Multiple sclerosis and Capgras' syndrome

Psychotic disorders in patients with multiple sclerosis (MS), although reported in the literature, are quite rare. The maniac psychosis is increased in MS patients, especially after steroid use, but a pure paranoid (delusional) state is very uncommon. We report a case of a patient with MS complicated by Capgras' syndrome. This disorder, characterized by misidentification and also known as "illusion of double", was first described by the French psychiatrist Joseph Capgras in 1923. Our patient was a 36-year-old female, with a negative psychiatric history; the diagnosis of MS dated back to the age of 18. Subsequently, after a treatment with high dosage of steroids for optic neuritis, her psychiatric symptoms (delusion of references) began and she was then treated with clozapine. Thereafter she had repeated relapses. Immunomodulatory treatments with beta-interferon first and azathioprine then were stopped for intolerance. She came to our hospital for a new relapse with severe dynamic ataxia. After a treatment with corticosteroids the patient developed a paranoid disorder characterized by persecutory delusion (illusion of double) towards her husband. Treatment with glatiramer acetate and quetiapine improved her neuropsychiatric condition.     

Effects of naltrexone on cortisol levels in heavy drinkers

The primary objectives of this study were to: (a) examine the neuroendocrine effects of naltrexone vs. placebo by comparing serum cortisol levels; and (b) test the biobehavioral correlates of naltrexone-induced changes in cortisol. Non-treatment seeking heavy drinkers (n=37) completed two intravenous alcohol administrations, one after naltrexone (50 mg) and one after placebo. Cortisol levels were measured at baseline and after alcohol intake (BrAC=0.06 g/dl) on both sessions, as were subjective responses to alcohol. Analyses revealed that naltrexone significantly raised overall cortisol levels compared to placebo. Cortisol levels decreased during alcohol administration and a stronger decrease was observed in the naltrexone condition. Cortisol levels were, in turn, inversely related to some of alcohol's the reinforcing effects (i.e., alcohol 'high,' vigor) and positively associated with some of its unpleasant effects (i.e., sedation and subjective intoxication). These results suggest that naltrexone alters cortisol levels in heavy drinkers and that its effects on subjective responses to alcohol may be related, in part, to naltrexone's ability to activate the HPA-axis.     

Evaluation of solid lipid microparticles produced by spray congealing for topical application of econazole nitrate

Objectives The aims of this study were to evaluate the suitability of the spray congealing technique to produce solid lipid microparticles (SLMs) for topical administration and to study the skin permeation of a drug from SLMs compared with solid lipid nanoparticles (SLNs). Methods Econazole nitrate was used as model drug and Precirol ATO 5 as the lipidic carrier. SLMs and SLNs were both prepared at 5: 1, 10: 1 and 12.5: 1 lipid: drug weight ratios and characterised in terms of particle size, morphology, encapsulation efficiency and chemical analysis of the particle surface. SLMs and SLNs were also incorporated into HPMC K 100M hydrogels for ex‐vivo drug permeation tests using porcine epidermis. Key findings SLMs had particle sizes of 18–45 μm, while SLNs showed a mean diameter of 130–270 nm. The encapsulation efficiency was 80–100%. Permeation profiles of econazole nitrate were influenced by both particle size (significant difference until 9 h) and the amount of lipid. Conclusions The results confirm the usefulness of SLNs as carriers for topical administration and suggest the potential of SLMs for the delivery of drugs to the skin.     

Colonic Manometry Catheter Placement with Primary Fluoroscopic Guidance

The purpose of this paper is to describe our experience with a new technique of colonic manometry catheter placement using fluoroscopic guidance. Between 2000 and 2004, 44 colonic manometry catheters were placed with primary fluoroscopic guidance in 38 patients (25 males; median age, 7 years; range, 0.4–31 years) with severe defecation disorders. Fourteen colonoscopic placements were reviewed to compare the different procedures. Manometry catheters were inserted through the rectum (16 patients), cecostomy (9), ileostomy (2), and colostomy (17). Placements through diverted colons were successful in 24 of 28 (86%). Insertion through the rectum was successful in 10 of 16 (63%) fluoroscopic-guided placements vs. 12 of 14 (86%) colonoscopic placements (P=0.23). Significantly longer fluoroscopic exposure was required for fluoroscopic compared to colonoscopic placement (P=0.004). In conclusion, placement of colonic manometry catheters with primary fluoroscopic guidance is feasible in children. An important disadvantage of the fluoroscopic methodology is the prolonged fluoroscopic exposure time.     

Right hepatectomy with anterior approach for ruptured liver cell adenoma

We report a case of a 37-year-old woman who was referred to a peripheral hospital with severe abdominal pain, vomiting and hemorrhagic shock. Ultrasonography and CT scan showed a large ruptured adenoma of the right liver. Because of hemodynamic instability, she underwent laparotomy with gauze packing and then she was referred to our department with a bleeding persisting at a rate of about 100 mL per hour from the abdominal drain. She underwent relaparotomy and a ruptured liver cell adenoma with a huge hepatic hematoma completely involving the right liver and part of segment 4 was confirmed. Considering the size of the lesion and the presence of a large hematoma, a right hepatectomy with anterior approach was performed. In case of emergency liver resections, the anterior approach is preferable not only to avoid tumor manipulation and the risk of its rupture, but mainly to reduce liver bleeding and to prevent sudden fall of the blood pressure due to inferior vena cava twisting in a hemodynamically instable patient. Intraoperative blood loss was 1500 mL. The postoperative course was uneventful. The patient is doing well ten months after operation.     

Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity

Pathway-specific therapy is the future of cancer management. The oncogenic phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in solid tumors; however, currently, no reliable test for PI3K pathway activation exists for human tumors. Taking advantage of the observation that loss of PTEN, the negative regulator of PI3K, results in robust activation of this pathway, we developed and validated a microarray gene expression signature for immunohistochemistry (IHC)-detectable PTEN loss in breast cancer (BC). The most significant signature gene was PTEN itself, indicating that PTEN mRNA levels are the primary determinant of PTEN protein levels in BC. Some PTEN IHC-positive BCs exhibited the signature of PTEN loss, which was associated to moderately reduced PTEN mRNA levels cooperating with specific types of PIK3CA mutations and/or amplification of HER2. This demonstrates that the signature is more sensitive than PTEN IHC for identifying tumors with pathway activation. In independent data sets of breast, prostate, and bladder carcinoma, prediction of pathway activity by the signature correlated significantly to poor patient outcome. Stathmin, encoded by the signature gene STMN1, was an accurate IHC marker of the signature and had prognostic significance in BC. Stathmin was also pathway-pharmacodynamic in vitro and in vivo. Thus, the signature or its components such as stathmin may be clinically useful tests for stratification of patients for anti-PI3K pathway therapy and monitoring therapeutic efficacy. This study indicates that aberrant PI3K pathway signaling is strongly associated with metastasis and poor survival across carcinoma types, highlighting the enormous potential impact on patient survival that pathway inhibition could achieve.