Propylthiouracil blocks extrathyroidal conversion of thyroxine to triiodothyronine and augments thyrotropin secretion in man.

Propylthiouracil (PTU) inhibits peripheral deiodination of thyroxine (T4) and triiodothyronine (T3) and decreases the metabolic effectiveness of T4 in animals. To assess the effect of PTU on extrathyroidal conversion of T4 to T3 in man, 15 studies were performed in athyreotic patients treated with 100 or 200 mug of L-T4 daily for 1 mo before the addition of PTU, 250 mg every 6 h for 8 days. serum T3, T4, and thyrotropin (TSH) were measured daily by radioimmunoassay; serum TSH response to 500-mug thyrotropin-releasing hormone (TRH) was measured before and on the last day of giving PTU. On the 100-mug LT4 dose, serum T3 fell from 120 plus or minus 5 (SE) to 83 plus or minus 6 ng/dl (P less than 0.005) with return to 113 plus or minus 5 ng/dl after stopping PTU; serum T4 (4.5 plus or minus 0.3 mug/dl) did not change. Similar results were seen in patients taking 200 mug of L-T4 daily. On the 100-mug dose of L-T4 the fall in T3 was accompanied by a reciprocal rise in serum TSH to 195 plus or minus 33% of initial concentration (P less than 0.01) with return to 104 plus or minus 8% after PTU. The serum TSH response to TRH (DELTAMUU/ml over base line) was greater during PTU therapy than during the control period. On 100-mug L-T4 DELTA TSH rose from 64 plus or minus 19 to 101 plus or minus 23 muU/ml (P less than 0.005). Expressed as percent of base-line TSH concentration, TSH rose from 140 plus or minus 52 to 280 plus or minus 44% (control vs. PTU) at 15 min, 265 plus or minus 72 to 367 plus or minus 63% at 30 min, 223 plus or minus 54 to 313 plus or minus 54% at 45 min, 187 plus or minus 45 to 287 plus or minus 51% at 60 min, and 145 plus or minus 22 to 210 plus or minus 28% at 120 min after TRH. The data suggest that PTU blocks extrathyroidal conversion of T4 to T3, thus increasing pituitary TSH secretion and augmenting the TSH response to TRH.

Diabetes care in health maintenance organizations.

An increasing amount of health care today is directed to the amelioration of chronic diseases for which there are no cures. Technological advances and the aging of the population have increased the costs of that care. In an attempt to control costs and increase the efficiency of health care, it is being increasingly delivered in alternate health-care systems where third-party payors influence the access, use, and quality of that care. This article traces the history of the development of alternative health-care delivery systems and describes how they attempt to deal with the tension between cost and quality in the context of the delivery of health care to people with diabetes. Systems for home health care, health education and dietary counseling, prescriptions and durable medical equipment, medical technology assessment, quality management, peer review, and cost containment in the various alternative health-care settings are described. Theoretically, the health maintenance organization offers an ideal system for delivering care that is accessible, affordable, and of good quality.

Treatment of hyperthyroidism with sodium ipodate (oragrafin) in addition to propylthiouracil and propranolol.

Ten patients with hyperthyroidism due to Graves' disease were treated with sodium ipodate (1 g daily) in addition to propranolol (P) plus propylthiouracil (PTU; 100 mg every 8 h) and were compared with a control group of 8 patients treated with P and PTU. Patients on P and PTU had a mean (+/- SEM) basal free T3 index of 387 +/- 59 (normal, 70--160) compared with that of 409 +/- 47 (P greater than 0.05) in the sodium ipodate group. The respective basal free T4 index values (normal, 4.5-10.9) were 21.3 +/- 2.8 for the controls and 25.9 +/- 2.8 for the ipodate group (P greater than 0.5), and the basal rT3 values were 192 +/- 49 and 210 +/- 41 (normal, 16--50 ng/dl; P greater than 0.05). The average percent changes in each thyroid index and rT3 were calculated. The first 3 days on P and PTU served as the basal period for the control group, and comparisons were made to the following 9 days. The ipodate group received P and PTU for 2.7 +/- 3.0 days, and comparisons were made with the interval on ipodate, P, and PTU (mean, 9.1 +/- 0.9 days). For the free T3 index, the control group showed a mean decrement of 20.5 +/- 4.4% compared with 50.2 +/- 3.1% for the ipodate group (P less than 0.001). The respective free T4 index decrements were 14.5 +/- 4.4% and 18.5 +/- 2.7% (P greater than 0.05). The respective changes in rT3 were -13.4 +/- 7.6% and +140 +/- 26.9% (P less than 0.001). In patients with hyperthyroidism, short term daily therapy with sodium ipodate plus P and PTU produces a greater reduction of free T3 index values than that caused by P and PTU alone.

