Unilateral biportal endoscopic spine surgery for lumbar spinal stenosis: a systematic review and meta-analysis.

OBJECTIVE: Lumbar spinal stenosis is the most common spinal degenerative disease in patients over 60 years, and the unilateral biportal endoscopic (UBE) spine surgery treatment of lumbar spinal stenosis (LSS) has achieved preliminary clinical results. This systematic review and meta-analysis aimed to reveal the clinical efficacy of UBE for LSS and provide evidence for clinical practice. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Cochrane databases were searched for literature. The papers selected were those published from inception till October 2021. The selected pieces of literature were graded for evidence using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). Outcomes measures were operation time, blood loss, complication rate, admission period, Visual Analogue Scale (VAS)-back, VAS-leg, and Oswestry Disability Index (ODI) score, and radiological outcomes. The mean comparisons were based on VAS and ODI scores. RESULTS: A total of 823 patients with a single LSS segment were included from the selected nine studies. There were nine studies comparing UBE clinical outcomes and micro-endoscopic unilateral laminotomy for bilateral decompression (M-ULBD). The meta-analysis revealed that the UBE group had better VAS-leg and -back scores in the first week postoperatively [total: mean difference (MD) = -0.96, 95% confidence interval (CI): -1.19, -0.74, p < 0.00001; total: MD = -1.69, 95% CI: -1.93, -1.45, p < 0.00001], 1st month postoperatively (total: MD = -0.35, 95% CI: -0.61, -0.08, p = 0.01; total: MD = -0.40, 95% CI: -0.68, -0.12, p = 0.005), 6th month postoperatively (total: MD = -0.22, 95% CI: -0.35, -0.08, p = 0.002; total: MD = -0.24, 95% CI: -0.40, -0.07, p = 0.005), and UBE group also performed better in ODI score at 1st month postoperatively (total: MD = -3.36, 95% CI: -4.26, -2.46, p < 0.00001). There was no significant difference in VAS-leg and -back scores between both groups at the 3rd and 12th month postoperatively, and ODI scores did not significantly differ between both groups at 3, 6, and 12 months postoperatively (all p > 0.05). CONCLUSIONS: UBE has achieved good preliminary clinical results and may be a minimally invasive alternative surgery for patients with single segmental LSS.

Estimating Local Cellular Density in Glioma Using MR Imaging Data.

BACKGROUND AND PURPOSE: Increased cellular density is a hallmark of gliomas, both in the bulk of the tumor and in areas of tumor infiltration into surrounding brain. Altered cellular density causes altered imaging findings, but the degree to which cellular density can be quantitatively estimated from imaging is unknown. The purpose of this study was to discover the best MR imaging and processing techniques to make quantitative and spatially specific estimates of cellular density. MATERIALS AND METHODS: We collected stereotactic biopsies in a prospective imaging clinical trial targeting untreated patients with gliomas at our institution undergoing their first resection. The data included preoperative MR imaging with conventional anatomic, diffusion, perfusion, and permeability sequences and quantitative histopathology on biopsy samples. We then used multiple machine learning methodologies to estimate cellular density using local intensity information from the MR images and quantitative cellular density measurements at the biopsy coordinates as the criterion standard. RESULTS: The random forest methodology estimated cellular density with R 2 = 0.59 between predicted and observed values using 4 input imaging sequences chosen from our full set of imaging data (T2, fractional anisotropy, CBF, and area under the curve from permeability imaging). Limiting input to conventional MR images (T1 pre- and postcontrast, T2, and FLAIR) yielded slightly degraded performance (R2 = 0.52). Outputs were also reported as graphic maps. CONCLUSIONS: Cellular density can be estimated with moderate-to-strong correlations using MR imaging inputs. The random forest machine learning model provided the best estimates. These spatially specific estimates of cellular density will likely be useful in guiding both diagnosis and treatment.

Imaging-Based Algorithm for the Local Grading of Glioma.

