Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Imaging of thoracic aortic dissection

Acute thoracic aortic dissection has a high mortality if untreated, so the diagnosis must be rapidly made if mortality is to be lowered significantly. Multiple imaging techniques are often used. This retrospective study from 1988 to 1993 assesses the usefulness in diagnosis of chest X-rays, computed tomography (CT) scanning, aortography, magnetic resonance imaging (MRI), trans-thoracic (TTE) and trans-oesophageal (TOE) echocardiography. Forty-two patients with a final clinical diagnosis of dissection were studied. The diagnosis was confirmed in 16 (13 at surgery and three at autopsy). Three died with dissection given as the only cause for death. Chest X-ray abnormalities were seen in all 19 patients with surgery or death from dissection, with a widened mediastinum and/or dilated aorta being present in 17. In the group of 16 patients with surgery or autopsy proof, CT scans found dissections in 9 of 12 patients studied and correctly classified the type in only five. Aortography was performed in five, with accurate depiction of dissection and type in all. TTE found dissections in three of eight patients imaged by this method. MRI and TOE were performed each on two patients, with accurate depiction of dissection and type in each. Because of the relatively low sensitivity of CT scanning in defining aortic dissections Westmead Hospital is currently assessing the use of TOE as the prime imaging modality prior to surgical intervention.     

Comparison of washed nasopharyngeal cells and whole nasal secretions for detection of respiratory syncytial virus antigens by enzyme-linked immunosorbent assay.

We compared washed nasal epithelial cells with unfractionated nasal secretions as sources of respiratory syncytial virus (RSV) antigens in an indirect enzyme-linked immunosorbent assay (ELISA). Of 28 infants positive for RSV by virus isolation or direct immunofluorescence or both, 27 (96%) were positive by ELISA with whole nasal secretions, whereas only 19 (68%) were positive by ELISA with the matching washed-cell fractions. Furthermore, the ELISA absorbances obtained with nasal secretions were significantly greater than those seen with washed-cell fractions, indicating that whole nasal secretions contain relatively greater amounts of RSV antigens as measured by ELISA.     

A double mutant [N543H+2393del9] allele in the LDL receptor gene in familial hypercholesterolemia: effect on plasma cholesterol levels and cardiovascular disease

Familial hypercholesterolemia is a genetic disorder caused by mutations in the LDL receptor gene. During a survey of mutations of LDL receptor gene in Spanish FH patients we found two mutations in the same allele: a missense N543H mutation in exon 11 and a 9bp inframe deletion (2393del9) located in exon 17. This double mutant allele was founded in 10 out of 458 unrelated patients: one homozygous FH [N543H+2393del9] + [N543H+2393del9], one compound heterozygote [N543H+2393del9] + [W-18X+E256K] and 8 heterozygotes. Flow cytometric analysis showed a defective LDL binding (20% of normal value) and internalization (23%) in lymphocytes from the homozygous patient; furthermore, studies of mitogen-stimulated lymphocytes demonstrated that the ability of LDL to support cell proliferation was impaired. Unexpectedly, not all carriers of the double mutant allele develop hypercholesterolemia and, furthermore, cholesterol-lowering treatment of the homozygous patient resulted in a 58% LDL cholesterol reduction. In conclusion, the phenotypic expression in the homozygous and heterozygous patients presented here, as well as the LDL-receptor residual activity, allowed the classification of this mutation as mild extending the group of mild mutations found at homozygosity.     

单克隆抗体—表阿霉素免疫偶合物的制备和体外活性

用双功能试剂己二酰肼制备腙键连接的聚谷氨酸—表阿霉素,通过控制交联条件,所得产物克服了大分子自身交联的缺点,交联率较高。聚谷氨酸的载药量与分子量呈正比,平均每8～11个谷氨酸单体连接1分子表阿霉素。分子量为14300的聚谷氨酸做载体其载药量为1:11,与单抗交联所得的偶合物McAb:PGA:PAR为1:2:22。偶合物较好地保留了抗体活性,体外细胞毒性较游离药物略有下降,但表现出单抗介导的靶细胞选择性杀伤作用。本研究用腙键交联法成功地制备了药/抗比高且体外有效的免疫偶合物,为进一步制备细胞靶向的肿瘤化疗制剂奠定了基础。     

固相萃取GC-FID和GC-MS分析血浆中碱性药物

报道了用X-5固相萃取分离、毛细管GC-FID和GC-MS定性定量分析人血浆中34种碱性药物的方法。在优化的提取条件下,大部分药物的最低检测浓度在0.5～2.0μg·ml^-1之间,线性范围、定量精密度等满足临床中毒分析的要求。     

Serum levels of sex hormone-binding globulin (SHBG) are not associated with lower levels of non-SHBG-bound testosterone in male newborns and healthy adult men

