I first read Davidson 30 years ago: at that time it was already in its 5th edition. A brief comparison shows that it then contained about 440,000 words in 1,100 pages: the current edition has compressed 625,000 words into 800 pages. I think I bought it as a student because it was cheap: but also because it seemed to be comprehensive and straightforward, and I have used it as a basis for my medical knowledge ever since. So I miss some of the old pictures of the acute skin rashes such as scarlet fever: in fact infectious disease has been transferred to the back and genetic factors take the first chapters. But careful linguistic comparison will still uncover the old phrases which some of us know by heart-there are minor changes such as 'alarming reactions to intravenous iron are uncommon, but have occasionally been noted', which becomes 'alarming systemic anaphyllactic reactions can occur'. Sir Stanley Davidson made 'no attempt to describe every rare disease or syndrome, but devoted most of the space available to those disorders most commonly encountered in practice'. I have grown up with successive editions, and have gradually come to appreciate the problems of the authors in the compression of knowledge. Having got to know many of them personally as real people rather than as names I can still recommend the book. It is the essential starting point for the study of internal medicine and for many doctors will remain their base reference work. The present editors have kept up-to-date and been prepared to prune the dead wood. There are many competitors in the market, and the publishers must take care with layout and illustration, although Davidson is still the best value for money. I will continue to recommend it to my clinical students: they will need to read it and know it to pass final MB. Postgraduates will need to remember the facts, but also to be able to place them in a broader perspective. The older consultant will still happily read it, and to get to know the authors themselves is really to complete your medical education. Dr John Macleod and his team have successfully kept alive the primary objective 'to provide a rational and easily comprehensible basis for the practice of medicine'. The book is economical in price and compact in size, but still contains the essential truths for the practice of good medicine.

Davidson's Principles and Practice of Medicine

The Food and Drug Administration (FDA) is a regulatory agency of the United States federal government This article describes the scope of work of each of the FDA's major components, and addresses the role of statisticians at FDA


Keywords:

drug regulation;
clinical trials;
medical devices;
safety;
bioassay

Food and Drug Administration (FDA)

Hyponatremia is a common water balance disorder that often poses a diagnostic or therapeutic challenge. Therefore, guidelines were developed by professional organizations, one from within the United States (2013) and one from within Europe (2014). This review discusses the diagnosis and treatment of hyponatremia, comparing the two guidelines and highlighting recent developments. Diagnostically, the initial step is to differentiate hypotonic from nonhypotonic hyponatremia. Hypotonic hyponatremia is further differentiated on the basis of urine osmolality, urine sodium level, and volume status. Recently identified parameters, including fractional uric acid excretion and plasma copeptin concentration, may further improve the diagnostic approach. The treatment for hyponatremia is chosen on the basis of duration and symptoms. For acute or severely symptomatic hyponatremia, both guidelines adopted the approach of giving a bolus of hypertonic saline. Although fluid restriction remains the first-line treatment for most forms of chronic hyponatremia, therapy to increase renal free water excretion is often necessary. Vasopressin receptor antagonists, urea, and loop diuretics serve this purpose, but received different recommendations in the two guidelines. Such discrepancies may relate to different interpretations of the limited evidence or differences in guideline methodology. Nevertheless, the development of guidelines has been important in advancing this evolving field.

/pdf/diagnosis-and-treatment-of-hyponatremia-compilation-of-the-49n6hhz39n.pdf

Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines.

https://www.kidney-international.org/article/S2157-1716(15)32142-0/pdf

Current treatment practice and outcomes. Report of the hyponatremia registry

Antibodies to glutamic acid decarboxylase (GAD) have been associated with several neurological syndromes, including stiff-person syndrome, cerebellar ataxia and epilepsy. These antibodies were first described in 1988, but several controversies about GAD autoimmunity still remain. No criteria exist to establish when a neurological syndrome is pathogenically linked to GAD antibodies, often leading to the assumption that any syndrome in which these antibodies are present is immune mediated, sometimes resulting in misdiagnosis and unnecessary treatment. In this Review, we provide recommendations for assessing the association between a neurological syndrome and the presence of GAD antibodies, and we critically review the evidence on the pathogenicity of GAD antibodies. Given that stiff-person syndrome is usually autoimmune, the presence of GAD antibodies in the cerebrospinal fluid is sufficient to confirm a pathogenic link with GAD autoimmunity. However, for cerebellar ataxia, epilepsy and other syndromes with different aetiologies, we propose that confirmation of a pathogenic link with GAD autoimmunity requires demonstration of intrathecal GAD antibody synthesis. Nevertheless, the evidence that GAD antibodies are directly pathogenic is not yet convincing. Studies in animal models are needed to demonstrate whether neurological syndromes are directly caused by specific disruption of GAD function by GAD antibodies. Antibodies to glutamic acid decarboxylase (GAD) are associated with several neurological syndromes but their importance and role are controversial. In this Review, Graus et al. propose criteria for assessing the association between GAD antibodies and neurological syndromes and discuss the pathogenicity of GAD antibodies.

