[Percutaneous pedicle screw fixation combined expandable tubular retractor in the treatment of spinal metastases].

OBJECTIVE: To investigate the effectiveness of percutaneous pedicle screw fixation combined expandable tubular retractor in the treatment of patients with spinal metastases. METHODS: In the study, 12 patients of spinal metastases treated with percutaneous pedicle screw fixation combined expandable tubular retractor in our hospital were retrospectively reviewed between June 2017 and October 2019. Among the 12 patients, 9 were males and 3 were females; the median age was 62.5 years [(65.1±2.9) years]. The decompression segment of 7 patients was located at the lower thoracic spine (including 1 patient with incomplete paraplegia) and the decompression segment of 5 patients was located at the lumbar spine; Tomita score was 6.0±0.6. Perioperative data of the patients were reviewed. Visual analog scale (VAS score), Karnofsky score, and Eastern Cooperative Oncology Group (ECOG) score were compared before and after surgery. The patient's survival, adjuvant treatment, and internal fixation failure were observed in the follow-up period. RESULTS: All the 12 patients had a successful operation with percuta-neous pedicle screw fixation combined expandable tubular retractor. The average operative time, blood loss, and blood transfused of the patients were (247.0±14.6) min, (804.2±222.3) mL and (500.0±100.0) mL, respectively. The average amount of drainage was (240.8±79.3) mL. Drainage tubes were pulled out early postoperative [(3.2±0.3) d], allowing early mobilization. The patients discharged (7.8±0.8) d postoperative. All the patients were followed up for 6-30 months, and the average overall survival time was (13.6±2.4) months. During the follow-up period, 2 patients experienced screw displacement, the internal fixation was stable after conservative treatment and no revision surgery was performed. The VAS of the patients was 7.1±0.2 before surgery, which decreased to 2.3±0.1 and 2.8±0.4 at 3 and 6 months after surgery (P < 0.05). The Karnofsky score of the patients was 59.2±1.9 before surgery, which increased to 75.0±1.9 and 74.2±3.1 at 3 and 6 months after surgery (P < 0.05). The ECOG of the patients was 2.3±0.2 before surgery, which decreased to 1.7±0.1 and 1.7±0.2 at 3 and 6 months after surgery (P < 0.05). CONCLUSION: For selected patients with spinal metastases, minimally invasive surgical treatment of spinal metastases (percutaneous pedicle screw internal fixation combined with expandable tubular retractor) can effectively relieve the clinical symptoms and improve the quality of life, with satisfactory clinical outcome.

[Perioperative clinical characteristics of patients with pathological fracture of proximal femur].

OBJECTIVE: To investigate the perioperative clinical characteristics of patients with pathological fracture of proximal femur. METHODS: A retrospective study reviewed 28 patients who received proximal resection and tumor hemiarthroplasty for malignant proximal femoral tumor in Peking University First Hospital from January 2011 to February 2017. According to the fracture, the patients were divided into two groups: pathological fracture group and non-pathological fracture group. We investigated the clinical characteristics during perioperative period between the two groups. RESULTS: Of the 28 patients, 14 (50.0%) patients suffered pathological fracture, and there was no significant difference between the two groups in the patient's age, gender, limb involvement, and tumor source (P>0.05). There was no significant difference between the two groups in hemoglobin (HGB), hematocrit (Hct), and lower extremity thrombosis. The albumin (ALB) of pathological fracture group were lower in contrast to non-pathological fracture group (P=0.031). There was no significant difference between the two groups in decline of HGB and Hct on postoperation day 1, operative time, bleeding during operation, time for walking with help of ambulation aid postoperative, and postoperative hospital stay (P>0.05). On post-operation day 7, HGB (P=0.025) and Hct (P=0.039) of pathological fracture group were significant lower in contrast to non-pathological fracture group. Whereas, the total blood loss calculated by Gross equation of pathological fracture group was significant higher in contrast to non-pathological fracture group [(2 066.3±419.8) mL vs. (786.0±152.6) mL, P=0.039]. The patient needed blood transfusion during operation (7/14 vs. 1/14, P=0.033) and postoperative (8/14 vs. 1/14, P=0.013) in pathological fracture group were more than in non-pathological fracture group. At last, Barthel daily life ability score (P=0.009) of pathological fracture group was lower in contrast to non-pathological fracture group, and visual analogue scale (VAS) score was higher (P<0.001). They were almost equal when the patients were discharged (P>0.05). CONCLUSION: Patients with pathological fracture had lower ALB during perioperative period. Pathological fracture had no effect on operative time, bleeding during operation and function outcomes. However, the patients with pathological fracture had more total blood loss and lower HGB, Hct in contrast to the patients without pathological fracture. Blood transfusion was more needed in pathological fracture patients.