BACKGROUND AND PURPOSE: Gliomas are highly heterogeneous tumors, and optimal treatment depends on identifying and locating the highest grade disease present. Imaging techniques for doing so are generally not validated against the histopathologic criterion standard. The purpose of this work was to estimate the local glioma grade using a machine learning model trained on preoperative image data and spatially specific tumor samples. The value of imaging in patients with brain tumor can be enhanced if pathologic data can be estimated from imaging input using predictive models. MATERIALS AND METHODS: Patients with gliomas were enrolled in a prospective clinical imaging trial between 2013 and 2016. MR imaging was performed with anatomic, diffusion, permeability, and perfusion sequences, followed by image-guided stereotactic biopsy before resection. An imaging description was developed for each biopsy, and multiclass machine learning models were built to predict the World Health Organization grade. Models were assessed on classification accuracy, Cohen κ, precision, and recall. RESULTS: Twenty-three patients (with 7/9/7 grade II/III/IV gliomas) had analyzable imaging-pathologic pairs, yielding 52 biopsy sites. The random forest method was the best algorithm tested. Tumor grade was predicted at 96% accuracy (κ = 0.93) using 4 inputs (T2, ADC, CBV, and transfer constant from dynamic contrast-enhanced imaging). By means of the conventional imaging only, the overall accuracy decreased (89% overall, κ = 0.79) and 43% of high-grade samples were misclassified as lower-grade disease. CONCLUSIONS: We found that local pathologic grade can be predicted with a high accuracy using clinical imaging data. Advanced imaging data improved this accuracy, adding value to conventional imaging. Confirmatory imaging trials are justified.

Clinicopathological and prognostic significance of preoperative serum epidermal growth factor levels in patients with oral squamous cell carcinoma.

Epidermal growth factor (EGF) promotes tumourigenesis and tissue repair of epithelial and mesenchymal cells and has a role in chemotaxis, mitogenesis, cell motility, and cytoprotection. It also enhances the growth of cancers. EGF may therefore have a role in the initiation or promotion of oral carcinogenesis. The cases of 152 patients with oral squamous cell carcinoma whose preoperative serum EGF level was determined by enzyme-linked immunosorbent assay were analyzed retrospectively, along with those of 40 age- and sex-matched controls. Patients with higher levels of EGF were more likely to have neck lymph node metastasis (P=0.026), advanced stage cancer (P=0.04), and a worse survival status (P=0.0019). Multivariate analysis using the Cox proportional hazards model indicated that the EGF level was an independent predictor of poor survival (hazard ratio 1.99, P=0.018). Patients with higher preoperative serum EGF levels had significantly poorer cancer-specific survival by Kaplan-Meier analysis (P=0.032). This study indicates that a higher preoperative serum EGF level is associated with neck lymph node metastasis, more advanced stage, and poor survival. EGF should be considered as a potential prognostic biomarker and a therapeutic target for patients with oral cancer.

[Enhancing Soft-tissue Reattachment with Artificial Mesh in Joint Endoprosthetic Reconstruction for Bone Tumors].

