Background: Dienogest is a potential treatment for pelvic pain associated with endometriosis, a condition of significant concern in gynaecology. The current study was conducted as a crossover-randomized bioequivalence...Background: Dienogest is a potential treatment for pelvic pain associated with endometriosis, a condition of significant concern in gynaecology. The current study was conducted as a crossover-randomized bioequivalence assessment of two oral Dienogest 2 mg formulations, aiming to provide valuable insights for healthcare professionals and researchers in this field. Objective: The primary aim of this research was to evaluate and compare the pharmacokinetic characteristics of Dienogest 2 mg tablets. Dinogest (Dienogest 2 mg) tablets, manufactured by Nuvista Pharma Limited in Bangladesh, and Visanne (Dienogest 2 mg) tablets, manufactured by Bayer Pharma in Germany, were the test and reference formulations, respectively. Materials and Method: The study was an open-label, balanced, randomized, two treatments, two sequences, two periods, two-way crossover, laboratory blind, single oral dose bioequivalence study conducted in healthy adult females under fasting conditions. The study was carried out on 13 healthy, non-pregnant female subjects, and all the subjects completed both study periods with a 15-day washout in between. Randomization was used to assign the test and reference formulations to the subjects. Following each oral administration, a series of blood samples were obtained at different time intervals from pre-dose to 72 hours post-dose and analyzed for Dienogest concentrations using a validated bio-analytical method. A standard non-compartmental model was used to analyze the pharmacokinetic parameters. The primary pharmacokinetic parameters were peak plasma drug concentration (C<sub>max</sub>), the area under the plasma concentration-time curve from time zero to time t (AUC<sub>0–t</sub>), and AUC from t = 0 to infinity (AUC<sub>0–∞</sub>). The other PK parameters included time to reach C<sub>max</sub> (T<sub>max</sub>), terminal elimination rate constant (K<sub>el</sub>), and half-life (t<sub>1/2</sub>). Result: The ratios and 90% CI for the geometric mean test/reference were 95.53% (86.70% - 105.26%) for C<sub>max</sub>, 101.75% (95.42% - 108.49%) for AUC<sub>0</sub><sub>−</sub><sub>t</sub>, and 101.54% (95.59%% - 107.87%) for AUC<sub>0</sub><sub>−</sub><sub>∞</sub>. The formulations were bioequivalent since the 90% CIs for the geometric mean test/reference ratios were 80% to 125%, according to the predetermined range of US Food and Drug Administration (FDA) requirements. Conclusion: This single-dose investigation shows that the Dienogest test and reference formulations exhibited a rate and degree of absorption that met the regulatory requirements for bioequivalence.展开更多
Aim: To determine maternal and neonatal morbidities associated with instrumental vaginal delivery. Methods: This retrospective study consisted of 233 women undergoing instrumental vaginal deliveries from April 2020 to...Aim: To determine maternal and neonatal morbidities associated with instrumental vaginal delivery. Methods: This retrospective study consisted of 233 women undergoing instrumental vaginal deliveries from April 2020 to March 2021 at Paropakar Maternity and Women Hospital, a tertiary care hospital in Kathmandu, Nepal. Neonatal and maternal complications were analyzed. Results: Of 233 women, 102 (43.7%) and 131 (56.2%) had vacuum and forceps deliveries, respectively. The use of instruments was more frequent in infants with higher birth weight and gestational age. There were no significant differences in Apgar scores between the two groups. Two main indications of instrumental deliveries were fetal distress and prolonged second stage labor. Forceps, compared with vacuum, more often caused 3<sup>rd</sup>/4<sup>th</sup> perineal tears, tear extending to fornices, and postpartum hemorrhage. Neonatal outcomes were similar in both types of instrumental deliveries. Conclusion: Instrumental vaginal delivery caused maternal morbidity and procedure/judgment training for it is essential.展开更多
Background: Thyroid disorders are the most common endocrine disorders in pregnancy accounting for 10% of subclinical hypothyroidism in all pregnancies. Screening for hypothyroidism is essential in all pregnant women, ...Background: Thyroid disorders are the most common endocrine disorders in pregnancy accounting for 10% of subclinical hypothyroidism in all pregnancies. Screening for hypothyroidism is essential in all pregnant women, especially in Nepal, a low-income region where women have an increased risk of developing iodine deficiency during pregnancy. Hence this study is to analyze fetomaternal outcomes in maternal hypothyroidism complicating pregnancies. Methods: This retrospective observational study was carried out at Paropakar Maternity and Women Hospital, a tertiary center located in Kathmandu, Nepal. The Subjects of this study were 330 antenatal women with a singleton pregnancy with hypothyroidism admitted for delivery in the obstetrics ward, and informed consent was obtained. Women were chosen irrespective of age, parity, residency, and socioeconomic status. Women with multiple pregnancies and any preexisting medical disorders including heart disease, diabetes, and hypertension were excluded. Routine hematological parameters and estimations of T3, T4, and thyroid stimulating