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By O. Taklar. University of California, Berkeley.

These autonomously secreting tu- therapy in patients with diabetes mellitus may increase mors occur in an intrinsically normal thyroid gland and the requirement for insulin or oral hypoglycemic result from point mutations in the TSHRs on thyroid agents buy biaxin 500mg lowest price. Tumor growth is progressive over many years biaxin 250mg on line, and with growth, a progressively larger share of thyroid hormone secretion is assumed by the adenoma; TSH secretion is inhibited, while the remainder of the gland is unstimu- THYROTOXICOSIS lated and may atrophy. Continued autonomous growth Thyrotoxicosis is any condition in which the body tis- results in excessive secretion of T4 and T3 and thyrotox- sues are exposed to supraphysiological concentrations icosis. This designation is preferred to the term hyperthyroidism to describe this disorder be- Clinical Manifestations of Thyrotoxicosis cause its origin may not result from excessive thyroid gland secretion. Thyrotoxicosis factitia arises from the The signs and symptoms of thyrotoxicosis, regardless of ingestion of excessive quantities of thyroid hormone the cause, may include the following: increased basal rather than from overactivity of the thyroid gland. The metabolic rate, heat intolerance, tachycardia, widened term hyperthyroidism is reserved for disorders that re- pulse pressure, cardiac arrhythmias, skeletal muscle sult from overproduction of hormone by the thyroid it- weakness, muscle wasting, tremor, hyperreflexia, emo- self. This distinction is important because only condi- tional instability, nervousness, insomnia, change in men- tions caused by hyperthyroidism respond to treatment strual pattern, frequent bowel movements (occasionally with agents that decrease iodine uptake, thyroid hor- diarrhea), and weight loss despite an increased appetite. These ocular manifestations appear to be due presence or absence of extrathyroidal manifestations, largely to increased adrenergic stimulation and are and the specific disorder producing the thyrotoxicosis. In these patients, serum concentrations of T4,T,3 and TSAB are elevated, while TSH levels are sup- Thyrotoxic crisis, thyroid storm, or accelerated hyper- pressed. Thyroid storm is ent until the preexisting intrathyroidal store of thyroid usually abrupt in onset and occurs in patients whose pre- hormone is depleted. Thyrotoxic crisis may be related to cytokine re- Tapazole) are the most commonly used preparations in lease and an acute immunological disturbance caused by the United States. In the thyroid gland, they inhibit Although the serum thyroid hormone levels may not be the activity of the enzyme TPO, which is required for appreciably greater than those in uncomplicated thyro- the intrathyroidal oxidation of I, the incorporation of toxicosis, the clinical picture is severe hypermetabolism I into Tg, and the coupling of iodotyrosyl residues to with fever, profuse sweating, tachycardia, arrhythmias, form thyroid hormones. With progression of the disorder, apa- Propylthiouracil, but not methimazole, also inhibits D1, thy, stupor, and coma may supervene, and hypotension which deiodinates T4 to T3. There are no foolproof criteria by which se- action, propylthiouracil is often used to provide a rapid vere thyrotoxicosis complicated by some other serious alleviation of severe thyrotoxicosis. In any event, the differentiation amide drugs may also exert an immunosuppressive ef- between these alternatives is of no great significance be- fect. As the drug is concentrated in thyroid follicular cause treatment of the two is the same, directed at sys- cells, the expression of thyroid antigen and the release temic support and amelioration of the thyrotoxicosis. Thion- amides also inhibit the generation of oxygen radicals in T cells, B cells, and particularly the antigen-presenting DRUGS USED IN THE TREATMENT cells within the thyroid gland. Thus, thionamides may OF HYPERTHYROIDISM cause a decline in thyroid autoantibody titers, although Treatment of hyperthyroidism is directed at reducing the clinical importance of immunosuppression is un- the excessive synthesis and secretion of thyroid hor- clear. This may be accomplished by inhibiting thy- Thionamide drugs are well absorbed from the gas- roidal synthesis and secretion with antithyroid drugs, by trointestinal tract. Although they have short plasma reducing the amount of functional thyroid tissue, or by half-lives (propylthiouracil 1. Unfortunately, only a small proportion of patients hours), they accumulate in the thyroid gland, and a sin- treated with antithyroid drugs obtain long-term remis- gle daily dose may exert effects for greater than 24 sion of their hyperthyroidism. Since many of the signs and symptoms of hy- form glucuronides and are excreted in the bile and perthyroidism reflect increased cellular sensitivity to urine. Nevertheless, few glucuronide conjugates are adrenergic stimulation, a -adrenergic antagonist is of- found in the feces because they are absorbed from the ten used adjunctively. It of hyperthyroidism and thyrotoxic crisis and in the may reduce thyrotoxicosis-induced tachycardia, palpita- preparation of patients for surgical subtotal thyroidec- tions, tremor, sweating, heat intolerance, and anxiety, tomy. Although the use of thionamides alone may re- which are largely mediated through the adrenergic store euthyroidism, it is difficult to adjust the dosage in nervous system. The use of propranolol is contraindi- and-replace regimens in which a full blocking dose of cated in thyrotoxic patients with asthma or chronic thionamide plus a levothyroxine supplement is pre- obstructive pulmonary disease because it impairs bron- scribed. It is also contraindicated in patients with perthyroidism during pregnancy, they should be given heart block and those with congestive heart failure, un- in minimally effective doses to avoid inducing infantile less severe tachycardia is a contributory factor. If given in excessive amounts over a long period, Thionamides thionamides may cause hypothyroidism and enlargement Thionamides are the primary drugs used to decrease of the thyroid gland. They do not inhibit secre- granulocytopenia and agranulocytosis, which occur in tion of stored thyroid hormone, and therefore, when about 0. The most frequently observed adverse 65 Thyroid and Antithyroid Drugs 751 effect is rash.

