Complete response, as determined by prostate-specific antigen level, to chlormadinone acetate withdrawal persisting longer than 2 years in patients with advanced prostate cancer: Two case reports

Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in prostate cancer. However, responses to AWS are usually of limited duration, and a complete response (CR) is extremely rare. We present two patients who exhibited a chemical CR for more than 2 years after the discontinuation of steroidal antiandrogen chlormadinone acetate use. Whether patients who respond to antiandrogen withdrawal include a group of patients with a better prognosis remains uncertain. However, considering that the usual survival period of patients with hormone-resistant prostate cancer is approximately 12 months, both of the patients reported here, who are present in excellent physical condition, exhibiting an improved quality of life, and attending their hospital as outpatients, obviously acquired a prolonged survival because of AWS.     

Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and is often limited by side effects. Cyclosporine A (CsA) is a potent immunosuppressant widely used in organ transplantation. We conducted a pilot study to determine whether CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male: female = 9:1) who did not respond to IFN therapy previously and who had elevated serum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their mean duration of hepatitis was 15 years. Oral CsA was given for 3 months in a dose that was increased at 1 month intervals from 1.5–2.0 to 2.0–3.0 and 3.0–4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild non-symptomatic hypertension. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 ± 82 to 62 ± 48 IU/L; P < 0.02). The ALT levels fell to the normal range in five patients, although once therapy was discontinued the enzyme levels tended to return to pretreatment levels. Serum aspartate aminotransferase and g-glutamyl transpeptidase levels similarly decreased. The serum HCV-RNA titre, determined by competitive RT-PCR, did not change in any patient throughout the study period. There were no appreciable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkaline phosphatase levels. These findings suggest that CsA, even in a relatively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic-hepatitis C, although an antiviral effect was not noted.     

High-performance Liquid Chromatographic Determination of Trazodone and 1-m-Chlorophenylpiperazine with Ultraviolet and Electrochemical Detector

A high-performance liquid chromatographic (HPLC) assay was developed for the determination of trazodone and its metabolite, 1-m-chlorophenylpiperazine (m-CPP), in plasma. The high level of trazodone in plasma was detected by ultraviolet absorbance at 254 nm and the low level of m-CPP in plasma was detected by coulometric electrochemical detection at 840 mV on the series arrangement of two detectors. Pilsicainide as an internal standard for both compounds was monitored by both detectors. Trazodone and m-CPP in plasma were extracted by a rapid and simple procedure based on CN bonded-phase extraction, and C₈ reversed-phase HPLC separation. Determination was possible for trazodone in the concentration range 100–2000 ng mL^?1 and for m-CPP in the concentration range 5–100 ng mL^?1. The recoveries of trazodone and m-CPP added to plasma were 81·0–84·2 and 68·0–73·2%, respectively, with coefficients of variation of less than 7·3 and 8·2%, respectively. The method is applicable to high level monitoring of trazodone and low level monitoring of m-CPP in plasma of healthy volunteers and patients treated with trazodone.     

Effects of Gadolinium Chloride on the Rat Lung Following Intratracheal Instillation

The metabolic behavior, clearance, and pulmonary effects ofgadolinium (Gd), one of the rare earth elements, were investigatedafter single intratracheal instillation of gadolinium chloride(GdCl₃) in male Wistar rats. There was a dose-related increasein Gd content of lung tissue. Gd content in the supernatantof bronchoalveolar lavage fluid (BALF) did not exceed 5 µgGd/ BALF even at a dose of 100 µg Gd/rat. Gd in the lungtissue decreased very slowly with a biological half-life of136 days at a dose of 50 µg Gd/rat. On the other hand,Gd content in the super natant of BALF was not detectable after31 days. These results suggest that intratracheally instilledGd can be retained in epithelial lining fluid only to a limitedextent as soluble forms and is deposited in the lung tissueprobably in insoluble forms which are metabolized very slowly.Calcium (Ca) content in BALF increased more rapidly than othertoxicological indices such as lactate dehydrogenase activity,protein concentration, and inflammatory cell counts. In thelung tissue, levels of Ca in Gd-instilled groups did not differfrom the control value. Although these data suggest that theorigin of Ca may be blood plasma, biological and/or toxicologicalsignificance of increased Ca is not known. The number of neutrophilsreached the maximum at 12 hr after instillation, indicatingthat Gd has the potency to cause acute lung toxicity. Summarizingthe observation, Gd instilled intratracheally into rats wasdeposited in the lung tissue in nonsoluble forms with an extremelylong half-life, while the metal caused a rapid and selectiveinfiltration of serum Ca before acute lung toxicity.     

