Cardiac Injury Is a Common Postmortem Finding in Thrombotic Thrombocytopenic Purpura Patients: Is Empiric Cardiac Monitoring and Protection Needed?

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal disease. Early implementation of therapeutic plasma exchange (TPE) has decreased the mortality rate from >90% to <10%. However, fatalities still occur in these patients. The goal of this study was to characterize the causes of death and related postmortem findings in patients with TTP in the current era of emergent TPE to identify possible areas for improvement in the care of these patients. We analyzed clinical history, laboratory and histopathologic findings, and causes of death of patients with active TTP or TTP in clinical remission autopsied at our institution over 22 years. Of 18 patients, 15 had TTP judged to be a cause of death: it was an underlying cause of death in five cases, intermediate in three, and contributing in seven. The most common immediate causes of death were cardiac arrest and myocardial infarction. The most common TTP‐related findings at autopsy were thrombi/emboli in heart (9), lung (11), brain (3), kidney (7), followed by hemorrhages in heart (7), lung (8), brain (2), kidney (7), and infarcts in heart (5), lung (4), brain (6) and kidney (3). Analysis of the cases with TTP as a cause of death suggests that the mechanism of death is commonly cardiac in origin. Proactive measures to monitor and protect the heart may be beneficial in these patients.     

Glucosamine for pain in osteoarthritis: Why do trial results differ?

Objective

Investigators in trials of glucosamine report a range of estimates for efficacy, making conclusions difficult. We undertook this study to identify factors that explain heterogeneity in trials of glucosamine.

Methods

We searched for reports of trial results in Ovid Medline, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and proceedings of scientific conferences. We selected reports of randomized, double‐blind, placebo‐controlled trials of glucosamine for pain from osteoarthritis of the knee or hip. We extracted data regarding features of design, subjects, and markers of industry involvement, including industry funding, whether a drug was supplied by industry, industry participation, and industry‐affiliated authorship. We examined which factors best accounted for differences in the effect sizes of studies grouped by these characteristics, and we examined changes in I², a measure of heterogeneity.

Results

Fifteen trials met our inclusion criteria. The summary effect size was 0.35 (95% confidence interval 0.14, 0.56). I² was 0.80. Except for allocation concealment, no feature of study design explained this substantial heterogeneity. Summary effect sizes ranged from 0.05 to 0.16 in trials without industry involvement, but the range was 0.47–0.55 in trials with industry involvement. The effect size was 0.06 for trials using glucosamine hydrochloride and 0.44 for trials using glucosamine sulfate. Trials using Rottapharm products had an effect size of 0.55, compared with 0.11 for the rest.

Conclusion

Heterogeneity among trials of glucosamine is larger than would be expected by chance. Glucosamine hydrochloride is not effective. Among trials with industry involvement, effect sizes were consistently higher. Potential explanations include different glucosamine preparations, inadequate allocation concealment, and industry bias.

     

Thrombotic Thrombocytopenic Purpura as an Initial Presentation of Primary Sjo¨gren’s Syndrome

A healthy woman presented with ecchymoses due to thrombocytopenia, with numerous bone marrow megakaryocytes, microangiopathic haemolytic anaemia, disorientation, irritability, and normal renal function. Thrombotic thrombocytopenic purpura (TTP) was diagnosed and treated successfully by plasma exchange therapy, both on presentation and during a further three relapses. The TTP was considered idiopathic until, 4 months later, definite primary Sjo¨gren’s syndrome (1°SS) was diagnosed following the appearance of sicca symptoms. Only four similar cases have been cited in the literature. TTP should be added to the varied haematological manifestations that may occur in patients with 1°SS. The possible presentation of 1°SS not with classic sicca symptoms but rather with haematological abnormalities, including TTP, should be recognised. Received: 26 January 2001 / Accepted: 23 July 2001     

Cardiovascular alteration and treatment of hypertension: do men and women differ?

Cardiovascular disease is one of the most common causes of mortality affecting both men and women in industrialized nations. Sex-related differences have been well established with regard to heart and vascular function as well as cardiovascular disease processes. Nevertheless, the precise mechanisms of action behind these gender-related differences are poorly understood. Premenopausal women have a relatively lower arterial blood pressure compared to age-matched men and post-menopausal women, suggesting a role of ovarian hormones in blood pressure regulation. Sex-related differences in vasculature and neuroendocrine systems are also present that can affect hemostasis, vascular reactivity, and vascular tone. Treatment for cardiovascular disease and hypertension has been challenging and unsatisfactory. Men and women may require different antihypertensive regimens due to differences in the progression and presentation of hypertension. Additionally, hormone replacement therapy in postmenopausal women has been controversial, producing both beneficial and detrimental effects. Therefore, this review will focus on sex-related differences in the heart and vasculature, and treatments for cardiovascular disease, such as hypertension.     

Gastrointestinal endoscopy in children and adults: How do they differ?

Gastrointestinal endoscopy has grown dramatically over the past century, and with subsequent improvements in technology and anaesthesia, it has become a safe and useful tool for evaluation of GI pathology in children. There are substantial differences between paediatric and adult endoscopy beyond size, including: age-related patho-physiology and the different spectrum of diseases in children. Literature on endoscopic procedures in children is sparse but significant. The present review aims at describing the current knowledges on paediatric endoscopy practice and highlights the main areas of differences between paediatric and adult practice.     