hormone (TSH) were conducted. Patients with hypothyroidism were divided into overt and subclinical and were subsequently assessed for maternal and fetal complications. The occurrence of maternal outcomes and perinatal outcomes were recorded. Result: Out of 470 total hypothyroid cases, 330 were enrolled in the study and the remaining 140 were excluded. In our study, the incidence of hypothyroidism in pregnancy was 2.11% with 1.7% of subclinical hypothyroidism and 0.31% of overt hypothyroidism. The mean age of the patient was >30 years with 53.3% (n = 176) primigravida. Mostly 70.3% (n = 232) from rural areas. Pre-Eclampsia, gestational diabetes abruptio placenta, and postpartum hemorrhage were the adverse maternal outcome with a higher percentage of these in overt hypothyroidism which was statistically significant. Concerning fetal outcome APGAR score <6 in 5 min, Intrauterine growth restriction (IUGR), NICU admission, neonatal Respiratory distress syndrome (RDS), Intrauterine fetal death (IUFD), and congenital anomaly were found with a higher percentage in overt hypothyroidism. Conclusion: Since the impact of hypothyroidism on fetomaternal morbidities have been identified so screening for hypothyroidism to be included as a routine screening test and should be treated accordingly to improve maternal and fetal outcome.展开更多
Chromobacterium violaceum is a Gram negative, facultative anaerobe, generally present in water, soil in tropical and subtropical regions. This bacterium is an emerging environmental pathogen that causes life threateni...Chromobacterium violaceum is a Gram negative, facultative anaerobe, generally present in water, soil in tropical and subtropical regions. This bacterium is an emerging environmental pathogen that causes life threatening infection in humans and animals. It can cause wound infection, visceral abscess, septicaemia, meningitis, diarrhoea, UTI. It is associated with significant mortality due to severe systemic infection. As the bacteria have high spreading tendency leading to sepsis, early identification and prompt treatment is necessary. Here we report a case of Chromobacterium violaceum wound infection in a 9 years old male from Dhaka, who was successfully treated with combination of cefixime and flucloxacillin antibiotics as per culture sensitivity report.展开更多
Vaginal bleeding is a common symptom in the emergency department of obstetrics and gynecology hospitals;however,post-hysterectomy vaginal bleeding is a rare phenomenon.Uterine artery pseudoaneurysm(UAP)is a rare condi...Vaginal bleeding is a common symptom in the emergency department of obstetrics and gynecology hospitals;however,post-hysterectomy vaginal bleeding is a rare phenomenon.Uterine artery pseudoaneurysm(UAP)is a rare condition that can lead to fatal bleeding and most commonly occurs as a long-term complication after invasive surgery or even in non-invasive procedures,such as cesarean section,myomectomy,dilatation and curettage,cervical conization and vaginal delivery.[1-3]Pseudoaneurysm is a pulsatile hematoma formed after arterial injury and rupture.展开更多
Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors ...Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes.Advantages of image-based brachytherapy include:improved tumor coverage(especially for large volume disease), decreased dose to critical organs(especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging(MRI),computed tomography(CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. Forpractical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE(an international study of MRI-guided brachytherapy in locally advanced cervical cancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervical cancer patients.展开更多
AIM: To characterize the correlation between severity of hepatopulmonary syndrome (HPS) and degree of hepatic dysfunction,and to explore how intestinal endotoxemia (IETM) affects the development of HPS in cirrhotic ra...AIM: To characterize the correlation between severity of hepatopulmonary syndrome (HPS) and degree of hepatic dysfunction,and to explore how intestinal endotoxemia (IETM) affects the development of HPS in cirrhotic rats. METHODS: Male Wister rats were fed with a diet containing maize flour,lard,cholesterol,and alcohol and injected subcutaneously with CCl4 oil solution every two days for 8 wk to induce typical cirrhosis and development of HPS. The animals were also given a nitric oxide (NO) production inhibitor,Nω-nitro-L-arginine methyl ester (L-NAME) intraperitoneally,and an iNOS inhibitor,aminoguanidine hydrochloride (AG) via gavage daily from the end of the 4th wk to the end of the 6th or 8th wk,or a HO-1 inhibitor,zinc protoporphyrin (ZnPP) intraperitoneally 12 h prior to killing. Blood,liver and lung tissues were sampled. RESULTS: Histological deterioration of the lung paralleled to that of the liver in the cirrhotic rats. The number of pulmonary capillaries was progressively increased from 6.1 ± 1.1 (count/filed) at the 4th wk to 14.5 ± 2.4 (count/filed) at the 8th wk in the cirrhotic rats. Increased pulmonary capillaries were associated with increased blood levels of lipopolysaccharide (LPS)(0.31 ± 0.08 EU/mL vs control 0.09 ± 0.03 EU/mL),alanine transferase (ALT,219.1 ± 17.4 U/L vs control 5.9 ± 2.2 U/L) and portal vein pressure. Compared with normal control animals,the number of total cells in bronchoalveolar lavage fluid (BALF) of the cirrhotic rats at