Tissue oxygenation response to mild hypercapnia during cardiopulmonary bypass with constant pump output.

BACKGROUND: Tissue oxygenation is the primary determinant of wound infection risk. Mild hypercapnia markedly improves cutaneous, subcutaneous (s.c.), and muscular tissue oxygenation in volunteers and patients. However, relative contributions of increased cardiac output and peripheral vasodilation to this response remains unknown. We thus tested the hypothesis that increased cardiac output is the dominant mechanism. METHODS: We recruited 10 ASA III patients, aged 40-65 yr, undergoing cardiopulmonary bypass for this crossover trial. After induction of anaesthesia, a Silastic tonometer was inserted s.c. in the upper arm. S.C. tissue oxygen tension was measured with both polarographic electrode and fluorescence-based systems. Oximeter probes were placed bilaterally on the forehead to monitor cerebral oxygenation. After initiation of cardiopulmonary bypass, in random order patients were exposed to two arterial CO(2) partial pressures for 30 min each: 35 (normocapnia) or 50 mm Hg (hypercapnia). Bypass pump flow was kept constant throughout the measurement periods. RESULTS: Hypercapnia during bypass had essentially no effect on Pa(CO(2)) , mean arterial pressure, or tissue temperature. Pa(CO(2)) and pH differed significantly. S.C. tissue oxygenation was virtually identical during the two Pa(CO(2)) periods [139 (50-163) vs 145 (38-158), P=0.335] [median (range)]. In contrast, cerebral oxygen saturation (our positive control measurement) was significantly less during normocapnia [57 (28-67)%] than hypercapnia [64 (37-89)%, P=0.025]. CONCLUSIONS: Mild hypercapnia, which normally markedly increases tissue oxygenation, did not do so during cardiopulmonary bypass with fixed pump output. This suggests that hypercapnia normally increases tissue oxygenation by increasing cardiac output rather than direct dilation of peripheral vessels.

Magnesium sulphate only slightly reduces the shivering threshold in humans.

BACKGROUND: Hypothermia may be an effective treatment for stroke or acute myocardial infarction; however, it provokes vigorous shivering, which causes potentially dangerous haemodynamic responses and prevents further hypothermia. Magnesium is an attractive anti-shivering agent because it is used for treatment of postoperative shivering and provides protection against ischaemic injury in animal models. We tested the hypothesis that magnesium reduces the threshold (triggering core temperature) and gain of shivering without substantial sedation or muscle weakness. METHODS: We studied nine healthy male volunteers (18-40 yr) on two randomly assigned treatment days: (1) control and (2) magnesium (80 mg kg(-1) followed by infusion at 2 g h(-1)). Lactated Ringer's solution (4 degrees C) was infused via a central venous catheter over a period of approximately 2 h to decrease tympanic membrane temperature by approximately 1.5 degrees C h(-1). A significant and persistent increase in oxygen consumption identified the threshold. The gain of shivering was determined by the slope of oxygen consumption vs core temperature regression. Sedation was evaluated using a verbal rating score (VRS) from 0 to 10 and bispectral index (BIS) of the EEG. Peripheral muscle strength was evaluated using dynamometry and spirometry. Data were analysed using repeated measures anova; P<0.05 was statistically significant. RESULTS: Magnesium reduced the shivering threshold (36.3 [SD 0.4] degrees C vs 36.6 [0.3] degrees C, P = 0.040). It did not affect the gain of shivering (control, 437 [289] ml min(-1) degrees C(-1); magnesium, 573 [370] ml min(-1) degrees C(-1); P=0.344). The magnesium bolus did not produce significant sedation or appreciably reduce muscle strength. CONCLUSIONS: Magnesium significantly reduced the shivering threshold. However, in view of the modest absolute reduction, this finding is considered to be clinically unimportant for induction of therapeutic hypothermia.

Block-dependent sedation during epidural anaesthesia is associated with delayed brainstem conduction.

