IMPROVING AFTER-HOURS CALLS TO ENDOCRINOLOGY FELLOWS.

OBJECTIVE: To analyze the frequency and nature of after-hours calls to endocrinology fellows and employ interventions to direct appropriate care to primary endocrinologists. METHODS: The on-call fellows logged calls that came to them during the after-hours and marked them as urgent or nonurgent. We analyzed these calls and then implemented interventions to educate patients on calls that can wait until the next business day. We also trained providers to provide script refills during clinic visits and educated fellows on how to best manage and document these after-hours calls. RESULTS: From July to August 2017, 100 calls were logged. The average number of calls per 24 hours was 1.61, and 47% were marked nonurgent. From January to March 2018, the fellows logged 0.64 calls per 24 hours, and 51% were logged as nonurgent. Most of these calls were for insulin and testing supply refills. CONCLUSION: Many after-hours calls to the fellows were nonurgent and could have waited until the next business day. Our continuing interventions aim at improving both physician and patient satisfaction, as well as patient care.

Loss of MKK4 expression in ovarian cancer: a potential role for the epithelial to mesenchymal transition.

In the current study, we investigated the mechanism relating downregulation of mitogen-activated protein kinase kinase 4 (MKK4) expression to development of ovarian cancer. Over-expression of the MKK4 gene in TOV-21 G cells, a line with homozygous deletion of MKK4, resulted in morphologic changes in which cells growing in a scattered, fibroblast-like pattern formed tightly packed colonies. Based on a wound healing assay and a Matrigel invasion assay, we determined that both motility and invasiveness of MKK4-transfected TOV-21G cells were significantly reduced compared to control vector-transfected cells. To confirm that MKK4 expression related to tumor invasion resulted from an epithelial to mesenchymal transition (EMT)-like morphological change, we used 2 independent but complementary approaches. MKK4 gene knockdown in MDAH 2774 cells over-expressing MKK4 increased invasion activity. Additionally, engineered expression of MKK4 in SKOV3 cells, a line with low endogenous MKK4 expression, produced a phenotype similar to that of TOVG-21G. Interestingly, we found that MKK4 upregulation caused downregulation of phosphorylated NF-κB and Twist, as well as upregulation of E-cadherin, in TOVG-21G and SKOV3 cells. Reciprocal results were obtained in MDAH 2774 cells with MKK4 knockdown. Our results suggest that MKK4 downregulation causes increased phosphorylation NF-κB. This promotes Twist over-expression, resulting in E-cadherin downregulation that induces EMT in ovarian cancer.

MKK4 acts as a potential tumor suppressor in ovarian cancer.

Our previous studies indicate that loss of MKK4 expression is associated with the progression of ovarian cancer. However, direct evidence that MKK4 inhibits the malignant phenotype of ovarian cancer cells is limited. In the current study, we investigated the mechanism relating loss of MKK4 expression to the development of ovarian cancer. Using cell growth and anchorage-independent assays, we determined that both the growth and colony-forming ability of MKK4-transfected TOV-21G cells, a line with a homozygous deletion of MKK4, were significantly reduced compared to control vector-transfected cells. Overexpression of the MKK4 gene in TOV-21G cells resulted in reduced proliferative activity and increased apoptosis. To confirm that MKK4 expression related to tumor suppress function, we used two independent but complementary approaches. MKK4 gene knockdown in OVK18#2 and MDAH2774 cells, which overexpressed MKK4, increased proliferation activity. Additionally, the engineered expression of MKK4 in SKOV3 cells, a line with low endogenous MKK4 expression, produced a phenotype similar to that of TOV-21G. Similar results were produced in tumor xenografts in nude mice. These results indicated that MKK4 acts as a tumor suppressor and may represent an important therapeutic target for the treatment of ovarian cancer.

Microwave endometrial ablation is a highly efficacious way to emergently control life-threatening uterine hemorrhage.

OBJECTIVE: To asses the effectiveness of microwave endometrial ablation (MEA) using a new curved applicator for the emergent control of uterine hemorrhage. STUDY DESIGN: Seven patients received emergency MEA. Three out of seven patients were treated with MEA as their primary procedure, and four out of seven patients were treated for an intraoperative hemorrhage. RESULTS: In all three patients treated preoperatively, MEA was highly effective and successfully controlled acute uterine hemorrhage. Four out of seven patients were treated with MEA for a hemorrhage following resection of a submucosal myoma or polyp. MEA successfully controlled bleeding in all four patients, thereby preventing them from undergoing hysterectomy. CONCLUSION: Our results suggest that emergency MEA is a promising way to control a life-threatening uterine hemorrhage.

