info about surgical procedures. Social media offer great opportunities for sharing knowledge and diffusion of new ideas but greater attention to their reliability is mandatory.

Cardiac remodeling in patients with primary aldosteronism.

OBJECTIVE: To evaluate the morpho-functional changes of the myocardium in patients with primary aldosteronism (PA). DESIGN: An observational study in a university referral center for blood pressure diseases. PATIENTS: Twenty- three patients with PA, 24 patients with essential hypertension (EH), and 15 normotensive controls (C) underwent conventional echocardiography with integrated backscatter (IBS) and tissue Doppler imaging (TDI) analysis. The corrected IBS (C-IBS) values and the systo-diastolic variation of IBS (CV-IBS) were performed at both interventricular septum and the posterior wall levels. TDI myocardial systolic (Sm), early diastolic (Em), and late diastolic (Am) velocities of both left ventricular walls were also determined. RESULTS: In PA patients, septal and posterior wall CV-IBS were significantly lower than C (p<0.0001) and EH patients (p<0.001). In EH, CV-IBS was significantly lower than C (p<0.001). Patients with PA exhibited lower Sm, lower Em, and higher Am, and a subsequently reduced Em/Am ratio than C (p<0.001 for all) and EH (p<0.01 for all) at interventricular septum and lateral wall levels. In the latter, Sm, Em, and Em/Am ratio were lower and Am was higher than C (p<0.001 for all). In PA and EH patients, CV-IBS at both septum (r=-0.66, p<0.001) and posterior wall levels (r=-0.67, p<0.001) and Sm peak of both septum (r=-0.52, p<0.001) and lateral wall (r=-0.55, p<0.001) were inversely related to plasma aldosterone. CONCLUSIONS: Patients with PA showed myocardial wall remodeling characterized by increased myocardial fibrosis and early left ventricular systodiastolic function abnormalities.

Excellent long-term results in de novo renal transplant recipients treated with proliferation signal inhibitors and reduced calcineurin inhibitors exposure.

BACKGROUND: A new class of immunosuppressants, proliferation signal inhibitors (PSI)--sirolimus and everolimus--has the potential to prevent chronic allograft nephropathy (CAN). This retrospective analysis reports a 6-year practice using PSI at a single center, comparing a regimen based on reduced-dose calcineurin inhibitors (CNI) and PSI versus full-dose CNI and mycophenolic acid (MPA). METHODS: The study population included 70 patients (group A) who received de novo PSI therapy in combination with reduced dose of CNI, standard steroids, and basiliximab induction, and 216 patients (group B) with full-dose CNI, MPA, steroids, and basiliximab induction. RESULTS: No statistically significant differences were recorded in the baseline donor and recipient characteristics. A difference was observed in cold ischemia time, which could represent a bias for the analysis. No differences were recorded in actuarial patient survival, delayed graft function, biopsy-proven acute rejection rates, and renal function analysis. A significant difference was recorded in the actuarial graft survival rate at years 2, 3, and 4 (P< .01), as well as overall graft survival rates (P= .025). DISCUSSION: The reduction of cold preservation time seemed to be an important factor to improve both short- and long-term renal function. This regimen revealed a long-term trend toward better renal function and graft survival. The use of PSI with reduced doses of CNI seems to be indicated for suboptimal grafts, especially when a reduced quality of the kidney is associated with prolonged cold ischemia time.

Treatment of abdominal aortic aneurysms associated with pancreatic tumors: personal experience and review of the literature (1967-2006).

The aim of the present study was to discuss the approach to a rare, but challenging, clinical situation: the coexistence of an abdominal aortic aneurysm (AAA) and a pancreatic tumor. The authors present their experience and a review of the literature of the last 40 years. From January 1988 to December 2006 the authors faced 3 cases of associated AAA and pancreatic neoplasia. Through a Medline search the authors found 15 cases of this comorbidity reported in the literature from 1967 to 2006, obtaining a total number of 18 cases. The treatment of the two diseases was in a single stage in 4 cases (22%) and in two stages in 5 cases (28%), while only one pathology was treated in 7 cases (39%) and no treatment at all was attempted in 2 cases (11%). Mortality was 0%, while morbidity was 22%, i.e. in 4 cases out of 18, although no aortic prosthesis infection was recorded. From literature analysis and their experience the authors concluded that the surgical strategy in cases of AAA and a pancreatic tumor is to be chosen depending on the pancreatic tumor prognosis, the AAA dimensions and the schedule of chemotherapy. According to the authors, AAA surgical repair is recommended in case of pancreatic cystic adenoma and neuroendocrine neoplasia, in view of their good prognosis, while endovascular repair (EVAR), when feasible, is better in patients with pancreatic adenocarcinoma.

