Metronidazole loaded pectin microspheres for colon targeting

A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit® S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4229–4236, 2009     

Substitution of oral (18)F-FDG for intravenous (18)F-FDG in PET scanning

The aim of this study was to see whether oral administration of (18)F-FDG could be substituted-without significant loss of information-for intravenous injection of (18)F-FDG in patients with difficult intravenous access of any cause, such as that often seen in cancer patients after many cycles of chemotherapy. METHODS: PET after both oral and intravenous administration of (18)F-FDG was performed on 2 healthy volunteers and 7 patients. An interval of 48 h was maintained between the oral administration and the intravenous administration. All scans were visually analyzed. Semiquantitative analysis of specific areas was done by calculating standardized uptake values (SUVs). Scanning was performed 60 min after intravenous tracer administration and 90 min after oral tracer administration. RESULTS: All lesions seen after intravenous administration were visualized on the oral study as well. SUVs were lower on the oral study than on the intravenous study. CONCLUSION: Oral (18)F-FDG can successfully be substituted for intravenous (18)F-FDG in patients with difficult intravenous access. However, because of the large amount of (18)F-FDG retained in the gut, careful interpretation will be required when disease of the gastrointestinal tract is being evaluated.     

Cost-effectiveness of intensive atorvastatin therapy in secondary cardiovascular prevention in the United Kingdom, Spain, and Germany, based on the Treating to New Targets study

The Treating to New Targets (TNT) clinical trial found that intensive 80 mg atorvastatin (A80) treatment reduced cardiovascular events by 22% when compared to 10 mg atorvastatin (A10) treatment. We evaluated the cost-effectiveness of intensive A80 vs A10 treatment in the United Kingdom (UK), Spain, and Germany. A lifetime Markov model was developed to predict cardiovascular disease-related events, costs, survival, and quality-adjusted life-years (QALYs). Treatment-specific event probabilities were estimated from the TNT clinical trial. Post-event survival, health-related quality of life, and country-specific medical-care costs were estimated using published sources. Intensive treatment with A80 increased both the per-patient QALYs and corresponding costs of care, when compared to the A10 treatment, in all three countries. The incremental cost per QALY gained was € 9,500, € 21,000, and € 15,000 in the UK, Spain, and Germany, respectively. Intensive A80 treatment is estimated to be cost-effective when compared to A10 treatment in secondary cardiovascular prevention.      

Ovarian clear cell carcinoma with papillary features: a potential mimic of serous tumor of low malignant potential

The differential diagnostic problems usually associated with clear cell carcinoma (CCC) of the ovary have been well characterized and include primitive germ cell tumor, sex cord stromal tumor, and metastasis. Distinction from other types of surface epithelial carcinoma may also pose a diagnostic challenge, but the potential for misdiagnosis of serous tumor of low malignant potential (S-LMP) is not well recognized. We report 13 cases of ovarian CCC with prominent papillary architecture that were initially misdiagnosed as S-LMP or low-grade serous carcinoma either on frozen section or at final diagnosis. The ages of the patients ranged from 39 to 65 years (mean, 52.2 y). All patients presented with a pelvic mass; 1 was undergoing evaluation for infertility. Macroscopically, most were described as unilateral, multilocular cysts with internal papillary structures. On microscopic examination, each tumor had a papillary architecture that accounted for 30% to 95% of the tumor; in 6 cases, the cores of the papillae were hyalinized. The neoplastic cells covering the papillae had clear to granular and eosinophilic cytoplasm. Hobnail cells were focal and often subtle. Most had a low mitotic index (9/13) and/or deceptively bland cytology (8/13); only careful attention to the cytologic features and/or mitotic index allowed correct identification of the tumor type in 5 cases. Six were associated with pelvic/ovarian endometriosis. Ten were Federation of Gynecology and Obstetrics stage I (8 IA, 2 IC), 2 were stage II (1 IIB, 1 IIC), and 1 stage IIIC. CCC with prominent papillary architecture is uncommon, but may pose a challenging differential diagnosis with S-LMP, resulting in inadequate staging and delayed treatment. Features most helpful in distinguishing papillary CCC are unilaterality, nonhierarchical branching, monomorphous cell population, and the presence of more typical CCC patterns elsewhere in the tumor. The presence of endometriosis, although not specific, should also prompt consideration for papillary CCC. Increased numbers of mitotic figures may not be present and high-grade cytologic atypia may be focal, requiring careful examination of multiple tumor sections for detection. As CCC and S-LMP exhibit significantly different immunoreactivity for Wilms' Tumor 1 and estrogen receptor, these markers may also be useful adjunctive tests in problematic cases.     