Biological role and prognostic significance of NAC1 in ovarian cancer.

OBJECTIVE: This study examined the biological and clinical significance of NAC1 expression in ovarian cancer and assessed whether NAC1 has the potential to be a therapeutic target. METHODS: NAC1 expression and gene amplification were assessed in ovarian cancers by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected by a retrospective chart review. NAC1 gene knockdown using silencing RNA and a NAC1 gene transfection system were used to assess NAC1 function in ovarian cancer tissue samples. RESULTS: The frequency of positive NAC1 expression in serous adenocarcinomas (50.0%:22/44) was significantly higher than that in the other histological subtypes (33.3%: 10/30). NAC1 gene amplification was identified in seven (9.5%) of 74 ovarian carcinomas. Positive NAC1 expression significantly correlated with shorter disease-free and overall survival (P = 0.002, P = 0.0048). A multivariate analysis showed that positive NAC1 expression was an independent prognostic factor for disease-free and overall survival after standard platinum-taxane chemotherapy (P = 0.0027, P = 0.0302). Profound growth inhibition, increased apoptosis, decreased cell proliferation, and decreased cell migration and invasion were observed in silencing RNA-treated cancer cells with NAC1 overexpression compared with cancer cells without NAC1 expression. NAC1 overexpression stimulated proliferation, migration, and invasion in ovarian cancer cell lines KF28 and TOV-21G, which normally lacked NAC1 expression. CONCLUSION: These findings indicate that NAC1 over-expression is critical to the growth and survival of ovarian cancers. Furthermore, they suggest that NAC1 silencing RNA-induced phenotypes depend on the expression status of the targeted cell line. Therefore, NAC1-targeted therapy may benefit ovarian cancer patients with NAC1 expression.

Expression of nuclear Notch3 in cervical squamous cell carcinomas and its association with adverse clinical outcomes.

OBJECTIVE: The aim of this study was to clarify the functional role of Notch3 in human cervical carcinomas. METHODS: Notch3 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. We used dual-color fluorescence in situ hybridization (FISH) to analyze DNA copy number alterations in cervical cancer. Inactivation of Notch3 and knocking down Notch3 gene were done using gamma-secretase inhibitor and Notch 3 specific SiRNA to asses Notch3 function in cervical cancer either in vivo or in vitro. RESULTS: Immunohistochemical analysis revealed that Notch3 was significantly overexpressed in cervical squamous cell carcinomas compared with adenocarcinomas. In contrast to normal cervical tissue and cervical intraepithelial neoplasms [CINs], squamous cell carcinomas demonstrated higher nuclear Notch3 immunoreactivity. Notch3 amplification was not found in any cervical carcinomas using FISH analysis. Notch3 nuclear expression was significantly correlated with Jagged-1, a putative Notch3 ligand, and Pbx1b, a potential Notch3 downstream target (P<0.05).Patients with cervical carcinomas positive for nuclear Notch3 expression had significantly shorter overall survival than their peers whose tumors did not express nuclear Notch3. Inactivation of Notch3 decreased cell proliferation and induced apoptosis in ME180 and SKGIIIb cell lines that overexpressed Notch3. Injection of a gamma-secretase inhibitor into ME180 cell tumors established on mice, demonstrated a reduction in tumor growth. CONCLUSION: Our findings suggest that Notch3 might play important role for the proliferation and survival of Notch3 overexpressing tumors and that inactivation of Notch3 may represent a new therapeutic avenue for cervical squamous cell carcinomas.

Expression of a BTB/POZ protein, NAC1, is essential for the proliferation of normal cyclic endometrial glandular cells and is up-regulated by estrogen.