Objective: To investigate the operative method and clinical application of the BARD(®) Mesh in enhancing joint stability and function of endoprosthetic reconstruction for bone tumors. Methods: From Jan 2013 to Jun 2015, the clinical data of 51 patients aged (44.75±23.18) years underwent wide resection of tumor and endoprosthetic reconstruction using the BARD(®) Mesh were collected. Among them, 27 were male and 24 were female. The surgical treatments received by these patients included 5 shoulder arthroplasties, 12 elbow replacements, 12 hip replacements and 32 knee replacements (including 24 femoral tumors and 8 tibial tumors). According to the pathologic type, there were 12 metastatic tumors, 20 osteosarcomas, 7 chondrosarcomas, 5 malignant fibrous histiocytomas, 4 giant cell tumors of bone, 1 Ewing sarcoma, 1 leiomyosarcoma and 1 pigmented villonodular synovitis (pvns). These patients received extensive tumor resection, tumorous prosthesis replacement, preserved articular capsule and muscles repair with artificial mesh and endoprosthesis wrapping. The curative effect including joints range of motion and Musculoskeletal Tumour Society Scores (MSTS) were evaluated. Results: The median follow-up time was (19.75±8.17) months. The drainages were removed out on an average of 4 days after operation. The postoperative complications included 2 superficial incision infection, 1 deep incision infection and 1 osteofascial compartment syndrome, infection or dislocation of prosthesis wasn't observed. The mean active flexion of shoulder joint after replacement was (34.00±10.84)°, mean active abduction was (20.00±9.35)° and the mean MSTS was 19.80±9.54. The superior rate of shoulder flexion function was 0. The mean active flexion of elbow joint after replacement was (75.00±7.07)°, mean active abduction was (-5.00±7.07)° and the mean MSTS was 25.00±2.83. The superior rate of elbow flexion function was 50.0% (1/2). The mean active flexion of hip joint after replacement was (86.67±20.60)°, mean active abduction was (2.08±4.98)° and the mean MSTS was 25.42±1.78. The superior rate of hip flexion function was 83.3% (10/12). The mean active flexion of knee joint after replacement was (89.69±22.39)°, mean active abduction was (-0.63±1.68)° and the mean MSTS was 23.31±2.09. The superior rate of knee flexion function was 50.0%(16/32). Among them, the superior rate of femoral flexion function was 66.7% (16/24), the superior rate of tibial flexion function was 0. All of patients were satisfied with the curative effect of operation at the end of follow-up time. Conclusions: The BARD(®) Mesh may enhance the attachment of soft-tissue to endoprosthesis, improve the joint stability, decrease the endoprosthetic infection and dislocation, facilitate the attachment of tendon to endoprosthesis and recover the muscular motivation after endoprosthetic reconstruction. This plays an important role in joint stability and motivation reconstruction of soft-tissue impairment, effectively prevents surgical complications.

Patient outcomes and amotosalen/UVA-treated platelet utilization in massively transfused patients.

BACKGROUND: Amotosalen/UVA-treated platelet concentrates (PCs) have demonstrated efficacy for treating and preventing bleeding in clinical trials and in routine use; however, most studies were performed in haematology/oncology patients. We investigated efficacy during massive transfusion (MT) in general hospitalized patients. METHODS: Universal amotosalen/UVA treatment (INTERCEPT Blood System) of platelets was introduced at a large Austrian medical centre. We performed a retrospective cohort analysis comparing component use, in-hospital mortality and length of stay after MT that included platelet transfusion, for two periods (21 months each) before and after implementation. RESULTS: A total of 306 patients had MT. Patients were mostly male (74%) and ≥18 years old (99%), including 93 liver transplant, 97 cardiac or vascular surgery and 51 trauma patients. There were no differences in demographics between the periods. Component use on the day and within 7 days of the MT event was unchanged post-IBS implementation, except trauma patients received fewer RBCs on the day. The mean ratio of RBC:platelets:plasma on the day of the MT was close to 1:1:1 in both periods, except for liver transplants with MT who received more plasma components. Overall, in-hospital mortality (preimplementation = 27·6% vs. postimplementation = 24·0%; P = 0·51) and median time to discharge (preimplementation = 27 vs. postimplementation = 23 days; P = 0·37) did not change, except for cardiac and vascular surgery patients who were discharged earlier. CONCLUSION: The introduction of amotosalen/UVA-treated, pathogen-reduced PC did not adversely affect clinical outcomes in massively transfused patients in terms of blood product usage, in-hospital mortality and length of stay for a range of clinical indications for platelet transfusion support.

Impact of platelet pathogen inactivation on blood component utilization and patient safety in a large Austrian Regional Medical Centre.

