Drug-Related Side Effects and Adverse Reactions ; Emergency Service, Hospital ; Hospitals, General ; Humans ; Pharmaceutical Preparations ; Poisoning ; Retrospective Studies

OBJECTIVES: To study the clinical effect of full-dose prednisone for 4 or 6 weeks in the treatment of children with primary nephrotic syndrome and its effect on recurrence. METHODS: A prospective non-randomized controlled clinical trial was performed on 89 children who were hospitalized and diagnosed with incipient primary nephrotic syndrome from December 2017 to May 2019. The children were given prednisone of 2 mg/(kg·day) (maximum 60 mg) for 4 weeks (4-week group) or 6 weeks (6-week group), followed by 2 mg/(kg·day) (maximum 60 mg) every other day for 4 weeks and then a gradual reduction in dose until drug withdrawal. The children were regularly followed up for 1 year. The two groups were compared in terms of the indices including remission maintenance time and recurrence rate. A Cox regression analysis was used to assess the risk factors for recurrence. RESULTS: Within 3 months after prednisone treatment, the 4-week group had a significantly higher recurrence rate than the 6-week group (P<0.05). After 1-year of follow-up, there was no significant difference between the two groups in the recurrence rate, remission maintenance time, and recurrence frequency (P>0.05). The risk of recurrence increased in children with an onset age of ≥6 years or increased 24-hour urinary protein (P<0.05). CONCLUSIONS For the treatment of incipient primary nephrotic syndrome, full-dose prednisone regimen extended from 4 weeks to 6 weeks can reduce recurrence within 3 months. The children with an onset age of ≥6 years or a high level of urinary protein should be taken seriously in clinical practice, and full-dose prednisone treatment for 6 weeks is recommended to reduce the risk of recurrence.
Child ; Glucocorticoids ; Humans ; Nephrotic Syndrome ; Prednisone ; Prospective Studies ; Recurrence ; Risk Factors

BACKGROUND/AIMS: Small intestine motility is governed by an electrical slow wave activity, and abnormal slow wave events have been associated with intestinal dysmotility. High-resolution (HR) techniques are necessary to analyze slow wave propagation, but progress has been limited by few available electrode options and laborious manual analysis. This study presents novel methods for in vivo HR mapping of small intestine slow wave activity. METHODS: Recordings were obtained from along the porcine small intestine using flexible printed circuit board arrays (256 electrodes; 4 mm spacing). Filtering options were compared, and analysis was automated through adaptations of the falling-edge variable-threshold (FEVT) algorithm and graphical visualization tools. RESULTS: A Savitzky-Golay filter was chosen with polynomial-order 9 and window size 1.7 seconds, which maintained 94% of slow wave amplitude, 57% of gradient and achieved a noise correction ratio of 0.083. Optimized FEVT parameters achieved 87% sensitivity and 90% positive-predictive value. Automated activation mapping and animation successfully revealed slow wave propagation patterns, and frequency, velocity, and amplitude were calculated and compared at 5 locations along the intestine (16.4 +/- 0.3 cpm, 13.4 +/- 1.7 mm/sec, and 43 +/- 6 microV, respectively, in the proximal jejunum). CONCLUSIONS: The methods developed and validated here will greatly assist small intestine HR mapping, and will enable experimental and translational work to evaluate small intestine motility in health and disease.
Electrodes ; Electrophysiology ; Forced Expiratory Volume ; Gastrointestinal Motility ; Interstitial Cells of Cajal ; Intestine, Small ; Intestines ; Noise

BACKGROUNDInflammation and coagulation are two intimately cross-linked defense mechanisms of most, if not all organisms to injuries. During cardiopulmonary bypass (CPB), these two processes are activated and interact with each other through several common pathways, which may result in subsequent organ dysfunction. In the present study, we hypothesized that the addition of nitric oxide, prostaglandin E1 (PGE1), and aprotinin to the systemic circulation, hereby referred to as blood hibernation, would attenuate the inflammation and coagulation induced by CPB.

METHODSThirty adult mongrel dogs were equally divided into five groups, anesthetized and placed on hypothermic CPB (32 degrees C). Each group received respectively the following treatments: (1) inhalation of 40 ppm nitric oxide; (2) intravenous infusion of 20 ng x kg(-1) x min(-1) of PGE1; (3) 80,000 kallikrein inhibitor units (KIU)/kg of aprotinin; (4) the combination of all three agents (blood hibernation group); and (5) no treatment (control group) during CPB. Activation of leukocyte, platelet, endothelial cell, and formation of thrombin were assessed after CPB.

RESULTSAs compared with the other four groups, leukocyte counts were higher, while plasma elastase, interleukin-8, CD11b mRNA expression, myeloperoxidase activities and lung tissue leukocyte counts were lower in the blood hibernation group (P < 0.05 versus other four groups after CPB). Plasma prothrombin fragment (PTF)1+2, and platelet activation factors were lower, while platelet counts were higher in the blood hibernation group (P < 0.05 versus other four groups at 6 and 12 hours after CPB). Electron microscopy showed endothelial pseudopods protrusion, with cell adherence in all four groups except the blood hibernation group where endothelial cells remained intact.