A radioimmunoassay for measurement of thyronine and its acetic acid analog in urine.

A sensitive and specific RIA has been developed to measure thyronine (To) in urine. The RIA used an anti-To antibody obtained from a rabbit immunized with a L-To-human serum albumin conjugate and [3H]To as the radioligand. The acetic acid analog of To (ToAc), that is the diphenyl structure with an acetic acid side-chain, cross-reacted strongly with the antibody. Relative to To, it cross-reacted 160% in phosphate-buffered saline, pH 7.4, and 100% in 0.075 mol/L barbital buffer, pH 8.6, containing sodium salicylate (final concentration, 8 mg/mL). The latter conditions were employed for the RIA, and the results reported thus reflect the presence of To and/or ToAc. 3-Monoiodothyronine, 3'-monoiodothyronine, 3',5'-diiodothyronine, and 3,5-diiodothyronine cross-reacted with the anti-To antibody 1.9%, 1.7%, 0.3%, and 0.2%, respectively; the cross-reactivity of other To derivatives and tyrosine and its derivatives was less than 0.05%. Urinary To and/or ToAc excretion in 12 normal subjects averaged 16 +/- 2 (+/- SE) micrograms/day (59 +/- 9 nmol/day) or 14 +/- 2 micrograms/g creatinine (5.9 +/- 0.6 nmol/mmol creatinine). Treatment of urine from normal subjects with beta-glucuronidase or sulfatase did not significantly alter the To content. Column and thin layer chromatographic studies revealed that 83% and 61%, respectively (range, 37-100%), of urinary To immunoreactivity was attributable to ToAc. The mean daily excretion of To in 20 patients with nonthyroidal illness [NTI; 22 +/- 4 micrograms/day (82 +/- 17 nmol/day)] was similar to that in normal subjects, but was elevated when expressed as nanomoles per mmol creatinine (20 +/- 2; P less than 0.001), because creatinine excretion was reduced in the NTI patients. The mean daily urinary To excretion in 13 patients with hyperthyroidism due to Graves' disease was slightly elevated [29 +/- 6 micrograms/day (108 +/- 21 nmol/day); P less than 0.1], but was clearly elevated when expressed as nanomoles per mmol creatinine (37 +/- 8; P less than 0.001), again because creatinine excretion was reduced in these patients. The mean urinary To excretion was subnormal in 13 patients with hypothyroidism and was significantly (P less than 0.005) less than that in the NTI patients regardless of the manner in which the results were expressed. Analysis of pronase hydrolysates of thyroid glands obtained at autopsy from euthyroid patients suggested that the To content of the thyroid approximates only 1.2% that of T4, supporting the thesis that prior iodination of tyrosine is critical for the coupling process in the thyroid.(ABSTRACT TRUNCATED AT 400 WORDS)

Patterns off recovery of the hypothalamic-pituitary-thyroid axis in patients taken of chronic thyroid therapy.

