[Gout due to disorder of urate binding proteins (the urate-binding alpha 1-2 globulin deficiency)].
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Biomedical subjects
Publications and source records attributed to K Ushijima.
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A 57-year-old male without pre- or intraoperative arrhythmia developed ventricular tachyarrhythmia immediately following hepatectomy. Postoperative examination of plasma electrolytes revealed severe hypomagnesemia (0.16 mmol.l-1). The arrhythmia may have been caused by hypomagnesemia and an imbalance between supply and demand of oxygen in the myocardium, due to hypovolemia and severe anemia from massive hemorrhage. We recommend that measurement of plasma magnesium concentration be included in all perioperative laboratory examinations.
A delta wave, which had not been detected in the preoperative electrocardiogram (ECG), was observed just before induction of anesthesia in a 53-year-old male scheduled for partial pancreatectomy. His ECG, diagnosed as intermittent Wolff-Parkinson-White (WPW) conduction, varied markedly displaying different wide QRS complexes with a short PR interval, and then returned abruptly to normal during anesthesia. WPW syndrome belongs to the category of pre-excitation syndromes, which is characterized by the accelerated abnormal conduction to the ventricle and paroxysmal tachyarrhythmias caused by an accessory pathway. We should consider the influence of anesthesia-related agents on atrioventricular conduction, and aim at preventing and managing tachyarrhythmias caused by this syndrome.
A 73-year-old female weighing 41 kg who had undergone ilecolostomy under general anesthesia showed extremely prolonged apnea. Despite only 7 mg of vecuronium, she needed postoperative mechanical ventilation for more than 24 hours. A postoperative examination revealed hypermagnesemia, which probably potentiated the effect of vecuronium. Her hypermagnesemia might be caused by chronic renal failure with hypocalcemia and administration of magnesium sulfate as a cathartic. Plasma magnesium concentration should be measured perioperatively in all surgical cases.
An eleven-year-old girl underwent an open biopsy of a mediastinal tumor extending from the foreneck to the tracheal carina under general anesthesia. Immediately following the bucking developed at the end of the surgery, she fell into serious ventilatory difficulty. A bronchoscopic examination revealed that the tracheal membrane had protruded into the tracheal lumen by its contraction concurring with the bucking, resulting in the obstruction of the endotracheal tube outlet. Endotracheal anesthesia might accompany tracheal stenosis by bucking, particularly in patients with a tumor surrounding the trachea.
To clarify the optimal timing of second look operation (SLO) for advanced ovarian cancer, we retrospectively reviewed the records of 53 patients with FIGO stage 2, 3 and 4 epithelial ovarian cancer. SLOs were performed more than 12 months after primary surgery in 35 patients (late SLOs), and immediately after first-line chemotherapy in 18 patients (early SLOs). We examined data on SLO findings and patients' clinical courses. SLO findings were positive 5 (27.7%) of 18 in the early SLO group and in 11 (31.4%) of 35 in late SLO group. Positive findings were detected by washing cytology in 3 (60%) of the 5 in the early SLO group compared with 2 (18.2%) of the 11 in the late SLO group. Patients with microscopic disease had better prognosis than patients with macro lesions. False-negative SLO findings were 30.8% in the early SLO group and 12.5% in the late SLO group. All patients who recurred after negative SLOs had grade 2 and 3 tumors. The benefits of SLO were limited to accurate evaluation of first-line chemotherapy and early detection of persistent disease. In these implications, early performance of SLO is recommended.
We present a case of anesthesia machine (NAR-KOMED 2CTM; N2C) malfunction caused by dew condensation. N2C is electronically controlled by an alarm-panel using the remote display. Abnormally high humidity in the operating room made dew condensation in the alarm-panel resulting in an electronic short circuit. Of great importance may be the damp proof improvement on medical equipment including anesthesia machines which have electronic circuits.
