Evaluation of the effect of neoadjuvant chemotherapy on tumor and axillary lymph nodes in locally advanced breast cancer： a study of 50 patients

Objective： The purpose of the study was to correlate between effect of pre-neoadjuvant chemotherapy （NACT） and post-NACT clinical, sonographic and pathologic features of the tumor and axillary lymph nodes （ALNs） and to raise the possibility of applying the concept of sentinel lymph node biopsy （SLNB） in patients with initially positive ALNs before NACT. Methods： A prospective study of 50 female patients with locally advanced breast cancer （LABC） with clinically palpable.and cytologically （under ultrasonographic guidance） positive ALNs. All patients received NACT and then referred for ultrasono- graphic assessment of the axilla regarding any detectable sonographic criteria of metastatic deposits in ALNs as well as the tumor size in relation to its prechemotherapy size, All patients were then subjected either to modified radical mastectomy or breast conserving surgery. The clinical, sonographic and pathological response of the tumor and the ALNs were documented, classified and correlated with each other. Results： Patients＇ mean age was 47.7±9.1 years. The mean clinical tumor size was 6.7 ± 1.4 cm; stage IliA that was presented in 32 patients （64%） and IIIB was presented in 18 patients （36%）. Chemotherapy was given for a median of 4 cycles, there was reduction of the mean clinical tumor size from 6.7 ± 1.4 cm to 4.3 ± 2.7 cm （P 〈 0.001）. Clinical response was complete in 5 （10%） tumors, complete pathological tumor response （post-neoadjuvant） was detected in 6 （16%） of patients. Complete clinical nodal response （post-neoadjuvant） in 23 （46%） axillae, on sonographic assessment of the axilla, response was complete in 17 （34%） axillae. Complete pathological nodal response occurred in 16 （32%） axillae. Out of 17 axillae that showed complete sonographic response 11 axillae showed complete pathological nodal response （P 〈 0.001）. Conclusion： Formal axillary lymph node dissection can be avoided and replaced by SLNB post NACT in patients with L     

Thyrotoxicosis Associated Wernicke’s Encephalopathy

Summary Background Wernicke’s encephalopathy is a rare disorder resulting from nutrition deficiency in thiamine (vitamin B1). It is most often associated with chronic alcohol abuse. It can accompany other disorders such as hyperemesis gravidarum and hyperthyroidism. Case We present a case of severe Wernicke’s encephalopathy that developed in a male non-alcoholic inpatient that was precipitated by poor nutritional intake and development of thyrotoxicosis. It is likely that the hypermetabolic state from thyrotoxicosis contributed to the development of Wernicke’s encephalopathy, which was extremely debilitating. Conclusion Wernicke’s encephalopathy is a severe, life-threatening illness that can be a consequence of hyperthyroidism in addition to alcohol abuse and can be easily prevented with appropriate supplementation of thiamine.     

Three-dimensional analysis of temporomandibular joint in Chinese adults with normal occlusion and harmonious skeleton

Oral Radiology - This study aimed to analyze the detailed three-dimensional measurements of temporomandibular joint (TMJ) in Chinese adults with normal occlusion and harmonious skeleton. In 51...     

Prediction of spontaneous preterm birth: salivary progesterone assay and transvaginal cervical length assessment after 24 weeks of gestation,another critical window of opportunity

Objectives: Measurement of salivary progesterone (SP4) levels and cervical length (CL) after 24 weeks to assess their potential predictive value among asymptomatic women at high risk of spontaneous preterm birth (PTB).

Methods: This prospective observational (noninterventional) study consecutively recruited asymptomatic women at high risk of spontaneous PTB. SP4 and CL were measured at recruitment (24–28 weeks of gestation) then repeated after 3–4 weeks. All recruited women were followed up regularly till delivery. The primary outcome measure was the occurrence of spontaneous PTB.

Results: One hundred and thirty four women completed the study, 22 (16.4%) and 32 (23.9%) women had early (<34 weeks) and late (≥34 weeks) PTB, respectively. Initially, the mean CL was 3.2?±?0.6?cm and the mean SP4 was 4062.8?±?814.6?pg/ml; with follow up, the mean CL became 3.0?±?0.6?cm and the mean SP4 became 3871.6?±?1136.9. Women with early PTB had significantly lower initial and follow up CL and SP4 measures when compared to women with late PTB and those who had birth at term. The rate of drop in SP4 and CL measurements between the two visits was also significantly higher among women with early PTB than those with late PTB and term birth. Receiver-operating characteristic (ROC) curves showed that, CL was a good predictor but SP4 was a better predictor of PTB as the area under the curve (AUC) for CL was less than that for SP4 at both visits (i.e. 0.858 and 0.868 versus 0.986 and 0.990 at the initial and follow up visits, respectively). There was a statistically significant correlation between CL and SP4 measurements. Multivariable binary logistic regression analysis revealed that follow up SP4 measurement was the only independent predictor of spontaneous PTB, and neither BMI, maternal age, SP4 nor CL were independent predictors of early spontaneous PTB.

Conclusions: After 24 gestational weeks, SP4 assessment is a simple and reliable promising tool to predict spontaneous PTB among asymptomatic high-risk women, with a little superior performance than CL measurement.     

