Hypotensive and hypertensive effects of acetaldehyde on blood pressure in rats

Intravenous injection of acetaldehyde produced hypotensive actions in pentobarbital-anaesthetised whole rats, but hypertensive actions in pithed rats. The hypotensive effects of acetaldehyde in whole rats were abolished by pre-treatment with yohimbine. In pithed rats, the hypertensive effects of acetaldehyde were significantly attenuated by prazosin and phentolamine, and in rats that had been pre-treated with reserpine. Our results suggest that the hypertensive actions of acetaldehyde in pithed rats are due to the release of catecholamines, which subsequently leads to vasoconstriction. In whole rats the hypotensive actions of acetaldehyde may be due to alpha2-adrenoceptor stimulation in the central nervous or peripheral system.     

The treatment of unruptured tubal pregnancy with intratubal methotrexate injection under laparoscopic control

Nine patients with unruptured tubal pregnancies of 6-9 weeks' duration were treated with methotrexate intratubal injection under laparoscopic control. Urinary hCG levels decreased immediately after completion of the procedure, with a median time of 11 days (range 1-29) to resolution. Tubal patency on the side of the ectopic gestation was confirmed by hysterosalpingography 1-3 months after the procedure in all cases. This method requires a reduced methotrexate dosage compared with intramural or intravenous therapy. The indications are unruptured tubal pregnancy of 4 cm or less in diameter and urinary hCG levels of 8000 mIU/mL or lower.     

Gastrin Receptor Gene Expression in Several Human Carcinomas

Gastrin has been shown to enhance the growth of various human tumors. The present study was designed to examine the gastrin receptor gene expression in various human carcinoma cell lines and in surgically resected carcinoma tissues. By Northern blot analysis, gastrin receptor mRNA was detected in 3 out of 7 small cell lung carcinoma cell lines. Gastrin receptor mRNA was also expressed in one out of 8 colon carcinoma cell lines and 2 out of 10 colon carcinoma tissues. Moreover, one of two small cell carcinoma cell lines of the stomach clearly expressed gastrin receptor mRNA. However, none of the gastric adenocarcinoma cell lines or surgically resected gastric adenocarcinomas tested had any detectable expression of gastrin receptor gene. These findings may suggest a role of gastrin receptor in the growth and differentiation of certain human carcinomas.     

Comparison of mortality between respondents and non-respondents in a mail survey

We conducted a population-based mail survey and prospectively compared mortality between respondents and non-respondents. Age-adjusted mortality rates for all causes were higher among non-respondents than among respondents in both sexes. Age-adjusted rate ratios were 1.50 for males and 1.33 for females. Non-respondents also had, in both sexes, higher mortality for three leading causes of death, namely, cancer, heart diseases and stroke than respondents. In particular, the difference between the two groups was much greater for cardiovascular disease than for cancer. Our results suggested that prospective studies using data from respondents to mail surveys in Japan would have underestimated the mortality for cardiovascular disease.     

Reactivity of anti-AraC-resistant cell monoclonal antibody, YU-311, in formalin-fixed paraffin-embedded specimens of various hematopoietic disorders

YU-311 is a monoclonal antibody reacting with cytosine arabinoside (AraC)-resistant human leukemic cell line and identifies a 92 kDa membrane protein. We have examined YU-311 reactivity with various hematopoietic disorders by an immunohistochemical method and evaluated a correlation between YU-311 expression and refractoriness to chemotherapy, retrospectively. YU-311 reacted with AraC-resistant human leukemia cell lines, in which a 92 kDa membrane protein was identified by Western blotting, whereas drug-resistant cell lines to other than AraC failed to express YU-311 antigen. The frequency of YU-311 positivity was significantly increased in relapsed cases. Only five cases were positive for YU-311 at diagnosis and 24 cases at relapse. Unexpectedly, only eight cases of relapsed leukemia/lymphoma expressed YU-311 and P-glycoprotein simultaneously. Most of the YU-311-positive relapsed cases showed clinical refractoriness for chemotherapy and then failed to induct complete remission or relapsed at short periods with short disease-free duration. These findings indicate that YU-311 expression is closely associated with some aspects of drug resistance, especially with AraC resistance.     