A 5-year-old girl with Rubinstein-Taybi syndrome (RTS) was scheduled for ophthalmic surgery under general anesthesia. RTS is a well-defined syndrome with facial abnormalities including a high palate and micrognathia, broad thumbs and big toes, and mental retardation as main clinical features, which may be complicated with repeated respiratory infections, cardiac anomalies, and so on. Anesthesia was uneventfully induced and maintained with the inhalation of oxygen, nitrous oxide and sevoflurane. Special attention was paid to the possibilities of the difficult airway, aspiration pneumonia and cardiovascular dysfunction during anesthesia. No complications were observed throughout the perioperative procedures.
A 41-year-old man weighing 68 kg was scheduled for bilateral tonsillectomy because of palmoplantar pustulosis. The patient had been diagnosed as schizophrenic 10 years earlier. Psychotropic agents, mosapramine (75 mg.day-1), bromperidol (6 mg.day-1), cloxazolam (3 mg.day-1), biperiden (1 mg.day-1) and nitrazepam (5 mg as needed), were administered until the day before surgery. On the day of surgery, atropine (0.g mg) and midazolam (4 mg) were administered intramuscularly as premedication. Anesthesia was induced by intravenous propofol (120 mg) and fentanyl (100 microgram) followed by nasotracheal intubation using vecuronium (7 mg). Anesthesia was maintained with inhalation of oxygen and nitrous oxide (2 l.min-1 each) and the intravenous infusion of propofol (5-10 mg.kg-1 x h-1) supplemented by fentanyl (100 microgram). The patient recovered from anesthesia uneventfully. Immediately after surgery, intravenous haloperidol (5 mg) and intramuscular biperiden (1 mg) were given. The daily oral administration of psychotropics was resumed on the first postoperative day. There were no complications such as hypotension, arrhythmia, or worsening of the mental condition, throughout the course.
Five promising new drugs for gynecological cancer were reviewed. Taxans (Paclitaxel: Taxol and Docetaxel: Taxotere) diterpenoid plant products enhance the polymerization of tublin. Taxol showed significant activity for platinum refractory ovarian cancer in a phase 1 clinical trial in the United States. The combination with cisplatin (CDDP) showed superior results to CDDP plus Cyclophosphamide and has been recognized as a new standard in adjuvant chemotherapy for advanced ovarian cancer. The major toxicities are myelosuppression, alopecia, and hypersensitivity reactions (HSRs). HSRs were overcome by pretreatment with anti-histamines and over 24 hours administration. It was also reported that Taxol was administered safely by over 3 hours infusion with reduced myelotoxicity, but the incidence of HSRs may be increased. Clinical trials of intraperitoneal administration and combination with Carboplatin (CBDCA) are ongoing. Taxotere, an analog of Taxol, is also effective as Taxol with a low incidence of HSRs. Topoisomerase inhibitors (Irinotecan hydrochloride: CPT-11 and Topotecan) have promising antitumor activity for ovarian and cervical cancer. CPT-11 is a semisynthetic camptothesin analog developed in Japan. It was also effective for platinum-resistant ovarian cancer, such as mucinous and clear cell carcinoma. An adverse effect was observed in the combination of CPT-11 and CDDP. The phase 1 clinical trial showed a 40% response rate against recurrent ovarian cancer. CPT-11 50-60 mg/m2 (day 1,8,15) and CDDP 50-60 mg/m2 (day 1) are a recommended schedule. The major toxicities are neutropenia and diarrhea. Thrombocytopenia is not severe and diarrhea is also controllable. Topotecan is also a promising topoisomerase inhibitor and reported superior result to Taxol for platinum refractory ovarian cancer. A phase II trial is ongoing for ovarian and cervical cancer in Japan. Nedaplatin, a new analog of cisplatin, has similar activity especially for cervical cancer with less myelotoxicity and nephrotoxicity.
