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Extensive primary repair of the thoracic aorta in Stanford type A acute aortic dissection by means of a synthetic vascular graft with a self-expandable stent.

OBJECTIVES: To minimize any residual false lumen when operating on patients with an acute type A aortic dissection, we tried to perform extensive primary repair of the thoracic aorta with the modified elephant trunk technique. The early and midterm results of these surgical interventions are reported and evaluated. METHODS: Among the acute type A aortic dissections with extensive false lumen encountered since December 1997, 19 consecutive patients, 15 DeBakey type I with the tear in the ascending, transverse, or both aortas, and 4 DeBakey type III-D with the tear located in the descending aorta, underwent insertion of a synthetic graft with a distally anchored stent in the descending thoracic aorta. The interpolation method was used as an introducer combined with total replacement of the aortic arch by using a synthetic branching graft with only a median sternotomy. RESULTS: One patient died, and 18 were discharged after full recovery. Postoperative computed tomographic scans showed that no residual false lumina were present proximal to the diaphragmatic level, and no false lumina were found in 10 patients. Two patients with acute ischemia of the right kidney caused by narrowing of the true lumen, as demonstrated by radiographic computed tomography, improved significantly after surgical intervention with restoration of blood flow in the true lumen. Paraplegia was not observed in any patient. CONCLUSIONS: In emergency operations for an acute type A aortic dissection, the operation is often limited to replacing the ascending aorta because priority is given to saving the patient's life. However, it is possible to perform extensive primary repair of the thoracic aorta with relative safety by interpolating a synthetic graft with a self-expandable stent.

Aged↗

[In vitro antifungal activity of itraconazole, a new triazole antifungal agent, against clinical isolates from patients with dermatomycoses].

In vitro antifungal activities of itraconazole (ITZ), a triazole antifungal agent, against clinical isolates obtained from patients with superficial and subcutaneous mycoses were examined using the agar dilution method on casitone agar. The clinical isolates tested were 7 species and 263 isolates including Trichophyton mentagrophytes (104 isolates), Trichophyton rubrum (103 isolates), Microsporum canis (3 isolates), Epidermophyton floccosum (2 isolates), Candida albicans (32 isolates), Malassezia furfur (7 isolates) and Sporothrix schenckii (12 isolates). The results are summarized as follows: 1. MIC values of ITZ for the isolates of dermatophytes and M. furfur distributed in a range of less than 0.0012-5 micrograms/ml indicating that ITZ had greater in vitro activities. These in vitro activities of ITZ were greater than those of clotrimazole or bifonazole. 2. C. albicans isolates were divided into 2 groups in terms of ITZ-susceptibilities, a high susceptibility group and low-susceptibility group with MIC values of 0.02-0.08 micrograms/ml and greater than 10 micrograms/ml, respectively. 3. The in vitro activities of ITZ against S. schenckii isolates with a geometric mean MIC of 0.119 micrograms/ml were greater than those of ketoconazole, miconazole or amphotericin B used as reference drugs.

Amphotericin B↗

Experimental model for predicting metastatic ability of tumors using chick embryo.

At present, there is no established diagnostic method by which the metastatic ability of an individual human cancer can be accurately predicted. We used chicken chorioallantoic membrane (CAM) to predict the metastatic ability of three B16 murine melanoma variant lines and also of human giant-cell carcinoma of the lung. Tumor cells were deposited on the CAM of eggs 10 days after fertilization. On day 7 after the tumor inoculation, the embryos were killed, and the lungs removed, minced and implanted on the CAM of other 10-day-old embryos. On day 7 after this inoculation, the tumors on the CAM were inspected under a surgical microscope, and were also checked histologically. The results accurately reflected the differing metastatic abilities of the B16 melanoma variant lines. Metastases were observed in the lungs of the embryo bearing human giant-cell carcinoma of the lung on the CAM. Using CAM seems to be a suitable way of predicting the malignancy of tumors with metastatic ability.

Animals↗

Intravenous diltiazem versus isosorbide dinitrate for unstable angina: comparison of coronary angiographic morphology in the unstable and stabilized states.

