Surgical Considerations of Certain Hip Lesions

Advances in orthopedic surgery have made it possible to deal successfully with many disturbing hip lesions. The tolerance of the body to the inert metals has made many of these advances possible.     

Viral infections that affect the fetus

Several viral infections besides rubella are known to cause fetal anomalies and disease. Cytomegalovirus, for example, may adversely affect the fetus in a number of ways. Either herpesvirus or hepatitis B virus is transmissible from mother to offspring. Viruses whose potential for fetal harm is less clear are those of varicella, mumps, and influenza.     

Computer-Based Patient Interviewing

Before the computer can become truly useful in clinical research, diagnosis and therapy, new ways to collect data must be developed. The computer itself can be adapted to take medical histories directly from patients. These data, in computer- processable form, are then available for physician use in patient care and clinical research. Results obtained with computer-based histories are reviewed and the technic is compared with traditional methods. Also discussed is the potential role of computer-based interviewing in modern medical practice.     

Treatment of Rheumatoid Arthritis

This section is reserved for commentaries and brief essays dealing with matters of interest to physicians. Material for consideration should not exceed Ave double-spaced typewritten pages. An honorarium of $75 is offered at the time of publication. Submissions should be addressed to: Editor, POSTGRADUATE MEDICINE, 4530 W 77th St, Minneapolis, MN 55435.     

A Simple Amidolytic Method for the Determination of Functionally Active Antithrombin III

A simple amidolytic method for the determination of the concentration of functionally active antithrombin III is described. Plasma is diluted with buffer containing EDTA and Polybrene®. In stage I, diluted plasma is incubated with thrombin. EDTA retards fibrin polymerization, and plasma fibrinogen does not influence the assay. Polybrene makes the assay result independent of heparin. In stage II, remaining thrombin is determined with the chromogenic substrate benzoyl-Phe-Arg-p-NA. The method is simpler and has a higher accuracy than clotting methods. There is a close correlation between the results obtained with this assay and with immunoassay of antithrombin III.     

Immune tolerance induction for the eradication of inhibitors in patients with hemophilia A

Background: Both genetic and environmental factors contribute to the formation of alloantibodies that bind to functional domains on the Factor VIII (FVIII) molecule and inhibit its function. Patients with hemophilia A who develop high-titer inhibitors are at increased risk for serious hemorrhage and disability, particularly arthropathy, because bleeding events do not respond to standard therapy. Immune tolerance induction (ITI) is usually attempted to eradicate newly diagnosed inhibitors, restore replacement FVIII pharmacokinetics, and improve bleed management and quality of life. Objective: This paper summarizes regimens used for ITI, predictors of success and failure, and adjunctive therapies for patients failing ITI therapy. Methods: This is a systematic review of published reports on ITI regimens, data from registries capturing response rates and predictors of success, and reports of adjunctive treatments used to enhance ITI therapy. Results/conclusion: Many issues remain unresolved, chief among them optimal dose and dosing regimen, choice of FVIII product, and the role of adjunctive therapy. Resolution of these issues, as well as new approaches to inhibitor management, may come from ongoing basic science research and clinical trials.     

Pharmacotherapy of haemophilia A

Introduction: Haemophilia A is due to factor VIII (FVIII) deficiency. The main treatment is replacement therapy with FVIII concentrates. However, these concentrates carried a high risk of blood-borne viral infections and still have a high risk of inducing anti-FVIII inhibitors.

Areas covered: An overview of products available and therapeutic options for haemophilia A management in order to help in decision making. A literature search using Medline with the keywords: ‘haemophilia’, ‘factor VIII’, ‘therapy’, ‘inhibitor’, ‘concentrate’, ‘bleeding’, ‘prophylaxis’, ‘on demand’, ‘plasma-derived’, ‘recombinant’, ‘coagulation factors’, ‘immunotolerance’ was performed. The years 1960 – 2010 are included.

Expert opinion: Progress in management of patients with haemophilia A has allowed increased life expectancy and quality of life. There is evidence that prophylaxis prevents or, at least, slows down arthropathy development when started early in childhood. FVIII concentrates have achieved high levels of blood-borne pathogen safety. However, treatment is frequently complicated by development of FVIII-neutralizing inhibitors, which prevent control of bleeding and predispose to a high morbidity and mortality risk. Bypassing agents are effective in bleeding treatment in a high percentage of cases. Prophylaxis with bypassing agents and their use in combination are offering opportunities in management of inhibitor patients. More evidence is necessary to understand how to prevent and manage this complication.     

Current situation of zalutumumab

Background: Increased EGFR expression has been observed in many tumours. This overexpression usually correlates with a more advanced disease stage, a poorer prognosis and a worse chemotherapy response. EGFR inhibition has been considered an attractive approach in cancer treatment. Various strategies to intervene in EGFR signalling have been developed, mainly receptor inhibition of extracellular domain using anti-EGFR monoclonal antibodies and receptor inhibition on the intracytoplasmic domain using small-molecule tyrosine kinase inhibitors. Cetuximab and panitumumab are the most developed anti-EGFR monoclonal antibodies, and there is plenty of published information about their current status Objective/methods: In this review we focus on Zalutumumab, an IgG1 completely human anti-EGFR monoclonal antibody. Results/conclusions: Apart from EGFR inhibition, another anti-neoplastic effect of zalutumumab has also been postulated, mediated by immune mechanisms, specifically by antibody-dependent cell cytotoxicity. Zalutumumab is under clinical development, mainly for squamous cell cancer of head and neck and there are also ongoing trials in NSCLC and colorectal cancer.     

Hormone-based therapies in the regulation of fuel metabolism and body weight

Background: The integrated central actions of hormones secreted from pancreatic islets, the gut and adipocytes regulate both energy homeostasis and body weight. Dysregulation in these neurohormonal pathways probably contributes to pathogenesis of obesity and type 2 diabetes. Objective: To examine hormone-based therapies targeting these interrelated pathways as potential treatments for obesity and diabetes. Methods: Preclinical and clinical data on therapies based on hormones secreted from the pancreas (glucagon, insulin, amylin and pancreatic polypeptide), gut (glucagon-like peptide-1, glucose dependent insulinotropic polypeptide, cholecystokinin and peptide YY) and adipose tissue (leptin and adiponectin) as potential treatments for diabetes and obesity are reviewed. Results/conclusions: In diabetes, hormone-based treatments have translated into new clinical platforms including insulin analogs, the GLP-1-like peptide receptor agonist exenatide and amylinomimetic pramlintide, which due to their complex interplay and the progressive nature of diabetes, can be utilized in different settings. Various peptide hormones and agonists/antagonists are currently under investigation as new approaches to treatment of obesity and diabetes.     

Prevention of cardioembolic stroke in patients with atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia and an important independent stroke risk factor, especially in the elderly. This article provides the reader with an overview as well as an update on primary and secondary stroke prevention strategies in patients with AF. Vitamin K antagonists remain the cornerstone therapy in AF patients at high risk of stroke. Both aspirin monotherapy and the combination of aspirin and clopidogrel are inferior to vitamin K antagonists in patients with AF. The new direct thrombin inhibitor dabigatran is at least as effective as warfarin and leads to a significant and clinically relevant decrease in hemorrhagic stroke and intracranial bleeds. Interventional therapies such as percutaneous closure of the left atrial appendage or radiofrequency catheter ablation have not yet been proven to decrease the stroke risk in patients with AF.