Modified-release recombinant human TSH (MRrhTSH) augments the effect of (131)I therapy in benign multinodular goiter: results from a multicenter international, randomized, placebo-controlled study.

BACKGROUND: Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). OBJECTIVE, DESIGN, AND SETTING: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. PATIENTS AND INTERVENTION: Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. MAIN OUTCOME MEASURES: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. RESULTS: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. CONCLUSION: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.

Giant cell arteritis as a cardiovascular entity.

Giant cell arteritis (GCA) is a relatively infrequent disorder that is underdiagnosed and little appraised in the field of general cardiology. However, it is important to be familiar with the clinical picture of this disease, especially because of the risk of developing fatal aortic aneurysms. If the disease is suspected after a thorough history and clinical examination combined with laboratory investigation, the diagnosis can be confirmed with (18)F-2-deoxy-glucose positron emission tomographic (FDG-PET) imaging. Early recognition of giant cell arteritis followed by prompt treatment with glucocorticosteroids will decrease the risk of developing large-vessel complications. (Neth Heart J 2009;17:281-3.).

Effect of subtotal colectomy on gastric emptying of a solid meal in slow-transit constipation.

BACKGROUND: Idiopathic slow-transit constipation is considered a panenteral disease in which patients may have delayed gastric emptying. The effects of total abdominal colectomy and ileorectal anastomosis on upper gut motility are unknown. The aim of this study was to evaluate gastric emptying in patients with idiopathic slow-transit constipation before and after subtotal colectomy. METHODS: Gastric emptying of a solid meal was studied by scintigraphic technique in 11 patients with idiopathic slow-transit constipation. The total colonic transit time was more than 72 hours in all patients studied, with delay in transit in all segments of the colon. The gastric emptying test was repeated 3 to 6 months after total abdominal colectomy and ileorectal anastomosis in ten of these patients. Before and after surgery, patients filled out a questionnaire to record upper gut symptoms. RESULTS: Solid gastric emptying was delayed (T1/2 > upper limit of normal) in 7 of 11 patients with idiopathic slow-transit constipation. Gastric emptying T1/2 was almost similar before and after surgery. Mean +/- standard deviation was 142 +/- 91 minutes before surgery and 146 +/- 67 minutes after surgery. Symptoms of vomiting and belching improved significantly after surgery. Symptoms of nausea, bloating, and pyrosis also decreased, but these changes failed to reach statistical significance. CONCLUSION: Despite a reduction in upper gut symptoms, total abdominal colectomy and ileorectal anastomosis does not improve delayed gastric emptying in patients with idiopathic slow-transit constipation.

Graves' disease induced by Na(131)I therapy for toxic multinodular goitre.

A 59-year-old woman developed manifestations of Graves' disease several months after treatment with radioiodine (Na(131)) for toxic multinodular goitre. During subsequent treatment with additional radioiodine therapy Graves' ophthalmopathy developed which was severe and required treatment with prednisone and orbital radiotherapy. The literature on development of Graves' disease following Na(131) therapy is reviewed and possible pathophysiological mechanisms are discussed. In this case, possibly the first radioiodine therapy has illicited Graves' thyrotoxicosis and the subsequently added radioiodine treatments for the persistent Graves' thyrotoxicosis led to serious ophthalmopathy. Physicians should recognise Graves-like disease as a complication of Na(131)I therapy for toxic multinodular goitre and carefully consider the timing of consecutive radioiodine therapy.

The effect of cisapride on duodenal acid exposure in the proximal duodenum in healthy subjects.