Lower airway inflammation before and after house dust mite nasal challenge: an age and allergen exposure-related phenomenon.

BACKGROUND: Upper and lower airways allergic disease is currently considered unitarily. Allergic inflammation in one site can extend to other sites of the respiratory tract. OBJECTIVE: To evaluate bronchial inflammation before and after allergen-specific nasal challenge (ASNC) in rhinitic and asthmatic children, considering the different levels of allergen exposure, i.e. summer (low) and winter (high). METHODS: Fourteen children with rhinitis and 15 with rhinitis and asthma, all monosensitized to mites and 10 healthy controls were studied. Nasal IgE were measured before ASNC in summer and in winter season. Nasal clinical score, eosinophil cationic protein (ECP), nasal tryptase, bronchial clinical score, FEV(1), PEF, sputum ECP, sputum tryptase and exhaled nitric oxide (eNO) were evaluated before and after ASNC in summer and winter season. RESULTS: Nasal scores significantly increased after ASNC in rhinitic and asthmatic children in both seasons. Nasal IgE were significantly higher in summer compared to winter. Bronchial symptoms, FEV(1) and PEF showed no mean differences in rhinitic and asthmatic children after ASNC, with an increase of bronchial symptoms and a decrease of FEV(1) and PEF occurring in 3/15 asthmatic children. In both groups nasal tryptase and ECP after ASNC significantly increased in summer and winter, while sputum tryptase was undetectable before or after ASNC in both groups. Sputum ECP and eNO at baseline were significantly higher in patients than in controls (summer P=0.002, winter P=0.001). Sputum ECP significantly increased after ASNC in 3/15 asthmatics in summer and in 11/15 in winter, as well as in 3/14 rhinitics in summer and in 4/14 in winter. eNO significantly increased after ASNC in 3/15 asthmatics in summer and in 10/15 in winter, and in 1/14 rhinitics in summer and in 4/14 in winter. A significant median increase of sputum ECP (P=0.0007) and eNO (P=0.0012) after ASNC in asthmatic and of eNO (P=0.013) in rhinitic children was also found in winter. CONCLUSIONS: Basal sputum ECP and eNO values, significantly higher before ASNC in rhinitic patients compared to control subjects, confirm the inflammatory link of upper and lower airways. The more frequent detection of inflammatory changes induced by ASNC in winter suggests that allergen exposure favours the transfer of nasal inflammation to lower airways.

Impact of molecular subtypes classification concordance between preoperative core needle biopsy and surgical specimen on early breast cancer management: Single-institution experience and review of published literature.

BACKGROUND: Core needle biopsy (CNB) plays a crucial role as diagnostic tool for breast cancer (BC). The characterization of biomarkers status before surgical treatment is crucial when primary systemic therapy is a therapeutic option. The aim of this analysis was to report concordance between preoperative CNB and surgical specimen (SS) in evaluating biomarkers and molecular subtypes. METHODS: Data have been collected from a cohort of 101 patients affected by early BC treated at Careggi Florence University Hospital, between January 2014 and March 2015. The conformity between molecular subtype classification was tested using kappa (κ) test. RESULTS: Mean age was 57.5 years (range 29-86). There was concordance between the estrogen receptor (ER) assessment on CNB and SS in 95 cases (94.1%). Concordance of the progesterone receptor (PgR) assessment was observed in 89 cases (88.1%). Concordance for detecting immunohistochemistry-assessed BC molecular subtypes was 87.1% (κ = 0.78). Concerning Ki-67 evaluation, we report a concordance rate of 88.1% (κ = 0.68). The evaluation of luminal A plus luminal B/HER negative subgroup showed a κ-value of 0.65. CONCLUSIONS: CNB showed good accuracy in evaluating hormonal receptors status, HER2, and BC molecular subtypes. Evaluation of Ki67 status was less accurate than other biomarkers; therefore, we recommend that it should be detected both on CNB and SS samples, especially in hormonal positive HER2 negative tumors, in order to avoid a misclassification of tumor subtypes that could lead to an omission of potential effective systemic therapy.

