Tourette's Syndrome Mimicking Asthma

Tourette's syndrome is a neurological disorder consisting of chronic motor tics and involuntary vocalizations. Some of these vocalizations include coughing, grunting, and wheezing. We report two adolescents with a history of chronic coughing who presented for further evaluation of previously diagnosed asthma. A careful history suggested that Tourette's syndrome might be responsible for the patients' symptoms. Neurology evaluation confirmed the correct diagnosis of Tourette's syndrome for both patients. Treatment specific for this disease led to ablation of all symptoms. A history of repetitive coughing in adolescents may be the presenting symptom of Tourette's syndrome, thereby mimicking cough-equivalent asthma.     

Tourette's syndrome

As our knowledge of Gilles de la Tourette's syndrome increases, so does our appreciation for the pathogenic complexity of this disorder and the challenges associated with its treatment. Advances in the neurosciences have led to new models of pathogenesis, whereas clinical studies have reinvigorated early hypotheses. The interdependent roles of genes and environment in disease formation have yet to be fully elucidated. Results of epidemiological studies have prompted debate on how best to characterise and diagnose this disorder. Absence of ideal anti-tic drugs, combined with knowledge that uncomplicated cases of childhood Tourette's syndrome frequently have a favourable outcome, has led to striking changes in care and treatment of patients. This seminar focuses on these changing views and offers a new perspective on our understanding of the pathogenesis of Tourette's syndrome and on principles for treatment of patients with this disorder.     

The biochemistry of bone

The study of mineralized tissues has witnessed unprecedented advances as a result of recent technical breakthroughs in protein chemistry, and cell and molecular biology. Procedures for the nondegradative extraction of proteins present in mineralized matrices, along with improved chromatographic techniques, have resulted in the identification and purification of most, if not all, of the major structural proteins as well as less abundant (growth factors) proteins in these tissues. Many antibodies have become available against the intact proteins, as well as against synthetic peptides of the amino acid sequence from different parts of molecules. Along with mRNA determinations by in situ hybridization, these have been instrumental in determining when and where a matrix constituent is present in bone. Development of cell culture methods that maintain phenotypic expression has provided experimental systems to study the synthesis, secretion, and deposition of matrix, and the regulation of these processes. These model systems also have served as a source of genetic material for the making of cDNA libraries, which have been used for isolation of cDNA probes and ultimately for the isolation and characterization of the genes. By using these techniques, it is now feasible to develop procedures for the assessment of the role of matrix proteins in mineralized tissue, which will most certainly provide information that is critical to our understanding of bone metabolism in health and disease.     

The biochemistry of lipoproteins

Lipids are transported in the blood in four major classes of lipoproteins. The triacylglycerol-rich lipoproteins are chylomicrons and very-low-density lipoproteins (VLDL) which are produced by the small intestine and liver, respectively. These lipoproteins mainly carry fatty acids to adipose tissue and muscle where the triacylglycerol is hydrolysed by lipoprotein lipase. The resulting particles that remain in the blood are chylomicron remnants and low-density lipoprotein (LDL), respectively. The remnant is taken up by the liver via endocytosis which is mediated by a specific receptor for apolipoprotein E (apoE). LDL, which are rich in cholesterol, can also be taken up by the liver or extrahepatic tissues by a receptor-mediated endocytosis that specifically recognises apoB or apoE. Nascent high-density lipoprotein (HDL) particles are secreted by the liver and intestine and then undergo modification to become HDL₃ and then HDL₂ as they acquire cholesterol ester. They facilitate the reverse transport of cholesterol back to the liver.Little is known of the hormonal regulation of lipoprotein uptake by the liver. Recently, we have shown that insulin and tri-iodothyronine (T₃) increase the specific binding of LDL to cultured hepatocytes whereas dexamethasone (a synthetic glucocorticoid) has the opposite effect. The changes in binding produced by insulin and dexamethasone are paralleled by alterations in the rate of degradation of apoB. These findings may in part explain the hypercholesterolaemia and increased risk of premature atherosclerosis that can be associated with poorly controlled diabetes or hypothyroidism.     

The biochemistry of aging muscle

Between the ages of 20 and 80, humans lose approximately 20-30% of their skeletal muscle mass. This age-related loss of muscle mass, sometimes described as 'sarcopenia of old age', is the consequence of complicated multifactorial processes and is commonly associated with osteopenia or osteoporosis. Consequences of the aging changes in muscle are declining physiological function and loss of muscle strength, typically associated with reduced physical activities. Consequently, falls and subsequent serious injuries are prevalent in the elderly. Thus, it is imperative to try and understand the processes, leading to age-related muscle loss, in order to develop means to retard this phenomenon leading to improved quality of life in the elderly. It is possible to divide the causes of muscle aging to intrinsic factors, involving changes at the molecular and cellular levels, and to extrinsic or environmental factors. The purpose of this review is to describe some of the biochemical processes and the possible mechanisms of muscle aging and to evaluate the importance of various extrinsic factors such as nutrition, exercise and limb immobilization. Changes in the aging skeletal muscle are reviewed with regard to: (a) enzyme activities, protein turnover and repair capacities (b) mitochondrial functioning and energy reserve systems (c) ion content and regulation (d) oxidative stress and free radicals (e) nutrition and caloric restriction (f) exercise and limb immobilization.     

The clinical biochemistry of obesity-more than skin deep

While obesity has a high prevalence in developed countries, the routine abnormalities seen from the clinical biochemistry laboratory that may be caused by obesity related pathology do not seem to be as common. Insulin resistance, which is often associated with obesity, is difficult to assess as formal procedures are too complex for clinical practice. Furthermore the interpretation of insulin levels is hampered by their in vivo variability, assay differences and the lack of reference intervals from an unaffected reference population. Interpretation of fasting glucose levels between 5.5 and 6.0mmol/L are also being debated however, it is useful to understand the age related changes in this parameter, which may also be due to increasing obesity in the reference population. The association of obesity and dyslipidaemia in the metabolic syndrome should focus on elevated triglycerides (>1.5mmol/L), which is associated with low HDLC and correlates with atherogenic small dense LDL. High triglycerides are also predictive of fatty liver and the common abnormality of an elevated ALT may not be appreciated if laboratories allow their reference intervals to increase as the population gets more obese with aging. SHBG levels fall with insulin resistance/hyperinsulinaemia and this needs to be taken into account when testosterone is measured. However, low SHBG is showing huge potential as a disease and prognostic marker in obesity. These commonly available tests provide useful insights for the obese patient and their utility may improve with future research into the growing problem of obesity.