BACKGROUND: The efficacy of intravenous infusion of diltiazem was compared with that of isosorbide dinitrate (ISDN) for the early treatment of unstable angina. METHODS: Sixty-four patients with at least 70% organic stenosis of the culprit artery and prolonged rest angina were enrolled. Coronary angiography was performed on admission. Subsequently, patients were randomly assigned to receive either intravenous diltiazem or ISDN. Coronary angiography was repeated when the angina was under control, and the findings were compared with those on admission. RESULTS: Diltiazem was more effective than ISDN, and symptoms were resolved in 84% of the diltiazem group compared with 47% of the ISDN group (P = 0.0038). Repeat coronary angiography showed that the degree of stenosis remained unchanged in the majority of patients (n = 47, 75.8%). There was no difference between the two groups with regard to the coronary angiographic findings. CONCLUSIONS: Since diltiazem was more effective than ISDN even though the coronary angiographic findings of the two groups were similar, it is possible that some action other than vasodilatation (such as a direct protective effect on the myocardium) may be responsible for the remission of unstable angina.

Aged↗

Localization of hepatitis B surface antigen in the human parotid gland.

Localization of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the human parotid gland and liver was studied by an immunohistochemical method in four cases with seropositive HBsAg. Neither HBsAg nor HBcAg could be detected in the parenchymal cells of the parotid gland in any of the cases. However, one of four cases, which had the highest titer of serum HBsAg, showed HBsAg immunoreactivity in the vascular wall and luminal fluid of the parotid gland. In liver, HBsAg was detected in three and HBcAg in two of the four cases, respectively. HBsAg was localized in the cytoplasm of hepatocytes, while HBcAg was localized mainly in their nuclei. The detection of HBsAg in the parotid gland and liver was correlated with the serum titer of the antigen. The results indicate that the HB virus does not have an affinity for or a replicate in the parotid gland. Also, it is suggested that the HBsAg found in saliva is derived from HBsAg circulating through the oral mucosa by capillary leakage and not from secretion into the mouth by the salivary gland.

Adolescent↗

A novel murine model of oral candidiasis with local symptoms characteristic of oral thrush.

A conventional and easy method to establish a murine oral candidiasis model, which has not only a stable yeast population in the oral cavity but also symptoms characteristic of oral thrush, was developed by using a sedative agent. Mice were immunosuppressed with prednisolone and were given tetracycline hydrochloride. They were orally infected with 10(6) viable cells of Candida albicans by means of a cotton swab and enough chlorpromazine chloride had been injected to keep them in a sedative state about for 3 hr after inoculation. From day 3 to day 7 post inoculation, 10(5)-10(6) colony forming units of Candida were recovered from the oral cavity of each mouse and whitish, curd-like patches were observed on most parts of tongue. Microscopically, germ tubes had appeared on the tongue surface. This model would be a useful experimental oral candidiasis for investigating the pathogenesis of C. albicans oral infection and the efficacy of various antifungal agents microbiologically and symptomatically.

Amphotericin B↗

Neutrophil priming as a surgery-related risk factor for postoperative infectious complications in patients with ulcerative colitis.

AIMS: The present study was designed to assess whether preoperative neutrophil priming under surgical stress has causal effects on the postoperative clinical outcomes of ulcerative colitis (UC) patients. PATIENTS AND METHODS: In 63 consecutive UC patients, perioperative changes in cytokines and neutrophil elastase (NE) were quantified and their relationships to postoperative infectious complications (PICs) were evaluated. RESULTS: A preoperative increase in NE (high group: Group H) was associated with longer disease duration and greater preoperative total amount of steroids administered. Patients in Group H developed more PICs than those in the low NE group when they underwent surgery >240 min. In Group H, the NE level remained high after longer duration surgery, but decreased rapidly after shorter duration surgery. Multivariate analyses revealed that the total amount of steroids used and preoperative NE level were independent risk factors for predicting PICs in the longer operation group. CONCLUSION: Preoperative neutrophil activation may become a risk factor for postoperative morbidity when the patients undergo intense surgical stress. The most important procedures for preventing postoperative morbidity in high-risk UC patients may be reducing surgical stress and/or controlling neutrophil activation perioperatively.

Adult↗

Enhanced antitumor efficacy of nedaplatin with 5-fluorouracil against human squamous carcinoma xenografts.