BACKGROUND: In clinical studies, pathogen inactivation (PI) of platelet concentrates (PC) with amotosalen and UVA light did not impact patient risk for haemorrhage but may affect transfusion frequency and component utilization. We evaluated the influence of platelet PI on PC, red cell concentrate (RCC) and plasma use and safety in routine practice in a large regional hospital. STUDY DESIGN AND METHODS: Comparative effectiveness of conventional vs. PI-treated PC was analysed during two 21-month periods, before and after PI implementation. RESULTS: Similar numbers of patients were transfused in the pre-PI (control, 1797) and post-PI (test, 1694) periods with comparable numbers of PC (8611 and 7705, respectively). The mean numbers of PC per patient transfused (4·8 vs. 4·5, P = 0·43) were not different but days of PC support (5·9 vs. 5·0, P < 0·01) decreased. Most patients received RCC (86·8% control vs. 84·8% test, P = 0·90) with similar mean numbers transfused (10·8 vs. 10·2 RCC, P = 0·22), and fewer patients (55·4% control vs. 44·7% test, P < 0·01) received less plasma units (mean 9·9 vs. 7·8, respectively, P < 0·01) in the test period. The frequencies of transfusion-related adverse events (AE) were comparable (1·3% vs. 1·4%, P = 0·95). Analysis of haematology-oncology (522 control, 452 test), cardiac surgery (739 control, 711 test), paediatric (157 control, 130 test) and neonate (23 control, 20 test) patients revealed no increase in PC, plasma and RCC utilization, or AE. CONCLUSION: Component utilization and patient safety were not impacted by adoption of PI for PC. RCC use per patient was comparable, suggestive of no increase in significant bleeding.

Kallistatin, a novel anti-angiogenesis agent, inhibits angiogenesis via inhibition of the NF-κB signaling pathway.

Development of a novel angiogenesis inhibitor will be essential for the improvement of therapeutics against cancer. Kallistatin had been recognized as an endogenous angiogenesis inhibitor. Here, we demonstrated kallistatin's strong anti-angiogenesis and anti-metastasis activity stimulated by breast cancer cells (MCF-7) and its mechanism of action in vitro. The anti-angiogenesis effect in vivo was evaluated by chicken chorioallantoic membrane (CAM) neovascularisation. Because of the underlying molecular mechanism of its anti-angiogenesis activity remains poorly understood. In this study, we examined whether the NF-κB signaling pathway was involved in the anti-angiogenesis and anti-metastasis activity of kallistatin. Kallistatin significantly inhibited TNF-α-induced nuclear factor-κB activation in a dose-dependent manner. Addition of kallistatin inhibited TNF-α induced IκBα degradation; phosphorylation of IκBα kinase (IKK), nuclear factor-κB-p65 protein; and nuclear translocation of p65/50. Meanwhile, we investigated the effects of kallistatin on the expression of vascular endothelial growth factor (VEGF) and other angiogenesis-related gene in human umbilical vein endothelial cells (HUVECs). We found that kallistatin decreased the expression of VEGF and some angiogenesis-related genes, which promoted angiogenesis in cancer. Taken together, we suggested that kallistatin would inhibit tumor angiogenesis via inhibition of the NF-κB signaling pathway and finally abrogate NF-κB-dependent gene expression. All the results revealed that kallistatin would have potential as a novel.

Recombinant human kallistatin inhibits angiogenesis by blocking VEGF signaling pathway.

Kallistatin has been recognized as an endogenous angiogenic inhibitor. However, the underlying molecular mechanism remains poorly understood. Taking it into account that vascular endothelial growth factor (VEGF) has been implicated in all aspects of normal and pathological vasculogenesis and angiogenesis. In this study, we investigated whether VEGF signaling pathway was impacted by the anti-angiogenic effect of recombinant human kallistatin (rhKal). We found that the rhKal inhibited proliferation as well as induced apoptosis of cultured human umbilical vein endothelial cells (HUVECs) in both concentration- and time-dependent manners. The rhKal also suppressed the VEGF-induced migration and tube formation of HUVECs. Furthermore, our data revealed that the rhKal suppressed the VEGF165-stimulated tyrosine phosphorylation of VEGFR-2 as well as its downstream signal molecular activation. The inhibition of receptor phosphorylation was correlated with a decrease in VEGF-triggered phosphorylation of angiogenesis signal molecules AKT and ERK, but not stress-related JNK. Taken together, these findings added the knowledge for us to understand the anti-angiogenic mechanism of kallistatin, which suggested that the rhKal could be worth as a candidate compound for further development for the purpose of anti-angiogenic therapies.

MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo.

MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375-mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3'-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase-PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2'-O-methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo, and highlight the therapeutic potential of miR-375 in HCC treatment.

