Chemotherapy-induced anemia in patients with primary lung cancer.

To elucidate the factors which influence the value of hemoglobin, the nadir value of hemoglobin, frequency of blood transfusion and prognostic value of blood transfusion in patients with primary lung cancer during intensive chemotherapy, the hematological features of 124 patients entered into a randomized phase III study containing cisplatin were retrospectively analyzed. There was no difference in the percent nadir hemoglobin value of the first course of chemotherapy (% of pretreatment value) in any of the subgroups with respect to sex, body weight loss, performance status, age, stage, number of metastatic sites or treatment arms. The only predictive indicator for the nadir hemoglobin value in the first course of chemotherapy was the pretreatment value of hemoglobin. The equation for the regression line was y = 1.07 + 0.73x (R2 = 0.663, p < 0.001). The lowest nadir hemoglobin value (% of pretreatment value) during all chemotherapy courses was significantly lower in the subgroups older than 60 years and those with body weight loss. There was an inverse correlation between the accumulated dose of cisplatin and the lowest nadir hemoglobin value (p < 0.05). The frequency of blood transfusion in patients with more than two metastatic sites was significantly higher than in those with one or no metastatic sites (p < 0.05). Survival of patients who had required blood transfusion after chemotherapy was significantly shorter than that of patients who had not (p < 0.05).     

Change in apoptosis in the gastric surface epithelium and glands after eradication of Helicobacter pylori

BACKGROUND: Change in apoptosis in gastric glands after eradication of Helicobacter pylori has never been reported. AIMS: The purpose of this paper is to investigate the change in apoptosis in gastric glands after eradication of Heliobacter pylori. PATIENTS AND METHODS: We studied 23 Heliobacter pylori-positive patients with duodenal and gastric ulcers, who were monitored for 6-12 months after eradication, and eight controls. Biopsies were taken from the antrum and body. Apoptosis was evaluated immunohistochemically using anti-single stranded DNA antibody. Apoptotic index was calculated by counting immunostained cells in surface epithelial and glandular cells. RESULTS: In the surface epithelium, Apoptotic indexes were significantly higher in patients than in controls. In the upper portion of fundic glands, apoptotic indexes were significantly higher in patients with gastric ulcers (14.2% (9.3, 17.8)) (median (1st quartile, 3rd quartile)) than in controls (8.0% (2.0, 9.0), p < 0.01) and decreased significantly after eradication (3.4% (2.0, 5.3)), p < 0.01). In pyloric glands, apoptotic indexes were no different between patients and controls. In the lower portion of fundic glands, apoptotic indexes were very low, both in patients and in controls. CONCLUSIONS: Our results showed that apoptosis, not only of surface epithelial cells but also of glandular cells in the upper portion of fundic glands, increased in Heliobacter pylori-positive patients with gastric ulcers and decreased to normal levels after eradication of Heliobacter pylori.     

Malfunction of arterial sarcoplasmic reticulum leading to faster and greater contraction induced by high-potassium depolarization in young spontaneously hypertensive rats.

The contribution of sarcoplasmic reticulum was studied with regard to the increase in arterial contraction induced by a high-potassium depolarization in spontaneously hypertensive rats (SHR). The 20 mmol/l potassium-induced contraction of femoral arteries was faster and greater in 6-week-old SHR than in age-matched normotensive Wistar-Kyoto (WKY) rats. Relaxation after washing the arteries with a Krebs solution was slower in SHR than in WKY rats. When the sarcoplasmic reticulum of SHR arteries had been depleted of calcium by caffeine in a calcium-free solution, the rate of high-potassium-induced contraction of the calcium-depleted SHR arteries was slowed, the same result as that with non-calcium-depleted WKY arteries. In ryanodine-treated arteries, the rate and magnitude of high-potassium-induced contraction were enhanced slightly in SHR and greatly in WKY rats, resulting in no final difference between SHR and WKY rats. Ryanodine slowed the relaxation rate in WKY rats but not in SHR. These results suggest that the diminution in ability of sarcoplasmic reticulum to sequester calcium may be responsible for the faster rate and greater magnitude of high-potassium-induced contraction with the slower relaxation in SHR arteries. We postulated that genetic malfunction of sarcoplasmic reticulum causes the increased contraction of arterial smooth muscle leading to the enhanced vasoconstriction and elevated blood pressure in SHR.     

Normothermic cardiopulmonary bypass: effect on the incidence of persistent postoperative neurological dysfunction following coronary artery bypass graft surgery

We retrospectively reviewed the records of 250 consecutive patients undergoing coronary artery bypass graft surgery (CABG) from January 1994 through January 1996 to determine the incidence of persistent postoperative neurological dysfunction after CABG and to compare normothermic and moderate hypothermic cardiopulmonary bypass (CPB). Normothermic CPB was used in 128 patients (36°–37°C) and hypothermic CPB (27°–28°C) in 122 patients. Postoperative neurological dysfunction included focal motor deficits, delayed recovery of consciousness (>24h) after surgery, and seizures within 1 week postoperatively. Persistent neurological dysfunction was diagnosed if complete resolution had not occurred within 10 days of surgery. The incidence of persistent postoperative neurological dysfunction was 4.1% in the hypothermic CPB group and 2.3% in the normothermic CPB group. There were no statistically significant differences between the two groups (P=NS). These results suggest that normothermic CPB did not increase the incidence of persistent postoperative neurological dysfunction compared to hypothermic CPB.     

Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor).

CTGF/CCN2, a hypertrophic chondrocyte-specific gene product, possessed the ability to repair damaged articular cartilage in two animal models, which were experimental osteoarthritis and full-thickness defects of articular cartilage. These findings suggest that CTGF/CCN2 may be useful in regeneration of articular cartilage. INTRODUCTION: Connective tissue growth factor (CTGF)/CCN2 is a unique growth factor that stimulates the proliferation and differentiation, but not hypertrophy, of articular chondrocytes in vitro. The objective of this study was to investigate the therapeutic use of CTGF/CCN2. MATERIALS AND METHODS: The effects of recombinant CTGF/CCN2 (rCTGF/CCN2) on repair of damaged cartilage were evaluated by using both the monoiodoacetic acid (MIA)-induced experimental rat osteoarthritis (OA) model and full-thickness defects of rat articular cartilage in vivo. RESULTS: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2. Therefore, CTGF/CCN2 was suspected to play critical roles in cartilage repair. In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage. Next, to examine the effect of rCTGF/CCN2 on the repair of articular cartilage, we created defects (2 mm in diameter) on the surface of articular cartilage in situ and implanted rCTGF/CCN2-hydrogel or PBS-hydrogel therein with collagen sponge. In the group implanted with rCTGF/CCN2-hydrogel collagen, new cartilage filled the defect 4 weeks postoperatively. In contrast, only soft tissue repair occurred when the PBS-hydrogel collagen was implanted. Consistent with these in vivo effects, rCTGF/CCN2 enhanced type II collagen and aggrecan mRNA expression in mouse bone marrow-derived stromal cells and induced chondrogenesis in vitro. CONCLUSION: These findings suggest the utility of CTGF/CCN2 in the regeneration of articular cartilage.     

A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

Malignant Rhabdoid Tumor of the Breast: A Case Report

A 66-year-old woman time of 10 days. One month after radicalmastectomy, there was local recurrence, followed by multiplepulmonary metastases, and the patient died of respiratory failure5 months after surgery. The gray-white-colored tumor measured13x12x;10 cm, and its border was well defined. The tumor wascomposed of diffusely growing round or polygonal cells withvesicular nuclei, prominent nucleoli, and ample cytoplasm containingeosinophilic inclusions. Lymph node involvement was widespread.Both vimentin and keratin were clearly demonstrated by immunohistochemicalstaining. Ultrastructural studies revealed that the MRT cellscontained cytoplasmic whorls of intermediate filaments.     

Developmental changes in beta-adrenoceptors, muscarinic cholinoceptors and Ca2+ channels in rat ventricular muscles.

1. In an attempt to explain the previous electrophysiological data on the ontogeny of beta-adrenergic and muscarinic cholinergic interactions on cardiac Ca2+ current, biochemical studies were performed on the ontogeny of beta-adrenoceptors, muscarinic cholinoceptors and Ca2+ channels in cardiac muscle of developing rats: 16-20 days old foetuses, 0-20 days old neonates, and 2-3 months old adults. 2. Developmental changes in cardiac beta-adrenoceptors, muscarinic cholinoceptors, and Ca2+ channels were determined with the use of specific radioligands, [3H]-dihydroalprenolol (DNA), [3H]-quinuclidinyl benzilate (QNB), and [3H]-nitrendipine (NTD), respectively. 3. The Bmax value (fmol mg-1 tissue) for [3H]-DNA binding started to increase on post-gestation day 20, reached almost its maximum level on neonatal day 6, kept almost the same level until neonatal day 20, and then decreased slightly to its adult level. 4. The Bmax value (fmol mg-1 tissue) for [3H]-QNB binding started to increase on post-gestation day 16, reached almost its maximum level on neonatal day 0, remained almost constant until neonatal day 15, and then decreased to its adult level. 5. The Bmax value (fmol mg-1 tissue) for [3H]-NTD binding increased with age between post-gestation day 18 and neonatal day 15, stayed almost constant until neonatal day 20, and then decreased to its adult level. 6. The Kd values for [3H]-DHA, [3H]-QNB, and [3H]-NTD bindings remained almost constant during the developmental period examined.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peroxidase-antiperoxidase staining for estrogen and progesterone in scirrhous type of gastric cancer: possible existence of the estrogen receptor

Tissue specimens from patients with the scirrhous type of gastric carcinoma were stained using the peroxidase-antiperoxidase (PAP) method. Nine out of thirty-seven specimens (24 per cent) showed positive estrogen staining, and here tissues from male or older patients were usually stained. Cumulative survival rate in patients whose tissue showed a positive estrogen staining was higher than that in case of a negative estrogen staining. Four out of thirty-one specimens (13 per cent) stained positively for progesterone, all four patients being male. These results suggest that estrogen and progesterone may relate to the growth of the scirrhous type of gastric cancer.