Disposition and pharmacokinetics of [14C]finasteride after oral administration in humans.

The disposition of [14C]finasteride, a competitive inhibitor of steroid 5 alpha-reductase, was investigated after oral administration of 38.1 mg (18.4 microCi) of drug in six healthy volunteers. Plasma, urine, and feces were collected for 7 days and assayed for total radioactivity. Concentrations of finasteride and its neutral metabolite, omega-hydroxyfinasteride (monohydroxylated on the t-butyl side chain), in plasma and urine were determined by HPLC assay. Mean excretion of radioactivity equivalents in urine and feces equaled 39.1 +/- 4.7% and 56.8 +/- 5.0% of the dose, respectively. The mean peak plasma concentrations reached for total radioactivity (ng equivalents), finasteride, and omega-hydroxyfinasteride were 596.5 +/- 88.3, 313.8 +/- 99.4, and 73.7 +/- 11.8 ng/ml, respectively, at approximately 2 hr; the mean terminal half-life for drug and metabolite was 5.9 +/- 1.3 and 8.4 +/- 1.7 hr, respectively. Of the 24-hr plasma radioactivity, 40.9% was finasteride, 11.8% was the neutral metabolite, and 26.7% was characterized as an acidic fraction of radioactivity. Binding of [14C]finasteride to plasma protein was extensive (91.3 to 89.8%), with a trend suggesting concentration dependency (range 0.02 to 2 micrograms/ml). Little of the dose was excreted in urine as parent (0.04%) or omega-hydroxyfinasteride (0.4%). Urinary excretion of radioactivity was largely in the form of acidic metabolite(s)--18.4 +/- 1.7% of the dose was eliminated as the omega-monocarboxylic acid metabolite. Finasteride was scarcely excreted unchanged in feces. In humans, finasteride is extensively metabolized through oxidative pathways.(ABSTRACT TRUNCATED AT 250 WORDS)     

Wilson shaft osteotomy for hallux valgus

The results of a modified Wilson shaft osteotomy for hallux valgus in 77 feet of 51 patients were excellent or good in 62 feet after 2 to 4 years. The correction of the hallux valgus angle and intermetatarsal angle was excellent or good in 69 feet. The operation is technically simple provided dorsal angulation of the distal fragment is avoided in the early postoperative period.A     

Ecological effects of hepatotoxic cyanobacteria

Many species of cyanobacteria produce hepatotoxic peptides called microcystins. Toxic cyanobacteria have caused fish, wildlife, and cattle mortality in many countries, but the distribution and fate of toxins and their ecological effects are poorly known. Toxic cyanobacteria may affect sensitive organisms and populations, but also fundamental ecological processes, e.g., primary production and microbial activity. Many studies show negative effects of cyanobacteria on zooplankton, but information on the type and quantity of toxin(s) involved is usually missing. Mussels accumulate peptide toxins but accumulation in other organisms remains to be studied. Cyanobacterial blooms often affect the littoral zones, which are important reproduction and feeding areas for fish and birds.     

The human carotid atherosclerotic plaque stimulates angiogenesis on the chick chorioallantoic membrane.

The chick chorioallantoic membrane was used to determine whether the carotid atherosclerotic plaque stimulates angiogenesis. Carotid endarterectomy specimens (1 mm3) with fibromuscular plaque (n = 8) and complicated plaque (n = 11) were implanted on the membrane on day nine of incubation and the response evaluated on day 11. Following fixation in situ with 10% formalin the angiogenic response was evaluated by: (1) examining whole membrane mounts, (2) quantitatively from a vascular density index and (3) from a histological study. Unmanipulated chorioallantoic membrane (n = 11) and plaque boiled prior to implantation (n = 6) served as controls. The vascularity of whole mounts of both fibromuscular and complicated plaque was greater than the controls. Vessel density of the membrane was estimated by counting the number of vessels intersecting four concentric circles (144.5 mm total circumference) placed on the formalin fixed membrane. The vascular density index due to the fibromuscular plaque (390.6 +/- 8.3) and complicated plaque (391.0 +/- 14.9) were similar (P greater than 0.9) but were significantly greater (P less than 0.001) than the unmanipulated membrane (327.9 +/- 5.6) or after treatment with the boiled plaque (283.8 +/- 15.6). Transforming growth factor beta 1 confirmed the validity of the experimental model to study angiogenesis. The histology of the chorioallantoic membrane due to either type of plaque was similar. Numerous vessels surrounded the plaque, and intraplaque vessels containing nucleated chick erythrocytes were observed. Although scattered vessels surrounded the boiled plaque, intraplaque vessels were not observed. This study demonstrates that the atherosclerotic plaque has angiogenic properties that may account for the increase in vasa vasorum that is associated with the plaque.     

