Mucolipidoses—II: a report of three cases

Mucolipidoses II is a rare lysosomal storage disorder with autosomal recessive inheritance. There cases with typical clinical features in early infancy like coarse facial features, severe psychomotor retardation and joint contractures are being reported. All the cases had no mucopolysacchariduria. These cases had normal values of lysosomal enzymes in leucocytes but markedly increased values in serum thus confirming mucolipidoses II. Despite the fact that there is no specific treatment, genetic counselling and prenatal diagnosis is indicated.     

The Impact of Hot Melt Extrusion and Spray Drying on Mechanical Properties and Tableting Indices of Materials Used in Pharmaceutical Development

The impact of melt extrusion (HME) and spray drying (SD) on mechanical properties of hypromellose acetate succinate (HPMCAS), copovidone, and their formulated blends was studied and compared with that of reference excipients. Tensile strength (TS), compression pressure (CP), elastic modulus (E), and dynamic hardness (H_d) were determined along with Hiestand indices using compacts prepared at a solid fraction of ～0.85. HPMCAS and copovidone exhibited lower H_d, lower CP, and lower E than the reference excipients and moderate TS. HPMCAS was found to be highly brittle based on brittle fracture index values. The CP was 24% and 61% higher for HPMCAS after SD and HME, respectively, than for unprocessed material along with a higher H_d. Furthermore, the TS of HPMCAS and copovidone decreased upon HME. Upon blending melt-extruded HPMCAS with plastic materials such as microcrystalline cellulose, the TS increased. These results suggest that SD and HME could impact reworkability by reducing deformation of materials and in case of HME, likely by increasing density due to heating and shear stress in a screw extruder. A somewhat similar effect was observed for the dynamic binding index (BI_d) of the excipients and formulated blends. Such data can be used to quantitate the impact of processing on mechanical properties of materials during tablet formulation development.     

Matrix detachment and proteasomal inhibitors diminish Sulf-2 expression in breast cancer cell lines and mouse xenografts

Sulfatase 2 (Sulf-2) has been previously shown to be upregulated in breast cancer. Sulf-2 removes sulfate moieties on heparan sulfate proteoglycans which in turn modulate heparin binding growth factor signaling. Here we report that matrix detachment resulted in decreased Sulf-2 expression in breast cancer cells and increased cleavage of poly ADP-ribose polymerase. Silencing of Sulf-2 promotes matrix detachment induced cell death in MCF10DCIS cells. In an attempt to identify Sulf-2 specific inhibitor, we found that proteasomal inhibitors such as MG132, Lactacystin and Bortezomib treatment abolished Sulf-2 expression in multiple breast cancer cell lines. Additionally, we show that Bortezomib treatment of MCF10DCIS cell xenografts in mouse mammary fat pads significantly reduced tumor size, caused massive apoptosis and more importantly reduced Sulf-2 levels in vivo. Finally, our immunohistochemistry analysis of Sulf-2 expression in cohort of patient derived breast tumors indicates that Sulf-2 is significantly upregulated in autologous metastatic lesions compared to primary tumors (p < 0.037, Pearson correlation, Chi-Square analysis). In all, our data suggest that Sulf-2 might play an important role in breast cancer progression from ductal carcinoma in situ into an invasive ductal carcinoma potentially by resisting cell death.     

On the Role of Ultrasonography and CT Scan in the Diagnosis of Acute Appendicitis

