Endobronchial ultrasonography in the assessment of centrally located early-stage lung cancer before photodynamic therapy

To evaluate the utility of endobronchial ultrasonography (EBUS) in selecting appropriate candidates with centrally located early-stage lung cancer for photodynamic therapy (PDT) with curative intent, we performed EBUS before PDT in 18 biopsy-proven squamous cell carcinomas (including three carcinoma in situ) that had been considered to be appropriate candidates for PDT by conventional bronchoscopy and high-resolution computed tomography (HR-CT). Nine lesions were diagnosed as intracartilaginous by EBUS and subsequently PDT was performed. Long-term complete remission has been achieved in these patients with a median follow-up term after PDT of 32 months. The remaining nine lesions were diagnosed as extracartilaginous by EBUS and were considered candidates for other therapies such as surgical resection, chemotherapy, and radiotherapy, although two were invisible by HR-CT, three were superficial, and five were < or = 1 cm in diameter on observation by bronchoscopy. The depth of tumor invasion estimated by EBUS was proven to be accurate by histopathologic findings in six specimens after surgical resection. We conclude that EBUS is a useful technique that might be considered in addition to conventional bronchoscopy and HR-CT to improve the efficacy of PDT in patients with centrally located early-stage lung cancer.     

Changes in adiposity and excess body weight correlate with growth responses but not with decreases in low-density lipoprotein cholesterol levels during GH treatment in GH-deficient children

BACKGROUND AND AIMS: GH has profound effects on body composition and lipid metabolism in children as well as in adults. The relationship between such metabolic effects and the growth-promoting effects of GH has not been studied thoroughly in children with GH deficiency. This prospective study was designed to determine the relationship between growth and lipid metabolism during long-term GH treatment. PATIENTS AND METHODS: Twenty-two boys with idiopathic GH deficiency were studied. Height, per cent overweight (%OW), per cent body fat (%BF) and serum low-density lipoprotein (LDL) cholesterol levels were determined every 6 months during 3 years of GH treatment. RESULTS: After 3 years of GH treatment, the mean height SD score had increased significantly from -2.70 SD to -1.59 SD (P < 0.0001), while the mean %OW and LDL cholesterol level had decreased significantly from 7.0% to 1.3% (P < 0.0001) and from 2.69 mmol/l to 2.04 mmol/l (P < 0.0001), respectively. The mean %BF fell significantly from 15.5% to 11.1% during the first 6 months of GH treatment (P < 0.0001). The 6-month reduction in %BF correlated significantly with the 3-year increase in height SD score (r = -0.58, P = 0.008). The decrease in %OW also correlated negatively with the change in height SD score (r = -0.48, P = 0.03). However, there was no correlation between the changes in LDL cholesterol levels and those in %BF, %OW or height SD score. CONCLUSION: We conclude that the growth-promoting effects of GH correlate significantly with the reductions in %BF and %OW but not with the decrease in LDL cholesterol level in children with GH deficiency. The changes in LDL cholesterol did not correlate with any of the changes in body composition parameters, suggesting that the various actions of GH may have different mechanisms of regulation.     

Efficacy and safety of growth hormone (GH) in the treatment of adult Japanese patients with GH deficiency: a randomised, placebo-controlled study.

OBJECTIVE: The aim of this study was to assess the effect of growth hormone (GH) replacement therapy on lean body mass (LBM) and other variables including body fat mass, serum lipids and quality of life measures in GH-deficient Japanese adults. DESIGN: This was a multicentre, double-blind, placebo-controlled, parallel group study. Following initial screening, patients were randomly assigned to GH treatment (n=37) or placebo (n=36). GH treatment was started at an initial dose 0.003 mg/kg/day s.c. each day for the first 4 weeks after which the dose was increased to 0.006 mg/kg/day for 4 weeks and then to 0.012 mg/kg/day for the last 16 weeks (n=37). Body composition, serum lipids, serum IGF-I and IGFBP-3 levels were measured during the 24-week study. Short Form-36 and Quality of Life Assessment of GH Deficiency in Adults scores were also determined. RESULTS: LBM was significantly increased from baseline at 24 weeks in GH-treated patients, with a mean (+/-SD) increase of 4.7% (+/-5.3%) compared with an increase of 1.0% (+/-4.4%) in the placebo group (p<0.0001 versus baseline, p=0.0003 versus placebo). Percentage body fat decreased significantly from baseline in GH-treated patients (9.3%, p<0.0001), compared with a non-significant 0.2% increase in the placebo group (p<0.0004 for difference between treatment groups). In addition, significantly increased serum IGF-I and IGFBP-3 levels and improvements in the patients' serum lipid profiles were observed in patients who received GH therapy. Changes in quality of life measures did not differ between treatments, probably because of the small number of patients studied. GH therapy was well tolerated, with adverse events of any cause reported in 86.5% of the GH treatment group and 83.3% of the placebo group. CONCLUSION: GH treatment significantly improved body composition and serum lipid profiles in adult Japanese patients with GH deficiency compared with placebo and had no clinically relevant adverse effects.     