Long-term outcome of renal transplantation from marginal donors.

Long-term survival of kidneys from suboptimal donors is known to be not as good as that from optimal ones. However, the shortage of donors has led many transplant centers to consider accepting older donors with comorbidities. We analyzed 238 patients who received deceased donor renal transplants in the period 2000-2005. The recipients were matched to be no more than 15 years older or younger than the corresponding donors. Among them 125 received a single and 18 a double transplantation from donors considered marginal, according to UNOS criteria for expanded criteria donor (ECD). Most kidneys were evaluated with a pretransplant biopsy, using the scoring system introduced by Karpinski in 1999. The analysis indicated clearly better results in the non-ECD group: both patients and graft survival rates were 10% higher at 1, 2, and 3 years. However, the ECD group showed satisfactory outcomes, confirming the utility of this procedure. The long-term survival rates of single or double grafts from marginal donors are satisfactory, confirming the practice of allocating kidneys after a preimplantation histological evaluation, allowing expansion of the donor pool and providing older patients access to the waiting lists.

A randomized trial for the treatment of high-grade soft-tissue sarcomas of the extremities: preliminary observations.

A new trial for evaluating the effectiveness of adjuvant chemotherapy in high-grade soft-tissue sarcomas of the extremities in adult patients is presented. All patients after local treatment were randomized into two arms, one without further therapy and the other to receive adjuvant chemotherapy (Adriamycin [Farmitalia-Carlo Erba, Milan, Italy], 450 mg/m2). The preliminary results of the study are reported at a median observation period of 27.6 months. Of the 59 patients who entered the study, 79.1% in the chemotherapy group are without sign of disease, whereas the corresponding figure in the nonadjuvant chemotherapy group is 54.3%. The difference between the two groups is statistically significant (P less than .005, log rank test). These preliminary observations encourage continuation of the study.

Cytomegalovirus infection with multiple colonic perforations in a renal transplant recipient.

Cytomegalovirus (CMV) continues to be potentially the most important pathogen affecting organ transplant recipients. Severe gastrointestinal complications have been reported to occur in about 10% of renal transplant recipients, sometimes with dramatic presentations. We report the case of a 57-year-old CMV-seropositive woman with end-stage renal failure who developed CMV-related colonic multiple perforation 30 days after cadaveric CMV-positive renal transplantation. CMV pp65 antigenemia test and CMV-PCR had always been negative on all the weekly controls routinely performed in the postoperative period. Only after the sudden onset of this complication did the antigenemia and PCR become positive. The relationship between infection and perforation has been established beyond any doubt, as the histology of the resected colonic segment revealed florid CMV infection with evidence of typical inclusions in both macrophages and endothelial cells. Colonic perforations are often fatal in transplant recipients because of inability to contain the perforation, and only a rapid diagnosis and an aggressive surgical treatment can improve the prognosis.

Kidney transplantation from donors aged 65 years or more as single or dual grafts.

AIM: The organ shortage and aging donor population force transplant centers to accept donors previously considered unusable for kidney transplantation. We report the experience of two Italian transplant centers with single (SKTx) and dual (DKTx) kidney transplantation from donors aged 65 years or more. METHODS: The study population comprised 75 SKTx (mean donor age 70.5 years) and 28 DKTx (mean donor age 75.0 years). Kidneys from donors with a calculated admission creatinine clearance <50 mL/min, a Karpinski's score on kidney biopsy between 5 and 7, or both were allocated to DKTx. Grafts with better function or lower biopsy scores were employed for SKTx. RESULTS: Delayed graft function occurred in 45.3% of SKTx and in 39.3% of DKTx. After a mean follow-up period of 30.0 +/- 19.5 months, the acute rejection rate was 24.0% in SKTx and 7.1% in DKTx. Mean serum creatinine was 1.8 +/- 0.9 and 1.8 +/- 1.3 mg/dL in SKTx, and 1.8 +/- 1.6 mg/dL and 1.3 +/- 0.2 mg/dL in DKTx at 1 and 5 years, respectively. Patient survival was 93.3% and 91.2% in SKTx, and 92.9% and 92.9% in DKTx at 1 and 5 years, respectively. Graft survival was 92.0% and 88.3% in SKTx, and 89.3% and 89.3% in DKTx at the same time intervals. Keeping preservation time below 16 hours and avoiding calcineurin inhibitors were both associated with improved graft survival and function. CONCLUSION: Careful donor selection, short preservation time, and tailored immunosuppression allow safe and efficient use of elderly donor kidneys.