BACKGROUND: Neuraxial anaesthesia produces a sedative and anaesthetic-sparing effect. Recent evidence suggests that spinal cord anaesthesia modifies reticulo-thalamo-cortical arousal by decreasing afferent sensory transmission. We hypothesized that epidural anaesthesia produces sensory deafferentation-dependent sedation that is associated with impairment of brainstem transmission. We used brainstem auditory evoked potentials (BAEP) to evaluate reticular function in 11 volunteers. METHODS: Epidural anaesthesia was induced with 2-chloroprocaine 2%. Haemodynamic and respiratory responses, sensory block level, sedation depth and BAEP were assessed throughout induction and resolution of epidural anaesthesia. Sedation was evaluated using verbal rating score (VRS), observer's assessment alertness/sedation (OAA/S) score, and bispectral index score (BIS). Prediction probability (PK) was used to associate sensory block with sedation, as well as BIS with other sedation measures. Spearman's rank order correlation was used to associate block level and sedation with the absolute and interpeak BAEP latencies. RESULTS: Sensory block level significantly predicted VRS (PK=0.747), OAA/S score (PK=0.748) and BIS. BIS predicted VRS and OAA/S score (PK=0.728). The latency of wave III of BAEP significantly correlated with sedation level (rho=0.335, P<0.01) and sensory block (rho=0.394, P<0.01). The other BAEP parameters did not change during epidural anaesthesia. Haemodynamic and respiratory responses remained stable throughout the study. CONCLUSIONS: Sedation during epidural anaesthesia depends on sensory block level and is associated with detectable block-dependent alterations in the brainstem auditory evoked responses. Sensory deafferentation may reduce CNS alertness through mechanisms related to brainstem neural activity.

A new system to target the effect-site during propofol sedation.

BACKGROUND: We evaluated a new, integrated, covariate-adjusted, target-controlled infusion system during sedation with propofol combined with 50% nitrous oxide (N2O) and with propofol only (Air). METHODS: The protocol consisted of sequential 15-minute cycles in 20 volunteers. After a 15-minute control period, propofol was infused to an initial target effect-site concentration of 0.25 microg x ml-1 (N2O) or 1.5 microg x ml-1 (Air). Subsequently, the target effect-site concentration was increased by 0.25 (N2O) or 0.5 microg x ml-1 (Air) for 15 min This sequence was continued until the volunteers lost consciousness as defined by an Observer's Assessment Alertness/Sedation (OAA/S) score = 2. RESULTS: Venous plasma propofol concentrations at the beginning(9 elapsed minutes) and end(15 elapsed minutes) of the pseudo-steady state period differed by only 0.00 +/- 0.16 microg x ml-1 (P = 0.78) during the N2O and 0.00 +/- 0.25 microg x ml-1 (P = 0.91) during the Air trial. OAA/S scores and bispectral index values, as surrogate measures of pharmacodynamic effect, were not different during this time in either trial. The median(25th, 75th percentiles) of the median performance error (%) was -13 (-24, -1) during the N2O and -18 (-26, -9) during the Air trial. The median absolute performance error (%) was 17 (10, 24) in the N2O and 22 (12, 28) in Air trial. The divergence (%/h) was -10 (-26, 4) in the N2O and 14 (-21, 26) in Air trial. The wobble was 7 (5, 10) in the N2O and 6 (4, 8) in the Air trial. CONCLUSIONS: When tested with venous blood samples, our TCI system for propofol, using a covariate-adjusted, integrated pharmacokinetic model to target effect-site concentrations, demonstrated a clinically acceptable accuracy and stability during mild to moderate sedation.

Automated responsiveness test and bispectral index monitoring during propofol and propofol/N2O sedation.

BACKGROUND: Sedation practice, especially when non-anaesthesia personnel are involved, requires efficient anaesthetic depth monitoring. Therefore, we used prediction probability (PK) to evaluate the performance of the bispectral index (BIS) of the EEG and automated responsiveness test (ART) to predict sedation depth and loss of subject's responsiveness during propofol sedation, with and without N2O. METHODS: Twenty volunteers were studied during propofol administration with (N2O) and without (Air) N2O. The protocol consisted of sequential 15-min cycles. After a control period, propofol was infused to a target effect-site concentration of 0.25 microg/ml (N2O) or 1.5 microg/ml (Air), which was subsequently increased by 0.25 or 0.5 microg/ml, respectively, until loss of responsiveness was detected by loss of response to command [observer's assessment of alertness/sedation (OAA/S) score

Effect of intra-operative end-tidal carbon dioxide partial pressure on tissue oxygenation.

