Effects of percutaneous balloon mitral valvuloplasty and exercise training on the kinetics of recovery oxygen consumption after exercise in patients with mitral stenosis

AIMS: Kinetics of recovery oxygen consumption after exercise plays an important role in determining exercise capacity. This study was performed to assess the kinetics of recovery oxygen consumption in mitral stenosis and evaluate the effects of percutaneous balloon mitral valvuloplasty and exercise training on the kinetics. METHODS AND RESULTS: Thirty patients with mitral stenosis (valve area < or =1.0 cm2) and same sized age- and size-matched healthy volunteers were included for this study. All subjects performed maximal upright graded bicycle exercise. Thirty consecutive patients who underwent successful percutaneous balloon mitral valvuloplasty (valve area > or =1.5 cm2 and mitral regurgitation grade < or =2), were randomized to an exercise training group or non-training group. The exercise group performed daily exercise training for 3 months. Half-recovery time of peak oxygen consumption was significantly delayed in mitral stenosis as compared to normal subjects (120+/-42 s vs 59+/-5, P<0.01). Peak oxygen consumption (ml x min(-1) x kg(-1)) was significantly increased in both the training (16.8+/-4.9 to 25.3+/-6.9) and non-training groups (16.3+/-5.1 to 19.6+/-6.0) 3 months after percutaneous balloon mitral valvuloplasty. Half-recovery time of peak oxygen consumption was significantly shortened in the training group (124+/-39 to 76+/-13, P<0.01), but not in the non-training group (114+/-46 to 109+/-44 s, P=0.12) at 3 months follow-up. The degrees of symptomatic improvement after percutaneous balloon mitral valvuloplasty were more closely correlated with the changes of the half-recovery time of peak oxygen consumption than those of peak oxygen consumption. CONCLUSION: Kinetics of recovery oxygen consumption was markedly delayed in mitral stenosis, which was improved after exercise training but not after percutaneous balloon mitral valvuloplasty alone. These results suggest that adjunctive exercise training may be useful for improvement of recovery kinetics and subjective symptoms after percutaneous balloon mitral valvuloplasty.     

Post-transplant changes of segment 4 after living related liver transplantation

Cocaine-induced thrombosis has been reported in the literature; however, its mechanism is not fully understood. Most cases are of small caliber vessels, such as the coronaries and cerebral vasculature. We report a case of a 36-year-old man with signs and symptoms of acute arterial insufficiency in his right lower extremity. At angiography, the right common iliac artery and the popliteal artery were occluded. The patient was successfully treated with thrombolytic therapy. Cocaine-induced thrombosis should be suspected in a patient with history of cocaine abuse who presents with acute arterial insufficiency in an extremity, without an identifiable source.     

Accuracy of grading gliomas on CT-guided stereotactic biopsies: a survival analysis

The class I tyrosine kinase growth-factor receptors include epidermal growth factor receptor (EGFR), ErbB2 (c-erbB-2, HER-2/neu), ErbB3 and ErbB4. To elucidate their role in the regulation of homeostasis and carcinogenesis, we examined the expression of the receptors in normal urothelium and in urothelial carcinoma by immunohistochemistry. EGFR was expressed in the basal cells of normal urothelium, while ErbB2, ErbB3 and ErbB4 were present mainly in the superficial layer. A distinct reciprocal distribution was observed between the EGFR and the remaining members of the subclass (P = 0.0001). Both BCL-2 protein and Ki-67 antigen (MIB-1) showed a strong positive association with EGFR (P = 0.002) and an inverse correlation with ErbB2, ErbB3 or ErbB4 (P = 0.0004, 0.0000, and 0.001, respectively). With regard to carcinoma, there was no important relationship between receptor overexpression and tumour grading (P > 0.1), while only EGFR overexpression was correlated with muscular invasion (P = 0.02). Coexpression of EGFR-ErbB3 and ErbB3-ErbB4 was more often detected in high-grade tumours and correlated with the extent of tumour invasion. Our data indicate that class I receptors are differentially expressed in normal urothelium in vivo, but an orchestrated expression pattern does not exist during tumorigenesis.     

Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia

Glutathione peroxidase, a selenium-containing enzyme, is believed to protect cells from the toxicity of hydroperoxides. The physiological role of this enzyme has previously been implicated mainly using animals fed with a selenium-deficient diet. Although selenium deficiency also affects the activity of several other cellular selenium-containing enzymes, a dramatic decrease of glutathione peroxidase activity has been postulated to play a role in the pathogenesis of a number of diseases, particularly those whose progression is associated with an overproduction of reactive oxygen species, found in selenium-deficient animals. To further clarify the physiological relevance of this enzyme, a model of mice deficient in cellular glutathione peroxidase (GSHPx-1), the major isoform of glutathione peroxidase ubiquitously expressed in all types of cells, was generated by gene-targeting technology. Mice deficient in this enzyme were apparently healthy and fertile and showed no increased sensitivity to hyperoxia. Their tissues exhibited neither a retarded rate in consuming extracellular hydrogen peroxide nor an increased content of protein carbonyl groups and lipid peroxidation compared with those of wild-type mice. However, platelets from GSHPx-1-deficient mice incubated with arachidonic acid generated less 12-hydroxyeicosatetraenoic acid and more polar products relative to control platelets at a higher concentration of arachidonic acid, presumably reflecting a decreased ability to reduce the 12-hydroperoxyeicosatetraenoic acid intermediate. These results suggest that the contribution of GSHPx-1 to the cellular antioxidant mechanism under normal animal development and physiological conditions and to the pulmonary defense against hyperoxic insult is very limited. Nevertheless, the potential antioxidant role of this enzyme in protecting cells and animals against the pathogenic effect of reactive oxygen species in other disorders remains to be defined. The knockout mouse model described in this report will also provide a new tool for future study to distinguish the physiological role of this enzyme from other selenium-containing proteins in mammals under normal and disease states.     

Midazolam for caudal analgesia in children: comparison with caudal bupivacaine

In a randomized, double-blind study we have examined the analgesic efficacy of caudal administration of midazolam, bupivacaine, or a mixture of both drugs in 45 children, undergoing inguinal herniotomy. They were allocated randomly into three groups (n = 15 in each) to receive a caudal injection of either 0.25% bupivacaine 1 ml.kg-1 with or without midazolam 50 micrograms.kg-1 or midazolam 50 micrograms.kg-1 with normal saline 1 ml.kg-1. There were no differences in quality of pain relief, postoperative behaviour or analgesic requirements between the midazolam group and the other two groups. Times to first analgesic administration (paracetamol suppositories) were longer (P < 0.001) in the bupivacaine-midazolam group than in the other two groups. Further, the bupivacaine-midazolam group received fewer (P < 0.05) doses of paracetamol than the bupivacaine group. Side effects such as motor weakness, respiratory depression or prolonged sedation were not observed in patients who received caudal epidural midazolam only. We conclude that caudal midazolam in a dose of 50 micrograms.kg-1 provides equivalent analgesia to bupivacaine 0.25%, when administered postoperatively in a volume of 1 ml.kg-1 for children following unilateral inguinal herniotomy.     

Formation of native hepatitis C virus glycoprotein complexes

The hepatitis C virus (HCV) glycoproteins (E1 and E2) interact to form a heterodimeric complex, which has been proposed as a functional subunit of the HCV virion envelope. As examined in cell culture transient-expression assays, the formation of properly folded, noncovalently associated E1E2 complexes is a slow and inefficient process. Due to lack of appropriate immunological reagents, it has been difficult to distinguish between glycoprotein molecules that undergo productive folding and assembly from those which follow a nonproductive pathway leading to misfolding and aggregation. Here we report the isolation and characterization of a conformation-sensitive E2-reactive monoclonal antibody (H2). The H2 monoclonal antibody selectively recognizes slowly maturing E1E2 heterodimers which are noncovalently linked, protease resistant, and no longer associated with the endoplasmic reticulum chaperone calnexin. This complex probably represents the native prebudding form of the HCV glycoprotein heterodimer. Besides providing a novel reagent for basic studies on HCV virion assembly and entry, this monoclonal antibody should be useful for optimizing production and isolation of native HCV glycoprotein complexes for serodiagnostic and vaccine applications.     

5-fluorouracil and low-dose leucovorin as surgical adjuvant therapy from viewpoint of long-term outcome

Biochemical modulation of 5-FU by leucovorin (LV) has been demonstrated to increase the therapeutic effect compared to single agent 5-FU in the treatment of patients (pts) with advanced colorectal cancer. The purpose of this study was to determine the effectiveness of the 5-FU + LV combination as adjuvant therapy following surgery in pts with Dukes' B, C colon cancer. Pts were entered in a stratified clinical trial comparing two different combination chemotherapeutic regimens to single agent 5-FU, given orally as a control. This report summarized the result of treatment in 61 pts who were 5-FU oral alone and 32 pts who were 5-FU (375 mg/m2) and low-dose LV (20 mg/m2) intravenously for 5 days with 5-FU oral intake. 5-FU with LV regimen was associated with an improved survival compared with the single agent 5-FU oral intake (p < 0.05). 5-FU with LV regimen resulted in less recurrence in liver and lung compared with single-agent 5-FU oral intake.     

Quality of life (QOL) assessment of MIP (mitomycin, ifosfamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC)

BACKGROUND: Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. METHODS: From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. RESULTS: The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). CONCLUSIONS: MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.