[Long-term results of neoadjuvant radiochemotherapy in squamous carcinoma of the thoracic esophagus]. / Risultati a lungo termine del trattamento chemio-radioterapico neoadiuvante del carcinoma squamoso dell'esofago toracico.

AIM: Surgery is considered the mainstay of therapy for clinically resectable esophageal cancer, even though neoadjuvant treatments are frequently added. The aim of this study was to analyse our experience on neoadjuvant treatment of squamous cell carcinoma of the thoracic esophagus with special reference to long-term METHODS: The results of 66 patients who underwent neoadjuvant chemo-radiotherapy for squamous cell carcinoma of the thoracic esophagus at the 1(st) Division of General Surgery, University of Verona, from February 1995 to December 2002 were analysed statistically. The median follow-up period for the surviving patients was 65.3 months. RESULTS: The induction treatment was completed in 93.9% of cases, with a null treatment related mortality and a complication rate of 34.8%. Sixty-one out of the 66 patients (92.4%) underwent resection with a R0-resection rate of 83.9%. A major pathological response (responders) was gained in 42.6% of the cases, with a complete response (pTONO) observed in 29.5% of the cases. Overall 5-year survival for the 66 patients was 30%, while the 5-year survival rate raised to 43% in R0-patients. A better long-term survival was observed for responders with respect to ''non-responders'' with a 5-year survival rate of 70% and 13%, respectively (P<0.001). CONCLUSIONS: This neoadjuvant protocol regimen represents a feasible treatment with an acceptable morbidity. The tumor efficacy in term of pathological responses was similar to literature RESULTS: An high rate of R0-resections was achieved with a possibility of cure limited to this group of patients. A better long-term survival was observed in patients with major pathological responses.

Tuning the target composition of amine-grafted CPO-27-Mg for capture of CO2 under post-combustion and air filtering conditions: a combined experimental and computational study.

A computational and experimental screening of hypothetical and real compounds exhibiting different degrees of ethylenediamine grafted to the CPO-27-Mg or Mg-DOBDC skeleton is performed in order to determine the target composition that optimizes the CO2 adsorption properties under flue gas and air filtering conditions. On the basis of the [Mg2(dobdc)] formula, eighteen hypothetical models involving 15-100% of functionalization of the coordinatively unsaturated sites (CUS) were considered by means of Grand Canonical Monte Carlo simulations to evaluate the CO2 adsorption at 298 K. In addition, post-synthesis modification was applied to CPO-27-Mg leading to three kinds of samples exhibiting 15, 50, and 60% of CUS functionalization with ethylenediamine, named CPO-27-Mg-a, CPO-27-Mg-b and CPO-27-Mg-c. Compounds were characterized using elemental analysis, TGA, FTIR spectroscopy, PXRD and DSC. Finally, bare and functionalized CPO-27-Mg materials were evaluated using gas adsorption and microcalorimetry in the 0.001-1 bar range, which is pertinent for the mentioned applications. Valuable information related to design criteria for synthesis of tuned CO2 adsorbents is derived through this computational and experimental investigation.

Layered exfoliable crystalline materials based on Sm-, Eu- and Eu/Gd-2-phenylsuccinate frameworks. Crystal structure, topology and luminescence properties.

