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"Leukerin ® powder 10%" containing mercaptopurine (6-MP) is an oral anticancer drug that requires careful handling. As a powder formulation, there are risks of exposure due to scattering during dispensing and possible 6-MP contamination to other drugs due to adhesion to the packaging machine. We previously reported that wiping with an alcohol-containing towel is useful for removing scattered powder after dispensing. However, it is recommended to wipe disk-type powder-packaging machines with water instead of cleaning with the alcohol-containing towel. Hence, we scattered 6-MP powder 100 mg (total amount of 6-MP: 10 mg), and then wiped with water three times using different types of cloth each time. We confirmed that third time wiping cloth did not have any 6-MP. Furthermore, we confirmed that the adhering 6-MP could be removed by wipe-cleaning (water-wiping twice and dry-wiping once) after dispensing 6-MP powder at two pharmacies that routinely dispensed 6-MP powder using a disk-type powder-packaging machine. In addition, we confirmed the adhesion of 6-MP in parts of the machine not cleaned by wipe-cleaning and also in parts that were washed only with water, in both the pharmacies. Based on the above observations, we recommend the following steps for cleaning disk-type powder-packaging machines after dispensing 6-MP powder: (1) wipe-cleaning that includes water-wiping twice and then dry-wiping once, (2) cleaning all areas of the packaging machine, and (3) wipe-cleaning with water before washing with water.

The immunosuppressant azathioprine (AZA) is classified as a hazardous drug. AZA contamination during tablet-splitting increases exposure risk. However, there is no study on contamination and exposure during AZA tablet splitting and dispensing. AZA tablet splitting and dispensing methods were classified based on whether tweezers are used during splitting and packaging. In Dispensing Method (1), no tweezers were used in either step. In Dispensing Method (2), no tweezers were used during tablet splitting, but were used during packaging. In Dispensing Method (3), tweezers were used in both steps. After AZA half-tablet split-dispensing, we quantified the adherent AZA removed from the tools, packaging machines, and dispensing counters by three consecutive wipings with water-dampened polypropylene cloths. A large amount of AZA adhered to the gloves used in Dispensing Methods (1) and (2), wherein tablets were placed with gloved hands, compared with Dispensing Method (3), wherein tablets were held with tweezers. Thus, the gloves must be replaced before touching the packaging paper during the final step. After three consecutive wipings, AZA was not detected at most of the sites in the third round. Thus, we recommend that (1) AZA tablet splitting should be performed while wearing gloves, (2) the gloves should be changed before packaging the half tablets, and (3) the tools, packaging machines, and dispensing counters should be wiped twice or thrice with a water-dampened cloth after dispensing.

Dilatation of the colon in severe and fulminating ulcerative colitis is a sign of toxic megacolon and emergency surgery is usually the favored treatment option. Here we describe our experience with three cases of ulcerative colitis with megacolon in which surgery was avoided by treating the patients with a continuous intravenous infusion of cyclosporine, with full cooperation of the surgeons. We recommend that continuous intravenous infusion of cyclosporine be considered as an effective option for the conservative management of severe, fulminating ulcerative colitis with megacolon.

A 2-year and 4-month-old boy developed Langerhans cell histiocytosis (LCH) at the left parietal region of the skull. After treatment with chemotherapy, the patient achieved remission but experienced three relapses. After 3 years, he complained of headache, blurred vision, and lethargy. Brain magnetic resonance imaging revealed multiple dura-based meningeal masses. Biopsy was performed, and the patient was then diagnosed with juvenile xanthogranuloma (JXG). The analysis of both LCH/JXG tissues revealed BRAF V600E mutation. The JXG masses were not responsive to prednisolone, which was injected locally, radiotherapy (24 Gy), and chemotherapy (2-chlorodeoxy-adenosine). In addition, since the patient developed macrophage activation syndrome associated with systemic JXG progression, he received unrelated cord blood transplantation (u-CBT) at the age of 10 years and 11 months. Engraftment was performed at day 42, and significant GVHD was not observed. Four months after CBT, the patient was treated with infliximab (Remicade ® ) and dexamethasone palmitate (Limethasone ® ). The size of the intracranial JXG masses gradually decreased after u-CBT and disappeared after 4 years. Currently, the patient is doing well at the age of 25 years and is receiving androgen replacement therapy.