the 8th wk was not changed,but the number of macrophages and the ratio of macrophages to total cells were increased by nearly 2-fold,protein expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) started to increase significantly at the 4th wk,and reached its peak at the 8th wk in the lung of cirrhotic rats. The increase of iNOS expression appeared to be quicker than that of eNOS. NO2-/NO3-was also increased,which was correlated to the increase of iNOS (r = 0.7699,P < 0.0001) and eNOS (r = 0.5829,P < 0.002). mRNA expression of eNOS and iNOS was highly consistent with their protein expression. CONCLUSION: Progression and severity of HPS as indicated by both increased pulmonary capillaries and histological changes are closely associated with LPS levels and progression of hepatic dysfunction as indicated by increased levels of ALT and portal vein pressure. Intestinal endotoxemia plays a central role in the development of HPS in the cirrhotic rat model by inducing NO and/or CO.展开更多
There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their si...There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their size and on the presence of specific clinical and genetic information provided in the published material from 2001 to 2005. Twelve studies provided raw data to carry out comparisons of disease location while ten studies included analysis of NOD2/CARD15 genotypes. NOD2/CARD15 variant frequency in ileal disease did not differ significantly among studies, whereas a comparison of disease location demonstrated highly significant differences among studies. Meta-analysis confirmed significant associations between NOD2/CARD15 variants and both ileal and ileocolonic disease locations, and with both stricturing and penetrating forms of disease behavior. This review underlines the significant phenotypic differences that exist among populations, including similar ethnic groups, and has demonstrated the need for further studies of patients with long-term “inflammatory” Crohn’s disease.展开更多
BACKGROUND: Emergency physicians frequently encounter patients with acute small bowel obstructions(SBO). Although computed tomography(CT) imaging is the current gold standard in the assessment of patients with suspect...BACKGROUND: Emergency physicians frequently encounter patients with acute small bowel obstructions(SBO). Although computed tomography(CT) imaging is the current gold standard in the assessment of patients with suspected SBO in the emergency department, a few studies have examined the use of ultrasound as an alternative imaging technique. METHODS: We evaluated the accuracy of ultrasound performed in the ED by a variety of providers(physicians with various levels of training, physician assistants) compared to CT imaging in 47 patients with suspected SBOs. RESULTS: Our data demonstrated a sensitivity of 93.8% and a specificity of 93.3% when compared to abdominal CT, and a sensitivity of 94.3% and specificity of 95.2% using a composite endpoint of abdominal CT and discharge diagnosis. CONCLUSION: Ultrasound can play an important role in the identification of small bowel obstructions in ED patients.展开更多
Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment.Herein,we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the“prec...Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment.Herein,we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the“precise strike”of hypoxic tumors through the dual-targeting effects from surface-modified hyaluronic acid(HA)and hypoxia-dependent factor carbonic anhydrase IX(CA IX)-inhibitor acetazolamide(AZ).The core of nanobullets is the special zinc(II)phthalocyanine aggregates(ZPA)which could heat the tumor tissues upon 808-nm laser irradiation for photothermal therapy(PTT),along with the alkyl chain-functionalized thermally decomposable radical initiator ACVA-HDA on the side chain of HA for providing oxygen-independent alkyl radicals for ablating hypoxic cancer cells by thermodynamic therapy(TDT).The results provide important evidence that the combination of reverse hypoxia hallmarks CA IX as targets for inhibition by AZ and synergistic PTT/TDT possess incomparable therapeutic advantages over traditional(reactive oxygen species(ROS)-mediated)cancer treatment for suppressing the growth of both hypoxic tumors and their metastasis.展开更多
The Ou MC decrescendo phenomenon (OuDP) involves the placing of the contralateral hand of the examiner on the acute abdomen of female patients (Ou MC manipulation), which results in an alleviation of pain [1]. Two fro...The Ou MC decrescendo phenomenon (OuDP) involves the placing of the contralateral hand of the examiner on the acute abdomen of female patients (Ou MC manipulation), which results in an alleviation of pain [1]. Two front-end observations showed that placement of the contralateral hand on the acute abdomen of women alleviated pain (78 of 81 women or 96.3%), while placement of the ipsilateral hand did not (0 of 39 women or 0%). This method named as Ou MC handing remedy (HR) was used to observe the immediate and cumulative effects of OuDP on 38 cases, of which 27 were self-administered and 11 were administered by the therapist. The mean age of the patients was 55.8 years (standard deviation, 22.9 years). Five minutes after initial self-administered HR, there was pain alleviation in 14 cases and symptoms or signs beyond pain improved for another 6 cases while 7 cases unevaluated. Final results showed 9 cured, 5 with partial remission and the remaining 13 with complete remission. Five minutes after initial therapist-administered HR, pain alleviation was found with 10 cases while 1 case unevaluated. The final results showed 7 cases cured, 2 with partial remission, and 2 with complete remission. The resolution of non-infectious conditions (23/ 38) with OuDP is consistent with the restoration of normal tissue function, which seems to contribute to pain alleviation and defense against infections and tumors. Interestingly, the OuDP is capable of being invoked by either the patient or the therapist. These findings warrant further investigation.展开更多