Complications of ankle fracture in patients with diabetes

Ankle fractures in patients with diabetes mellitus have long been recognized as a challenge to practicing clinicians. Complications of impaired wound healing, infection, malunion, delayed union, nonunion, and Charcot arthropathy are prevalent in this patient population. Controversy exists as to whether diabetic ankle fractures are best treated noninvasively or by open reduction and internal fixation. Patients with diabetes are at significant risk for soft-tissue complications. In addition, diabetic ankle fractures heal, but significant delays in bone healing exist. Also, Charcot ankle arthropathy occurs more commonly in patients who were initially undiagnosed and had a delay in immobilization and in patients treated nonsurgically for displaced ankle fractures. Several techniques have been described to minimize complications associated with diabetic ankle fractures (eg, rigid external fixation, use of Kirschner wires or Steinmann pins to increase rigidity). Regardless of the specifics of treatment, adherence to the basic principles of preoperative planning, meticulous soft-tissue management, and attention to stable, rigid fixation with prolonged, protected immobilization are paramount in minimizing problems and yielding good functional outcomes.     

Improved outcomes for laparoscopic appendectomy compared with open appendectomy in the pediatric population

INTRODUCTION: The appendectomy is a common emergent surgical procedure in the pediatric population. The aim of this study was to examine our institution's experience and outcomes in the appendectomy in the pediatric population early in our transition from open surgery to a predominantly laparoscopic approach. METHODS: We retrospectively studied all pediatric patients (age 20 years) that underwent an appendectomy at a tertiary care center over 2 years. The data collected included patient demographics, comorbidities, operative details, outcomes, and complications. RESULTS: Two hundred twenty-three consecutive patients, with a mean age of 9.5 (3.9) years, were included in the study. Forty-four laparoscopic and 179 open appendectomies were performed. Two of the laparoscopic cases were converted to open appendectomies. Significant differences were seen between the two groups, with longer operative times (P < 0.0001) and lower estimated blood loss (P = 0.007) in the laparoscopic group. Operative times improved significantly for the laparoscopic group as the surgeons became more experienced (P = 0.03). The laparoscopic group used intravenous pain medication for a shorter time (0.8 vs. 1.9 days; P = 0.0003) and had a shorter postoperative hospital length of stay (2.2 vs. 3.4 days; P = 0.004). The laparoscopic group had fewer wound infections (2.3% vs. 6.2%; P = 0.3), intra-abdominal abscesses (4.5% vs. 5.6%; P = 0.8), and postoperative ileus (0% vs. 2.2%; P = 0.3), although these differences did not reach statistical significance. CONCLUSION: The laparoscopic appendectomy procedure is a safe alternative to open appendectomy in pediatric patients and results in shorter hospital stays with less postoperative pain.     

Idiopathic Central Nervous System Inflammatory Disease in the Setting of HLA-B27 Uveitis

Purpose: The purpose of the article is to describe a novel case of idiopathic central nervous system inflammatory disease with bilateral human leukocyte antigen (HLA)-B27-positive anterior uveitis.

Methods/Results: A 15-year-old African American boy with bilateral HLA-B27-positive anterior uveitis controlled with topical and oral steroids for 8 months acutely developed headaches, left eyelid ptosis, and binocular diplopia. Imaging showed lesions in the right midbrain, superior colliculus, cerebellar peduncles, and cerebellar vermis and leptomeningeal enhancement along the vermian foliae. Cerebral spinal fluid tests showed mild lymphohistiocytic pleocytosis with negative cytology; inflammatory and infectious workup were negative. He received intravenous methylprednisolone without initial symptomatic improvement; repeat magnetic resonance imaging (MRI) showed reduced lesion burden. Oral steroids were continued; his symptoms resolved in 1 month. Repeat MRI 2 months after presentation showed almost complete lesion resolution.

Conclusions: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was diagnosed. HLA-B27 positivity may represent a novel association with CLIPPERS.