Impairment of acid-neutralizing capacity and lesion formation in the rat duodenum during hemorrhagic shock: comparative study with indomethacin

The effects of hemorrhagic shock (HE) on duodenal pH, acid-neutralizing capacity and mucosal tolerance to acid were investigated in anesthetized rats, and they were compared with those of indomethacin. HE was performed by bleeding from the carotid artery to reduce arterial blood pressure to about 55 mmHg (3 ml of bleeding per 200 g of body weight), and indomethacin was given s.c. in a dose of 5 mg/kg. Duodenal pH was determined in the outflow from the proximal duodenum (1.7 cm) which was perfused with 10(-4) M HCl, and acid-neutralizing capacity was measured by back-titration of the perfusate to pH 4.0 with 10 mM HCl. Under these conditions, duodenal pH was kept at around 6.0 as the result of neutralization in the loop (approximately 8 microEq/hr). Both HE and indomethacin significantly decreased the pH and acid-neutralizing capacity. Administration of 16,16-dimethyl prostaglandin E2 (16-dmPGE2: 30 micrograms/kg, s.c.) significantly increased both pH and acid-neutralizing capacity in normal and indomethacin-treated rats, but failed to affect these parameters in rats under HE conditions. When the duodenal loop was perfused with 50 mM HCl for 1.5 hr, both HE and indomethacin induced extensive damage in the mucosa. Pretreatment with 16-dmPGE2 significantly reduced the formation of duodenal lesions induced by indomethacin but not by HE. These results suggest that HE as well as indomethacin impaired duodenal acid-neutralizing capacity to reduce the tolerance to acid of the mucosa. The deleterious effects of HE on the mucosa may be mainly due to a decreased mucosal blood flow, but not due to a deficiency of endogenous prostaglandins.     

Monoclonality of both pale cells and cuboidal cells of sclerosing hemangioma of the lung.

Sclerosing hemangioma of the lung remains poorly understood, and it is still unclear whether this lesion is neoplastic or not. It consists of two major cell types, pale cells and cuboidal cells. We analyzed the clonality of each cell types from six female cases of surgically resected sclerosing hemangioma. The pale cells and cuboidal cells were separated by microdissection from methanol-fixed sections, and DNA was extracted for clonal analysis based on an X-chromosome-linked polymorphic marker, the human androgen receptor (HUMARA) gene or the phosphoglycerate kinase (PGK) gene. The HUMARA and PGK genes were found to be amplified with or without digestion by the methylation-sensitive restrictive endonuclease HpaII. Five of six cases were informative. Pale cells and cuboidal cells showed the same monoclonality in all of the informative cases, whereas the control cells showed a polyclonal pattern. Our results demonstrated that sclerosing hemangioma is caused by monoclonal expansion of cells, confirming that it is a neoplasia. Moreover, the present data indicate that both pale cells and cuboidal cells are derived from the same cell.     

Phase I Study of Paclitaxel by Three-hour Infusion: Hypotension Just after Infusion Is One of the Major Dose-limiting Toxicities

The primary objectives of this study were to determine the maximum tolerated dose (MTD) of paclitaxel administered by 3-h infusion to patients with solid tumors, and to characterize the pharmacokinetics of a 3-h infusion in comparison with those of a 24-h infusion. Twenty-seven patients each received one of six levels of paclitaxel, 105, 135, 180, 210, 240 and 270 mg/m², with premedication. Two patients given 240 mg/m² and one patient given 270 mg/m² unexpectedly had grade 3/4 hypotension just after finishing the paclitaxel infusion. Peripheral neuropathy was also dose-limiting at 270 mg/m². Although granulocytopenia was significantly less severe than with a 24-h infusion, more than half of the patients experienced grade 4 toxicity at doses of 240 or 270 mg/m². Severe hypersensitivity reactions (HSRs) were not observed. Pharmacokinetic studies using high performance liquid chromatography demonstrated proportionally greater increases in the peak plasma concentration and area under the curve, and decreases in clearance and volume of distribution with increasing dose, suggesting non-linear pharmacokinetics of paclitaxel when given by 3-h infusion. The MTD of paclitaxel given as a 3-h infusion was determined to be 240 mg/m² with dose-limiting toxicities of granulocytopenia, peripheral neuropathy and hypotension. Hypotension just after infusion, induced by 3-h infusion of paclitaxel, is a new observation which has not been reported previously. The recommended dose for phase II study is 210 mg/m². Although hypotension was observed as an unexpected toxic effect, paclitaxel could be administered safely over 3 h with premedication and proper monitoring, resulting in reduced myelotoxicity and with no increase in the incidence of HSRs as compared with a 24-h infusion.     