[Analysis of influencing factors for pathogen culture result in patients with pyogenic spondylitis].

OBJECTIVE: To investigate the effect of clinical factors on the pathogen culture results in the patients with pyogenic spondylitis, and to find out clinical controllable factors which could increase the positive rate of the pathogen culture. METHODS: A retrospective study reviewed 40 patients who were diagnosed with pyogenic spondylitis in Peking University First Hospital from January 2011 to July 2017. The patients were divided into two groups depending on the culture results, culture negative or culture positive. The influence of clinical uncontrollable factors [the patient's age, gender, predisposing factors, infection site except spine, visual analogue score (VAS), course of disease, spinal segment, white blood cell (WBC), (neutrophilic granulocyte)% (NE%), the incidence of systemic inflammatory response syndrome (SIRS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the incidence of paravertebral abscess] and controllable factors (prior antibiotics exposure within 2 weeks, tissue homogenate, surgical approach) on pathogen culture results were analyzed. RESULTS: Of the 40 patients, 18 patients were female and 22 patients were male. Causative germ was identified in 24/40 patients (60.00%) and dominant by gram positive cocci (68.00%). For clinical uncontrollable factors, there was no significant difference between the two groups in the patient's age, gender, predisposing factors, infection site except spine, VAS, course of disease, spinal segment, WBC, NE% and the incidence of SIRS. ESR [(94.38±6.91) mm/h, P=0.023)], CRP [(64.74±13.51) mg/L, P=0.040], and the incidence of paravertebral abscess (75%, P=0.018) in culture negative group were lower in contrast to culture positive group. For clinical controllable factors, prior antibiotics exposure within 2 weeks (P=0.058, OR=4.030, 95%CI: 0.956-16.993) and tissue homogenate (P=0.014, OR=0.171, 95%CI: 0.042-0.695) were significantly associated with the pathogen culture result. Surgical approach was not significantly associated with pathogen culture result. CONCLUSION: Patients with high level of ESR, CRP, and paravertebral abscess, would have high positive rate of pathogenic culture. Prior antibiotics exposure was associated with lower positive pathogen culture rate. Culture with tissue homogenate was more likely to find the causative germ, especially for patients without paravertebral abscess who had low level of ESR, CRP and prior antibiotics exposure.

Bone morphogenetic proteins and Dickkopf-1 in ankylosing spondylitis.

