Clinical Studies with Mazindol

An anoerxiant, mazindol suppresses food intake by 1)stimulating β-adrenergic receptors, 2)inhibiting the feeding center and, 3)stimulating the satiety center in the hypothalamus. In Japan, mazindol is available for clinical use. We examined the effects of mazindol on 1) body weight, appetite, and abnormalities of obesity-related diseases in long-term use 2)maintenance of the reduced body weight after very-low-calorie diet (VLCD) therapy 3)combined use with VLCD therapy and, 4)inhibition of body weight gain in Prader-Willi syndrome. In long-term effects of mazindol, the average reduction of individual body weight was around 6.8 kg. The appetite of 59% of obese subjects was moderately suppressed. Systolic blood pressure, serum GOT, serum triglyceride, serum cholesterol, and glucose tolerance were also improved. With mazindol, 53.3% of obese subjects kept the reduced body weight after VLCD, in contrast, 20.0% of them kept it without mazindol. Combined use of mazindol with VLCD made the VLCD therapy more effective in out patients. Two of 3 patients with Prader-Willi syndrome inhibited their body weight gain with mazindol. Thus, mazindol produced positive effects in these studies, although the effects were limited.     

Clinical Studies with Liposomal Doxorubicin

Abstract

To present data on a continuing phase I study of liposomal doxorubicin at this time may seem like a giant leap backwards. Liposomally encapsulated doxorubicin has been available for clinical use for some years. Phase I studies have been completed, and phase II studies have been conducted in patients with breast cancer (1,2). Two major obstacles to the commercial exploitation of drugs encapsulated in liposomes were evident. the first was to find a preparation that could be given safely to humans. the second was to develop a pharmaceutical preparation that could be commercially exploited by fulfilling the requirements for manufacture and sale as a drug. the first of these problems was solved a number of years ago, but only recently have we had preparations that fulfilled the second requirement. Two of these have entered clinical trials at Roswell Park Memorial Institute (RPMI). One of these, the liposomally encapsulated muramyl tripeptide derivative (MTP-PE), has been presented previously (3,4). Accordingly, in this paper we will focus on our studies of liposomally encapsulated doxorubicin.     

Clinical and Bacteriological Studies with Clindamycin

Fifty patients have been treated with clindamycin, a chemical analogue of lincomycin. Forty-four responded satisfactorily to treatment. Gastrointestinal side-effects were rare though five patients developed rashes. Most recently isolated staphylococci are clindamycin-sensitive.     

显微镜下锁孔手术的临床应用研究

目的：探讨显微镜下锁孔手术的临床应用。方法：回顾性分析近10年来收治的锁孔手术459例的手术经验,总结锁孔手术临床应用。经眉弓锁孔入路治疗颅内病变的手术270例。经翼点锁孔入路治疗颅内病变的手术52例。经后颅窝锁孔入路的手术137例。结果：外伤及高血压引起脑内血肿23例,经翼点锁孔入路治疗效果良好。颅内肿瘤全切除266例（74．7％）,次全切除90例（25．3％）。术后并发症发生率为3．8％,无与手术入路相关并发症。结论：显微镜下锁孔手术是一种安全、有效的微创手术,值得进行深入研究和广泛应用。     

Clinical Studies of Human Pancreatic Enzyme Synthesis

Very little is known of the effects of diet and disease on panceratic enzyme syntheis in humans as conventional tests measure the secretory response to secreagogues, such as CCK, and secretion may be unrelated to synthesis because of the masking effect of a large intracellular pool of stored enzymes (zymogens). In order to obtain information on enzyme synthesis, as well as secretion, we have measured the incorporation characteristics of isotopically labelled amino acids (e.g., ¹⁴C or ¹³C leucine tracer) into amylase and trypsin protein, extracted by affinity chromatography from duodenal secretions during pancreatic stimulation with CCK-8The results of our studies in healthy volunteers and patients have suggested that (a) it takes between 75 and 101 min for the participation of newly synthesized pancreatic enzymes in the digestive process, and that zymogen stores are replaced at a rate of between 12 percent and 47 percent per hour in normal healthy subjects, (b) the synthesis and production rates of trypsin and amylase are parallel in healthy subjects, but can diverge under stressful conditions such as hypersecretory states, post-acute pancreatitis and protein malnutrition, (c) hyperphagia stimulates the synthesis of enzymes whilst malnutrition diminishes the synthesis of trypsin to a greater extent than amylase, (d) intravenous glucose and amino acids exert negative feedback control on the synthesis and release of amylase and trypsin, and (e) the decreased secretion of pancreatic enzymes in Type 1 insulin-dependent diabetics is more a consequence of defective enzyme release from zymogen stores than defective synthesis.In conclusion, our results indicate that changes in pancreatic enzyme secretion noted in patients do not always reflect changes in enzyme synthesis, and that the production of individual enzymes may diverge under certain circumstances. Based on the methodology described, it should be possible to develop more sensitive clinical tests of pancreatic function that provide information not only on the abiltiy of the pancreas to secrete enzymes under certain disease states, but also information on the gland''s synthetic activity     

Anemia in Patients With Diabetes and Prediabetes With Normal Kidney Function: Prevalence and Clinical Outcomes

