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Biomedical subjects

H Minami

Publications and source records attributed to H Minami.

At least 91 records · Page 5Linked to original sources

[Promotion of phagocytosis and prevention of phagosome-lysosome (P-L) fusion in human peripheral blood monocytes by serotype specific glycopeptidolipid (GPL) antigen of Mycobacterium avium complex (MAC)].

Mycobacterium avium complex (MAC) is one of the most important opportunistic pathogens co-infected with HIV (AIDS) and a typical intracellular parasitic bacteria similar to M. tuberculosis. It is also noticed that M. avium infection causes immunosuppression especially in the cellular immunity of host animals, and specific serotype-subspecies such as sero-2, -4 or -8 can be isolated frequently in human infection. Furthermore, the prognosis after infection differs by the serotypes and serotype-4 shows heavy infection in general, while serotype-16 shows rapid improvement. Therefore, we have been interested in the immunomodifying activity of surface glycopeptidolipid (GPL) antigen. However, to date, no information has been available on the virulence factor of MAC related directly with intracellular bactericidal activity. Recently, we have tested the effect of various GPLs purified form MAC complex on phagocytic processes of human peripheral blood monocytes (PBMC). We have used GPL-coated heat-killed staphylococcal cells to be phagocytosed by PBMC, and phagosome-lysosome (P-L) fusion was estimated by the acridine orange staining of fused vesicles including bacteria. It was revealed that the serotype-4, -12 and -17 GPLs showed strong phagocytosis promotion and marked inhibition of P-L fusion, while serotype-9, -13, -16 and -19 GPLs showed neither promotion of phagocytosis, nor inhibition of P-L fusion in phagocytic cells. Serotype-5, -7, -8 and -10 GPLs showed stimulation of both phagocytosis and P-L fusion, concomitantly. These effects may be due to unknown interaction between specific carbohydrate chain of MAC and phagocytic cell membranes, and serotype-4, -12 and -17 GPLs may be one of the possible virulence factors in MAC.

Antigens, Bacterial↗

Adjustment of creatinine clearance improves accuracy of Calvert's formula for carboplatin dosing.

Carboplatin clearance depends on the glomerular filtration rate (GFR), and Calvert's formula is frequently used to achieve a target area under the time vs concentration curve (mg ml(-1) min). Creatinine clearance is a substitute for GFR when creatinine values are determined by the Jaffé method, which is being replaced by the enzymatic method. When the enzymatic method is used, the corresponding creatinine clearance theoretically exceeds GFR, and the use of creatinine clearance as GFR in Calvert's formula results, accordingly, in overdosing of carboplatin. In this study, we have established a model for adjusting the creatinine clearance to offset this bias based on a relationship between creatinine values measured by the Jaffé method and by the enzymatic method: adjusted creatinine clearance (ml min(-1)) = creatinine clearance (ml min(-1)) x [serum creatinine (mg dl(-1))]/[serum creatinine (mg dl(-1)) + 0.2]. Subsequently, we validated this model using the data from 35 lung cancer patients. Estimated clearances of carboplatin with the original equation [creatinine clearance + 25] were systematically higher than observed clearances [mean prediction error (MPE) +/- standard error (s.e.) = 26 +/- 5%]. This positive bias was corrected by the adjustment (MPE +/- s.e. = 5 +/- 4%). When the enzymatic method is used, the adjusted creatinine clearance should be used in Calvert's formula.

Adult↗

PCR-RFLP analysis as an aid to genetic counseling of families of Japanese patients with group A xeroderma pigmentosum.

Because Japanese patients with complementation group A xeroderma pigmentosum (XP-A) show early skin cancer and severe neurologic dysfunction, their family members are greatly concerned about the risk of inherited disease. In contrast to western XP-A patients, almost all Japanese XP-A patients have two of the three mutations (nonsense mutation in exon 3, splicing mutation in intron 3, and non-sense mutation in exon 6), which are easily detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. This work was aimed to see whether PCR-RFLP analysis is useful for genetic counseling of XP patients' siblings who are potential carriers of an XP-A gene mutation. In two of the three case studies presented, the probands were homozygous for the splicing mutation in intron 3 of the gene. In their siblings receiving genetic counseling, no mutation was found in the mutation site in one case, and one splicing mutation was found in the second case. In the third case, the proband was a compound heterozygote for the splicing mutation and for an unidentified mutation; in her sibling, no mutation was found in either of these mutation sites. No mutation was found in the siblings' spouses. On the basis of these findings, we reassured the prospective parents that there was little probability of having XP children, but in the second and third cases, we told them that their apparently unaffected children might be carriers. Each couple subsequently had one unaffected child. Thus, PCR-RFLP analysis is useful for genetic counseling of family members of XP-A patients.

Adult↗

Pharmacokinetic study of carboplatin given on a 5-day intravenous schedule.