Objective: To investigate the clinical effect of rituximab (RTX) in the management of progressive rheumatoid arthritis related interstitial lung disease (RA-ILD). Methods: A total of 10 patients with progressive RA-IL...Objective: To investigate the clinical effect of rituximab (RTX) in the management of progressive rheumatoid arthritis related interstitial lung disease (RA-ILD). Methods: A total of 10 patients with progressive RA-ILD were enrolled into this 48-week, open-label treatment study. Treatment was with RTX at 1000 mg at day 1, day 15, and again at weeks 24 and 26, with concomitant methotrexate therapy. Results: The study included 4 men and 6 women. Of 7 evaluable patients at week 48, the diffusing capacity to carbon monoxide had worsened by at least 15% in 1 patient, was stable in 4 patients, and increased by >15% of baseline value in 2 patients. The forced vital capacity declined by at least 10% in 1 patient, was stable in 4 patients, and increased by at least 10% in 2 patients. High resolution computed tomo-graphy of the chest showed improvement in 1 patient, and was unchanged in 5. Three patients were withdrawn, one who had an infusion reaction at week 0, one at week 5 who was hospitalized for congestive heart failure at week 5 and who later died at week 32 of complications following a traumatic hip fracture, and one died at week 6 of possible pneumonia. Conclusions: In this pilot study of 10 patients with RA-ILD treated with RTX, measures of lung disease remained stable in the majority of study completers. Further research is needed to clarify whether this treatment has a role in management of RA-ILD.展开更多
Background. Villoglandular adenocarcinoma (VGA) of the cervix is reported as a variant of a cervical adenocarcinoma with a good prognosis. Cases. We present two cases histologically reported as a villoglandular adenoc...Background. Villoglandular adenocarcinoma (VGA) of the cervix is reported as a variant of a cervical adenocarcinoma with a good prognosis. Cases. We present two cases histologically reported as a villoglandular adenocarcinoma of the cervix that have recurred and progressed rapidly since initial treatment. External histopathological review suggested both had a prominent villoglandular pattern but with an associated underlying well-differentiated adenocarcinoma. Conclusion. The diagnosis of VGA is difficult. Current literature is not entirely consistent in the presented definition, and further clarity is needed. Because of the rarity of VGA and the difficulty but importance of the diagnosis, we would feel that a central review of all cases of VGA is warranted. This would assist in diagnosis and also in obtaining accurate follow-up data.展开更多
Objective: Hepatocellular carcinoma(HCC) development among hepatitis B surface antigen(HBs Ag) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We a...Objective: Hepatocellular carcinoma(HCC) development among hepatitis B surface antigen(HBs Ag) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBs Ag-positive male adults.Methods: HBs Ag-positive males of 35-69 years old(N=6,153) were included from a multi-center populationbased liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using Bultrasonography and α-fetoprotein(AFP). We used logistic regression models to determine potential risk factors,built and examined the operating characteristics of a point-based algorithm for HCC risk prediction.Results: With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT(γ-glutamyl-transpeptidase), counts of platelets, white cells,concentration of DCP(des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91(0.90-0.93), larger than existing models. At 1.5 points of risk score,26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk,with positive prediction value of 22.85% and 12.35%, respectively.Conclusions: Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.展开更多
Achondrogenesis is a very rare lethal skeletal disorder. Here we describe a case of prenatally diagnosed achondrogenesis typeⅡ in a 28 year-old woman at (17+4) wk. She had history of 5 first trimester missed abortion...Achondrogenesis is a very rare lethal skeletal disorder. Here we describe a case of prenatally diagnosed achondrogenesis typeⅡ in a 28 year-old woman at (17+4) wk. She had history of 5 first trimester missed abortions. The couple is consanguineous. Ultrasonography showed extreme micromelia, short neck and trunk, large head and prominent abdomen. Delayed ossification in sacral bones was detected and ossification of pubic rami was poor. There were associated large cystic hygroma, anasarca and also high occipital cephalocele. Posterior fossa was normal. Mild hypothelorism, depressed nasal bridge, low set ear and mild retrognathia were identified too. Amniocentesis result was compatible with a normal female fetus. Post mortem whole body radiography confirmed the diagnosis. To our knowledge, this is the second case report with association of cephalocele and achondrogenesis typeⅡ.展开更多