To determine the patterns of recovery of the hypothalamic-pituitary-thyroid axis following long-term thyroid hormone therapy, TRH tests were performed on 8 euthyroid nongoitrous patients, 5 euthyroid goitrous patients, and 5 hypothyroid patients while they were taking full doses of thyroid hormone and 3, 7, 10, 14, 17, 21, 28, 35, 42, 49, and 56 days after stopping it. Serum TSH, T3, and T4 were measured before and at multiple intervals over a 4-h period after giving 500 mug TRH iv. In euthyroid non-goitrous patients, the mean duration of suppressed TSH response to TRH (maximum deltaTSH less than 8 muU/ml) was 12 +/- 4 (SE) days after stopping thyroid hormone and the mean time to recovery of normal TSH response to TRH (maximum deltaTSH greater than 8 muU/ml) was 16 +/- 5 days. None of the euthyroid nongoitrous patients ever hyperresponded to TRH; their average maximal deltaTSH was 24.5 +/- 2.2 muU/ml. Serum T4 fell below normal in 4 euthyroid non-goitrous patients, reaching lowest values at 4 to 28 days. While serum T4 was low, deltaTSH was subnormal. Normal increments of T4 and T3 after TRH occurred at 19 +/- 5 and 22 +/- 6 days, respectively. In the 5 goitrous patients, patterns of recovery of pituitary and thyroid function assessed by the same parameters were much less consistent. In the 5 hypothyroid patients, the mean duration of suppressed basal TSH and suppressed deltaTSH was 13 +/- 3 days; mean time to attain a supranormal basal TSH (greater than 8 muU/ml) was 16 +/- 4 days and to reach a supranormal deltaTSH (greater than 38 muU/ml) after TRH was 29 +/- 8 days. Following prolonged thyroid therapy in euthyroid patients, recovery of normal TSH responsiveness to TRH preceded recovery of the normal T3 and T4 response to TRH by 3 to 6 days. Basal serum TSH may be used to differentiate euthyroid from hypothyroid patients 35 days after withdrawal of thyroid therapy; the response to TRH does not improve this differentiation.

Beta-adrenergic blockade for the treatment of hyperthyroidism.

PURPOSE: To review the clinical and biochemical effects of beta-adrenergic blocking drugs on hyperthyroidism. MATERIALS AND METHODS: Studies published since 1972 were identified through a computerized search of MEDLINE and extensive searching of the bibliographies of the articles identified. Based on an understanding of the differences in beta-blocker metabolism in euthyroid and hyperthyroid patients, we reviewed the differences in pharmacokinetics and metabolic and clinical outcomes during their use in hyperthyroidism, as reported in the articles reviewed. RESULTS: beta Blockers have been used to modify the severity of the hyperadrenergic symptoms of hyperthyroidism for the past 20 years. The clinical efficacy of these agents is affected by hyperthyroid-induced alterations in their gastrointestinal absorption, hepatic metabolism, and renal excretion. The mechanisms whereby these clinical changes are effected is unknown. The agents differ in their beta 1 cardioselectivity, membrane-stabilizing activity, intrinsic sympathomimetic activity, and lipid solubility. They do not appear to alter synthesis or secretion of thyroid hormone by the thyroid gland. Their effects on thyroxine metabolism are contradictory. Decreased thyroxine to triiodothyronine conversion is caused by some, but not all, beta blockers, and this appears to correlate with membrane-stabilizing activity. There does not appear to be any alteration in catecholamine sensitivity during beta-adrenergic blockade. CONCLUSIONS: The principal mechanism of action of beta blockers in hyperthyroidism is to antagonize beta-receptor-mediated effects of catecholamines. beta Blockers are effective in treating hypermetabolic symptoms in a variety of hyperthyroid states. Used alone, they offer significant symptomatic relief. They are also useful adjuvants to antithyroid medications, surgery, and radioactive iodide treatment in patients with Graves' disease and toxic nodular goiters.

Sleep disorder in alien hand syndrome.