AIM: To investigate the effect of the prokinetic drug, cisapride, on fasting and postprandial acid exposure in the proximal duodenum. METHODS: Using a double-blind, placebo-controlled crossover study design, 12 healthy male volunteers were studied. After 1 week of dosing (cisapride 20 mg b.d. orally or placebo), fasting and postprandial antroduodenal pH-and pressure-recordings were made. Using a small-caliber (4 mm) catheter, containing one antral and two duodenal pH electrodes, and two antral and three duodenal pressure recording sites. Transmucosal potential difference was measured to ensure proper catheter position. Infusions of 0.1 N HCl were given in the duodenal bulb. RESULTS: Endogenous acidification of the duodenal bulb occurred more frequently during phase II and postprandially, compared to phase I (P<0.001). During phase I, alkalinization of the antrum was observed. Cisapride significantly increased the postprandial number of duodenal acidic periods (P<0.02), but shortened their duration (P<0.04). The duodenal motor response elicited by exogenous acid was lower during phase I (P<0.05). CONCLUSIONS: Antral and proximal duodenal acidity vary with the phases of the interdigestive motor complex. Cisapride shortens the individual periods of duodenal acidification.

Autoimmune hyperthyroidism occurring late after radioiodine treatment for volume reduction of large multinodular goiters.

131I treatment is an effective alternative to surgery in patients with a large, (non-)toxic, compressive goiter. Late development of hyperthyroidism after 131I therapy for nontoxic nodular goiter is considered rare. We have seen this complication in 3 of approximately 80 patients treated with radioiodine for volume reduction of a large, multinodular goiter. Three women, aged 60 to 71 years, had large, multinodular goiters causing tracheal compression. They were clinically euthyroid before 131I therapy and had normal free thyroxine (FT4) levels. Serum thyroid-stimulating hormone (TSH) levels were normal in 2 patients and undetectable in 1 patient. Patients 1 and 2 received a single dose of 86 and 48 mCi 131I, respectively. Patient 3 received 20 mCi 131I twice (interval 1 month). Clinical and biochemical thyrotoxicosis with high thyroid radioactive iodide uptake (RAIU) developed 10, 6, and 3 months after 131I therapy, respectively, although at control visits 1 to 3 months earlier, serum TSH and FT4 levels were normal. Thyrotoxicosis responded well to methimazole in all three patients. The late occurrence of thyrotoxicosis, high RAIU, and good response to methimazole argue against thyroiditis as the cause of thyrotoxicosis. Serum levels of TSH receptor antibodies, which were undetectable before therapy (patients 1 and 2), were clearly elevated in all three patients during thyrotoxicosis. This is in favor of autoimmune hyperthyroidism as the cause of thyrotoxicosis. These cases illustrate that severe autoimmune hyperthyroidism may occur several months after radioiodine treatment for nontoxic, multinodular goiter. Information about symptoms of hyperthyroidism and regular control visits in the first year after therapy are important in these patients.

Relationship between surface electrogastrography and antropyloric pressures.

The cutaneous electrogastrogram (EGG) and intraluminal antropyloroduodenal pressures were recorded in 12 healthy volunteers for 30-min periods during phase II of the interdigestive motor complex, during intraduodenal infusion of 10% triglyceride, and after intravenous erythromycin (3 mg/kg). During phase II, the frequency of the EGG was relatively constant in each individual, with a median frequency of 0.046 Hz [2.8 counts per minute (cpm)]. EGG frequency was greater (P < 0.05) than the median rate of antral pressure waves (1.8 cpm). The suppression of antral pressure waves (P < 0.05) and stimulation of isolated pyloric pressure waves (IPPWs) (P < 0.05) produced by triglyceride infusion were not associated with changes in EGG frequency compared with phase II. The frequency of the EGG and the rate of IPPWs were comparable. After erythromycin, EGG frequency was 0.03 Hz (1.8 cpm), less than during both phase II and triglyceride infusion (P < 0.05) and almost identical to the rate of antral pressure waves. Pressure waves were nearly always associated with an EGG signal. In contrast, the temporal relationship between the EGG signal and pressure waves was variable. During triglyceride infusion (r = 0.83, P < 0.001) and after erythromycin (r = 0.83, P < 0.001) there was a close (approximately 1:1) relationship between the rate of pressure waves and EGG frequency. However, there was no significant relationship (r = 0.32, not significant) between the number of pressure waves and EGG frequency frequency during pase II.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereospecific effects of tryptophan on gastric emptying and hunger in humans.