To evaluate the diagnostic implications of immunohistochemical markers in uterine smooth muscle tumors. Methods: Formalin-fixed paraffin-embedded tissue blocks were selected from 17 uterine leiomyosarcomas, 40 uterine...To evaluate the diagnostic implications of immunohistochemical markers in uterine smooth muscle tumors. Methods: Formalin-fixed paraffin-embedded tissue blocks were selected from 17 uterine leiomyosarcomas, 40 uterine unusual leiomyomas and 25 uterine usual leiomyomas. Utilizing immunohistochemical techniques with antigen retrieval, serial sections of each tumor for immunoreactivity with myogenic markers, ovarian steroid receptors, CD44v3, proliferating cell nuclear antigen and mast cells were assessed. Results: Although the myogenic markers and CD44v3 showed less frequent positivity in uterine leiomyosarcomas than those in unusual leiomyomas, they were not reliable markers for differentiating leiomyosarcoma from leiomyoma. Uterine leiomyosarcoma tended to have lower ovarian steroid receptors immunoreactivity rates than leiomyoma. Leiomyoma tended to have a higher quantity of intratumoral mast cells than leiomyosarcoma, while the expression of proliferating cell nuclear antigen was lower in them. Conclusion: Because the estimation of mitotic count was subject to significant variation, the immunohistochemical expression of ovarian steroid receptors, mast cells and proliferating cell nuclear antigen seemed to be helpful for the discrimination of unusual leiomyoma from leiomyosarcoma.展开更多
文摘Background: Dienogest is a potential treatment for pelvic pain associated with endometriosis, a condition of significant concern in gynaecology. The current study was conducted as a crossover-randomized bioequivalence assessment of two oral Dienogest 2 mg formulations, aiming to provide valuable insights for healthcare professionals and researchers in this field. Objective: The primary aim of this research was to evaluate and compare the pharmacokinetic characteristics of Dienogest 2 mg tablets. Dinogest (Dienogest 2 mg) tablets, manufactured by Nuvista Pharma Limited in Bangladesh, and Visanne (Dienogest 2 mg) tablets, manufactured by Bayer Pharma in Germany, were the test and reference formulations, respectively. Materials and Method: The study was an open-label, balanced, randomized, two treatments, two sequences, two periods, two-way crossover, laboratory blind, single oral dose bioequivalence study conducted in healthy adult females under fasting conditions. The study was carried out on 13 healthy, non-pregnant female subjects, and all the subjects completed both study periods with a 15-day washout in between. Randomization was used to assign the test and reference formulations to the subjects. Following each oral administration, a series of blood samples were obtained at different time intervals from pre-dose to 72 hours post-dose and analyzed for Dienogest concentrations using a validated bio-analytical method. A standard non-compartmental model was used to analyze the pharmacokinetic parameters. The primary pharmacokinetic parameters were peak plasma drug concentration (C<sub>max</sub>), the area under the plasma concentration-time curve from time zero to time t (AUC<sub>0–t</sub>), and AUC from t = 0 to infinity (AUC<sub>0–∞</sub>). The other PK parameters included time to reach C<sub>max</sub> (T<sub>max</sub>), terminal elimination rate constant (K<sub>el</sub>), and half-life (t<sub>1/2</sub>). Result: The ratios and 90% CI for the geometric mean test/reference were 95.53% (86.70% - 105.26%) for C<sub>max</sub>, 101.75% (95.42% - 108.49%) for AUC<sub>0</sub><sub>−</sub><sub>t</sub>, and 101.54% (95.59%% - 107.87%) for AUC<sub>0</sub><sub>−</sub><sub>∞</sub>. The formulations were bioequivalent since the 90% CIs for the geometric mean test/reference ratios were 80% to 125%, according to the predetermined range of US Food and Drug Administration (FDA) requirements. Conclusion: This single-dose investigation shows that the Dienogest test and reference formulations exhibited a rate and degree of absorption that met the regulatory requirements for bioequivalence.
文摘Aim: To determine maternal and neonatal morbidities associated with instrumental vaginal delivery. Methods: This retrospective study consisted of 233 women undergoing instrumental vaginal deliveries from April 2020 to March 2021 at Paropakar Maternity and Women Hospital, a tertiary care hospital in Kathmandu, Nepal. Neonatal and maternal complications were analyzed. Results: Of 233 women, 102 (43.7%) and 131 (56.2%) had vacuum and forceps deliveries, respectively. The use of instruments was more frequent in infants with higher birth weight and gestational age. There were no significant differences in Apgar scores between the two groups. Two main indications of instrumental deliveries were fetal distress and prolonged second stage labor. Forceps, compared with vacuum, more often caused 3<sup>rd</sup>/4<sup>th</sup> perineal tears, tear extending to fornices, and postpartum hemorrhage. Neonatal outcomes were similar in both types of instrumental deliveries. Conclusion: Instrumental vaginal delivery caused maternal morbidity and procedure/judgment training for it is essential.