OBJECTIVES: To determine bone morphogenetic proteins (BMPs) and Dickkopf homologue-1 (Dkk-1) levels in ankylosing spondylitis (AS). METHOD: Serum BMPs and Dkk-1 were measured in 72 AS patients and 30 healthy controls. For AS patients, we recorded the demographic data, disease activity, functional index, and global assessment with questionnaires, and image changes with roentgenography. We also measured human leucocyte antigen-B27 and systemic inflammatory reactants. RESULTS: BMPs were higher but Dkk-1 was significantly lower in AS patients than in controls. Dkk-1 was higher in AS patients who received non-steroidal anti-inflammatory drugs (NSAIDs) regularly in the past year (p = 0.001). Serum BMP-7 level and the BMP-7/Dkk-1 ratio correlated significantly with sacroiliitis severity, Bath Ankylosing Spondylitis Radiology Index (BASRI)-total, modified Stoke Ankylosing Spondylitis Spinal Score, and disease duration. There were also significant positive correlations among serum levels of BMP-2, -4, and -6, BASRI-total, and disease duration (p < 0.05). However, BMP-2/Dkk-1 was only significantly correlated with disease duration. The calculated area under the standard receiver operating characteristics curve suggested that BMP-2/Dkk-1 and serum BMP-2 are good indicators to predict disease activity, functional index, and patient global assessment in AS patients. CONCLUSION: BMPs and BMPs/Dkk-1 were significantly correlated with disease activity, and radiological and functional indices in AS patients. Dkk-1 was lower in AS patients than in controls. Among AS patients, Dkk-1 was higher in those taking NSAIDs regularly. BMP or Dkk-1 may be taken as a biomarker for disease severity or a treatment outcome predictor in AS, but this needs further study.

[Clinical characteristics and prognosis of cultured negative pyogenic spondylitis].

OBJECTIVE: There are limited data describing the clinical characteristics and prognosis of culture negative pyogenic spondylitis. The aim of this study was to investigate the treatment, prognosis and clinical characteristics of culture negative pyogenic spondylitis. METHODS: A retrospective study reviewed 74 patients who were diagnosed with spondylitis in Peking University First Hospital from January 2010 to December 2015. A total of 27 patients suffered from pyogenic spondylitis. According to the pathogenic culture results, the patients were divided into two groups: culture negative group and culture positive group. The clinical characteristics and treatment outcomes between the two groups were compared. RESULTS: The elder were more vulnerable to pyogenic spondylitis, and of the 27 patients, 12 patients were female and 15 male. All patients had no history of administration of antibiotics prior to obtaining culture samples. A causative germ was identified in 14/27 patients (51.9%) with Staphylococcus aureus being the most common pathogen. There was no significant difference between the two groups in the patient's age, gender, visual analogue score (VAS), predisposing factor, clinical symptom, sign and spinal segment (P>0.05). Erythrocyte sedimentation rate (ESR) (P=0.056) and C-reactive protein (CRP) (P=0.040) of culture negative group were lower in contrast to culture positive group. The incidence of vertebral abscess in culture negative group was higher than in culture positive group (P=0.046). After treatment, ESR dropped almost equally in both groups, and CRP dropped faster in the culture positive group (P=0.192). At last, there was no significant difference between the two groups in hospital stay, pain relief, open debridement operation rate, and recurrence rate of infection. CONCLUSION: ESR and CRP of the culture negative patient were lower than those of the culture positive patient, and the incidence rate of paravertebral abscess was higher than that of the culture positive patient. After administration of antibiotics, there was no significant difference between the two groups in duration of antibiotics, open debridement operation rate and recurrence rate of infection. So, culture negative may not necessarily be a negative prognostic factor for pyogenic spondylitis. However, we should watch out for the drug resistant bacteria or double infection, due to the long term use of wide-spectrum antibiotic in culture negative patients.

Efficient diode-pumped acousto-optic Q-switched Er:Yb:GdAl(3)(BO(3))(4) pulse laser at 1522 nm.

End-pumped by a continuous-wave 976 nm diode laser, efficient 1522 nm laser operation was demonstrated in an Er:Yb:GdAl(3)(BO(3))(4) crystal when a sapphire crystal was used as a heat diffuser. A continuous-wave 1522 nm laser with a maximum output power of 750 mW and slope efficiency of 36% was realized at an absorbed pump power of 4.1 W. The pulse performances of an acousto-optic Q-switched laser with various repetition frequencies were investigated in detail. In a repetition frequency range of 1-10 kHz, 1522 nm pulse lasers with a slope efficiency of about 10%, peak output power at the kilowatt level, and width of about 50 ns were first obtained in an Er:Yb:GdAl(3)(BO(3))(4) crystal pumped by a continuous-wave diode laser. The results indicate that the crystal is a promising gain medium for an actively Q-switched 1.5 µm laser.

