Rationalizing neuroleptic polypharmacy in chronic schizophrenics: effects of changing to a single depot preparation.

This study investigated the effects of transferring patients on combined depot and oral neuroleptics to a single depot preparation; a secondary objective was to assess the effects of transferring patients from one depot neuroleptic to another. It was found that, whereas transferring from one depot preparation (flupenthixol) to another (fluphenazine) had no clear disadvantage for the patients, changing over from a combined oral and depot (fluphenazine) regimen to equivalent doses of depot alone resulted in an unacceptably high rate of relapse. The reasons for this may relate to either the unique pharmacokinetics of these drugs or subtle qualitative differences between them. It is suggested that caution is necessary whenever attempts are made to rationalize polypharmacy in schizophrenic patients.     

Normal coronary artery dimensions in Indians

Background There is no available data on normal coronary artery size in the Indian population. We attempted to establish a database for normal dimensions of the coronary artery segments during life by using quantitative coronary angiography and compared these with Western estimates of coronary artery size. Material and Methods Between december 2003 and June 2004, 94 patients who underwent quantitative coronary angiography for evaluation of symptoms of ischemic heart disease and were found to have no coronary artery disease form the sample size. Results The dimensions of branches in the left coronary system in our patients were less and those of the distal circumflex, and the proximal and distal left anterior descending coronary arteries were significantly greater than those of Indian Asians living in the United Kingdom and the native Caucasians but the dimensions of the right coronary artery were significantly greater in our patients. Conclusions Coronary artery dimensions for at least some branches of the left coronary system are similar to that reported in the West and the dimensions of the right coronary are greater. These findings contradict the general perception that Indians have smaller coronary arteries.     

Effect of cell donor age on the synthetic properties of fibroblasts obtained from phenytoin-induced gingival hyperplasia

Diploid fibroblasts obtained from explants of human gingiva and maintained in vitro undergo a several-fold decrease in protein and collagen synthesis as a function of increasing donor age. Using drug-induced gingival hyperplasia as a model, we performed experiments to learn whether fibroblasts derived from hyperplastic tissue behave in a similar manner. Fibroblast strains were established from explants of hyperplastic gingiva obtained from 10 patients chronically ingesting phenytoin and ranging in age from 9 to 45 years. Protein production and degradation were compared to previously reported data similarly obtained from periodontally normal donors ranging in age from 12 to 68 yr. The total quantity of protein and collagen produced by the phenytoin cells was significantly greater than previously reported for cells from normal gingiva. No donor age-related decrease in protein and collagen production nor in the proportion of cell synthetic activity committed to collagen production was observed for cultures of phenytoin cells. The gross pattern of proteins produced, as assessed by 2-dimensional gel electrophoresis, was unrelated to donor age in both normal and phenytoin cells, but three polypeptides ranging in size from about 20 kD to 40 kD that were not found in the cultures of normal cells were produced by five of seven phenytoin cells strains. The observations demonstrate that the phenytoin cells do not undergo the donor age-dependent decrease in synthesis observed for normal cells. This abnormality may account in part for the phenytoin-induced hyperplasia. The phenytoin cells appear to be a unique phenotype.     

Endonasal Ethmoidectomy and Bifrontal Craniotomy with Craniofacial Approach for Resection of Frontoethmoidal Osteoma Causing Tension Pneumocephalus

Tension pneumocephalus is an unusual, potentially life-threatening complication of frontal fossa tumors. We present an uncommon case of a frontoethmoidal osteoma causing a tension pneumocephalus and neurological deterioration prompting a combined endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach for resection. A 68-year-old man presented with a 1-week history of worsening headache, slowness of speech, and increasing confusion. Standard computed tomography scan revealed a marked tension pneumocephalus with ventricular air and 1-cm midline shift to the right. Further studies showed a calcified left ethmoid mass and a left anterior cranial-base defect. A team composed of neurosurgery and otolaryngology performed a combined endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach to resect a large frontoethmoid bony tumor. No abscess or mucocele was identified. The skull base defect was repaired with the aid of a transnasal endoscopy, a titanium mesh, and a pedunculated pericranial flap. Postoperatively, the pneumocephalus and the patient's symptoms completely resolved. Pathology was consistent with a benign osteoma. This is an uncommon case of a frontoethmoidal osteoma associated with tension pneumocephalus. Recognition of this entity and timely diagnosis and treatment, consisting of an endonasal ethmoidectomy and a bifrontal craniotomy with craniofacial approach, may prevent potential life-threatening complications.     

