Acute accidental overdosage of haloperidol in children.

We report the details of an accidental overdosage of haloperidol in 24 children in one hospital in Kyushu, Japan. Evidence of acute toxicity included disturbances in consciousness (24/24), tremors in the extremities (16/24), an oculogyric or similar crisis (14/24), dysarthria (9/17), drooling (8/24), akathisia (6/20), hyperreflexia (6/24) and opisthotonos (3/24). Laboratory examinations revealed late-onset transient thrombocytosis (5/24), elevated AST and GPT (1/24) and abnormal ECG with prolonged QT interval in 2 of 8 children. We detected haloperidol in 11 of 18 children whose blood was specifically examined within four days after the final haloperidol administration. The maximum serum haloperidol level was 28.9 ng/ml. The mean half-life of haloperidol in the serum of five children (age range 2-10 years) was 18.6 +/- 12.2 h (mean +/- SD) (range 9.1-39.4 h).

Association of the Sendai virus C protein with nucleocapsids.

The subcellular localization of the nonstructural protein C of Sendai virus was investigated by means of indirect immunofluorescence microscopy of Sendai virus-infected cells, using an antiserum specific for C protein. In infected cells, C protein was detected exclusively in the cytoplasm as granular fluorescence, which coincided very well with the distribution of nucleocapsid protein NP and phosphoprotein P, which were also detected with specific antisera. This suggested that these proteins are present together in inclusions, probably forming nucleocapsids. In contrast, when the NP and C proteins were individually expressed in COS cells by transfection with expression plasmids containing cDNA for these proteins, their distribution patterns in the cytoplasm were found to be quite different from each other. Protein-blot analyses of purified virions revealed the presence of a significant amount of the C protein in virions, which indicated that C protein is integrated into virions. Under conditions in which most of the envelope-associated proteins, such as HN, F, and M, were removed from the virions by a detergent, the C protein remained tightly associated with the nucleocapsids--about 40 molecules per nucleocapsid.

[Prostatic tissue and fluid levels of lomefloxacin (NY-198)].

The concentration of Lomefloxacin (NY-198), a new quinolone, in human prostatic tissue and fluid was examined. Lomefloxacin was concentrated in prostatic gland and the mean ratios of prostatic tissue levels to serum levels (P/S) were 1.39-1.83 during 2 to 6 hrs after administration. Concerning prostatic fluid concentrations, there were no significant differences between healthy volunteers and patients with chronic prostatitis. The mean ratios of prostatic fluid levels to serum levels (Pf/S) were 0.36-0.77 during 1 to 4 hrs after administration. The concentration of Lomefloxacin in the prostatic tissue and fluid is high enough to eradicate the majority of pathogens causing bacterial prostatitis.

[Clinical study of ofloxacin in complicated urinary tract infection].

Ofloxacin (OFLX) was administered at a dose of 200 mg, three times daily (600 mg) for 14 days, to 15 patients suffering from complicated urinary tract infection. According to the criteria for clinical evaluation by the UTI committee, excellent and moderate responses were seen in 54% at 5 days evaluation, and in 91% at 14 days evaluation. No serious side effects were recognized and no changes in laboratory examination data were observed. We conclude that OFLX was useful in treatment of urinary tract infection.

[A clinical survey on malignant tumors of upper urinary tract in a 10-year period].

A clinical survey was done on 107 patients with malignant tumor of the upper urinary tract (50 renal tumors, 25 renal pelvic tumors, 32 ureteral tumors) treated at our Department during the last 10 years (1976-1985). All types of tumors occurred more frequently in males than in females. The age groups of patients in which renal, renal pelvic and ureteral tumors were seen most frequently were those in their sixties, sixties and seventies, respectively. The most frequent primary symptom in patients with these three tumors was gross hematuria. The 5-year actual survival rate for the patients with renal, renal pelvic and ureteral tumors was 48.1, 37.9 and 31.8%, respectively. For all 3 kinds of tumors, the prognosis of patients with high-grade and high-stage cancer was worse than that of patients with low-grade and low-stage cancer. One-hour erythrocyte sedimentation rate for all the tumor types, weight of resected kidney in the case of renal tumor, and the class of urinary cytology and drip infusion pyelography findings in the case of renal pelvic and ureteral tumors were considered to be the factors possible influencing prognosis.

[Treatment of advanced bladder cancer with intra-arterial infusion of cisplatinum (CDDP) and aclacinomycin (ACR), combined with angiotensin II].

Ten patients with advanced bladder cancer were treated with intra-arterial infusion therapy. The patients consisted of nine males and one female between 55 and 82 years old (median: 70 years). In all patients, cisplatinum (CDDP) (2 mg/kg), aclacinomycin (ACR) (0.5 mg/kg) and Angiotensin II (25 mg) were infused via the internal iliac artery for a period of about 30 minutes. Seven patients also received X-ray therapy with a linac. The efficacy of this therapy was assessed by computed tomographic scanning, sonography and cystoscopy. As a result of this assessment, 2 patients were rated complete response "(CR)", 6 partial response (PR) (showing 50% or more reduction in the lesion) and 2 no change "(NC)". To compare the efficacy of this therapy for two histopathologically defined groups of patients (patients with grades 2 and 3 cancer), one patient was rated "CR", four "PR" and two "NC" in the grade 3 group (total 7 patients), while one was rated "CR" and two "PR", in the grade 2 group (total 3 patients). In effective cases, pollakiuria and miction pain disappeared shortly following intra-arterial infusion therapy. As for side effects of the therapy, mild nausea or vomiting was observed in all patients, while leukopenia was noted in one patient.

