Bone Metastases from Soft Tissue Sarcomas

The incidence, distribution, time of appearance, and radiologic findings of bone metastases from soft tissue sarcomas, exclusive of lymphomas, were evaluated in 320 patients with soft tissue sarcomas. Thirty patients (9.4%) had evidence of 58 bone metastases. Five of 30 patients presented with metastases, and 25 of 30 patients developed metastases up to 66 months after presentation with a mean time interval of 21.3 months. The incidence of skeletal metastases differed among histologic subtypes of sarcomas; alveolar soft part sarcoma (5 of 8), dedifferentiated liposarcoma (2 of 4), angiosarcoma (2 of 4), and rhabdomyosarcoma (5 of 16) tended to show a higher incidence of bone metastases. The sarcomas metastasized to the regional bones close to the primary tumor in 16 (53%) of 30 patients and to the axial bones in 18 (60%). On conventional radiographs, the osseous metastases demonstrated predominantly osteolytic changes, and evidence of pathological fracture was observed in 31% of 58 metastases.     

Successful treatment of tracheomalacia associated with esophageal atresia without a tracheoesophageal fistula by aortopexy: Report of a case

Tracheomalacia (TM) is well known as a complication associated with esophageal atresia (EA) and tracheoesophageal fistula (TEF); however, the occurrence of TM requiring surgical treatment in a patient having EA without a tracheoesophageal fistula has never been reported. We describe herein a rare case of TM associated with EA without TEF. Respiratory distress was caused by compression of the trachea by a severely dilated upper esophageal pouch with weakness of the tracheal wall. Aortopexy was performed, and an excellent postoperative result was achieved.     

Changes in optic nerve head blood flow and retrobular hemodynamics following calcium-channel blocker treatment of normal-tension glaucoma

Background: Because calcium channel blockers reduce vascularresistance, they may have a clinical application in the treatment ofnormal-tension glaucoma (NTG). This study investigates changes inboth the optic disc blood flow and the hemodynamics of retrobulbarvessels in NTG patients after the systemic administration of a calcium channel blocker. Methods: Twelve eyes of 12 NTG patients (meanage 57 6 ± 15.3 years) were examined before and after a 4-weektreatment with 2 mg b.i.d. oral nilvadipine, an L-typc calcium channel blocker. By scanning laser-Doppler flowmetry (SLDF), we obtained the velocity, flow, and volume from within a 10 × 10 pixel windowplaced on the temporal rim region of the optic disc perfusion map. Byultrasound color Doppler imaging (CDI), we measured the peak systolicvelocity (PSV) and the end diastolic velocity (EDV) of the ophthalmicartery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA), and temporal posterior ciliary artery (TPCA). We then calculated a resistance index (RI) for each vessel. Results: After treatment, the flow and velocity of the optic disc blood flow significantly increased (P < 0.05).Nilvadipine also significantly reduced RIs of the CRA, NPCA, and TPCA(P <0 .05), and increased both the PSV of the NPCA and the EDVs of the CRA, NPCA, and TPCA. The percent change in velocity correlated significantly with the percent changes of the CRA RI and NPCA RI. Conclusions: Oral nilvadipine appears to reduce orbital vascular resistance, which consequentlyincreases the optic disc blood flow. Abbreviations.BP – blood pressure;CRA – central retinal artery;CDI – ultrasound color Doppler imaging;EDV – end diastolic velocity;NPCA – short posterior ciliary arteries located nasal to optic nerve;NTG – normal-tension glaucoma;OA – ophthalmic artery;PP – perfusion pressure;PSV – peak systolic velocity;RI – resistance index;SLDF scanning laser-Doppler flowmetry;TPCA – short posterior ciliary arteries locatedtemporal to optic nerve.     

Dynamic acquisition with a three-headed SPECT system: application to technetium 99m-SQ30217 myocardial imaging

A method for SPECT data acquisition, "continuous repetitive rotation acquisition," was developed with a high-sensitivity three-headed SPECT system. The method was applied to the dynamic imaging of 99mTc-SQ30217, a new myocardial imaging agent. After acquisition and reconstruction of SPECT data every minute, projection images at arbitrary intervals were used for tomographic reconstruction to determine the best timing of SPECT imaging in 99mTc-SQ30217. Based on a comparison of several possible acquisition intervals, SPECT data acquisition within 9 min after injection is recommended because of high myocardial uptake (myocardium-to-lung ratio, 2.83 +/- 0.42 (mean +/- s.e.m.) at 3-6 min) and relatively low hepatic uptake (myocardium-to-liver ratio, 0.85 +/- 0.13 at 3-6 min). The rate constant of the clearance of 99mTc-SQ30217 from the myocardium obtained by SPECT was: k1 = 0.249 +/- 0.050 per min (average half-life = 2.8 min) and k2 = 0.012 +/- 0.004/min (average half-life = 58 min). The continuous repetitive rotation acquisition SPECT study appears useful for imaging SQ30217 with its rapidly changing myocardial distribution.     

