State III large cell carcinoma of the lung cured by radiotherapy--a case report

Presented is the case of a 61-year-old male whose chief complaints were hoarseness, cough, and bloody sputum. Chest radiography demonstrated a left hilar mass with mediastinal widening, a peripheral localized infiltrate and the elevation of the left hemidiaphragm. By means of a mediastinoscopy, a biopsy was done on the enlarged mediastinal lymph node and a histological diagnosis of a large cell carcinoma was confirmed. He was graded as in Stage III (T2N2M0) and was placed under radiotherapy with 60Co. Complete response was obtained after a total dose of 6150 cGy. Following this radiotherapy, he was given multiple courses of mild chemotherapy and the disease as of this report has been under control for 7 years. This case may be unusual, but suggests the possibility of a cure of lung cancer by irradiation under certain conditions.     

The N-terminus of the Montano virus nucleocapsid protein possesses broadly cross-reactive conformation-dependent epitopes conserved in rodent-borne hantaviruses

The hantavirus nucleocapsid (N) protein is an important immunogen that stimulates a strong and cross-reactive immune response in humans and rodents. A large proportion of the response to N protein has been found to target its N-terminus. However, the exact nature of this bias towards the N-terminus is not yet fully understood. We characterized six monoclonal antibodies (mAbs) against the N protein of Montano virus (MTNV), a Mexican hantavirus. Five of these mAbs recognized eight American hantaviruses and six European and Asian hantaviruses, but not the Soricomorpha-borne Thottapalayam hantavirus. The N protein-reactive binding regions of the five mAbs were mapped to discontinuous epitopes within the N-terminal 13-51 amino acid residues, while a single serotype-specific mAb was mapped to residues 1-25 and 49-75. Our findings suggest that discontinuous epitopes at the N-terminus are conserved, at least in rodent-borne hantaviruses, and that they contribute considerably to N protein cross-reactivity.     

Clinical efficacy and value of redistributed subclavian arterial infusion chemotherapy for locally advanced breast cancer

Purpose

The aim of this study was to evaluate the efficacy and safety of redistributed subclavian arterial infusion chemotherapy (RESAIC). We have focused on the local response, quality of life (QOL), and complications. We have also investigated factors that influence the local response of RESAIC.

Materials and methods

The subjects were patients with locally advanced breast cancer whose tumors were resistant to standard systemic chemotherapy (at least more than two regimens), those who were physically unable to tolerate systemic chemotherapy, and patients with locally recurrent breast cancer. The registration period was between April 2006 and May 2009.

Results

A total of 24 cases in 22 patients (mean age 59.5 years, range 36?C82 years) were entered in the study. The local response rate of RESAIC was 77.3% (17/22). The QOL score showed improvement on average. There were no serious complications during catheter port implantation, and there was hematological toxicity over grade 3 in 27.3% (6/22) of patients. A significant difference between responders and nonresponders was seen in patients with a replaced type tumor (on imaging, diffuse contrast enhancement was seen in whole quadrants) (P = 0.043), and the patients underwent radiotherapy (P = 0.043).

Conclusion

RESAIC is an effective, safe treatment for locally advanced breast cancer. Because it was reviewed in only a few cases, however, large-scale studies are warranted.     

Hepatic artery-targeting guidewire technique during transjugular intrahepatic portosystemic shunt

Objective

This study evaluated the feasibility and safety of the transjugular intrahepatic portosystemic shunt (TIPS) procedure using the hepatic artery-targeting guidewire technique for the puncture step.

Methods

We retrospectively reviewed 11 consecutive patients (5 men and 6 women, aged 46–76 years (mean 64 years)) with portal hypertension in whom the TIPS procedure was performed. As the first step in the TIPS procedure in all cases, a micro-guidewire was inserted into the hepatic arterial branch accompanying the portal venous branch through a microcatheter coaxially advanced from a 5-French catheter positioned in the coeliac or common hepatic artery. At the puncture step, the tip of the metallic cannula was aimed 1 cm posterior to the distal part of this micro-guidewire, after which the TIPS procedure was performed. Success rate, number of punctures and complications were evaluated.

Results

The TIPS procedure was successfully performed in all 11 patients. The mean number of punctures until success in entering the targeted portal venous branch was 5 (range 1–14). In 3 patients (27%), the right portal venous branch was entered at the first puncture attempt. The hepatic artery was punctured once in one patient and the bile duct was punctured once in another patient. No serious procedure-induced complications occurred.