The present study investigated the long-term outcomes of restorative proctocolectomy in pediatric patients with ulcerative colitis (UC). We report a series of 25 patients who underwent total proctocolectomy with ileal pouch-anal canal anastomosis (IACA). Surgery was performed for medically intractable colitis and severe colitis in 14 and 11 patients, respectively. Early and late complications were observed in 6 (24%) and 14 (56%) patients, respectively. The long-term quality of life outcomes were satisfactory, including both bowel function and social function. Growth retardation was observed in 6 patients. Five patients exhibited catch-up growth and 3 patients overcame growth retardation. Patients with growth retardation tended to have a younger onset and longer duration of UC, as well as a longer duration and higher total dose of steroid use. In conclusion, the long-term outcomes of pediatric patients with UC undergoing IACA are satisfactory. Furthermore, to minimize the risk of growth retardation, surgery should be performed without delay.

We describe a 42-year-old-man with HIV infection who developed ulcerative colitis. Ulcerative colitis was diagnosed on the basis of clinical symptoms, and the findings of colonoscopy, pathology and culture. Although remission of ulcerative colitis was induced by PSL and SASP, HIV infection progressed. Treatment with highly active antiretroviral therapy (HAART) was started. HIV viral load decreased to less than 50copies/ml and CD4 counts increased to over 400/microl. After discontinuance of PSL and SASP, he is still in good condition. This is the first report of HIV infection associated with ulcerative colitis in Japan. A relationship between immune disorder in advanced HIV infection and inflammatory bowel disease was suggested. Ulcerative colitis might be an important complication in HIV infection.

Treatment strategies for follicular lymphoma have not been established. We report the outcome after combination therapy with rituximab and cladribine (RC) for 8 patients with follicular lymphoma treated between January 2005 and December 2006 in our hospitals. Median patient age was 57 (range 42 approximately 73) years. There were 4 males and 4 females. Only 1 patient had refractory disease, while the others had untreated disease. On the follicular lymphoma international prognostic index, 4 patients were in the low-risk group, 3 in the intermediate-risk group and 1 in the high-risk group. The median follow-up period was 36 (range 22 approximately 90) weeks. The RC protocol consisted of intravenous rituximab at a dose of 375 mg/m (2) on day 1 and cladribine at a dose of 0.1 mg /kg per day for 2-hours on day 1 through 5. The median number of RC courses was 5 (range 3 approximately 8). The median interval between the 2 courses was 7 (range 3 approximately 26) weeks. The overall response rate was 87.5%. Grade 3 neutropenia was observed in 50% patients, although G-CSF was not needed. There was no apparent thrombocytopenia or anemia. Herpes zoster was observed after treatment in 1 patient. RC is considered highly effective and well tolerated.

Purpose: We conducted a randomized controlled study to evaluate the safety and usefulness of a combined treatment of radiotherapy and chemotherapy with doxifluridine (5'-DFUR) plus tamoxifen (TAM) as an adjuvant therapy for breast cancer patients after conservative surgery. The complications observed in this trial are reported herein., Methods: A total of 550 patients were registered and randomized (based on factors such as T, N, with/without radiotherapy) to groups A and B. Drug regimens were: group A, 5'-DFUR 600 mg/body/day for 6 months and TAM 20 mg/body/day for 2 years; group B, 5'-DFUR 600 mg/body/day for 2 years and TAM 20 mg/body/day for 2 years. Radiotherapy (2 Gy x 5 times/week, for 5 weeks) was administered to 88.6% of evaluable patients (481/543). Radiation-related acute adverse reactions occurred in 28.5% of the 481 patients and moderate to severe reactions occurred in 1.5% of the patients. Delayed radiation-related adverse reactions occurred in 23.8% of the patients but none were severe. Chemo-endocrine therapy-related adverse reactions occurred in 17.9% of group A patients and 25.6% of group B patients. Grade 3 reactions occurred in 6 of the group A patients (2.4%) and in 5 of the group B patients (1.9%); all adverse reactions subsided after dose reduction or discontinuation. These findings suggest that the combination therapy of irradiation and 5'-DFUR with TAM is safe for patients after breast conserving surgery.