The bile steroid chenodeoxycholate is a potent antagonist at NMDA and GABA(A) receptors.

The bile steroids (BS) cholic acid and chenodeoxycholic acid are produced in hepatocytes and in the brain. Nothing is known about neuronal actions of BS. Deficiency in a 27-hydroxylase enzyme coincides with reduced production of chenodeoxycholic acid (CDCA) and a relative increase in cholic acid in an inherited lipid storage disease, cerebrotendinous xanthomatosis, characterized by neurological dysfunctions, which can be treated by dietary CDCA. We have examined the modulation of hypothalamic network activity by nine common BS. Cholate and CDCA significantly reduced the firing of hypothalamic neurons and synchronized network activity with CDCA being nearly 10 times more potent. The synthetic BS dehydrocholate synchronized the activity without affecting the firing rate. Gabazine, a GABA(A) receptor antagonist, occluded synchronization by BS. Whole-cell patch clamp recordings revealed a block of NMDA- and GABA(A)-receptors by BS. Potencies of nine common BS differed between NMDA and GABA(A) receptors, however in both cases they correlated with BS affinities for albumin but not with their lipophilicity, supporting a direct action at ligand gated ion channels. GABAergic synaptic currents displayed a faster decay under BS. Our data provide new insight into extrahepatic functions of BS revealing their neuroactive potential.

Analysis of thrombin-antithrombin complex contents in plasma and hematoma fluid of hypertensive intracerebral hemorrhage patients after clot removal.

BACKGROUND AND PURPOSE: Animal experiments indicate that the cerebral thrombin is associated with secondary brain damage after intracerebral hemorrhage (ICH). This study was aimed to investigate the concentrations of thrombin-antithrombin complex (TAT) in hematoma fluid and plasma of the patients with ICH after surgery and analyze the correlation between TAT complex levels and severity of ICH. METHODS: Sixty patients with ICH were enrolled. Craniotomy for removal of intracranial blood clot was performed within 24h after ICH. Hematoma fluid and plasma were collected on postoperative days 1, 2, and 4. The plasma obtained from healthy subjects and cerebrospinal fluid from patients without cerebrovascular diseases served as controls, respectively. Enzyme-linked immunosorbent assay was used to determine the concentrations of TAT complex in the patients and controls. RESULTS: TAT complex concentrations in both postoperative plasma and hematoma fluid of patients with ICH were significantly higher than those of the controls (P<0.01). In patients with ICH, hematoma fluid had a higher TAT complex level than plasma (P<0.01). The preoperative hemorrhage volume and postoperative TAT complex levels in plasma and hematoma fluid correlated positively with National Institutes of Health stroke scale and negatively with Glasgow coma score (P<0.01). CONCLUSION: This study indicates that TAT complex levels of plasma and hematoma fluid correlate positively with the severity of ICH. Determination of the plasma TAT complex concentration is helpful for the evaluation of the severity of post-ICH brain injury.

Genomic sequence of an avian paramyxovirus type 1 strain isolated from Muscovy duck (Cairina moschata) in China.

The complete sequence of an avian paramyxovirus type 1 (APMV-1) strain, FP1/02, isolated from Muscovy duck in China, was determined. Sequence analysis indicated that the complete genome of strain FP1/02 contained 15,192 nucleotides (nt), following the rule of six. The genome contained an extra 6-nt insertion in the non-coding region of the NP gene when compared with other APMV-1 strains, such as strains La Sota and Beaudette C. The cleavage site of the F protein was (112)R-R-Q-K-R↓F(117), indicating that the FP1/02 strain was virulent, but the morbidity and mortality varied with the species of duck. Genotypic analysis based on the F gene revealed that APMV-1 FP1/02 was a member of genotype VII. Phylogenetic analysis showed that the FP1/02 strain shared high identity with other APMV-1 strains such as ZJ1, SF02 and NA-1 isolated from geese.

Hair follicle: a reliable source of recipient origin after allogeneic hematopoietic stem cell transplantation.