BACKGROUND: The antitumor efficacy of a combination of Nedaplatin (NDP) with 5-fluorouracil (5-FU) was evaluated using human squamous carcinomas in vivo. Because NDP was developed as a second generation platinum complex, we also compared the antitumor activity of NDP with 5-FU with that of Cisplatin (CDDP) with 5-FU. MATERIALS AND METHODS: 5-FU was injected daily for five days and either NDP or CDDP was injected once via the tail vein of mice implanted with KB3-1, OCC-1-JCK, LJC-1-JCK and Ma44 human squamous carcinomas. In some experiments, continuous administration of 5-FU using an osmotic pump was utilized. RESULTS: The sequential administration of 5-FU prior to NDP or CDDP (FN or FC therapy) resulted in enhanced inhibition of tumor growth in comparison with NDP, CDDP or 5-FU monotherapy against KB3-1, OCC-1-JCK and LJC-1-JCK squamous carcinomas. The combination of FN treatment was synergistic and as effective as that of FC treatment. FN treatment with continuous infusion of 5-FU using an osmotic pump, also led to enhanced tumor growth inhibition and prolonged survival against Ma44 squamous carcinoma. CONCLUSION: The results demonstrated the antitumor efficacy NDP with 5-FU against four human squamous carcinoma xenografts and suggested the clinical effectiveness of FN treatment.

Animals↗

[Comparative genomic hybridization for analysis of chromosomal changes in cisplatin-resistant ovarian cancer].

In our attempt to find characteristic genetic changes in resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers, using the comparative genomic hybridization (CGH) method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy in comparison with 14 tumors from patients who completely responded to the chemotherapy. We found gains in chromosomal region 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators and regulators of the apoptotic pathway are found to be located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance for cisplatin-based chemotherapy in ovarian cancer patients based on the CGH analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients prior to cisplatin-based chemotherapy.

Antineoplastic Agents↗

[General anesthesia for disabled patients undergoing dental treatment in a general hospital].

BACKGROUND: General anesthesia for dental treatment in disabled patients may present particular problems, especially when it is done in a general hospital, compared with specialized dental hospitals. METHODS: We surveyed 24 patients who underwent dental treatment under general anesthesia in our institution during the last decade. RESULTS: Electrocardiography or chest x-ray photography was not obtained in 8 patients owing to lack of patients' cooperation. Slow induction with sevoflurane was selected in 5 patients, because intravenous cannulae could not be placed owing to their rejection. Nasotracheal intubation was performed in all patients, but no difficulty in intubation was documented. As postoperative complications, we observed convulsion in one patient and muscle rigidity in another, but no critical troubles related to circulatory or respiratory status. In patients who were treated for more than ten teeth, we observed differences in age, body weight, duration of anesthesia, maximum concentration of sevoflurane administered during anesthesia, and use of postoperative analgesics compared with the other patients. CONCLUSIONS: We found particular problems of anesthesia for disable patients undergoing dental treatment in a general hospital, and suggest that information on numbers of teeth to be treated is helpful.

Adolescent↗

Cytokine responsiveness in cultured human small airway epithelial cells in relation to lung transplantation.

BACKGROUND: We report a new method for collecting and establishing small airway epithelial cells (SAEC). This method enables the evaluation of the cytokine responsiveness of SAEC, which is still unknown. In this study we evaluated intercellular adhesion molecule-1 (ICAM-1) expression on SAEC stimulated with several inflammatory cytokines and compared it with that on large airway epithelial cells (LAEC). MATERIALS AND METHODS: LAEC and SAEC were treated with IFN-gamma, TNF-alpha, IL-1beta, or their combination. ICAM-1 expression under various conditions was quantified by flow cytometry. Furthermore, immunocytochemical staining was performed to determine intranuclear displacement of signal transducer and activator transcription 1 (Stat1) during ICAM-1 expression by various cytokine stimulations. RESULTS: 1) ICAM-1 expression on both LAEC and SAEC was significantly increased by IFN-gamma stimulation alone and synergistically enhanced by IFN-gamma plus TNF-alpha or IL-1beta stimulation, 2) intranuclear displacement of Stat1 in SAEC by the stimulation with IFN-gamma plus TNF-alpha or IL-1beta was recognized earlier in comparison with that by IFN-gamma stimulation alone. CONCLUSION: The previously unknown peripheral cytokine responsiveness and its mechanisms of SAEC were revealed by this study, which contributes to the understanding of chronic lung allograft rejection recognized around small airways.

Adult↗

Effect of mercuric ion on attraction to light of artemia sp nauplii.