Human spumaretrovirus antibody reactivity in multiple sclerosis

The role of human spumaretrovirus (HSRV) infections in the pathogenesis of multiple sclerosis (MS) was investigated with recombinant HSRV env-specific enzyme-linked immunosorbent assay. The presence of HSRV antibodies was determined in pairs of serum and cerebrospinal fluid (CSF) samples from 60 MS patients. In 7 of these patients serial serum and CSF samples were obtained in relation to the clinical activity of the disease during a period of 2 years. No increased antibody reactivity was demonstrable in the MS population compared with 14 aseptic meningitis patients, 50 blood donors and 16 healthy controls. Slightly elevated levels of antibodies were demonstrable in serum and/or CSF in 4 MS patients but also in 1 patient with aseptic meningitis, 1 blood donor and 1 child. No marked serum or CSF HSRV antibody fluctuation was observed in the MS patients followed longitudinally. Thus, this study does not support the involvement of HSRV in the pathogenesis of MS.     

Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion.

Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators considered important for thrombus formation, and were previously shown to synergistically increase platelet aggregation. Here we investigate synergistic activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich plasma from healthy blood donors together with adrenaline and/or LPA were added to protein-coated microplates. Platelets were allowed to adhere and the amount of adhesion detected enzymatically. The LPA and adrenaline combination induced a synergistic increase of platelet adhesion to a normally non-adhesive albumin surface. The degree of synergy varied markedly between individuals; these variations could not be explained by age, gender, blood type or different amounts of platelets, oxidized low-density lipoprotein, insulin or glucose in plasma. There was a trend indicating increased synergistic effect for platelets sensitive to adrenaline stimulation. The synergistic effect was blocked by the alpha2-adrenoceptor antagonist yohimbine and inhibited by the ADP scavenger system creatine phosphate/creatine phosphokinase and antibodies against alphaIIbbeta3. Furthermore, platelets adhering to albumin after adrenaline and LPA treatment expressed P-selectin. In conclusion, LPA and adrenaline act synergistically to increase alphaIIbbeta3-mediated platelet adhesion to albumin, dependent on alpha2-adrenoceptor signalling and platelet secretion. We also confirm that synergistic platelet activation achieved with LPA and adrenaline is highly donor dependent.     

原发性胃肠道粘膜相关淋巴组织淋巴瘤47例临床病理分析

目的 探讨原发性胃肠道粘膜相关淋巴组织淋巴瘤(GIL-MALT)的临床病理特点。方法 回顾性分析1990～2000年我院经手术及病理证实的47例胃肠道MALT患者临床病理资料。结果 47例患者平均年龄57．2岁，男女比例2．1：1。以腹痛和发热为主。病变分布为胃32例，小肠4例，回盲部及盲肠5例，大肠6例。内窥镜下息内型15例，溃疡型25例，弥漫型7例。除1例为T细胞淋巴瘤，其余均为B细胞淋巴瘤。结论 胃肠道粘膜相关淋巴瘤以中老年为主，男性居多，临床误诊率较高。内窥镜下多次多点活检、深凿活检可提高本病的确诊率。     

Diagnosis of scaphoid fractures:A prospective multicenter study of 1,052 patients with 160 fractures

In a prospective multicenter study of 1,052 patients with clinical signs of a scaphoid fracture, mammo-graphic films and fine intensifying screens were used at the radiographic examination. 5 standardized projections including 3 special projections focused on the scaphoid were taken. 150 fractures were diagnosed at the first examination but in 10 cases the fracture was first diagnosed at a second radiographic examination after 10-14 days.

The second examination still seems mandatory despite the use of high quality radiographs with optimal spatial resolution and contrast, and the value of supplementary special projections.     

端粒酶和妇科肿瘤的研究进展

端粒酶是一种RNA依赖的逆转录酶 ,能够延长染色体末端的端粒长度。它由三个主要部分组成———端粒酶RNA亚单位、端粒酶催化亚单位及连接二者的端粒酶相关蛋白。端粒酶激活是细胞永生化和肿瘤形成的关键步骤 ,其活性受到多种因素的调控。端粒酶催化亚单位hTERTmRNA可能是其激活的关键限速步骤。在妇科肿瘤的癌变过程中 ,端粒酶活性不同程度地升高 ,hTERT不断上调。端粒酶及其催化亚单位有可能成为妇科肿瘤筛查的一种重要的肿瘤标志物     

Pancreatic juice peptides as possible regulators of reparative processes in the pancreas in acute and chronic pancreatitis]

The experiments were performed on 34 dogs. The subcutaneous injection of boiled pancreatic juice was established to increase the survival of dogs in acute destructive pancreatitis (p < 0.001) and to decrease the specific volume damage to acinar (p < 0.01) and interstitial (p < 0.05) pancreatic tissue. It was also shown that boiled pancreatic autojuice exerted the therapeutic effect in chronic pancreatitis complicated by pancreatic fistulas. Five peptide components with a molecular mass from 4168 D to 1000 were discovered in the canine boiled pancreatic juice by liquid high pressure chromatography. Fractions with a molecular mass between 2187 and 1348 D were found to correspond to biologically active peptides, in particular to somatostatin. It is assumed that the therapeutic effect of boiled pancreatic juice used in acute pancreatitis may be due to somatostatin. Apparently pancreatic juice may turn an efficient therapeutic agent in acute pancreatitis and pancreatic fistulas.