Extensive lymphadenectomy for thoracic esophageal carcinoma: A two-stage operation for high-risk patients

Extensive lymphadenectomy (ELA) for esophageal carcinoma has always been limited to low-risk patients; however, we have developed a two-stage operation which extends the indications for ELA to include certain high-risk patients. Of 70 patients who underwent transthoracic subtotal esophagectomy for thoracic esophageal carcinoma between 1986 and 1991, 48 qualified for ELA which was performed on 45, including 27 low-risk patients (group A) whom underwent the traditional one-stage operation, while 18 high-risk patients underwent the two-stage operation (group B). The number of hospital deaths and postoperative complications was similar between the two groups. The median survival was 26 months in group B and 17 months in group A. The 40-day delay in resection of the neck and abdominal nodes in the two-stage operation did not significantly affect lymph node metastases, postoperative recurrence, or long-term survival. Thus, the two-stage operation is an oncologically meaningful approach to the treatment of high-risk patients who present with thoracic esophageal carcinoma.     

Peritoneoscopic Findings of Autoimmune Hepatitis

Abstract: To clarify the morphologic differences between hepatitis C virus (HCVI-negative autoimmune hepatitis (AIH) and HCV-positive AIH, peritoneoscopic findings were studied. Among twenty three patients with AIH according to the Japanese criteria (1992), 15 were HCV-negative and 8 were HCV-positive. The terms grooved depression, coarse depression, coarse elevation, coarse undulation, and round-shaped reddish marking (RM) were used in this study to evaluate the peritoneoscopic findings. Grooved depressions, coarse depressions, coarse elevations, coarse undulations and round-shaped RMs were all common findings (53%, 87%, 73%, 80%, and 80%, respectively) in HCV-negative AIH patients, but they were less common (13%, 25%, 13%, 13%, and 0%, respectively) in HCV-positive AIH patients. This study revealed that HCV-negative AIH patients had different peritoneoscopic findings from HCV-positive AIH patients. Thus HCV-negative AIH may be typical AIH, and HCV-positive AIH may essentially be a subset of type C chronic hepatitis.     

Prediction of iopromide reduction rates during haemodialysis using an in vitro dialysis system.

BACKGROUND: In clinical studies, it has been difficult to evaluate the influence of haemodialysis (HD) parameters on HD clearance (CL(HD)) and reduction rate (RR) of non-ionic contrast medium during HD sessions. We therefore predicted clinical values of CL(HD) and RR of iopromide, a non-ionic contrast medium, from findings obtained from in vitro experiments, and confirmed that these predictive values were comparable with the actual values in clinical cases. METHODS: We developed a correlation equation for predicting CL(HD) on the basis of in vitro HD experiments by varying blood flow rates between 100 and 200 ml/min with a cuprammonium rayon dialyser (AM-SD-10H). Total body clearance of iopromide (CL(PT)) was estimated by the Cockroft-Gault equation. The volume of distribution (V(d)) was obtained from the reported value. By using the HD and three pharmacokinetic parameters (CL(HD), CL(PT) and V(d)), we predicted CL(HD) and RR for seven patients undergoing HD after the administration of iopromide. RESULTS: In the in vitro study, the mean values (+/-SD) of iopromide clearance at blood flow rates of 100, 150 and 200 ml/min were 45.35 (2.54), 53.88 (6.46) and 57.61 (4.72) ml/min, respectively. There were highly significant correlations between clearance and blood flow rate (r = 0.975). Although the predicted CL(HD) showed a tendency towards underestimation, a good correlation was found. Predicted RR values were similar to observed values except for one case. CONCLUSION: The in vitro model used in the present study provides pertinent information about CL(HD) and is helpful for predicting RR during HD in individual patients undergoing HD.     

Ultrasonic flowmetry and neodymium-yttrium aluminum garnet laser for nephrolithotomy

Intraoperative Doppler flowmetry was used for localization of the intrarenal arteries. To reduce blood loss during nephrolithotomy, a neodymium-yttrium aluminum garnet (YAG) laser beam was used clinically as a cutting instrument. The combination of intraoperative localization of intrarenal arteries by Doppler flowmetry and cutting through renal parenchyma using the neodymium-YAG laser beam was used in 7 patients with stag-horn calculi or recurrent stones. The average blood loss was only 185 ml. Postoperative renal function was normal. Intravenous pyelograms revealed prompt function and no evidence of contrast extravasation. The data indicate that this technique is effective, diminishes blood loss, and does not impair renal function.     