PURPOSE: The purpose of this study was to investigate the expression and localization of NAC1, a member of the BTB/POZ gene family in the human cyclic endometrium. EXPERIMENTAL DESIGN: NAC1 expression in normal cyclic endometrium was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. To elucidate the molecular mechanisms of NAC1 expression in the normal endometrium endometrial carcinoma cell lines (Ishikawa, HHUA; ER+, PR+) and primary cultured normal endometria were tested in a sex steroid induction assay and a NAC1 knockdown assay using siRNA. RESULTS: Expression of NAC1 in glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases. Both NAC1 RNA and protein expression were up-regulated by treatment with 10 nmol/L 17beta-Estradiol (E2) in Ishikawa, HHUA and primary cultured normal endometrial cells. The estrogen receptor antagonist ICI 182,780 significantly attenuated E2-induced NAC1 expression. NAC1 gene knockdown inhibited cell growth and induced apoptosis in Ishikawa, HHUA, and normal endometria, all of which expressed NAC1. Furthermore, NAC1 siRNA significantly abrogated estrogen-driven cellular proliferation in Ishikawa, HHUA, and primary cultured normal endometrial cells, whereas the control siRNA had no effect on cell growth in any of these cells. CONCLUSIONS: These findings suggest that NAC1 is functionally involved in E2-induced cell growth of the normal endometrial glandular cells. Because NAC1 is thought to have oncogenic potential, the current findings may provide new insight into the mechanism of estrogen induced endometrial carcinogenesis.

[Paclitaxel + carboplatin (TC)-resistant stage Ic squamous cell carcinomas arising in mature cystic teratomas of the ovary].

Malignant transformation of an ovarian mature cystic teratoma is very rare; it arises in about 1-2% of all dermoid cysts. No standard treatment has been established for advanced and recurrent disease. In Case 1, a 78-year-old woman was diagnosed with squamous cell carcinoma arising from a mature cystic teratoma of the ovary after undergoing right salpingo-oophorectomy (RSO). She was treated with chemotherapy(TC), but the carcinoma recurred 2 months after completing first-line chemotherapy. She began second-line chemotherapy (PEC: CBDCA+PEP+etoposide), but became disoriented on the second day of treatment, and could not complete the schedule. She died 2 months after the recurrence. Case 2 was a 60-year-old woman diagnosed with stage Ic disease when she underwent a computed tomography scan during chemotherapy for breast cancer recurrence in her liver. She underwent bilateral salpingo-oophorectomy (BSO), and was treated with chemotherapy (TC+trastuzumab). She received 5 courses, but the breast cancer metastases enlarged and her chemotherapy regimen was changed. Five months later, after completing 5 courses of TC+trastuzumab, she had disseminated recurrence in the pelvis and also had a mass. She developed ileus and underwent a colostomy. She then underwent transcatheter arterial embolization via the inferior mesenteric artery and received cisplatin (100 mg/body) as second-line chemotherapy. The tumor was reduced in size about 30%, for a partial remission. However, her breast cancer recurrence was exacerbated and she died. The results of TAE, however, showed that it may be an effective second-line therapy for recurrent squamous cell carcinoma arising from a mature cystic teratoma.

Hypovitaminosis D and Its Relationship with Diabetes Mellitus among the Postmenopausal Women in Jashore, Bangladesh.

BACKGROUND AND OBJECTIVES: Vitamin D has diversity of functions including diabetes mellitus by its anti-inflammatory and immuno-modulatory effects. With the scarcity of the regarding data in Bangladesh, the aim of this study was to assess the relationship between hypovitaminosis D and diabetes mellitus among the postmenopausal women. METHODS: An observational study conducted from 1st July to 31st December, 2018 in Jashore, Bangladesh that recruited 152 eligible apparently healthy natural postmenopausal women above 45 years without having any chronic diseases and drugs interfering vitamin D metabolism. Data was taken by face to face interview through self-administered questionnaires. Independent t-test, one-way analysis of variance (ANOVA) were used to extract P value and Hochberg's post-hoc test used as equal variance assumed in homogeneous sample to evaluate deference between different groups. RESULTS: Among 152 study subjects, the frequency of diabetes and prediabetes were 28.3% and 31.6%, respectively, among the postmenopausal women by fasting blood sugar level according to the ADA guideline. The study revealed 86 (52.58%) deficient, 56 (36.84%) insufficient, and only 10 (6.58%) sufficient Vitamin D level. Illiterate subjects had less hypovitaminosis D than literate subjects. Urban subjects had more in deficiency state of Vitamin D than rural subjects' on the other hand rural subjects had more insufficiency of Vitamin D. Obese individuals suffered more in hypovitaminosis D than others. There was no significant statically relationship found between FBS and 25(OH)D Level in this study. CONCLUSION: With high frequency of diabetes and hypovitaminosis D among the postmenopausal women but there is no statically significant relationship found between diabetes and hypovitaminosis D in this study.