Conclusion

The TIPS procedure can be accomplished safely, precisely and relatively easily using the hepatic artery-targeting guidewire technique.Transjugular intrahepatic portosystemic shunt (TIPS) placements have continued to increase since the first such procedure was performed in 1988 [1]. Currently, this procedure is accepted as an effective treatment for the complications of portal hypertension, such as variceal bleeding [2] and intractable ascites [2^,3]. In many institutions, including ours, however, this procedure is rarely performed and it might be difficult to maintain the necessary skills.During the TIPS procedure, the puncture from the proximal portion of the hepatic vein (usually a right hepatic vein) to the proximal portion of a branch of the intrahepatic portal vein (usually the right portal vein) is the most important and difficult step [1^,2]. In 1994, Matsui et al [4] introduced a simple technique to assist in this puncture step. This technique was aided by a targeting guidewire in the hepatic arterial branch accompanying the portal venous branch to be punctured. To our knowledge, there has been no subsequent literature on the use of this simple technique, which we have adopted in our institution. This study evaluated the application of the hepatic artery-targeting guidewire technique for the puncture step of the TIPS procedure. We also assessed the occurrence of procedure-induced complications in order to clarify the value of this technique to inexperienced or infrequent operators such as those in our institution.     

In vitro activity of E1210, a novel antifungal, against clinically important yeasts and molds

E1210 is a new antifungal compound with a novel mechanism of action and broad spectrum of antifungal activity. We investigated the in vitro antifungal activities of E1210 compared to those of fluconazole, itraconazole, voriconazole, amphotericin B, and micafungin against clinical fungal isolates. E1210 showed potent activities against most Candida spp. (MIC(90) of ≤0.008 to 0.06 μg/ml), except for Candida krusei (MICs of 2 to >32 μg/ml). E1210 showed equally potent activities against fluconazole-resistant and fluconazole-susceptible Candida strains. E1210 also had potent activities against various filamentous fungi, including Aspergillus fumigatus (MIC(90) of 0.13 μg/ml). E1210 was also active against Fusarium solani and some black molds. Of note, E1210 showed the greatest activities against Pseudallescheria boydii (MICs of 0.03 to 0.13 μg/ml), Scedosporium prolificans (MIC of 0.03 μg/ml), and Paecilomyces lilacinus (MICs of 0.06 μg/ml) among the compounds tested. The antifungal action of E1210 was fungistatic, but E1210 showed no trailing growth of Candida albicans, which has often been observed with fluconazole. In a cytotoxicity assay using human HK-2 cells, E1210 showed toxicity as low as that of fluconazole. Based on these results, E1210 is likely to be a promising antifungal agent for the treatment of invasive fungal infections.     

AT1 receptor blockade prevents microvascular dysfunction induced by ischemia/reperfusion injury

Ischemia/reperfusion (I/R) in post-arterior post-capillary venules induces an acute inflammatory response, characterized by increased adherence and emigration of leukocytes and vascular permeability, all of which play important roles in cardiovascular disease. The aim of this study was to determine the roles of angiotensin II and AT1 receptor blockade in microvascular I/R injury in rats. Rats were anesthetized and intubated, then the peritoneum was opened and the mesentery was revealed. Small post-capillary venules were examined by in vivo fluorescence microscopy. The flow of erythrocytes and leukocytes was observed under the microscope and video recorded for later dynamic analyses. The superior mesenteric artery (SMA) was ligated with polyethylene tubing and released to induce I/R (20 min of ischemia/60 min of reperfusion). Subsequently, leukocyte adhesion, emigration and albumin leakage were compared with those of non-I/R controls. I/R injury was significantly suppressed by superfusing tissues with the AT1 receptor antagonist losartan (LO; 10 microM). The beneficial effects of LO were inhibited by topical application of either the bradykinin B2 receptor antagonist HOE140 (10 nM) or nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME 10 microM). The effects of LO were lost in the presence of AT2 receptor blocker PD 123319 (PD).In conclusion, LO suppressed and protected against I/R injuries. The possible interaction between AT1 and AT2 receptors was also suggested.     

