Impact of intra-arterial chemotherapy including internal carotid artery for advanced paranasal sinus cancers involving the skull base.

BACKGROUND: The most significant problem of intra-arterial chemotherapy for advanced paranasal sinus carcinomas and residual cancers supplied by internal carotid artery (ICA) and involving the skull base is the lack of salvage therapies. OBJECTIVE: The objective of the study was to evaluate the usefulness of intra-arterial chemotherapy including ICA infusion for treating advanced paranasal sinus carcinomas, which have invaded the skull base. METHODS: Forty-six patients with advanced paranasal sinus carcinomas supplied by ICA were treated by intra-arterial chemotherapy using CDDP and sodium thiosulphate (STS) as a neutraliser of CDDP toxicity. After evaluating CT angiography, 150 mg m(-2) of CDDP was superselectively administered weekly to each feeding artery including ICA four times. RESULTS: The 10-year overall survival rate and progression-free survival rate were 70.7 and 60.2%, respectively. Compared with control group without infusing ICA, recurrences at anterior skullbase or anterior ethomoid sinus were significantly diminished. Of 32 patients in which the orbital apex had been invaded, 29 patients were treated with successful preservation of orbital contents. The CT angiography could efficiently determine all feeding arteries supplying the cancers. Consequently, chemotherapy could be administered on schedule, and side effects were minimal and acceptable. CONCLUSIONS: This new method has promising applications in the treatment of advanced paranasal sinus carcinomas involving the skull base.

Proline-glutamic acid-proline-lysine repetition peptide as an antigen for the serological diagnosis of strangles.

The reactivity of the proline-glutamic acid-proline-lysine (PEPK) repetition peptide antigen in 3176 serum samples was investigated to evaluate its utility as an antigen for the serological diagnosis of strangles. The reactivity of the sera of horses infected with Streptococcus equi subspecies equi was high when the peptide had several PEPK repetitions. However, as the number of PEPK repetitions increased, the reactivity of the antigen with the sera of horses infected with Streptococcus equi subspecies zooepidemicus also increased. In horses infected experimentally with S equi, the reactivity of the PEPK antigen with five repetitions increased one week after inoculation and continued to increase during the following four weeks. The optical density (OD) values of test sera from horses infected experimentally with S equi and sera from horses that had recovered from strangles were high. The od values of sera from horses that had recovered from an experimental infection with S zooepidemicus and of sera from healthy horses were comparatively low.

[Rapidly enlarging giant left ventricular pseudo-false aneurysm after myocardial infarction; report of a case].

A 71-year-old man was admitted to our hospital with acute myocardial infarction and cardiac tamponade. After pericardial drainage, his hemodynamics was improved. Because more than 3 days had been passed after the onset of myocardial infarction and he had severe renal dysfunction, emergent coronary angiography (CAG) was not performed. After improvement of his general status, coronary angiography and percutaneous catheter intervention was carried out, and his course was uneventful. But transthoracic echocardiography before discharge revealed a giant posterior psudoaneurysm. Patch closure and coronary artery bypass grafting was carried out under cardiopulmonary bypass, and postoperative course was uneventful. Postoperative left ventriculogram revealed disappearance of pseudoaneurysm, but relatively large akinetic area of posterior-inferior wall was left around a patch. Pseudo-false aneurysm was diagnosed by histological examination.

Randomized trial of phosphodiesterase inhibitors versus catecholamines in patients with acutely decompensated heart failure.

Increased neurohormone and cytokine concentrations are associated with adverse outcome in patients with congestive heart failure, so minimizing these increases may improve outcome, even in the acute phase of decompensated heart failure. The present study was designed to test the hypothesis that phosphodiesterase inhibitors, but not catecholamines, could favorably affect neurohormone and cytokine profiles in patients with acutely decompensated heart failure. Twenty-nine patients underwent monitoring using a Swan-Ganz catheter and were randomly allocated to receive phosphodiesterase inhibitors (PDEI group, n=19) or catecholamines (CA group, n=10). Pulmonary capillary wedge pressure decreased significantly in both groups and cardiac output showed a slight, but not statistically significant increase, in both groups. There was a significant decrease in plasma brain natriuretic peptide concentration in the PDEI group, but not in the CA group, whereas plasma interleukin-6 concentration increased in the CA group, but not in the PDEI group. Phosphodiesterase inhibitors favorably affect neurohormone and cytokine concentrations in patients with acutely decompensated heart failure.

Autoimmunity against the second extracellular loop of beta(1)-adrenergic receptors induces beta-adrenergic receptor desensitization and myocardial hypertrophy in vivo.