Theoretical basis for herbal medicines, Tokishakuyaku-San and Sairei-To, in the treatment of recurrent abortion: enhancing the production of granulocyte-macrophage colony-stimulating factor in decidual stromal cells

PROBLEM: To get insight into the basis for the empirical usage of herbal medicines, such as Tokishakuyaku-san (Toki) and Sairei-to (Sai) in the treatment of recurrent abortion and intrauterine growth restriction, we examined whether these medicines modulate the production of granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine working as an important mediator for intercellular communication in the embryonic development, in decidual stromal cells (DSCs). METHOD OF STUDY: Human DSCs were cultured with either Toki or Sai at several different concentrations. The effect on cell proliferation was assessed by WST-8 assay. GM-CSF released into culture medium was analyzed using enzyme-linked immunosorbent assay, and semi-quantitative polymerase chain reaction was carried out to see GM-CSF mRNA expression in DSCs. RESULTS: Sai inhibited the proliferation of cultured DSCs, while no interference was observed in the presence of Toki. Both Toki and Sai enhanced the release of GM-CSF into culture medium. The amount of GM-CSF mRNA in cultured DSCs was as well increased by either Toki or Sai. CONCLUSION: Considering the significance of GM-CSF in embryonic development, clinical benefit of these herbal medicines in the treatment of recurrent abortion might be based on the shown pharmacological reaction related to GM-CSF.     

Allelic and non-allelic heterogeneities in pyridoxine dependent seizures revealed by ALDH7A1 mutational analysis

Pyridoxine dependent seizure (PDS) is a disorder of neonates or infants with autosomal recessive inheritance characterized by seizures, which responds to pharmacological dose of pyridoxine. Recently, mutations have been identified in the ALDH7A1 gene in Caucasian families with PDS. To elucidate further the genetic background of PDS, we screened for ALDH7A1 mutations in five PDS families (patients 1-5) that included four Orientals. Diagnosis as having PDS was confirmed by pyridoxine-withdrawal test. Exon sequencing analysis of patients 1-4 revealed eight ALDH7A1 mutations in compound heterozygous forms: five missense mutations, one nonsense mutation, one point mutation at the splicing donor site in intron 1, and a 1937-bp genomic deletion. The deletion included the entire exon 17, which was flanked by two Alu elements in introns 16 and 17. None of the mutations was found in 100 control chromosomes. In patient 5, no mutation was found by the exon sequencing analysis. Furthermore, expression level or nucleotide sequences of ALDH7A1 mRNA in lymphoblasts were normal. Plasma pipecolic acid concentration was not elevated in patient 5. These observations suggest that ALDH7A1 mutation is unlikely to be responsible for patient 5. Abnormal metabolism of GABA/glutamate in brain has long been suggested as the underlying pathophysiology of PDS. CSF glutamate concentration was elevated during the off-pyridoxine period in patient 3, but not in patient 2 or 5. These results suggest allelic and non-allelic heterogeneities of PDS, and that the CSF glutamate elevation does not directly correlate with the presence of ALDH7A1 mutations.     

A simple technique for isolating healthy heart cells from mouse models

Single heart cells of mouse models provide powerful tools for heart research. However, their isolation is not easy, and it imposes a significant bottleneck on their use in cellular studies of the heart. Aiming to overcome this problem, this report introduces a novel technique that reproducibly isolates healthy heart cells from mouse models. Using simple devices that ensure easy handling and the rapid aortic cannulation of a small mouse heart, cell isolation was done under physiological conditions without using the "KB" medium or 2,3-butanedione monoxime (BDM). The isolated cells consistently had a healthy appearance and a high viability of 75 +/- 5% (mean +/- SD) in Tyrode solution containing 1.8 mM Ca2+. After 8 h of storage at 37 degrees C, they still had a viability of 45 +/- 12%. The cells showed normal contraction properties when field-stimulated, and they generated normal action potentials and membrane currents under the whole-cell clamp condition. The beta-adrenergic signal transduction of the cells was also normal when it was examined with the isoproterenol enhancement of the L-type Ca2+ current.     

The cross-bridge dynamics during ventricular contraction predicted by coupling the cardiac cell model with a circulation model

The force-velocity (F-V) relationship of filament sliding is traditionally used to define the inotropic condition of striated muscles. A simple circulation model combined with the Laplace heart was developed to get a deeper insight into the relationship between the F-V characteristics and the cardiac ventricular inotropy. The circulation model consists of a preload and an afterload compartments. The linear F-V relationship for filament sliding in the NL model (Negroni and Lascano 1996) was replaced by the exponential F-V relation observed by Piazzesi et al. (2002). We also modified the NL model to a hybrid model to benefit from the Ca(2+) cooperativity described by the Robinson model (Robinson et al. 2002). The model was validated by determining the diastolic ventricular pressure-volume relationship of the Laplace heart and the F-V relation of the new hybrid model. The computed parameters of the cardiac cycle agreed well with the physiological data. Computational results showed that the cross-bridge elongation (h in the NL model) temporally undershot the equilibrium h(c) during the ejection period and overshot it during the rapid refilling phase. Thereby the time course of ejection and refilling was retarded. In a simulation where the velocity of the mobile myosin head (dX/dt) was varied, the systolic peak pressure of the ventricle varied from a minimum value at dX/dt = 0 to a saturating value obtained with a constant h(c), providing in silico evidence for a functional impact of the cross-bridge sliding rate on the ventricular inotropy.