文摘Background: Thyroid disorders are the most common endocrine disorders in pregnancy accounting for 10% of subclinical hypothyroidism in all pregnancies. Screening for hypothyroidism is essential in all pregnant women, especially in Nepal, a low-income region where women have an increased risk of developing iodine deficiency during pregnancy. Hence this study is to analyze fetomaternal outcomes in maternal hypothyroidism complicating pregnancies. Methods: This retrospective observational study was carried out at Paropakar Maternity and Women Hospital, a tertiary center located in Kathmandu, Nepal. The Subjects of this study were 330 antenatal women with a singleton pregnancy with hypothyroidism admitted for delivery in the obstetrics ward, and informed consent was obtained. Women were chosen irrespective of age, parity, residency, and socioeconomic status. Women with multiple pregnancies and any preexisting medical disorders including heart disease, diabetes, and hypertension were excluded. Routine hematological parameters and estimations of T3, T4, and thyroid stimulating hormone (TSH) were conducted. Patients with hypothyroidism were divided into overt and subclinical and were subsequently assessed for maternal and fetal complications. The occurrence of maternal outcomes and perinatal outcomes were recorded. Result: Out of 470 total hypothyroid cases, 330 were enrolled in the study and the remaining 140 were excluded. In our study, the incidence of hypothyroidism in pregnancy was 2.11% with 1.7% of subclinical hypothyroidism and 0.31% of overt hypothyroidism. The mean age of the patient was >30 years with 53.3% (n = 176) primigravida. Mostly 70.3% (n = 232) from rural areas. Pre-Eclampsia, gestational diabetes abruptio placenta, and postpartum hemorrhage were the adverse maternal outcome with a higher percentage of these in overt hypothyroidism which was statistically significant. Concerning fetal outcome APGAR score <6 in 5 min, Intrauterine growth restriction (IUGR), NICU admission, neonatal Respiratory distress syndrome (RDS), Intrauterine fetal death (IUFD), and congenital anomaly were found with a higher percentage in overt hypothyroidism. Conclusion: Since the impact of hypothyroidism on fetomaternal morbidities have been identified so screening for hypothyroidism to be included as a routine screening test and should be treated accordingly to improve maternal and fetal outcome.
文摘Chromobacterium violaceum is a Gram negative, facultative anaerobe, generally present in water, soil in tropical and subtropical regions. This bacterium is an emerging environmental pathogen that causes life threatening infection in humans and animals. It can cause wound infection, visceral abscess, septicaemia, meningitis, diarrhoea, UTI. It is associated with significant mortality due to severe systemic infection. As the bacteria have high spreading tendency leading to sepsis, early identification and prompt treatment is necessary. Here we report a case of Chromobacterium violaceum wound infection in a 9 years old male from Dhaka, who was successfully treated with combination of cefixime and flucloxacillin antibiotics as per culture sensitivity report.
基金Zhejiang Province Health Innovative Talent Project(A0466)Key Projects of the Science and Technology Coconstruction by National Administration of Traditional Chinese Medicine and Zhejiang Provincial Administration of Traditional Chinese Medicine(GZY-ZJ-KJ-23082)。
文摘Vaginal bleeding is a common symptom in the emergency department of obstetrics and gynecology hospitals;however,post-hysterectomy vaginal bleeding is a rare phenomenon.Uterine artery pseudoaneurysm(UAP)is a rare condition that can lead to fatal bleeding and most commonly occurs as a long-term complication after invasive surgery or even in non-invasive procedures,such as cesarean section,myomectomy,dilatation and curettage,cervical conization and vaginal delivery.[1-3]Pseudoaneurysm is a pulsatile hematoma formed after arterial injury and rupture.
文摘Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes.Advantages of image-based brachytherapy include:improved tumor coverage(especially for large volume disease), decreased dose to critical organs(especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging(MRI),computed tomography(CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. Forpractical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE(an international study of MRI-guided brachytherapy in locally advanced cervical cancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervical cancer patients.
基金Supported by the Awards to University Academic Leaders Granted by the Government of Shanxi Province of China to Hui-Ying Zhang and partially by the US National Institute of Health, NIAAA, Grant R01 AA014428 to Cheng Ji
文摘AIM: To characterize the correlation between severity of hepatopulmonary syndrome (HPS) and degree of hepatic dysfunction,and to explore how intestinal endotoxemia (IETM) affects the development of HPS in cirrhotic rats. METHODS: Male Wister rats were fed with a diet containing maize flour,lard,cholesterol,and alcohol and injected subcutaneously with CCl4 oil solution every two days for 8 wk to induce typical cirrhosis and development of HPS. The animals were also given a nitric oxide (NO) production inhibitor,Nω-nitro-L-arginine methyl ester (L-NAME) intraperitoneally,and an iNOS inhibitor,aminoguanidine hydrochloride (AG) via gavage daily from the end of the 4th wk to the end of the 6th or 8th wk,or a HO-1 inhibitor,zinc protoporphyrin (ZnPP) intraperitoneally 12 h prior to killing. Blood,liver and lung tissues were sampled. RESULTS: Histological deterioration of the lung paralleled to that of the liver in the cirrhotic rats. The number of pulmonary capillaries was progressively increased from 6.1 ± 1.1 (count/filed) at the 4th wk to 14.5 ± 2.4 (count/filed) at the 8th wk in the cirrhotic rats. Increased pulmonary capillaries were associated with increased blood levels of lipopolysaccharide (LPS)(0.31 ± 0.08 EU/mL vs control 0.09 ± 0.03 EU/mL),alanine transferase (ALT,219.1 ± 17.4 U/L vs control 5.9 ± 2.2 U/L) and portal vein pressure. Compared with normal control animals,the number of total cells in bronchoalveolar lavage fluid (BALF) of the cirrhotic rats at the 8th wk was not changed,but the number of macrophages and the ratio of macrophages to total cells were increased by nearly 2-fold,protein expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) started to increase significantly at the 4th wk,and reached its peak at the 8th wk in the lung of cirrhotic rats. The increase of iNOS expression appeared to be quicker than that of eNOS. NO2-/NO3-was also increased,which was correlated to the increase of iNOS (r = 0.7699,P < 0.0001) and eNOS (r = 0.5829,P < 0.002). mRNA expression of eNOS and iNOS was highly consistent with their protein expression. CONCLUSION: Progression and severity of HPS as indicated by both increased pulmonary capillaries and histological changes are closely associated with LPS levels and progression of hepatic dysfunction as indicated by increased levels of ALT and portal vein pressure. Intestinal endotoxemia plays a central role in the development of HPS in the cirrhotic rat model by inducing NO and/or CO.
