Gold complex research in medical science. Difficulties with experimental design

Despite the use of gold complexes in modern medicine for over 100 years and the use of gold complexes in the management of rheumatoid disease for more than 60 years, the definitive mechanisms of action for efficacy and for toxicity have not been established. Gold is a group 1b metal in the periodic table with several oxidation states but it is only Au(I) which is active in the biological milieu. Gold sodium thiomalate is not only a polymeric structure, but also has the chiral ligand, thiomalic acid. Gold sodium thiomalate thus can exist in several different physical states which may have different biological activity. In addition the pharmacokinetic profile of gold complexes has been of little value in the understanding of either the mechanism of action, efficacy or toxicity for both the injectable and the oral gold complexes. Many authors have misinterpreted research data on the activities of gold complexes because they compared gold complexes of different structures, and gold complexes which exist at different pH. Experimental work in our laboratory has identified that gold sodium thiomalate is a mixture and can exist as either a yellow or a colourless solution. These have some similar but several different biological activities. Many factors contribute to the lack of understanding of the action of gold complexes. Some of these factors are related to the wide variation in physical structure and biological activities exhibited by these compounds.     

TEN YEARS' EXPERIENCE IN LOW VISION PRACTICE

The Low Vision Clinic at the Palmerston North Hospital has now been oerating for 70 years. Over the course of these ten years a number of factors have emerged which can be as readily applied to general ophthalmological practice as to low vision practice. The philosophy of low vision care is one of which all ophthalmologists should be aware and includes factors to be taken into account when dealing with children, people in the workplace, and everyday factors involved in daily living activities, all of which are equally relevant in routine ophthalmological practice. This paper endeavours to share some thoughts on these factors and also discusses means by which the visually handicapped can be helped in areas where specialist low vision services are not readily available.     

The Application of Number Needed to Treat (NNT) to Clinical Problems in Radiotherapy

The goals of this report are: 1) to review the number needed to treat (NNT) concept, which, although well established in many sectors of medicine, is still relatively new to the radiotherapy community; 2) to discuss several clinical radiotherapy examples illustrating the inherent advantages of the NNT approach; and 3) to discuss potential future roles of the NNT concept within radiotherapy.     

霉酚酸酯对肾病综合征大鼠肾组织白细胞介素8的影响

目的 探讨白细胞介素8(IL-8)在肾病综合征大鼠蛋白尿形成中的作用及霉酚酸酯(MMF)对其的影响。方法 应用阿霉素肾病模型，用MMF对肾病形成过程进行干预。采用放射免疫法测定血清及肾组织IL-8含量。结果MMF可减轻肾病蛋白尿，降低肾组织IL-8含量。结论 MMF降低肾组织IL-8含量，可能是其对肾病综合征大鼠保护作用的机制之一。     

性别差异对脓毒症大鼠肝脏Toll样受体4和髓样分化蛋白-2基因表达的影响

目的探讨性别差异对脓毒症大鼠肝脏组织Toll样受体4(TLR4)和髓样分化蛋白- 2(MD-2)基因表达的影响。方法以脂多糖(LPS)按5 mg/kg体重由大鼠腹腔注射制作脓毒症动物模型,注射后2 h留取肝脏组织检测TLR4、MD-2和肿瘤坏死因子-α(TNF-α)基因表达,同时测定各组大鼠血浆中丙氨酸氨基转移酶(ALT)及雌二醇含量。结果正常雌雄性大鼠肝脏组织均可表达少量TLR4、MD-2、TNF-α基因,其中雌性组分别为0．175±0．034、0．211±0．044、0．201±0．068; 雄性组分别为0．205±0．061、0．243±0．049、0．243±0．063,两组数据差异无统计学意义(P> 0．05),但LPS刺激后雌性大鼠肝脏组织上述指标分别为0．615±0．089、0．708±0．181、0．730± 0．118,血浆中ALT含量为(81．07±10．72)U／L;雄性组分别为0．723±0．091、1．123±0．272、 0．881±0．156,ALT含量为(106．39±14．21)U／L,雌性组各项指标均明显低于雄性大鼠(P< 0．05)。相关分析表明雌性及雄性脓毒症大鼠肝脏组织TLR4及TNF-α基因表达与相应性别大鼠血浆中雌二醇含量呈显著负相关(P<0．05)。结论 LPS刺激后大鼠肝脏组织TLR4、MD-2及 TNF-α基因表达存在性别差异,内源性雌激素的作用可能导致雌性脓毒症大鼠肝脏组织损伤较雄性轻。     

ANALYSIS OF BURIED BUMPER SYNDROME AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY DUE TO USE OF A BUTTON‐TYPE KIT