We developed MR-dacryocystography as a non-invasive, safer imaging technique for canaliculi, the nasolacrimal duct and lacrimal sac by dropping saline solution and diluted Gd-DTPA solution into the eye. The diluted Gd-DTPA solution was found to create no local irritation in the eyes of rabbits and normal volunteers. Lacrimal sacs and ducts were well visualized in all of 10 normal volunteers by using the saline solution or the diluted Gd-DTPA solution. Canaliculi were visualized in 4-7 cases on thin-slice axial images. MR-dacryocystography was suggested to be a useful screening examination for lacrimal outflow disorders.

To obtain simultaneous embolization of feeding arteries and portal veins in the hepatocellular carcinoma, we performed a new treatment, balloon occluded ethanol ablation therapy (BEAT), in 7 patients. A Balloon catheter was inserted into the hepatic vein draining the tumor bearing segment of the liver. During occlusion of the hepatic vein by balloon catheter, an absolute ethanol-Lipiodol emulsion was injected through a microcatheter or a microballoon catheter placed in the feeding artery. There were no major side effects. Histological examination of the specimen taken from one case showed complete necrosis of the tumor and accumulation of Lipiodol within the portal veins of the surrounding tissue.

We evaluated re-diagnostic ability of dynamic MRI as compared with T2 weighted image in the diagnosis of primary therapeutic effect and tumor recurrence after transcatheter arterial embolization (TAE) for hepatocellular carcinoma. Thirty-four nodules in 30 patients with hepatocellular carcinoma were estimated based on operative and angiographic findings. According to the time when dynamic MRI was taken, nodules were classified as a short-term observation group consisting of 15 nodules obtained within a month after TAE, or as a long-term observation group consisting of 19 nodules obtained over a month after TAE. In the short-term observation group, sensitivity, specificity, accuracy was 89%, 100%, 93% on dynamic MRI and 78%, 67%, 73% on T2WI, respectively. In the long-term observation group, these were 94%, 100%, 95% on dynamic MRI and 100%, 33%, 89% on T2WI and 94%, 67%, 89% on Lipiodol-CT, respectively. In both groups, dynamic MRI was superior in accuracy. Conclusively, we consider that dynamic MRI is a most accurate diagnostic method that should be added to routine MRI after TAE. Especially in the case diagnosed positive on T2WI, the usefulness of dynamic MRI should be emphasized to determine the schedule of the therapy, because the cases that were false positive on T2WI were accurately diagnosed on dynamic MRI.

To evaluate the dynamics of extravascular perfusion, dynamic CT with two different molecular sized contrast media was performed on VX2 tumor of rabbit. The first dynamic CT was performed with a bolus injection of iopamidol (IP:120 mgI/ml, 5 ml). After ascertaining that the tumor attenuation had returned to the pre-contrast level, the second dynamic CT was performed on the same slice with bolus injection of iodoethylated starch (IES:120 mgI/ml). The time-density (T-D) curves of the same tumor area on the images obtained by two contrast media were compared. The T-D curve with IP showed definitely higher level than that with IES. This occurrence can be explained that IP, 13 A in size, has higher permeability distributing not only in the intravascular space, but also into the extravascular space. On the other hand, IES, 200 A in size, will stay mostly in the intravascular space. From this, we consider that the attenuation difference between the two curves will be an indicator for the dynamics of extravascular perfusion, suggesting to become a new method for CT diagnosis.