Continuous glucose monitoring reduces pubertal hyperglycemia of type 1 diabetes.

Background Physiologic hyperglycemia of puberty is a major contributor to poor glycemic control in youth with type 1 diabetes (T1D). This study's aim was to determine the effectiveness of continuous glucose monitoring (CGM) to improve glycemic control in pubertal youth with T1D compared to a non-CGM cohort after controlling for age, sex, BMI, duration, and insulin delivery methodology. The hypothesis is that consistent CGM use in puberty improves compliance with diabetes management, leading to increased percentage (%) time in range (TIR70-180 mg/dL) of glycemia, and lowering of HbA1c. Methods A longitudinal, retrospective, case-controlled study of 105 subjects consisting of 51 T1D controls (60.8% male) age 11.5 ± 3.8 y; and 54 T1D subjects (48.1% male) age 11.1 ± 5.0 y with confirmed CGM use for 12 months. Pubertal status was determined by Tanner staging. Results were adjusted for baseline HbA1c and diabetes duration. Results HbA1c was similar between the controls and the CGM group at baseline: 8.2 ± 1.1% vs 8.3 ± 1.2%, p=0.48 respectively; but was significantly lower in the CGM group 12 months later, 8.2 ± 1.1% vs. 8.7 ± 1.4%, p=0.035. Longitudinal change in HbA1c was similar in the prepubertal cohort between the control- and CGM groups: -0.17 ± 0.98% vs. 0.38 ± 1.5%, p=0.17. In contrast, HbA1c increased with advancing age and pubertal status in the pubertal controls but not in the pubertal CGM group: 0.55 ± 1.4 vs -0.22 ± 1.1%, p=0.020. Percent TIR was inversely related to HbA1c in the CGM group, r=-0.6, p=0.0004, for both prepubertal and pubertal subjects. Conclusions CGM use significantly improved glycemic control in pubertal youth with T1D compared to non-CGM users.

A BTB/POZ gene, NAC-1, a tumor recurrence-associated gene, as a potential target for Taxol resistance in ovarian cancer.

PURPOSE: We previously determined that NAC-1, a transcription factor and member of the BTB/POZ gene family, is associated with recurrent ovarian carcinomas. In the current study, we investigated further the relationship between NAC-1 expression and ovarian cancer. EXPERIMENTAL DESIGN: NAC-1 expression was assessed by immunohistochemistry, and clinical variables were collected by retrospective chart review. SiRNA system and NAC-1 gene transfection were used to asses NAC-1 function in Taxol resistance in vivo. RESULTS: Overexpression of NAC-1 correlated with shorter relapse-free survival in patients with advanced stage (stage III/IV) ovarian carcinoma treated with platinum and taxane chemotherapy. Furthermore, overexpression of NAC-1 in primary tumors predicted recurrence within 6 months after primary cytoreductive surgery followed by standard platinum and taxane chemotherapy. NAC-1 expression levels were measured and compared among the human ovarian cancer cell line (KF28), cisplatin-resistant cell line (KFr13) induced from KF28, and paclitaxel-resistant cell lines (KF28TX and KFr13TX) induced by exposing KF28 and KFr13 to dose-escalating paclitaxel. Overexpression of NAC-1 was observed in only the Taxol-resistant KF28TX and KFr13 TX cells but not in KF28 or cisplatin-resistant KFr13 cells. To confirm that NAC-1 expression was related to Taxol resistance, we used two independent but complementary approaches. NAC-1 gene knockdown in both KF28TX and KFr13TX rescued paclitaxel sensitivity. Additionally, engineered expression of NAC-1 in RK3E cells induced paclitaxel resistance. CONCLUSIONS: These results suggest that NAC-1 regulates Taxol resistance in ovarian cancer and may provide an effective target for chemotherapeutic intervention in Taxol-resistant tumors.

