Vulvar hibernoma

A 35 year old woman presented with 18 months history of a painless, soft, well-circumscribed, vulvar subcutaneous lump which measured approximately 7 cm. The lesion was completely excised and microscopically was consistent with a hibernoma. According to the available literature in English, this is the first reported case of hibernoma of the vulva.     

Rapid monitoring of iron-chelating therapy in thalassemia major by a new cardiovascular MR measure: the reduced transverse relaxation rate

In iron overload, almost all the excess iron is stored intracellularly as rapidly mobilizable ferritin iron and slowly exchangeable hemosiderin iron. Increases in cytosolic iron may produce oxidative damage that ultimately results in cardiomyocyte dysfunction. Because intracellular ferritin iron is evidently in equilibrium with the low-molecular-weight cytosolic iron pool, measurements of ferritin iron potentially provide a clinically useful indicator of changes in cytosolic iron. The cardiovascular magnetic resonance (CMR) index of cardiac iron used clinically, the effective transverse relaxation rate (R(2)*), is principally influenced by hemosiderin iron and changes only slowly over several months, even with intensive iron-chelating therapy. Another conventional CMR index of cardiac iron, the transverse relaxation rate (R(2)), is sensitive to both hemosiderin iron and ferritin iron. We have developed a new MRI measure, the 'reduced transverse relaxation rate' (RR(2)), and have proposed in previous studies that this measure is primarily sensitive to ferritin iron and largely independent of hemosiderin iron in phantoms mimicking ferritin iron and human liver explants. We hypothesized that RR(2) could detect changes produced by 1 week of iron-chelating therapy in patients with transfusion-dependent thalassemia. We imaged 10 patients with thalassemia major at 1.5 T in mid-ventricular short-axis planes of the heart, initially after suspending iron-chelating therapy for 1 week and subsequently after resuming oral deferasirox. After resuming iron-chelating therapy, significant decreases were observed in the mean myocardial RR(2) (7.8%, p < 0.01) and R(2) (5.5%, p < 0.05), but not in R(2)* (1.7%, p > 0.90). Although the difference between changes in RR(2) and R(2) was not significant (p > 0.3), RR(2) was consistently more sensitive than R(2) (and R(2)*) to the resumption of iron-chelating therapy, as judged by the effect sizes of relaxation rate differences detected. Although further studies are needed, myocardial RR(2) may be a promising investigational method for the rapid assessment of the effects of iron-chelating therapy in the heart.     

Hiatal Hernia, Lower Esophageal Sphincter Incompetence, and Effectiveness of Nissen Fundoplication in the Spectrum of Gastroesophageal Reflux Disease

Background and Aims  Gastroesophageal reflux disease (GERD) is a spectrum of disease that includes nonerosive reflux disease (NERD), erosive reflux disease (ERD), and Barrett’s esophagus (BE). Treatment outcomes for patients with different stages have differed in many studies. In particular, acid suppressant medication therapy is reported to be less effective for treating patients with NERD and Barrett’s esophagus. The aims of this study were to investigate (1) the role of mechanical factors including hiatal hernia and lower esophageal sphincter (LES) competence in the spectrum of GERD and (2) outcomes of Nissen fundoplication. Methods  From the records of patients who had undergone laparoscopic Nissen fundoplication after an abnormal pH study, we identified 50 symptomatic consecutive patients with each of the GERD stages: (1) NERD, (2) mild ERD, defined as esophagitis that was healed with acid suppression therapy, (3) severe ERD, defined as esophagitis that persisted despite medical therapy, and (4) BE. Exclusion criteria were normal distal esophageal acid exposure, esophageal pH monitoring performed elsewhere, antireflux surgery less than 1 year previously or previous fundoplication, and a named esophageal motility disorder or distal esophageal low amplitude hypomotility. Patients who could not be contacted for the study were also excluded. All patients completed a detailed preoperative questionnaire; underwent preoperative upper gastrointestinal endoscopy, stationary manometry, and distal esophageal pH monitoring; and were interviewed at least 1 year after operation. Results  One hundred sixty patients meeting the entry criteria were studied. The mean follow-up period was 36.7 months. The only significant preoperative symptom difference was that patients with BE had more moderately severe or severe dysphagia compared to patients with NERD. Patients with severe ERD or BE had a significantly higher prevalence of hiatal hernia, lower LES pressures, and more esophageal acid exposure. Hiatal hernia and hypotensive LES were present in most patients with severe ERD or BE but in only a minority of patients with NERD or mild ERD. Surgical therapy resulted in similarly excellent symptom outcomes for patients in all GERD categories. Conclusions  Compared to mild ERD and NERD, severe ERD and BE are associated with significantly greater loss of the mechanical antireflux barrier as reflected in the presence of hiatal hernia and LES measurements. Restoration of the antireflux barrier and hernia reduction by laparoscopic Nissen fundoplication provides similarly excellent symptom control in all patients.     

