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Biomedical subjects

N Miyazawa

Publications and source records attributed to N Miyazawa.

At least 19 recordsLinked to original sources

Possible effect of pigment on the pharmacokinetics of ofloxacin and its excretion in hair.

The mechanism of excretion of the antimicrobial ofloxacin in human scalp hair was investigated. When black and white hairs were taken from a patient with grizzled hair, who had been treated with ofloxacin, a much larger quantity of the drug was detected in the black hair. To study this difference and to elucidate the cause, ofloxacin (6, 20, and 60 mg/kg/day, b.i.d.) was administered ip for 5 weeks to albino and pigmented rats, whose backs had been depilated beforehand. In the last week of administration, the time-plasma concentration profile of ofloxacin was determined. One week after the last dosing, the newly grown hair on the depilated area was collected, and the drug concentration in hair was measured. The concentration in hair of the pigmented rats correlated significantly with the daily dose, area under the plasma concentration curve (AUC), and maximum plasma concentration (Cmax) at steady state, whereas that in the albino rats correlated with the dose and Cmax only, because AUC did not increase linearly with the dose in the albino rats. Moreover, the drug concentration in the hair of the pigmented rats was always much larger than that in the hair of the albino ones, although AUC and Cmax did not differ greatly between both rat groups. The findings suggest that ofloxacin is excreted in the hair in relation to the dose administered, and that the mechanism of the excretion is closely linked with the presence of melanin.

Animals

Phase II study of cisplatin as a 5-day continuous infusion with vindesine plus recombinant human granulocyte-colony-stimulating factor in the treatment of advanced non-small-cell lung cancer.

A total of 36 patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of 5-day continuous i.v. infusion of cisplatin (25 mg/m2 daily), bolus infusion of vindesine (3 mg/m2) on days 1 and 8, and s.c. injection of recombinant human granulocyte-colony-stimulating factor (2 micrograms/kg daily) on days 6-21. Treatment was repeated every 3-4 weeks. Responding patients with stage IIIA or IIIB disease received chest radiation therapy (50-60 Gy) after this treatment. One complete response and 23 partial responses were observed, for an overall response rate of 66.7% (24/36; 95% confidence limits, 51.3%-82.1%). The median duration of response was 5.7 months and the median overall survival was 10.1 months. WHO grade 3 or 4 leukopenia and neutropenia occurred in 22 (61%) and 27 (75%) patients, respectively, but the mean duration of leukopenia (< 2,000/mm3) and neutropenia (< 1,000/mm3) was 3.4 and 3.5 days, respectively, and there was no instance of life-threatening infection. Thrombocytopenia and anemia of grade 3 or 4 occurred in 28% and 36% of our subjects, respectively. Grade 2 nausea and vomiting occurred in 47% of the patients. Elevated serum creatinine levels (> 1.5 mg/dl) were observed in 3 (8%) of the 36 patients. One patient died of acute renal failure induced by hemorrhage of a gastric ulcer. This regimen is effective in the treatment of NSCLC and further studies of this combination are warranted.

Actuarial Analysis

Invasive thymoma with intracaval growth into the right atrium.

We report an unusual case of invasive thymoma with intracaval growth into the right atrium. Computed tomography and venacavography demonstrated this manner of extension of thymoma. The tumor was completely removed by means of cardiopulmonary bypass after four courses of chemotherapy. Multidisciplinary treatment for invasive thymoma with this growth pattern is thought to be useful.

Aged

Analysis of ofloxacin in hair as a measure of hair growth and as a time marker for hair analysis.

The distribution of ofloxacin (OFLX) along a single hair shaft was analyzed in detail for use as an index of hair growth and as a time marker for drug analysis in hair. A single hair obtained from each of seven subjects, who had taken OFLX for 1-4 days (total of 200-1,200 mg) 2.7-5.3 months before hair sampling, was cut into 1-cm-long portions successively from its scalp end. OFLX in each hair portion was measured by high-performance liquid chromatography with a fluorescence detector, and the distance from the scalp end of the hair portion containing OFLX was determined. Then the other 2-cm long segment of hair, which had the above-determined distance at its middle, was cut successively into 2-mm-long pieces and OFLX was determined in each piece. This procedure was repeated in a total of three to four hair strands collected from one subject. OFLX was observed to distribute only in one to three consecutive 2-mm-long pieces of hair, showing no large diffusion of OFLX along the hair shaft with time. Therefore, OFLX distribution may serve as a time marker for analyzing other drugs in hair. Hair growth rate could be thus estimated and ranged from 0.99 to 1.27 cm/month (1.12 +/- 0.11 cm/month, mean +/- SD) among individuals. The intraindividual variability of hair growth rate was 4.8-18.1% (10.3 +/- 5.1%) as coefficient of variation.

