Indicators of dehydration and haemoconcentration are associated with the prevalence and severity of coronary artery disease

1. The vascular endothelium is injured by blood flow abnormalities exacerbated by different risk factors, including markers of haemoconcentration. The aim of the present study was to assess the association between markers of haemoconcentration and dehydration and the prevalence and severity of coronary artery disease (CAD). 2. Subjects in the present study (189 men and 126 women) were classified as either CAD cases or controls according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and the extent of lesions on coronary arteries. Serum electrolytes, osmolality and haematological parameters were measured. 3. Compared with control subjects, patient with CAD had increased levels of serum osmolality, calculated osmolality, tonicity, sodium, glucose and blood urea nitrogen (BUN). Significant differences were also observed in the haematocrit and haemoglobin concentration, but not in erythrocyte counts and total serum protein. On multiple logistic regression analysis adjusting for major risk factors, serum osmolality, glucose and BUN exhibited significant associations with CAD, but the correlations were lessened by diabetes. Analysis using anova showed a significant correlation between serum osmolality, sodium, glucose and BUN and the severity of CAD. The area under the receiver operating characteristic curves, as a relative measure of the test's efficiency, was the highest and significant for serum osmolality, BUN and glucose. 4. The results indicate that some of the markers of dehydration and haemoconcentration are associated significantly with the prevalence and severity of CAD, but the independence of these correlations is questioned. These markers may play a role in the pathogenesis of atherosclerosis.     

Rectal misoprostol versus intravenous oxytocin for prevention of postpartum hemorrhage

Objective

To assess the effectiveness of 800 μg of rectal misoprostol compared with an intravenous infusion of 5 IU of oxytocin as prophylaxis against postpartum hemorrhage (PPH).

Methods

A total of 514 women in labor were randomized into two groups (257 women in each). Within 1 minute of delivery of the anterior shoulder participants in group 1 received 800 μg of rectal misoprostol and 1 ampoule of normal saline in 5 mL lactated Ringer solution intravenously; group 2 received a rectal placebo tablet and 5 IU of oxytocin in 5 mL lactated Ringer solution intravenously.

Results

Both groups were comparable regarding the need for uterotonics, blood transfusion, and hematocrit drop of 10% or greater, 24 hours post partum (P = 0.54, P = 0.25, and P = 0.85, respectively). Fever was significantly higher among misoprostol patients (18.7% vs 0.8%, P < 0.001).

Conclusions

Routine use of 800 μg of rectal misoprostol was effective in reducing blood loss after delivery. We recommend the regimen for low-resource, busy obstetric settings.     

Bilateral uterine artery ligation plus B-Lynch procedure for atonic postpartum hemorrhage with placenta accreta

Objective

To assess the effectiveness of bilateral uterine artery ligation followed by B-Lynch compression suturing in women with atonic postpartum hemorrhage and placental site bleeding due to adherent placenta accreta.

Method

This protocol was followed in 26 women undergoing cesarean delivery for placenta accreta.

Results

Two women died from disseminated intravascular coagulopathy. In the remaining 24 women, placental remnants completely disappeared within 8 months and ovulation resumed after a mean ± SD of 51.6 ± 3.2 days. Moreover, 18 women (75%) became pregnant within 12 months.

Conclusion

Atonic postpartum hemorrhage and placental site bleeding due to adherent placenta accreta can be safely controlled by bilateral uterine artery ligation followed by B-Lynch compression suturing in women who desire to remain fertile.     

Intelligence Quotient at the Age of Six years of Iranian Children with Congenital Hypothyroidism

Objective

To evaluate the success rate of the National newborn screening program in maintenance of intelligent quotient (IQ) of children with congenital hypothyroidism in Iran.

Design

Retrospective cohort study.

Methods

The IQ scores, in three subsets of verbal, non verbal (Performance) and full scale IQ, of 240 children diagnosed with Transient congenital hypothyroidism (TCH) and Permanent congenital hypothyroidism (PCH), from 5 provinces in 5 different geographical areas of Iran, were measured at the age of 6 years using revised Wechsler pre school and primary scale of intelligence and compared with 240 healthy children. We used independent sample t test and two-way ANOVA for data analysis.

Results

Mean of verbal, performance, and full scale IQ scores were lower in the CH cases (permanent and transient) than the control group. Most of the IQ differences in two studied groups related to the PCH cases (P=0.005). Mean difference of IQs between children in the two groups in Yazd province (center of Iran) was higher than other provinces, and they also had significantly lower IQ than their control (healthy) children (P=0.001). No treated child had IQ<70.

Conclusion

Although mean IQs of CH children was lower than their controls, IQ of all treated CH cases were close to the healthy children.