文摘There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their size and on the presence of specific clinical and genetic information provided in the published material from 2001 to 2005. Twelve studies provided raw data to carry out comparisons of disease location while ten studies included analysis of NOD2/CARD15 genotypes. NOD2/CARD15 variant frequency in ileal disease did not differ significantly among studies, whereas a comparison of disease location demonstrated highly significant differences among studies. Meta-analysis confirmed significant associations between NOD2/CARD15 variants and both ileal and ileocolonic disease locations, and with both stricturing and penetrating forms of disease behavior. This review underlines the significant phenotypic differences that exist among populations, including similar ethnic groups, and has demonstrated the need for further studies of patients with long-term “inflammatory” Crohn’s disease.
文摘BACKGROUND: Emergency physicians frequently encounter patients with acute small bowel obstructions(SBO). Although computed tomography(CT) imaging is the current gold standard in the assessment of patients with suspected SBO in the emergency department, a few studies have examined the use of ultrasound as an alternative imaging technique. METHODS: We evaluated the accuracy of ultrasound performed in the ED by a variety of providers(physicians with various levels of training, physician assistants) compared to CT imaging in 47 patients with suspected SBOs. RESULTS: Our data demonstrated a sensitivity of 93.8% and a specificity of 93.3% when compared to abdominal CT, and a sensitivity of 94.3% and specificity of 95.2% using a composite endpoint of abdominal CT and discharge diagnosis. CONCLUSION: Ultrasound can play an important role in the identification of small bowel obstructions in ED patients.
基金the National Natural Science Foundation of China(51903203,51703178,81770728)the China Postdoctoral Science Foundation(2019M653661,2019M663742)+3 种基金the Natural Science Foundation of Shaanxi Province(2020JQ-046)Natural Science Foundation of Zhejiang Province(LWY20H180002)the Natural Science Foundation of Guangxi Zhuang Autonomous Region(2017GXNSFBA198028).Y.H.,M.G.,Y.S.Z.,G.H.and X.Z.were not supported by any of these fundsinstead,support by MIT,Harvard,Stanford University and the Brigham Research Institute are acknowledged.
文摘Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment.Herein,we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the“precise strike”of hypoxic tumors through the dual-targeting effects from surface-modified hyaluronic acid(HA)and hypoxia-dependent factor carbonic anhydrase IX(CA IX)-inhibitor acetazolamide(AZ).The core of nanobullets is the special zinc(II)phthalocyanine aggregates(ZPA)which could heat the tumor tissues upon 808-nm laser irradiation for photothermal therapy(PTT),along with the alkyl chain-functionalized thermally decomposable radical initiator ACVA-HDA on the side chain of HA for providing oxygen-independent alkyl radicals for ablating hypoxic cancer cells by thermodynamic therapy(TDT).The results provide important evidence that the combination of reverse hypoxia hallmarks CA IX as targets for inhibition by AZ and synergistic PTT/TDT possess incomparable therapeutic advantages over traditional(reactive oxygen species(ROS)-mediated)cancer treatment for suppressing the growth of both hypoxic tumors and their metastasis.
文摘The Ou MC decrescendo phenomenon (OuDP) involves the placing of the contralateral hand of the examiner on the acute abdomen of female patients (Ou MC manipulation), which results in an alleviation of pain [1]. Two front-end observations showed that placement of the contralateral hand on the acute abdomen of women alleviated pain (78 of 81 women or 96.3%), while placement of the ipsilateral hand did not (0 of 39 women or 0%). This method named as Ou MC handing remedy (HR) was used to observe the immediate and cumulative effects of OuDP on 38 cases, of which 27 were self-administered and 11 were administered by the therapist. The mean age of the patients was 55.8 years (standard deviation, 22.9 years). Five minutes after initial self-administered HR, there was pain alleviation in 14 cases and symptoms or signs beyond pain improved for another 6 cases while 7 cases unevaluated. Final results showed 9 cured, 5 with partial remission and the remaining 13 with complete remission. Five minutes after initial therapist-administered HR, pain alleviation was found with 10 cases while 1 case unevaluated. The final results showed 7 cases cured, 2 with partial remission, and 2 with complete remission. The resolution of non-infectious conditions (23/ 38) with OuDP is consistent with the restoration of normal tissue function, which seems to contribute to pain alleviation and defense against infections and tumors. Interestingly, the OuDP is capable of being invoked by either the patient or the therapist. These findings warrant further investigation.