Adult

[A case of pulmonary metastasis from carcinosarcoma of uterus with subcutaneous implantation of tumor cells along the needle tract after percutaneous needle biopsy of lung].

A 68-year-old female who had undergone total hysterectomy for carcinosarcoma five months previously was noted to have a solitary nodular shadow in the right lung on chest X-ray. Percutaneous needle biopsy of the lung was performed via the right anterior chest wall, and the histologic findings showed metastasis from carcinosarcoma of uterus. Two months after needle biopsy, a chest wall mass appeared of the site of puncture of the lung needle biopsy. The mass was resected to relieve the chest wall pain and the specimen showed carcinosarcoma of uterus histologically. We consider that tumor cells were implanted to the chest wall along the needle tract after percutaneous needle biopsy of the lung. The postoperative chest computed tomogram showed the route of tumor implantation from the metastasis of right lung into the right chest wall. Dissemination and chest wall implantation of malignant cells after percutaneous lung needle biopsy have been rarely reported. However there are no reports of tumor implantation of sarcoma. The possibility of implantation of tumor cells along the needle tract after percutaneous lung needle biopsy should be carefully considered in cases of carcinosarcoma.

Aged

[Effect of isoflurane, enflurane and halothane on hemodynamics during the induction of anesthesia].

The effects of isoflurane(I), halothane(H) and enflurane(E) on hemodynamics of 36 patients (12, 11 and 13, respectively) were studied during the inhalation of 1.5 MAC of each anesthetics before the surgery. Mean arterial pressure(MAP), heart rate(HR), cardiac index(CI), systemic vascular resistance index(SVRI), and stroke volume index (SVI) were measured noninvasively using the automatic blood pressure manometer and the ultrasonic Doppler method (Accucom). MAP decreased with I, E and H, but a larger decrement was observed with E than with H. CI and SVI with H were less than with E. SVRI decreased with I and E but a significant difference was observed between E and H. Each value with I was between those with H and E. These results indicate that isoflurane causes the depression of blood pressure mostly by its effect to decrease afterload during the induction of anesthesia, although its depressing effect is less than that of enflurane.

Adult

Penile metastasis from lung cancer.

A case of metastatic tumor of the penis from lung cancer is reported. The patient, who had received a right pneumonectomy 17 months previously for a squamous cell carcinoma of the lung, complained of urinary retention and painful erection of the penis. He underwent an emergency suprapubic cystostomy. Twenty days after the procedure, he died of disseminated lung carcinoma. The autopsy demonstrated massive metastasis to the penis from squamous cell carcinoma of the lung. Penile metastasis from lung cancer is a very rare condition and only 14 cases of this secondary carcinoma have been reported.

Aged

Three-dimensional computed tomography image of small pulmonary lesions.

To evaluate diagnostic imaging of small lesions in the peripheral lung, three-dimensional (3D) reconstruction CT images were used to study 36 cases (including which had been 19 resected) of pulmonary nodules less than 3 cm in diameter. Rapid scanning was employed in 17 cases and helical scanning (in which the X-ray tube rotates continuously with simultaneous table sliding) in 19 cases. The rapid scanning could not be evaluated in two cases because respiratory motion resulted in discontinuous image data. We were able to evaluate 34 cases. The addition of 3D images to the conventional images made it possible for us to obtain useful information on visualizing relations between nodules and vascular structures in 32% (11/34) of the cases. The 3D images enabled us to visualize the lesions and pulmonary vessels three-dimensionally. It was, however, difficult to evaluate lesion shape since we were able to obtain useful information in only 3% (1/34) of the cases. In helical scanning, data are acquired from an extensive area within a short time, providing consecutive axial-slice images remain free of any respiratory artifacts. In this regard, helical scanning is suitable for generating 3D images. A diagnostic procedure based on 3D lesion analysis should be developed and standardized.

Aged

[A new method for endotracheal intubation with the Bullard laryngoscope].

The Bullard laryngoscope is an anatomically shaped rigid fiber optic instrument designed for indirect laryngoscopy and intubation. It requires no neck extension nor flexion to perform laryngeal intubation. This characteristic is especially useful in the case of difficult airway. The Bullard laryngoscope, however, with which it is easy to visualize the cords, has not been popular yet, because using the intubating forceps mechanism requires a certain amount of skill. The intubation method developed by us with Bullard laryngoscope has been tried on 26 patients with difficult airway and ten patients with normal airway. An endotracheal tube is inserted through nostril, and intubation is performed viewing the tube and larynx during all the processes of intubation. Three kinds of endotracheal tubes, i.e. Magill type plain tubes, styletted tubes, and directional tip tubes, are compared. The method using a directional tip tube (Endotrol) is concluded as the best among them. The Endotrol tube itself has such a suitable shape for nasal intubation that it can be introduced to the larynx with little directional change. Therefore, our method is mastered with a shorter training period than the intubation method with fiber-optic laryngoscopes. In conclusion, our intubation method with the Bullard laryngoscopes using the directional tip tubes (Endotrol) is useful for patients with difficult airways, and is also nontraumatic and easy to perform.