Hairpin antisense oligodeoxyribonucleotides containing 2'-methoxynucleosides were more active in the micromolar concentration range than linear and DNA hairpin phosphorothioate oligonucleotides with the same sequence. Furthermore, the abilities of hairpin antisense and random hairpin phosphorothioate oligonucleotides to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-oligomers of the same length or with the same internucleotide modification. Four different target sites (gag, pol, rev, and tat) within the HIV-1 genome were studied with regard to the inhibition of HIV-1 replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of the initiation sequences of gag were most effective. The [32P]-labeled hairpin phosphorothioate oligonucleotide was rapidly assimilated by MOLT-4 cells, whereas the [32P]-labeled hairpin phosphodiester oligonucleotide was not. In MOLT-4 cells treated with the FITC-hairpin phosphorothioate oligonucleotide containing 2'-methoxynucleosides by a confocal laser scanning microscope, diffuse fluorescence was observed in the cytoplasm. Interestingly, fluorescent signals accumulated in the nuclear region of chronically infected MOLT-4/HIV-1 cells after a 60 min incubation.
Phenanthroline was attached covalently to the 5'-terminus of the unmodified and modified (3'-terminal phosphorothioate) oligonucleotide sequences, TTTTTTCTTCTCTTTCC (OP-17 mer) and TTTTTTTCTTCTCTTTCsC (OPRp-17 mer or OPSp-17 mer) via a phosphoramidite bond. Simian virus 40 DNA contains a single target site for these oligonucleotides. In the presence of copper ions, the efficient double-stranded cleavage at 37 degrees C and pH 7.0 was observed by agarose gel electrophoresis. The asymmetric distribution of the cleavage sites on the two strands revealed that the cleavage reaction took place in the minor groove, even though the linker was located in the major groove. Of particular interest are the 3'-terminal phosphorothioate oligonucleotide-phenanthroline derivatives (Rp or Sp), which were found to have cleavage activities of the same order as for the oligonucleotide phenanthroline (OP-17 mer). Furthermore, the OPSp-17 mer was intact after incubation in 10% fetal bovine serum for 24 h, whereas, the OPRp-17 mer was slightly more unstable than the OPSp-17 mer. However, the OP-17 mer was completely degraded. An increased resistance to nucleases has been observed by the introduction of phosphorothioate groups on the 3'-terminus of oligonucleotide-phenanthroline derivatives. This stabilization should help us to design much more efficient chemical recognition enzymes and antisense nucleic acid based anti-viral therapies, which could be used as tools in cellular biology.
Microspheres consisting of L-lactic acid and glycolic acid copolymer containing cisplatin (CDDP-PLGA) were developed to improve the delivery of cisplatin. We evaluated the effects of intraperitoneal administration of cisplatin prepared as CDDP-PLGA in rats with ovarian cancer. The toxicity, platinum distribution, and therapeutic effects of CDDP-PLGA were evaluated as compared with those in the case of cisplatin aqueous solution. The LD50 of CDDP-PLGA was almost four-fold higher than that of cisplatin aqueous solution. CDDP-PLGA released cisplatin slowly and achieved a higher concentration in the peritoneal cavity and in peritoneal tumors for prolonged periods, while the tissue concentration of cisplatin was reduced elsewhere in the body, as compared with the case of cisplatin aqueous solution. The survival of rats with peritoneal carcinomatosis was increased by this delivery system relative to cisplatin aqueous solution. CDDP-PLGA thus allows a higher dose to be given without increasing systemic toxicity, enhancing the therapeutic effect of cisplatin.
We retrospectively reviewed 91 patients with epithelial ovarian cancer who underwent second-look operation (SLO). SLO identified a persistent tumor in 18 (19.8%) of 91 patients. Of these 18 patients, 13 (72.2%) showed disease progression after SLO. Patients with a positive SLO in which the identification of the persistent disease was only possible by washing cytological study showed better prognosis than patients with macroscopic lesions. Of the 73 patients with a negative SLO, 12 (16.4%) developed recurrence after cessation of treatment. These 12 patients were from stage 1c to 3 with Grade 2 and 3 tumors. The SLO findings were more sensitive than the serum tumor marker in identifying persistent disease. Also we reviewed 55 patients having no SLO. Among 57 cases in stage 1 and 2 with Grade 1 tumor, there were no cases of recurrence, regardless of whether they had SLO or not. Our results suggest that SLO findings correlate well with the patient's prognosis. SLO may not be needed for patients in stage 1 and 2 with Grade 1 tumor. Patients with advanced stage disease with Grade 2 and 3 tumors have high-risk for recurrence after negative SLO. While SLO is still of benefit in management of ovarian cancer, refinements are needed to determine its indication and scheduling.