A 63-year-old right-handed woman developed an alien hand syndrome (AHS) after an acute infarction in the territory of the left anterior cerebral artery. The uncontrolled hand movements were present during the daytime and eventually disturbed sleep. Polysomnography revealed that these motor actions only appeared when the patient was awake. These awakenings emerged mostly from NREM sleep stage 2 during the first half of the night. There was no evidence of any epileptiform activity, dyssomnia or parasomnia. These movements were controlled making her wear an oven mitt during sleep. The temporal distribution of this motor activity seems to follow the progressive hyperpolarization of anterior horn neurons that occurs when sleep deepens. The accommodation of the grasp reflex in AHS probably helps control this unwanted motor activity.

Hemispheric specialization for speech perception in four-year-old children from low and middle socio-economic classes.

Four-year-old male and female children from low and middle socio-economic class (SEC) were presented a dichotic syllable task. Both low and middle SEC males evidenced significant right-ear advantages. Neither low nor middle SEC females evidenced a significant right-ear advantage. The similar ear advantage in the low and middle SEC populations replicates a previous study with six-year-olds and suggests that the variations in rearing conditions which occur in low and middle SEC classes does not affect hemispheric lateralization for speech perception.

Implicit word cues facilitate impaired naming performance: evidence from a case of anomia.

Word-finding difficulties observed in some patients with anomia have been attributed to an insufficient activation of phonology by semantics. There are, however, few direct tests of this hypothesis. This paper reports the case of FR, who presented with anomic aphasia following temporal lobe epilepsy and a cavernoma in the left superior temporal lobe. His anomic deficit was characterized by: (1) no apparent associated semantic impairment; (2) item consistency for accuracy and errors across different administrations; (3) accuracy strongly correlated with word frequency; and (4) a partial, albeit weak, knowledge of the gender of unnamed items. We conducted a naming experiment in which target pictures were implicitly primed by briefly presented masked words. Results showed that the prior presentation of the written target name improved accuracy. When compared with unprimed trials, the presence of the primes also increased phonological errors and decreased semantic errors. We argue that automatic phonological activation derived directly from the implicit written primes interacted with the remaining phonological input from the picture's semantic representation leading to increased accuracy and a change in the balance of error types.

Pharmacokinetics and clinical effects of atenolol in therapy of hyperthyroidism.

The pharmacokinetics of atenolol and the effect of the drug on the clinical and laboratory features of hyperthyroidism were studied in 23 patients with hyperthyroidism. In the hyperthyroid state, the time to peak plasma concentration (Tmax) occurred significantly earlier, the elimination half-life was significantly shorter, and the areas under the curve were also significantly less compared to the euthyroid state, but there was no significant difference in peak plasma concentrations (Cmax) between these states. Administration of atenolol once daily resulted in marked clinical improvement in 2 to 4 weeks. The clinical index of thyrotoxic symptoms and signs decreased from 23.2 +/- 10.8 to 8.4 +/- 5.3 (p less than 0.005). Pulse similarly decreased significantly from 93.9 +/- 15.7 to 77.8 +/- 10.5. In contrast to the marked clinical improvement, there was no change in any of the serum concentrations of thyroid hormones T4, free T4, T3 and free T3 at the time of maximal clinical effect compared to pretreatment values. These data show that the beneficial effect of atenolol in hyperthyroidism is not due to changes in thyroid hormone metabolism.

Feature characteristics of spontaneous speech production in young deaf children.

Sixty-five 6-yr-old deaf children from state supported schools were given an adaptation of the Goldman Fristoe test of articulation to assess their spontaneous speech production. Responses were measured in terms of features of manner, place, voice visibility, position, and error type and compared to imitative samples. A rank order of difficulty for each phoneme, error type, and word position is presented. Results show that of the phonemes, low back vowels, diphthongs, laterals, and voiced consonants were more easily produced. A relationship could be found between fundamental frequency, formant frequency, intensity, and phoneme production, suggesting that these variables and features may be providing the governance underlying the phonological rules in the development of speech in the deaf. Suggestions for training are given.

Assessment of language comprehension of 6-year-old deaf children.