Three new layered metal-organic frameworks (MOFs) based on 2-phenylsuccinic acid (H2psa) and lanthanide ions with the formula [Ln2(C10H8O4)3(H2O)] (Ln = Eu, Sm and Eu-Gd) have been synthesized under solvothermal conditions and fully characterized by single-crystal X-ray diffraction, thermal and vibrational analyses. The compounds are isostructural featuring 2D frameworks that consist of infinite zigzag chains composed of [LnO8] and [LnO8(H2O)] edge-sharing polyhedra linked by psa ligands leading to layers further connected by weak π-π interactions in an edge orientation. Moreover, a topological study was carried out to obtain the simplified net for better comparison with structurally related compounds. The crystals were exfoliated into nanolayers after miniaturization by addition of sodium acetate as a capping agent in the reaction medium. Scanning electron microscopy was applied to characterize the miniaturized samples whereas the exfoliated hybrid nanosheets were studied by atomic force microscopy. The photoluminescence (PL) properties of the bulk compounds as well as the miniaturized and exfoliated materials were investigated and compared with other related ones. An exhaustive study of the Eu(iii)-based MOFs was performed on the basis of the obtained PL parameters (excitation and emission spectra, kr, knr, intrinsic quantum yields and lifetimes) to explore the underlying structure-property relationships.

Studies on the acute and chronic effects of reboxetine on extracellular noradrenaline and other monoamines in the rat brain.

1 The effect of reboxetine, a novel antidepressant drug that potently and selectively inhibits neuronal noradrenaline (NA) uptake, on brain extracellular monoamines was studied by microdialysis. 2 Fifteen mg kg-1 i.p. reboxetine raised extracellular NA in the frontal cortex (by 242%) and dorsal hippocampus (by 240%). 3 Idazoxan (1 mg kg-1 s.c.), given 60 min after 15 mg kg-1 reboxetine, markedly potentiated the effect on extracellular NA in the frontal cortex (by 1580%) and dorsal hippocampus (by 1360%), but had no effect by itself. 4 Twenty-four hours after the last injection of a chronic schedule (15 mg kg-1 i.p. once daily for 14 days) reboxetine had no effect on basal extracellular concentrations of NA in the dorsal hippocampus and a challenge dose of reboxetine (15 mg kg-1) raised extracellular NA similarly in rats treated chronically with reboxetine (by 353%) and saline (by 425%). 5 Ten and 20 microg kg-1 i.p. clonidine dose-dependently reduced hippocampal extracellular NA similarly in rats given chronic reboxetine (by 32% and 57%) and saline (by 42% and 56%). 6 Extracellular concentrations of dopamine and 5-HT in the striatum were similar in rats treated chronically with reboxetine and saline. A challenge dose of reboxetine (15 mg kg-1) had no effect on striatal extracellular dopamine and slightly increased striatal extracellular 5-HT to a similar extent in rats treated chronically with reboxetine (by 137%) and saline (by 142%). 7 The results suggest that combining reboxetine with an alpha2-adrenoceptor antagonist may facilitate its antidepressant activity. Repeated treatment confirmed that reboxetine is fairly selective for the noradrenergic system but provided no evidence of adaptive changes in that system that could facilitate its effect on extracellular NA.

Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.

We designed a randomized, placebo-controlled, multicentre trial involving 51 relapsing-remitting multiple sclerosis patients to determine the clinical efficacy of mitoxantrone treatment over 2 years. Patients were allocated either to the mitoxantrone group (27 patients receiving I.V. infusion of mitoxantrone every month for 1 year at the dosage of 8 mg/m2) or to the placebo group (24 patients, receiving I.V. infusion of saline every month for 1 year) using a centralized randomization system. Disability at entry and at 12-24 months was evaluated by four blinded neurologists trained in the application of the Kurtzke Expanded Disability Scale (EDSS). In addition, the number and clinical characteristics of the exacerbations over the 24 months were recorded by the local investigators. MRI, at 0, 12 and 24 months, was performed with a 0.2 T permanent unit. MRI data were analysed by two blinded neuroradiologists. All patients underwent a clinical evaluation. A statistically significant difference in the mean number of exacerbations was observed between the mitoxantrone group and placebo group both during the 1st and the 2nd year. Although there was no statistically significant benefit in terms of mean EDSS progression over 2 years, the proportion of patients with confirmed progression of the disease, as measured by a one point increase on the EDSS scale, was significantly reduced at the 2nd year evaluation in the mitoxantrone group. Forty-two (23 mitoxantrone, 19 placebo) patients underwent all MRI examinations during the 24-month period. We observed a trend towards a reduction in the number of new lesions on T2-weighted images in the mitoxantrone group. Our study suggests that mitoxantrone might be effective in reducing disease activity, both by decreasing the mean number of exacerbations and by slowing the clinical progression sustained by most patients after 1 year from the end of treatment.

