Treating depression in patients with borderline personality disorder: clinical clues on the use of antidepressants.

Personality disorders (PD) are described as enduring patterns of markedly deviant and pervasive inner experiences and behaviors, with onset in adolescence, which lead to severe distress or impairment. Patients suffering from major depressive disorder (MDD) display higher rates of comorbidity with personality disorders, often complicating the treatment, and worsening the outcomes. Borderline personality disorder (BPD) is the most common of PD and is frequently associated with MDD, with which shares several features. The most part of research agrees on the fact that comorbid BPD in MDD patients quite doubles the poor response to treatments. Moreover, no treatment strategy stands out currently to emerge as more effective in these cases, thus urging the call for the need of new approaches. Herein, we revise the current literature on BPD, its neurobiology and comorbidity with MDD, as well as the more recent treatment strategies used. Then, based on its pharmacology, we propose a possible role of trazodone as a valuable tool to approach comorbid BPD-MDD.

Sustained zero-order delivery of GC-1 from a nanochannel membrane device alleviates metabolic syndrome.

BACKGROUND/OBJECTIVES: Our objective was to assess the sustained, low-dose and constant administration of the thyroid receptor-ß (TRß)-selective agonist GC-1 (sobetirome) from a novel nanochannel membrane device (NMD) for drug delivery. As it known to speed up metabolism, accomplish weight loss, improve cholesterol levels and possess anti-diabetic effects, GC-1 was steadily administered by our NMD, consisting of an implantable nanochannel membrane, as an alternative to conventional daily administration, which is subject to compliance issues in clinical settings. SUBJECTS/METHODS: Diet-induced obese C57BL/J6 male mice were fed a very high-fat diet (VHFD) and received NMD implants subcutaneously. Ten mice per group received capsules containing GC-1 or phosphate-buffered saline (control). Weight, lean and fat mass, as well as cholesterol, triglycerides, insulin and glucose, were monitored for 24 days. After treatment, plasma levels of thyroid-stimulating hormone (TSH) and thyroxine were compared. mRNA levels of a panel of thermogenic markers were examined using real-time PCR in white adipose tissue (WAT) and brown adipose tissue (BAT). Adipose tissue, liver and local inflammatory response to the implant were examined histologically. Pancreatic islet number and ß-cell area were assessed. RESULTS: GC-1 released from the NMD reversed VHFD-induced obesity and normalized serum cholesterol and glycemia. Significant reductions in body weight and fat mass were observed within 10 days, whereas reductions in serum cholesterol and glucose levels were seen within 7 days. The significant decrease in TSH was consistent with TRß selectivity for GC-1. Levels of transcript for Ucp1 and thermogenic genes PGC1a, Cidea, Dio2 and Cox5a showed significant upregulation in WAT in NMD-GC-1-treated mice, but decreased in BAT. Although mice treated by NMD-GC-1 showed a similar number of pancreatic islets, they exhibited significant increase in ß-cell area. CONCLUSIONS: Our data demonstrate that the NMD implant achieves steady administration of GC-1, offering an effective and tightly controlled molecular delivery system for treatment of obesity and metabolic disease, thereby addressing compliance.

Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is advised as a treatment option for epithelial ovarian cancer (EOC) with peritoneal carcinomatosis. This study was designed to define the pharmacokinetics of cisplatin (CDDP) and paclitaxel (PTX) administered together during HIPEC. METHODS: Thirteen women with EOC underwent cytoreductive surgery (CRS) and HIPEC, with CDDP and PTX. Blood, peritoneal perfusate and tissue samples were harvested to determine drug exposure by high-performance liquid chromatography and matrix-assisted laser desorption ionization imaging mass spectrometry (IMS). RESULTS: The mean maximum concentrations of CDDP and PTX in perfusate were, respectively, 24.8±10.4 µg ml(-1) and 69.8±14.3 µg ml(-1); in plasma were 1.87±0.4 µg ml(-1) and 0.055±0.009 µg ml(-1). The mean concentrations of CDDP and PTX in peritoneum at the end of HIPEC were 23.3±8.0 µg g(-1) and 30.1±18.3 µg(-1)g(-1), respectively. The penetration of PTX into the peritoneal wall, determined by IMS, was about 0.5 mm. Grade 3-4 surgical complications were recorded in four patients, five patients presented grade 3 and two patients presented grade 4 hematological complications. CONCLUSIONS: HIPEC with CDDP and PTX after CRS is feasible with acceptable morbidity and has a favorable pharmacokinetic profile: high drug concentrations are achieved in peritoneal tissue with low systemic exposure. Larger studies are needed to demonstrate its efficacy in patients with microscopic postsurgical residual tumours in the peritoneal cavity.