Postsurgical infection risk is correlated with subcutaneous tissue oxygenation. Mild hypercapnia augments cutaneous perfusion. We tested the hypothesis that peripheral tissue oxygenation increases as a function of arterial PCO2 in surgical patients. Twenty patients were randomly assigned to intra-operative end tidal PCO2 of 3.99 (control) or 5.99 kPa (hypercapnia). All other anaesthetic management was per protocol. Tissue oxygen partial pressure, transcutaneous oxygen tension, cerebral oxygen saturation, and cardiac output were measured. Mean (SD) subcutaneous tissue oxygen tension was 8.39 (1.86) kPa in control and 11.84 (2.53) kPa hypercapnia patients (p = 0.014). Cerebral oxygen saturation was 55 (4)% for control vs. 68 (9)% for hypercapnia (p = 0.004). Neither cardiac index nor transcutaneous tissue oxygen tension differed significantly between the groups. Mild intra-operative hypercapnia increased subcutaneous and cerebral oxygenation. Increases in subcutaneous tissue oxygen partial pressure similar to those observed in patients assigned to hypercapnia are associated with substantial reductions in wound infection risk.

Blood pressure response to thermoregulatory vasoconstriction during isoflurane and desflurane anesthesia.

BACKGROUND: Mild perioperative hypothermia produces morbid cardiac outcomes that may result from sympathetically induced hypertension. However, volatile anesthetics produce vasodilatation that may reduce the hemodynamic response to hypothermia. We tested the hypothesis that the volatile anesthetics isoflurane and desflurane blunt the normal cold-induced hypertensive response. METHODS: We analyzed prospective data from three analogous studies: 1) 10 volunteers given desflurane (2.6 volume percentage) maintained in left-lateral position; 2) nine volunteers without anesthesia or anesthetized with various doses of desflurane; and 3) eight volunteers given various concentrations of isoflurane. Mean skin temperature was reduced to 31 C, which decreased core body temperature and triggered thermoregulatory vasoconstriction. Mean arterial pressures were determined before and after hypothermia provoked intense thermoregulatory vasoconstriction. RESULTS: The hemodynamic responses to thermoregulatory vasoconstriction were similar without anesthesia and at all concentrations of desflurane and isoflurane. On average, mean arterial pressure increased 14 (SD = 5) mmHg with and without anesthesia. CONCLUSION: We conclude that thermoregulatory vasoconstriction significantly increases arterial pressure with or without isoflurane or desflurane anesthesia.

T4 but not T3 administration is associated with increased recurrence of Graves' disease after successful medical therapy.

TSH has been incriminated in Graves' disease for increasing the production of antibodies against TSH receptor (TRAb). It has been, therefore, suggested that T4 administration after successful antithyroid drug (ATD) treatment may indirectly decrease the production of TRAb and, therefore, the frequency of recurrence of hyperthyroidism. To study the role of T4 and T3 on the recurrence rate of Graves' disease 108 patients with Graves' disease (22 males, age: 49.8 +/- 14.3 yr, mean +/- SD, and 86 females, age: 41.7 +/- 12 yr) were followed-up for 24 months after successful treatment with ATD (carbimazole). During the follow-up period, patients daily received either 100 microg T4 or 25 microg T3 or placebo after random and double-blinded assignment into three groups. They were evaluated trimonthly up to 12 months and at 24 months. Plasma TRAb levels were measured at the beginning and at 12 months. At 12 months of the follow-up period, 14 out of 33 (42.4%), 6 out of 38 (15.8%), and 9 out of 37 (24.3%) patients receiving T4, T3 and placebo, respectively, recurred. Recurrence rate of T4-treated patients was statistically higher than that of the T3-treated patients or controls (p < 0.05). At the beginning of the follow-up period patients who were going to recur had significantly higher TRAb levels and goiter weight than patients who were not (p < 0.05). At 24 months of the follow-up period, from the patients who did not drop out of the study, none out of 11 (0%), 2 out of 19 (10.5%) and 1 out of 12 (8.3%) receiving T4, T3 and placebo, respectively, recurred. We conclude that T4 administration after successful ATD treatment of Graves' disease is associated with increased recurrence of hyperthyroidism as compared to the T3 or placebo administration. High TRAb levels and goiter weight at the end of ATD treatment may hint at recurrence.

Use of selective opiate receptor inhibitors to prevent postoperative ileus.