Expression of the bric-a-brac tramtrack broad complex protein NAC-1 in cervical carcinomas seems to correlate with poorer prognosis.

PURPOSE: Recent studies have suggested a novel oncogenic role of a bric-a-brac tramtrack broad complex (also known as POZ) domain gene, NAC-1, in ovarian carcinomas. The aim of this study was to clarify the functional role of NAC-1 in human cervical carcinomas. EXPERIMENTAL DESIGN: NAC-1 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. NAC-1 gene knockdown using small interfering RNA and a NAC-1 gene transfection system were used to asses NAC-1 function in cervical cancer in vivo. RESULTS: Immunohistochemical and gene expression analysis revealed that NAC-1 is significantly overexpressed in cervical adenocarcinomas and adenosquamous carcinomas compared with squamous cell carcinomas. Patients with squamous cell carcinomas positive for NAC-1 expression who received radiotherapy had significantly shorter overall survival than peers whose tumors did not express NAC-1, and multivariate analysis showed that NAC-1 expression was an independent prognostic factor for overall survival after radiotherapy. Overexpressions of the NAC-1 gene stimulated cell proliferation in cervical carcinoma cells of the TCS, CaSki, and HeLa P3 lines, which do not have endogenous NAC-1 expression. NAC-1 gene knockdown inhibited cell growth and induced apoptosis in HeLa, HeLa TG, and ME180 cells, all of which overexpressed NAC-1. CONCLUSIONS: Our findings suggest that NAC-1 may play an important role in cervical carcinomas; moreover, these findings provide a rationale for future development of NAC-1-based therapy for cervical carcinomas that overexpress this candidate oncogene.

A case of bilateral pelvic lymph node involvement in stage 1a1 squamous cell carcinoma of cervix and a review of the literature.

Stage1a1 cervical cancer has been established to define a subset of the disease in patients who may safely be managed more conservatively and who have an excellent prognosis. Recently, however, a number of stage 1a1 cases with lymph node metastasis have been reported. Some of these cases had positive lymphovascular space invasion (LVSI), which some studies have identified as a negative prognostic factor. There is still, however, disagreement between the International Federation of Gynecology and Obstetrics (FIGO) and the Society of Gynecologic Oncologists (SGO) regarding whether LVSI may be used as a staging criterion. We report a 36-year-old patient with stage 1a1 cervical cancer who was diagnosed with multiple pelvic and parametrial lymph node metastases. Histopathology showed extensive LVSI. While stage 1a1 cases may still be managed conservatively, physicians must consider the possibility of lymph node metastasis, particularly in patients with positive LVSI, and counsel patients accordingly.

Microwave endometrial ablation as an alternative to hysterectomy for the emergent control of uterine bleeding in patients who are poor surgical candidates.

BACKGROUND: Microwave endometrial ablation is a new, minimally invasive treatment option for menorrhagia. Its popularity in many countries is increasing due to its safety and simplicity. CASES: We treated menorrhagia due to submucosal myomas in two patients with a modified microwave endometrial ablation device. Surgery was contraindicated in the first patient secondary to medical co-morbidities and in the second patient because of acute hemorrhagic shock. In both cases, the operation was highly effective and each patient was satisfied with her treatment outcome. CONCLUSION: Given its safety, simplicity, and effectiveness, microwave endometrial ablation may be widely adopted for the emergent control of uterine bleeding in patients with poor surgical candidates.

[A case of PEP(BEP)-resistant ovarian dysgerminoma successfully treated by VeIP therapy].

Ovarian germ cell tumors are malignant tumors which commonly develop during childhood, and which are sensitive to chemotherapy. We have had a case of germ cell tumors which showed resistance to first-line PEP(BEP)chemotherapy. As second-line chemotherapy, VeIP therapy was used, because it is possible that this therapy is effective against recurrent testicular germ cell tumors. The patient was fourteen years old. She experienced acute abdominal pain and visited the hospital, where she was diagnosed with torsion of an ovarian tumor. An emergency laparotomy and right salpingoophorectomy were performed, the pathological diagnosis being stage Ia ovarian dysgerminoma G1. She was followed for two years until her serum hCG-CTP elevated to 1.4 mIU/mL. An MRI revealed an abnormal signal in the left ovary, so we diagnosed this as a recurrence of the dysgerminoma. Then she received chemotherapy PEP(BEP), but after eight months of PEP (BEP), her serum hCG-CTP was again elevated to 14.5 mIU/mL. A recurrence was detected with an MRI and PET-CT, and another laparotomy was performed. The recurrent region was detected in the left ovary. A left ovarian cystectomy was performed in which CDDP ip was used. After the operation, the patient again underwent chemotherapy. VeIP (vinblastine+ifosfamide+cisplatin)was chosen as the second-line regimen. After 6 courses of this therapy, she had a follow-up operation. No recurrence region was found in the pelvic area. She remains without recurrence of this disease 24 months after VeIP therapy. This case suggests that VeIP therapy might be an effective second-line therapy for patients with PEP(BEP)-resistant ovarian dysgerminoma.