CONCLUSIONBlood hibernation, effected by the addition of nitric oxide, PGE1 and aprotinin to the circulating blood during extra-corporeal circulation, was observed to attenuate the inflammation and coagulation induced by cardiopulmonary bypass, most likely by inhibiting the important common intermediates between the two cross-linked processes.

Alprostadil ; pharmacology ; therapeutic use ; Animals ; Aprotinin ; pharmacology ; therapeutic use ; Blood Coagulation ; drug effects ; CD11b Antigen ; genetics ; Cardiopulmonary Bypass ; adverse effects ; Dogs ; Inflammation ; drug therapy ; etiology ; Male ; Nitric Oxide ; pharmacology ; therapeutic use ; Reverse Transcriptase Polymerase Chain Reaction

Introduction: In line with the regional aim of eliminating rubella and congenital rubella syndrome (CRS), phased introduction of rubella-containing vaccines (RCV) in the Philippines’ routine immunization programme began in 2010. We estimated the burden of CRS in the country before widespread nationwide programmatic RCV use. Methods: We performed a retrospective chart review in four tertiary hospitals. Children born between 1 January 2009 and 31 December 2014 and identified as possible CRS cases based on the presence of one or more potential manifestations of CRS documented in hospital or clinic charts were reviewed. Cases that met the clinical case definition of CRS were classified as either confirmed (with laboratory confirmation) or probable (without laboratory confirmation). Cases that did not fulfil the criteria for either confirmed or probable CRS were excluded from the analysis. Results: We identified 18 confirmed and 201 probable cases in this review. Depending on the hospital, the estimated incidence of CRS ranged from 30 to 233 cases per 100 000 live births. The estimated national burden of CRS was 20 to 31 cases per 100 000 annually. Discussion: This is the first attempt to assess the national CRS burden using in-country hospital data in the Philippines. Prospective surveillance for CRS and further strengthening of the ongoing measles-rubella surveillance are necessary to establish accurate estimates of the burden of CRS and the impact of programmatic RCV use in the future.

STUDY DESIGN: Retrospective case series observational study. PURPOSE: Cancer patients are often aged and are further weakened by their illness and treatments. Our goal was to evaluate the efficiency and safety of using minimally invasive techniques to operate on spinal fractures in these patients. OVERVIEW OF LITERATURE: Vertebroplasty is now considered to be a safe technique that allows a significant reduction of the pain induced by a spinal tumoral fracture. However, few papers describe the kyphosis reduction that can be achieved by combining percutaneous fixation and anterior vertebral reconstruction. METHODS: We studied 35 patients seen between December 2013 and October 2016 who had at least one pathological spinal fracture and multiple vertebral metastases. The population’s mean age was 67 years, and no patients included had preoperative neurological deficits. The patients underwent a minimally invasive surgery consisting of a percutaneous pedicular fixation with cement-enhanced screws and anterior reconstruction comprising kyphoplasty when possible or corpectomy in cases of excessive damage to the vertebral body. Back pain, traumatic local and regional kyphosis, and Beck’s Index were collected pre- and postoperatively, and at 3-, 6-, and 12-month follow-ups. RESULTS: Mean follow-up time was 13.4 months. Significant reductions in back pain (p<0.001) and local (p<0.001) and regional kyphosis (p=0.006) were found at the 6-month follow-up (alpha risk level <0.05). Beck’s Index was also significantly increased, indicating good restoration of the anterior vertebral height. By the final follow-up, no screws had fallen/pulled out. There were no infectious or neurological complications. CONCLUSIONS: Percutaneous cement-enhanced fixation for pathological fractures has proven a safe and efficient technique in our experience, enabling weak patients to rapidly become ambulatory again without complications. Further follow-up of the patients is necessary to assess the long-term effects of this technique and the continued quality of life of our patients.
Back Pain ; Cementoplasty ; Follow-Up Studies ; Fractures, Spontaneous ; Humans ; Kyphoplasty ; Kyphosis ; Minimally Invasive Surgical Procedures ; Neoplasm Metastasis ; Observational Study ; Quality of Life ; Retrospective Studies ; Spinal Fractures ; Vertebroplasty

Cholesterol-dependent cytolysins (CDC) are pore forming toxins. A prototype of the CDC family members is perfringolysin O (PFO), which directly binds to the cell membrane enriched in cholesterol, causing cell lysis. However, an exception of this general observation is intermedilysin (ILY) of Streptococcus intermedius, which requires human CD59 as a receptor in addition to cholesterol for its hemolytic activity. A possible explanation of this functional difference is the conformational variation between the C-terminal domains of the two toxins, particularly in the highly conserved undecapeptide termed tryptophan rich motif. Here, we present the crystal structure of suilysin, a CDC toxin from the infectious swine pathogen Streptococcus suis. Like PFO, suilysin does not require a host receptor for hemolytic activity; yet the crystal structure of suilysin exhibits a similar conformation in the tryptophan rich motif to ILY. This observation suggests that the current view of the structure-function relationship between CDC proteins and membrane association is far from complete.
Amino Acid Sequence ; Animals ; Bacterial Toxins ; chemistry ; Bacteriocins ; chemistry ; Cholesterol ; chemistry ; Crystallography, X-Ray ; Cytotoxins ; chemistry ; Hemolysin Proteins ; chemistry ; genetics ; Molecular Sequence Data ; Point Mutation ; Protein Structure, Tertiary ; Sequence Alignment ; Streptococcus suis ; metabolism ; Swine