We investigated whether carboplatin pharmacokinetics is altered when the drug is delivered daily over 5 days, compared to a single-day infusion. Carboplatin was infused in 11 patients with lung cancer, who were randomly assigned to 2 groups. In the first group, the agent was administered on a conventional single-day schedule in the first course and then on a 5-day schedule in the second course. In the second group, the order was reversed (crossover design). The dose was calculated using Calvert's formula with 24 h creatinine clearance (Ccr, ml/min) as a substitute for glomerular filtration rate (GFR): carboplatin (mg) = AUCx(Ccr+25), where AUC denotes the area under the concentration versus time curve (mg ml-1 min). No difference of carboplatin clearance between the single-day and 5-day schedule was observed (94.8 +/- 19.9 versus 96.1 +/- 29.9 ml/min, P = 0.818, paired t test). The formula systematically overestimated the carboplatin clearance: the ratio of estimated clearance/ observed clearance ranged from 1.01 to 1.58 (median 1.28; 95% confidence interval, 1.18 to 1.39). We concluded that the individual dosing strategy based on renal function can be applied with a 5-day schedule as well as a single-day schedule. Carboplatin is overdosed when Ccr is substituted for GFR in Calvert's formula.

Aged↗

Prediction of drug responses in schizophrenia: a method using a test dose of chlorpromazine.

Thirty-seven newly admitted schizophrenic patients were treated with an open and flexible dosage of chlorpromazine for 3 months after receiving a test dose. Levels of chlorpromazine, demethylated chlorpromazine and chlorpromazine sulfoxide 3 h after the test dose were measured. Twenty-three patients responded to long-term chlorpromazine treatment but 14 did not, a rate of 62.2%. A discriminant function analysis was performed using variables relating to the patients, backgrounds added to the ratios of plasma drug levels separately by sex to increase predictability over the level of previous studies. The obtained equations were applied to 23 newly admitted schizophrenic patients, with the prescription of chlorpromazine for designated responders and haloperidol for designated non-responders for 4 weeks. The patients in the latter study responded better than those of the former with chlorpromazine alone; 71.4 and 88.9% of chlorpromazine- and haloperidol-treated groups improved, respectively, for an overall rate of 78.3%. However, the chlorpromazine-treated group had a lower level of positive symptoms than the haloperidol-treated group before treatment and this and other differences between the groups should be further examined.

Adult↗

A phase II study of carboplatin and prolonged administration of oral etoposide in patients with small-cell lung cancer.

Prolonged oral administration of etoposide may have a theoretical advantage over intravenous infusion, and carboplatin has a more favorable toxicity profile than cisplatin. A combination of carboplatin 300 mg/m2 and oral etoposide 40 mg/m2/day for 21 days was assessed in 74 (42 limited, 32 extensive disease) previously untreated patients with small-cell lung cancer. Response rate was 69% (CR 19%, PR 50%,) for limited disease and 72% (CR 9%, PR 63%) for extensive disease. Median response duration and overall survival was 6.6 and 10.1 months for limited disease, and 5.3 and 9.1 months for extensive disease, respectively. One-year and two-year survival was 36 and 10% for limited disease and 31 and 2% for extensive disease, respectively. The major toxicity was hematological with grade 4 or greater neutropenia in 36% and grade 4 thrombocytopenia in 16%, and one patient died of neutropenic fever. Non-hematologic toxicities were mild and grade 3 emesis was observed in 5% of patients. Carboplatin combined with 21-day oral etoposide showed only modest activity against small-cell lung cancer with high toxicity and did not merit further evaluation.

Administration, Oral↗

[Three patients with Gilbert's syndrome associated with constitutional excretory defect of indocyanine green].

We routinely perform, as a preoperative liver function test, the indocyanin green (ICG) test in patients scheduled for operations under general anesthesia. Doubts have been raised, however, concerning the necessity for this test, since no abnormalities have ever been detected by it. Nonetheless, we noted a high level of ICG retention and a slight increase in indirect bilirubin in 3 patients, and further investigation led to a diagnosis of Gilbert's syndrome accompanied by constitutional impairment of ICG excretion. This syndrome can be associated with perioperative jaundice in patients with malnutrition and those who received halothane, morphine, or some other agents. Although the indirect bilirubin level increased briefly after surgery, no other abnormalities occurred in the 3 patients. Since this syndrome is asymptomatic and is detected incidentally, the preoperative ICG test was considered to be useful.

Adolescent↗

[Coronary artery bypass surgery in patients aged 75 years and older].

