En-bloc esophagectomy for esophageal cancer

BACKGROUND: The operative approach for esophageal cancer varies from simple palliative resection to extended esophagectomy with 3-field lymph-node dissection or en-bloc esophagectomy (EBE) depending on tumor and patient status and surgical strategy of the surgeon. The merits and demerits of such EBE are yet to be determined. METHODS: A literature review was done regarding EBE for esophageal cancer. RESULTS: Twenty articles describing EBE were reported from experienced institutions during the last 20 years and were selected for this study. The conclusions drawn from those articles showed that EBE would be a safe procedure with acceptable morbidity and low mortality rates when performed by an experienced surgeon. When strict patient selection criteria were maintained, this procedure decreased locoregional recurrence and improved long-term survival rates. CONCLUSIONS: EBE would be the treatment of choice in selected patients presenting with esophageal cancer. Development of meticulous preoperative risk assessment and optimum postoperative care may further improve the acceptability of this procedure with minimum morbidity and acceptable mortality rates.     

Emergency stent placement after descending aortic replacement with chronic aortic dissection

A 49-year-old man with asymptomatic chronic aneurysmal dissection was admitted to our hospital. He had undergone ascending aortic replacement for type A aortic dissection 7 months before. We performed descending aortic replacement for chronic aneurysmal dissection. Renal dysfunction appeared 1 day after the operation. Contrast-enhanced computed tomography indicated that the true lumen was severely compressed by a false lumen, and that the origins of the renal artery were occluded. We performed emergency endovascular stent placement to dilate the true lumen. Immediately after this procedure, renal ischemia improved. The postoperative course was uneventful. An endovascular approach using bare stent can be a treatment option that is less invasive and prompter for a patient with renal ischemia resulting from aortic dissection.     

Changes in cyclic nucleotide phosphodiesterase activity and calmodulin concentration in heart muscle of cardiomyopathic hamsters

Cyclic nucleotides (cAMP and cGMP) phosphodiesterase (PDE) activities and expression are altered in the cardiac muscle of cardiomyopathic heart failure, and PDE inhibitors improve the abnormal muscle condition through changing the cyclic nucleotide concentration. These observations prompted us to investigate the role of calmodulin (CaM) in the regulation of cyclic nucleotide PDE activities, and moreover to study the modulation of the PDE isozymes in heart failure, using cardiac muscles of cardiomyopathic hamster. The CaM concentrations in the heart muscle of the normal control and cardiomyopathic hamsters (each of three to four hamsters) varied with cell fraction and with the age of the animal. The CaM concentrations in the soluble fraction obtained from cardiomyopathic hamster tissue were significantly increased at 25 and 32 weeks of age (2.02 +/- 0.62 microg/mg protein (mean +/- S.E.), and 3.21 +/- 0.95) compared with that obtained from the control (0.60 +/- 0.04) or cardiomyopathic (0.95 +/- 0.12) hamsters at 8 weeks of age. The solubilized PDE isolated from the hamster heart muscle (three or four hamsters in each age) by column chromatography on diethylaminoethyl (DEAE)-cellulose revealed three peaks of activity, which may correspond to the isozymes of PDE classified recently, namely PDE I, II, and III. These three peaks of activity, particularly peak III, seen in the soluble fraction of cardiomyopathic hamster heart declined in proportion to the age of the animal compared with that of the control hamster heart. In the cGMP-PDE assay system, the concentration of CaM inhibitor W-7 required for 50% inhibition (IC(50)) of PDE I, II, and III peak activities was 140, 29, and 46 microM, respectively, suggesting that PDE II is more sensitive to W-7. These results suggest that alteration in these isozyme activities accompanied with changes of CaM concentration may influence the cardiac muscle contractility in cardiomyopathic hamster via changes of cyclic nucleotide concentration.     