The amino acid tryptophan (tryp) is a potent inhibitor of gastric emptying in both animals and humans. Animal studies suggest that this effect may be specific for the L-enantiomer. The effects of D- and L-tryptophan on gastric emptying, intragastric distribution and appetite in humans were evaluated. Ten volunteers ingested 300 mL of either L-tryp (50 mmol/L), D-tryp (50 mmol/L) or normal saline labelled with 99mTc sulfur colloid on three occasions, separated by between 3 and 7 days. Hunger and fullness were measured with a visual analogue scale at -2, 15, 30 and 60 min after ingestion of each drink. Saline emptied faster from the stomach than both L-tryp and D-tryp (P < 0.05) and D-tryp emptied faster than L-tryp (P < 0.005). Emptying from the proximal stomach was fastest for saline (P < 0.05) and faster for D-tryp than L-tryp (P < 0.005). Emptying from the distal stomach was faster for saline than both D- and L-tryp (P < 0.05). A reduction in hunger (P < 0.05) and a non-significant trend for an increase in fullness were observed after all three drinks. At 60 min, fullness was greater after L-tryp than after ingestion of D-tryp (P < 0.01). These observations indicate that the effect of tryptophan on gastric emptying in humans is stereospecific, consistent with the concept that stereospecific receptors for tryptophan exist in the human small intestine.

Listeria meningitis presenting as enteritis in a previously healthy infant: a case report.

A previously healthy 1-year-old infant was admitted with pyrexia and mild gastro-intestinal symptoms. A blood culture, taken on admission, showed growth of Listeria monocytogenes (serotype 4b) on the 3rd day, at which time a lumbar puncture revealed a listeric meningitis. Despite the delay of antibiotic treatment, the infant never showed any neurological symptoms. She recuperated without any residual effects.

Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects.

The relationships between gastric emptying and intragastric distribution of glucose and oral glucose tolerance were evaluated in 16 healthy volunteers. While sitting in front of a gamma camera the subjects drank 350 ml water containing 75 g glucose and 20 MBq 99mTc-sulphur colloid. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide were obtained at--2, 2,5,10,15,30,45,60,75,90,105,120 and 150 min. Gastric emptying approximated a linear pattern after a short lag phase (3.3 +/- 0.8 min). The 50% emptying time was inversely related to the proximal stomach 50% emptying time (r = -0.55, p < 0.05) and directly related to the retention in the distal stomach at 120 min (r = 0.72, p < 0.01). Peak plasma glucose was related to the amount emptied at 5 min (r = 0.58, p < 0.05) and the area under the blood glucose curve between 0 and 30 min was related to the amount emptied at 30 min (r = 0.58, p < 0.05). In contrast, plasma glucose at 120 min was inversely related to gastric emptying (r = -0.56, p < 0.05) and plasma insulin at 30 min (r = -0.53, p < 0.05). Plasma insulin at 120 min was inversely related (r = -0.65, p < 0.01) to gastric emptying. The increase in plasma gastric inhibitory polypeptide at 5 min was related directly to gastric emptying (r = 0.53, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of posture on gastric emptying and intragastric distribution of oil and aqueous meal components and appetite.