The difference of vascular permeability and hemodynamics between Iotrolan and Iopamidol was experimentally studied on dynamic CT and angiography. A hemodialyzer with 60 A pores were applied as a phantom of a target organ with capillaries and extravascular space. Dynamic CT scans and DSA of the phantom were performed with injection of each contrast medium and time-density curves obtained from several regions of interest were compared. The dynamic CT scans performed at 40 seconds after the completion of injection, showed that Iopamidol was mostly distributed at the site of inlet, while Iotrolan was mostly at the center of the phantom. Time-density curves on DSA with Iotrolan revealed lower and shorter peak density and time than did Iopamidol. In conclusion, Iotrolan has lower permeability than that of Iopamidol because of its larger molecular size. Iotrolan has slower flow through catheters and capillaries than that of Iopamidol because of its higher viscosity. One should be aware the difference between the two contrast media and be careful to the analysis of time-density curves of dynamic CT and DSA.

E2A gene rearrangements and E2A-PBX1 chimeric mRNA produced by t(1;19) were examined in 50 cases with acute lymphoblastic leukemia (ALL). Nine of 10 ALL cases with t(1;19) showed the rearrangement by Southern blotting using the E2A gene probe when digested with Xba I, Bgl II, and Eco RI, and the remaining one having hyperdiploidy which was considered to be a sign of good prognosis, lacked E2A rearrangement. Six of 7 ALL cases with t(1;19) that were tested showed the predicted 164 bps band of E2A-PBX1 chimeric mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR), while a case having t(1;19) without E2A rearrangement and 10 cases lacking t(1;19) did not. Three ALL cases tested did not have E2A-PBX1 mRNA at the time complete remission 4 months after diagnosis. Forty ALL cases lacking t(1;19), including 4 cases with t(11;19), did not reveal rearrangement of E2A. We conclude that t(1;19)-ALL can be molecularly diagnosed, and minimal residual disease could be detected by the RT-PCR method.

Opacification of lymph nodes on CT was attempted by means of indirect lymphography with iodinated starch (IS). Sixty percent solutions of two different molecular weights of IS were prepared (5,000 mol wt and 70,000 mol wt in average). After subcutaneous injection of IS solutions to the pedal area of dogs, CT scans were performed to evaluate opacification of the popliteal lymph nodes. The lymph nodes began to be opacified from 10 min after the injection of each solution. The high molecular weight IS showed higher attenuation and longer duration of opacification than did the low molecular weight IS. Homogeneity of opacification was better with latter. The optimum molecular weight for this purpose is considered to be between 5,000 and 70,000 mol wt.

A 72 year-old woman was admitted to our hospital for hematoemesis. After admission, endoscopic examination showed esophageal varices with a red color sign which indicated endoscopic injection sclerotherapy (EIS). Concurrently, however, laboratory findings revealed severe neutropenia in peripheral blood, while bone marrow examination showed marked reduction of mature granulocytes with mild myeloid hyperplasia. As a result of those hematological abnormalities, EIS was halted. Concerning the pathogenesis of this neutropenia, immunofluorescence technique using flow cytometry disclosed the presence of anti-neutrophil autoantibody in the serum, giving a clinical diagnosis of autoimmune neutropenia (AIN). Thereafter, a conventional regimen of corticosteroids as an initial therapy and steroid pulse therapy as a succeeding maneuver were instituted, but in vain. As a last resort, 125 micrograms/body of rhG-CSF was given daily subcutaneously. As a consequence, significant increase in granulocyte count, though transient, was attained, which made EIS possible without any episodes of infections. It seems most likely that a high dose of rhG-CSF exerts beneficial effects as a prophylactic and therapeutic regimen against infections in patients with AIN.