Living organisms exhibit a phototactic response which can be altered by certain environmental toxic chemical species. The analysis of photobehavior can help in elucidating environmental factors that influence photomotility reactions of the organisms. A method has been developed that measures the phototactic response of Artemia nauplii under the influence of mercuric ion (Hg2+) in synthetic seawater. The phototactic response of Artemia nauplii was manifested by movement of the organisms from a darkened half to lighted half of an experimental vessel containing synthetic seawater. The density as a function of time of Artemia nauplii is determined by removing aliquots from both light and dark sides and then plating on agar for counting under the dissecting microscope. Measurements consistently show a significant movement of nauplii to the lighted side within 45 min of the start of the experiments. The present investigation demonstrated that at concentrations as low as 0.010 mg HgCl2/liter there is an enhancement of phototactic effect on Artemia nauplii by mercuric ion as compared with control. The phototactic response of Artema nauplii is altered by mercuric ion in a dose-related manner, but the mechanism of this effect is presently unknown.

Animals↗

Cilostazol inhibits leukocyte integrin Mac-1, leading to a potential reduction in restenosis after coronary stent implantation.

OBJECTIVES: The aim of this study was to confirm clinically a hypothesis that cilostazol inhibits leukocyte Mac-1, leading to prevention of post-stent restenosis. BACKGROUND: The platelet phosphodiesterase III inhibitor called cilostazol also inhibits alpha-granule release of P-selectin in platelets. The P-selectin-mediated platelet-leukocyte interaction promotes activation and upregulation of leukocyte Mac-1 after coronary stenting, which plays a key role on the mechanism of restenosis. Thus, cilostazol's potential inhibition of this process may lead to prevention of restenosis. METHODS: Using flow cytometric analysis of whole blood obtained from the coronary sinus, the expression of platelet membrane glycoproteins and neutrophil adhesion molecules was observed in 70 consecutive patients undergoing coronary stenting. The patients were randomly assigned to either a cilostazol or ticlopidine group before stent placement. RESULTS: The restenosis rate was lower (15% vs. 31%, p < 0.05) in the cilostazol group (n = 34) than in the ticlopidine group (n = 32). A stent-induced increase in platelet P-selectin (CD62P) expression and an increase in neutrophil Mac-1 (CD11b) expression were suppressed in the cilostazol group compared with the ticlopidine group. Angiographic late lumen loss was correlated with the relative changes in platelet P-selectin and neutrophil Mac-1 at 48 h after coronary stenting. CONCLUSIONS: Cilostazol may have effects on suppression of P-selectin-mediated platelet activation, platelet-leukocyte interaction, and subsequent Mac-1-mediated leukocyte activation, which might lead to a reduced restenosis rate after coronary stent implantation.

3',5'-Cyclic-AMP Phosphodiesterases↗

Format of cases affects learning outcomes in first year medical students.

CONTEXT: Longitudinal problem-based learning (PBL) tutorials are practiced at the Tokyo Women's Medical University. First year medical school students - most of whom are high school graduates with no medical background - often encounter difficulty identifying problems while solving PBL cases in basic science. The format of PBL case presentation may affect learning. OBJECTIVES: This study compares the learning outcomes of two cohorts of first year students who learned basic human biology through PBL cases presented in clinical vs. non-clinical formats. METHODS: All first year students in 1995 and 2000 undertook PBL tutorials. The 1995 case was presented in a non-clinical format; the 2000 case was presented in a clinical format. Both cases had five identical pre-set learning objectives in basic science. By examining all written materials generated during the tutorial sessions, learning outcomes were categorized and the accomplishment of preset objectives was analysed. FINDINGS: In 2000, the number of learning outcomes for clinical medicine was more than double compared to 1995, whereas the numbers of total and basic science learning outcomes were not significantly different. The number of preset objectives accomplished by the students was significantly higher in 2000. Thus, PBL case format affected the learning outcomes, enabling these first year students to achieve basic science objectives, while enhancing their interest in the clinical aspects of human biology. CONCLUSION: Learning outcomes in first year medical students may be enhanced when PBL cases designed to learn basic science contain relevant clinical elements.

Biological Science Disciplines↗

Protection of monkeys against Shiga toxin induced by Shiga toxin-liposome conjugates.