     

儿童和青少年癌症患者治疗相关性食管并发症的处理

背景和目的：在儿童肿瘤患中，由治疗引起的严重食管狭窄和气管食管瘘很少见，本详细报道了作治疗这类并发症的经验。方法：本回顾性分析了过去23年间，作治疗儿童肿瘤患食管并发症的经验。严重并发症指食管狭窄进行性加重，需要接受食管扩张术或食管造瘘术。本研究的对象为15例患儿，其中5例在以前的研究中曾报道过。结果：13例发生食管狭窄的患儿中，有2例伴有气管食管瘘。另外2例气管食管瘘的患儿不伴有食管狭窄。从癌症诊断到发生食管并发症的间隔期为3．5年（极差0．4～11．8年）。     

Discovery of pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives as novel CDK2 inhibitors: synthesis,biological and molecular modeling investigations

CDK2 inhibition is an appealing target for cancer treatment that targets tumor cells in a selective manner. A new set of small molecules featuring the privileged pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffolds (4–13) as well as the thioglycoside derivatives (14, 15) were designed, and synthesized as novel CDK2 targeting compounds. The growth of the three examined cell lines was significantly inhibited by most of the prepared compounds. Results revealed that most of the compounds showed superior cytotoxic activities against MCF-7 and HCT-116 with IC₅₀ range (45–97 nM) and (6–99 nM), respectively, and moderate activity against HepG-2 with IC₅₀ range of (48–90 nM) compared to sorafenib (IC₅₀: 144, 176 and 19 nM, respectively). Of these compounds, 14 & 15 showed the best cytotoxic activities against the three cell lines with IC₅₀ values of 45, 6, and 48 nM and 46, 7, and 48 nM against MCF-7, HCT-116 and HepG-2, respectively. Enzymatic inhibitory activity against CDK2/cyclin A2 was achieved for the most potent anti-proliferative compounds. Compounds 14, 13 and 15 revealed the most significant inhibitory activity with IC₅₀ values of 0.057 ± 0.003, 0.081 ± 0.004 and 0.119 ± 0.007 μM, respectively compared to sorafenib (0.184 ± 0.01 μM). Compound 14 displayed potent dual activity against the examined cell lines and CDK2, and was thus selected for further investigations. It exerted a significance alteration in cell cycle progression, in addition to apoptosis induction within HCT cells. Molecular docking simulation of the designed compounds confirmed the good fit into the CDK2 active site through the essential hydrogen bonding with Leu83. In silico ADMET studies and drug-likeness studies using a Boiled Egg chart showed suitable pharmacokinetic properties which helped in structure requirement prediction for the observed antitumor activity.

A new set of pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffolds (4–13) as well as the thioglycoside derivatives (14, 15) were designed, and synthesized as novel CDK2 targeting compounds.     

COVID-19 outbreak and surgical practice: The rationale for suspending non-urgent surgeries and role of testing modalities

One-hundred years after the 1918-19 H1N1 flu pandemic and 10 years after the2009 H1N1 flu pandemic, another respiratory virus has now inserted itself into the human population. Severe acute respiratory syndrome coronavirus has become a critical challenge to global health with immense economic and social disruption. In this article we review salient aspects of the coronavirus disease2019(COVID-19) outbreak that are relevant to surgical practice. The emphasis is on considerations during the pre-operative and post-operative periods as well as the utility and limitations of COVID-19 testing. The focus of the media during this pandemic is centered on predictive epidemiologic curves and models. While epidemiologists and infectious disease physicians are at the forefront in the fight against COVID-19, this pandemic is also a "stress test" to evaluate the capacity and resilience of our surgical community in dealing with the challenges imposed to our health system and society. As recently pointed out by Dr. Anthony Fauci,the virus decides the timelines in the models. However, the models can also change based on our decisions and behavior. It is our role as surgeons, to make every effort to bend the curves against the virus' will.     

Distribution of Serotypes,Genotypes, and Resistance Determinants among Macrolide-Resistant Streptococcus pneumoniae Isolates