A 32-year-old man who had bilateral non-palpable testis underwent microsurgical orchidopexy of the right abdominal testis. Inferior epigastric vessels were used for the recipient vessels. Ischemic time during the operation was 40 minutes. Postoperative doppler readings revealed excellent blood flow to the testis, and HCG-stimulating test revealed good response. Now, 2 years after surgery, no sign of atrophy is found.

In order to reduce the arterial damage following arterial chemo-infusion, arterial reaction to anti-cancer drugs and Corticosteroid were studied experimentally and clinically. In experiment, chemo-infusions (Mitomycin C, Adriamycin, Cisplatin) with or without Corticosteroid were carried out into the auricular and femoral arteries of rabbits, and the arterial changes were examined angiographically and histopathologically. The histologic examination showed the damages of various degrees characterized by intimal edema with pyknosis of endothelial cells, thrombus formation and detachment of intimal layer. The degree and frequency of the damage increased as the drug dose and concentration increased. However, higher blood flow and Corticosteroid could reduce the damages in some degrees. Clinically, bronchial arterial infusion of Cisplatin with or without Corticosteroid were studied. In conclusion, when angiography following ACI reveals narrowing and/or irregularity of the target artery, reduction of drug concentration and dose as well as elongation of infusion intervals are advised.

We performed transcatheter embolization in two cases with huge pulmonary arteriovenous fistula (AVF) using a metallic "spider" and spring embolus. Conventional spring embolus or detachable balloon could not be used in these cases. Metallic spider was indicated for pulmonary AVF with a feeding artery diameter of more than 16 mm to prevent embolus passing through the AVF. In the first case, we used large handmade metallic spiders of 25 mm in diameter followed by embolization by numerous spring coils. At that time, a partial monorail technique was newly devised to carry the large metallic spider into the feeding artery, otherwise the spider could not pass into a 9F catheter. After embolization, symptoms and PaO2 in arterial blood improved remarkably in both cases. In the second case, a spring coil migrated into the normal pulmonary artery, but no infarction resulted. In conclusion, the metallic spider was very useful for embolization of hugee pulmonary AVF to avoid the embolus passing through and to tangle spring coils together with it. If commercially available "spiders" are too small, ones can be made easily.

To establish a safer puncture method for TIPSS (Transjugular Intrahepatic Portosystemic Stent Shunt), we developed a new percutaneous puncture technique to penetrate portal and hepatic vein trans-hepatically under ultrasonography (US technique). Experimentally we compared this technique with conventional transjugular technique puncturing portal vein through hepatic vein using Ross needle (Ross Needle technique). Success rate is 100% in US technique and 50% in Ross needle technique. Seven complication including intraperitoneal bleeding occurred in Ross needle technique, but no complication in US technique. Conclusively, US technique is a safer and more reliable method than that using Ross needle in the puncture method for TIPSS.

The histopathological responses of the rabbit esophagus to high-dose-rate intracavitary irradiation were investigated. After 5, 10 or 15 Gy irradiation using a remote afterloading system, the rabbits were sacrificed on different occasions. The esophagus was excised from each animal and examined histopathologically. Esophageal ulcer was observed 7 to 28 days after the irradiation of the highest dose. Edema and cell infiltration in the lamina propria proceeded mucosal changes like ulcer. Chronic injuries such as mucosal necrosis were seen at 6 months.