Cyclooxygenase-2 Expression in Hepatocellular Carcinoma,Cirrhosis and Chronic Hepatitis in the United States

Aberrant expression of cyclooxygenase-2 in hepatocellular carcinoma was described in Asia. Using immunohistochemistry, we studied the expression of cyclooxygenase-2 in hepatocellular carcinoma, chronic hepatitis, and cirrhosis in a US institution. A staining score of 0–5 representing the sum of an intensity score and a distribution score was used. The mean scores were 2.2±1.60 for chronic hepatitis, 4.37±1.15 for cirrhosis, and 4.76±0.54 for hepatocellular carcinoma. We found a significant difference in mean staining scores between chronic hepatitis and cirrhosis (p < 0.0001), as well as between chronic hepatitis and hepatocellular carcinoma (p < 0.0001). Fibrosis correlated with cyclooxygenase-2 staining score (r=0.65). In conclusion: (1) Cyclooxygenase-2 expression is higher in cirrhosis and hepatocellular carcinoma when compared to chronic hepatitis. (2) Cyclooxygenase-2 expression correlates with the stage of fibrosis. (3) These results imply that in chronic hepatitis and possibly in cirrhosis, hepatocarcinogenesis may be a cyclooxygenase-2 dependent mechanism.     

Formulation development of ambroxol hydrochloride soft gel with application of statistical experimental design and response surface methodology

The purpose of present work was to develop ambroxol hydrochloride soft gel formulation with the application of statistical experimental design and response surface methodology (RSM). A two-factor, three-level (3(2)) full factorial design of experiment with RSM was run to evaluate the main and interaction effect of two independent formulation variables that included the amount of low-acetylated gellan gum and sodium citrate. The dependent variables included viscosity (Y(1)), amount of drug release at 10 min (Y(2)) and 30 min (Y(3)), and gelation time (Y(4)). In order to obtain a formulation having the maximum amount of drug release at 10 min and minimum gelation time, RSM optimization was used. The prepared formulations were evaluated for pH, viscosity, rheological properties, gelation time, drug content, in vitro drug release, appearance, and taste. All the formulations showed a gelation time in the range of 6 to 48 min. The drug content in all the formulations was within limit (99.6 ± 1.56%). The viscosity of all the formulations was found in the range of 1872-12,182 cP. Dissolution studies of the formulations showed drug release in the range of 40.56-72.46% within 10 min and 80.2-100.5% within 30 min. Human evaluation tests revealed that all the gels possessed acceptable characteristics. This study showed that the soft gel formulation GA5, containing 0.3% of gellan gum and 0.4% of sodium citrate, has potential use as an immediate release soft gel for oral drug delivery. LAY ABSTRACT: The objective of this investigation was to develop a new, immediate-release, soft gel dosage form for ambroxol hydrochloride, an oral expectorant and mucolytic agent. This novel soft gel dosage form needs to be suitable for pediatric and geriatric patients as well as patients with dysphagia. A statistical technique was used for optimization of the gel formulation. The methodology, called a design of experiment with response surface methodology, evaluated several independent formulation variables, including the amount of two ingredients, low-acetylated gellan gum and sodium citrate. Their effects were studied by comparing physical properties of the gel such as viscosity, amount of drug release at 10 and 30 min, and gelation time. The final optimized formulation (0.3% of gellan gum and 0.4% of sodium citrate) was chosen to maximize the amount of drug release at 10 min, minimize gelation time, and optimize viscosity in a reasonable range. After this optimization exercise, the prepared ambroxol hydrochloride soft gel formulations were evaluated for pH, viscosity, rheological properties, gelation time, drug content, in vitro drug release, appearance, and taste. Human evaluation tests revealed that all the gels possessed acceptable organoleptic characteristics.     

Impact of the integration of water treatment and handwashing incentives with antenatal services on hygiene practices of pregnant women in Malawi

Access to safe drinking water and improved hygiene are important for reducing morbidity and mortality from diarrhea. We surveyed 330 pregnant women who participated in an antenatal clinic-based intervention in Malawi that promoted water treatment and hygiene through distribution of water storage containers, sodium hypochlorite water treatment solution, soap, and educational messages. Program participants were more likely to know correct water treatment procedures (62% versus 27%, P < 0.0001), chlorinate drinking water (61% versus 1%, P < 0.0001), demonstrate correct handwashing practices (68% versus 22%, P < 0.0001), and purchase water treatment solution after free distribution (32% versus 1%, P < 0.0001). Among participants, 72% had at least three antenatal visits, 76% delivered in a health facility, and 54% had a postnatal check. This antenatal-clinic-based program is an effective new strategy for promoting water treatment and hygiene behaviors among pregnant women. Participants had high use of antenatal, delivery, and postnatal services, which could improve maternal and child health.