Sixty-five 6-yr-old children from the New York State Schools for the Deaf were given the assessment of children's language comprehension (ACLC), administered orally and manually, along with a specially designed test of receptive language, the syntax screening test. The responses on the ACLC were analyzed according to selected word types. The test stimuli were analyzed and classified into a hierarchy of linguistic complexity to evaluate the children's comprehension of various linguistic structures. Results show that comprehension of word types (nouns, verbs, etc.) and linguistic structure can be orderly, producing a hierarchy of complexity similar to that found in normally hearing children. However, performance was about 3 yr behind that of normally hearing peers.

The cognitive use of language by disadvantaged and nondisadvantaged children.

The cognitive use of language was evaluated among sixth-grade disadvantaged and nondisadvantaged children by eliciting spontaneous language samples in response to a series of 14 auditory stimuli, each depicting one or more human and/or mechanical sounds. -responses were analyzed according to the following dimensions: (a) units of thought: (b) concept formation; (c) parts of the sound responded to; (d) integration; (e) manner of verbalization; and (f) identification. Disadvantaged children manifested significantly fewer units of thought than their advantage counterparts. Several significant trends were noted for several of the remaining dimensions and were discussed. The general cognitive styles of the subject groups were related to the field-dependency-independency dichotomy described in the literature by Witkin and his associates.

Speech and language assessment scales of deaf children.

Six year old deaf children with an average PTA of 105.7 dB were evaluated for speech and language skills using rating scales. Five rating scales were designed to assess language production, sign ability, overall communication skills, speech reception and speech intelligibility. Each scale incorporated five categories ranging from inability to complete ability to demonstrate a given skill. For several ratings, classroom teachers, given instruction, were asked to make judgments which were later correlated with examiner's scores, Mean ratings indicate that comprehension skills superceded performance skills. A hierarchy of ability among communication skills can be seen.

[Delayed hospitalization of the patient with acute stroke]. / Retraso en la hospitalización del paciente con ictus agudo.

INTRODUCTION AND OBJECTIVE: We analyze the main factors influencing the time delay between onset and admission to the hospital in acute stroke. PATIENTS AND METHODS: Consecutive series of 1,344 patients with acute stroke or transient ischemic attack admitted at two reference hospitals of Valencia and included at the same stroke register. Factors assessed were age, sex, vascular risk factors, stroke onset and arrival at hospital, stroke severity and stroke subtype. RESULTS: In 30% of patients the stroke onset time was unknown. 70.7% of patients with acute stroke, and known onset, arrived to the hospital in the first six hours. The median time from onset to admission was: TIA, 2 hours; cerebral infarct, 3 hours (lacunar infarcts 5 hours, non-lacunar infarcts 2 hours) and intracerebral hemorrhage, 2 hours. Patients with severe stroke arrive earlier at the hospital (p < 0.001). Neither sex, age, nor vascular risk factors influence the delay time. CONCLUSIONS: The arrival time varies with stroke subtype: patients with intracerebral hemorrhage or TIA arrive earlier than those with cerebral infarct, and non-lacunar infarcts earlier than lacunar ones. Furthermore, patients with severe stroke are admitted sooner at the hospital.

[Lacunar infarct and deep cerebral hemorrhage: a comparison of the risk factors]. / Infarto lacunar y hemorragia cerebral profunda: comparación de factores de riesgo.

