A simple technique for arthroscopic suture fixation of displaced fracture of the intercondylar eminence of the tibia using folded surgical steels.

SUMMARY: The purpose of this article is to describe a new and simple technique for arthroscopic suture fixation of avulsion fractures of the intercondylar eminence of the tibia using surgical steels as both suture passers and suture. The looped ends of 2 folded surgical steels being used as suture passers were inserted through 2 tibial drill holes and through the reduced bone fragment into the knee joint cavity and pulled out through the anteromedial portal in front of the knee joint. Outside the knee joint, a third unbent surgical steel to be used as a suture was tied to the 2 small loops of the folded surgical steels very easily. The ends of the folded surgical steels outside the tibia were then retracted back through the tibial drill holes, thereby automatically bringing the third surgical steel through the holes while making a loop over the avulsed fragment. The advantage of this technique is that the suture can be tied to the suture passers outside of the knee joint.

Identification of catalytically essential residues in Escherichia coli esterase by site-directed mutagenesis.

Escherichia coli esterase (EcE) is a member of the hormone-sensitive lipase family. We have analyzed the roles of the conserved residues in this enzyme (His103, Glu128, Gly163, Asp164, Ser165, Gly167, Asp262, Asp266 and His292) by site-directed mutagenesis. Among them, Gly163, Asp164, Ser165, and Gly167 are the components of a G-D/E-S-A-G motif. We showed that Ser165, Asp262, and His292 are the active-site residues of the enzyme. We also showed that none of the other residues, except for Asp164, is critical for the enzymatic activity. The mutation of Asp164 to Ala dramatically reduced the catalytic efficiency of the enzyme by the factor of 10(4) without seriously affecting the substrate binding. This residue is probably structurally important to make the conformation of the active-site functional.

Lymph node spread from carcinoma of the gallbladder.

BACKGROUND: Lymph node spread is the most common pattern of progression in gallbladder carcinoma (GBC) and is a prognostic factor. The purpose of this study was to determine the prevalence of lymph node metastases in patients with resected advanced GBC, and to evaluate the curative effects of radical surgery for patients with lymph node metastasis. METHODS: One hundred and eleven consecutive patients who had undergone radical surgery for GBC were included in this study. The pattern of lymph node metastases was examined histopathologically, using the TNM staging of the American Joint Committee on Cancer. RESULTS: There was no neurovascular invasion or lymph node involvement in 15 patients with pT1 tumors. Sixty of 96 patients with pT2-4 tumors had lymph node metastases. The pericholedochal lymph node was the most common metastatic lymph node, followed by the cystic lymph node. The frequency of metastases in retroportal, posterosuperior pancreaticoduodenal, and interaorticocaval lymph nodes was >15% in all cases. pT3-4 tumors had significantly more lymph node involvement (79%) and significantly higher N2:N1 ratios (2.5) than pT2 tumors (46% and 0.6, respectively). There was no difference in 5-year survival between N0 and N1 groups in pT2-4 tumors (66% in N0 and 53% in N1). Patients with N2 disease had a significantly worse prognosis, but 4 patients survived >5 years. CONCLUSIONS: The cystic and pericholedochal lymph nodes are the initial site of spread from GBC. The frequency of lymph node involvement is strongly influenced by the depth of invasion of the primary tumor. GBC limited to such lymph node metastases can be cured by surgery in >50% of such cases.

APC, K-ras codon 12 mutations and p53 gene expression in carcinoma and adenoma of the gall-bladder suggest two genetic pathways in gall-bladder carcinogenesis.

Current histopathological evidence suggests that gall-bladder cancer has two main morphological pathways for its development: de novo (ab initio) origin and adenoma-carcinoma sequence. In order to investigate the genetic difference between them, APC mutations were examined by RNase protection analysis, K-ras mutations by nested polymerase chain reaction-restriction fragment length polymorphism analysis, and p53 gene overexpression by immunohisto-chemical analysis in both tumors and benign lesions of the gall-bladder. Overexpression of the p53 gene was detected in 105 of 164 (64%) de novo carcinomas regardless of size and depth of invasion, but not in 16 tumors of carcinoma-in-pyloric-gland-type adenoma, or in 51 adenomas (47 pyloric gland-type and 4 intestinal-type). K-ras codon 12 mutation was detected in 4 of 40 (10%) de novo carcinomas, all four being associated with p53 gene overexpression, but not in 12 tumors of carcinoma in adenoma or 16 adenomas (14 pyloric gland-type and 2 intestinal-type). APC mutation was not found in 16 de novo carcinomas or the one pyloric gland-type adenoma examined. These results suggest that there are two distinct genetic pathways in gall-bladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, and carcinoma-in-pyloric-gland-type adenoma develops from p53-, K-ras-, and APC-gene-unrelated, as yet unknown, alteration.