OBJECTIVE: It is generally accepted that SHBG decreases the bioavailability and activity of testosterone (T). In in vitro experiments increased levels of SHBG will be associated with decreased levels of non-SHBG bound testosterone (non-SHBG-T). However, in vivo SHBG can alter both production and clearance rates and thus plasma levels of T. DESIGN AND PATIENTS: In order to study the effect of SHBG on the levels of non-SHBG-T in vivo in the presence of an active hypothalamo-pituitary-gonadal (HPG) axis we conducted a cross sectional study in 400 healthy adult men with an age range of 40-80 years and in 106 newborn boys. MEASUREMENTS: In both groups, regression coefficients (beta) and partial correlation coefficients (r) were calculated for the relationship between SHBG and T or non-SHBG-T. Adult men were divided into age groups per decade (40-50 years, 51-60 years, 61-70 years and 71-80 years) to study possible differences in the impact of SHBG on the level of non-SHBG-T throughout ageing. RESULTS: Higher levels of SHBG were associated with higher levels of total testosterone in neonates (beta = 0.02 +/- 0.004, r = 0.44, P < 0.001) but not with non-SHBG-T (beta = -0.001 +/- 0.001, r = 0.05, P = 0.52). In adult men there was a significant age related increase in levels of SHBG and an age-related decrease of both total and non-SHBG-T. Higher SHBG was strongly associated with higher total testosterone in all age groups (beta = 0.26, 0.26, 0.26 and 0.23 for 40-50 years, 51-60 years, 61-70 years and 71-80 years, respectively, P < 0.001 for all age groups). Higher SHBG was not or only slightly associated with higher non-SHBG-T beta = 0.02 (P = 0.32), beta = 0.04 (P = 0.03), beta = 0.04 (P = 0.02) and beta = 0.02 (P = 0.16) for 40-50 years, 51-60 years, 61-70 years and 71-80 years, respectively. CONCLUSIONS: In contrast to general belief, SHBG levels barely influence levels of non-SHBG-bound testosterone both in male newborns and healthy adult men: the influence, if any, is positive. Consequently the age related increase of SHBG does not account for the age related decline in non-SHBG-T in healthy adult men.     

Renal function in tyrosinaemia type I after liver transplantation: A long-term follow-up

Summary Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent porphyria. When treated with liver transplantation, tyrosinaemia type I was considered to be cured. Some years after the first liver transplantations in these patients, some reports focused on the renal function after transplantation. These reports showed that urinary succinylacetone excretion remained but that tubular function normalized. In this report we discuss the long-term renal follow-up (mean follow-up time 11 years, range 7–14 years) after liver transplantation in 9 patients with tyrosinaemia type I treated by liver transplantation in our centre. An evaluation was made of renal function and succinylacetone excretion in urine. In all patients we found a persistent excretion of succinylacetone in the urine. With respect to the glomerular function, we can conclude that there is no clear change in GFR. At the same time, tubulopathy persisted in some patients. We consider that excretion of metabolites such as succinylacetone will be an important contributing factor to tubular dysfunction after liver transplantation in patients with tyrosinaemia type I. Therefore, notwithstanding the major effect of liver transplantation on tyrosine metabolism, renal tubular dysfunction remains at risk and needs careful monitoring. Progressive tubular dysfunction can cause glomerular damage. The use of low-dose NTBC might be considered after liver transplantation in case of tubulopathy to prevent progression of tubular and glomerular dysfunction. An erratum to this article is available at .     

Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice

The present studies report erythropoietin (Ep) production in primary cultures of a human renal carcinoma from a patient with erythrocytosis that has been serially transplanted to BALB/c nude mice. The levels of erythropoietin in the culture media were estimated using the exhypoxic polycythemic mouse assay (EHPCMA), fetal mouse liver erythroid colony- forming technique (FMLC), and a radioimmunoassay (RIA). The spent culture media of the exponentially growing cells contained less than 10 mU/ml of Ep measured by RIA. However, after the cells became confluent, Ep levels (RIA) in the spent media showed a marked increase to approximately 300 mU/ml. Ep levels estimated using the FMLC and EHPCMA were approximately 2/3 and 1/10, respectively, of those measured by RIA. Rabbit antiserum to highly purified human urinary Ep (70,400 U/mg protein) was utilized for immunocytochemical (peroxidase-antiperoxidase method) localization of Ep in the cultured cells. Very few of the cells in exponential growth exhibited Ep-like immunoreactivity, whereas intense Ep-like immunoreactivity was observed in the cytoplasm of the cells maintained in culture for a prolonged period after reaching confluency. The most intense staining was observed in some of the cells forming domes. The domes developed after the cells reached confluency, and their numbers increased with increasing time in confluent culture, in parallel with the increase in Ep levels in the spent media. This primary cell culture system of a renal cell carcinoma maintained in nude mice, which produces immunologically and biologically active Ep, may provide a useful model for studies of the mechanism of Ep production.     

Plant neighbor detection through touching leaf tips precedes phytochrome signals

Plants in dense vegetation compete for resources, including light, and optimize their growth based on neighbor detection cues. The best studied of such behaviors is the shade-avoidance syndrome that positions leaves in optimally lit zones of a vegetation. Although proximate vegetation is known to be sensed through a reduced ratio between red and far-red light, we show here through computational modeling and manipulative experiments that leaves of the rosette species Arabidopsis thaliana first need to move upward to generate sufficient light reflection potential for subsequent occurrence and perception of a reduced red to far-red ratio. This early hyponastic leaf growth response is not induced by known neighbor detection cues under both climate chamber and natural sunlight conditions, and we identify a unique way for plants to detect future competitors through touching of leaf tips. This signal occurs before light signals and appears to be the earliest means of above-ground plant-plant signaling in horizontally growing rosette plants.