土茯苓二氢黄酮醇类成分研究

目的 :研究土茯苓的化学成分。方法 :用硅胶、大孔树脂、ODS柱色谱及HPLC方法进行分离纯化 ,根据理化性质和光谱数据进行结构鉴定。结果 :分离鉴定了 5个二氢黄酮醇苷类化合物 ,分别为落新妇苷 (1) ,新落新妇苷 (2 ) ,异落新妇苷 (3) ,新异落新妇苷 (4 ) ,(2R ,3R) 花旗松素-3′-O-β-D-吡喃葡萄糖苷 (5 )。 结论 :化合物 2 ,4 ,5为首次从该植物中分离得到。     

Twenty-four hour monitoring of blood pressure and heart rate in patients with chronic renal failure or renal transplant recipients: Analysis by the cosinor method

Hypertension is a major problem of patients with chronic renal failure or renal transplant recipients. To clarify the characteristics of blood pressure, heart rate, and circadian rhythms of these patients we used an ambulatory blood pressure monitor (ABPM) for 24 h monitoring and analyzed the data by the cosinor method. In eight chronic renal failure patients without dialysis the midline estimating statistic of rhythm (MESOR) of diastolic blood pressure was higher than in controls, but the MESOR of systolic blood pressure was not. Of 11 patients on dialysis some had hypertension and some had hypotension. In 14 renal transplant recipients, especially those with chronic graft rejection, the MESOR of systolic and diastolic pressures were higher than controls, and the increase of blood pressure MESOR had a significant correlation with the elevation of serum creatinine levels. Circadian rhythms of blood pressure were frequently absent in the patients on dialysis, but circadian rhythms of heart rate were not. The use of an ABPM is a non-invasive method to monitor patients and allowed us to know changes of blood pressure and heart rate in the daytime as well as during the night. For the control of hypertension in chronic renal failure, monitoring with an ABPM seems to provide invaluable information.     

Clinical Trial with Authentic Recombinant Somatropin in Japan

Recombinant somatropin, produced by recombinant DNA technology, was administered by injection in daily doses of 8 IU to six healthy young volunteers. Daily injection for 4 days did not cause any significant change in the results of physical examination, blood count or urinalysis. Non-esterified fatty acid levels increased significantly from 0.45 ± 0.16 to 1.08 ± 0.12 mEq/litre (mean SEM) at 4 hours after the first injection (p<0.001). Plasma IGF-1 levels increased from 0.80 ± 0.14 units/ml to 1.72 ± 0.50, 3.22 ± 1.02, 3.17 ± 1.20 and 3.63 ± 0.78 units/ml at 24 hours after each daily injection for 4 days (p<0.001). Plasma hGH reached peak levels at 3 hours after intramuscular injection of recombinant somatropin, 4 IU, and this peak value was 57.3 ± 2.8 ng/ml. A total of 21 patients with pituitary dwarfism were also treated with recombinant somatropin for 6 months at a dose of 0.5 IU/kg/week. Their heights increased by 2.2–5.0 cm during the 6 months of treatment, which was calculated to be equivalent to 4.4–10.0 cm/year with a mean growth rate of 7.4 ± 0.4 cm/year. Anti-hGH antibody with a titre of 10 was observed in two patients at the end of 6 months of treatment.     

Normal levels of IgG subclass in childhood determined by a sensitive ELISA

Normal values of all IgG subclasses were determined using a sensitive ELISA in children aged from newborn to 14 years. The upper and lower limits of normal values of all IgG subclasses were obtained in all the age groups using 29 umbilical cord blood samples from full-term newborns and 308 venous blood samples from normal infants and children. The trends in the levels of IgG1, IgG2 and IgG3 with age were almost similar to previous reports. IgG4 levels decreased gradually until reaching the lowest level at 7 to 12 months and increased gradually with age, reaching a plateau at 12 to 14 years of age. Thus, the lower limit of serum IgG4 levels was determined using our method.     

Effects of human neonatal serum on DNA synthesis in suckling and adult rat hepatocytes in primary culture

The effect of human neonatal serum on DNA synthesis in suckling and adult rat hepatocytes in primary culture was investigated to characterize growth regulating factors of the liver in neonates and to confirm whether the stimulatory factor is human hepatocyte growth factor (hHGF). Neonatal serum stimulated DNA synthesis of both adult and suckling rat hepatocytes. The stimulatory effect was dose-dependent up to 20% in volume. The molecular weight of the stimulatory substance in neonatal serum was between 12 500 and 25 000, as estimated by gel filtration. Its activity was stable after heating at 56°C for 20 min, but was lost after heating at 90°C for 30 s, and easily passed through S- or heparin-Sepharose columns. The concentration of hHGF quantified by ELISA was too low to stimulate DNA synthesis in vitro. Biological and biochemical properties of the growth stimulatory activity in neonatal serum differed from that of hHGF. The presence of other growth factors in human neonatal serum for suckling and adult hepatocytes was suggested.