Chronic treatment with desipramine facilitates its effect on extracellular noradrenaline in the rat hippocampus: studies on the role of presynaptic alpha2-adrenoceptors.

Adaptive phenomena such as desensitization of autoreceptors are considered an important factor in the achievement of therapeutic efficacy of antidepressant drugs after chronic treatment. We have studied whether a chronic treatment with desipramine had a greater effect than a single dose on the extracellular concentrations of noradrenaline in the dorsal hippocampus. Administration of 10 mg/kg i.p. desipramine once daily for 14 days significantly raised the basal extracellular noradrenaline in the dorsal hippocampus 24 h but not 48 h after the last drug injection. A challenge dose of desipramine increased extracellular noradrenaline in rats treated chronically with vehicle and desipramine. The effect was significantly higher in rats treated chronically with desipramine 48 h but not 24 h after the last injection. An intraperitoneal administration of the alpha2-adrenoceptor agonist clonidine at the dose of 10 microg/kg significantly reduced extracellular noradrenaline in the control group but not in animals chronically treated with desipramine whereas 30 microg/kg clonidine produced a similar decrease in both groups. Three concentrations of clonidine (0.05, 0.5 and 1 microM) infused into the hippocampus significantly reduced extracellular noradrenaline to a similar extent in rats chronically treated with saline or desipramine. Fourty-eight hours after the last injection of the chronic treatment, [3H]RX-821002 binding to alpha2-adrenoceptors in the rat locus coeruleus measured by autoradiography was not significantly modified. A slight (17%) but significant decrease of neuronal uptake of [3H]noradrenaline was found in synaptosome preparations from dorsal hippocampus of rats chronically treated with desipramine, but this was likely due to a decrease in affinity. The results suggest that a repeated treatment with desipramine (10 mg/kg i.p. once daily for 14 days) facilitates its effect on extracellular noradrenaline in the dorsal hippocampus and induces adaptive changes probably involving desensitization of alpha2-adrenoceptors, with no changes in their density, on noradrenergic neurons in the locus coeruleus.

Plasmapheresis in a child affected by acute disseminated encephalomyelitis.

We describe an eight year old girl with acute relapsing disseminated encephalomyelitis (ADEM) who began to improve concomitantly with plasmapheresis therapy. The patient had previously undergone high-dose intravenous methylprednisolone, intravenous immunoglobulins and Interferon beta-1b treatment which did not control the clinical course of the disease. The long term follow-up suggests that plasmapheresis is effective in this disorder and may give better results than steroids or IVIG.

Hair analysis for driving licence in cocaine and heroin users. An epidemiological study.

Diagnosis of drug exposure is strongly supported by analysis of hair samples. In the province of Brescia, Italy, for regranting driving license to drug addicts or occasional abusers, a control programme was adopted including analysis of illicit drugs in two hair segments (0-3 and 3-6 cm) and in urine. From January 1998 to April 1999, upon request of the Local Medical Commission, 697 hair samples were tested in our laboratory. One hundred and eighty subjects resulted positive in hair for one or two of the controlled drug classes (73.3% for cocaine, 10% for opiates, 16.7% for both). Positive subjects were classified by residence, age, sex and license category. Seventy-two subjects were called back after 6-12 months and submitted to a second hair and urine analysis: in 34 cases the result of the first analysis was confirmed (19 negatives, 15 positives for one or both drug classes). Another 37 cases tested positive at the first control and negative at the second, suggesting the hypothesis that a strict control may have a significant deterrent function. The high percentage of negative results at the second control may be explained by the prevalence of cocaine users in the examined population. Our results allow us to conclude that the strict application of control rules lead to a decrease of social risk behaviours.