Thoracoscopic removal of middle mediastinal schwannoma originating from recurrent nerve

Schwannomas of the left recurrent nerve are rare and there is no agreement on how to manage them without causing recurrent nerve dysfunction. We present a 63-year-old male with unspecific clinical symptoms in whom a middle mediastinal mass with a diameter of 5 cm was found incidentally. At thoracoscopic surgery,we found that the encapsulated tumor originated from left recurrent nerve and we performed tumor enucleation without sacrificing the recurrent nerve. The patient did experience postoperative hoarseness and vocal cord paralysis even though we preserved the recurrent nerve. To our knowledge, thoracoscopic removal of a left recurrent nerve schwannoma has not been reported in the literature before.     

Soy β-conglycinin improves glucose uptake in skeletal muscle and ameliorates hepatic insulin resistance in Goto-Kakizaki rats

Although the underlying mechanism is unclear, β-conglycinin (βCG), the major component of soy proteins, regulates blood glucose levels. Here, we hypothesized that consumption of βCG would normalize blood glucose levels by ameliorating insulin resistance and stimulating glucose uptake in skeletal muscles. To test our hypothesis, we investigated the antidiabetic action of βCG in spontaneously diabetic Goto-Kakizaki (GK) rats. Our results revealed that plasma adiponectin levels and adiponectin receptor 1 messenger RNA expression in skeletal muscle were higher in βCG-fed rats than in casein-fed rats. Phosphorylation of adenosine monophosphate–activated protein kinase (AMP kinase) but not phosphatidylinositol-3 kinase was activated in βCG-fed GK rats. Subsequently, βCG increased translocation of glucose transporter 4 to the plasma membrane. Unlike the results in skeletal muscle, the increase in adiponectin receptor 1 did not lead to AMP kinase activation in the liver of βCG-fed rats. The down-regulation of sterol regulatory element-binding factor 1, which is induced by low insulin levels, promoted the increase in hepatic insulin receptor substrate 2 expression. Based on these findings, we concluded that consumption of soy βCG improves glucose uptake in skeletal muscle via AMP kinase activation and ameliorates hepatic insulin resistance and that these actions may help normalize blood glucose levels in GK rats.     

Spondylocostal dysostosis with tetralogy of Fallot and herniation of the spleen through the diaphragm

Spondylocostal dysostosis (SCD) is a very rare syndrome characterized by vertebral malformation and rib deformity. Some of the patients with SCD have other birth defects in the central nervous system, the genitourinary tract, diaphragm or heart and so forth. There have been reported SCD with complex congenital heart disease, such as pulmonary atresia, double outlet right ventricle, and d‐transposition of great arteries. However, there have been no reported SCD patients with confirmed tetralogy of Fallot (TOF). Here, a patient with SCD having a very rare combination of rib defects on the right side and left‐sided scoliosis, tetralogy of Fallot, and diaphragmatic spleen herniation, which had not been reported before, was described.     