Although immunoapheresis removing autoantibodies against the second extracellular domain of beta(1)-adrenergic receptors (ARs) improves cardiac function in patients with cardiomyopathy, the underlying mechanisms have not been defined. We examined the role of autoimmunity against the domain in the development of cardiac dysfunction in vivo. Japanese white rabbits were immunized with a synthetic peptide corresponding to the second extracellular loop of beta(1)-AR once a month with (beta+biso rabbits, n=10) or without (beta rabbits, n=13) bisoprolol treatment (2 mg/kg per day). Control rabbits received vehicle without bisoprolol treatment (n=13). Autoantibodies of IgG isotype against the domain were persistently detected in beta and beta+biso rabbits. Purified IgG from sera of beta and beta+biso rabbits increased cAMP production in a rabbit cardiac membrane preparation, which was blocked by bisoprolol. At 3 months, beta-AR uncoupling with increased G protein-coupled receptor kinase 5 (GRK5) expression was found in beta rabbits. At 6 months, left ventricular hypertrophy was noted with hemodynamic derangements in beta rabbits. This was accompanied by decreased beta(1)-AR density and increased inhibitory G protein and GRK5 expression, which were related to marked decrease in membrane cAMP production. These changes in beta rabbits at 6 months were prevented in beta+biso rabbits. There was no difference in the plasma norepinephrine concentration in the 3 groups over the observation period. Thus, autoimmunity against the second extracellular loop of beta(1)-ARs induced profound beta-AR desensitization and myocardial hypertrophy in vivo, associated with cardiac dysfunction. Sustained sympathomimetic-like actions of autoantibodies against the domain may be partly responsible for these changes.

Absence of preinfarction angina is associated with a risk of no-reflow phenomenon after primary coronary angioplasty for a first anterior wall acute myocardial infarction.

BACKGROUND: No-reflow phenomenon after primary coronary angioplasty is associated with poorer left ventricular (LV) function and prognosis after acute myocardial infarction (AMI). The purpose of this study was to determine the clinical significance of preinfarction angina in the no-reflow phenomenon. METHODS AND RESULTS: A total of 40 patients with first anterior AMI were examined. All patients underwent primary balloon angioplasty or stenting within 12 h of the onset of AMI. No-reflow, defined as TIMI grade 2 flow or less without residual stenosis after angioplasty, was observed in 15 patients. Patients with no-reflow were older (67+/-9 vs. 58+/-10 years, P=0.006) and had a lower incidence of preinfarction angina (7% vs. 48%, P=0.01) than those without no-reflow. Patients with no-reflow had poorer LV function at predischarge and a higher incidence of pump failure, LV aneurysm, malignant ventricular arrhythmias or cardiac death during the hospital course in association with higher peak serum C-reactive protein levels (12.7+/-8.0 vs. 7.1+/-5.5 mg/dl, P=0.02). Multivariate analysis showed that the absence of preinfarction angina was a major independent determinant of no-reflow (RR=17.1, P=0.02). CONCLUSIONS: The absence of preinfarction angina is more frequently observed in patients with no-reflow. The beneficial effect of preinfarction angina on LV function may be explained, at least in part, by prevention of no-reflow after reperfusion.

Pathogenicity of Rhodococcus equi expressing a virulence-associated 20 kDa protein (VapB) in foals.

Rhodococcus equi strains of intermediate virulence (IMV) for mice possess a 20kDa protein designated Virulence Associated Protein B (VapB) and a virulence plasmid of 79-100kb, and can be recovered from the submaxillary lymph nodes of pigs. The pathogenicity of such R. equi strains for foals is unknown. In this study, two foals, 42 and 43 days of age, were infected intratracheally with 10(6) and 10(9) cells of R. equi IMV strain A5, respectively. The foal infected with 10(9) cells of strain A5 became clinically ill, with the onset of illness (pyrexia and depression) occurring 21 days after inoculation. R. equi was isolated from the feces and tracheal washings of the foal from 14 to 28 days after inoculation. The foal infected with 10(6) cells of A5 showed no clinical signs, and no R. equi was isolated from any of the samples of feces or tracheal washings during the 28 days of observation. Two foals of 45 and 50 days of age were infected with 10(5) or 10(6) of virulent R. equi ATCC 33701 having 15-17kDa surface proteins designated VapA. Both exhibited severe clinical signs (pyrexia, depression and anorexia) at 12 and 13 days after inoculation. Histopathological examination revealed that strain A5 caused focal granulomatous pneumonia in the foals. R. equi IMV strain A5 was isolated from lung lesions of both foals and from the contents of the intestinal tracts of the foal infected with 10(9) bacteria. These results suggest that IMV R. equi having VapB is less virulent than virulent R. equi having VapA in foals. This finding supports our previous results on the pathogenicities of R. equi strains having these virulence-associated antigens assessed by mouse pathogenicity tests.

