An Attempt to Assess the Replacement Dose of Human Growth Hormone in the Treatment of Growth Hormone Deficient Children

Hibi, I., Tanaka, T., Yano, H., Umezawa, S., Kagawa, J., Tanae, A. and Ishikawa, E. (National Children's Medical Research Center, Tokyo, the National Children's Hospital, Tokyo and the Department of Biochemistry, Miyazaki Medical College, Miyazaki, Japan). Acta Paediatr Scand [Suppl] 337:87, 1987.
In 25 patients with hGH deficiency, who had been treated long-term with hGH, the mode of hGH administration was switched from the conventional method (0.3–0.5 IU/kg/week, in two or three divided doses, intramuscularly) to daily subcutaneous injection at 1900–2100 hours with a dose of 0.46 ± 0.07 IU/kg/week (equivalent to 14.7 ± 2.0 IU/m²/week). After 1–3 months of this new mode of hGH administration, blood and urine were sampled at 0900 hours after overnight fasting. Blood glucose, plasma insulin, plasma IGF-1 and plasma total IGF (after extraction) were analysed in blood samples. IGF-1 and hGH were measured in urine samples. These measurements indicated that the dose studied was close to a replacement one, but might be slightly higher than the exact replacement dose.     

Prospective follow-up study of hepatitis C virus infection in patients undergoing maintenance haemodialysis: Comparison among haemodialysis units

A prospective follow-up study on hepatitis C virus (HCV) infection was conducted in seven haemodialysis units from April 1990 to March 1995. A total of 634 patients were undergoing maintenance haemodialysis in the seven units. Of those, 302 patients participated in the follow-up study; 179 were initially HCV antibody negative and 123 were initially positive. Nine of the 179 initially negative patients became positive for HCV antibody during the follow-up period. In accordance with the appearance of HCV antibody, indicating new infection of HCV, all nine of these patients were diagnosed with HCV viraemia. As no other routes were apparent, HCV infection in all nine patients was likely due to nosocomial transmission. Prevalence of HCV antibody at the start of follow up was significantly higher ( P < 0.001) in haemodialysis units A-C (37.9%) than in haemodialysis units D-G (17.0%). Incidence of new HCV infection was significantly higher ( P = 0.005) in the former units (2.2% per year) than in the latter (0.2% per year). Ten of the 123 patients who were initially positive for the HCV antibody exhibited a loss of reactivity during the follow-up period; of these 10 patients, nine were negative for HCV-RNA from the start of the study. In conclusion, the incidence of new HCV infection seen in patients undergoing haemodialysis suggests that their risk of acquiring HCV infection is directly related to the prevalence of HCV antibody positive patients being treated in the units.     

Reentrant Ventricular Outflow Tract Tachycardia Arising from Focal Scar Detected by Delayed Enhancement Magnetic Resonance Imaging

A 58‐year‐old man was referred to our emergency room with hemodynamically unstable sustained ventricular tachycardia (VT). The morphology of the VT exhibited a left bundle branch block and inferior axis deviation. He had no past history of cardiovascular disease. Echocardiography, cardiac catheterization, cardiac biopsy, gallium scintigram, myocardial scintigram, T1,T2‐weighted magnetic resonance imaging (MRI), and gadolinium‐enhanced cine MRI did not detect any structural heart disease or abnormal cardiac function. However, delayed‐enhancement MRI (DE‐MRI) detected a focal intramural scar within the septal ventricular outflow tract. An electrophysiological study revealed a sustained VT with several morphologies and the entrainment phenomenon. Radiofrequency catheter ablation to the site corresponding to the focal scar detected by DE‐MRI successfully eliminated the VT. (PACE 2012;35:e349–e352)     

Antitumor Activity and Pharmacokinetics of Estra-1,3,5 (10)-Triene-3,17{beta}-Diol, 3-Benzoate, 17-((4-(4-(Bis (2-Chioroethyl)Amino)Phenyl)-1-Oxobutoxy) Acetate) (Bestrabucil) in Human Tumor Xenografts Serially Transplanted into Nude Mice