ObjectiveAnemia is a known complication of diabetes mellitus (DM); however, its prevalence and prognostic relevance in patients with DM and pre-DM with normal kidney function have not been well defined. This study assessed the prevalence of anemia in patients with DM and pre-DM and evaluated its association with clinical outcomes during a 4-year follow-up period.MethodsThis retrospective analysis included patients with DM and pre-DM referred to the Meir Medical Center Endocrine Institute in 2015. Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min or any other recognized cause of anemia were excluded. The risk of developing microvascular or macrovascular complications or of death during the 4-year follow-up period was determined.ResultsA total of 622 patients (408 with DM and 214 with pre-DM) were included. The mean age of the patients was 64 ± 10.6 years, and 70% were women. The baseline hemoglobin A1C level was 7.1% ± 1.7% (54 mmol/mol), and the eGFR was 86.1 ± 15.3 mL/min. At the time of inclusion, 77 patients (19%) with DM and 23 (11%) with pre-DM had anemia (hemoglobin level 11.9 ± 0.8 and 11.8 ± 0.8 g/dL, respectively), compared with normal hemoglobin levels of 13.8 ± 0.9 and 13.7± 0.9 g/dL, respectively, in the others. A multivariable analysis demonstrated an inverse correlation between baseline hemoglobin (as a continuous variable) and mortality (P = .035), microvascular complications (P = .003), and eGFR decline (P < .001) but not between baseline hemoglobin and macrovascular complications (P = .567).ConclusionThis study found a significant prevalence of anemia unrelated to renal failure, both in patients with DM and pre-DM. Anemia in these patients is associated with the development of microvascular complications, eGFR decline, and mortality. These results underscore the need for intensive lifestyle and pharmacologic interventions in these patients.     

重组人尿激酶原的临床研究概况

尿激酶原或尿激酶型纤溶酶原激活剂具有特异性溶解血栓作用,引起人们的极大兴趣。西方国家1986年开始进行临床研究,A-74187或Sp2/0表达的糖基化尿激酶原以及大肠杆菌表达的非糖基化尿激酶原治疗急性心肌梗死阻塞相关血管开通率为70%~80%。德国Grünenthal公司用大肠杆菌表达的非糖基化尿激酶原(Saruplase)治疗急性心肌梗死研究采用20 mg推注,60 mg/60 min滴注,分别与重组组织型纤溶酶原激活剂、尿激酶、链激酶进行比较,并做了1698名心肌梗死患者的开放性临床试验,梗塞相关血管的开通率达到70%~80%。Saruplase与链激酶在104个临床研究中心,入组3089名急性心肌梗死患者进行大规模临床试验。结果表明,Saruplase对阻塞相关血管开通率、30天死亡率、出血合并症等副作用与链激酶没有明显差异,而出血性中风发生率高于链激酶,欧盟未批准Saru plase上市。国产重组人尿激酶原也进行了探索研究,用于治疗急性心肌梗死给药剂量为30~60 mg,给药时间为30或60 min,阻塞相关血管开通率为63.4%~80.0%,而尿激酶为52.2%~66.7%(平均58.0%)。此外,国外用重组人尿激酶原治疗深层静脉血栓和缺血性中风进行了探索研究,但病例数较少,尚须进一步研究。     

A Systematic Review of Studies Comparing Diagnostic Clinical Prediction Rules with Clinical Judgment

Background

Diagnostic clinical prediction rules (CPRs) are developed to improve diagnosis or decrease diagnostic testing. Whether, and in what situations diagnostic CPRs improve upon clinical judgment is unclear.

Methods and Findings

We searched MEDLINE, Embase and CINAHL, with supplementary citation and reference checking for studies comparing CPRs and clinical judgment against a current objective reference standard. We report 1) the proportion of study participants classified as not having disease who hence may avoid further testing and or treatment and 2) the proportion, among those classified as not having disease, who do (missed diagnoses) by both approaches. 31 studies of 13 medical conditions were included, with 46 comparisons between CPRs and clinical judgment. In 2 comparisons (4%), CPRs reduced the proportion of missed diagnoses, but this was offset by classifying a larger proportion of study participants as having disease (more false positives). In 36 comparisons (78%) the proportion of diagnoses missed by CPRs and clinical judgment was similar, and in 9 of these, the CPRs classified a larger proportion of participants as not having disease (fewer false positives). In 8 comparisons (17%) the proportion of diagnoses missed by the CPRs was greater. This was offset by classifying a smaller proportion of participants as having the disease (fewer false positives) in 2 comparisons. There were no comparisons where the CPR missed a smaller proportion of diagnoses than clinical judgment and classified more participants as not having the disease. The design of the included studies allows evaluation of CPRs when their results are applied independently of clinical judgment. The performance of CPRs, when implemented by clinicians as a support to their judgment may be different.

Conclusions

In the limited studies to date, CPRs are rarely superior to clinical judgment and there is generally a trade-off between the proportion classified as not having disease and the proportion of missed diagnoses. Differences between the two methods of judgment are likely the result of different diagnostic thresholds for positivity. Which is the preferred judgment method for a particular clinical condition depends on the relative benefits and harms of true positive and false positive diagnoses.