A sensitive and a rapid multiplex polymerase chain reaction for the identification of Candida species in concentrated oral rinse specimens in patients with diabetes

Objectives: Oral candidiasis is being frequently recognized in patients with diabetes, and is associated with multiple pathogens including Candida albicans, Candida parapsilosis, Candida glabrata and Candida tropicalis. The aim of this study was to evaluate a usefulness of a Multiplex Polymerase Chain Reaction as a rapid diagnostic tool for identification of four oral Candida pathogens in patients with diabetes.

Materials and methods: A multiplex PCR was optimized to identify four Candida species in concentrated oral rinse samples. Common reverse primer, ITS4 and four species-specific forward primers targeting ITS1 and ITS2 regions of yeast genome were used. Species-specific single amplicon were detected by agarose gel electrophoresis. Performance efficacy of multiplex PCR was compared with phenotypic identification.

Results: Out of 100 oral rinse samples, 72 were culture positive and of these 43 were at risk of oral Candida infection (>600cfu/ml). Multiple Candida species including C. albicans, C. parapsilosis and C. tropicalis were identified in 22 samples which had risk of oral Candida infection. In total, 85 patients were positive for Candida by multiplex PCR and of them 49 had multiple Candida species. All 43 colonized specimens were also positive by multiplex PCR. C. albicans was the most predominant organism (75/85) followed by C. parapsilosis (47/85), C. tropicalis (17/85) and C. glabrata (6/85). In specimens with multiple species, the two most common organisms were C. albicans and C. parapsilosis. Multiplex PCR yielded a sensitivity of 10 Candida cells/ml of oral rinse sample.

Conclusions: Multiplex PCR is found to be rapid, sensitive and specific than phenotypic identification methods in discriminating multiple Candida species in oral rinse specimens.     

A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)

Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases such as diabetes and Gaucher’s disease, providing evidence for safety of this class of compounds. The in vitro antiviral activity of iminosugars has been described in several publications with a subset of these demonstrating in vivo activity against flaviviruses, herpesviruses, retroviruses and filoviruses. Although there is compelling non-clinical in vivo evidence of antiviral efficacy, the efficacy of iminosugars as antivirals has yet to be demonstrated in humans. In the current study, we report a novel iminosugar, UV-12, which has efficacy against dengue and influenza in mouse models. UV-12 exhibits drug-like properties including oral bioavailability and good safety profile in mice and guinea pigs. UV-12 is an example of an iminosugar with activity against multiple virus families that should be investigated in further safety and efficacy studies and demonstrates potential value of this drug class as antiviral therapeutics.     

Hyaluronan in the Treatment of Chronic Rhinosinusitis with Nasal Polyposis

Chronic rhinosinusitis (CRS) is a common condition and affects the quality of life of approximately 16 % of adults in US and 10.9 % in Europe. Hyaluronan (HA) is a nonsulphate glycosaminoglycan found in the extracellular matrix of connective tissues, and plays an important role in the healing process and repair of mucosal surfaces. We aim to evaluate the effect of HA on nasal symptoms and endoscopic appearance in patients with CRS and nasal polyps (NP) who have not undergone sinus surgery. Eighty patients older than 18 years old were randomized to receive either open-label nebulized saline solution (NS) or intranasal corticosteroid spray (ICS) 200 µg bid or nebulized sodium hyaluronate (NHA, YABRO^®) or both ICS and NHA. Results were collected at 1 month, 3 months and 3 months after treatment. Significant improvements in nasal symptoms scores, endoscopic appearance scores, radiologic scores, rhinomanometry and saccharine clearance test were observed in the NHA, ICS and ICS + NHA groups after 1 month and 3 months of treatment compared with baseline (all p ≤ 0.005). The use of oral steroids was significantly reduced after 3 months of therapy in the same groups versus baseline (all p < 0.05). The incidence of adverse events at 3 months was similar between the 4 groups (all p > 0.05). Throat irritation, nasal burning and drug-related epistaxis were not reported in the group NHA. HA, as a nebulized nasal douche preparation, improved nasal symptoms and endoscopic appearances in patients with CRS and NP who have not undergone sinus surgery.