Abnormal movements in brindled mutant mouse heterozygotes: as related to the development of their offspring--biochemical and morphological studies

As a possible preventive measure for brain dysfunction in Menkes disease, prenatal treatment by maternal administration of zinc, vitamin E and copper was examined in brindled mutant mice. During pregnancy and lactation, female heterozygous mice received 20 ppm zinc or 0.004% alpha-tocopherol acetate (vitamin E) throughout and 6 ppm copper from gestational day 13 in the drinking fluid, ad libitum. The maternal administration of zinc and vitamin E, as antioxidants, or copper resulted in decreased fetal and neonatal death of offspring, especially those of hemizygous males, as compared with the administration of water only. When offspring did not grow, maternal abnormal movements, which comprised rotatory movements of high speed with tremor and ataxia, were frequently observed. In the heterozygotes with abnormal movements, the level of lipid peroxidation in cerebrum and the concentration of copper in kidney were much higher than those in the heterozygotes with normal movement. Morphologically, in cerebellum of the heterozygotes with abnormal movements, the loss of Purkinje cells, abundance of lipofuscin granules and abnormal mitochondria or degenerative bodies of high electron density were frequently observed, as compared with heterozygotes with normal movement. These findings suggest that the development of hemizygous male mice may be influenced by both copper and oxygen radical metabolism.     

NATURAL ORIFICE TRANSLUMENAL ENDOSCOPIC SURGERY FOR PREOPERATIVE STAGING IN A PANCREATIC CANCER PATIENT

Background: Many experimental studies have shown the technical feasibility of natural orifice translumenal endoscopic surgery (NOTES). We report the first clinical application of natural orifice transgastric endoscopic peritoneoscopy in Japan for preoperative staging in a patient with pancreatic cancer. Methods: A submucosal tunnel was created for safe peritoneal access and secure closure of the gastric‐incision site. Results: Transgastric peritoneoscopy provided an excellent view and allowed approach to various areas of the abdominal cavity. After confirmation of operative curability, the patient underwent an open standard operation without complication. Conclusions: Natural orifice transgastric endoscopic peritoneoscopy for cancer staging using the submucosal tunnel technique appears to be feasible and safe.     

Improved Short-Term Outcomes of Primary Coronary Stenting Compared to Primary Balloon Angioplasty in Acute Myocardial Infarction at Experienced Centers: The PAMI Study Group Experience

To study the additive benefits of routine stent implantation in patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) at experienced centers, we compared the outcomes of the 982 patients undergoing PTCA for acute myocardial infarction (AMI) in the Primary Angioplasty in Myocardial Infarction-2 (PAMI-2) trial (only 1% of whom were stented) to the 312 patients in the PAMI Stent Pilot Trial (236 [76%] of whom were stented). The inclusion and exclusion criteria, PTCA methodology, and definitions used were prespecified to be identical between the two trials. Compared to the primary PTCA approach in PAMI-2, the strategy of stenting all eligible lesions in the PAMI Stent Pilot Trial was associated with reduced rates of in-hospital death (0.6% vs 2.7%, P = 0.03), reinfarction (1.3% vs 4.6%, P = 0.008), recurrent ischemia (3.5% vs 11.6%, P < 0.0001), target vessel revascularization (7.3% vs 11.4%, P = 0.04), and a shorter hospital stay (6.4 ± 4.4 vs 7.1 ± 6.2 days, P = 0.01). By multiple logistic regression analysis in 1,294 patients, stent implantation versus PTCA only was the strongest predictor of freedom from the composite in-hospital end point of death, reinfarction, or target vessel revascularization (TVR) (8.3% vs 15.0%, multivariate odds ratio = 0.4, P < 0.0001). These data strongly suggest that despite the excellent results achieved when primary PTCA is performed by experienced operators, the short-term outcomes of mechanical reperfusion can be further improved by a primary stent strategy.     

Synergistic effect of electric pulses and bleomycin on cultured rabbit subconjunctival fibroblasts

• Background: The combined effect of electric pulses (EP) and antiproliferative agents on the proliferation of rabbit Tenon’s capsule fibroblasts was investigated. • Methods: Rabbit Tenon’s capsule fibroblasts were cultured. Some of these cells were exposed to various intensities of EP alone (500–2500 V/cm). Other cells were then exposed for 30 min to an antiproliferative agent: bleomycin (BLM; 0.0005-50 μmol/l), mitomycin C (MMC; 0.0005-50 μmol/l), 5-fluorouracil (5-FU; 0.05-5000 μmol/l), or streptomycin (SM; 0.0005-50 μmol/l) with or without EP (2000 V/cm, 99 μs, eight pulses). Cell proliferation was assessed by cell counting on day 3 and by a ³H-thymidine uptake assay. DNA fragmentation was assessed by flow-cytometric analysis and agarose gel electrophoresis. • Results: A significant reduction in the cell number was observed only at 2500 V/cm (P<0.05). BLM, MMC and 5-FU treatment inhibited cell proliferation in a dose-dependent manner either with or without EP (ID₅₀: BLM alone, 0.029 μmol/l; BLM and EP, 0.00022 μmol/l; MMC alone, 41.6 μmol/l; MMC and EP, 27.5 μmol/l; 5-FU alone, 1045 μmol/l; 5-FU and EP, 690.2 μmol/l; P<0.05). EP treatment induced an inhibitory effect of BLM on cell proliferation which was 100 times more prominent than BLM alone (0.0005 μmol/l of BLM alone 103.4 ± 4.4%, 0.0005 μmol/l of BLM and EP 26.0 ± 4.4%; P = 0.021). BLM treatment with EP also augmented the apoptotic-like DNA fragmentation in both a flow-cytometric DNA histogram and agarose gel electrophoresis. • Conclusion: EP treatment enhanced the inhibitory effect of BLM on the cell proliferation of Tenon’s capsule fibroblasts of rabbits. The combination of electric pulses and antiproliferative drug treatments may therefore reduce the necessary dose of antiproliferative agents in filtering surgery.     