Humans

Diagnosis of mediastinal lymph node metastases in lung cancer.

We studied CT and mediastinoscopy as methods for preoperatively diagnosing mediastinal lymph node metastases (N2) in 133 resected lung cancers, and determined the optimal criterion for a CT diagnosis based on node size. All 133 patients were examined with CT, with a resulting sensitivity of 57% and specificity of 81%. The optimal CT criterion for metastasis was a short node axis of greater than or equal to 10 mm. Where nodes with short axes of greater than or equal to 20 mm, for squamous cell carcinoma, and greater than or equal to 15 mm, for adenocarcinoma, were selected, 100% specificity was obtained. It can thus be considered that nodes of this size on CT show definite metastatic disease. Thirty-three patients who satisfied the selection criteria out of a total 80 patients underwent mediastinoscopy as a clinical trial, with a sensitivity of 70% and a specificity of 100%. Of these, the nine CT false positives (eight squamous cell carcinomas) and three out of the six CT false negative (all adenocarcinomas) were properly diagnosed. We compared 80 cases diagnosed as N2 by CT alone and by CT plus mediastinoscopy, and obtained the following results: accuracies of 67.5 and 82.5%, sensitivities of 54 and 67% and specificities of 73 and 89%, respectively, showing the addition of mediastinoscopy significantly to improve the diagnosis of N2 disease (P = 0.03). We now routinely include a mediastinoscopy except in cases where greatly enlarged nodes are visible on X-ray or in patients who are not candidates for neoadjuvant chemotherapy.

Adenocarcinoma

[Clinical evaluation of the laryngeal mask airway using capnogram].

The laryngeal mask airway (LMA) was clinically evaluated using capnogram in patients who breathed spontaneously under the combination of general and spinal anesthesia. Using the LMA, the airway was maintained without jaw lift and no remarkable hemodynamic change was observed during its insertion and removal. Capnogram was useful to confirm the intact airway and to monitor the respiration. Respiratory depression was observed after thiopental administration and enflurane inhalation. The respiration recovered promptly following the increase of respiratory rate (RR) and tidal volume at first, and it made a further recovery following increase in RR. The use of the LMA under light inhalation anesthesia is hence a useful combination with regional anesthesia.

Adult

[Anesthetic management of the patient with a permanent pacemaker].

Anesthetic management of two patients with a permanent pacemaker is reported; patient no. 1 had the VVI mode pacemaker and patient no. 2 had the DDD mode pacemaker. In patient no. 1, the hypotensive response of the 'pacemaker syndrome' occurred during general anesthesia. Patient no. 2 had no anesthetic problems but careful attention should be paid to the DDD mode pacemaker, because the newer widely used dual lead systems (DDD) are more susceptible to electromagnetic interference. Anesthetists often encounter patients with pacemakers. Knowledge of pacemakers available of the increasingly wide range is necessary to ensure safe management of these patients, many of whom are frail and elderly.

Aged

An evaluation of serum microelement concentrations in lung cancer and matched non-cancer patients to determine the risk of developing lung cancer: a preliminary study.

In a case-control study to determine the risk of developing lung cancer, the serum levels of vitamins A and E, carotene and selenium were determined in 31 patients, newly diagnosed as having lung cancer, and in matched controls, the said controls being selected from outpatients with no cancer. A significant, inverse association was found between serum vitamins A and E and lung cancer. The relative risk for the low vs high tertiles were, respectively, 5.94 for serum vitamin A and 8.44 for serum vitamin E. Taking histological cancer subtype into account, no relation was revealed between the microelements and squamous cell carcinoma of the lung. The relative risk for lung cancer was 6.50, however, when three, or all four, microelement levels were in the lowest tertile, compared with there being fewer than three in the lowest tertile. Even when three microelements, excluding vitamin E which had the most significant inverse association with lung cancer, were considered, the relative risk was 7.50 when any two or all three were in the lowest tertile, compared with there being just one microelement or none at all in the lowest tertile. A combined effect of vitamins A and E, carotene and selenium on the development of lung cancer has, therefore, been suggested. Further studies will thus be necessary to elucidate the cumulative effect of the serum micronutrients and trace elements, as well as the effect of single elements, on the development of lung cancer.

Adenocarcinoma

The measurement of ofloxacin in hair as an index of exposure.

