An outreach activity to enhance biochemistry pedagogy.

Students are self-motivated to learn when provided opportunities that connect theory and real-world applications. Here, we describe for biochemistry majors a newborn screening-focused outreach activity that seeks to develop students' mastery of disciplinary content and soft skills (e.g., critical thinking, teamwork, effective communication, community engagement) and to enhance student engagement.

Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base.

The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed.

Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal.

Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.

Immunizations for patients with metabolic disorders.

Individuals with underlying metabolic disorders are a potential high-risk group for vaccine-preventable diseases. Newborn metabolic screening has provided a means of early identification and treatment for many of these disorders, whereas childhood immunization is one of the most effective means of decreasing the morbidity and mortality resulting from communicable diseases worldwide. There are very few contraindications to the routine administration of vaccines to the healthy, immunocompetent individual. In certain high-risk groups, such as immunocompromised patients, gravid females, and those with a history of previous anaphylactic reaction to a vaccine or its components, selective withholding of immunizations must be considered to decrease potential adverse events. A detailed analysis of the medical literature revealed few specific recommendations regarding appropriate immunization techniques for patients with metabolic disorders. In this review we detail the major metabolic disorder subtypes, elaborate on the available literature on immunizations for patients with these disorders, and provide suggested vaccine recommendations.

The role of nutrition in chronic renal insufficiency of childhood: how much do we know?

Dietary protein restriction in the treatment of symptomatic renal failure has been utilized for many years, especially as a means for reduction of 'fixed acid" load. Studies in animal models of renal failure suggest that low protein intake may retard the progression of renal disease as well. However, large, well-organized investigations into this question in humans have fallen prey to difficulties that are almost impossible to overcome. Chief among these difficulties is the problem of chronically reducing protein intake in patients with a lifelong intake far above the recommended daily allowance (RDA). Another is the fact that all previous studies have been performed in patients with moderate to severe compromise of renal function. Thus, the potential efficacy of reduced protein intake in the retardation of the progression of renal disease remains an open question. In this article, we discuss the current state of knowledge and propose an approach to answering this question.

Pediatric obstructive uropathy: clinical trials.

As the powerful tools of molecular biology continue to delineate new concepts of pathogenesis of diseases, new molecular-level therapeutic modalities are certain to emerge. In order to design and execute clinical trials to evaluate outcomes of these new treatment modalities, we will soon need a new supply of investigators with training and experience in clinical research. The slowly-progressive nature of chronic pediatric kidney disease often results in diagnosis being made at a time remote from initial insult, and the inherently slow rate of progression makes changes difficult to measure. Thus, development of molecular markers for both diagnosis and rate of progression will be critical to studies of new therapeutic modalities. We will review general aspects of clinical trials and will use current and past studies as examples to illustrate specific points, especially as these apply to chronic kidney disease associated with obstructive uropathy in children.

Hyperammonemia, bane of the brain.

Ammonia, normally produced from catabolism of amino acids, is a deadly neurotoxin. As such, the concentration of free ammonia in the blood is very tightly regulated and is exceeded by two orders of magnitude by its physiologic derivative, urea. The normal capacity for urea production far exceeds the rate of free ammonia production by protein catabolism under normal circumstances, such that any increase in free blood ammonia concentration is a reflection of either biochemical or pharmacologic impairment of urea cycle function or fairly extensive hepatic damage. Clinical signs of hyperammonemia occur at concentrations > 60 micromol/L and include anorexia, irritability, lethargy, vomiting, somnolence, disorientation, asterixis, cerebral edema, coma, and death; appearance of these findings is generally proportional to free ammonia concentration, is progressive, and is independent of the primary etiology. Causes of hyperammonemia include genetic defects in the urea cycle ("primary") or organic acidemias ("secondary"), as well as genetic or acquired disorders resulting in significant hepatic dysfunction. Thus, because of the neurotoxic implications of hyperammonemia and the typical absence of other specific laboratory abnormalities, appearance of the clinical signs should trigger an emergent search for elevated blood ammonia concentration.

Evaluation of the hypertensive infant: a rational approach to diagnosis.

This article reviews the literature and describes a methodologic approach to the diagnosis of hypertension in the young infant. The numerous etiologies of hypertension have been discussed and normative blood pressure data for neonates and infants have been provided. Techniques for accurate blood pressure measurement in the intensive care setting and for routine outpatient settings, are discussed. The lengthy discussion of radiologic approach to imaging can be summarized with the following suggested algorithm. Initial screening should be performed with gray-scale sonography, to identify renal parenchymal or collecting system abnormalities, including mass lesions and congenital anomalies. Further imaging with color and duplex Doppler sonography detects renal arterial or aortic thrombosis, and alterations in the arterial waveform caused by intrinsic or extrinsic renal artery narrowing. The major limitation of Doppler sonography is the recognition that disease in accessory renal arteries or in small segmental intrarenal arteries may frequently be undetected. Functional imaging with ACEI renography should follow renal sonography to detect hemodynamically significant renovascular disease (with a sensitivity and specificity of approximately 90%); intravenous enalaprilat is the preferred ACEI. Angiography should be reserved for older children in whom interventional percutaneous angioplasty may be more feasible. A young infant with hypertension caused by renal artery stenosis should be controlled medically until he or she is large enough to undergo angiography and angioplasty successfully. CT angiography and MR angiography, although promising in the adult population, may not adequately resolve the small intrarenal vessels, which are frequently the culprit in renovascular hypertension of infancy.

Cystinosis and cystinuria: differences in outcome.

Cystinosis and cystinuria, both recessive genetic disorders, are fundamentally different in their pathophysiologic mechanisms. Cystinosis is a disease of cystine storage in which the kidney is the initial, but not the sole target organ. Cystinuria is a disease of renal tubular cystine transport in which excessive loss of this insoluble amino acid causes precipitation at physiologic urine pH and concentration. The former disorder uniformly results in the need for renal allograft despite recent advances in medical therapy. Cystinuria has a variable severity of expression and may be amenable to long-term medical treatment in some patients. Others may have frequent stone recurrence and infection and progress to chronic renal failure in the long term. It is the purpose of this review to provide the reader with an understanding of the respective diseases and the reasons for the differences in their prognoses and long-term outcomes.

Obstructive uropathy: an important cause of chronic renal failure in children.

Care of individuals with renal failure continues to impose a tremendous burden on our national health care budget. Chronic renal failure is the final common denominator of a multiplicity of pathologic processes, some of which progress silently over years. Of these, obstructive uropathy is a prominent cause of kidney failure, accounting for 16.5% of all pediatric renal transplants in 1997. The pathophysiology of obstructive uropathy is reviewed as the basis for a differential diagnosis. In view of the significant role played by obstructive uropathy in the development of renal failure, early and definitive treatment of this clinical entity is imperative.