Selective delivery of a high level of cisplatin (CDDP) to the omentum, intraperitoneal disseminated tumors and lymph nodes was studied using a dosage form of CDDP-activated carbon. Although intraperitoneal CDDP-activated carbon delivered much higher levels of CDDP to the omentum, tumors and lymph nodes, a primary burst phenomenon of CDDP occurred just after administration. This indicates that activated carbon is an unsuitable particle to provide a slow steady release of CDDP.
It has been reported that the antitumor effect of CPT-11 is manifested through the inhibition of topoisomerase I by SN-38 which is an active metabolite of CPT-11 produced by intracellular carboxylesterase, and that CPT-11 is effective against recurrent ovarian carcinoma. We investigated the antitumor effect and adverse reactions in the combined therapy with CPT-11 and CDDP in patients with prior chemotherapy for recurrent carcinoma, and in 7 patients without prior chemotherapy, consisting of 4 patients with postoperative adjuvant chemotherapy for clear cell carcinoma and 3 patients with metastatic ovarian carcinoma. CDDP was administered on day 1 and CPT-11 was administered three times on days 1, 8 and 15. The dose of both CDDP and CPT-11 was 50 mg/m2 or 60 mg/m2. Adverse reactions were investigated in all patients and the antitumor effect was assessed in 12 patients with recurrent carcinoma who had measurable lesions. (1) The DLF was neutropenia. The neutrophil count nadiar occurred on day 18 or 19. Grade 3 or 4 adverse reactions were observed in 60% or more of the patients, but they disappeared following short term administration of G-CSF. In patients with recurrent carcinoma given CDDP and CPT-11 at 60 mg/m2, the incidence of grade 3 or 4 adverse reactions and number of occasions on which CPT-11 administration had to be postponed were higher than those in patients given 50 mg/m2. (2) Mild platelet reduction was observed. (3) Grade 3 or 4 diarrhea was observed in 3.2% of patients with recurrent carcinoma and in 7.7% of patients with metastatic ovarian carcinoma. (4) The antitumor effect was evaluated in 12 patients with recurrent carcinoma: CR in 2 patients. PR in 3, NC in 6, and PD in one. The response rate was 41.7%. (5) An antitumor effect was observed in 2 patients with serous carcinoma and in one patient each with mucous carcinoma, clear cell carcinoma and endometrial carcinoma. In conclusion, adverse reactions caused by the combination therapy with CPT-11 and CDDP (CPT-11: 50-60 mg/m2 on days 1, 8 and 15, CDDP: 50-60 mg/m2 on day 1) can be relieved by short term administration of G-CSF and it is suggested that the combination therapy may be effective in treating ovarian carcinoma.
We treated a 1-year 9-month-old boy with severe hemophilia A who developed high level of F VIII inhibitor. A placement of an implantable intravenous access device was scheduled under general anesthesia. After a slow induction using oxygen, nitrous oxide and sevoflurane, a peripheral venous line was placed and plasma-derived F VII a was infused. A catheter was inserted via the jugular vein to the SVC and it was connected to the device placed subcutaneously in his right chest wall. The peroperative blood loss was slight, and anesthesia and surgery went uneventfully.
Carbohydrate malabsorption is a very important clinical entity, particularly in pediatrics, where, if untreated, it can lead to malnutrition and failure to thrive. Malabsorption that can be treated readily with elimination of the offending carbohydrate. Knowledge by the physician of the specific mechanisms involved in the physiology of carbohydrate absorption and digestion will help in the handling of the clinical situation of malabsorption.