A case report: Severe bone marrow suppression caused by 6-mercaptopurin in Crohn's disease patient]

A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.     

Immunochemical studies of human prolidase with monoclonal and polyclonal antibodies: absence of the subunit of prolidase in erythrocytes from a patient with prolidase deficiency

Prolidase was highly purified from human liver and erythrocytes. NaDodSO4/acrylamide gel electrophoresis revealed that these preparations contained a major protein with MW = 56,000. The mass of prolidase was estimated on gel filtration to be MW = 97,000, for both enzyme preparations. A monoclonal antibody was raised against the liver enzyme and a specific antiserum against the erythrocyte enzyme. The monoclonal antibody (EP-2) recognized prolidase from erythrocytes and liver, in equal proportions. The antiserum also recognized the enzyme from erythrocytes and liver. Immunoprecipitation studies with these antibodies suggested only a single species of prolidase in erythrocytes and liver. Using an immobilized monoclonal antibody (EP-2) as an immunoadsorbent, prolidase was partially purified from crude extracts, and the protein of the partially purified enzyme was identified by immunoblotting using antiserum. A protein band with a MW = 56,000 was demonstrated specifically when crude extracts from the liver and erythrocytes were examined using NaDodSO4/acrylamide gel electrophoresis. The subunit protein was absent in erythrocytes from a patient with prolidase deficiency. We propose that the absence of the subunit is one cause of the prolidase deficiency.     

The correlation of the treadmill exercise test with cardiac hemodynamics in patients with previous myocardial infarction

The correlation between the treadmill exercise test results and the hemodynamic data of 152 patients with previous myocardial infarction were investigated. The patients were classified into 4 groups as follows: H1 left ventricular end-diastolic pressure (LVEDP) less than or equal to 12 mmHg and cardiac index (CI) greater than or equal to 3.0 L/min/m2; H2 LVEDP greater than 12 mmHg and CI greater than or equal to 3.0 L/min/m2; H3 LVEDP less than or equal to 12 mmHg and CI less than 3.0 L/min/m2; and H4 LVEDP greater than 12 mmHg and CI less than 3.0 L/min/m2. The duration of the exercise was significantly shortened for group H4 than group H1 (p less than 0.01). The maximal ST segment elevation (mSTe) was significantly increased for group H3 and group H4, versus group H1 (p less than 0.05). The number of ST segment elevations and mSTe/maximal heart rate were significantly increased for group H3 (p less than 0.05) and group H4 (p less than 0.01) versus group H1. The incidence of exercise-induced premature ventricular contractions (PVCs) was significantly increased in group H3 and group H4, versus group H1 (p less than 0.05). There were no significant differences in the maximal heart rate, double product, and ST segment depression among the 4 groups. Our data indicate that the groups with impaired left ventricular functions tend to decrease the duration of the exercise and to increase ST segment elevation and PVC frequencies during exercise.     

St. Jude Medical valve replacement: clinical experience with 1,039 patients

St. Jude Medical valve replacement was performed in 1,039 patients; 320 had aortic (AVR), 543 mitral (MVR), and 176 had double valve replacement (DVR). There were 44(4.2%) early deaths. Follow-up extended in 995 patients from 10 to 130 months, with a cumulative period of 2,730 patients-years. The overall survival rates of AVR, MVR, and DVR patients at 10 years were 60.5%, 89.6%, 90.3% respectively. The linearized incidences of valve thrombosis, thromboembolism, anticoagulation-related hemorrhage, prosthetic valve endocarditis, and significant hemolysis were as follows: 0.11%/pt-yr, 1.33%/pt-yr, 0.04%/pt-yr, 0.18%/pt-yr, and 0.11%/pt-yr, respectively. There were no structural failure after 10 years follow-up. Reoperation (explant and re-replacement or suture repair) was required in 10 patients. Seven of them had periprosthetic leakage, 2 had valve thrombosis, and one underwent reoperation because of a technical error. Actuarially over 98% of patients were free of valve-related mortality at 10 years. St. Jude Medical valve is an excellent alternative for use in the surgical treatment of valvular heart disease.     

Case of severe ulcerative colitis successfully treated with intravenous cyclosporine without high dose corticosteroid]

A 44-year-old women developed marked myopathy one year earlier, when she was treated with intravenous prednisolone for acute severe exacerbation of ulcerative colitis. When she was admitted to our hospital for another severe exacerbation, intravenous cyclosporine A was administered as monotherapy because she could not tolerate corticosteroid. The treatment was successful and she obtained complete remission. Cyclosporine A monotherapy is considered to be a valuable alternative to proctocolectomy for severe ulcerative colitis patients who cannot tolerate corticosteroid.     

Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: a single-institution retrospective study.