Pharmacokinetic study of low- versus high-dose medroxyprogesterone acetate (MPA) in women

The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and 14 received 1200 mg daily. Detailed PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition, multiple data for the minimum steady-state concentration (Css min) were analyzed. The MPA serum concentrations were measured by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day 1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax), area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more frequently in the high-dose group (P<0.01). Liver dysfunction (n=5) did not influence the PK of MPA. Five patients demonstrated extremely low AUC and Cmax (<10 ng/ml) values on day 1. Phenobarbital, dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view. Received: 2 May 1997 / Accepted: 13 October 1997     

Pain and Bradykinin Receptors--sensory transduction mechanism in the nociceptor terminals and expression change of bradykinin receptors in inflamed condition]

Bradykinin (BK), an endogenous algesic and sensitizing substance, excited nociceptors and sensitized their heat responses. These effects were mediated by B2 receptors (B2Rs) in normal condition, and B1 receptors were additionally recruited in inflammation. B2Rs were coupled with Gq/11 and their activation resulted in diacylglycerol and inositol triphosphate release. Diacylglycerol activated protein kinase (PK) Cepsilon in sensory neurons. To clarify what channel was modulated by PKC to depolarize nociceptor terminals, we examined the heat activation threshold (Tt) of heat-sensitive capsaicin receptor (TRPV1). Tt was lowered down to 31 degrees C by BK in concentration dependent manner through activation of PKCepsilon in cells heterologously expressing TRPV1 and B2Rs. Thus both excitation and sensitization to heat could be explained by one mechanism, lowering Tt of TRPV1. The same was observed in capsaicin-sensitive primary sensory neurons. However, TRPV1 knockout mice showed almost no change in BK-induced nociceptive behavior and nociceptor excitation, although BK-induced heat hyperalgesia completely disappeared, suggesting that TRPV1 was not the sole channel that was modulated by BK to depolarize nociceptor terminals. In addition nociceptor sensitivity to BK was augmented in inflamed animals, with B2R mRNA and protein upregulated. The mechanism for prostaglandin-induced augmentation of BK response is left open for future study.     

TH1/TH2 and regulatory cytokines in adults with otitis media with effusion.

OBJECTIVE: Otitis media with effusion is one of the most common and intractable ear diseases. However, the role of Th1, Th2, and immunoregulatory cytokines on the pathogenesis of the disease in adult patients remains to be determined. The aim of this study is to disclose the cytokine expression in middle ear effusions (MEEs) in adults and to compare the profile on the basis of the presence of allergic rhinitis and the type of effusions. STUDY DESIGN: A prospective controlled clinical study. PATIENTS: MEEs were collected from 80 adult subjects. The concentration of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, and interferon (IFN)-gamma in MEEs were determined by using enzyme-linked immunosorbent assay. RESULTS: IL-2, IL-4, IL-5, IL-10, IL-12, and IFN-gamma in MEEs were detected in 60 (75.0%), 33 (41.3%), 42 (52.5%), 14 (17.5%), 80 (100%), and 66 (82.5%) samples, respectively. Among these cytokines, only the concentration of IL-4 in the allergic rhinitis-positive group was significantly higher than that in the allergic rhinitis-negative group. On the other hand, IL-2, IL-12, and IFN-gamma were detected, regardless of the presence of allergic rhinitis, and the concentration of these cytokines correlated with each other. The correlation between the concentration of IL-4 and IL-5 was also detected. In addition, both the incidence rate and the concentration of IL-10 in MEEs were significantly higher in the mucoid type compared with those in the serous type effusions. CONCLUSION: Regardless of allergic status, IL-12 may play a critical role in the pathogenesis of otitis media with effusion by affecting the production of IL-2 and IFN-gamma. In addition, IL-4 may have some impact on the immunologic condition in adults with allergic rhinitis. IL-10 potentially affects the viscosity of MEEs.     

Somatic mutations of epidermal growth factor receptor in colorectal carcinoma.

PURPOSE: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non-small cell lung carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA. EXPERIMENTAL DESIGN: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction and PCR, we examined EGFR mutations by sequencing genomic DNA. RESULTS: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma. CONCLUSIONS: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these tumors may be susceptible to gefitinib treatment.     

Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

PURPOSE: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. EXPERIMENTAL DESIGN: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. RESULTS: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC. CONCLUSION: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.