INTRODUCTION: Lacunar infarcts (LI) and deep cerebral hemorrhages (DCH) have the same localization and a vasculopathy which appears to be similar, at the level of the small perforating arteries, classically attributed to arterial hypertension (AHT). OBJECTIVES: To compare the vascular risk factors of patients with lacunar ictus (LIc) and those with DCH, to try to determine how these may affect the appearance of one type of stroke or another. PATIENTS AND METHODS: We analyzed a prospective consecutive series of patients with cerebral vascular accidents (CVA), selecting 1,540 patients in the first 1,155 with a first CVA. We recorded demographic data and the following risk factors: previous transient ischemic accident (TIA), AHT, diabetes mellitus (DM), hypercholesterolemia, ischemic cardiopathy, atrial fibrillation and the presence of silent infarcts on CT. RESULTS: Two hundred and four patients had LIc and 163 had DCH. There was a significant dissociation between LIc and a history of TIA, DM, hypercholesterolemia and the presence of silent lacunar-type infarcts on CT. However, after multivariant analysis, DM did not continue to be an independent variable. Arterial blood pressure was found to be greater in the DCH group. CONCLUSIONS: The presence of different risk factors for LIc and DCH may be the key to understanding the mechanism which leads to one type or other of CVA.

[The management of acute cerebrovascular disorders at the Emergency Services at the Castellon General Hospital]. / Enfermedad vásculocerebral aguda atendida en el servicio de Urgencias del Hospital General de Castellón.

OBJECTIVE: To analyse the policy for hospital admission in the case of the patients who come to the Emergency Ward with acute cerebrovascular disorders. METHOD: The study was based on a retrospective analysis of the release reports from the Emergency Ward of Castellón General Hospital in the course of 1991, in which stroke, or transitory ischemic attack (TIA) were diagnosed. RESULTS: 514 patients were attended to who went to the Emergency Ward because of cerebrovascular disorder. Of these, 57.2% were referred to hospital, with 42% being sent home. It was observed that 10.65% (n = 23) they did not accomplish the criteria for stroke. There was an overwhelming number of cases of TIA diagnosed (50.2%) in patients who were not admitted, contrasting with only 7.5% being selected for admission. We considered possible explanations for this. CONCLUSIONS: We observed that as far as making the decision to admit a patient with acute cerebrovascular disorder, priority for admission was given in those cases which showed the worst neurological deficiencies, and had a worse prognosis as a consequence. Similarly, the older age (average 76.5 years old) was a prominent factor as far as those who were not admitted.

[A study of mortality in patients with acute cerebrovascular pathology in the Castellon General Hospital]. / Análisis de mortalidad en pacientes con patología cerebrovascular aguda en el Hospital General de Castellón.

OBJECTIVE: To analyse the hospital death rate caused by acute cardiovascular disorder and their factors conducted. METHODS: We made a retrospective review of all patients suffering from this pathology who had gone into the Casualty Ward of the Castellón General Hospital in the course of 1991: we also looked for all patients with acute cardiovascular disorder who had died in the hospital. We studied the risk factors for the patients referred using a univariant analysis, comparing those still living with those who had died. RESULTS: We find 514 patients diagnosed as having acute cardiovascular disorder, with an stroke/TIA incidence rate of 188 cases per 100,000 inhabitants. The proportion of referred patients was 52%. Among these, the death rate was 27.8%. Factors affecting the death rate were the age of the patients, the reduction in the level of consciousness, and lateral gaze at the start of the stroke. CONCLUSIONS: We believe that the high death rate in our selection was due to the severity of the strokes and the advanced age of the patients, as was in accordance with the methodology used in the gathering of data, which made it possible to include patients who died early.

Oral stereognostic ability among tongue thrusters with interdental lisp, tongue thrusters without interdental lisp and normal children.

30 children, i.e., 10 children per group, 8 yr. of age, were given an oral stereognostic test. This test of 10 geometric forms varying in shape were developed by NIDR. 47 stimuli pairs were used and 10 pairs were repeated to measure test reliability. Subjects were blindfolded and asked to respond whether Items 1 and 2, presented consecutively, were the same or different. Results indicated that both groups of tongue thrusters with and without interdental lisp scored significantly more poorly than did normal children (t = 4.68, P less than .001; t = 5.00, P less than .001), respectively. There were no significant differences, however, between tongue thrusters with and without interdental lisp (t = .33, P greater than .05). Observations indicated that normal children used the tongue tip more frequently and accurately when discriminating the geometric forms than did the other groups.