Vaginal misoprostol before copper IUD insertion after previous insertion failure: a double-blind,placebo-controlled,parallel-group,randomised clinical trial

Objective: The aim of the study was to assess whether vaginal administration of misoprostol before copper intrauterine device (IUD) insertion increased the success of the procedure among parous women with previous insertion failure.

Methods: A single-centre, parallel-group, double-blind, placebo-controlled, randomised clinical trial was conducted at Ain Shams University Maternity Hospital, Cairo, Egypt, between October 2015 and August 2016. The study comprised 90 parous women undergoing TCu380A IUD insertion after a failed attempt. A computer-generated list of random numbers was used to assign participants to receive either misoprostol 200?μg or a placebo tablet, applied vaginally 10?h and 4?h prior to the second attempted IUD insertion, without ultrasound guidance. The primary outcome was the success of IUD insertion. Secondary outcomes were to establish the effect on insertion success of cervical dilation, cervical softening and previous mode of delivery.

Results: Forty-two women (93.3%) in the misoprostol group and 24 women (53.3%) in the placebo group had a successful IUD insertion (p?<?.001). Cervical dilation was required in 24 women in the misoprostol group and 44 women in the placebo group. Misoprostol application significantly increased insertion success in women with previous caesarean delivery (p?<?.001) but did not affect insertion success in women with previous vaginal delivery (p?=?.481).

Conclusion: Vaginal misoprostol before IUD insertion in parous women with previous insertion failure increased the rate of successful insertion, particularly in women with previous caesarean delivery.     

Cyclooxygenase-2 in normal,hyperplastic and neoplastic follicular cells of the human thyroid gland

This study was undertaken to investigate cyclooxygenase-2 (COX-2) expression in follicular cells of the human thyroid. COX-2 expression was studied immunohistochemically in a total of 174 samples. COX-2 immunoreactivity was confined to the cell cytoplasm with the nuclei remaining unlabelled. COX-2 expression was observed in five cases (17.2%) of normal follicular cells and in one case (16.6%) of solid cell nests. Follicular carcinoma expressed COX-2 more frequently than follicular adenoma (93.4% vs 21.1%) (p0.001). A higher percentage of cases of papillary microcarcinomas up-regulated COX-2 in comparison with all papillary carcinomas (p0.05). However, we could not establish any relationships among COX-2, patients ages or lymph node metastases in papillary carcinomas. COX-2 expression was found in 12 (92.3%) poorly differentiated carcinomas and in 13 (92.8%) undifferentiated carcinomas. We found that COX-2 is not always useful as a marker of malignancy. Our results suggest that COX-2 plays a role in progression of all thyroid carcinomas, but in papillary carcinomas, seems more important only in the early stages. COX-2 expression in the undifferentiated carcinoma deserves special consideration due to its prognosis and to the fact that selective COX-2 inhibitors were found to enhance tumour response to radiation in some studies.     

Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model

Most patients with hypertrophic cardiomyopathy and congenital heart diseases express the atrial essential myosin light chains (ALC-1) in their ventricles, partially replacing the ventricular essential light chains (VLC-1). This VLC-1/ALC-1 isoform shift is correlated with an increase in cross-bridge cycling kinetics as measured using skinned fibers from the hypertrophied ventricles of human hearts.To study the functional importance of hALC-1 in the intact perfused heart, we generated a transgenic rat model (TGR) overexpressing hALC-1 in the heart. Twelve-week-old TGR rats expressed 17±4 g hALC-1 per mg of whole SDS-soluble protein. Their perfused heart contractility parameters were evaluated using the Langendorff preparation. Expression of hALC-1 was accompanied by statistically significant improvements (P<0.001) in the contractile parameters of the hearts of the TGR compared to the age matched control (WKY) animals, represented by increases from 20.8±2.3 to 45.1±3.6 mmHg/g heart weight in the developed left ventricular pressure, 1,035.7±89.8 to 2,181±135.4 mmHg/s in the contraction rate, and 713±60.2 to 1,364±137.4 mmHg/s in the relaxation rate in the WKY and the TGR groups respectively. Characterizing the functional effects of hALC-1 at the whole organ level represents a step towards gene therapy of heart failure.     

Novel aspects of the molecular mechanisms controlling insulin secretion

Pancreatic β-cells secrete insulin by Ca²⁺-dependent exocytosis of secretory granules. β-cell exocytosis involves SNARE (soluble NSF-attachment protein receptor) proteins similar to those controlling neurotransmitter release and depends on the close association of L-type Ca²⁺ channels and granules. In most cases, the secretory granules fuse individually but there is ultrastructural and biophysical evidence of multivesicular exocytosis. Estimates of the secretory rate in β-cells in intact islets indicate a release rate of ∼15 granules per β-cell per second, 100-fold higher than that observed in biochemical assays. Single-vesicle capacitance measurements reveal that the diameter of the fusion pore connecting the granule lumen with the exterior is ∼1.4 nm. This is considerably smaller than the size of insulin and membrane fusion is therefore not obligatorily associated with release of the cargo, a feature that may contribute to the different rates of secretion detected by the biochemical and biophysical measurements. However, small molecules like ATP and GABA, which are stored together with insulin in the granules, are small enough to be released via the narrow fusion pore, which accordingly functions as a molecular sieve. We finally consider the possibility that defective fusion pore expansion accounts for the decrease in insulin secretion observed in pathophysiological states including long-term exposure to lipids.