Bestrabucil (KM2210), the benzoate of an estradiol-chlorambucilconjugate, was used experimental cancer chemotherapy against13 human tumor xenografts serially transplanted into nude mice,and its pharmacokinetics was studied. The tumors were one esophageal,two gastric, six colon, one cholecystic and three breast carcinomas.Two tumor tissue fragments approximately 3x3x3 mm were inoculatedinto BALB/cA nude mice, which were then treated with KM2210at doses of 100, 200 and 300 mg/Kg/day orally starting 24 hrafter the transplantation or when the tumor reached a weightof 100–300 mg. The concentration of KM2210 and its derivativesin the tumor xenografts, normal muscular tissue and blood wereassayed by high performance liquid chroma-tography. Six out of 13 xenografts were found to be sensitive to KM2210.The concentrations of KM2210 and its derivatives in the tumortissues of the sensitive xenografts were five to 10 times higherthan those in blood and muscular tissue, and the antitumor activitycorrelated well with the area under the curve of active metabolitesof KM2210 in the tumor.     

Anticardiolipin Antibodies in Patients With Pregnancy Loss Induce Factor Xa Production in the Presence of (β2-Glycoprotein I

PROBLEM : Anticardiolipin antibodies (aCL) are commonly associated with recurrent pregnancy loss, though the mechanism is uncertain. Some investigators have indicated that aCL may be directed at a complex made up of cardiolipin and a blood anticoagulant, β2-glycoprotein I (β2GPI). We therefore investigated the effects of β2GPI-dependent aCL IgG enriched fractions, isolated from sera of patients with pregnancy losses, on blood coagulation. METHOD : β2GPI-dependent aCL were prepared from sera of three women with second trimester pregnancy losses, by cardiolipin affinity column chromography, following by anti-β2GPI affinity column chromatography. The effects of β2GPI and β2GPI-dependent aCL on the activation of factor X in vitro were examined. RESULTS : β2GPI inhibited the activation of factor X and β2GPI-dependent aCL blocked this inhibitory effect in a dose dependent manner. CONCLUSION : These results imply the possibility of β2GPI-dependent aCL induce hypercoagulation or thrombus by blocking the inhibitory effect of β2GPI on activation of factor X, which may result in pregnancy loss.     

Characterization of Fatty Acids in a Tissue of Neuroblastoma by Gas Liquid Chromatography-Chemical Ionization Mass Spectrometry-Computer System

To verify the possibility of chemical ionization mass spectrometryfor the characterization of various kinds of fatty acids, thoseisolated from a tissue of neuroblastoma were analyzed by gasliquid chromatography-chemical ionization mass spectrometry-computersystem. Twenty seven fatty acids, including some positionalisomers, were identified in the tissue and this system was proveduseful both for the separation and for the structural determinationof fatty acids of minute concentrations.     

Distribution of an Unphysiological Isomer of Eicosatrienoic Acid and Other Fatty Acids in a Tissue of Hepatocellular Carcinoma

The mode of distribution of the unphysiological isomer of eicosatrienoicacid, 5,8,11-eicosatrienoic acid, was analyzed together withthe other fatty acids in a tissue of hepatocellular carcinomaobtained at surgery from a 59-year-old female. The concentrationof this fatty acid was higher in the central portion of thesmall nodule of hepatocellular carcinoma and was detected onlyin traces in the surrounding liver tissue. It is conceivable that this fatty acid is the product of neoplastictissue and is not secondary to a systemic essential fatty aciddeficiency of the patient.     

Metastatic Bone Tumors: Diagnosis and Treatment

Seventy-four cases of metastatic bone tumors were reviewed inorder to study the actual problems concerning their diagnosisand treatment. Sixty-five of the 74 tumors were carcinoma metastasesand the remaining nine were other malignancies. Diagnosis: In our study, as has often been reported elsewhere,there was a high incidence of metastasis of lung and breastcancer (27% and 9%, respectively). In all patients in this series,the existence of bone metastasis itself was shown by plain radiogramsat the time of their admission. In 51 patients, primary siteswere identified by clinical records and/or various clinicalexaminations. Autopsy revealed additional seven primary sites. Treatment: Limb surgery which directly intends a resection ofthe metastatic lesion generally provided good palliation and,on occasion, relatively long survival. Of the seven patientswhose bone lesions were enthusiastically resected, three survivedfor 15, 27 and 36 months postoperatively and one has survivedup to the present (18 months). On the other hand, laminectomy and other procedures of vertebralsurgery which do not directly intend a resection did not givegood results in either quad vitam vol functionem. Twenty of21 patients died within a relatively short time (1 to 13 months,average 3.6 months) without any functional recovery.