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Its application in studies of the blind has revealed that blind subjects are about 30% better than the sighted discount biaxin 500 mg on line,25 buy biaxin 250mg line,84 although a study from our laboratory failed to find such a difference. Evidence in favor of this is with only 3–4 d practice, sighted subjects can do just as well as the blind on the hyperacuity task. Also favoring the idea of use dependent neural plasticity was the finding of a 30% lower threshold on the Braille reading finger than on other fingers tested,84 although it must be noted that our study found no superiority of hyperacuity on the hand used for reading Braille27 and another study found no significant difference on grating orientation discrimination between those who read Braille and those who did not. The representation of the Braille reading finger in somatic sensorimotor cortex is expanded,48 and varies dynamically as a function of short term use. Finger amputation in owl monkeys leads to expansion of the cortical representation of adjacent digits. Two of the pyscho- physical studies cited above25,27 included both early-blind and late-blind subjects. Neither study revealed a significant performance difference between the early and late blind, although there were trends for the early blind to be better. Thus, at present there is no clear evidence that visual deprivation during a critical period in early life favors the acquisition of superior tactile capabilities. Remark- ably, blindfolding sighted subjects for just a few days improves their ability to © 2005 by Taylor & Francis Group. However, these findings suggest that there are nonvisual sensory inputs into visual areas, consistent with recent anatomical19,66 and earlier physiological28 work in macaque monkeys as well as an accumulating body of evidence from human studies that many visual cortical areas are active during,75 and functionally involved in,92 tactile perception even in sighted subjects. Accordingly, exuberance of multi-sensory inputs into and recruitment of visual cortex during tactile perception in the blind could reflect quantitative rather than qualitative differences compared to the sighted. INTER-MANUAL REFERRAL OF TACTILE SENSATION Following on observations, reviewed elsewhere,1,56 that tactile stimuli can be referred ipsilaterally from intact body parts to phantoms of resected body parts, Ramachan- dran and colleagues reported that tactile stimuli applied to the intact hand of arm amputees could evoke contralateral percepts referred in a topographic manner to the phantom hand. In these patients, touch- ing the normal hand can elicit a referred percept in the anesthetic hand at a mirror symmetric location. It may be related to performance improvement reported on grating orientation discrimination, associated with enhanced somatosen- sory evoked potentials, caused by acute somatosensory deprivation on the contralat- eral hand. This led to the conclusion71 that such referred percepts are unlikely to depend on neurons in area 3b, which exhibit fine grained spatial resolution and topographic organization. This would fit with the suggestion made earlier in this chapter, in Section IID on perceptual learning, that these areas which are higher than area 3b in the somatosensory cortical hierarchy, are more likely to be the locus of neural changes underlying perceptual learning and its transfer. However, a caveat is that under unusual circumstances, multi-digit recep- tive fields88 as well as rapid inter-hemispheric transfer of receptive field plasticity7 © 2005 by Taylor & Francis Group. It is also interesting that, in both amputees54 and patients with sensory loss,71 visual input tended to strengthen referred percepts, suggesting a role for multisensory convergence. The exact mechanisms mediating inter-manual referral of tactile percepts and their relation to those involved in perceptual learning remain unknown but merit further study. ACKNOWLEDGMENTS I thank my present and former colleagues for their involvement in the studies reviewed here, which were supported by grants from the National Institute of Neu- rological Disorders and Stroke and the National Eye Institute at the NIH. Aglioti S (1999) "Anomalous" representations and perceptions: implications for human neuroplasticity. Ahissar M, Hochstein S (1997) Task difficulty and the specificity of perceptual learning. Boroojerdi B, Bushara KO, Corwell B, Immisch I, Battaglia F, Muellbacher W, Cohen LG (2000) Enhanced excitability of the human visual cortex induced by short term light deprivation. Büchel C, Price C, Frackowiak RSJ, Friston K (1998) Different activation patterns in the visual cortex of late and congenitally blind subjects. Burton H, Snyder AZ, Conturo TE, Akbudak E, Ollinger JM, Raichle ME (2002) Adaptive changes in early and late blind: A fMRI study of Braille reading. Calford MB, Tweedale R (1990) Inter-hemispheric transfer of plasticity in the cerebral cortex. Cascio C, Sathian K (2001) Temporal cues contribute to tactile perception of rough- ness. Cohen LG, Celnik P, Pascual-Leone A, Corwell B, Faiz L, Dambrosia J, Honda M, Sadato N, Gerloff C, Catala MD, Hallett M (1997) Functional relevance of cross modal plasticity in blind humans. Cohen LG, Weeks RA, Sadato N, Celnik P, Ishii K, Hallett M (1999) Period of susceptibility for cross modal plasticity in the blind. Craig JC (1988) The role of experience in tactual pattern perception: a preliminary report. Crist RE, Kapadia MK, Westheimer G, Gilbert CD (1997) Perceptual learning of spatial localization: Specificity for orientation, position, and context.

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