Surgical treatment of lung cancer: promise and problems of early diagnosis

Recent studies have shown that the survival of patients with lung cancer is improved if the tumour is resected before it becomes larger than 3 cm in diameter and before it spreads to lymph nodes. While this suggests a positive benefit from early detection, recent mass-screening studies have claimed that the benefit obtained from this procedure is illusory because it relates to a lead-time bias. This study reports the results of surgical resection of 143 primary lung cancers. The data confirmed that the predicted 5-year survival was greatest (74%) following resection of lesions that were less than 3 cm in diameter without node involvement. Analysis showed that the age of these patients was 63 +/- 8 years, the same as in patients with larger tumours and more extensive node involvement. This suggests that tumours progress rapidly from a stage at which resection is beneficial to stages at which it is not. Although it is desirable that tests predict the presence of small tumours, the high requirements for sensitivity and specificity at current prevalence rates for lung cancer make this goal impractical.     

Concentration of cefotaxime and its metabolite in human bone marrow blood

Cefotaxime (CTX) was intravenously administered in an amount of 2.0 g to each of 34 adult patients before the surgery mainly of the hip joint. Samples of the blood from the bone marrow around the trochanter were taken at the time of the operation. At the same time blood samples were taken from peripheral veins. The sample was centrifuged and the supernatant was analyzed for CTX and desacetyl-CTX. The concentration of CTX in the marrow blood was 150.9 micrograms/ml and that in the blood was 182.5 micrograms/ml in the earliest samples taken at 20 minutes after injection. In the 44 pairs of samples, the concentration of CTX in the marrow blood was lower than that in the peripheral blood in all the cases except 4. The concentration of desacetyl-CTX (Des-CTX), however, in the marrow blood was higher than in the peripheral blood in 33 of the 44 pairs of specimens. Since the degradation of the drug progresses with time, the ratio of Des-CTX to CTX increased with time. This trend was particularly marked in the bone marrow blood and can be expressed as Y = 113.0 + 0.32 t, when Y is the ratio percentage (Des-CTX/CTX) and t is time after the injection of the drug in minute. Thus, CTX transferred into the bone marrow tends to remain there and transformed into the desacetyl form.     

Rationale and design for a study using intravascular ultrasound to evaluate effects of rosuvastatin on coronary artery atheroma in Japanese subjects: COSMOS study (Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects).

BACKGROUND: There have been few multicenter studies using intravascular ultrasound (IVUS) to assess the process of atherosclerosis in a Japanese population with hypercholesterolemia that is being treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for control of low-density lipoprotein-cholesterol. METHODS AND RESULTS: An open-label multicenter study is planned to evaluate with IVUS whether treatment with rosuvastatin for 76 weeks results in regression of coronary artery atheroma volume in patients who have coronary heart disease (CHD) and hypercholesterolemia. Sample size is 200 subjects with CHD who are to undergo percutaneous coronary intervention. The planned duration is between October 2005 and October 2008. CONCLUSIONS: The COSMOS study will be the first multicenter cardiovascular study in a Japanese population and may provide new evidence on the effects of rosuvastatin on the progression of coronary atherosclerotic lesions.     

Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion

Alphaviruses have the ability to induce cell-cell fusion after exposure to acid pH. This observation has served as an article of proof that these membrane-containing viruses infect cells by fusion of the virus membrane with a host cell membrane upon exposure to acid pH after incorporation into a cell endosome. We have investigated the requirements for the induction of virus-mediated, low pH-induced cell-cell fusion and cell-virus fusion. We have correlated the pH requirements for this process to structural changes they produce in the virus by electron cryo-microscopy. We found that exposure to acid pH was required to establish conditions for membrane fusion but that membrane fusion did not occur until return to neutral pH. Electron cryo-microscopy revealed dramatic changes in the structure of the virion as it was moved to acid pH and then returned to neutral pH. None of these treatments resulted in the disassembly of the virus protein icosahedral shell that is a requisite for the process of virus membrane-cell membrane fusion. The appearance of a prominent protruding structure upon exposure to acid pH and its disappearance upon return to neutral pH suggested that the production of a "pore"-like structure at the fivefold axis may facilitate cell penetration as has been proposed for polio (J. Virol. 74 (2000) 1342) and human rhino virus (Mol. Cell 10 (2002) 317). This transient structural change also provided an explanation for how membrane fusion occurs after return to neutral pH. Examination of virus-cell complexes at neutral pH supported the contention that infection occurs at the cell surface at neutral pH by the production of a virus structure that breaches the plasma membrane bilayer. These data suggest an alternative route of infection for Sindbis virus that occurs by a process that does not involve membrane fusion and does not require disassembly of the virus protein shell.     