The induction heating to ferromagnetic implants (Ferromagnetic Induction Heating: FIH) has been developed for the purpose of selective hyperthermia on deep-seated tumors. In this investigation, the procedure of FIH combined with hepatic arterial embolization (HAE) was experimentally studied on VX2 liver tumor of rabbit. The induction heating unit is composed of radiofrequency generator (500 KHZ, 6-12 KW) and circular applicator (60 cm in diameter). Ferromagnetic implant used was pure iron particles (100 mu in size), which were suspended in tenacious polysaccharide solution to be injectable through a needle. After HAE with gelatin sponge powder had been made, iron particle suspension was injected into the cavity of tumor with subsequent exertion of induction heating (9KW) for 15 minutes. The measurement of temperature was made on the tumor and the liver parenchyma by fluoroptic thermometer with thin, flexible probe which readily passed through a needle. The temperature measured at peripheral area of tumor elevated at range from 2.5 to 7.1 degrees C, corresponding to the dose of iron particles injected; 2.5 degrees C with 1 g, 4.9 degrees C with 2 g, 7.1 degrees C with 3 g. In contrast, the temperature of liver parenchyma elevated at range of less than 2.5 degrees C, to indicate a successful selective heating of liver tumor. An additional experiment for the effect of heat on normal liver of rabbit were made using a microwave heating system. The histological and serologic examinations after heating of below 40 degrees C did not show any abnormal findings. After heating of 42-43 degrees C, however, serum GOT and GPT transiently elevated more than 3 times to that of before heating. Histologically, there were extensive degeneration and necrosis of liver tissue. From the results we concluded that FIH combined with HAE could provide an intensive therapeutic effect for treatment of well-localized liver tumors with minimal damages to the liver parenchyma, because of selective heating of the tumor.

To improve distribution of drug by intraarterial infusion a new catheter system with sideholes, tip of which was able to be occluded by an embolus, was developed. Inner diameter of the catheter was 0.038 inch. Tip of the catheter was so smoothly tapered to 0.025 inch in inner diameter that it could be occluded by an embolus of 0.038 inch in diameter. After occlusion of the tip, drug flowed out rectangly to catheter axis from only sideholes, resulting that drug flowed out was mixtured by blood stream to make a uniform distribution of it.

A forty-year-old woman who developed brain abscess was found to Rendu-Osler-weber syndrome with multiple arteriovenous fistulas of the left lung. Therapeutic embolization of pulmonary arteriovenous fistulas was performed for the prevention against brain abscess and improvement of hypoxia.

We undertook hepatic artery infusion of high dose adriamycin (ADR) in three patients with unresectable hepatocellular carcinoma utilizing direct hemoperfusion (DHP) under hepatic venous isolation (HVI). 5 minutes continuous infusion of ADR at dosages of 100 and 150 mg/m2 was combined with DHP of 20 and 30 minutes, respectively. HVI was established by occlusions of suprahepatic and retrohepatic vena cava using a tourniquet tape and a cuff-cannula. During HVI, hepatic venous outflow was directed toward DHP and joined with the rest of the intra-caval blood before the centrifugal pump connected to a return cannula to the left axillary vein. Systemic levels of ADR were maintained less than 2 micrograms/ml during the treatments in three patients. The estimated drug removal rates were 72.3%, 51.2% and 31.1% respectively. Hematologic changes due to DHP were tolerable and transient. Highest values of serum transaminases were demonstrated on day 2 and rapidly recovered to the pretreatment levels within a week. Postoperative CT studies revealed also marked reduction in tumor size. We consider this method an attractive therapeutic option for patients with advanced hepatocellular carcinoma.

We reported a case of interstitial pneumonia immediately after hepatic arterial infusion of Lipiodol anticancer drug emulsion for hepatocellular carcinoma. The reason was considered that Lipiodol-anticancer drug emulsion ran through an A-V shunt to alveolar septum resulting in alveolitis.

Clinical studies of imipenem/cilastatin sodium (IPM/CS) were conducted in 40 pediatric patients. 29 out of the 40 patients were treated for infections and 11 for prophylaxis. The following results were obtained. 1. The response rate in 29 patients with infections was 79.3%. Among the 29 patients, 16 patients who presented with malignant diseases showed the response rate of 68.8%. The response rate was lower in patients with severe infections than in those with mild or moderate infections, and a lower response rate was associated with severe neutropenia. However, there were no differences in the response rates between patients who had previously been treated and those who had been untreated with other antibiotics. The response rate in 6 patients from whom causative organisms were isolated was 83.3% and that in the remaining 23 patients was 78.3%. 2. The response rate in 11 patients to whom IPM/CS was administered prophylactically was 63.6%. 3. As for side effects, a rash was observed in 1 patient and hematuria in another, and the abnormal laboratory test results observed were elevations of GOT and GPT in 1 patient. However, they were not clinically significant. From the above results, it appears that IPM/CS may be used as a drug of the first choice for the treatment of patients with severe infections in which the causative organisms are unknown, and for the prophylaxis of infection in patients with neutropenia.