Hemolytic anemia provoked by recombinant alpha-interferon.

A 30-year-old female with chronic hepatitis C treated with recombinant alpha-interferon developed serious hemolytic anemia after receiving 10 million units a day for 4 weeks. The results of Coombs' tests were negative before and after interferon therapy. The hemolytic anemia gradually improved after the withdrawal of recombinant alpha-interferon and the administration of methyl-prednisolone. The clinical course suggested that the recombinant alpha-interferon had provoked the hemolytic anemia.

Late onset hepatic failure due to hepatitis B virus with mutations in the pre-core region.

A 60-year-old man complained of severe general fatigue on October 11, 1992. Pertinent laboratory findings were: aspantate aminotransferase (AST) 1920 IU, alanine aminotransferase (ALT) 2050 IU, and total bilirubin (T. Bil) 124 micromol/l (normal range, 0-17 micromol/l). Virological assay revealed that hepatitis B surface antigen (HBsAg), anti-hepatitis B e (HBe), anti-HBc, and immunoglobulin M (IgM) anti-HBc were positive, and anti-HBs, HBeAg, and anti-delta antibody were negative. A diagnosis of acute hepatitis due to hepatitis B virus was made. Despite a decrease in transaminase, jaundice worsened and prothrombin time was prolonged. On the 60th day of hospitalization, massive ascites developed, but the patient's consciousness was not impaired. Although, albumin and diuretics were given, the ascites further increased. Paracentesis of 2000 ml of ascitic fluid was performed twice a week. On the 120th day of hospitalization, the patient passed black stools and he exhibited renal failure 3 weeks later. Although severe jaundice persisted, he was still alert. On the 150th day of hospitalization, massive gastrointestinal bleeding occurred, due to hemorrhagic gastritis. Despite receiving intensive care, the patient died. Determination of the HBV DNA sequence revealed two point mutations in the pre-core region; these have not been reported elsewhere.

p53 immunostaining distinguishes malignant from benign lesions of the gall-bladder.

The expression of p53 protein was studied in formalin-fixed paraffin-embedded specimens of 41 well-differentiated adenocarcinomas of the gall-bladder, six cases of acute cholecystitis and 23 cases of chronic cholecystitis, using a monoclonal p53 (PAb 1801) antibody and streptavidin-biotin. p53 staining was divided into diffuse, focal or sporadic patterns. The relationship between the p53 Labeling Index (p53 LI) and cellular proliferation was also investigated using monoclonal Ki-67 (MIB1) antibody. Twenty-four of the 41 carcinomas (58.5%) had a diffuse staining pattern with a high p53 LI (47-93%) and 9.8% (4/41) had a focal staining pattern with an intermediate p53 LI (22-34%), with no relation to pT stage, tumor size, histologic type or grade of cytologic atypia. The p53 LI was higher than the Ki-67 LI in these tumors except for one. On the other hand, p53 staining was completely sporadic in the non-neoplastic specimens with a low p53 LI (0.2-2.8%). The p53-positive cells in these specimens were located only within areas of Ki-67-positive cells. In conclusion, p53-protein overexpression occurs as an early event in approximately 70% of well-differentiated adenocarcinomas of the gall-bladder, and this alteration is maintained during progression from intramucosal to invasive carcinoma. p53 immunostaining can distinguish malignant from benign lesions of the gall-bladder.

[Late phase II study of CGS16949A, a new aromatase inhibitor--a multicentral cooperative study (Western Japan Group)].