Ileus is a common postoperative complication after major abdominal surgery. Surgical manipulation of the bowel and stimulation of opiod receptor are the main causes of ileus. An investigational drug (ADL 8-2698, Alvinopam) a selective opioid antagonist with a very low oral absorption was recently introduced to clinical medicine. Unlike other opioid antagonist its activity is restricted to GI tract, it is potent, has a long duration of action, is orally effective, does not readily cross the blood-brain barrier even after intravenous administration in animals. Two randomized controlled clinical studies tested its effects in humans. Liu et al.'s study confirmed peripheral restriction of ADL 8-2698 by its lack of central effect on morphine analgesia and pupil miosis. They also showed that ADL 8-2698 prevents increases in gastrointestinal transit time. Taguchi et al. concluded that high dose (6 mg) of ADL 8-2698 archived fast recovery of gastrointestinal function, without antagonising analgesic efficacy of systemic opioid. In summary, selective inhibition of gastrointestinal opioid receptor by a peripherally restricted oral antagonist speeds recovery of bowel function, shortens times of hospitalization and preserves the analgesic effects of opiods.

Buspirone and meperidine synergistically reduce the shivering threshold.

UNLABELLED: Mild hypothermia (i.e., 34 degrees C) may prove therapeutic for patients with stroke, but it usually provokes shivering. We tested the hypothesis that the combination of buspirone (a serotonin 1A partial agonist) and meperidine synergistically reduces the shivering threshold (triggering tympanic membrane temperature) to at least 34 degrees C while producing little sedation or respiratory depression. Eight volunteers each participated on four randomly-assigned days: 1) large-dose oral buspirone (60 mg); 2) large-dose IV meperidine (target plasma concentration of 0.8 microg/mL); 3) the combination of buspirone (30 mg) and meperidine (0.4 microg/mL); and 4) a control day without drugs. Core hypothermia was induced by infusion of lactated Ringer's solution at 4 degrees C. The control shivering threshold was 35.7 degrees C +/- 0.2 degrees C. The threshold was 35.0 degrees C +/- 0.8 degrees C during large-dose buspirone and 33.4 degrees C +/- 0.3 degrees C during large-dose meperidine. The threshold during the combination of the two drugs was 33.4 degrees C +/- 0.7 degrees C. There was minimal sedation on the buspirone and combination days and mild sedation on the large-dose meperidine day. End-tidal PCO2 increased approximately 10 mm Hg with meperidine alone. Buspirone alone slightly reduced the shivering threshold. The combination of small-dose buspirone and small-dose meperidine acted synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. IMPLICATIONS: Mild hypothermia may be an effective treatment for acute stroke, but it usually triggers shivering, which could be harmful. Our results indicate that the combination of small-dose buspirone and small-dose meperidine acts synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. This combination may facilitate the induction of therapeutic hypothermia in stroke victims.

Neither nalbuphine nor atropine possess special antishivering activity.

The special antishivering action of meperidine may be mediated by its kappa or anticholinergic actions. We therefore tested the hypotheses that nalbuphine or atropine decreases the shivering threshold more than the vasoconstriction threshold. Eight volunteers were each evaluated on four separate study days: 1) control (no drug), 2) small-dose nalbuphine (0.2 microg/mL), 3) large-dose nalbuphine (0.4 microg/mL), and 4) atropine (1-mg bolus and 0.5 mg/h). Body temperature was increased until the patient sweated and then decreased until the patient shivered. Nalbuphine produced concentration-dependent decreases (mean +/- SD) in the sweating (-2.5 +/- 1.7 degrees C. microg(-1). mL; r(2) = 0.75 +/- 0.25), vasoconstriction (-2.6 +/- 1.7 degrees C. microg(-1). mL; r(2) = 0.75 +/- 0.25), and shivering (-2.8 +/- 1.7 degrees C. microg(-1). mL; r(2) = 0.79 +/- 0.23) thresholds. Atropine significantly increased the thresholds for sweating (1.0 degrees C +/- 0.4 degrees C), vasoconstriction (0.9 degrees C +/- 0.3 degrees C), and shivering (0.7 degrees C +/- 0.3 degrees C). Nalbuphine reduced the vasoconstriction and shivering thresholds comparably. This differs markedly from meperidine, which impairs shivering twice as much as vasoconstriction. Atropine increased all thresholds and would thus be expected to facilitate shivering. Our results thus fail to support the theory that activation of kappa-opioid or central anticholinergic receptors contribute to meperidine's special antishivering action.