Macrolide resistance in Streptococcus pneumoniae has emerged as an important clinical problem worldwide over the past decade. The aim of this study was to analyze the phenotypes (serotype and antibiotic susceptibility), genotypes (multilocus sequence type [MLST] and antibiotic resistance gene/transposon profiles) among the 31% (102/328) of invasive isolates from children in New South Wales, Australia, in 2005 that were resistant to erythromycin. Three serotypes—19F (47 isolates [46%]), 14 (27 isolates [26%]), and 6B (12 isolates [12%])—accounted for 86 (84%) of these 102 isolates. Seventy four (73%) isolates had the macrolide-lincosamide-streptogramin B (MLS_B) resistance phenotype and carried Tn916 transposons (most commonly Tn6002); of these, 73 (99%) contained the erythromycin ribosomal methylase gene [erm(B)], 34 (47%) also carried the macrolide efflux gene [mef(E)], and 41 (55%) belonged to serotype 19F. Of 28 (27%) isolates with the M phenotype, 22 (79%) carried mef(A), including 16 (57%) belonging to serotype 14, and only six (19%) carried Tn916 transposons. Most (84%) isolates which contained mef also contained one of the msr(A) homologues, mel or msr(D); 38 of 40 (95%) isolates with mef(E) (on mega) carried mel, and of 28 (39%) isolates with mef(A), 10 (39%) carried mel and another 11(39%) carried msr(D), on Tn1207.1. Two predominant macrolide-resistant S. pneumoniae clonal clusters (CCs) were identified in this population. CC-271 contained 44% of isolates, most of which belonged to serotype 19F, had the MLS_B phenotype, were multidrug resistant, and carried transposons of the Tn916 family; CC-15 contained 23% of isolates, most of which were serotype 14, had the M phenotype, and carried mef(A) on Tn1207.1. Erythromycin resistance among S. pneumoniae isolates in New South Wales is mainly due to the dissemination of multidrug-resistant S. pneumoniae strains or horizontal spread of the Tn916 family of transposons.Streptococcus pneumoniae is an important cause of respiratory tract infections, bacteremia, and meningitis, for which antibiotic treatment is often difficult because of resistance to penicillin and other antibiotics, especially macrolides. During the last decade, macrolide resistance among S. pneumoniae isolates has increased, with considerable geographical variation among the genotypes and phenotypes involved (3, 14, 17, 34, 35).Macrolide resistance in S. pneumoniae is mediated by two main mechanisms. Target modification due to a ribosomal methylase, encoded by erm(B) confers high-level resistance to macrolides, lincosamides, and streptogramin B (MLS_B phenotype). In S. pneumoniae and related Streptococcus spp., the frequent association of erythromycin and tetracycline resistance is often related to insertion of erm(B) into a conjugative transposon of the Tn916 family that harbors tet(M) and carries integrase (int) and excisase (xis) genes. Members of this family, which carry erm(B), include Tn6002, Tn1545 (which also carries the kanamycin resistance gene aphA3), and Tn3872 (which also carries transposase genes tnpA and tnpR) (2, 8).The second macrolide resistance mechanism is an efflux pump system encoded by mef which confers resistance to 14- and 15-member macrolides only (M phenotype) (22). The two main subclasses of mef in S. pneumoniae, mef(E) and mef(A), are carried on different, but related elements: mef(A) on the defective transposon Tn1207.1 (32, 33) or the closely related Tn1207.3 and mef(E) on an element named “macrolide efflux genetic assembly” (mega) (11, 19). Both of these elements carry an open reading frame downstream of mef, designated msr(D) (9, 10) or mel (1, 11, 19), which are homologues of msr(A), which codes for an ATP-dependent efflux pump in Staphylococcus spp. (31). msr(D) and mel are cotranscribed with mef and contribute to an erythromycin-inducible dual efflux system in S. pneumoniae (1, 9, 19). Different investigators have reported and named these msr(D) homologues separately, and it is not clear whether or not they are identical.The prevalence of isolates carrying both mef and erm(B) has reportedly increased as a result of the worldwide spread of a limited number of multidrug-resistant clonal complexes (CCs), of which the most prevalent is Taiwan^19F-14 (CC-271) (15). Recently, two new composite elements of the Tn916 family, containing tet(M) plus mega (Tn2009) and tet(M), erm(B), and mega (Tn2010), have been described (10, 12). The distribution of these transposons and the genes they carry also vary in different geographic regions (4, 9) and provide a clue to the origins of antibiotic-resistant strains of S. pneumoniae.This study is the first to analyze the distribution of antibiotic susceptibility patterns and phenotypic and genotypic characteristics of erythromycin-resistant invasive S. pneumoniae isolates in Australia, including the transposons on which resistance genes are carried. The isolates studied had been referred to the Pneumococcal Reference Laboratory at the Centre for Infectious Diseases and Microbiology, which receives all sterile-site isolates from patients with invasive pneumococcal disease, in New South Wales, for serotyping (30). The 7-valent pneumococcal conjugate vaccine (PCV7) first became available in Australia in 2001, with limited uptake. It was introduced into the routine infant immunization schedule in January 2005 as a 3-dose regimen given at 2, 4, and 6 months.     

Pharmacotherapy of schizophrenia: ploypharmacy approaches

Schizophrenia is a debilitating illness, rating as one of the leading causes of lost years of quality of life. The illness imposes a disproportionate burden on patients and their families, healthcare systems and society. Pharmacological management is the cornerstone of treatment of schizophrenia, and antipsychotics, both first generation of antipsychotics and second generation of antipsychotics, are efficacious in reducing levels of psychopathology in acute episodes of schizophrenia. Clearly a need for innovative treatment strategies in schizophrenia that will ensure increased effectiveness against negative symptoms and cognitive dysfunction dysfunction. Therefore, in majority of cases polypharmacy is one of the effective approaches. This review focused on polypharmacy in the treatment of schizophrenia and in particular negative symptoms.