A late phase II study of a new non-steroidal aromatase inhibitor CGS16949A was performed in postmenopausal patients with advanced or recurrent breast cancer. The drug was given orally, 1 mg twice daily for 12 weeks or more. Of 72 evaluable cases, there were 1-CR, 10-PR, 17-"long NC", 12 NC and 32-PD, with "long NC" defined as disease stabilization for more than 6 months. Median time to the onset of PR and median duration of objective tumor responses were 85 and 278 days, respectively. Maximum and median duration of long NC were 471 and 243 days, respectively. Adverse effects were observed in 5 (7.8%) of 64 cases. In laboratory evaluations, slight abnormalities were observed in 11 (17.2%) of 64 cases. No adverse effect and laboratory abnormality was found worse than Grade 1 toxicity. As for Global Utility Rating, treatment with CGS16949A was considered to be useful or better in 24 (32.9%) of 73 cases. Plasma estradiol and estrone concentrations at one month after initiation of the treatment decreased significantly in comparison with pre-treatment levels. Plasma cortisol, testosterone and androstenedione was not changed. Thus, CGS16949A showed good efficacy, tolerability and usefulness in postmenopausal patients with advanced or recurrent breast cancer.

[Eosinophil activation in acute asthma attacks evaluated by electronmicroscopic findings of eosinophils and the concentration of eosinophil cationic protein in sputum].

We evaluated the activation of eosinophils in the airways of patients with acute asthma attacks by measuring the concentration of sputum eosinophil cationic protein (ECP) and changes in the electron densities of the eosinophil specific granules in sputum. In six hospitalized patients with asthmatic attacks, sputum samples were collected for seven consecutive days after admission and were used for the evaluation of eosinophil activation. The concentration of sputum ECP, the incidence of changes in the electron densities of eosinophil specific granules and the severity of asthma attacks were highest on the day of admission and decreased in association with each other after treatment. A significant correlation was found between the concentration of sputum ECP and the incidence of changes in the electron densities of eosinophil specific granules. These findings suggest that the eosinophils in the airways are markedly activated and degranulated in asthma attacks.

[Silent myocardial ischemia in diabetics--by treadmill exercise testing].

We examined silent myocardial ischemia in diabetics by treadmill exercise testing. There were 28 diabetic men and 64 diabetic woman without angina, with a mean age of 59 +/- 11 years. Symptom-limited treadmill exercise testing was performed, and we used the electrocardiogram during exercise and immediately after exercise for judgement. ST segment depression was defined as positive if there was at least 0.1 mV of ST depression 80 ms from the J point. It was defined as negative if max heart rate (HR) was more than 80% of target HR and there was no significant ST depression. It was defined as equivocal if there was no significant ST depression but max HR was less than 80% of target HR. In 92 diabetics, 21 patients (23%) showed positive ST depression, 35 (38%) showed negative ST depression, 36 (39%) showed equivocal ST depression. In 56 diabetics exclusive of treadmill equivocal patients, 38% of patients showed positive ST depression. Treadmill positive diabetics had a significantly higher rate of smokers, patients with hypertension, and a higher triglyceride level as compared with treadmill negative diabetics. Coronary arteriography, which was performed in six treadmill positive diabetics, revealed coronary stenosis of more than 75% in four patients.

Induction of colorectal tumors in rats by sulfated polysaccharides.

Some sulfated polysaccharides, such as d-CGN, APS, and DSS, have carcinogenicity to the rat colorectum. These materials first induced colitis, secondly squamous metaplasia, and finally tumors at the colorectum. Initially, colitis was located in the columnar epithelium of the rectum and extended proximally thereafter. Squamous metaplasia persisted in almost all experimental rats and progressed irreversibly. The tumors were adenoma, adenocarcinoma, squamous cell papilloma, and squamous cell carcinoma. Macrophages containing these materials were observed in the lamina propria mucosa and submucosa of the colorectum. There were differences in the molecular weight of the substances and their tumor incidences. However, with regard to their carcinogenicity, these sulfated polysaccharides were inferred to be similar to each other in their target organs and process of tumor development. Consequently, these sulfated polysaccharides may be one entity of carcinogenic sulfates.

A study on carcinogenesis induced by degraded carrageenan arising from squamous metaplasia of the rat colorectum.

We have undertaken studies on carcinogenesis arising from precancerous lesions, such as squamous metaplasia and ulcerative lesions of the rat colorectum, after termination of degraded carrageenan administration. Rates of tumor incidence in groups that were given a 10% diet of degraded carrageenan for 2, 6 and 9 months were 5 rats out of 39 (12.8%), 8 out of 42 (19.0%) and 17 out of 42 (40.5%), respectively. The colorectal squamous metaplasia persisted in all rats and progressed irreversibly. Degraded carrageenan was deposited not only in the colorectal propria mucosa, but also in the other reticuloendothelial organs. These results show that, even with short-term degraded carrageenan administration, degraded carrageenan is carcinogenic to the colorectum of the rat after a prolonged period.