The purposes of this study were to revisit the utility of ultrasonography (USG) as a primary imaging modality in acute appendicitis (AA) and to establish the role of CT scan as a second-line/problem-solving modality. All cases of suspected AA were referred for urgent USG. USG was done with standard protocol for appendicitis. Limited computed tomographic (CT) scan [NCCT ± CECT (IV contrast only)] was done for the lower abdomen and pelvis where sonographic findings were equivocal. One hundred and twenty-one patients were referred for USG for suspected appendicitis. Eight-four patients underwent surgery for AA based on clinical as well as imaging findings, of whom 76 had appendicitis confirmed at histopathology. Three patients were misdiagnosed (3.6 %) on USG as appendicitis. Of 76 patients of appendicitis confirmed histopathologically, 63 (82.8 %) had features of appendicitis on USG and did not require any additional imaging modality. Of 121 patients, 12 (10 %) needed CT scan because of atypical features on USG. Of these 12 patients, seven had retrocecal appendicitis, and three high-up paracolic appendicitis. USG alone had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 81, 88, 92.6, 71.6, and 83 %, respectively. When combined with CT scan in select cases, the sensitivity, specificity, PPV, NPV, and accuracy of combined USG + CT scan were 96 % (P?=?0.0014), 89 %, 93 %, 93.5 % (P?=?0.0001), and 93 % (P?=?0.0484), respectively. Twenty-eight (23 %) patients were given alternative diagnosis on USG. Dedicated appendiceal USG should be used as a primary imaging modality in diagnosing or excluding AA. Appendiceal CT can serve as a problem-solving modality.     

Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML)

Strategies that augment a GVL effect without increasing the risk of GVHD are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of immunomodulatory T regulatory cells (Tregs) in animal models. Reasoning that AZA might selectively augment a GVL effect, we studied the immunologic sequelae of AZA administration after allogeneic SCT. Twenty-seven patients who had undergone a reduced intensity allogeneic transplantation for acute myeloid leukemia were treated with monthly courses of AZA, and CD8(+) T-cell responses to candidate tumor Ags and circulating Tregs were measured. AZA after transplantation was well tolerated, and its administration was associated with a low incidence of GVHD. Administration of AZA increased the number of Tregs within the first 3 months after transplantation compared with a control population (P = .0127). AZA administration also induced a cytotoxic CD8(+) T-cell response to several tumor Ags, including melanoma-associated Ag 1, B melanoma antigen 1, and Wilm tumor Ag 1. These data support the further examination of AZA after transplantation as a mechanism of augmenting a GVL effect without a concomitant increase in GVHD.     

Laparoscopic drainage of cryptogenic liver abscess

Background

To retrospectively compare the outcomes of percutaneously drained and laparoscopically drained liver abscesses.

Methods

Eight-five consecutive patients with radiological evidence of liver abscess were treated at National University Hospital of Singapore from 2005 to 2011. Multivariable logistic regression was used to identify failures of intervention. This was defined as persistent objective signs of sepsis. Complications, length of antibiotic therapy, and hospital stay were recorded but not used as indicators for failure of intervention. A propensity score analysis was used to adjust for possible confounders.

Results

Twenty-seven (40.3 %) patients in the percutaneous group did not respond to primary intervention compared to 2 patients (11.1 %) in the laparoscopic group (p = 0.020). Two patients within the percutaneous group died from progression of sepsis despite intervention. In the multivariate model with propensity score, laparoscopic drainage had a protective effect against failure compared to percutaneous drainage of liver abscess (odds ratio [OR], 0.03; 95 % confidence interval [CI], [0–0.4]; p = 0.008). There were no differences in complications related to the intervention (p = 0.108). Mean duration of antibiotics (p = 0.437) and hospital stay (p = 0.175) between the groups was similar.

Conclusions

Laparoscopic drainage of cryptogenic liver abscesses should be considered as an option for drainage of liver abscess.     

Single-Institution Retrospective Comparison of Preoperative Versus Definitive Chemoradiotherapy for Adenocarcinoma of the Esophagus

Purpose

We sought to determine the impact of esophagectomy on survival in patients with adenocarcinoma of the esophagus cancer after chemoradiotherapy (CRT).

Methods

A database of esophageal cancer was queried for nonmetastatic patients with adenocarcinoma treated between 2000 and 2011 with CRT. Overall survival (OS) and recurrence-free survival (RFS) curves were calculated according to the Kaplan–Meier method and log-rank analysis. Multivariate analysis was performed by the Cox proportional hazard model.