Correlations between bone mineral density and demographic, lifestyle, and biochemical variables in community-dwelling Japanese women 69 years of age and over

Introduction A few epidemiologic studies have comprehensively attempted to identify risk factors for low bone mineral density (BMD) in elderly Asian women. The purpose of this study was to identify demographic, lifestyle, and biochemical factors correlated with BMD in elderly Japanese women 69 years of age and over.Methods The study design was cross-sectional. The subjects were 583 ambulatory women aged 69 years and over, and their average age was 74.3 (SD 4.4) years. Predictor variables were age, reproductive history, anthropometric indices, grip strength, calcium intake, lifestyle information, and serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D (1,25(OH)₂D), osteocalcin (OC), and undercarboxylated osteocalcin (ucOC) values. The outcome variable was forearm BMD measured with a DTX-200 osteometer.Results Simple linear regression analyses showed that BMD was significantly positively associated with body height, weight, body mass index, grip strength, serum albumin concentration, and “housework,” and negatively associated with age, years since menopause, age at menarche, number of children, serum 1,25(OH)₂D concentration, serum OC concentration, and ucOC concentration. The stepwise multiple regression analysis showed that weight (β=0.00316, SE=0.00028, R²=0.180), age (β=−0.00321, SE=0.00050, R²=0.108), log-transformed serum OC (β=−0.0445, SE=0.0064, R²=0.053), log-transformed serum 1,25(OH)₂D (β=−0.0401, SE=0.0074, R²=0.050), “farmwork” (β=0.00904, SE=0.00426, R²=0.005), and serum 25(OH)D concentration (β=0.000281, SE=0.000120, R²=0.003) were significantly associated with BMD.Conclusion It was concluded that body weight is a major predictor of forearm BMD among the factors measured in this study in independent Japanese women 69 years of age and over and that serum 1,25(OH)₂D concentration may be associated with cortical BMD. Maintenance of body weight is very important for maintaining BMD in this population, unless a large weight aggravates obesity-related diseases. A follow-up study is needed to confirm these findings.     

Surgical treatment of native valve endocarditis]

Twenty eight patients with native valve endocarditis (NVE) were subjected to this study. Thirteen patients underwent an operation at the chronic phase, and 15 patients at the active phase. One of the 13 patients at the chronic phase died of cardiac rupture due to myocardial infarction which had occurred preoperatively, and one of 10 patients at active phase without annular infection died of rupture of mycotic cerebral aneurysm early postoperatively. Among 5 patients at the active phase with annular infection, prosthetic valve endocarditis occurred in one patient 1.5 months after supraannular aortic valve replacement, and the second operation with a translocation technique was needed. This patient was lost from low output syndrome. Another patient in this group, who underwent a translocation technique because of mycotic annular abscess, died of intestinal infarction late postoperatively. The other 24 patients went a good postoperative course. Five patients with annular infection at the active phase had a shorter duration from the infectious onset to operation (20 days to 2 months, average 38 days), and the causative microorganisms were streptococcus faecalis, staphylococcus epidermidis and gram-negative coccus. One patient, who died of mycotic cerebral aneurysmal rupture, had candida albicans as a causative microorganism. For patients with NVE, an early aggressive operation is essential before infection extends to the annulus or to other vital organs, especially when these microorganisms are identified.     