Neuronavigation has become an effective therapeutic modality and is used routinely for intra-axial tumor removal. This retrospective study was conducted to evaluate the clinical impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas. Between 1990 and 2002, 76 adult patients with pathologically confirmed malignant astrocytomas underwent craniotomy and removal of the tumors at the Toyama Medical and Pharmaceutical University Hospital. Of these 76 patients, 42 were treated using neuronavigation with conventional microneurosurgery and the other 34 were treated with conventional microneurosurgery alone. Postoperative early MRI with contrast enhancement was done, and gross total resection was defined as the complete absence of residual tumor. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. In univariate analysis, age (< 65), grade 3, preoperative KPS (>/= 80), use of neuronavigation, and gross total resection were significantly associated with longer survival. However, when the data were submitted to multivariate analysis, grade 3, preoperative KPS (>/= 80), and gross total resection were independent prognostic factors. The median survival periods of patients receiving gross total resection (vs. partial resection) and neuronavigation (vs. no neuronavigation) were 16 (vs. 9) months and 16 (vs. 10) months, respectively. The percentage of a gross total resection was significantly higher in the neuronavigation group compared to that in the no-navigation group (64.3 % vs. 38.2 %, p < 0.05). Neurological deterioration occurred in 4 of 42 (9.5 %) and in 6 of 34 (17.6 %) patients after surgery with neuronavigation and surgery without neuronavigation, respectively, although this difference was not statistically significant. Our results showed that neuronavigation increases the radicality in the resection of malignant astrocytomas and is objectively useful for improving survival time.     

Epinephrine is an enhancer of rat intestinal absorption.

Some physiological substances, including acetylcholine and nitric oxide, are useful candidates for stimulation of intestinal absorption of drugs. In the present study, we elucidated the ability of epinephrine (Epi) to stimulate the intestinal absorption of drugs. We evaluated the ability of Epi to enhance absorption of macromolecules using dextran (Mw 4000 Da), which is poorly absorbed from the intestine, as a model compound in situ in a closed loop of the rat jejunum. Treatment of the jejunum with Epi resulted in significant increase in absorption of dextran in a dose-dependent fashion. The area under the curve (AUC) from 0 to 4 h in the Epi-treated jejunum was 13-fold higher than that in the vehicle-treated jejunum. The absorption-enhancing activity of Epi was 40-fold higher than that of caprate, a clinically used absorption-enhancer of drugs. In the experimental conditions used in this study, histological injury of the mucosa and perturbation of the mucosal membrane were not observed in the Epi-treated jejunum. Treatment with an antagonist of alpha-adrenergic receptors attenuated the stimulation of intestinal absorption by Epi, and treatment with an agonist of alpha-adrenergic receptors resulted in enhancement of intestinal absorption. While an antagonist of beta-adrenergic receptors enhanced the absorption-enhancing effect of Epi, an agonist of beta-adrenergic receptors stimulated intestinal absorption. These results indicate that stimulation of adrenergic receptors may be a novel strategy for intestinal absorption of drugs.     

Chronological changes in the complement system in sepsis

The time courses of serum complement levels and the severity of sepsis were compared in two groups of septic patients, one in which the patients survived (surviving group) and one in which they did not (nonsurviving group). The components of the complement system, namely, C3a, C4a, C5a, CH50, C3, C4, and C5, were measured at several points in time after the diagnosis of sepsis had been established. A 2-antibody radioimmunoassay was used to measure C3a, C4a, and C5a; the latex agglutination test was used to measure C3 and C4; nephelometry was used to measure C5; and Meyer's 50% hemolysis method was used to measure CH50. Following the diagnosis of sepsis, the levels of CH50, C3, and C4 were significantly lower in the nonsurviving than the surviving group, while the levels of C3a and C4a were significantly higher in the nonsurviving than the surviving group. The C5a levels were significantly higher in the nonsurviving than the surviving group, although no significant intergroup differences were subsequently noted. These results suggest that the serum levels of C3a, C4a, C5a, CH50, C3, and C4 could serve as indices of the severity of sepsis. Thus, monitoring the complement system may be useful for predicting the outcome of patients with sepsis.     

Hypereosinophilic syndrome in Hodgkin's disease with increased granulocyte-macrophage colony-stimulating factor

We report a patient with eosinophilia accompanied by Hodgkin's disease who showed remarkable increase in granulocyte-macrophage colony-stimulating factor (GM-CSF) in plasma but no increase in interleukin-5 (IL-5). The plasma GM-CSF level normalized as eosinophilia and lymphadenopathy disappeared after chemotherapy. Immunohistochemical study with immunoperoxidase staining technique showed a positive stain in lymph node cells by monoclonal anti-GM-CSF antibody. Eosinophilia is often accompanied by Hodgkin's disease, and several cases have been reported to show high levels of plasma IL-5. To our knowledge, this is the first report to show a high level of plasma GM-CSF in Hodgkin's disease with eosinophilia.