Carbon-ion beams induce production of an immune mediator protein,high mobility group box 1, at levels comparable with X-ray irradiation

X-ray radiotherapy activates tumor antigen-specific T-cell responses, and increases in the serum levels of high mobility group box 1 (HMGB1) induced by X-ray irradiation play a pivotal role in activating anti-tumor immunity. Here, we examined whether carbon-ion beams, as well as X-rays, can induce HMGB1 release from human cancer cell lines. The study examined five human cancer cell lines: TE2, KYSE70, A549, NCI-H460 and WiDr. The proportion of cells surviving X- or carbon-ion beam irradiation was assessed in a clonogenic assay. The D₁₀, the dose at which 10% of cells survive, was calculated using a linear–quadratic model. HMGB1 levels in the culture supernatants were assessed by an ELISA. The D₁₀ dose for X-rays in TE2, KYSE70, A549, NCI-H460 and WiDr cells was 2.1, 6.7, 8.0, 4.8 and 7.1 Gy, respectively, whereas that for carbon-ion beams was 0.9, 2.5, 2.7, 1.8 and 3.5 Gy, respectively. X-rays and carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of A549, NCI-H460 and WiDr cells at 72 h post-irradiation with a D₁₀ dose. Furthermore, irradiation with X-rays or carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of all five cell lines at 96 h post-irradiation. There was no significant difference in the amount of HMGB1 induced by X-rays and carbon-ion beams at any time-point (except at 96 h for NCI-H460 cells); thus we conclude that comparable levels of HMGB1 were detected after irradiation with iso-survival doses of X-rays and carbon-ion beams.     

Late giant coronary aneurysm associated with a fracture of sirolimus eluting stent: a case report

A 73-year-old female underwent percutaneous coronary intervention (PCI) because of stable angina. An elective PCI for the RCA lesion was first performed with deploying sirolimus eluting stents (SES). Three weeks later, PCI was also provided in the residual LAD lesion. Eight months later, she presented with new angina. CAG revealed an in-stent restenosis in the mid LAD and a large eccentric saccular coronary aneurysm (17 mm x 9 mm) at the proximal RCA. Intravascular ultrasound (IVUS) showed absence of stent struts around the orifice of aneurysm, which suggested a fracture of SES stent. The entry of coronary aneurysm was finally sealed with a polytetrafluoroethylene-covered stent. This report documented a rare case of late giant coronary artery aneurysm associated with a fracture of SES.     

Risk factors for patients developing a fulminant course with acute myocarditis.

BACKGROUND: A fulminant course can be difficult to predict at the onset of acute myocarditis, so the aim of the present study was to identify the predictive clinical symptoms/signs or laboratory findings. METHODS AND RESULTS: Thirty-nine patients with acute lymphocytic myocarditis, excluding 8 who manifested shock at admission, were studied. The fulminant group was defined as 12 patients who developed shock after admission, requiring intraaortic balloon pumping or percutaneous cardiopulmonary support, and the non-fulminant group comprised the 27 patients without shock. Various parameters at admission were compared between the 2 groups, together with multiple logistic regression analysis, excluding 6 patients with partially missing values. In the fulminant group, C-reactive protein (7.0 +/- 7.0 vs 2.3 +/- 2.2 mg/dl, p<0.01) and creatine kinase (1,147 +/- 876 vs 594 +/- 568 IU/L, p<0.05) concentrations were higher, intraventricular conduction disturbances were more frequent (9/12 vs 7/27 patients, p<0.01) and the left ventricular ejection fraction was lower (40.7 +/- 13.9 vs 50.1 +/- 10.6%, p<0.05) than in the non-fulminant group. In the multiple logistic regression analysis model with the presence/absence of a fulminant course considered as the independent variable, and C-reactive protein, creatine kinase, intraventricular conduction disturbances, and left ventricular ejection fraction as dependent variables, a high-risk group (expected proportion of fulminant course > or = 0.5) and a low-risk group (<0.5) could be differentiated. A fulminant course occurred in 9/13 (69%) patients in the high-risk group, but in only 2/20 (10%) patients in the low risk group (p<0.001). CONCLUSIONS: The risk of a fulminant course of acute myocarditis was high in patients with elevated C-reactive protein, and creatine kinase concentrations, decreased left ventricular ejection fraction, and intraventricular conduction disturbances at the time of admission.     

A case of left ventricular aneurysm associated with an anomalous coronary artery

A 54-year-old man presented with continual angina pectoris at rest, associated with an anomalous coronary artery. He also had an aneurysm at the submitral region of the left ventricular postero-lateral wall, without evidence or prior myocardial infarction, which showed hypokinetic inward motion during systole. We assume that this was a rare case of left ventricular aneurysm without prior myocardial infarction, the etiology which might related to the anomalous coronary artery.     

Recombinant Leishmania infantum Heat Shock Protein 83 for the Serodiagnosis of Cutaneous,Mucosal, and Visceral Leishmaniases

Routine serological diagnoses for leishmaniases, except in visceral cases, are performed using whole-parasite antigens. We used enzyme-linked immunosorbent assay (ELISA) to evaluate the performance of Leishmania infantum rHsp83 compared with L. major-like total promastigote antigen in the diagnosis of cutaneous (CL), mucosal (ML), and visceral leishmaniases (VL). ELISA-rHsp83 was significantly more sensitive than ELISA–L. major-like when considering either CL/ML (P = 0.041) or all leishmaniasis patients (P = 0.013). When samples from other infectious disease patients were evaluated for cross-reactivity, ELISA-rHsp83 was more specific than ELISA–L. major-like, specifically for Chagas disease samples (P < 0.001). We also evaluated the anti-rHsp83 antibody titers months after treatment and observed no significant difference in ML (P = 0.607) or CL (P = 0.205). We recommend ELISA–L. infantum-rHsp83 as a routine confirmatory serological assay for the diagnosis of Leishmania infection because of the high sensitivity, the specificity, and the insignificant cross-reactivity with other infectious diseases.