A clinical evaluation of MK-0787/MK-0791 for long-term administration in urological infections

MK-0787 (Imipenem)/MK-0791 (Cilastatin sodium), a new compound of Thienamycin, was administered in treatment of 35 patients (36 cases) with chronic complicated UTI or for prevention of serious infections with much complicated factors. The patients were principally treated at a daily dose of 1 g for over 10 days. The efficacy rate of 26 patients who were evaluable in the early phase (4-7 days) was 88.5%, while it became up to 92.3% in the final phase judgment. As for clinical usefulness, the result was obtained to be as high as that of the clinical efficacy. In bacteriological study, 35 strains were clinically isolated including 7 strains of P. aeruginosa from UTI. All the strains disappeared with an eradication rate of 100% after treatment. Strains appearing after Imipenem/Cilastatin sodium treatment mainly consisted of fungi. Usefulness judgements tended to be greater in the final phase than in the early phase. As for side effects, vomiting was recorded in one case, in which the administration was discontinued. In laboratory findings there were 3 cases with elevated GPT, 2 cases with elevated GOT, one case with elevated gamma-GTP, one with thrombocytopenia, and one with eosinophilia each, but these abnormal values were slight and transient. In summary our clinical study showed that Imipenem/Cilastatin sodium was a very effective antibiotic in treatment on moderate or serious UTI or preventive use for infections in compromised hosts. Considering the features of this agent, it might be more effective and useful for clinical use in treatment on polymicrobial infections including stubborn organisms than any other antimicrobial compounds. Furthermore, it was safe and well tolerable in a long term treatment.     

Hemopoietic neoplasms in lethally irradiated mice repopulated with bone marrow cells carrying the human c-myc oncogene: a repopulation assay.

Bone marrow (BM) cells from two transgenic mice carrying the human c-myc oncogene were separately harvested, and each sample was injected into 25 lethally irradiated mice. We observed the contribution of the myc gene to the occurrence of hemopoietic neoplasms in the BM-repopulated mice, establishing a new experimental system for analyzing oncogene expression in the hemopoietic system in vivo. The hybrid gene that was transferred into the original transgenic mice was a combination of the human c-myc gene with a regulatory unit consisting of a murine immunoglobulin-heavy chain with an SV40 early-T promoter gene (Ig/Tp-myc). Among the transgenic lines, the tested BM cells were chosen from two lines that had been low-prone in leukemia; in these lines hemopoietic neoplasms did not appear for greater than or equal 200 days after birth. Lethally irradiated controls received BM cells from litters of transgenic mice that did not carry c-myc. The lifetime incidence of hemopoietic neoplasms was 94% and 91% in the two groups of mice repopulated with myc+ BM. By contrast, only 15% of control mice with myc- BM developed hemopoietic lesions. The incidence of hemopoietic malignancies combined with nonthymic lymphomas and myeloma cases (88% and 65%) was higher in the repopulated mice than the incidence of pre-B cell lymphomas in the original transgenic lines (56%). Thirty-two of the 40 myc+ mice that were examined showed the presence of the transferred gene in either the normal hemopoietic tissue or in the hemopoietic neoplasm. Furthermore, 18 of 22 hemopoietic neoplasms studied by Northern hybridization expressed mRNA from the transgenic gene; in other four neoplasms, expression was weak or absent.     

A case of polycythemia vera complicated by chronic renal failure under hemodialysis requiring parathyroidectomy for secondary hyperparathyroidisim

A case of polycythemia vera complicated by chronic renal failure under maintenance hemodialysis requiring parathyroidectory (PTH) for secondary hyperparathyroidism (2° HPT) is reported. A 62 year old female presented with 75000 white blood cells (WBC)/μl, 703×10⁴ red blood cells (RBC)/μl, 23×10⁴ platelets (PLT)/μl, hyperuricemia and hypertension in 1970 and the diagnosis of polycythemia vera was made. Hemodialysis was started in October 1974 for chronic renal failure. Blood cells in peripheral blood rapidly decreased in number after the beginning of dialysis, reaching the level of 10000∼20000 WBC/μl, and 150∼250×10⁴RBC/μl. In August 1988, marked bone resorption in X-ray picture and high serum alkaline phosphatase and parathyroid hormone (PTH) noted along with 17400 WBC/μl, 370×10⁴RBC/μl and 35.9×10⁴PLT/μl. After subtotal PTX removing 3.21g parathyroid gland, serum PTH rapidly fell. At 3 months after PTX, WBC rose to 23600/μl, RBC 372×10⁴/μl and PLT 94.0×10⁴/μl. At 6 months, WBC was to 31000/μl, RBC 429×10⁴/μl and PLT 78.0×10⁴/μl, suggesting an inhibitory action of PTH on not only RBC, but also WBC and PLT.     