Recurrent Wegener's granulomatosis with subglottic granulation.

While following the course of patients with Wegener's granulomatosis (WG) in which it had been possible to achieve a remission, we encountered a patient in whom we observed granuloma formation in the subglottis. A tracheotomy was performed because of the risk of respiratory distress, and after that there was a recrudescence of the patient's WG. During the course of the above, the patient remained cANCA (anti-neutrophil cytoplasmis antibody with cytoplasmic pattern)-negative. When these facts were considered, it appeared that when the lesions are localized and progressing gradually, cANCA positivity does not develop. While cANCA test has gradually become a powerful tool for the diagnosis of WG, a comprehensive physical examination to identify localized lesions, together with biopsy and histopathological examination, should allow the diagnosis of WG.

Salmonella Abortusequi strains of equine origin harbor a 95kb plasmid responsible for virulence in mice.

Most Salmonella choleraesuis subsp. choleraesuis serovar Abortusequi strains of equine origin harbor a 95kb plasmid, pSA95. Results of PCR and Southern blot analysis suggest that pSA95 contains spv genes. A pSA95-cured strain of S. Abortusequi was 48 times less virulent to mice than its parental strain. Virulence was restored by reintroduction of pSA95. These results provide clear evidence that pSA95 confers virulence on S. Abortusequi in mice. This is the first report describing a virulence plasmid of S. Abortusequi.

Adenylylcyclase increases responsiveness to catecholamine stimulation in transgenic mice.

BACKGROUND: The cellular content of cAMP generated by activation of adenylylcyclase (AC) through the beta-adrenergic receptor (betaAR) is a key determinant of a cell's response to catecholamine stimulation. We tested the hypothesis that increased AC content, independently of betaAR number, increases responsiveness to catecholamine stimulation in vivo. METHODS AND RESULTS: Transgenic mice with cardiac-directed expression of ACVI showed increased transgene AC expression but no change in myocardial betaAR number or G-protein content. When stimulated through the betaAR, cardiac function was increased, and cardiac myocytes showed increased cAMP production. In contrast, basal cAMP and cardiac function were normal, and long-term transgene expression was not associated with abnormal histological findings or deleterious changes in cardiac function. CONCLUSIONS: The amount of AC sets a limit on cardiac beta-adrenergic signaling in vivo, and increased AC, independent of betaAR number and G-protein content, provides a means to regulate cardiac responsiveness to betaAR stimulation. Overexpressing an effector (AC) does not alter transmembrane signaling except when receptors are activated, in contrast to receptor/G-protein overexpression, which yields continuous activation and has detrimental consequences. Our findings establish the importance of AC content in modulating beta-adrenergic signaling in the heart, suggesting a new target for safely increasing cardiac responsiveness to betaAR stimulation.

N-acetyl-beta-D-glucosaminidase is not a predictor, but an indicator of kidney injury in patients with cardiac surgery.

The urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was evaluated in terms of its ability to predict renal failure following open-heart surgery. Twenty-two patients were divided into three groups; 6 patients with post-operative renal failure (RF group), 9 without renal failure (non-RF group) and 7 who underwent non-cardiac surgery (non-ECC group). NAG levels during operation were significantly higher in the non-RF group than in the non-ECC group (2.28 +/- 0.50 U vs. 0.39 +/- 0.06 U, p < 0.01). NAG levels in the RF group were not significantly different from those in the non-ECC group (1.12 +/- 0.28 U/hr vs. 0.39 +/- 0.06 U/hr, p > 0.1), and in the non-RF group (1.12 +/- 0.28 U/hr vs. 2.28 +/- 0.50 U/hr, p > 0.1). Post-operative NAG levels were not significantly different between the RF and non-RF groups, whereas post-operative creatinine clearance values were significantly different (on 2, 6 and 7 post-operative day, p < 0.05). Our data suggest that the kidney is predisposed to renal failure by cardiopulmonary bypass and the chance of renal failure depends in some part on post-operative patient management.

Dissociation between regional dysfunction and beta-adrenergic receptor signaling in heart failure.