Results

We identified 154 patients (60 without surgery; 94 with surgery) who were included in the analysis. The only differences between the 2 groups were more advanced disease stage, improved performance status, and younger age in the surgery group. Patients undergoing surgery had significantly higher survival. Median and 5-year OS for surgical patients were 4.1 years and 43.6 %, versus 1.9 years and 35.6 % for nonsurgical patients (p = 0.007). Multivariate analysis for OS and RFS revealed that factors associated with increased survival were surgical resection, tumor length < 5 cm, male gender, and lower stage. Age, tumor location, radiation dose/technique, and induction chemotherapy were not prognostic. There was a trend toward improved survival on univariate analysis (p = 0.10) and multivariate analysis (p = 0.063) for surgical patients compared to nonsurgical patients who were healthy enough for surgery before CRT (n = 38), and no difference in OS in nonsurgical patients healthy enough for surgery after CRT (n = 22).

Conclusion

Esophagectomy after CRT is associated with improved survival in patients with adenocarcinoma after CRT. Trimodal therapy should continue to remain the standard of care for esophageal adenocarcinoma.     

The Evaluation of Efficacy of Post-Operative Antibiotics in the Open Reduction of the Zygomatic and Mandibular Fracture: A Prospective Trial

Introduction

The administration of pre and post-operative antibiotics for open reduction and internal fixation of facial fracture is the usual norm followed. Although the benefit of antibiotic has been established in the literature, the value of post-operative administration has been questioned and yet not extensively studied or investigated. There are rising concerns over the duration and undesired effects of antibiotics. The purpose of the study was to evaluate necessity and/or efficacy of post-operative antibiotics in the open reduction of zygomatic and mandibular fracture.

Methods

Sixty patients who underwent open reduction and internal fixation were divided into two groups for the trial. Ab group (30 patients) received pre, intra and post-operative antibiotics. Non-Ab group (30 patients) did not receive post-operative antibiotics though pre and intra-operative antibiotics were administered. Patients were evaluated for post-op infection at the end of 1st and 3rd week after operation.

Results

Among 60 patients, 2 patients (1 from Ab group and 1 from non-Ab group) were infected; so statistically no significant difference in result was obtained (Fisher’s exact test, P value = 1).

Conclusion

In this trial, the use of post-operative antibiotics in the open reduction and internal fixation of facial fracture was shown to confer no benefit/efficacy in reducing the chances of infection.     

Assessment of changing patterns of Le fort fracture lines using computed tomography scan: an observational study

Objectives. To assess the changing mid-face fracture patterns using a computed tomography scan. Methodology: Fifty patients with mid-face trauma requiring open reduction and fixation were studied using 1.6 mm axial, sagittal, coronal and 3D images. Images were evaluated clinically, intra-operatively and finally were compared with standard Le Fort lines. Results. The male population dominated the female at a ratio of 11.5:1. The majority of the mid-face fractures were seen in the age group of 21–30 years. Road traffic accident (78%) was the major etiological factor followed by work-related accidents (12%) and assaults (10%). The CT scan analysis included categorizing the patients into three groups: (1) Fracture patterns resembling Le Fort lines (24%); (2) Fracture patterns partially resembling Le Fort lines (56%); and (3) Fracture patterns that do not resemble Le Fort lines (20%). Conclusion. With the change in the velocity of wounding object, there is a change in the mid-face fracture patterns. The majority of the cases present as a variant of classical Le Fort fractures. Computed tomography is a valuable diagnostic tool in assessing the fractures of the mid-face. 2D images are more sensitive than 3D images. However, both the images are required in delivery of an optimal treatment plan.     

A Novel Obturator Device for Management of Dilated Trachea-esophageal Puncture Tract Fistulas

Voice rehabilitation in laryngectomized patients by tracheoesophageal puncture is a time tested technique. In some patients the tracheoesophageal puncture gets inordinately dilated leading to leakage around the prosthesis. Most of these fistulas are managed by a variety of conservative treatments like temporary removal of prosthesis, placement of silastic ring over the prosthesis, placement of nasogastric tube and airway protection by a cuffed tracheostomy tube. Intractable fistulas are tackled by surgical closure but are fraught with failures. We hereby suggest a novel temporary obturator that can be can be easily made at a very low cost in any hospital having prosthetic rehabilitation services and obviates the need for a tracheostomy tube, nasogastric tube and repeated hospital visits.