Real-world effectiveness of long acting aripiprazole: Treatment persistence and its correlates in the Italian clinical practice.

OBJECTIVES: To identify the variables that are associated with persistence to Aripiprazole-Long Acting (A-LAI), in adult patients with schizophrenia. METHODS: Observational, retrospective, non-interventional study involving 261 patients with schizophrenia. RESULTS: Eighty-six percent of study subjects were persistent for at least 6 months. All subjects with baseline CGI-S of 1 or 2, 95% of subjects with CGI-S of 3, 86% with CGI-S of 4, 82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7 were persistent. A-LAI treatment continuation rate was higher in patients with: 1) baseline CGI score ≤ 4; 2) schizophrenia dimension (LDPS) mania score ≤ 5; 3) psychotic spectrum schizoid score ≤ 11. CONCLUSIONS: A relatively high number of patients (n = 225, 86%) were persistent to A-LAI for at least 6 months. Not surprisingly, very severe patients were more unlikely to be persistent. However, it is noteworthy that a large number of subjects with high CGI score at the time when A-LAI was started (82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7) were persistent. Larger, controlled, prospective and longer studies are warranted.

LAI versus oral: A case-control study on subjective experience of antipsychotic maintenance treatment.

BACKGROUND: To present real-world evidence on the differences between long-acting injectable (LAI) and oral antipsychotic maintenance treatment (AMT) in terms of subjective well-being, attitudes towards drug and quality of life in a sample of remitted schizophrenic subjects. METHODS: Twenty outpatients with remitted schizophrenia treated with either olanzapine or paliperidone and switching from the oral to the LAI formulation of their maintenance treatment were recruited before the switch (LAI-AMT group). A group of 20 remitted schizophrenic subjects with oral AMT and matching main sociodemographic, clinical and treatment variables made up the control group (oral-AMT group). All participants were assessed in terms of objective (PANSS, YMRS, MADRS) and subjective (SWN-K, DAI-10, SF-36) treatment outcomes at baseline (T0) and after 6 months (T1). RESULTS: Between T0 and T1, general psychopathology of the PANSS, DAI-10, and all but one of the SWN-K dimensions (except for social integration), showed significantly higher percentages of improvement in the LAI-AMT group compared to the oral-AMT group. A generalized expansion of health-related quality of life, with better functioning in almost all areas of daily living, was reported by the LAI-AMT group after the 6-month period. In contrast, the oral-AMT group reported a significant worsening of health-related quality of life in the areas of emotional role and social functioning in the same period. CONCLUSIONS: Our study indicates possible advantages of LAI over oral antipsychotic formulation in terms of subjective experience of maintenance treatment in remitted schizophrenic patients. Size and duration of this study need to be expanded in order to produce more solid and generalizable results.

Double-blind trial with oral versus intravenous clomipramine in primary depression.

Intravenous clomipramine and oral clomipramine at a daily dose of 2 mg/kg body weight were compared in a double-blind study of 40 inpatients with primary depressive illness. No significant differences between the two routes of clomipramine administration were found, either in response or in side effects. Steady state was not attained at the 4th week of treatment in 30% of patients. However, combined plasma levels of clomipramine (CI) plus desmethylclomipramine (DMCI) were similar in the two groups at all stages of treatment. The only significant pharmacokinetic difference that was found was in the ratio of DMCI to CI, which was higher among the patients who received the drug orally, but this did not correlate with clinical response. Conversely, Day 28 plasma concentrations of CI, DMCI, and the sum CI + DMCI were significantly related to clinical outcome in the patients treated orally. Among the patients who received the drug intravenously only CI was significantly associated with the percentage reduction of symptoms. By pooling the two groups, CI, DMCI, and their sum all bore relationships to clinical response significant at the 0.01 level.

Plasma levels and clinical response during treatment with clomipramine.

The plasma levels of clomipramine (CI) and its major metabolite desmethylclomipramine (DMCI) may be related to clinical response during treatment of depression. Not all workers have been able to demonstrate such a relationship. The many factors which may affect clinical response include sample selection, assessment and its quantification and kinetic factors. A further investigation into the relationship between plasma levels and response was, therefore, carried out taking these into account and attempting to control them. Sixty-two patients with depressive illness were included. The plasma levels of CI + DMCI as measured on the 28th day of treatment were correlated against clinical response at the time. Patients with the highest combined plasma levels showed the best response. Patients with intermediate plasma levels showed more modest response, whilst lowest plasma levels tended to be shown by patients who exhibited an inadequate response or who relapsed during subsequent outpatient follow-up. The threshold value for satisfactory antidepressant effect appeared to be a combined CI + DMCI plasma level of 160-200 mg/ml.