Symptoms Predictive for Efficacy of Naftopidil in Patients with Benign Prostate Hyperplasia

Objectives: To evaluate the lower urinary tract symptoms predicting the efficacy of the α1‐adrenoreceptor (AR) antagonist naftopidil in patients with benign prostate hyperplasia. Methods: The efficacy of naftopidil was examined on the basis of changes in the international prostate symptom score (IPSS). All patients received naftopidil (50 mg/day) for 12 weeks. We defined a “responder” as a patient whose total IPSS improved by five or more points and assessed the lower urinary tract symptoms predicting the efficacy of treatment by performing multivariate and probit analyses. Results: Among 132 patients whose data could be analyzed, the efficacy rate was 50.8%. All IPSS items except the urgency score were significantly higher in the responders than the non‐responders before treatment, and all IPSS items were lower in the responders after treatment. In the responder group, significant improvements were observed in the total IPSS score, quality of life (QOL) index, maximum flow rate (Q_max), residual urine volume, and all IPSS items after treatment. In contrast, in the non‐responder group, no parameter except the QOL index improved significantly. The probit analysis demonstrated that the score for weak stream (≥3) or nocturia (≥4) in the IPSS were factors predicting an effective response to naftopidil treatment. Conclusions: Weak stream and/or nocturia are the key symptoms that predict the efficacy of naftopidil treatment in patients with benign prostatic hyperplasia. Those with a score of ≥3 for weak stream or of ≥4 for nocturia are expected to achieve a good response in the subjective symptoms with administration of naftopidil.     

Loss or Somatic Mutations of hMSH2 Occur in Hereditary Nonpolyposis Colorectal Cancers with hMSH2 Germline Mutations

Hereditary nonpolyposis colorectal cancer (HNPCC) is a major cancer susceptibility syndrome known to be caused by the inheritance of mutations in DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2 . To investigate the role of genetic alterations of hMSH2 in HNPCC tumorigenesis, we analyzed 36 Japanese HNPCC kindreds as to hMSH2 germline mutations. Moreover, we also examined somatic mutations of hMSH2 or loss of heterozygosity at or near the hMSH2 locus in the tumors from the hMSH2 -related kindreds. Germline mutations were detected in five HNPCC kindreds (5/36, 14%). Among them, three were nonsense mutations, one was a frameshift mutation and the other was a mutation in an intron where the mutation affected splicing. Loss of heterozygosity in four and somatic mutations in one were detected among the eight tumors with hMSH2 germline mutations. All these alterations were only detected in genomic instability(+) tumors, i.e., not in genomic instability(-) ones, indicating that mutations of hMSH2 were responsible for at least some of the tumors with genomic instability. These data establish a basis for the presymptomatic diagnosis of HNPCC patients, and constitute further evidence that both DNA mismatch repair genes and tumor suppressor genes may share the same requirement, i.e., two hits are necessary to inactivate the gene function.     

Effects of a 1 day fast on biohumoral variables associated with human circadian rhythmicity

1. The aim of the present study was to investigate the effects of a short (1 day) fast by testing biohumoral variables associated with the human circadian rhythm. 2. Fifteen clinically healthy male volunteers (32 +/- 8 years old) participated in the study. Subjects were fed a control diet for 7 days. The last day was a control day and the following 8th day was the fasting day. Each subject was asked to collect urine seven times over a 24 h period. Chemical and hormonal variables were measured in each fractionated urine specimen. The time- qualified urinary excretion rates were biometrically analysed using conventional and chronobiological methods. 3. During fasting, significant incremental changes were detected in the urinary excretion rates of potassium, aldosterone, 17-hydroxycorticosteroids and adrenaline and significant decremental changes were detected in the excretion rates of sodium, chloride, creatinine, urea nitrogen, uric acid, 17-ketosteroids, noradrenaline and dopamine. The circadian rhythmicity of the variables was well preserved and remained almost stable throughout the fasting phase. 4. Fasting affected the mean oscillatory levels and oscillatory amplitudes of variables, suggesting that nutrients may have played roles as tonic and phasic modulators on the mechanisms that physiologically regulate ircadian rhythmicity.     