Smoking, aging, and expression of proteins related to the FOXO3 signaling pathway in lung tissues.

We investigated the effects of smoking and aging on proteins involved in the forkhead box O3 (FOXO3) signaling pathways in the lungs. Sixteen senescence-accelerated mouse-resistant 1 (SAMR1) and senescence-accelerated mouse-prone 8 (SAMP8) mice at 3 months of age were divided into a normally aged, smoke-exposed group (4 SAMR1 mice), a normally aged, air-exposed group (4 SAMR1 mice), an aging-accelerated, smoke-exposed group (4 SAMP8 mice), and an aging-accelerated, air-exposed group (4 SAMP8 mice). Expression of genes and proteins related to the FOXO3 signaling pathways in each group was examined by western blot analysis and immunohistochemistry. FOXO3a expression was significantly increased in the normally aged, air-exposed group compared with the aging-accelerated, air-exposed group. FOXO3a expression was significantly reduced in the aging-accelerated, smoke-exposed group compared with the aging-accelerated, air-exposed group. Sirtuin 1, manganese superoxide dis-mutase, and phosphatidylinositol 3-kinase (PI3K)/Akt expression decreased significantly in the smoke-exposed groups compared with the air-exposed groups and in the aging-accelerated groups compared with the normally aged groups. Signal transduction pathways mediated by the transcription factor FOXO3a (such as the PI3K/Akt pathway) may be involved in the accelerated aging of lung tissues in chronic obstructive pulmonary disease. Smoking inactivates the transcription factor FOXO3, thus accelerating lung tissue aging during chronic obstructive pulmonary disease.

Effect of Esketamine on perioperative anxiety and depression in women with systemic tumors based on big data medical background.

OBJECTIVE: Perioperative anxiety and depression syndrome (PADS) is a common clinical concern among women with systemic tumors. Esketamine has been considered for its potential to alleviate anxiety and depressive symptoms. However, its specific application and effectiveness in PADS among women with systemic tumors remain unclear. This study aimed to analyze the utility of Machine Learning (ML) algorithms based on electroencephalogram (EEG) signals in evaluating perioperative anxiety and depression in women with systemic tumors treated with Esketamine, utilizing a large-scale medical data background. PATIENTS AND METHODS: A single-center, randomized, placebo-controlled (SC-RPC) trial design was adopted. A total of 112 female patients with systemic tumors and PADS who received Esketamine treatment were included as study participants. A moderate dose (0.7 mg/kg) of Esketamine was administered through intravenous infusion over a duration of 60 minutes. EEG signals were collected from all patients, and the EEG signal features of individuals with depression were compared to those without depression. In this study, a Support Vector Machine (SVM)-K-Nearest Neighbour (KNN) hybrid classifier was constructed based on SVM and KNN algorithms. Using the EEG signals, the classifier was utilized to assess the anxiety and depression status of the patients. The predictive performance of the classifier was evaluated using accuracy, sensitivity, and specificity measures. RESULTS: The C2 correntropy feature of the delta rhythm in the left-brain EEG signal was significantly higher in individuals with depression compared to those without depression (p<0.05). Moreover, the C2 correntropy feature of the Alpha, Beta, and Gamma rhythms in the left-brain EEG signal was significantly lower in individuals with depression compared to those without depression (p<0.05). In the right brain EEG signal, the C2 correntropy feature of the delta rhythm was significantly higher in individuals with depression (p<0.05), while the C2 correntropy feature of the alpha and gamma rhythms was significantly lower in individuals with depression compared to those without depression (p<0.05). Additionally, the C1 correntropy feature of the Gamma rhythm in the right brain EEG signal was significantly higher in individuals with depression compared to those without depression (p<0.05). The SVM classifier achieved accuracy, sensitivity, and specificity of 98.23%, 98.10%, and 98.56%, respectively, in recognizing the left-brain EEG signals, with a correlation coefficient of 0.95. In recognizing the right brain EEG signals, the SVM classifier achieved accuracy, sensitivity, and specificity of 98.74%, 98.43%, and 99.03%, respectively, with a correlation coefficient of 0.96. The improved SVM-KNN approach yielded an accuracy, recall, precision, F-score, area over the curve (AOC), and Receiver Operation Characteristics (ROC) of 0.829, 0.811, 0.791, 0.853, 0.787, and 0.877, respectively, in predicting anxiety. For predicting depression, the accuracy, recall, precision, F-score, AOC, and ROC were 0.869, 0.842, 0.831, 0.893, 0.827, and 0.917, respectively. CONCLUSIONS: Significant differences were observed in the brain EEG signals between individuals with depression and those without depression. The improved SVM-KNN algorithm developed in this study demonstrates good predictive capability for anxiety and depression.