Identification and quantification method of spiramycin and tylosin in feedingstuffs with HPLC-UV/DAD at 1 ppm level.

The use of the two macrolides antibiotics Spiramycin (S) and Tylosin (T) as growth promoters in animal feeding has been recently withdrawn in the European Union due to a concern about the outbreaks of farmacoresistance fenomena as a possible hazard for humans. For feed additives monitoring purposes, an analytical method has been developed for their extraction, purification and identification in different animal feedingstuffs (pelleted beef, pig, poultry feeds and calves milk replacer) at a minimum performance required limit (MRPL) of 1 microg g(-1) (ppm). Such limit has been established according to the lowest dosage of additives still able to elicit an appreciable growth promoting effect. Blank feeds were spiked at two concentration levels, 1.0 and 2.5 ppm in six replicates. After methanolic extraction, samples were cleaned up on SPE CN columns and extracts analysed in HPLC-UV/DAD, using a gradient elution. Detection limits, calculated as the tree time mean noise of 20 blank feeds, were 176 and 118 ng g(-1) for S and T, respectively. Results show good repeatability (CV% not exceeding the value of 15) and mean recovery in the range of 99-74% and 81-53% for S and T, respectively, at 1 ppm. When the standards were injected up to 250 ng the chromatographic method can resolve the components of analytes (Spiramycin I, II and III; Tylosin A and B) but can not resolve the components on real feed samples at the spiked levels considered. For this reason the identification and quantification of analytes on matrix were carried out considering the main compound of the drugs (Spiramycin I and Tylosin A). As a verification, the overlapping of UV spectra in the range 220-350 nm between analytical standards and the compounds in the matrix were considered.

[Palliative cholangiojejunostomy on the duct of hepatic segment III. Our experience]. / Colangiodigiunostomia palliativa sul dotto del 3o segmento epatico. La nostra esperienza.

BACKGROUND: Aim of the paper is to prove that indications for cholangiojejunostomy, in cases when a mean and long term palliation may be expected, are better than those offered by the use of prostheses, without the well known and early bile duct complications. METHODS: Between 1984 and 1995, 12 patients with obstructive jaundice due to malignancy at the hepatic hilum were treated by segment III Roux-en-y or omega cholangiojejunostomy. In 1 patient with no communication between right and left lobe of the liver, biliary-enteric bypass to segment VI duct was also undertaken; in another with neoplastic stenosis of pylorus gastrojejunostomy was performed. Seven patients had carcinoma of the gallbladder, three hilar cholangiocarcinoma, one gastric carcinoma and one recurrent pancreatic carcinoma. RESULTS: There were two postoperative deaths, one for myocardial infarction and one for biliary peritonitis. Six patients had complications: four biliary fistulas with spontaneous resolution and two wound infections. Seven of the ten surviving patients experienced complete resolution of jaundice for at least 4 months. The mean survival of surviving patients was 9.7 months. Nine patients developed recurrent jaundice. CONCLUSIONS: Segment III cholangiojejunostomy is a good palliative treatment in most patients with malignant hilar obstruction.

[Cholecystolithotomy with cholecystojejunostomy as surgical solution for cholelithiasis in portal hypertension caused by hepatic cirrhosis]. / La colecistolitotomia con colecistodigiunostomia come soluzione chirurgica della colelitiasi nella ipertensione portale da cirrosi epatica.

Cholecystolithotomy and cholecystojejunostomy has been carried out on 11 patients with severe hypertension from cirrhosis. The indications were frequently recurring attacks of biliary cholic or acute cholecystitis at onset. There was 1 postoperative death from cardiac infarction and only minor in-hospital morbidity. None of the remaining patients has to date developed post-cholecystojejunostomy sequelae. Except the case of extensive inflammation on gangrena, this procedure appears to be a safe and definitive operation, alternative to subtotal cholecystectomy.

[Contact thermography in breast pathology. A critical review]. / Termografia a contatto in senologia. Revisione critica.

The paper reports the Authors' experience in over 12,000 patients affected by manifest or presumed breast pathologies examined using contact thermography and assess the number of correct responses. This technique proved reliable in patients aged under 30 with benign pathologies or palpable nodules. On the other hand, it was not reliable in the case of pathologies with negative objectivity, and therefore in the context of screening programmes for the early diagnosis of tumours.