We have previously shown that left ventricular (LV) pacing-induced heart failure is associated with preserved wall thickening in the interventricular septum (IVS) compared with the posterolateral wall (PLW). The current study focuses on the relationship between regional myocardial function and altered beta-adrenergic receptor (beta-AR) signaling. We studied 15 pigs: 6 controls and 9 paced from the left ventricle (225 beats/min, 26 +/- 3 days). Heart failure was documented by decreased LV fractional shortening (P < 0.0001) and increased left atrial pressure (P < 0.0001). In heart failure, despite marked differences in basal regional function (percent wall thickening: IVS, 33 +/- 10% vs. PLW, 13 +/- 7%; P = 0.0003), there were no differences between the two regions in beta-AR responsiveness, measured by regional wall thickening in response to dobutamine infusion and any measurement of adrenergic signaling. Adenylyl cyclase activity, beta-AR number, and beta-AR/Gs coupling were markedly reduced in failing LV without regional differences. In animals with heart failure, LV G protein receptor kinase (GRK) isoform 2 content was unchanged and GRK5, the other major GRK isoform, was increased more than threefold (IVS, 0.51 +/- 0.20 vs. 0. 12 +/- 0.12 arbitrary densitometric units, P = 0.01; PLW, 0.47 +/- 0. 15 vs. 0.13 +/- 0.09 arbitrary densitometric units, P = 0.03), but again, there were no regional differences. These data indicate that systemic rather than regional factors govern LV adrenergic signaling and that regional adrenergic signaling abnormalities poorly predict wall thickening in the same regions.

[Moderately differentiated adenocarcinoma of the rectum: a case report of remarkable response to preoperative administration of FT suppository].

A 50-year-old man with moderately differentiated adenocarcinoma of the rectum was operated upon following preoperative administration of FT suppository. Digital examination, colonoscopy, and barium enema showed an elevated lesion with central ulcer of the rectum. Microscopically, the biopsy specimen demonstrated moderately differentiated adenocarcinoma. FT suppository (1,500 mg/day for 52 days, total 78 g) was administered on an outpatient basis. Rectal amputation including lymph node dissection was performed. The tumor markedly reduced in size and changed into a small ulcer in the resected specimen. Microscopically, the tumor degenerated and changed into xanthogranulomatous tissue with foamy histiocytes. Only two tubules of degenerated adenocarcinoma remained. FT suppository for rectal cancer is considered to be safe and effective.

Adenylyl cyclase and G protein receptor kinase expression during development of heart failure.

We examined alterations in left ventricular (LV) G protein receptor kinase (GRK) and adenylyl cyclase (AC) isoform expression during the development of pacing-induced congestive heart failure (CHF). AC isoform and GRK expression were assessed 4 (mild CHF) and 28 (severe CHF) days after initiation of pacing. LV beta-adrenergic receptor (beta-AR) number and G protein content were unchanged by mild CHF. LV AC isoform mRNA content was unaltered by mild CHF, but there were increases in total GRK activity (P < 0.01), total GRK5 protein content (P < 0.04), and GRK5 mRNA (P = 0.003); total GRK2 protein content and GRK2 mRNA were unchanged. Mild CHF was associated with decreased beta-AR coupling (P < 0.01) and reduced beta-AR stimulation of AC (P < 0.05). Severe CHF was associated with LV beta-AR downregulation (P = 0.0001) and uncoupling (P < 0.001) and marked generalized reduction of AC activity (mean P = 0.01). LV ACVI isoform mRNA content was reduced (P = 0.002), but ACII and ACV isoform mRNA contents were unaffected. Persistent elevations in LV total GRK activity (P < 0.01), total GRK5 protein content (P < 0.001), and GRK5 mRNA (P = 0.01) were found; in contrast, total GRK2 protein content was unchanged and GRK2 mRNA was reduced (P = 0.02). These studies indicate that increased GRK activity is an early charge in heart failure that predates alterations in AC isoform expression. Impaired hormonal stimulation of AC, associated with beta-AR uncoupling, may result from increased GRK5 expression. AC downregulation is isoform specific and accompanies severe but not mild CHF.

Pathogenicity and virulence of Rhodococcus equi in foals following intratracheal challenge.

Twelve foals, between 27 and 83 days old, were infected with 2 strains of Rhodococcus equi by intratracheal administration. Ten of the 12 foals were inoculated with 10(4)-10(10) colony forming units (cfu) of ATCC 33701 strain. The other 2 foals were inoculated with 10(9) cfu of a plasmid-cured derivative of the ATCC 33701 strain (ATCC 33701P-). All of the 10 foals challenged with the ATCC 33701 strain showed clinical signs of pulmonary disease within 5-13 days, such as gross lesions associated with acute bronchopneumonia and microscopic lesions associated with granulomatous pneumonia. The two foals challenged with the ATCC 33701P- strain showed neither clinical signs of disease nor gross lesions. Apparently, when lacking plasmid, the virulent Rhodococcus equi lost its pathogenicity.