Coronary artery bypass grafting (CABG) has been performed for elderly patients with increasing frequency. Several studies have shown that the rate of complications and mortality in elderly patients are higher than in younger ones. This report presents results of CABG in patients over 75 years old. From January 1989 to February 1997, 604 patients underwent CABG, of whom 20 patients (3.3%) were 80-86 years old (group A) and 57 patients (9.4%) were 75-79 years old (group B). We compared these two groups with 100 younger patients (group C). Preoperative use of intraaortic balloon pumping and the emergency operation were more frequent in patients of group A (emergency 45%, IABP 20%). And the proportion of the no blood transfusion procedures was lower in elderly patients (group A 20%, group B 18%, group C 82%). The number of grafts per patient (group A 2.45 +/- 0.62, group B 2.2 +/- 0.6, group C 3.2 +/- 0.6) and the number of arterial grafts (group A 1.25 +/- 0.62, group B 1.25 +/- 0.66, group C 2.1 +/- 0.53) were different between the groups. But CABG in elderly patients was performed with low hospital mortality (group A 0%, group B 0.18%) and significant symptomatic benefit. We conclude that CABG can be performed in elderly patients with acceptable mortality and acceptable quality of life, so patients should not denied operation because of an advanced age.

Adult↗

[Sleeve lobectomy for tuberculous bronchial stenosis: a case report].

We describe a patient with tuberculous bronchial stenosis who was subjected to bronchoplasty. The patient was a 33-year-old man who had stenosis of the left main bronchus. Because the lesion was associated with bronchomalacia, previous balloon dilatation therapy had failed. At thoracotomy, the left upper lobe was found not to be saved for the tuberculous lesion. Although there were many inflamed nodules in the left lower lobe due to repeated episodes of pneumonia, we decided to save it using bronchoplasty expecting its respiratory functional recovery. He ran uneventful course postoperatively and his lung function improved. We conclude that bronchoplasty may prove effective for patients with tuberculous bronchial stenosis associated with bronchomalacia; and thus, to avoid pneumonectomy, bronchoplasty should be attempted even if the reconstructed lung is mildly inflamed.

Adult↗

Prognostic value of pleural effusion in patients with non-small cell lung cancer.

This study was performed to determine whether pleural effusion in patients with advanced non-small cell lung cancer (NSCLC) has a negative impact on survival. We evaluated 12 prognostic factors in 197 patients with stage IIIB or IV NSCLC. Each factor was dichotomized, and survival curves calculated by the Kaplan-Meier technique were compared using the log-rank test. The Cox proportional hazards regression model was used to confirm the significance of each prognostic factor selected by univariate analysis. We compared the survival times for stage IIIB with pleural effusion with those of stage IIIB without effusion and stage IV. To determine the impact of the cytological results of the effusion on survival, we compared the survival times for cytologically positive and negative effusions. Univariate analysis identified eight significant prognostic factors: pleural effusion, node status, stage, performance status, weight loss, hemoglobin, albumin, and lactate dehydrogenase. Pleural effusion was selected as a prognostic factor in the multivariate analysis, together with stage, performance status, albumin, and node status. Median survival times for stage IIIB without effusion, stage IIIB with effusion, and stage IV were 15.3, 7.5, and 5.5 months, respectively (P < 0.0001). Survival time for stage IIIB with effusion was significantly different from that of stage IIIB without effusion (P = 0.0129) but not from that of stage IV (P = 0.0797). Among patients with effusion, no significant difference in survival time was observed between cytologically positive and negative effusions. We conclude that pleural effusion in advanced NSCLC is a prognostic factor. Survival time for stage IIIB with pleural effusion is more similar to that of stage IV rather than that of stage IIIB without effusion.

Adult↗

Incorporation of proteins in sphingomyelin-water gel phases.

Sphingomyelin from bovine milk and water form lipid gel phases at room temperature. A sample was used which incorporated of about 55% water, and X-ray diffraction data indicate an aqueous layer thickness of about 28 Angstrom. In order to accommodate proteins in the gel phase, the aqueous layer thickness was increased by solubilizing sodium palmitate into the sphingomyelin bilayer. In this way the gel phase could take up about 80% water. The incorporation of lysozyme, beta-lactoglobulin, and alpha-lactalbumin, was followed and the protein concentration for phase separation to occur was determined. It was found that the degree of incorporation was dependent on the salt concentration, thus the protein used was extensively dialysed. The amount of protein which can be dissolved in the thin aqueous layer of the gel phase was suggested to be limited by the dimensions of the layer. These are likely to be reduced as a consequence of the osmotic stress exerted by the 'outside' solution phase at high enough protein concentration.

Animals↗

Is there a circadian variation in plasma concentrations of etoposide given by prolonged continuous infusion?

The prolonged continuous infusion of low-dose etoposide is a new approach to treating cancer. Whether or not a circadian variation in the plasma levels of etoposide existed was investigated in nine patients with non-small-cell lung cancer. Etoposide was infused for 14 days and blood samples were obtained every 4 h for 1 day. There was no significant circadian variation, and the observed small within-day variations seemed to lack clinical significance.

Aged↗