[A family with early onset myopathy caused by MEGF10 gene defect and literature review].

Objective: To summarize the genetic and clinical phenotypic characteristics of patients with early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) caused by multiple epidermal growth factor 10 (MEGF10) gene defect. Methods: The clinical data of 3 infants in 1 family with EMARDD caused by MEGF10 gene defect diagnosed in the Department of Neonatology, Xiamen Children's Hospital in April 2022 were analyzed retrospectively. Using "multiple epidermal growth factor 10" "myopathy" or "MEGF10" "myopathy" as the key words, and searching the relevant literature reports of CNKI, Wanfang Database and PubMed Database from the establishment of the database to September 2022. Combined with this family, the main clinical information and genotype characteristics of EMARDD patients caused by MEGF10 gene defect were summarized. Results: The proband, male, first infant of monozygotic twins, was admitted to hospital 7 days after birth "due to intermittent cyanosis with weak sucking". The infant had dysphagia accompanied with cyanosis of lips during feeding and crying after birth. Physical examination on admission revealed reduced muscle tone of the extremities, flexion of the second to fifth fingers of both hands with limited passive extension of proximal interphalangeal joints, and limited abduction of both hips. He was diagnosed as dysphagia of newborn, congenital dactyly. After admission, he was given limb and oral rehabilitation training, breathing gradually became stable and oral feeding fully allowed, and discharged along with improvement. The younger brother of the proband was admitted to the hospital at the same time, and his clinical manifestations, diagnosis and treatment process were the same as those of the proband. The elder brother of the proband died at the age of 8 months due to the delayed growth and development, severe malnutrition, hypotonia, single palmoclal crease and weak crying. A whole exon sequencing of the family was done, and found that the 3 children were all compound heterozygous variations at the same site of MEGF10 gene, with 2 splicing variants (c.218+1G>A, c.2362+1G>A), which came from the father and mother respectively, and the new variation was consistent with the autosomal recessive inheritance model. Three children were finally diagnosed as EMARDD caused by MEGF10 gene defect. There are 0 Chinese literature and 18 English literature that met the search conditions. Totally 17 families including 28 patients were reported. There were 31 EMARDD patients including 3 infants from this family. Among them, there were 13 males and 18 females. The reported age of onset ranged from 0 to 61 years. Except for 5 patients with incomplete clinical data, 26 patients were included in the analysis of phenotypic and genotypic characteristics. The clinical features were mainly dyspnea (25 cases), scoliosis (22 cases), feeding difficulties (21 cases), myasthenia (20 cases), and other features including areflexia (16 cases) and cleft palate or high palatal arch(15 cases). Muscle biopsy showed non-specific changes, with histological characteristics ranging from slight muscle fiber size variation to minicores change which was seen in all 5 patients with at least 1 missense mutation of allele. In addition, the adult onset was found in patients with at least 1 missense variant of MEGF10 gene. Conclusions: MEGF10 gene defect related EMARDD can occur in the neonatal period, and the main clinical features are muscle weakness, breathing and feeding difficulties. Patients with myopathy who have at least 1 missense mutation and muscle biopsy indicating minicores change may be relatively mild.