Abnormal beta-adrenergic transmembrane signaling in rabbits with adriamycin-induced cardiomyopathy.

We investigated alterations in the beta-adrenergic receptor-adenylate cyclase system in rabbits with congestive heart failure induced by adriamycin cardiotoxicity. A dose of 24 mg/kg adriamycin was administered over 16 weeks in 16 rabbits. Five of them died and 4 of them could not tolerate the full dose of adriamycin. Complete data were obtained in the remaining 7 rabbits. Another 7 rabbits received physiological saline for the same period and served as controls. Plasma norepinephrine concentration increased in adriamycin-treated rabbits, but not in the control rabbits. Cardiac output was lower in the adriamycin-treated group than in the control group. Both the left and right ventricular end-diastolic pressure were higher in the adriamycin-treated group. The density of myocardial beta-adrenergic receptors and the norepinephrine content were reduced in both ventricles in the adriamycin-treated group. Basal and isoproterenol-, sodium fluoride- and forskolin-stimulated adenylate cyclase activities were lower in the adriamycin-treated group. Thus, alterations in beta-adrenergic signaling occurred in both ventricles in animals with chronic biventricular failure induced by adriamycin. These may be the result of post-receptor abnormalities, including abnormalities of guanine nucleotide-binding proteins or of the catalytic unit of adenylate cyclase.

[Surgical treatment of lung cancer complicated with liver cirrhosis, esophageal varices and pancytopenia: a case report].

Left upper lobectomy and lymph node dissection were successfully performed in a 75-year-old man with lung cancer combined with liver cirrhosis, esophageal varices and pancytopenia. No postoperative complications were encountered due to appropriate fluid transfusion, sufficient administration of fresh frozen plasma and well-chosen antibiotics. In lung operations on patients with liver cirrhosis, it is important to determine the operative indication according to natural history of liver cirrhosis and lung cancer, operative risk and prognosis. Furthermore, the management with special attention to complicated conditions of liver cirrhosis is necessary at the time of surgery.

Sudden hemorrhage of the breast caused by breast cancer without skin invasion: report of a case.

A rare case of sudden hemorrhage caused by breast cancer is herein presented. A 65-year-old woman was admitted to our hospital because of bleeding from her left breast. On physical examination, a continuous hemorrhage accompanied by an open cavity formation was observed in her left breast. She had no history of breast trauma. Her bleeding profile studies and liver function were both normal. In addition, no anticoagulation medication had been administered. The histological findings of the cavity wall indicated invasive ductal carcinoma without skin invasion. After carrying out chemotherapy, a standard radical mastectomy was performed.

[Perforation of the right ventricular wall and extraction into the left thoracic cavity by a permanent endocardial pacemaker lead: a case report].

A 80-year-old woman with right ventricular wall perforation and extraction into the left thoracic cavity by a permanent endocardial pacemaker (PM) lead was presented. The patient underwent an insertion of a permanent endocardial lead into the apex of the right ventricle for the treatment of sick sinus syndrome. The right ventricular perforation of the PM lead was incidentally diagnosed by recognizing it into the left thoracic cavity three months after the operation. Another PM lead could be inserted without removal of the former one.

Myelodysplastic syndrome associated with immunoblastic lymphadenopathy-like T-cell lymphoma: simultaneous clinical improvement with chemotherapy.

A 75-year-old woman presented with anemia, lymphadenopathy, hepatomegaly and lingual tumor, but no constitutional symptoms. The laboratory data showed pancytopenia and polyclonal hypergammaglobulinemia. A bone marrow aspirate represented an apparent myelodysplastic syndrome (MDS) feature, specifically, refractory anemia with excess of blasts. A lymph-node biopsy revealed the disappearance of normal architecture, small arborizing blood vessels, large lymphoid cells with prominent cytoplasm (so-called pale cells) and a clonal proliferation of T-lymphocytes. The patient was diagnosed as having MDS associated with immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma. She was subsequently treated with cyclophosphamide, adriamycin, vincristine and prednisolone for lymphoma which successfully induced a remission of not only the T-cell lymphoma but also the MDS. The case suggested that MDS might be a paraneoplastic complication of IBL-like T-cell lymphoma.