Magnetic resonance imaging and computed tomography were compared in a prospective study of 137 lung cancer patients proved by surgery or autopsy for determining the staging, evaluation of therapeutic effect and diagnosis of recurrent tumor. 1. Lung cancer staging In peripheral lung cancer, T1 and T2 relaxation times of the tumors before operation have some correlation with those of operated specimens. These relaxation times, however, are of limited nodule characterization. Hilar mass and adjacent pulmonary consolidation (obstructive pneumonia or collapse) can be distinguished on T2-weighted image (77%) and Gd-DTPA enhanced image (80%). Therefore these images help in distinguishing tumor from peripheral lung disease. In the diagnosis of tumor invasion to the heart and great vessels, MRI is superior to CT because MRI can be helpful in distinguishing true mass from heart and great vessels. As for the chest wall, MRI is more useful than CT in detecting tumor invasion especially to the thoracic inlet and superior regions. In the diagnosis of mediastinal and hilar lymphadenopathy, MRI is equivalent or slightly inferior to CT, but MRI can easily demonstrate the lymphadenopathy at subcarinal region on coronal image. 2. Evaluation of therapeutic effect in lung cancer patients treated by radiation and chemotherapy MRI patterns of therapeutic effect was divided into 3 types. It is suggested that there is some correlation between these patterns and histologic types. MRI can easily demonstrate necrotic area on T2-weighted and Gd-DTPA enhanced images. 3. Diagnosis of recurrent tumor in treated lung cancer Concerning detecting recurrent tumor after surgery or irradiation, and delineating tumor from radiation pneumonitis, T2-weighted and Gd-DTPA enhanced images are of clinical value.

In order to clarify the cause of arterial changes after intra-arterial infusion of anti-cancer drugs (AI-AD) experiments were made on the arteries of rabbits. Histopathologic sections, 7 days after AI-AD revealed endothelial damage characterized by pyknosis, hyalinization with edematous change of the intimal layer. Proliferation of the endothelial cells was also observed. The cause of narrowing or occlusion of the arteries was considered to occur with thrombus formation surrounded by the proliferated endothelial cells and this suggested that thrombolytic agents would be effective to prevent these arterial changes.

Cefixime (CFIX) was given orally in a single dose of 100 mg to 7 patients with varying degrees of impaired renal function (Ccr 12.0-56.7 ml/min) and serum concentrations and urinary excretion rates were measured with time for the first 24 hours by the bioassay method to investigate in vivo pharmacokinetics of the drug. The results obtained are summarized as follows. The mean peak serum concentration of CFIX in 3 patients with moderately impaired renal function (group I: Ccr greater than or equal to 30-less than 60 ml/min) was 2.04 micrograms/ml at 6 hours after dosing and gradually declined to 0.10 microgram/ml at 24 hours after dosing. The half-life was 4.15 hours. The mean peak serum concentration of CFIX achieved was 2.27 micrograms/ml at 8 hours after dosing in 4 patients with severely impaired renal function (group II: Ccr greater than or equal to 10-less than 30 ml/min) and the concentration of CFIX was 0.99 microgram/ml even after 24 hours. The half-life was prolonged to 11.05 hours. There was no great difference between groups I and II in the first 24-hour urinary excretion rates. However, the first 4-hour urinary excretion accounted for 2.14% of the administered dose of CFIX in group I but only 0.47% in group II. Urinary concentrations of CFIX peaked at 4-6 hours after dosing in both groups, and thereafter gradually decreased in group I. Whereas, they did not decline much in group II until 24 hours after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)