[Hemobilia secondary to percutaneous hepatic biopsy. Report of a clinical case]. / Emobilia secondaria a biopsia epatica percutanea. Discussione di un caso clinico.

The increasingly frequent use of invasive diagnostic and therapeutic procedures concerning the hepatobiliary system has led to a rise in the incidence of hemobilia as well as altering its etiological status. The authors report a clinical case of hemobilia secondary to percutaneous hepatic biopsy which was brought to their attention. This is followed by a short discussion of the etiopatogenesis and diagnostic and therapeutic strategies with special reference to the ratio between the advantages/limits of the methods now available.

[Castleman's disease with abdominal localization. Report of an unusual case]. / Malattia di Castleman a localizzazione addominale. Descrizione di un caso inusuale.

Castleman's disease is an unusual condition characterized by uncontrolled growth of lymphoid tissue. The first case was recorded by Castleman in 1956. In this paper a case of the above-mentioned disease is reported with regard to its unusual clinica-histologic aspect (localized form of plasmacellular type) and surgical therapeutic strategies.

Intratumor heterogeneity and its impact on drug distribution and sensitivity.

We provide an overview of the available information on the distribution of chemotherapeutics in human tumors, highlighting the progress made to assess the heterogeneity of drug concentrations in relation to the complex neoplastic tissue using novel analytical methods, e.g., mass spectrometry imaging. The increase in interstitial fluid pressure due to abnormal vascularization and stiffness of tumor stroma explains the variable and heterogeneous drug concentrations. Therapeutic strategies to enhance tumor drug distribution, thus possibly increasing efficacy, are discussed.

A prospective, observational study of the safety and effectiveness of intramuscular psychotropic treatment in acutely agitated patients with schizophrenia and bipolar mania.

This naturalistic, observational pan-European study assessed the safety and early effectiveness of intramuscular (IM) psychotropic treatments in patients with acute agitation suffering from schizophrenia or bipolar mania. One thousand nine hundred and forty of 1945 patients completed the 24-hour observation period after initial IM treatment. Patients from 12 European countries were included (mean age 39 years; 58% male, 66% schizophrenia). IM treatment was at the physician's discretion. The primary objective was to describe the acute tolerability of IM psychotropic therapies in clinical practice, with particular emphasis on EPS. At baseline, 68% of the patients received IM monotherapy, with IM olanzapine most commonly prescribed (36%). During the first 24 hours, 190 (9.8%) patients experienced EPS. The occurrence of EPS was statistically significantly lower in patients treated with IM olanzapine compared to those treated with other IM psychotropic medications (mainly typical antipsychotics and benzodiazepines): acute dystonia: 1.1%, 95% CI 0.5-2.3 and 2.9%, CI 2.0-4.0; akathisia: 2.3%, CI 1.3-3.7 and 5.5%, CI 4.3-6.9; Parkinsonism: 2.9%, CI 1.8-4.4 and 7.8%, CI 6.4-9.4, respectively. Anticholinergic treatment was given to 12% IM olanzapine versus 31% non-olanzapine treated patients. Acute agitation after 24 hours was reduced by 1.68 (95% CI 1.46-1.91) points on the Clinical Global Impression of Severity (CGI-S) in IM olanzapine patients and 1.51 (95% CI 1.30-1.73) points in non-olanzapine patients. Additional psychotropic medication was required for 90% of the patients during the first 24 hours of treatment. Results provide naturalistic evidence for low EPS rates and improvement of agitation with IM psychotropic medications during acute states of patients suffering from acute mania or schizophrenia.

[Prospects for general psychopathology in modern psychiatry]. / Considerazioni sulla prospettiva della psicopatologia generale nella psichiatria di oggi.

The Author describes the interest and the meaning of General Psychopathology in today's Psychiatry. The Author defines the methodological aspects necessary in psychopathology as well as their gnoseological and formative value. The "-structural constants" defined in psychopathology appear irreplaceable in the basic aspects of psychotic mind models, and other dimensions of contemporary psychiatry cannot disregard them. The Author emphasise the risk of an inaccurate and irresponsibly exhaustive use of psychopathological categories in psychiatric practice. However it seems that a conscious exercise of psychopathological methods can avoid confusion about investigatory psychiatric research, and may help recognizing basic structures of psychotic experience. These structures are not only necessary in a diagnostic field, but also for a correct pharmacotherapeutical epproach.