Case report of dysgerminoma in a patient with 46,XX pure gonadal dysgenesis

A clinicopathological study of a 42-year-old female with pure gonadal dysgenesis and dysgerminoma was made. At the age of 29, the patient with primary amenorrhea had been evaluated clinically and cytogenetically. (1) The results of cytogenetic studies were X-chromatin positive and revealed a karyotype in peripheral blood leukocytes of 46,XX. (2) Laboratory studies indicated hypergonadotropic hypogonadism and no response of the gonads to the human menopausal gonadotropin stumulation test. (3) At laparotomy, the gonads were streak-like. Pathological examinations of biopsy specimens from both gonads revealed dense, fibrous connective tissue resembling ovarian stroma and no primary follicles. Eleven years after the laparotomy, the patient complained of lower abdominal distention and severe pain, and laparotomy then revealed a 15 × 17-cm right solid adnexal mass occupying the pelvic cavity. The histological diagnosis of tissues from the partially removed tumor was pure dysgerminoma. Second-look operation after Linac X-ray irradiation showed complete remission of the residual tumor. Insofar as we are aware, the present patient represents the first case of dysgerminoma which occurred in the dysgenetic gonads of a phenotypic female with normal 46,XX sex-chromosomal constitutions in peripheral blood leukocytes and the skin fibroblasts although a possibility exists that mosaicism was possibly present but undetected, particularly since the streak gonads were not analyzed chromosomally.     

Multiple Ileal Diverticula Causing an Ileovesical Fistula: Report of a Case

We report a case of multiple ileal diverticula causing an ileovesical fistula in an 85-year-old man. The patient was admitted for investigation and treatment of intractable urethrocystitis, which he had suffered for 5 years. Cystography showed an ileovesical fistula, and contrast study of the small bowel revealed about 80 diverticula in the ileum. The segment involved by diverticula was resected and a pathological diagnosis of diverticulitis leading to ileovesical fistula was confirmed. His postoperative clinical course was uneventful. Received: September 13, 2001 / Accepted: March 5, 2002     

Effect of protein-bound uraemic toxins on the thermodynamic characteristics of human albumin

The ability of albumin to bind drugs and other lipophilic organic acids is decreased in chronic renal failure by the accumulation of albumin-bound uraemic toxins such as hippuric acid, indoxyl sulphate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF). This furan acid is the most highly bound and is not removed by haemodialysis. The inhibitory effects of these three uraemic toxins on the interaction of three marker ligands sodium octanoate (for medium chain fatty acids), salicylic acid and phenol red (bilirubin site/site I) with albumin have been investigated by differential scanning microcalorimetry and flow microcalorimetry. CMPF was the most potent inhibitor and its binding site coincided with that of bilirubin (site I). Indoxyl sulphate binds to the site for medium-chain fatty acids and tryptophan (site II) and hippuric acid, the weakest inhibitor, inhibited binding to the salicylic acid site.     

Practical issues and observations on the use of foreign clinical data in drug development

The International Conference on Harmonization (ICH) has recently developed the ICH guidelines, which are the common guidelines for regulatory requirements in the ICH regions, i.e., European Union, Japan, and the United States of America. The guidelines have been successively implemented in the ICH regions, and the people involved in drug evaluation in the pharmaceutical industry, such as statisticians and pharmaceutical scientists, have referred to the guidelines during their daily work. Probably one of the most influential ICH guidelines on the drug development process in the ICH regions, especially in Japan, is the ICH-E5 guideline, which is encouraging the pharmaceutical industry to use the mountain of foreign clinical data for the registration of a new drug. In this article, we review the issues concerning the ICH-E5 guideline discussed so far, and discuss some practical issues in applying the guideline, especially the design of the study conducted in a new region. This is called a "bridging study." In addition, we introduce some statistical approaches for evaluating the acceptability of foreign clinical data.     

A case of acid burn of the penis

A 27-year-old man presented to our hospital complaining of multiple mild injuries sustained in an attack of violence at the workplace. He had received chemical burns to the penis induced by hydrochloric acid and had developed severe phimosis. He complained of pain on erection and ballooning during urination. The foreskin was partially resected with foreskin grafting for the stricture. The postoperative outcome was favorable and his symptoms were relieved.