Diabetic cardiomyopathy: do women differ from men?

Although many aspects of cardiovascular disease are similar between women and men, it is becoming increasingly obvious that there are significant differences as well. Premenopausal women ususally have a lower risk of cardiovascular diseases than age-matched men and postmenopausal women. However, the “female advantage” disappears once women are affilicted with diabetes mellitus. Heart diseases are twice as common in diabetic men and five times as common in diabetic women. It is believed that differences in sex hormones and intrinsic myocardial and endothelial functions between men and women may be responsible for this female “advantage” and “disadvantage” in normal and diabetic conditions. Most experimental and clinical studies on diabetes only included male subjects and failed to address this important gender difference in diabetic heart complications. Although female hearts may be better tolerated to stress (such as ischemia) insults than their male counterparts, female sex hormone such as estrogen may interact with certain risk factors under diabetes which may compromise the overall cardiac function. The benefit versus risk of estrogen replacement therapy on cardiac function and overall cardiovascular health in diabetes remains controversial. This review will focus on gender-related difference in diabetic heart complication—diabetic cardiomyopathy—and if gender differences in intrinsic myocardial contraction, polyol pathway metabolism, and advanced glycation endproduct formation and other neuroendocrinal regulatory mechanisms to the heart may contribute to disparity in diabetic cardiomyopathy between men and women.     

Case Report: Can Colectomy Cure Immune Thrombocytopenic Purpura in a Patient with Ulcerative Colitis?

The association between ulcerative colitis (UC) and immune thrombocytopenic purpura (ITP) has been suggested by sporadic case reports. Prior reports have focused on the role of medical therapy and/or splenectomy for control of concurrent ITP and UC. We report a case of a patient with UC and ITP who was poorly controlled on maximal medical therapy for these two disorders and underwent a colectomy that cured both diseases.     

ATP-sensitive potassium channels and myocardial ischemia: Why do they open?

Summary There is evidence that the ATP-sensitive potassium channel opens, at least during the early stages of myocardial ischemia, despite relatively high ATP levels. Thus, channel opening may partially contribute to potassium efflux and accumulation of extracellular potassium, but probably much more profoundly to electrical abnormalities associated with ischemia, including the development of lethal arrhythmias. Several factors are discussed that may promote a significant open-channel probability of the channel, in spite of relatively high levels of ATP. It is argued that, even with a very low open probability, the magnitude of total membrane current carried by these channels may be substantial (comparable to other potassium currents) because of the high density and conductance of the ATP-sensitive potassium channel. Finally, it is shown how the ATP-sensitive potassium channel may play a role in various tissue types, ranging from the physiological to the pathophysiological. This potassium channel is therefore increasingly targeted for drug development and research.     

Why do aneurysms burst?

Aneurysms are defined as bulges twice the diameter of the nearby normal vessel. Aneurysms burst when the artery wall becomes too weak for the blood pressure within. Urgent clinical examination by a vascular surgeon, then an ultrasound or CT angiogram if time permits before repair, may save life. The result of a timely repair at Royal Melbourne Hospital of Epworth is 90-95% success, while only 50% of patients survive an attempt to repair the aneurysm once it has burst.     

Why do life spans differ? Partitioning mean longevity differences in terms of age-specific mortality parameters

Populations typically differ in mean life spans because of genetic, environmental, or experimental factors. In this paper methods are presented that clarify the relationship between differences in the longevity of two populations and differences in their underlying age-specific patterns of mortality. Data are examined from rodent and fruit fly (Drosophila melanogaster) experiments that investigated the longevity effects of a variety of environmental and genetic manipulations, including temperature, dietary restriction, laboratory selection for increased longevity, and severe inbreeding. Analyses suggest that longevity differences mediated by temperature and dietary restriction result predominantly from differences in the rate of increase in mortality with age. Increases in longevity through laboratory selection result primarily from a reduction in baseline mortality and not a slowing of the rate of aging. Although the methods are applied primarily in the context of simple mathematical models of mortality (e.g., the Gompertz model), they are quite general and can be applied to mortality models of arbitrary complexity. Mathematica protocols ("notebooks") and computer software have been developed to perform all the analyses discussed and are available from the first author.     

Why do adults contract diphtheria?

When diphtheria was a common disease, it most commonly affected children. Typically, at least 40% of diphtheria cases were children under 5 years of age, and some 70% of cases were children under 15 years of age. This classical pattern of diphtheria cases     

Why do we reject grafts?

One of the puzzles in clinical and experimental organ and tissue transplantation has been why it is that, with the exception of transplantation between genetically identical twin pairs, transplantation results in a rapidly progressing immune response to the point of tissue necrosis in a matter of a few days, even though the recipient has not been immunized to the donor. Indeed, the numbers of T lymphocytes predetermined to react against grafts are relatively abundant compared to those that recognize microbial antigens. Cellular, molecular, and genetic studies are now revealing the nature of T-cell recognition, and why it is that we cannot freely exchange tissue grafts.