Ethanol injection into autonomous thyroid adenomas.
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Biomedical subjects
Publications and source records attributed to J M Hansen.
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Renal function was investigated in eight normal subjects before and during infusion of dopamine (3 micrograms.kg-1 x min-1) at sea level (SL) and at high altitude (HA, 4,350 m). Lithium clearance (CLi) was used as an index of proximal tubular outflow. HA significantly increased arterial pressure, heart rate, and plasma norepinephrine. Effective renal plasma flow (ERPF) decreased at HA by 10% (P < 0.05), but glomerular filtration rate (GFR), CLi, sodium clearance (CNa), and urine flow remained unchanged compared with SL. Dopamine at SL and HA increased ERPF by 47% (P < 0.001) and 30% (P < 0.01), respectively, but the increase at HA was smaller than that at SL (P < 0.05). Dopamine increased GFR only at SL. CLi and CNa increased by 29% (P < 0.001) and 108% (P < 0.001) at SL and by 23% (P < 0.01) and 108% (P < 0.001) at HA. Whereas dopamine at SL increased urine flow by 46% (P < 0.01), this response was abolished at HA, and free water clearance decreased (P < 0.05). The decreased ERPF at HA suggests a constriction of the renal arterioles secondary to increased adrenergic nervous activity. Although the effect of dopamine on ERPF was attenuated in hypoxia, dopamine-induced increases in CLi and CNa remained unaltered, suggesting that natriuresis in both environments was secondary to an increased outflow from the proximal tubules. The absence of a diuretic response to dopamine at HA seemed to be caused by an effect on distal tubular function.
In order to determine observer variation in the assessment of the thyroid gland by ultrasonography, two specialists (one endocrinologist and one radiologist) independently evaluated 76 thyroid glands, and assessed the sonogram as homogeneous, inhomogeneous, containing a solitary solid lesion or a solitary cyst in each of 152 thyroid lobes. The observed agreement between the two observers ranged from 0.80 to 0.91. By the use of the kappa coefficient the observed agreement was adjusted for change agreement. Kappa can vary from -1 (total disagreement) to +1 (total agreement) and kappa values between 0.55 and 0.60 were found. Among 152 lobes a solitary solid lesion, i.e. a nodule, was found in 22 lobes by the two observers; however, they only agreed on a classification in 10 lobes (45%). Clinicians should be aware of the moderate agreement between observers in thyroid ultrasonography.
The interobserver variation among three experienced endoscopists in the endoscopic diagnosis and grading of reflux esophagitis was investigated in 150 dyspeptic patients. The interobserver variation was analyzed with kappa statistics to correct for the extent of agreement expected by chance alone. The observers diagnosed esophagitis in 22.7%, 32.7%, and 35.3% of the patients, respectively (p < 0.0002). Kappa values for grade-1 esophagitis varied from 0.34 to 0.47, a level generally considered to signify poor agreement, and despite partial agreement on the diagnosis in the individual patient there was almost complete disagreement on the features used to characterize grade 1. Kappa values for diagnosing erosive esophagitis (grades 2-4) were 0.68-0.79. Considering all three observers and all grades of esophagitis (grades 0-4) the overall chance-corrected agreement was 0.55. In patients with low-grade esophagitis without reflux-like dyspepsia and when the observers expressed uncertainty in the diagnosis, the agreement rates were particularly poor. Due to a large chance-corrected interobserver variation, the endoscopic diagnosis grade 1 esophagitis is not reliable and thus may be problematic as a selection criterion for clinical trials. Interobserver variation on the presence of erosive/ulcerative esophagitis is acceptable and comparable to the level for peptic ulcer.
Eradication of Helicobacter pylori is associated with a reduced recurrence of duodenal ulcer (DU). The relationship between H. pylori and DU has been interpreted as causal, but the evidence has been criticized for methodologic reasons. To ascertain whether an antibiotic with no effect on epithelial-cell integrity prevents DU recurrence, we conducted a randomized double-blind trial of phenoxymethylpenicillin (PEN), 2.4 twice daily, and placebo (PLA). Patients with an active DU and positive H. pylori culture from antral biopsy specimens were treated with 40 mg omeprazole daily for 4 weeks, but at week 2 they were allocated at random to PEN (85 patients) or PLA (85 patients) for up to 14 weeks. Those without recurrence during this treatment were followed up for another 6 months. Endoscopy and H. pylori culture were performed at the end of the treatment period and at the end of follow-up, and in between if ulcer symptoms recurred. During the treatment period the ulcer relapse rate was 5 of 58 (9%) in the PEN group and 34 of 68 (50%) in the PLA group (P < 0.0001, log-rank test), with 53% and 14%, respectively, of the patients in the two groups being H. pylori-negative. The relapse rate in the PEN group did not differ between H. pylori-negative and H. pylori-positive patients. The recurrence rate in the PEN group remained low for another 5 months but then approached the rate in the PLA group. The prevalence of H. pylori-negative patients at the end of follow-up was 20% in the PEN group and 10% in the PLA group. These data provide strong evidence that DU has a bacterial cause, with H. pylori as the likely agent.