Risk factors for 30-day readmission in general medical patients admitted from the emergency department: a single centre study.

BACKGROUND: Overcrowding in emergency departments (ED) around the world is an increasingly serious problem with an adverse impact on both patient flow and patient outcomes. A significant contributing factor to ED overcrowding is possibly due to readmission. Risk factors for readmission in patients admitted from ED are rarely studied, particularly in Asian countries where the length of stay is reportedly longer. METHODS: A retrospective study of patients admitted to general medical wards from the ED of a referral centre in northern Taiwan from November 2009 to April 2010 was conducted. The primary outcome was 30-day hospital readmission and clinical characteristics were analysed for predictors of readmission. RESULTS: Of the recruited 2698 patients, 451 (16.7%) were readmitted within 30 days after discharge. Age, gender, marital status and the activities of daily living (Barthel's score) were not associated with 30-day readmission. Higher Charlson score ((score 2-4) hazard ratio (HR): 1.42, 95% confidence interval (CI): 1.07-1.89; (score >4) HR: 1.93, 95% CI: 1.37-2.73), longer hospital stay ((8-14 days) HR: 1.51, 95% CI: 1.17-1.95; (15-28 days) HR: 1.64, 95% CI: 1.22-2.19; (>28 days) HR: 1.97, 95% CI: 1.43-2.71), and presence of underlying active malignancy (HR: 1.66, 95% CI: 1.27-2.16) and anaemia (HR: 1.26, 95% CI: 1.02-1.55) were independently associated with readmission. CONCLUSION: Medical patients admitted from the ED of a referral centre have a 30-day readmission rate of 16.7%. Post-discharge care should focus on patients with higher Charlson score, longer hospitalisation, anaemia and underlying active malignancy, which are independent predictive factors for 30-day readmission.

Using a bubble chart to enhance adherence to quality-of-care guidelines for colorectal cancer patients.

This study examines whether a higher rate of physician adherence to quality-of-care indicators for colorectal cancer patients is associated with improved survival and using a bubble chart to help interpret physician performance. A set of 13 core measures was used to evaluate the quality of care in 708 colorectal cancer patients treated from 2004 to 2007 at a hospital in Taiwan. A 100% adherence standard was used to measure the relationship of adherence to patient survival. Each indicator assigned by each cancer stage was dichotomously coded. The associations between the adherence and survival rates and demographic characteristics were assessed using Cox's proportional hazard regression. Physician adherence to core indicators was plotted using a bubble chart to motivate physicians' performance adhering to quality-of-care guidelines for colorectal cancer patients. The 100% adherence rate criterion contributed to a relatively low hazard ratio of 0.36 (95% confidence interval, 0.14-0.85; P= 0.02). The association between the adherence rate and survival indicated significant improvements for stage III patients compared with stage I patients. A graphical representation of bubble charts helped to monitor physician performance, which improved the adherence rate to quality-of-care guidelines for colorectal cancer patients.

Role of ER export signals in controlling surface potassium channel numbers.

Little is known about the identity of endoplasmic reticulum (ER) export signals and how they are used to regulate the number of proteins on the cell surface. Here, we describe two ER export signals that profoundly altered the steady-state distribution of potassium channels and were required for channel localization to the plasma membrane. When transferred to other potassium channels or a G protein-coupled receptor, these ER export signals increased the number of functional proteins on the cell surface. Thus, ER export of membrane proteins is not necessarily limited by folding or assembly, but may be under the control of specific export signals.

Nanocontact resistance and structural disorder induced resistivity variation in metallic metal-oxide nanowires.