Phototoxicity studies of pazufloxacin mesilate,a novel parenteral quinolone antimicrobial agent--in vitro and in vivo studies

Phototoxicity of pazufloxacin mesilate (PZFX mesilate), a novel parenteral quinolone antimicrobial agent, were evaluated in vitro and in vivo studies. In vitro, phototoxicity for cultured cells of PZFX, which is active principle of PZFX mesilate, was studied, and stability for long-wavelength ultraviolet (UVA) was examined. In vivo, phototoxicity tests in guinea pigs and rats, and photoallergenicity tests in guinea pigs were conducted. In the phototoxicity test on cultured cells, CHL/IU cells were irradiated UVA of 300-3000 mJ/cm2 in the presence of PZFX, ofloxacin (OFLX), lomefloxacin (LFLX) or sparfloxacin (SPFX) at 10 micrograms/mL. Phototoxic potencies for cultured cells of the quinolones tested were SPFX > LFLX > OFLX > PZFX. In addition, changes in ultraviolet absorption spectrum and residual rate of PZFX, OFLX, LFLX and SPFX were examined after UVA irradiation of 300-3000 mJ/cm2 to each solution. PZFX was stable for UVA compared with OFLX and LFLX. In the phototoxicity test of guinea pigs, each quinolone was administered intraperitoneally daily for 7 days, and UVA of about 11 J/cm2 was irradiated at 30 minutes after the last administration. Dose levels of each quinolone were 65 and 130 mg/kg of PZFX mesilate (dose levels converted to PZFX: 50 and 100 mg/kg), 50 and 100 mg/kg of nalidixic acid (NA), 100 mg/kg of OFLX, enoxacin (ENX), ciprofloxacin (CPFX), LFLX and SPFX. Grade of skin reaction (erythema) at 24 hours after UVA irradiation decreased in the order: SPFX > CPFX > NA > ENX = OFLX > LFLX > PZFX mesilate. Thus, PZFX mesilate was found to have the weakest phototoxicity. In the maximum plasma concentration of quinolones from 0.5 to 2.5 hours after administration, corresponding to the time of UVA irradiation, the concentration of the group administered PZFX mesilate was about 4.1 times higher than that of CPFX group, and about 1.3 times higher than that of SPFX group. The area under the blood concentration-time curve (AUC0.5-2.5) of the group administered PZFX mesilate was the same as that of SPFX group, and about 3.2 times larger than that of CPFX group. These data showed that phototoxicity of PZFX mesilate was also weaker than that of CPFX or SPFX in consideration of AUC0.5-2.5. In the phototoxicity test of rats injected intravenously, no phototoxicity was observed at 130 mg/kg of PZFX mesilate. In the photoallergenicity test of guinea pigs, no photoallergenicity was observed by PZFX mesilate. As mentioned above, from in vitro studies PZFX was found to be stable for UVA irradiation compared with OFLX and LFLX, and phototoxicity for cultured cells of PZFX was weaker than that of SPFX, LFLX or OFLX. In addition, from in vivo studies phototoxicity of PZFX mesilate was found to be weaker than that of NA, OFLX, ENX, CPFX, LFLX or SPFX, and no photoallergenicity was observed. Therefore, photosensitive potency of PZFX mesilate might be less than that of other quinolones.     

Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing alpha 7 receptors

1. Tramadol has been used clinically as an analgesic; however, the mechanism of its analgesic effects is still unknown. 2. We used bovine adrenal chromaffin cells to investigate effects of tramadol on catecholamine secretion, nicotine-induced cytosolic Ca(2+) concentration ([Ca(2+)](i)) increases and membrane current changes. We also investigated effects of tramadol on alpha7 nicotinic acetylcholine receptors (AChRs) expressed in Xenopus oocytes. 3. Tramadol concentration-dependently suppressed carbachol-induced catecholamine secretion to 60% and 27% of the control at the concentration of 10 and 100 microM, respectively, whereas it had little effect on veratridine- or high K(+)-induced catecholamine secretion. 4. Tramadol also suppressed nicotine-induced ([Ca(2+)](i)) increases in a concentration-dependent manner. Tramadol inhibited nicotine-induced inward currents, and the inhibition was unaffected by the opioid receptor antagonist naloxone. 5. Tramadol inhibited nicotinic currents carried by alpha7 receptors expressed in Xenopus oocytes. 6. Tramadol inhibited both alpha-bungarotoxin-sensitive and -insensitive nicotinic currents in bovine adrenal chromaffin cells. 7. In conclusion, tramadol inhibits catecholamine secretion partly by inhibiting nicotinic AChR functions in a naloxone-insensitive manner and alpha7 receptors are one of those inhibited by tramadol.