OBJECTIVE: The purpose of the present experiment was to evaluate functional biomechanics of the lesioned area in rabbits subjected to surgically placed vertebral lesions which may mimic a subluxation. It was hypothesized that wedging a bar between three adjacent vertebrae would lead to visual and palpatory alterations and also to a decrease in range of motion (ROM) at the affected segments. DESIGN: A controlled laboratory experiment was performed to measure directly ROM and to evaluate the functional and anatomic relationships of vertebrally lesioned rabbits. SUBJECTS: Twelve healthy adult New Zealand rabbits of either sex, weighing 3-5 kg, were maintained in the PCC animal facilities under normal husbandry conditions. Six operated controls and six experimentally lesioned rabbits were available for analysis. INTERVENTIONS: Rabbits were anesthetized and a vertebral lesion surgically placed at various locations along the thoracic spine. A stainless steel bar was implanted to produce a putative partial fixation and misalignment of three adjacent segments. The middle spinous process was forced contralaterally and slightly rotated relative to the adjacent two. At intervals ranging from a few weeks to several months postsurgery, the animals were evaluated for spinal ROM and also by visual and palpatory means for spinal misalignment. MAIN OUTCOME MEASURE: X rays, using rubber foam molds to standardize positioning, were taken pre- and postsurgery to measure ROM. Statistical analysis was made to compare ROM between the lesioned and adjacent areas of experimental and control animals. RESULTS: All but one of the experimental animals, but none of the controls, showed some reduced ROM on palpation at autopsy. Radiographic measures, however, showed that the ROM in the experimental animals as a group was not significantly reduced compared to control values, nor was there a significant ROM decrease compared to nonlesioned motor units within the experimental group. In some individual animals, however, there was a significant decrease in spinal ROM. CONCLUSIONS: This study failed to demonstrate any effect of the vertebral lesion on spinal ROM as measured radiographically, although by palpation the lesioned area did appear to be partially fixated in most animals. This surprising result may perhaps be explained by the large variability in measurements, the small number of subjects used or by inadequacies of X-ray positioning. Further work on biomechanical effects of vertebral lesions is clearly required.
Peptic ulceration is a common condition and is associated with considerable expense. Introduction of H2-blockers in the latter part of the nineteen seventies offered a new and effective therapeutic alternative for the patient with chronic peptic ulceration. On the basis of a review of the literature, the present authors have attempted to assess the consequences of the introduction of H2-blockers for the expenses of peptic ulceration. Introduction of medication is found to have reduced the expenses involved in peptic ulceration on account of elective operations but on account of the increased costs of medication, the total direct costs involved in the treatment of peptic ulceration have possibly increased after the introduction of the medication. Attempts are made to compare this with the reduction in the indirect costs achieved by reduction in loss of production involved by fewer early retirals and sick leaves on account of peptic ulceration, fewer deaths connected with peptic ulceration among young persons and, in general, improved quality of life for patients with peptic ulceration although it is difficult to provide a valid estimation of the savings involved.