Telmisartan prevents obesity and increases the expression of uncoupling protein 1 in diet-induced obese mice

The aim of the present study was to clarify the effect of telmisartan, an angiotensin II receptor blocker, on the development of obesity and related metabolic disorders in diet-induced obese mice. Treatment with telmisartan dissolved in drinking water at a dosage of 5 mg/kg per day for 14 days attenuated the diet-induced weight gain without affecting food intake in diet-induced obese mice compared with controls using nontreated water. Telmisartan treatment decreased the weight of visceral adipose tissue and the triglyceride content in the liver and skeletal muscle. In addition, hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in diet-induced obese mice all improved with telmisartan treatment. Furthermore, telmisartan treatment increased adiponectin mRNA in visceral white adipose tissue and was associated with a concomitant change in the serum adiponectin level. In contrast, the treatment reduced the serum level of resistin. Finally, telmisartan treatment increased the mRNA expression of uncoupling protein 1 in brown adipose tissue and was accompanied by an increase in oxygen consumption. In conclusion, telmisartan treatment might prevent the development of obesity and related metabolic disorders by altering the levels of adiponectin, resistin, and uncoupling protein 1 in diet-induced obese mice. Our results indicate that telmisartan can be used as a therapeutic tool for metabolic syndrome, including visceral obesity.     

A TNF receptor loop peptide mimic blocks RANK ligand-induced signaling, bone resorption, and bone loss

Activating receptor activator of NF-kappaB (RANK) and TNF receptor (TNFR) promote osteoclast differentiation. A critical ligand contact site on the TNFR is partly conserved in RANK. Surface plasmon resonance studies showed that a peptide (WP9QY) that mimics this TNFR contact site and inhibits TNF-alpha-induced activity bound to RANK ligand (RANKL). Changing a single residue predicted to play an important role in the interaction reduced the binding significantly. WP9QY, but not the altered control peptide, inhibited the RANKL-induced activation of RANK-dependent signaling in RAW 264.7 cells but had no effect on M-CSF-induced activation of some of the same signaling events. WP9QY but not the control peptide also prevented RANKL-induced bone resorption and osteoclastogenesis, even when TNFRs were absent or blocked. In vivo, where both RANKL and TNF-alpha promote osteoclastogenesis, osteoclast activity, and bone loss, WP9QY prevented the increased osteoclastogenesis and bone loss induced in mice by ovariectomy or low dietary calcium, in the latter case in both wild-type and TNFR double-knockout mice. These results suggest that a peptide that mimics a TNFR ligand contact site blocks bone resorption by interfering with recruitment and activation of osteoclasts by both RANKL and TNF.     

Smoking is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients

BACKGROUND: Smoking and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. This study tested the hypothesis that smoking is associated with insulin resistance/hyperinsulinaemia and cardiovascular autonomic dysfunction in type 2 diabetic patients who are not treated with insulin. MATERIALS AND METHODS: The study patients were 22 current smokers with type 2 diabetes mellitus (age: 57 +/- 5 years, mean +/- SD) and 30 age-matched never-smoked patients with type 2 diabetes mellitus (control group, 57 +/- 8 years). The quality of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin (F-IRI), homeostasis model assessment (HOMA) index and haemoglobin A1c (HbA1c). The severity of smoking status was expressed by the Brinkman index, which is calculated as number of cigarettes per day multiplied by years of smoking. Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart-rate variability, plasma norepinephrine concentration and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings. RESULTS: Baroreflex sensitivity was lower in the current smokers group than in the never-smoked group (P < 0.05). Early and delayed (123)I-MIBG myocardial uptake values were lower (P < 0.05, and P < 0.01, respectively) and the percentage washout-rate of (123)I-MIBG was higher (P < 0.0001) in the current smokers group than in the never-smoked group. Fasting immunoreactive insulin (F-IRI) concentration (P < 0.0001) and the homeostasis model assessment (HOMA) index (P < 0.0001) were higher in the current smokers group than the never-smoked group. Multiple logistic regression analysis revealed that smoking was independently predicted by F-IRI and the percentage washout-rate of (123)I-MIBG. CONCLUSIONS: The results of the study suggested that smoking was associated with cardiovascular autonomic dysfunction and hyperinsulinaemia and that F-IRI and the percentage washout-rate of (123)I-MIBG were independent predictors of smoking in these Japanese patients with type 2 diabetes mellitus.