GAD antibodies in neurological disorders — insights and challenges

Hyponatremia is one of the most commonly encountered electrolyte abnormalities occurring in up to 22% of hospitalized patients. Hyponatremia usually reflects excess water retention relative to sodium rather than sodium deficiency. Volume status and serum osmolality are essential to determine etiology. Treatment depends on several factors, including the cause, overall volume status of the patient, severity of hyponatremic symptoms, and duration of hyponatremia at presentation. Vasopressin antagonists like tolvaptan seem promising for the treatment of euvolemic and hypervolemic hyponatremia in heart failure. Low sodium concentrations cause cerebral edema, but the overly rapid sodium correction can also lead to iatrogenic cerebral osmotic demyelination syndrome. Demyelination may occur days after sodium correction or initial neurologic recovery from hyponatremia. The following case report analyzes the role of vasopressin antagonists in the treatment of hyponatremia and the need for daily dosing of tolvaptan and the monitoring of serum sodium levels to avoid rapid overcorrection which can result in osmotic demyelination syndrome (ODS).

/pdf/unpredictable-nature-of-tolvaptan-in-treatment-of-2kbs7az03f.pdf

Unpredictable nature of tolvaptan in treatment of hypervolemic hyponatremia: case review on role of vaptans.

Limbic encephalitis is a rare disorder affecting the medial temporal lobe of the brain, sometimes also involving hippocampus atrophy. It was initially considered to be only of paraneoplastic origin but now auto-immune (non-paraneoplastic) cases have also been reported. Most common non paraneoplastic antibodies associated with limbic encephalitis are Voltage gated potassium channel antibodies, NMDA receptor antibodies and GAD receptor antibodies. We present a case of limbic encephalitis which presented with sudden onset seizures which was preceded by confusion, disorientation and other psychiatric symptoms for a period of 5 weeks. No tumor was found on imaging and the classic paraneoplastic panel was negative. CSF and serum examination showed high titers GAD65 antibody guiding towards a diagnosis of non paraneoplastic limbic encephalitis. Her symptoms and GAD 65 antibody titers showed significant improvement following immunomodulatory therapy. The case presented here is unique and scientifically relevant, as it intends to raise awareness of Auto-immune Limbic Encephalitis, a potentially reversible cause of a medical emergency.

https://www.jocmr.org/index.php/JOCMR/article/viewFile/1080/562

GAD65 Positive Autoimmune Limbic Encephalitis: A Case Report and Review of Literature.

Superior vena cava and right atrium wall infective endocarditis in patients receiving hemodialysis

Topiramate (TMP) is a broad-spectrum anticonvulsant drug used to treat a wide variety of seizure disorders, for migraine prophylaxis, and for many other indications. An important side effect of TMP is metabolic acidosis, which is mediated by renal tubular defects. TMP inhibits carbonic anhydrase, an enzyme that is necessary for acid handling in the proximal renal tubule. Patients can present with asymptomatic serum electrolyte derangements, acute change in mental status, hyperventilation, cardiac arrhythmias, or other sequelae of metabolic acidosis and associated respiratory compensation. If taken chronically, TMP can cause renal stone formation, bone mineralization defects, and several other effects secondary to changes in serum and urine pH and electrolytes. There is no well-studied way to prevent metabolic acidosis in patients taking TMP, but physicians should be vigilant when prescribing this drug to patients with the history of renal diseases and other comorbidities, and aware of this potential etiology of metabolic acidosis. We present a literature review of the underlying mechanisms involved in the development of renal tubular acidosis secondary to TMP and its clinical consequences.

Type II Renal Tubular Acidosis Secondary to Topiramate: A Review.

Hyponatremia defined as a plasma sodium concentration of less than 135 mmol/L is a very common disorder, occurring in hospitalized patients. Hyponatremia often results from an increase in circulating arginine vasopressin (AVP) levels and/or increased renal sensitivity to AVP, combined with an increased intake of free water. Hyponatremia is subdivided into three groups, depending on clinical history and volume status: hypovolemic, euvolemic, and hypervolemic. Acute symptomatic hyponatremia is usually treated with hypertonic (3%) saline. Syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) and hypervolemic hyponatremia caused by heart failure or cirrhosis are treated with vasopressin antagonists (vaptans) since they increase plasma sodium (Na2+) concentration via their aquaretic effects (augmentation of free-water clearance). The role of tolvaptan in the treatment of acute hyponatremia and conversion of oliguric to nonoliguric phase of acute tubular necrosis has not been previously described.

/pdf/tolvaptan-in-the-treatment-of-acute-hyponatremia-associated-hjkny487k2.pdf

Kalyana C. Janga

Papers

Unpredictable nature of tolvaptan in treatment of hypervolemic hyponatremia: case review on role of vaptans.

GAD65 Positive Autoimmune Limbic Encephalitis: A Case Report and Review of Literature.

Superior vena cava and right atrium wall infective endocarditis in patients receiving hemodialysis

Type II Renal Tubular Acidosis Secondary to Topiramate: A Review.

Tolvaptan in the Treatment of Acute Hyponatremia Associated with Acute Kidney Injury