Effects of gender on prognosis of patients with known or suspected coronary artery disease undergoing contrast-enhanced dobutamine stress echocardiography.

BACKGROUND: Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease (CAD) undergoing contrast-enhanced dobutamine stress echocardiography (CE-DSE) have not been completely determined. METHODS AND RESULTS: Follow-up (30+/-17 months) data for 581 men and 309 women with known or suspected CAD who underwent CE-DSE (mean age: 66 years) were obtained. Hard cardiac events included cardiac death and nonfatal myocardial infarction. Total cardiac events included hard cardiac events, unstable angina, congestive heart failure, and late revascularization (>3 months). Cardiac events occurred in 123 male and 50 female patients. Positive results for CE-DSE were associated with worse prognosis in both men and women (2-year total event free rate: 73.5% vs 88.2% in men, p<0.0001, 80.3% vs 91.3% in women, p<0.01). Addition of CE-DSE results, including abnormal left ventricular end-systolic volume response and left ventricular ejection fraction at peak stress <50%, to the clinical and rest echocardiography model provided incremental information for predicting total cardiac events (increase in chi-square value for the model from 60 to 72, p<0.001) in men and (increase in chi-square value for the model from 17 to 32, p<0.001) in women. CONCLUSIONS: CE-DSE provides incremental information for predicting future cardiac events in both men and women.     

Molecular mechanisms underlying IFN-{gamma}-mediated tumor growth inhibition induced during tumor growth inhibition induced during tumor immunotherapy with rIL-12

The present studnt Investigates the molecular by which IFN-produced as a result of in vitroIL-12 addministration exertsits anty-tumor,rIL-12 was administered three or five times intomice bearing CDA1M fibrosarcoma, OV-HM ovarian carcinoma orMCH-1-A1 fibosarcoma. This regimen induced complete regressionof CSA1M and OV-HM tumors but only transient growth inhibitionof MCH-1-A1 tumors. The anty-tumor effects of Il-12 were associatatedwith enhanced induction of IFN-becouse these effects were abrogatedby pretreatment of hosts with anti-IFN- antibody.Exposure inin vitro of the three types of tumor cells to rIFN- resultedin moderate to potent inhibition of tumor cell growth.IFNstimulatedthe expression of mRNAs for an inducible type of NO synthasa(INOS)in CSA1M cells and indoleamine 2,3-dioxygenasa (IDO),an enzyme capable of degrading tryptophan, in OV-HM cells ,but induced only marginal levels of these mRNAs in MCH-I-ALcells. In association withiNOS gene expression, INF--stimulatedCSA1M cells produced a large amount of NO which functioned toinhibit their own growth in vitro. Although OV-HM and MCH-1-A1cells did not produce NO, they also exhibited NO susceptibility.Whereasthe tumor masses from IL-12-treated CSA1M-bearing mice inducedhigher levels of INOS (for CSA1M) or IDO and iNOS (for OV-HM)mRNAs,the MCH-1-A1 tumor mass expressed lower levels of iNOS mRNAalone.Moreover, massive infiltration of CD4⁺and CD8⁺ T cellsand Mac-1⁺ cells was seen only in the CSA1M and OV-HM tumors.Thus, these results indicate that IFN- produced after IL-12treatment induces the expression of various genes with potentialto modulate tumor cells and growth by acting directly on tumorecells or stimulating tumor-infiltrating lymphold cells and thatthe effectiveness of IL12 therapy is assoiated with the operation if these mechanisms.     

Endolymphatic perfusion with EGTA-acetoxymethyl ester inhibits asphyxia- and furosemide-induced decrease in endocochlear potential in guinea pigs

We examined the effect of the Ca(2+) concentration in the endolymph ([Ca](e)) or in the endolymphatic surface cells ([Ca](i)) on the endocochlear potential (EP) by using an endolymphatic or perilymphatic perfusion technique, respectively. (i) A large increase in [Ca](e) up to approximately 10(-3) M with a fall in the EP was induced by transient asphyxia ( approximately 2 min) or by the intravenous administration of furosemide (60 mg/kg), and a significant correlation was obtained between the EP and p[Ca](e) (= -log [Ca](e), r = 0.998). (ii) Perfusion of the endolymph with 10 mM EGTA for 5 min neither produced any significant change in the EP nor altered the asphyxia-induced change in EP (DeltaEP(asp)), suggesting that neither [Ca](e) nor the Ca(2+) concentration gradient across the stria vascularis contributed directly to the generation of the EP in the condition of low [Ca](e). In contrast, endolymphatic perfusion with high Ca(2+) (more than 10 mM) produced a decrease in EP and a significant correlation was obtained between the EP and the Ca(2+) concentration of perfusion solution (r = 0.982), suggesting that Ca(2+) permeability may exist across the stria vascularis. (iii) The administration of a Ca(2+) chelator, EGTA-acetoxymethyl ester (AM, 0.3 mM), to the endolymph, which produced a gradual increase in EP, suppressed significantly, by 60-80%, DeltaEP(asp) or furosemide-induced changes in EP. In contrast, perilymphatic administration of 0.5 mM EGTA-AM caused no significant suppression of the DeltaEP(asp). These findings suggest that [Ca](i) plays an important role in generating/maintaining a large positive EP.     

