Phase I Study of Paclitaxel by Three-hour Infusion: Hypotension Just after Infusion Is One of the Major Dose-limiting Toxicities

The primary objectives of this study were to determine the maximum tolerated dose (MTD) of paclitaxel administered by 3-h infusion to patients with solid tumors, and to characterize the pharmacokinetics of a 3-h infusion in comparison with those of a 24-h infusion. Twenty-seven patients each received one of six levels of paclitaxel, 105, 135, 180, 210, 240 and 270 mg/m², with premedication. Two patients given 240 mg/m² and one patient given 270 mg/m² unexpectedly had grade 3/4 hypotension just after finishing the paclitaxel infusion. Peripheral neuropathy was also dose-limiting at 270 mg/m². Although granulocytopenia was significantly less severe than with a 24-h infusion, more than half of the patients experienced grade 4 toxicity at doses of 240 or 270 mg/m². Severe hypersensitivity reactions (HSRs) were not observed. Pharmacokinetic studies using high performance liquid chromatography demonstrated proportionally greater increases in the peak plasma concentration and area under the curve, and decreases in clearance and volume of distribution with increasing dose, suggesting non-linear pharmacokinetics of paclitaxel when given by 3-h infusion. The MTD of paclitaxel given as a 3-h infusion was determined to be 240 mg/m² with dose-limiting toxicities of granulocytopenia, peripheral neuropathy and hypotension. Hypotension just after infusion, induced by 3-h infusion of paclitaxel, is a new observation which has not been reported previously. The recommended dose for phase II study is 210 mg/m². Although hypotension was observed as an unexpected toxic effect, paclitaxel could be administered safely over 3 h with premedication and proper monitoring, resulting in reduced myelotoxicity and with no increase in the incidence of HSRs as compared with a 24-h infusion.     

A case of pulmonary aspergillosis presenting pulmonary bulla and eosinophilic pneumonia

A rare case of a 25-year-old man with pulmonary aspergillosis is reported. Pulmonary bulla and eosinophilic pneumonia in the right upper lobe were diagnosed by chest roentgenogram and transbronchial lung biopsy. Because the patient developed infective bullae during steroid therapy, we performed transcutaneous thoracic drainage and right upper lobectomy. The resected lung tissue contained numerous hyphae of Aspergillus. Around the hyphae of Aspergillus, granulomatous reaction and eosinophilic infiltration were observed. Antibodies against Aspergillus were detected in the serum of the patient. The number of peripheral blood eosinophils decreased after right upper lobectomy. These findings suggest that pulmonary bullae and eosinophilic pneumonia may be a rare manifestation of pulmonary aspergillosis.     

CT and MR findings in diastematomyelia, with embryogenetic consideration.

Diastemstomyelia is an extremely rare disorder that is seldom found among the Japanese. This paper presents two Japanese patients, a newborn male and a newborn female, with diastematomyelia. CT demonstrated bony spurs more clearly than plain film, and magnetic resonance images indicated split cords and associated anomalies. Although the embryogenesis of diastematomyelia has not been clearly elucidated, the coincidence of levels of associated anomalies and diastematomyelia in our cases and in the literature supports Bremer's embryogenetic explanation of persistent accessory neurenteric canal.     

Fractal dimensions of ductal patterns in the parotid glands of normal subjects and patients with Sj?gren syndrome.

RATIONALE AND OBJECTIVES. The sialographic ductal patterns of the parotid glands in patients with Sj?gren syndrome were compared with those of normal patients by measuring the fractal dimensions. METHODS. Fractal dimensions were estimated using the modified pixel dilation method. RESULTS. The mean fractal dimension was 1.64 +/- 0.06 for the normal glands and 1.39 +/- 0.10 for the glands with Sj?gren syndrome (P < .005). No correlation between the age or sex and fractal dimension was observed for both groups. In Sj?gren syndrome, a significant difference in the fractal dimension was observed between the subgroup having punctuate fillings with a diameter less than 1 mm and the subgroup from 1 to 2 mm (P < .001). CONCLUSION. The fractal dimension is useful as a numeric grading of the complexity of the ductal pattern and the progression of parotid disease.     