Genetic classification of ovarian carcinoma based on microsatellite analysis: relationship to clinicopathological features and patient survival.

Ovarian carcinomas can progress through two pathways of genomic instability: chromosomal instability (CIN) and microsatellite instability (MSI). However, it is unknown whether these two mechanisms could be distinguished from each other in the molecular characteristics in ovarian carcinomas. We hypothesized that these two pathways are not always independent in ovarian carcinomas. We classified 51 ovarian carcinomas based on their MSI and CIN status using microsatellite analysis and assessed whether these carcinogenic pathways affect the clinicopathological features and patient survival. Of the 51 cases, 77.4% of the tumors were microsatellite stable (MSS), 5.9% were MSI-Low (MSI-L) whilst, 16.7% were MSI-High (MSI-H). Overall, 56.8% of the tumors had at least one loss of heterozygosity (LOH) event, i.e., 56.8% CIN. Notably, we identified a significant degree of overlap between the MSI and CIN pathways. Of the 34 tumors with LOH events (CIN), 5 (14.7%) were MSI-H. In addition, of the 7 tumors that were MSI-H, 5 (71.4%) had one or more LOH events (CIN). We also identified a group of 29.4% of all tumors that did not demonstrate any evidence of either of the two pathways of genomic instability as they were MSS/MSI-L with no evidence of LOH events (CIN negative). Furthermore, patients with CIN with MSS/MSI-L have a significantly shorter overall survival compared to those in other genetic categories (P=0.019). Cox regression analysis revealed that tumors with CIN with MSS/MSI-L exhibit a poor prognostic outcome after adjustment for FIGO stage and grade. These findings suggest that some ovarian carcinomas have a significant degree of overlap between the two pathways of genomic instability and that the genetic classification using microsatellite markers may represent a potential new biomarker of risk prediction in ovarian carcinoma.

Clinical and Biochemical Profile of Hepatitis A Virus infection in Children

Background: Acute hepatitis A virus infection in children in developing countries is a matter of concern though the incidence has come down in developed countries.To observe the clinical presentation and biochemical profile of hepatitis A virus infection in children hospitalized in a tertiary care center in Bangladesh.Material & Methods:In this cross-sectional observational study, data were collected from the records of pediatric patients who were admitted due to acute hepatitis. Demographic data were collected, and complete physical examination findings and laboratory data were also taken. Serum samples were tested for LFT, Anti-HAV IgM and other viral markers among them Anti-HAV IgM positive children were included in the study.Results:Among the total of 40 patients suffering from Acute Viral Hepatitis (AVH), male predominated over female with 57.5% vs. 42.5%. The majority of the study population (65%) came from the urban area. In this study, 65% of the patients used tap water and 35% used tube well water for drinking purposes while the majority 70% used boiled water. Most of the patients (80%) consumed both homemade and outside foods and drinks while 20% consumed only homemade food. Positive family history of viral hepatitis was found in 12.5% of cases. Common presentations were fever (100%), jaundice (100%), anorexia, nausea (95%), vomiting (85%), abdominal pain (50%) etc. On examination Jaundice (100%) and hepatomegaly (95%), splenomegaly (5%), and ascites (7.5%). Only 7.5% of patients developed complications like cholestasis,7.5% showed ascites,5% had relapsed and 2.5% develop liver failure.Conclusions:This study showed that poor sanitation and poor hygiene are the main risk factors for hepatitis A. The common presenting features which should alert the clinicians include fever, jaundice, anorexia, nausea, vomiting, diarrhea, abdominal distension, hepatosplenomegaly and ascites. In Bangladesh, safe water supplies and proper sanitation will constitute the best solution to eliminate endemic hepatitis A.

