Polyamines, polyamine antimetabolites and urogenital tumors. State of research and clinical results

The polyamine metabolism is pathologically changed in tumor tissues, and especially putrescine and spermidine demonstrate abnormally high values in kidney, bladder, and prostate cancer. The inductive processes which activate the biosynthetic polyamine enzymes in cancer are completely unknown. Of therapeutic interest is the fact that increased enzyme activities through irreversible inhibitors become significantly reduced, which consequently slows the tumor growth. Experimental therapy, especially in transplantable bladder and prostate cancer, displayed a 50% tumor destruction. In clinical studies using inhibitors of the polyamine biosynthesis, the dose had to be significantly reduced because of expressed toxicity. Additional investigations which tried a combination of reversible and irreversible inhibitors proved a similar antitumor activity, but less severe side effects.     

鲎试验对腹膜透析并发腹膜炎诊断价值的探讨

为寻求简便，快速诊断腹膜透析并发腹膜炎的有效方法，对６例持续性非卧床腹膜透析患者隔夜腹透液进行了６６次鲎试验观察。结果２１次为腹膜炎，其中鲎试验阳性７次，占３３．３％，用抗革兰阴性菌抗生素疗效佳。认为鲎试验是ＣＡＰＤ并发革兰阴性菌性腹膜炎的简便，快速的诊断方法，为及时使用有效抗生素提供了有力证据。     

Protein binding of drugs--the clinical significance.

Drug-protein binding is reviewed from a clinical and practical point of view. Commonly used drugs are discussed and the effects of disease, drug dosage and hypoalbuminaemia on drug-protein binding are reviewed. Doses of highly bound (greater than 80%) drugs in patients with hypoalbuminaemia, liver disease or renal failure should be regularly reviewed.     

The clinical significance of myocardial contusion.

In an attempt to identify a group of blunt trauma victims with asymptomatic myocardial contusion (MC) who do not benefit from intensive cardiac monitoring, we prospectively divided 336 patients admitted to the SICU with possible MC following blunt trauma in the 6 years prior to January 1990 into three groups: Group 1 (n = 155, age 30.5 +/- 9 years) consisted of those patients admitted for mechanism of injury, J-point elevation, with or without minor chest injury. None developed arrhythmias. Their SICU length of stay (LOS) was 2.41 +/- 0.77 days. Group 2 (n = 43, age 31.5 +/- 10 years) patients had the same admission criteria as the patients in group 1 plus an abnormal emergency department ECG, i.e., arrhythmia, heart block, ischemia. None had cardiac complications. Their SICU LOS was 2.47 +/- 0.94 days. Group 3 (n = 138, age 40 +/- 20 years) patients had four or more rib fxs, a pulmonary contusion, a flail chest, or extra-thoracic injuries or were greater than 60 years of age. All required SICU admission for their non-cardiac injuries. Nineteen patients had cardiac complications requiring treatment. None had a cardiac death. Their SICU LOS was 10 +/- 22 days. We conclude that young patients with minor blunt thoracic trauma and a normal or minimally abnormal ECG do not benefit from cardiac monitoring.     

Statistical significance versus clinical significance

Unfortunately, the data were statistically nonsignificant due to insufficient power and poor experimental design. Conversely, many large clinical trials obtain a high level of statistical significance with miniscule differences between groups, which are completely clinically irrelevant. However, with proper marketing, billions can be made from results of dubious clinical importance. In this article, the differences between statistical and clinical significance are briefly discussed.     

The visual analog scale for pain: clinical significance in postoperative patients.

BACKGROUND: The visual analog scale is widely used in research studies, but its connection with clinical experience outside the research setting and the best way to administer the VAS forms are not well established. This study defines changes in dosing of intravenous patient-controlled analgesia as a clinically relevant outcome and compares it with VAS measures of postoperative pain. METHODS: Visual analog scale measurements were obtained from 150 patients on the morning after intraabdominal surgery. On the same afternoon, 50 of the patients provided a VAS score on the same form used in the morning, 50 on a new form, and 50 were not asked for a second VAS measurement. RESULTS: Visual analog scale values and changes in value were similar for patients who were given a new VAS form in the afternoon and those who used the form that showed the morning value. The proportions of patients requesting additional analgesia were 4, 43, and 80%, corresponding to afternoon VAS scores of 30 or less, 31-70, and greater than 70, respectively. Change from morning VAS score had no apparent influence on patient-controlled analgesic dosing for patients with afternoon values of 30 or less or greater than 70, but changes in VAS scores of at least 10 did discriminate among patients whose afternoon values were between 31 and 70. CONCLUSIONS: When pain is an outcome measure in research studies, grouping final VAS scores into a small number of categories provides greater clinical relevance for comparisons than using the full spectrum of measured values or changes in value. Seeing an earlier VAS form has no apparent influence on later values.     

Searching for the stone of wisdom.

Sir, It is good that renewed attention of the dialysis world is beingdrawn to the control of extracellular volume as a vital partof adequate dialysis. The idea is gaining     

Searching for novel therapeutics and targets: insights from clinical trials

Recent advances behind the understanding of the molecular mechanisms of bladder tumorigenesis have contributed towards the identification of molecules that can act as potential therapeutic targets for novel agents. Concurrently, this has also led to the understanding that effective therapy for superficial and invasive bladder cancers will entail a combination of therapeutic agents that target multiple tumorigenic pathways. Management of bladder cancer patients, as is the case in many other solid tumors, may witness radical transformations in the coming years as we translate our molecular understanding of the disease into novel clinical trial designs and screening techniques.