Modulation of plasma glucose levels by thyrotropin-releasing hormone administered intracerebroventricularly in the rat

Thyrotropin-releasing hormone (TRH), but not histidyl-proline diketopiperazine (cyclo[His-Pro]), induced transient hyperglycemia associated with hyperglucagonemia and marked hyperinsulinemia when placed intracerebroventricularly (i.c.v.) in anesthetized rats. This TRH-induced hyperglycemia was prevented by acute adrenalectomy. However, adrenalectomy did not prevent TRH-induced hyperinsulinemia or hyperglucagonemia. In streptozotocin-induced diabetic rats, i.c.v. administration of TRH caused progressive and pronounced hyperglycemia. i.c.v. TRH-induced hyperinsulinemia was abolished by vagotomy and by systemic administration of hexamethonium or atropine. These results suggest that TRH induces hyperglycemia mediated by stimulation of the sympathetico-adrenal system and hyperinsulinemia by stimulation of the vagus nerve, and that the rapid decline of plasma glucose levels following transient hyperglycemia is due to hyperinsulinemia.     

Tc-99m tetrofosmin myocardial perfusion SPECT after dipyridamole combined with low-level exercise in the diagnosis of coronary artery disease

Tc-99m tetrofosmin is a lipophilic, cationic perfusion imaging agent that changes to Tl-201 in detecting coronary artery disease during exercise testing. The purpose of this study is to evaluate the usefulness of Tc-99m tetrofosmin dipyridamole stress imaging combined with low level exercise for the detection of coronary artery disease. We examined 42 patients and 10 normal volunteers who also underwent coronary angiography. A one-day protocol was used: in the stress study, 296 MBq of tetrofosmin was injected and in the rest study 888 MBq was injected. After intravenous administration of dipyridamole (0.142 mg/kg/min for 4 minutes), the patient was exercised on a bicycle ergometer for 3 min (25 Watts). Tetrofosmin was injected 2 minutes after dipyridamole infusion during the exercise. Single photon emission computed tomographic images were obtained 30 minutes after the tracer injection. Images were interpreted as abnormal in 36 of 42 patients with coronary artery disease, and normal in all of 10 normal volunteers. The overall sensitivity of detection of coronary artery disease was 83.3% and the normalcy rate was 100%. The diagnostic values for the detection of significant stenosis in the three major arteries were: LAD sensitivity 83%, specificity 92%; LCX sensitivity 47%, specificity 91%; RCA sensitivity 75%, specificity 83%. Of the 66 arteries with more than 50% stenosis, 48 arteries were correctly identified. Of the 36 with more than 70% stenosis, 31 were identified. Scintigraphic evidence of multivessel disease was found in only 9 patients (50%). A protocol of Tc-99m tetrofosmin SPECT combined with low level exercise after dipyridamole is therefore useful for the detection of the coronary artery disease.     

烧伤创面细菌分布对植皮存活率的影响

目的　通过对烧伤病人不同时间的痂下组织细菌定量培养及种类检测 ,探讨手术时间、菌量和菌种与植皮存活率的关系。方法　选择 3 65例病人于手术时取痂下组织以组织匀浆行细菌定量并鉴定菌种。结果　 45 0份标本中 3 90份为阳性 ,共培养出细菌 5 80株 ,以铜绿假单胞菌(2 7.93 %)及金黄色葡萄球菌 (16.2 0 %)为最常见种类 ;手术时间、菌量和菌种对植皮存活率均有不同程度的影响 (P <0 .0 1)。结论　手术时间越早 ,痂下组织细菌含量越少 ,菌种较单一 ,植皮存活率越高 (P <0 .0 1) ;金黄色葡萄球菌感染对植皮存活率影响较大 (P <0 .0 1)。     

A case report of aorto-pulmonary window associated with atrial septal defect]

The patient was a one-year-old boy, who underwent surgery with a diagnosis of atrial septal defect (ASD). During operation, aorto-pulmonary window (A-P window) which had not been detected by the preoperative examinations, was found. Therefore, the A-P window was divided prior to closing ASD. The patient is in good condition six months after the operation. The causes of the inaccurate preoperative diagnosis were discussed.