Several systems of metallic metal-oxide nanowires (NWs), including pure RuO2 and as-implanted and annealed Ru(0.98)Cu(0.02)O2 and Ru(0.93)Cu(0.07)O2 NWs, have been employed in two-probe electrical characterizations by using a transmission electron microscope-scanning tunneling microscope technique with a gold tip. Thermal, mechanical, and electron beam exposing treatments are consecutively applied to reduce the electrical contact resistance, generated from the interface between the NW and the gold tip, so as to evaluate the intrinsic NW resistance. It is found that the residual contact resistance cannot be entirely removed. For each system of metallic metal-oxide NWs, several tens of NWs are applied to electrical characterizations and the total resistances unveil a linear dependence on the ratio of the length to the area of the NWs. As a result, the average resistivity and the contact resistance of the metallic metal-oxide NWs could be evaluated at room temperatures. The average resistivities of pure RuO2 NWs agree well with the results obtained from standard two- and four-probe electrical-transport measurements. In addition, the as-implanted Cu-RuO2 NWs reveal disordered crystalline structures in high-resolution TEM images and give higher resistivities in comparison with that of pure RuO2 NWs. The residual contact resistances of all kinds of metallic metal-oxide NWs unveil, more surprisingly, an approximation value of several kilohms, even though the average resistivities of these NWs change by more than one order of magnitude. It is argued that the ductile gold tip makes one or more soft contacts on the stiff metal-oxide NWs with nanometer roughness and the nanocontacts on the NWs contribute to the electrical contact resistance.

Acute interstitial nephritis with prominent eosinophil infiltration.

AIMS: Acute interstitial nephritis (AIN) is common, but prominent eosinophil infiltration in patients with acute interstitial nephritis is rare. The possible etiologies, predisposing factors and treatment of such patients are the subjects of this study. METHODS: one patient was reported from our medical center; nine more patients with similar findings were reviewed from the literature. Suspected offending drugs, clinical presentations, predisposing factors and patient outcomes after therapy were recorded. RESULTS: A case of clam extract-associated acute interstitial nephritis with prominent eosinophil infiltration was reported. Ten cases including ours were analyzed. A variety of drugs was thought to be causative. In all, 7 of the 10 patients had a preexisting nephrotic syndrome, and eosinophilia was found in 6. Bone marrow biopsy was not performed in most cases and only available for 2 patients including ours. 9 patients treated with steroids had good responses but 1 patient died despite treatment. CONCLUSIONS: Acute interstitial nephritis with prominent eosinophil infiltration can be caused by a great diversity of drugs, which can include clam extract tablets. A preexisting nephrotic syndrome seemed to be a predisposing factor for this condition. This disease rarely led to fatality and most patients responded well to steroid therapy.

Protamine-associated hypotension in patients on hemodialysis: retrospective study and prevalence of antiprotamine antibodies.

AIMS: Protamine, when administered to neutralize heparin in cardiovascular surgery, is associated with occasionally severe antigen-antibody reactions associated with substantial morbidity and mortality. The objective of this study is to investigate whether patients on hemodialysis are more susceptible to the protamine adverse effects. METHOD: First, a retrospective analysis of a protamine-associated hypotension episode (PAHE) in 239 patients undergoing coronary artery bypass grafting surgery was performed for the incidence study in the period of 1999 to 2005. Second, an ELISA determination of serum anti-protamine IgG antibody in 255 serum samples from individuals without previous surgical histories was conducted for prevalence survey. In both studies, patients on HD were matched for age with non HD patients. RESULTS: The highest incidence (57%) of PAHE occurred in patients on hemodialysis using of M-insulin (a mixed type of insulin aspart 30%, insulin aspart protamine 70%) formulation, and this group also exhibited a high anti-protamine IgG antibody titer in serum (odds ratio: 18.31). CONCLUSIONS: A substantial proportion of patients on hemodialysis are at high risk of acquiring protamine adverse effects, but definite conclusion about the association between uremia and PAHE, however, still needs to be made with caution.

Protein kinase C enhances recombinant bovine alpha 1 beta 1 gamma 2L GABAA receptor whole-cell currents expressed in L929 fibroblasts.