Background: Buried bumper syndrome (BBS) is a rare complication of percutaneous endoscopic gastrostomy (PEG). Along with the widespread use of the button‐type kit, BBS is encountered frequently. Methods: In the present study, we examined causes and treatments for BBS among 1400 patients who had undergone PEG. Results: The causes of BBS after PEG were classified into two categories: early causes consisted of wound infection, inappropriate size of kit and severe lordosis, while late causes were inappropriate exchange of kit, rough management or weight gain. The treatments for BBS could be determined by the degree of wound infection, fistula and burial of the bumper. Conclusion: We prepared a flowchart for replacement, by which BBS can be managed safely and quickly without surgical or endoscopic intervention.     

Comparative genomic hybridization (CGH) of augmentation cystoplasties

OBJECTIVE: Tumors arising within augmentation cystoplasties are aggressive, have poor prognosis and the majority are not detected at follow-up cystoscopy. Genetic changes in tumors precede morphological abnormalities. Therefore, the aim of this study was to investigate whether genetic abnormalities detected by comparative genomic hybridization (CGH) could be used to identify those patients with augmentation cystoplasties at increased risk of tumorigenesis. METHODS: Bladder biopsy samples were obtained from 16 augmentation cystoplasty patients both distant from and near to the enterovesical anastomosis. CGH was used to detect genetic abnormalities in DNA extracted from the biopsies, archival specimens of two augmentation cystoplasties and two de novo bladder adenocarcinomas. RESULTS: A greater number of amplifications on 2p, 3q, 8q, 9p, 17p, 18pq and 20pq, were observed in bladder biopsies obtained near to the enterovesical anastomosis compared to those taken distant to the suture line. CGH of archival augmentation cystoplasty tumor DNA indicated abnormalities at several loci with amplifications at 2q, 5q, 10p and 21pq, while deletions occurred at 5p and 16p. CONCLUSIONS: The results of this study suggest that the urothelium adjacent to the bladder and/or bowel anastomosis in augmentation cystoplasties is genetically unstable. Furthermore, longitudinal studies are required to establish whether or not patients exhibiting genetic instability following augmentation cystoplasty are at greater risk of developing tumors than those with genetically stable epithelia.     

Urological emergency in neonates with congenital hydronephrosis

OBJECTIVE: It is well described that unilateral pelviureteric junction obstruction (PUJO) is a benign condition, because the dilatation resolves spontaneously and the function does not decrease in most of the kidneys. However, there is exceptional PUJO that requires emergent treatment in neonatal periods. The aim of this article is to report the urological emergency and management in neonates with PUJO. MATERIALS AND METHODS: Nine children (seven boys and two girls) with PUJO who underwent neonatal emergent treatment during the last 13 years were reviewed. Renal function was evaluated according to decay curve of serum creatinine (SCr) levels corresponding to gestational age (GA) at delivery. Physical examination, ultrasonographic monitoring, and chest and abdominal plain radiographs were repeated in each neonate. RESULTS: Eight patients were detected prenatally. In five patients, multicystic dysplastic kidney (MCDK) was demonstrated on the contralateral side. Three patients underwent percutaneous puncture of fetal hydronephrosis. Decrease of amniotic fluid was evident in three fetuses. Indications for emergent treatment included mass effect from hydronephrosis in three patients, renal dysfunction in five, and severe urinary tract infection in one. During neonatal periods, a percutaneous nephrostomy tube was placed in seven, and open nephrostomy in one with anorectal malformation. Repeated punctures of the dilated renal pelvis were done in one patient. Renal function after pyeloplasty was stable in eight patients, while it was moderately decreased in one who was associated with oligohydramnios in utero. CONCLUSION: Indications for emergent treatment in neonates with PUJO included mass effect from giant hydronephrosis, renal dysfunction and severe urinary tract infection. At birth, respiratory and circulatory conditions must first be stabilized. In neonates with hydronephrosis of the solitary kidney or severe bilateral PUJO, serial SCr should be monitored to evaluate renal function. Decrease of amniotic fluid suggested renal functional compromise that would not recover after urological management.     

Obstinate cough as a sole presenting symptom of non-metastatic renal cell carcinoma

Renal cell carcinoma (RCC) causes many kinds of symptoms such as hypercalcemia, hypertension, polycythemia and fever. Here we describe a rare case of RCC presenting with a persistent cough. After radical nephrectomy, the obstinate cough disappeared. When the tumor recurred locally, the cough also recurred. Furthermore, the cough disappeared completely again after the removal of the recurrent tumor. Although all the clinical findings suggested that the RCC caused the cough, we could not identify a specific humoral substance responsible for the cough.