Automated responsiveness test (ART) predicts loss of consciousness and adverse physiologic responses during propofol conscious sedation.

BACKGROUND: The authors evaluated a device designed to provide conscious sedation with propofol (propofol-air), or propofol combined with 50% nitrous oxide (N2O; propofol-N2O). An element of this device is the automated responsiveness test (ART), a method for confirming that patients remain conscious. The authors tested the hypotheses that the ART predicts loss of consciousness and that failure to respond to the ART precedes sedation-induced respiratory or hemodynamic toxicity. METHODS: The protocol consisted of sequential 15-min cycles in 20 volunteers. After a 15-min control period, propofol was infused to an initial target effect-site concentration of 0.0 microg/ml with N2O or 1.5 microg/ml with air. Subsequently, the propofol target effect-site concentration was increased by a designated increment (0.25 and 0.5 microg/ml) and the process repeated. This sequence was continued until loss of consciousness, as defined by an Observer's Assessment of Alertness/Sedation (OAA/S) score of 10/20 or less, or until an adverse physiologic event was detected. RESULTS: The OAA/S score at which only 50% of the volunteers were able to respond to the ART (P50) during propofol-N2O was 11.1 of 20 (95% confidence interval [CI]: 10.6-11.8); the analogous P50 was 11.8 of 20 (95% CI: 11.4-12.3) with propofol-air. Failure to respond to the ART occurred at a plasma propofol concentration of 0.7 +/- 0.6 microg/ml with propofol-N2O and 1.6 +/- 0.6 microg/ml with propofol-air, whereas loss of consciousness occurred at 1.2 +/- 0.8 microg/ml and 1.9 +/- 0.7 microg/ml, respectively. There were no false-normal ART responses. CONCLUSION: The ART can guide individual titration of propofol because failure to respond to responsiveness testing precedes loss of consciousness and is not susceptible to false-normal responses. The use of N2O with propofol for conscious sedation decreases the predictive accuracy of the ART.

The hypothalamic-pituitary-thyroid axis and the female reproductive system.

Increasing evidence derived from experimental and clinical studies suggests that the hypothalamic-pituitary-thyroid axis (HPT) and the hypothalamic-pituitary-ovarian axis (HPO) are physiologically related and act together as a unified system in a number of pathological conditions. The suggestion that specific thyroid hormone receptors at the ovarian level might regulate reproductive function, as well as the suggested influence of estrogens at the higher levels of the HPT axis, seems to integrate the reciprocal relationship of these two major endocrine axes. Both hyper- and hypothyroidism may result in menstrual disturbances. In hyperthyroidism the most common manifestation is simple oligomenorrhea. Anovulatory cycles are very common. Increased bleeding may also occur, but it is rare. Hypothyroidism in girls can cause alterations in the pubertal process; this is usually a delay, but occasionally it can result in pseudo-precocious puberty. In mature women hypothyroidism usually is associated with abnormal menstrual cycles characterized mainly by polymenorrhea, especially anovulatory cycles, and an increase in fetal wastage.

The predominant form of non-toxic goiter in Greece is now autoimmune thyroiditis.

Endemic non-toxic goiter (NTG) in Greece has been attributed primarily to iodine deficiency. Thirty years ago about 60% of the prepubertal boys and girls examined in endemic goiter regions presented with NTG and among them thyroid autoimmunity was rarely detected. Although iodine supplementation has corrected this deficiency during the past 30 years, new cases of NTG still appear. To evaluate the prevalence and type of NTG and the effect of iodine supplementation on them in Greece at present, we performed two cross-sectional clinical studies and a retrospective pathology one: (i) thyroid gland volume and urinary iodine excretion (UIE) were assessed in a representative sample of 1213 schoolchildren from previously endemic and non-endemic regions; (ii) serum thyroxine, tri-iodothyronine, TSH, thyroid autoantibodies (AAB) (anti-thyroid peroxidase and anti-thyroglobulin antibodies) and UIE (in 60 patients) were measured in 300 consecutive patients with NTG from Athens and Heraklion; and (iii) we compared the prevalence of autoimmunity among fine needle aspiration smears of benign thyroid pathologies performed by the same pathologist between 1985 and 1986 (975 cases) and between 1994 and 1995 (2702 cases). We found that 12. 5% of the schoolchildren examined in regions with a previous history of endemic goiter had NTG, whereas this percentage was only 1.7% in areas without such a history. In Athens (61.6%) and Heraklion (58. 5%) a substantial number of NTG patients were AAB positive and biochemically hypothyroid. UIE in Athens did not differ between patients with autoimmune goiter (ATG) and simple goiter. The prevalence of autoimmune stigmata in pathology smears has increased from 5.94% (years 1985-1986) to 13.91% (years 1994-1995) (P<0.05). We conclude that: (i) the persistence of endemic goiter in regional foci despite iodine deficiency correction suggests a possible role for a naturally occurring goitrogen; (ii) ATG is the predominant form of NTG in Greece nowadays; and (iii) the five-fold decrease in the prevalence of NTG during the past 30 years followed by the increase of ATG may support the relative character of the latter.