The beta 1 and gamma 2L subunits of the gamma-aminobutyric acid type A receptor (GABAR) contain phosphorylation sites for PKC. To determine the effect of PKC on GABAR function, whole-cell recordings were obtained from mouse fibroblasts expressing recombinant alpha 1 beta 1 gamma 2L receptors, and catalytically active PKC (PKM) was applied via the recording pipette. The first experiment was a population study. Intracellular application of PKM increased GABAR currents, and the enhancement was antagonized by coapplication of the PKC inhibitory peptide. No acceleration or deceleration of GABAR desensitization was observed. The second experiment was a reimpalement study in which paired recordings were made successively from individual cells. Enhancement of GABAR currents by PKM was again obtained. PKM increased GABAR currents at high (> 10 microM) but not at low (< 10 microM) GABA concentrations, resulting in increases in both EC50 and maximal GABAR current. Thus, PKC phosphorylation enhanced recombinant alpha 1 beta 1 gamma 2L GABAR current by increasing maximal current without increasing the affinity of GABA for the GABARs.

Yeast screen for constitutively active mutant G protein-activated potassium channels.

GIRK2 is a major contributor to G protein-activated inward rectifier potassium channels in the mammalian brain. How GIRK channels open upon contact with Gbetagamma remains unknown. Using a yeast genetic screen to select constitutively active mutants from a randomly mutagenized GIRK2 library, we identified five gating mutations at four residues in the transmembrane domain. Further mutagenesis indicates that GIRK channel opening involves a rotation of the transmembrane segments, bringing one of these residues (V188) to a pore-lining position in the open conformation. Combined with double-mutant studies, these findings suggest that GIRK channels gate by moving from the open conformation inferred from our yeast study of Kir2.1 to a closed conformation perhaps resembling the known KcsA structure.

Functional modulation of the ATP-sensitive potassium channel by extracellular signal-regulated kinase-mediated phosphorylation.

ATP-sensitive potassium (K(ATP)) channels play an important role in controlling insulin secretion and vascular tone as well as protecting neurons under metabolic stress. We have previously demonstrated that stimulation of the K(ATP) channel by nitric oxide (NO) requires activation of Ras- and extracellular signal-regulated kinase (ERK) of the mitogen-activated protein kinase (MAPK) family. However, the mechanistic link between ERK and the K(atp) channel remained unknown. To investigate how ERK modulates the function of K(ATP) channels, we performed single-channel recordings in combination with site-directed mutagenesis. The Kir6.2/SUR1 channel, a neuronal K(ATP) channel isoform, was expressed in human embryonic kidney (HEK) 293 cells by transient transfection. Direct application of the activated ERK2 to the cytoplasmic surface of excised, inside-out patches markedly enhanced the single-channel activity of Kir6.2/SUR1 channels. The normalized open probability (NPo) and opening frequency were significantly increased, whereas the mean closed duration was reduced. The single-channel conductance level was not affected. The ERK2-induced stimulation of Kir6.2/SUR1 channels was prevented by heat-inactivation of the enzyme. Furthermore, alanine substitutions of T341 and S385 to disrupt the potential ERK phosphorylation sites present in the Kir6.2 subunit significantly abrogated the stimulatory effects of ERK2, while aspartate substitutions of T341 and S385 to mimic the (negative) charge effect of phosphorylation rendered a small yet significant reduction in the ATP sensitivity of the channel. Taken together, here we report for the first time that ERK2/MAPK activates neuronal-type K(ATP) channels, and this stimulation requires ERK phosphorylation of the Kir6.2 subunit at T341 and S385 residues. The ERK2-induced K(ATP) channel stimulation can be accounted for by changes in channel gating that destabilize the closed states and by reduction in the ATP sensitivity. As Kir6.2 is the pore-forming subunit of K(ATP) channels, ERK2-mediated phosphorylation may represent a common mechanism for K(ATP) channel regulation in different tissues.