BACKGROUND: It is uncertain whether gastric emptying of fat is determined mainly by its physical characteristics or chemical composition. In particular, the intragastric distribution of extracellular fat and the importance of that distribution to gastric emptying of fat is controversial. The effects of posture on gastric emptying, intragastric distribution, and appetite after ingestion of a meal containing oil and aqueous phases was evaluated. METHODS: Eleven volunteers consumed 60 mL 99mTc-(V)-thiocyanate-labeled olive oil and 290 mL 113mIn-labeled soup while sitting and while lying in the left lateral decubitus position. Hunger before and after the meal was recorded. RESULTS: In the sitting position, oil emptied from the stomach more slowly (P < 0.01) whereas in the decubitus position oil emptied faster (P < 0.01) than the aqueous phase. Oil was preferentially retained in the proximal stomach when sitting (P < 0.01), and more oil was retained in the distal stomach in the decubitus position (P < 0.05). The amount of oil that emptied in the first 180 minutes was not different between the two postures. The aqueous phase emptied much more slowly (P < 0.01) in the decubitus position. At 120 minutes and 180 minutes, subjects were less hungry (P < 0.05) in the decubitus position. In the decubitus position, hunger at 120 minutes and 180 minutes was related to the retention of oil (r > or = 0.79; P < 0.01) in the stomach. CONCLUSIONS: These results indicate that (1) gravity has a major effect on the intragastric distribution and relatively little effect on total stomach emptying of oil, and (2) postprandial hunger is affected by posture and, in the decubitus position, is inversely related to the amount of oil that has entered the small intestine.

Effects of erythromycin on gastric emptying, alcohol absorption and small intestinal transit in normal subjects.

The effects of erythromycin on gastric emptying and intragastric distribution of a mixed solid/liquid meal, alcohol absorption and small intestinal transit were examined in eight male volunteers. Each subject received, in double-blind randomized order, either erythromycin as the lactobionate (3 mg.kg-1 i.v. over 20 min) or saline immediately before the consumption of a radioisotopically labeled test meal, which consisted of 330 g minced beef and 400 ml of orange juice containing ethanol (0.5 g.kg-1 body weight) and 10 g lactulose. Erythromycin increased the rate of total stomach emptying and proximal stomach emptying of both the solid and liquid components of the meal (p < 0.001), but slowed small intestinal transit (p < 0.01). Peak blood alcohol concentrations (p < 0.01) were higher after erythromycin, with a mean increase of 40%. There was a significant inverse relationship between peak blood alcohol concentrations and the 50% emptying time for the liquid component of the meal after saline (r = -0.70, p < 0.05), but not after erythromycin (r = -0.57, p < 0.1). The total area under the venous blood alcohol concentration time curve (i.e., total absorption) was greater (p < 0.01) after erythromycin. These results suggest that: faster emptying from the proximal stomach contributes to more rapid gastric emptying induced by erythromycin, erythromycin retards small intestinal transit and that erythromycin increases the total amount of alcohol absorbed as well as the rate of alcohol absorption. These latter effects are likely to reflect more rapid delivery of alcohol to the small intestine and reduced metabolism of alcohol by the gastric mucosa.

Use of technetium-99m(V)thiocyanate to measure gastric emptying of fat.

Technetium-99m(V)thiocyanate was evaluated as a radio-pharmaceutical for measuring gastric emptying of fat. Olive oil was labeled with 99mTc(V)thiocyanate by direct extraction from acidic thiocyanate solution. After incubation with dilute HCl (pH 1.4) at 37 degrees C for 3 hr, approximately 5% of the total radioactivity eluted into the aqueous phase. When incubated with human gastric juice (pH 1.8 and 2.2), approximately 8% of the activity was detected in the aqueous phase at 3 hr. Scintigraphic studies performed in two rabbits showed that olive oil labeled with 99mTc(V)thiocyanate emptied slowly from the stomach, with a gastric half-emptying time (T50) of more than 3 hr. A low-nutrient soup labeled with 113mIn-DTPA and mixed with 99mTc(V)thiocyanate labeled oil was consumed by six human volunteers. The oil emptied much more slowly (p less than 0.02) (median T50 = 198 min) than the aqueous component (median T50 = 30 min). These observations indicate that 99mTc(V)thiocyanate is a suitable pharmaceutical to measure gastric emptying of extracellular fat.