Comparative allelotype of early and advanced stage non-small cell lung carcinomas

To identify chromosomal loci of tumor suppressor genes involved in the genesis and progression of non-small cell lung carcinoma (NSCLC), comparative allelotype analysis was performed in 23 stage I primary lung tumors and in 22 metastatic lung tumors to the brain. In total, 84 loci on all 22 autosomal chromosomes were examined for loss of heterozygosity (LOH) by restriction fragment length polymorphism (RFLP) analysis with 40 polymorphic DNA probes and polymerase chain reaction (PCR)-LOH analysis of 44 polymorphic loci. LOH on chromosome arms 3p, 13q, and 17p was detected frequently (>60%) in both stage I primary lung tumors and brain metastases, whereas the incidence of LOH on chromosome arms 2q, 5q, 9p, 12q, 18q, and 22q was more than 60% only in brain metastases. In particular, the incidence of LOH on chromosome arms 2q, 9p, 18q, and 22q in brain metastases was significantly higher than that in stage I primary lung tumors (P < 0.05). These results indicate that tumor suppressor genes on chromosome arms 3p, 13q, and 17p are involved in the genesis of NSCLC, whereas those on several chromosome arms, especially on 2q, 9p, 18q and 22q, play an important role in the progression of NSCLC. Genes Chromosom Cancer 17:71–77 (1996). © 1996 Wiley-Liss, Inc.     

Diagnostic utility of programmed cell death ligand 1 (clone SP142) immunohistochemistry for malignant lymphoma and lymphoproliferative disorders: A brief review

The programmed cell death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumor cell escape from immune control and has been most extensively investigated for therapeutic purposes. However, PD-L1 immunohistochemistry is still not used widely for diagnosis. We review the diagnostic utility of PD-L1 (by clone SP142) immunohistochemistry in large-cell lymphomas, mainly consisting of classic Hodgkin lymphoma (CHL) and diffuse large B-cell lymphoma (DLBCL). Neoplastic PD-L1 (nPD-L1) expression on Hodgkin and Reed-Sternberg cells is well-established among prototypic CHL. Of note, EBV+ CHL often poses a challenge for differential diagnosis from peripheral T-cell lymphoma with EBV+ non-malignant large B-cells; their distinction is based on the lack of PD-L1 expression on large B-cells in the latter. The nPD-L1 expression further provides a good diagnostic consensus for CHL with primary extranodal disease conceivably characterized by a combined pathogenesis of immune escape of tumor cells and immunodeficiency. Compared with CHL, the nPD-L1 expression rate is much lower in DLBCL, highlighting some specific subgroups of intravascular large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and EBV+ DLBCL. They consist of nPD-L1-positive and -negative subgroups, but their clinicopathological significance remains to be elucidated. Microenvironmental PD-L1 positivity on immune cells may be associated with a favorable prognosis in extranodal DLBCL. PD-L1 (by SP142) immunohistochemistry has helped us to understand the immune biology of lymphoid neoplasms possibly related by immune escape and/or immunodeficiency. However, knowledge of these issues remains limited and should be clarified for diagnostic consensus in the future.     

Quantitative evaluation of extracellular glutamate concentration in postischemic glutamate re-uptake, dependent on brain temperature, in the rat following severe global brain ischemia

Changes in brain temperature are known to modulate the marked neuronal damage caused by an approximately 10-min intra-ischemic period. Numerous studies have suggested that the extracellular glutamate concentration ([Glu](e)) in the intra-ischemic period and the initial postischemia period is strongly implicated in such damage. In this study, the effects of intra-ischemic brain temperature (32, 37, 39 degrees C) on [Glu](e) were investigated utilizing a dialysis electrode combined with ferrocene bovine serum albumin (BSA), which allows oxygen-independent real-time measurement of [Glu](e). This system allowed separate quantitative evaluation of intra-ischemic biphasic glutamate release from the neurotransmitter and metabolic pools, and of postischemic glutamate re-uptake in ischemia-reperfusion models. The biphasic [Glu](e) elevation in the intra-ischemic period did not differ markedly among intra-ischemic brain temperatures ranging from 32 to 39 degrees C. Intra-ischemic normothermia (37 degrees C) and mild hyperthermia (39 degrees C) markedly inhibited [Glu](e) re-uptake during the postischemic period, although the intra-ischemic [Glu](e) elevation did not differ from that during intra-ischemic hypothermia (32 degrees C). It was assumed that normothermia or mild hyperthermia in the intra-ischemic period influences intracellular functional abnormalities other than the intra-ischemic [Glu](e) elevation, thereby inhibiting glutamate re-uptake after reperfusion rather than directly modulating intra-ischemic [Glu](e) dynamics.