Role of N-methyl-D-aspartate receptors and the nitric oxide pathway in nociception/hyperalgesia elicited by protease-activated receptor-2 activation in mice and rats

Activation of the peripheral protease-activated receptor-2 (PAR-2) triggers nociceptive behaviour and thermal hyperalgesia in rats. The present study created a novel mouse model for PAR-2-triggered nociception, and then examined the roles of NMDA receptors and the nitric oxide (NO) pathway in nociceptive processing by PAR-2. Intraplantar administration of the PAR-2 agonist SLIGRL-NH(2) elicited nociceptive responses in mice, an effect being more specific in mast cell-depleted mice. This PAR-2-triggered nociception was abolished by the NMDA receptor antagonist MK-801, but not the neuronal NO synthase inhibitor 7-nitro indazole. In contrast, the PAR-2-triggered thermal hyperalgesia in rats was blocked by both agents. Our study thus provides a novel mouse model for PAR-2-mediated nociception, and suggests that NMDA receptors are involved in PAR-2-triggered nociception and hyperalgesia, while NO contributes only to the latter.     

Immunohistochemical,ultrastructural and biochemical studies of an amylase-producing breast carcinoma

Summary We describe a breast cancer with ectopic production of amylase, found in the patient's serum, urine and in the tumour. Clinically, serum amylase levels reflected both the progression of the disease and regression induced by various therapies. Using agarose gel electrophoresis and a wheat protein inhibitor assay, the predominant serum amylase appeared to be identical to pancreatic-type isoenzyme. However, the action mode analysis using a new fluorogenic substrate revealed that the serum contained non-salivary, non-pancreatic amylase. The tumour had microscopic features of invasive ductal carcinoma with some argyrophilic differentiation. The component cells stained positively for amylase, and ultrastructurally numerous secretory granules were seen.     

Transcanal endoscopic ear surgery for perilymphatic fistula after electric acoustic stimulation

Transcanal endoscopic ear surgery (TEES) will become a very useful therapeutic option. A perilymphatic fistula (PLF) is defined as sudden sensorineural hearing loss and/or vertigo caused by leakage of the perilymph through a fistula from the oval window and/or round window. We report a case of PLF after electric acoustic stimulation (EAS), a kind of cochlear implant, successfully treated by TEES. A 38-year-old man presented to our hospital with vertigo and hearing loss (HL). His vertigo was induced by Valsalva maneuvers. Eight months ago, he underwent EAS for his right ear for congenital sensorineural HL. Although he maintained his hearing level after EAS, his pure tone audiogram this time showed deterioration of hearing at low frequencies in his right ear. A diagnosis of right PLF was made. After confirming the non-effectiveness of oral prednisolone treatment, PLF repair surgery to patch the oval and round windows by TEES was performed. His vertigo did not recur after the surgery. To the best of our knowledge, this is the first report of PLF repair surgery by TEES without a microscope. The wide-field view of the middle ear by TEES was useful to prevent electrode damage in a PLF patient with a cochlear implant.     

Liver-related events after direct-acting antiviral therapy in patients with hepatitis C virus-associated cirrhosis

Journal of Gastroenterology - Direct-acting antiviral (DAA) therapy enables a high rate of sustained virologic response (SVR) in patients with hepatitis C virus associated cirrhosis. However, the...     

Evaluation of salvaged myocardium after acute myocardial infarction using single photon emission computed tomography after 201Tl-glucose-insulin infusion.

BACKGROUND: GIK-201Tl imaging reportedly improves the detection of viable myocardium, so the present study evaluated whether it can detect myocardial viability after acute myocardial infarction (AMI). METHODS AND RESULTS: Resting 201Tl and 99mTc-pyrophosphate (PYP) dual single photon emission computed tomography (SPECT) and 201Tl SPECT after 201Tl with GIK (10% glucose, insulin 5 U, and KCl 10 mmol) infusion (GIK-201Tl) were performed in 25 AMI patients within 10 days of admission. GIK-201Tl SPECT images were obtained immediately and 4 h after infusion. Left ventriculography (LVG) was performed within 3 weeks and at 6 months when follow-up 201Tl SPECT was also performed. From 20 SPECT segments, both the summed defect score (RDS) and the number of defect segments (ES) were calculated. The infarcted area was defined as 99mTc-PYP uptake segments. Wall motion was estimated in 7 LVG segments. The ES of R-201Tl (5.5 +/- 2.8), immediate GIK-201Tl (4.0 +/- 2.3), and 4-h GIK-201Tl (5.6 +/- 2.7) were lower than that of 99mTc-PYP (7.5 +/- 4.1) (p<0.05), and the ES had significantly declined 6 months later on 201Tl (3.5 +/- 2.8) (p<0.05). Although the RDS of R-201Tl (11.3 +/- 7.9) and 4-h GIK-201Tl (11.2 +/- 6.3) were greater than at the 6-month 201Tl (7.1 +/- 6.5), immediate GIK-201Tl (7.4 +/- 6.5) was equivalent to follow-up 201Tl. The sensitivity of immediate GIK-201Tl was highest among the imaging methods. CONCLUSION: To detect myocardial viability after AMI, early imaging with GIK-201Tl is more useful than resting 201Tl imaging.