Dose doubling, relative potency, and dose equivalence of potassium-sparing diuretics affecting blood pressure and serum potassium: systematic review and meta-analyses.

BACKGROUND: Potassium-sparing diuretics (PSDs) are valuable antihypertensives with additional benefits unrelated to control of systolic blood pressure (SBP). However, their key parameters affecting SBP and serum potassium are poorly defined, fostering underutilization. METHOD: Consequently, we conducted systematic reviews and meta-analyses, yielding 3668 articles and ultimately 84 randomized comparisons. RESULTS: For office SBP, overall placebo-adjusted changes were triamterene -1.9 (low dose only), amiloride -9.9, spironolactone -13.2, and eplerenone -9.2. Differences in antihypertensive effect were due to potency rather than efficacy. Doubling amiloride, eplerenone, and spironolactone doses reduced SBP (95% confidence limits) on average by -2.3 (-3.1, -1.5). Relative antihypertensive potencies were spironolactone>amiloride>eplerenone. Spironolactone had significantly greater antihypertensive potency than amiloride, -4.0 (-7.4, -0.6), and eplerenone, -5.5 (-7.4, -3.6). Dose equivalencies were eplerenone-spironolactone 4.5-to-1 (e.g., eplerenone 125∼spironolactone 25), amiloride-spironolactone 3.3-to-1, and eplerenone-amiloride 1.4-to-1. Increases in serum potassium from amiloride and spironolactone at commonly used doses averaged 0.14-0.29 mEq/l; the dose doubling effect was 0.16 (0.10, 0.22). Spironolactone caused greater hyperkalemia than amiloride across their dose ranges: 0.14, P = 0.043. Seven features make important bias unlikely: a comprehensive literature search, adjustment for covariates, all models explaining 95-100% of the between-study variability, similar dose doubling effects among PSDs, two different methods giving the same potency sequence, similar results from double blind comparisons, and similar results for eplerenone versus spironolactone from analysing direct comparison data (i.e., no meta-regression) for office and 24-h SBP. CONCLUSION: This synthesis accomplishes for PSDs what has already been achieved for thiazide-type diuretics and other antihypertensives and can guide the application of these underutilized medicines.

Stem cells derived from tooth periodontal ligament enhance functional angiogenesis by endothelial cells.

In regenerative medicine approaches involving cell therapy, selection of the appropriate cell type is important in that the cells must directly (differentiation) or indirectly (trophic effects) participate in the regenerative response. Regardless of the mode of action of the cells, angiogenesis underlies the success of these approaches. Stem cells derived from tooth tissues, specifically the periodontal ligament of teeth (periodontal ligament stem cells [PDLSCs]), have recently been identified as a good source of multipotent cells for cell therapies. PDLSCs have demonstrated properties similar to mesenchymal stem cells (MSCs), yet, unlike MSCs, their vascular potential has not been previously demonstrated. Thus, the aim of this study was to determine if PDLSCs could modulate angiogenesis. In comparison to MSCs and stem cells derived from tooth pulp tissues (SHEDs), we first determined if PDLSCs released soluble proangiogenic factors with the capacity to induce vessel formation by endothelial cells (ECs). Next, the ability of PDLSCs to modulate angiogenesis was examined through their cotransplantation with ECs in subcutaneous sites of immunocompromised mice. Finally, the stability of the PDLSC-mediated vasculature was determined through evaluation of the maturity and functionality of the vessels formed following PDLSC transplantation. It was determined that PDLSCs produced appreciable levels of vascular endothelial growth factor and basic fibroblast growth factor-2, and additionally, were able to initiate in vitro angiogenesis of ECs comparable to MSC- and SHED-mediated angiogenesis. In vivo cotransplantation of ECs with PDLSCs significantly (>50% increase) enhanced the number of blood vessels formed relative to transplantation of ECs alone. Finally, vessels formed following PDLSC cotransplantation were more mature and less permeable than those formed after transplantation of EC alone. These data demonstrate for the first time that PDLSCs have vascular potential, which could make them a very attractive cell population for utilization in regenerative cell therapies.