The cerebral effects of carbon dioxide during digital subtraction angiography in the aortic arch and its branches in rabbits.

PURPOSE: We studied the neurotoxicity of carbon dioxide as a contrast agent in the central nervous system by performing CO2 digital subtraction angiography (DSA) in the aortic arch and its branches in experimental animals. METHODS: Twenty-five rabbits underwent intraarterial CO2 DSA while under general anesthesia, during which 50 angiograms were obtained after administration of 3 mL/kg CO2. MR imaging was performed before and after the angiographic procedure. The animals were killed 12 hours later and their brains examined macroscopically and microscopically. RESULTS: Three animals died of a cause irrelevant to CO2. No animal had clinical symptoms of hemiplegia or stroke. Neither MR imaging nor macroscopic and microscopic examination of the brain revealed any ischemic infarct hemorrhage, thrombosis, or foci of necrosis. CONCLUSION: The absence of neurologic symptoms, the lack of pathologic findings at MR imaging, and the negative pathologic findings in the brain encourage further research on CO2 neurotoxicity of the central nervous system and support its application in the imaging of intracranial vessels.

Hyperthyroidism in McCune-Albright syndrome with a review of thyroid abnormalities sixty years after the first report.

We present a patient with hyperthyroidism associated with McCune-Albright syndrome (MAS). MAS is a sporadic genetic disease characterized by polyostotic fibrous dysplasia, cafe au lait cutaneous spots and endocrinopathies (peripheral precocious puberty, thyroidopathies, acromegaly, etc.). It is caused by an activating mutation of the gene for the Gs alpha membrane-associated protein, which mediates the thyrotropin (TSH)-induced and other hormone-induced activation of adenylyl cyclase. A 13-month-old girl was diagnosed with MAS. Precocious puberty was treated initially with testolactone and later with oophorectomy. Subclinical hyperthyroidism was detected biochemically at birth, and 10 months later, it became clinically evident, albeit mild, with absence of goiter. A concomitant liver dysfunction precluded treatment with thionamides and she was sporadically treated with beta-blockers. The combination of increased free thyroxine (T4) and triiodothyronine (T3) with low plasma thyrotropin (TSH) levels in the absence of thyroid-stimulating autoantibodies persisted until the age of 6 years, when she was referred to our unit. Hyperthyroidism was then clinically evident with cardiac hyperactivity, and it was cured with administration of radioiodine (131I). Thyroid disease is the second most common endocrinopathy associated with MAS, and since 1936, 63 cases of thyroidopathies have been described, including 19 nodular (14 with and 5 without hyperthyroidism) and 23 diffuse (20 with and 3 without hyperthyroidism) goiters, and 18 cases of hyperthyroidism without goiter. The previously described somatic activating mutation of the gs alpha gene in the ovaries, the liver and the peripheral blood of our patient, in the absence of stigmata, autoimmunity might be incriminated for the secretory and mitotic activation of the thyroid gland. We suggest the treatment of choice of hyperthyroidism in MAS patients should be 131I administration because: (a) hyperthyroidism is very likely to recur after withdrawal of antithyroid medication; (b) the morbidity of these patients is elevated; (c) oophorectomized patients do not need to be advised to avoid procreation during the months after 131I administration; and (d) finally, even in the usual cases of hyperthyroidism in childhood, 131I treatment is becoming more popular worldwide.