Blood, buccal swab and hair follicles are among the most commonly used sources for forensic science, parentage testing and personal identification. A total of 29 patients who have had a sustained engraftment from 15 months to 21.5 years after allogeneic hematopoietic stem cell transplantation (HSCT) without rejection, relapse or chronic GVHD involving oral mucosa were enrolled for a chimerism study. PCR-amplified short tandem repeat analyses were conducted per patient every 3 months for at least three consecutive times. The results for blood were all donor type except one who had a mixed chimerism, 14.5 years after receiving a transplant for lymphoma. As for buccal swab, mixed chimerism ranging from 10 to 96% donor origin was noted for 28 recipients except the one who had mixed chimerism of blood and retained total recipient type. In contrast, hair follicles were 100% recipient type for the entire group. It is concluded that the hair follicle is devoid of adult stem cell plasticity and may serve as a reliable source of recipient's origin when pre-transplant DNA fingerprinting or reference DNA is not available for people who have successfully received allogeneic HSCT while in need of a personal identification.

Prevalence of erectile dysfunction and impacts on sexual activity and self-reported intercourse satisfaction in men older than 40 years in Taiwan.

In order to assess the prevalence of erectile dysfunction (ED), and its association with chronic diseases and impact upon sexual activity and satisfaction during sexual intercourse, a reproductive survey was conducted among 1002 Taiwanese men aged over 40 y. The information collected comprised age, gender, level of education, history of chronic diseases, and self-reported data pertaining to erectile function, sexual activity, and sexual satisfaction during sexual intercourse. The prevalence of ED amongst study subjects was 17.7%, and the frequency increased with age. A history of chronic diseases were significantly associated with ED (P<0.05). A reduced incidence of sexual activity and a decreased level of satisfaction during sexual intercourse were observed among subjects suffering from ED as compared to those not suffering such a condition. In conclusion, based upon the results of a community-based survey the prevalence of ED among Taiwanese men aged 40 y or more was 17.7% and it increased with age. It was also found that ED was associated with various chronic diseases and that it exerted a negative impact upon sexual activity and the level of satisfaction associated with its conduct.

Production of biologically active tethered ovine FSHbetaalpha by the methylotrophic yeast Pichia pastoris.

The pituitary-derived glycoprotein hormone FSH plays a central role in controlling vertebrate gonadal function. In female mammals the maturation of ovarian follicles is critically dependent upon stimulation by FSH. Moreover, injection of exogenous FSH is used extensively to stimulate increased numbers of follicles to ovulate. Structurally FSH is a heterodimeric glycoprotein composed of two non-covalently associated polypeptide subunits. The tertiary structures of both the alpha- and beta-subunits are constrained by intramolecular disulphide bonds and are post-translationally modified with two N-linked carbohydrate moieties, the structure of which appears to modulate in vivo biological activity. Here we report the expression of ovine FSH (oFSH) as a biologically active single-chain polypeptide using the methylotrophic yeast Pichia pastoris. Sequences encoding the mature oFSH alpha- and beta-proteins were fused to form a gene encoding a fusion protein with the C-terminus of the beta-chain joined to the N-terminus of the alpha-chain, with the chains separated by a two amino acid linker sequence. This fusion gene was itself fused to two alternative Pichia leader sequences (mating factor alpha and acid phosphatase) and transformed into the Pichia strains GS115 and SMD1168. The recombinant fusion protein (oFSHbetaalpha) was expressed at approximately 0.1 microg/ml in 'shake-flask' cultures. The Pichia-expressed tethered protein was biologically active in an in vitro bioassay, had a molecular mass of 28 kDa, as determined by SDS-PAGE, and bound the bovine FSH receptor with a binding profile similar to that of native oFSH.

Cytokine release in febrile non-haemolytic red cell transfusion reactions.