BACKGROUND: We previously reported that the purified Shiga toxins (Stx) Stx1 and Stx2, when coupled with liposomes, induced substantial production of anti-Stx1 and anti-Stx2 IgG antibody, respectively, in mice. The levels of anti-Stx antibody in the sera of mice immune to Stx-liposome correlated well with the protection against subsequent challenge with Stx. Furthermore, mice immunized with a mixture of Stx1-liposome and Stx2-liposome were successfully protected against oral infection with cytotoxin-producing Escherichia coli O157:H7. METHODS: In this study, the induction of protection against Stx2 by Stx2-liposomes was evaluated in monkeys. RESULTS: Stx2-liposomes induced a substantial amount of anti-Stx2 IgG antibodies as well as Stx2 neutralizing antibodies in monkeys. Test monkeys were successfully protected against challenge with lethal doses of Stx2. Moreover, these monkeys showed no apparent symptoms, while nonimmunized control monkeys died within 4 days with hemorrhagic gastroenteritis and renal disorder. In addition, as shown by other cases involving antigen-liposome conjugates, Stx2-liposome did not induce anti-Stx2 IgE antibody production, though it stimulated the production of a substantial amount of anti-Stx2 IgG antibodies. CONCLUSION: These results suggest that Stx-liposome conjugates may serve as candidate vaccines to induce protection against death caused by cytotoxin-producing E. coli infection.

Animals↗

[Intra-arterial chemotherapy with gemcitabine (GEM) for unresectable pancreatic cancer].

PURPOSE: Most patients with pancreatic cancer are unresectable because of local invasion and liver metastasis at the time of diagnosis. To date, no treatment has had a significant impact on this disease. To deliver a high concentration of drug to the cancer, intra-arterial chemotherapy with GEM was performed in two patients with unresectable advanced cancer. PATIENTS AND METHODS: One patient, a 70-year-old man with liver metastasis, was treated with arterial infusion of GEM 1,000 mg/body. Another patient, a 55-year-old woman with local invasion and distant metastatic lymphadenopathy, was given intra-arterial infusion of GEM 400 mg and intra-venous infusion of GEM 1,000 mg/body. The patients were given GEM weekly for 3 weeks followed by a week of rest. RESULTS: In the first patient, the pain went away and CEA was decreased for 6 months. After that, the patient died due to intra-abdominal dissemination within 4 months. In the other patient, the pain went away. Tumor markers, such as CEA and CA19-9, were normalized and primary pancreatic cancer was reduced locally. The patient currently has a metastatic liver tumor, but she has had a significant improvement in performance status. CONCLUSION: Intra-arterial chemotherapy with GEM may be tolerated in patients with unresectable pancreatic cancer.

Aged↗

Treatment of malignant esophagorespiratory fistulas with silicone-covered metallic Z stents.

PURPOSE: To prospectively evaluate the clinical efficacy of covered metallic Z stents in the treatment of esophagorespiratory fistulas (ERFs). PATIENTS AND METHODS: Twelve patients with severe aspiration symptoms from malignant ERFs were treated with silicone-covered, metallic, self-expanding Gianturco-Rösch Z (GRZ) stents. RESULTS: Fluoroscopically guided stent placement was successful and well tolerated in all patients. Immediate postprocedural endoscopy and esophagography showed excellent coverage of the fistulas in all cases. Aspiration symptoms were completely relieved in eight of 12 patients (67%). Four of 12 patients (33%) were improved and able to eat a soft diet. There were no stent-related deaths. Nine patients have died and three patients are alive. Mean follow-up for the entire group was 3.9 months (range, 1 week to 10.5 months). Nonfatal complications occurred in three of 12 patients (25%). Complications included one membrane disruption and one granulomatous reaction with a slight upward stent migration. CONCLUSION: GRZ stents are an effective and safe means of palliation in patients with malignant esophagorespiratory fistulas.

Adult↗

Age related variation of salivary testosterone values in healthy Japanese males.

OBJECTIVE: We examined age associated variation in salivary testosterone values among Japanese males as well as anthropometric measurements. METHODS: Salivary samples were collected in pretreated sodium azide treated tubes. The first series: 15-79-year-old males (n = 99); two morning and two evening samples were collected at home for two days. The second series: 90-year-old males (n = 29); one morning sample was collected. Testosterone values were determined using an iodine125-based radioimmunoassay kit modified for saliva. RESULTS: Results show 1) a significant decrease in salivary testosterone values from 20s to 40s and older, 2) no significant decline after 40 through 90 years old, 3) no significant age-related differences in the degree of intraindividual diurnal fluctuation across age groups of 40-70s, and 4) higher BMI is associated with the lower salivary testosterone among 40-70s. CONCLUSIONS: These results suggest that neither a constant decrease of salivary testosterone values or markedly reduced intraindividual fluctations are universal aspects of aging. Older males may maintain relatively high testosterone levels compared to younger men and a relatively 'robust' neuroendocrinological system.

Adolescent↗