Background: Early-onset sepsis (EOS) is a leading cause of morbidity and mortality among neonates. Diagnosis of EOS can be difficult as clinical signs are subtle. The use of the Neonatal EOS Calculator (NEOSC) may help screen high-risk neonates for EOS and may result in a significant reduction in unnecessary antibiotic use. Objective: To determine the diagnostic accuracy of the NEOSC in screening for EOS in neonates more than 35 weeks age of gestation. Methodology: This was a retrospective, case-control study where 245 septic (cases) and 245 non-septic (controls) neonatal and maternal medical records were reviewed. The EOS risk classification from the NEOSC was compared with the actual clinical outcome. An online statistical software (medcalc.org) was used to compute for the sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and accuracy of the NEOSC. Results: Based on the NEOSC, only 64 of 245 clinically septic neonates were truly positive for sepsis while 181 were falsely negative for sepsis. Of the 245 non-septic neonates, 3 were falsely positive for sepsis, while 242 were truly negative for sepsis. With a 95% confidence interval, the computed variables showed a Sn 26.12%, Sp 98.78%, PPV 76.12%, NPV 89.95%, PLR 21.33, and NLR 0.75. The accuracy of the NEOSC is 89.33%. Conclusion The NEOSC had poor sensitivity and is not recommended in screening for EOS in neonates more than 35 weeks age of gestation. It may be used as an adjunct in EOS diagnosis due to its high specificity and accuracy.
Neonatal Sepsis

BACKGROUNDCigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10% - 20% of chronic heavy cigarette smokers develop symptomatic disease. COPD is most likely the result of complex interactions between environmental and genetic factors. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST). In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population.

METHODSPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113-->His), exon 4 (His139-->Arg) and GSTP1 polymorphism in exon 5 (Ile105-->Val) in 100 COPD patients and 100 age- and sex-matched healthy controls.

RESULTSThe proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32%). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years was 2.96 (95% CI 1.24 - 7.09). There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls. When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1.00; and when COPD patients were smokers (current smokers and ex-smokers), the OR was less than 1.00. There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls.

CONCLUSIONSmEH exon 3 heterozygotes might be associated with susceptibility to COPD in China. The interaction might exist between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population.

Aged ; Epoxide Hydrolases ; genetics ; Female ; Genotype ; Glutathione S-Transferase pi ; Glutathione Transferase ; genetics ; Humans ; Isoenzymes ; genetics ; Male ; Middle Aged ; Mutation ; Polymorphism, Genetic ; Pulmonary Disease, Chronic Obstructive ; etiology ; genetics

BACKGROUNDEnhanced external counterpulsation (EECP) has been demonstrated to be effective in the treatment of patients with coronary artery disease (CAD). It has been proposed that the beneficial effects of EECP observed in clinical studies may be due to the formation of new blood vessels (angiogenesis) and collateral development. However, there is a relative paucity of basic studies to support the proposed mechanisms.

METHODSTwelve Beagle dogs were anesthetized with 3% sodium pentobarbital, 1 mg/kg intraperitoneal injection and mechanically ventilated for the development of myocardial infarction. After coronary occlusion, all animals were randomly assigned to either EECP or control. EECP was given one hour per day, 5 days a week, for a total of 28 to 30 hours treatment over a 6-week course. Immunohistochemical studies of alpha-actin and von Willebrand factor (vWF) were used to detect newly developed microvessels. Systemic and local vascular endothelial growth factor (VEGF) were identified by enzyme linked immunosorbent assay (ELISA) and reverse-transcriptional polymerase chain reaction (RT-PCR) analysis.

RESULTSThere was a significant increase in the density of microvessels per mm(2) in the infarcted regions of EECP group compared to control group (vWF, 15.2 +/- 6.3 versus 4.9 +/- 2.1, P < 0.05; alpha-actin, 11.8 +/- 5.3 versus 3.4 +/- 1.2, P < 0.05), along with significant increase of positive vWF and alpha-actin stained area. Both immunohistochemical staining and RT-PCR analysis documented a significant increase in VEGF expression. These factors associated with angiogenesis corresponded to improved myocardial perfusion by 99mTc-sestamibi single-photon emission computed tomography.

CONCLUSIONMicrovessel angiogenesis may be a mechanism of action for the improved myocardial perfusion after EECP therapy.

Animals ; Counterpulsation ; Dogs ; Hemodynamics ; Immunohistochemistry ; Male ; Microcirculation ; Myocardial Infarction ; physiopathology ; therapy ; Neovascularization, Physiologic ; RNA, Messenger ; analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; blood ; genetics ; Ventricular Function, Left