文摘Objective: To investigate the clinical effect of rituximab (RTX) in the management of progressive rheumatoid arthritis related interstitial lung disease (RA-ILD). Methods: A total of 10 patients with progressive RA-ILD were enrolled into this 48-week, open-label treatment study. Treatment was with RTX at 1000 mg at day 1, day 15, and again at weeks 24 and 26, with concomitant methotrexate therapy. Results: The study included 4 men and 6 women. Of 7 evaluable patients at week 48, the diffusing capacity to carbon monoxide had worsened by at least 15% in 1 patient, was stable in 4 patients, and increased by >15% of baseline value in 2 patients. The forced vital capacity declined by at least 10% in 1 patient, was stable in 4 patients, and increased by at least 10% in 2 patients. High resolution computed tomo-graphy of the chest showed improvement in 1 patient, and was unchanged in 5. Three patients were withdrawn, one who had an infusion reaction at week 0, one at week 5 who was hospitalized for congestive heart failure at week 5 and who later died at week 32 of complications following a traumatic hip fracture, and one died at week 6 of possible pneumonia. Conclusions: In this pilot study of 10 patients with RA-ILD treated with RTX, measures of lung disease remained stable in the majority of study completers. Further research is needed to clarify whether this treatment has a role in management of RA-ILD.
文摘Background. Villoglandular adenocarcinoma (VGA) of the cervix is reported as a variant of a cervical adenocarcinoma with a good prognosis. Cases. We present two cases histologically reported as a villoglandular adenocarcinoma of the cervix that have recurred and progressed rapidly since initial treatment. External histopathological review suggested both had a prominent villoglandular pattern but with an associated underlying well-differentiated adenocarcinoma. Conclusion. The diagnosis of VGA is difficult. Current literature is not entirely consistent in the presented definition, and further clarity is needed. Because of the rarity of VGA and the difficulty but importance of the diagnosis, we would feel that a central review of all cases of VGA is warranted. This would assist in diagnosis and also in obtaining accurate follow-up data.
基金supported by State Key Projects Specialized on Infectious Diseases (No. 2017ZX10201201-006)Key research projects for precision medicine (No. 2017YFC0908103)+1 种基金Innovation Fund for Medical Sciences of Chinese Academy of Medical Sciences (CIFMS, No. 2019-I2M-2-004, 2016-I2M-1-007, 2019-I2M-1-003)National Natural Science Foundation Fund (No. 81972628, No. 81974492)。
文摘Objective: Hepatocellular carcinoma(HCC) development among hepatitis B surface antigen(HBs Ag) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBs Ag-positive male adults.Methods: HBs Ag-positive males of 35-69 years old(N=6,153) were included from a multi-center populationbased liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using Bultrasonography and α-fetoprotein(AFP). We used logistic regression models to determine potential risk factors,built and examined the operating characteristics of a point-based algorithm for HCC risk prediction.Results: With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT(γ-glutamyl-transpeptidase), counts of platelets, white cells,concentration of DCP(des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91(0.90-0.93), larger than existing models. At 1.5 points of risk score,26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk,with positive prediction value of 22.85% and 12.35%, respectively.Conclusions: Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.
文摘Achondrogenesis is a very rare lethal skeletal disorder. Here we describe a case of prenatally diagnosed achondrogenesis typeⅡ in a 28 year-old woman at (17+4) wk. She had history of 5 first trimester missed abortions. The couple is consanguineous. Ultrasonography showed extreme micromelia, short neck and trunk, large head and prominent abdomen. Delayed ossification in sacral bones was detected and ossification of pubic rami was poor. There were associated large cystic hygroma, anasarca and also high occipital cephalocele. Posterior fossa was normal. Mild hypothelorism, depressed nasal bridge, low set ear and mild retrognathia were identified too. Amniocentesis result was compatible with a normal female fetus. Post mortem whole body radiography confirmed the diagnosis. To our knowledge, this is the second case report with association of cephalocele and achondrogenesis typeⅡ.
文摘To evaluate the diagnostic implications of immunohistochemical markers in uterine smooth muscle tumors. Methods: Formalin-fixed paraffin-embedded tissue blocks were selected from 17 uterine leiomyosarcomas, 40 uterine unusual leiomyomas and 25 uterine usual leiomyomas. Utilizing immunohistochemical techniques with antigen retrieval, serial sections of each tumor for immunoreactivity with myogenic markers, ovarian steroid receptors, CD44v3, proliferating cell nuclear antigen and mast cells were assessed. Results: Although the myogenic markers and CD44v3 showed less frequent positivity in uterine leiomyosarcomas than those in unusual leiomyomas, they were not reliable markers for differentiating leiomyosarcoma from leiomyoma. Uterine leiomyosarcoma tended to have lower ovarian steroid receptors immunoreactivity rates than leiomyoma. Leiomyoma tended to have a higher quantity of intratumoral mast cells than leiomyosarcoma, while the expression of proliferating cell nuclear antigen was lower in them. Conclusion: Because the estimation of mitotic count was subject to significant variation, the immunohistochemical expression of ovarian steroid receptors, mast cells and proliferating cell nuclear antigen seemed to be helpful for the discrimination of unusual leiomyoma from leiomyosarcoma.