Immunohistological localization of apolipoproteins in the glomeruli in renal disease: specifically apoB and apoE

Recently it has become clear that abnormalities of the lipid metabolism may play a large role in the progression of renal diseases. To investigate the relationship between lipids and kidney tissues, the authors employed an immunofluorescent technique to determine the presence of apolipoprotein (apo) B and E in kidney tissue, particularly the glomeruli, and analyzed the relationship between their deposition and the clinical and histological findings of a total of 49 patients with persistent proteinuria and/or hematuria (age range: 10 to 62 years). The patients were divided into 4 groups, as follows: both apoB and apoE negative cases (Group 1; 17 cases), apoB alone positive (Group 2; 7 cases), apoE alone positive (Group 3; 10 cases) and both apoB and apoE positive cases (Group 4; 15 cases). Group 2 had more severe proteinuria and a higher level of total cholesterol than Group 1. Group 3 exhibited a higher incidence of glomerular adhesion and interstitial changes than Group 1. Group 4, on the other hand, exhibited more severe mesangial hypercellularity and a higher incidence of glomerular sclerosis and interstitial scarrings than Group 1, a higher incidence of glomerular sclerosis than Group 2, more severe proteinuria, higher serum levels of total cholesterol, and lower serum levels of total protein than Groups 1 and 3 and higher level of uric acid than Group 1. These results suggest that the deposition of apoB and apoE accelerates the progression of mesangial lesions, resulting in greater proteinuria and glomerular sclerosis.     

PROSTATIC CANCER PRESENTING AS METASTATIC ADENOCARCINOMA OF SPHENOID SINUS

Prostatic cancer is commonly manifested by obstructive uropathy, regional lymphatic metastases, and hematogenous metastases to the axial skeleton. It is relatively rare that Initial signs begin with the involvement of other sites. Intracranial metastases especially are seldom found and may be unfamiliar to not only pathologists but also to physicians. In this article, we present a case where the metastasis was first manifest as a sphenoid sinus tumor prior to the demonstration of the primary site and the prostate was confirmed to be primary by biopsy specimen with immunoperoxidase method. In addition to discussing the route of the tumor spread, we deal with a prostatic specific antigen efficient for identifying the primary site.     

Comparison of local International Sensitivity Index calibration and ''Direct INR'' methods in correction of locally reported International Normalized Ratios: an international study

BACKGROUND: It is no longer feasible to check local International Normalized Ratios (INR) by the World Health Organization International Sensitivity Index (ISI) calibrations because the necessary manual prothrombin time technique required has generally been discarded. OBJECTIVES: An international collaborative study at 77 centers has compared local INR correction using the two alternative methods recommended in the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis guidelines: local ISI calibration and 'Direct INR'. METHODS: Success of INR correction by local ISI calibration and with Direct INR was assessed with a set of 27 certified lyophilized plasmas (20 from patients on warfarin and seven from normals). RESULTS: At 49 centers using human thromboplastins, 3.0% initial average local INR deviation from certified INR was reduced by local ISI calibration to 0.7%, and at 25 centers using rabbit reagents, from 15.9% to 7.5%. With a minority of commercial thromboplastins, mainly 'combined' rabbit reagents, INR correction was not achieved by local ISI calibration. However, when rabbit combined reagents were excluded the overall mean INR deviation after correction was reduced further to 3.9%. In contrast, with Direct INR, mean deviation using human thromboplastins increased from 3.0% to 6.6%, but there was some reduction with rabbit reagents from 15.9% to 10% (12.3% with combined reagents excluded). CONCLUSIONS: Local ISI calibration gave INR correction for the majority of PT systems but failed at the small number using combined rabbit reagents suggesting a need for a combined reference thromboplastin. Direct INR correction was disappointing but better than local ISI calibration with combined rabbit reagents. Interlaboratory variability was improved by both procedures with human reagents only.     

Venous air embolism following repositioning from sitting to supine

We have experienced a patient in whom venous air embolism reoccurred, when the patient's position was changed from sitting to supine. A 40 year old male with Arnold-Chiari malformation underwent suboccipital decompression and cervical laminectomy under the sitting position. During surgery, three episodes of venous air embolism were detected by high pitched sound through precordial ultrasound Doppler stethoscope, an abrupt increase in pulmonary arterial pressure, a decrease in end-tidal carbon dioxide concentration; and a small amount of bubbled air was removed from the central venous catheter. At the end of surgery when the patient was turned to supine position, the signs of venous air embolism reappeared and 3 ml of bubbled air was also removed. This case suggests that there is some remaining air in the large veins of the upper part of the body once the air embolism has occurred during sitting position and thus we need to confirm that no air is left in the large veins before repositioning. We should be cautious of reoccurrence of venous air embolism whenever patient's position is changed.