Several strands of hair were collected from each of patients who had been taking ofloxacin against bacterial infections some time in the past. In 10 out of total 14 subjects studied the drug was detected only in the hair portions corresponding to the administration period with the assumption of the hair growth rate of about 1 cm/month. Even in a subject who had received 300 mg/day of ofloxacin only for two days the drug could be detected in the corresponding portion. In 3 subjects the drug was detected in some other portion(s) than the corresponding ones. This might be due to the uncertainty of having used the drug on the other occasion. Only in one subject the dosage history could not be deduced from the drug distribution along hair length. In 3 subjects, who had taken the drug within 1 month, hair samples were collected every month for 3 or 4 consecutive months. The front of drug appearance in hair was clearly shown to move outwards along hair shaft every month at a pace of 1-1.5 cm/month. These results suggest that ofloxacin is excreted into human scalp hair, captured there and moves outwards along the hair shaft at its own growth rate. This leads to the concept that the distribution of ofloxacin along hair length can be used for knowing the individual exposure or non-exposure to the drug, and even for knowing hair growth rate when the innoculation(s) of the drug is strictly supervised and recorded.

Adult

Comparison of continuous and intermittent bolus infusions of metoclopramide during 5-day continuous intravenous infusion with cisplatin.

In order to decide the administration method of metoclopramide for prevention or control of chemotherapy-induced nausea and vomiting in multidrug chemotherapy, with cisplatin 5-day continuous intravenous infusion (25 mg/m2/day) for patients with advanced lung cancer, a randomised crossover study of intermittent bolus infusion (1 mg/kg, 30 min, every 8 h, day 1-5) and continuous infusion (3 mg/kg/24 h, 120 h) of metoclopramide was performed. Both regimens included methylprednisolone and diphenhydramine given concurrently. The acute and delayed antiemetic effects were examined. 21 cases could be evaluated. There were 6 and 10 cases (P = 0.048), respectively, of no nausea and no vomiting; 14 and 18 cases (P = 0.048), respectively, of no vomiting; and vomiting episodes were seen 27 and 9 times, respectively (P = 0.042). Thus, metoclopramide continuous infusion was significantly superior in antiemetic effect compared to bolus infusion. Neither method had any serious side-effects and both were safe.

Adult

Ofloxacin in human hair determined by high performance liquid chromatography.

A procedure is presented for quantitating ofloxacin (OFLX) in human scalp hair by high performance liquid chromatography (HPLC) with a fluorescence detector. An octadecylsilane (ODS) column was used and the mobile phase was a mixture of potassium phosphate buffer (pH 2.6) and acetonitrile. The recovery of OFLX was 90.9-93.8% and within- and between-run precisions were 0.35-1.41% and 1.41-5.49% as the coefficient of variation (CV), respectively, when 5-50 ng OFLX was added to 1 mg blank hair. The calibration curve was linear in the range of 0.5-50 ng/tube (0.5 ml). Interference with other quinolone derivatives could be avoided according to the difference in their retention times or fluorescence spectra. Several pieces of hair were obtained from each of twelve healthy male volunteers, who had taken OFLX (100, 300 or 900 mg total dose) over a 1-3 day period 2 weeks before the hair sampling. In all hair samples except one obtained from a volunteer, who had taken the lowest dose, the 2-cm long segments nearest the scalp contained OFLX (5-45 ng/mg hair), while the upper segments did not. A highly significant positive correlation was observed between the total dose and the concentration of OFLX in the 2-cm long hair segments. Such a positive correlation was also revealed in rat hair sampled after repeated i.p. administration of OFLX over a 5-week period. These results suggest that the measurement of OFLX in hair by the present method would be useful for testing patient compliance in clinical pharmacology as well as for application to forensic science.

Adult

Tumor invasion of the chest wall and mediastinum in lung cancer: evaluation with pneumothorax CT.

For preoperative evaluation of chest wall and mediastinal invasion by lung cancer, computed tomography (CT), combined with artificial pneumothorax (pneumothorax CT), was performed in 43 patients with lung cancer in whom conventional CT scans showed that the mass was contiguous to the chest wall (n = 30) and/or mediastinum (n = 25) but without evidence of definite tumor invasion. Invasion was diagnosed on the basis of whether an air space existed between the mass and the adjacent structures. In three patients pneumothorax was not produced. After the procedure, four patients developed symptomatic pneumothorax, and one, subcutaneous emphysema. Comparison of diagnoses based on findings at pneumothorax CT, surgery, and pathologic examination showed that pneumothorax CT is 100% accurate for chest wall invasion and 76% accurate for mediastinal invasion. The authors conclude that this procedure is helpful in accurate evaluation of the T criterion in lung cancer, especially for patients in whom findings at conventional CT suggest tumor invasion of the chest wall and mediastinum.

Adenocarcinoma