Studies on the massive flights of chironomid midges (Diptera: Chironomidae) as nuisance insects and plans for their control in the Lake Suwa area, central Japan. 1. Occurrence of massive flights of Tokunagayusurika akamusi

Adult Chironomidae (Diptera, particularly Chironomus plumosus and Tokunagayusurika akamusi) emerging from eutrophic lakes or polluted bodies of water in Japan have become intolerable because they pose a severe nuisance and cause economic problems. In the Lake Suwa area, massive flights of adult midges of T. akamusi have occurred frequently, and caused problems in the daily life of local residents or for the tourist business. The author tried to clarify the biological and hygienic problems involved in these massive flights. In order to control adult midges, the distribution of larvae in the lake, the period and quantity of emergence from water, the time of flight, and the dispersal range of T. akamusi midges were studied. The results obtained are as follows: 1. Larvae of T. akamusi are distributed over the whole lake, especially in the east and southeast part with high densities. Mean biomass was about 100 g wet weight/m2 in Lake Suwa. On the shore near these areas, dense swarms of adult midges were found. 2. Emergence of T. akamusi from Lake Suwa was observed at the end of September and lasted till the middle of November. The emergence peaked in the middle of October. The time of flight was mainly at 17: 30-19: 30. 3. The dispersal ranges of adult midges were confirmed with two methods, i.e. the ordinary light trap method and a questionnaire survey of 544 residents. The result obtained with the questionnaire survey was consistent with that of the light trap method and the questionnaire survey made it possible to collect information in a wider area than the usual one. 4. T. akamusi midges reached areas over 3 km from the lake, but more than 90 percent of the midges flew within 500 m of the lake's shoreline. However, even in the more distant places where there was a source of bright light there were many adult midges. 5. The wind (at 18: 30) was the main factor which expanded the dispersal range of adults. We observed that many adults appeared after a strong wind (6-7 m/s). 6. Many adult midges were collected by light trap at the top of a building with a height of 45 meters.     

Antitumor activities of KW-2152, a new isoquinon agent, against human tumor xenografts transplanted into nude mice

The antitumor activities of KW-2152, a new isoquinon derivative, were examined in thirteen human tumor xenografts, transplanted into nude mice. KW-2152 was administered intravenously at a schedule of q4d X 3, in daily doses of 7.3 mg/kg and 3.6 mg/kg, and q2d X 6 with a daily doses of 7.3 mg/kg, respectively. KW-2152 displayed significant antitumor activities against the human tumor xenografts in 3 out of 13 strains (23.1 per cent) at the schedule of q4d X 3, with a daily dose of 7.3 mg/kg. Depending on the schedule of administration, tumor activity was observed in 8 out of 13 strains (61.5 per cent) at a schedule of q2d X 6, with a daily dose of 7.3 mg/kg. SH-2 and SH-9 gastric tumors were sensitive to KW-2152 and growth was completely inhibited with the schedule of q4d X 3, and a daily dose of 7.3 mg/kg. Thus, KW-2152 seems to have a wide antitumor spectrum, and the possible antitumor effects for clinical use, warrant attention.     

Bleeding from gastric ulcer halted by laparoscopic suture ligation

In a 48-year-old Japanese man there was an uncontrollable and recurrent bleeding from a gastric ulcer and laparoscopic surgery was done. Two cannulae were placed in the gastric cavity through the abdominal wall and suture ligation of the bleeding vessel at the posterior wall of the stomach was done under videovisual control with endoscopic guidance. The bleeding ceased, complications were nil, and he remains well.This article reports on surgery done to repair uncontrollable, recurrent bleeding from a gastric ulcer. Two cannulae were placed in the gastric cavity through the abdominal wall and suture of the vessel at the posterior wall of the stomach was done with videovisual control and endoscopic guidance. This approach is concluded to have supplied minimal-access surgery, cost effectiveness, early discharge, less pain, and doctor-patient satisfaction.     

False positive accumulation in 18F fluorodeoxyglucose positron emission tomography scan due to sarcoid reaction following induction chemotherapy for lung cancer

We present a case of lung cancer that showed false positive accumulation in an ¹⁸F fluorodeoxyglucose positron emission tomography (FDG-PET) scan following induction chemotherapy for suspected metastasis and progression of malignancy. A 66-year-old man was diagnosed with squamous cell carcinoma in the lung, classified as clinical stage IIIA (T2N2M0), and underwent induction chemotherapy. An FDG-PET scan prior to chemotherapy demonstrated accumulation only in the tumor, whereas following treatment it revealed a strong accumulation not only in the tumor, but also in the supraclavicular lymph nodes, which indicated lymph node metastasis. The patient underwent a biopsy of the right supraclavicular lymph node and mediastinoscopy, after which all dissected lymph nodes showed sarcoid reactions and no tumor cells were found pathologically. We concluded that when evaluating the effect of induction chemotherapy for malignancy, a sarcoid reaction might lead to the false positive accumulation of FDG.     

Analgesic dose-response relation in cervical epidural block

The relationship between the age and the spread of analgesia from different epidural anesthetic doses was examined by studying analgesic dose responses in cervical epidural analgesia. Two different anesthetic doses (5ml or 10ml) of 2% mepivacaine were injected into the cervical epidural space at a constant pressure (80mmHg) using an intravenous apparatus, and the spread of analgesia to pinprick was assessed. The significant correlation was found between the patients age and the number of spinal segments blocked (5ml:r = 0.8498, P < 0.01, 10ml:r = 0.5988, P < 0.01). The inverse linear relationship was found between the patients age and the segmental dose requirement (5ml:r = –0.6754, P < 0.01, 10ml:r = –0.5784, P < 0.01). Patients under 39 years of age showed a direct relationship between the dose injected and the number of spinal segments blocked, enabling prediction of the number of segments blocked with a given dose of local anesthetic. Doubling the epidural dose approximately doubled the number of spinal segments blocked. The analgesic dose-response relation in patients over 60 years of age differed from that in patients under 39 years of age and doubling the epidural dose did not double the number of spinal segments blocked. Progressively more extensive analgesia was obtained from a given dose of local anesthetic with advancing age. It was difficult to limit the extent of analgesia by injecting a smaller dose of local anaesthetic in the elderly.(Hirabayashi Y, Matsuda I, Inoue S et al.: Analgesic dose-response relation in cervical epidural block. J Anesth 2: 22–27, 1988)