BACKGROUND AND OBJECTIVES: The aim of this study was to elucidate the role and identity of cytokines involved in febrile non-haemolytic red cell transfusion reactions (FNHTRs). MATERIALS AND METHODS: Eighty-one patients experiencing transfusion reactions after receiving packed red blood cells (RBCs) were divided into three groups, as follows, based on the reaction experienced: FNHTRs (n = 60); chills without fever (n = 8); and allergic reaction with urticaria (n = 13). The concentrations of interleukin (IL)-1beta, IL-6, IL-8 and tumour necrosis factor (TNF)-alpha were measured in the packed transfused unit and patients' plasma by using enzyme immunoassays. Wilcoxon's matched-pairs signed test was used to compare the difference in cytokine levels in patients' plasma before and after transfusion. The Kruskal-Wallis test was used first, followed by the Mann-Whitney test, to compare the pretransfusion cytokine levels in patients' plasma between groups and to compare the cytokine levels in packed RBCs transfused to each group of patients. RESULTS: The age of the implicated packed RBC was 11.5 +/- 5.7 days. Significant increases were observed in IL-6 (P < 0.001) and IL-8 (P < 0.001) patients' plasma levels, but not in IL-1beta or TNF-alpha levels, in those patients exhibiting FNHTR. No changes were observed in the patients' plasma samples of the other groups. Cytokine levels in the RBC concentrate supernatants were not appreciably elevated. CONCLUSIONS: Transfusion of packed RBCs may significantly increase intravascular levels of IL-6 and IL-8 in patients with FNHTRs.

Distinct CD8 T cell functions mediate susceptibility to histoplasmosis during chronic viral infection.

It has long been recognized that some viral infections result in generalized immune suppression. In acute infections, this period of suppressed immunity is relatively short. However, chronic infections associated with a prolonged period of immune suppression present far greater risks. Here, we examined the role of CD8 T cell responses following viral infection in immunity to systemic histoplasmosis. Although wild-type mice with systemic histoplasmosis were able to control the infection, those simultaneously infected with lymphocytic choriomeningitis virus clone 13 showed reduced immunity with greater fungal burden and high mortality. The immune suppression was associated with loss of CD4 T cells and B cells, generalized splenic atrophy, and inability to mount a granulomatous response. Removing the anti-viral CD8 T cells in the coinfected mice enabled them to reduce the fungal burden and survive the infection. Their lymphoid organs were replenished with CD4 T and B cells. In contrast to wild-type mice, perforin-deficient mice infected with lymphocytic choriomeningitis virus clone 13 and Histoplasma showed an absence of immunopathology, but the animals still died. These results show that CD8 T cells can suppress immunity through different mechanisms; although immunopathology is perforin-dependent, lethality is perforin-independent.

Transurethral microwave thermotherapy for symptomatic benign prostatic hyperplasia: long-term durability with Prostcare.

OBJECTIVE: To evaluate the long-term durability of transurethral microwave thermotherapy (TUMT) with Prostcare for symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: From August 1993 to July 1994, a total of 65 patients with symptomatic BPH who underwent TUMT using the Prostcare apparatus (Bruker Spectospin, Wissembourg, France) with low-energy protocol (maximal power 52 W) were enrolled into a short-term evaluation. Subsequent follow-up information was collected in July 1999. If patients had had any further therapy for BPH, the date of retreatment was considered as an endpoint of TUMT efficacy. If no further therapy for BPH had been needed, they were re-assessed for overall satisfaction. RESULTS: The median follow-up period was 49 months. Twenty patients were excluded for various reasons, including 17 with loss of follow-up and 3 with new diseases that could affect the voiding status. Thirty-eight (84.4%) of 45 valuable patients had received further therapy for BPH, including medication (n = 21, 46.7%), and endoscopic surgery (n = 17, 37.7%). The times to pharmacologic or endoscopic retreatment after TUMT were 8.9+/-11.1 and 23.0+/-14.4 months, respectively (p = 0.0003, log rank test). Only 7 (15.5%) patients had no further treatment, with 3 having satisfactory improvements, but 4 feel dissatisfied yet not needing any further therapy. In addition, 2 patients complained of erectile dysfunction after TUMT and 1 was diagnosed with prostate cancer 50 months after TUMT. In addition, there was no significant difference for all baseline values among three groups with no retreatment or retreatment with medication or endoscopic surgery. CONCLUSION: At the 5-year follow-up, the long-term durability of low-energy TUMT with Prostcare is only exhibited in a few patients and the overall retreatment rate was 84.4%. Thus, patient should be informed of the high probability of supplementary treatment after TUMT.