A case of Marfan syndrome with recurrent bilateral pneumothorax and anuloaortic ectasia

A 17-year-old male patient with Marfan syndrome was admitted due to recurrent bilateral pneumothorax which had recurred totally 11 times during the past 3 years. For the treatment of obstinately continuing right pneumothorax resection of bullae in combination with pleuropexy using OK 432 was effective. Two months thereafter Bentall operation with a composite graft consisting of a woven Dacron tube and a Bj?rk-Shiley 27 mm aortic valve prosthesis was performed for his anuloartic ectasia. Left pneumothorax recurred 2 weeks after Bentall operation. But it was treated successfully with OK 432 injection into the left pleural cavity. Now, he is doing well as a student.     

Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer.

Between April 1985 and May 1988, we conducted a randomized study comparing two standard chemotherapy regimens with the same regimens given on an alternating basis in patients with small-cell lung cancer. The patients were randomly assigned to receive cyclophosphamide at a dose of 800 mg/m2 intravenously (IV) on day 1, doxorubicin at 50 mg/m2 IV on day 1, and vincristine at 1.4 mg/m2 IV on day 1 (CAV); cisplatin at 80 mg/m2 IV on day 1 and etoposide at 100 mg/m2 IV on days 1, 3, and 5 (PE); or CAV alternating with PE (CAV/PE). Each regimen was repeated every 3-4 weeks. Three hundred patients were entered in the study, and 288 of them were eligible for analysis (97 for CAV, 97 for PE, and 94 for CAV/PE). The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%), while the complete response rates were similar (14%, 16%, and 15%, respectively). Nine (23%) of 39 patients who failed to respond to the initial CAV regimen responded to PE when they were crossed over. In contrast, only one (8%) of 13 patients responded to CAV after failing to respond to the PE regimen, suggesting that these two regimens were partially non-cross-resistant. The response duration on CAV/PE was significantly longer than that with CAV (P = .004). The survival time with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (P = .027) or that with PE (9.9 months) (P = .056). In patients with limited disease, the survival in the alternating arm was significantly superior to the survival in the CAV arm (P = .014) or the survival in the PE arm (P = .023). The toxic effects were acceptable in all three chemotherapy regimens. These results favor the alternating chemotherapy over either standard chemotherapy, such as CAV and PE, although the differences are not dramatic.     

Mutational screening of APP gene in patients with early-onset Alzheimer disease utilizing mismatched PCR-RFLP

To elucidate the frequency of mutations of the β/A4 amyloid protein precursor (APP) gene in early-onset Alzheimer disease, we designed a mismatched PCR-RFLP that can identify all kinds of missense mutations at codon 717 in addition to the seven kinds of known mutations at exon 17. When we screened mutations at exon 17 utilizing this method and the double missense mutations at exon 16 of the APP gene by PCR-RFLP, no cases revealed mutations of the APP gene among 13 familial and 54 sporadic cases, except one family (OS-1) that had previously been reported and used as a positive control of APP717(Val → Ile). Our results support the hypothesis that mutations in the APP gene are not major causes in early-onset Alzheimer disease.     

A case of sarcomatoid carcinoma of the thymus

A 57-year-old woman presented with a 10×10 cm anterior mediations mass. The tumor had Invaded the pericardium, both lungs and the left brachiocephallc vein, and was treated by partial resection and postoperative radiation therapy. Pathological examination of the tumor revealed squamous cell carcinoma with a spindle cell sarcomatous component. Immunohistochemically, keratin and epithelial membrane antlgen were posltive In both the spindle cell sarcomatous areas and the squamous cell carcinomatous area and thus, a diagnosis of thymic carcinoma of sarcomatoid type was made. The patient died of recurrent disease 1 year after surgery. This case is the seventh reported In the English literature Because of the poor outcome, adjuvant therapy is recommended.