Cortisol responsiveness to insulin-induced hypoglycemia in Cushing's syndrome with huge nodular adrenocortical hyperplasia.

A 51-yr-old male patient with a 3 yr history of Cushing's syndrome is described. The baseline plasma cortisol level was elevated, while the plasma ACTH levels remained at an undetectable level. Dynamic testing of pituitary-adrenal function revealed no suppression after 8 mg of dexamethasone, and there was no response to metyrapone or CRF, while plasma cortisol showed a hyperresponse to synthetic ACTH. Plasma cortisol responded to insulin-induced hypoglycemia without an obvious ACTH response. These and the computerized tomography data suggested a "huge" bilateral nodular adrenocortical hyperplasia which was later confirmed by surgery. The left and right adrenal glands weighed 55 and 76 g, respectively. In vitro experiments, using the adrenal tissue, showed that there was an adrenal cortisol response to 1-39 ACTH but not to regular insulin, arginine vasopressin, angiotensin II, norepinephrine or epinephrine. These results indicate that plasma cortisol responded to a slight hypoglycemia-induced plasma ACTH change which was not detected in the ACTH radioimmunoassay or to factors other than ACTH which might be induced by hypoglycemia.

[Pharmacokinetics of cisplatin and the effect of sodium thiosulfate].

The pharmacokinetics of cisplatin (cis-dichlorodiammineplatinum (II), CDDP) have been studied in 11 patients. Plasma and urine CDDP concentrations were determined by flameless atomic absorption spectrophotometry. The treatment schedule was administered either by a 3-hour and 4-hour i.v. infusion or a 1.5-hour i.a. infusion. In the 3-hour i.v. infusion, the peak level of plasma total CDDP was 4.09 micrograms/ml after the end of infusion and non-protein-bound CDDP was 0.78 microgram/ml. Plasma total CDDP level declined with two peaks, the half-life of the alpha phase being 3.3 hours and that of the beta phase being 5.29 days. The half-life of non-protein-bound CDDP was 1.6 hours. CDDP might have remained for a long time, because CDDP values were obtained 3 weeks after infusion and urinary recovery of CDDP showed low values. Its urinary recovery was 40.3% of the dose infusion in the first 24 hours and 48.0% in 96 hours. The protein-binding of CDDP was inhibited by sodium thiosulfate(STS) and renal urinary excretion was enhanced. Our data suggest that STS can be applied as a neutralizer of CDDP.

[Characteristics of lactate dehydrogenase (LDH) isozyme in human cancers transplanted into nude mice and its application to the evaluation of experimental chemotherapy].

Human lactate dehydrogenase (LDH) was universally detected and quantified from sera of nude mice bearing human tumors. The patterns of LDH isozyme in sera reflected exactly those in each tumor extract, and remained unchanged over several generations. In 16 human cancers (7 gastric, 4 colorectal, 2 pancreatic and 3 breast) examined, human LDH levels in serum showed proportional increase as the transplanted tumors grew. Assessment of experimental chemotherapy by measuring the LDH levels of a treated group versus a control group was compared with that obtained by calculating the tumor weight during (14 tests) or after (61 tests) treatments. The percentage inhibition assessed by LDH level was strongly correlated to inhibition rate assessed by tumor weight. Moreover, LDH expressed more rapidly the inhibitory effect of an administered agent than tumor weight. If the drug was effective, serum LDH level in the treated group exhibited a temporary sharp rise within 2 days, thereafter decreasing to a lower level than that of the control. These results imply usefulness in further clinical application.

[Usefulness of LDH isozyme for monitoring the therapy of human breast cancer transplanted in nude mice].

Human breast cancer (Br-13) serially transplanted in nude mice in ascitic form was used in this experiment. Released isozyme of human lactate dehydrogenase (LDH) was detected in the blood of the Br-13 tumor-bearing nude mice, and the serum levels of the isozyme rose associated with the increase of neoplastic cell number in ascitic fluid. After Br-13 bearing nude mice were treated with single drug or a combination of cyclophosphamide, adriamycin and 5-fluorouracil, serum LDH levels were monitored and compared with the change of ascitic cells. When effective treatment was performed, serum LDH-5 levels increased transitorily 1 or 2 days after drug administration, then decreased and became undetectable. These changes indicate a good correlation with the extent of the cell damage and the increase of life span of the mice. In conclusion, monitoring of human LDH isozyme in serum of nude mice was a useful marker for evaluating the efficacy of experimental chemotherapy in nude mice.

Relationship of chemotherapy on human cancer xenografts in nude mice to clinical response in donor patient.

Responsiveness of experimental chemotherapy on human cancer xenografts in nude mice was directly compared with clinical response to the same chemotherapy in their donor patients. These xenografts were 1 line of rectal cancer (H-26), two lines of gastric cancer (H-08 and H-22), and 1 line of breast cancer (H-62). Experimental chemotherapies studied were single-drug FT-207 to four lines of xenografts and a combination of mitomycin C, 5-FU, and cytosine arabinoside (MFC) to a line of gastric cancer H-08. Single-drug treatment with FT-207 to H-26 resulted in remarkable retardation of the tumor growth. The comparative treatment with FT-207 suppository to the donor patient of H-26 showed appreciable response. All the other chemotherapies to three other lines (H-08, H-22, and H-62) induced no significant response, which was parallel to the corresponding clinical response in each donor patient. The sensitivity to chemotherapeutic drugs was thought to be still preserved in human cancer xenografts in nude mice.