OBJECTIVE: We investigated possible changes in the pituitary-thyroid axis after radioactive iodine (RAI) treatment of multinodular non-toxic goitre. DESIGN: Consecutive patients with multinodular non-toxic goitre, who remained euthyroid after radioactive iodine (RAI) treatment. PATIENTS: Twenty-three women with multinodular non-toxic goitre were followed after treatment with RAI. MEASUREMENTS: Free T4 index (FT4I), FT3I, free T4, SHBG (immunoradiometric assay), and a third-generation TSH assay (chemiluminetric assay) TSH were measured. RESULTS: Three weeks after RAI treatment TSH had decreased and SHBG increased (P < 0.05). Only 2/18 patients actually had suppressed TSH values, while 12/18 had values in between euthyroid and toxic levels. Trend analysis from 1.5 to 24 months after RAI treatment demonstrated a progressive increase in TSH (P < 0.01) and gradual decrease in SHBG (P < 0.02). No changes in FT4I, FT3I, or free T4 were found. CONCLUSION: A third-generation TSH assay gave detailed information about changes in thyroid status when TSH was below normal values. FT4I, FT3I, and free T4 seem to be less sensitive parameters than TSH and SHBG for recording subtle changes in thyroid status after RAI treatment of nodular non-toxic goitre. We demonstrated that changes in the pituitary-thyroid axis continue for a long time after RAI treatment of multinodular non-toxic goitre. These patients should be followed up in order to detect possible late hypothyroidism.
Renal effects of altitude hypoxia are unclear. Renal and hormonal function was investigated in eight males at rest and during graded exercise at sea level (SL) and 48 h after rapid ascent to 4,350 m (HA). HA did not change resting values of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), sodium clearance (CNa), urine flow, or lithium clearance (CLi), which was used as an index of proximal tubular outflow. At rest, HA increased plasma norepinephrine concentration and decreased plasma concentrations of renin and aldosterone. Exercise decreased ERPF similarly in both environments. Normoxic exercise progressively reduced GFR, but at HA GFR only decreased during heavy exercise. This resulted in a higher filtration fraction during light and moderate hypoxic exercise. However, calculated absolute proximal reabsorption rate (GFR-CLi) at HA was higher during low-intensity exercise, and there were no significant differences between exercise-induced decreases in CLi, CNa, and urine flow at HA compared with SL. Exercise gradually increased plasma norepinephrine, but values were higher at HA during light and moderate exercise. The small changes in the renal response to low-intensity hypoxic exercise may be secondary to increased adrenosympathetic activity. However, antidiuretic and antinatriuretic effects of exercise were maintained in hypoxia and in both environments seemed to be the consequence of decreased proximal tubular outflow. The results demonstrate that renal glomerular and tubular function is well preserved in acute hypoxia despite marked hormonal changes.
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With the object of investigating whether the release of H2-blockers and sucralfate for over-the-counter sale in 1989 in Denmark and the simultaneous discontinuation of the general subsidy for potent ulcer medicine have had any influence on the frequency of hospitalisation for ulcer complications, the number of these were investigated in the County of Funen during a nine-year period prior to these alterations. The number of hospitalisations on account of ulcer complications during the first year after the alterations and thereafter were assessed on the basis of the prior tendency. In addition, the characteristics of the patients were assessed by a retrospective review of the case reports for the one-year periods before and after the alterations in the dispensing rules. The number of hospitalisations on account of ulcer complications in the County of Funen rose by 45% during the period 1.4.1980-31.3.1989. No increases in the number of hospitalisations after the alterations could be demonstrated. The number of patients admitted to Odense Hospital with ulcer complications and their characteristics are, similarly, unchanged after the alterations. Three case histories are, however, registered in which the alterations may have influenced the development of the ulcer complications. There appear to be good ground to continue registration of ulcer complications with the object of investigating the long-term consequences of these alterations particularly if potent ulcer medicine is used to a greater extent as over-the-counter medicine.
In spring 1989, H2-receptor blockers and sucralfate were released for sale over-the-counter in Denmark and, simultaneously, the automatic National Health Insurance subsidy for all ulcer medicine was discontinued. The consequences of these alterations for the pressure on the diagnostic measures for upper dyspepsia are assessed by analysis of the number of referrals for gastroscopy, outpatient history-taking or radiographic examination of the stomach and oesophagus. The consequences for the consumer pattern were assessed in questionnaire investigations both to the practitioners who prescribed ulcer medicine before the alterations were introduced and also to patients who bought ulcer medicine after these alterations. Only approximately 3% of ulcer medicine is sold directly over-the-counter without medical assessment or control. No problems in safety were observed as regards incorrect treatment or delayed diagnosis. The relative proportion of patients with demonstrated indications for necessary ulcer medicine has increased after the alterations primarily on account of decrease in employment of medicine in therapeutic trials. This does not appear, however, to have resulted in any marked increased in the diagnostic possibilities. Potent ulcer medicine has not become generally accepted as over-the-counter medicine. The health and health-economic consequences should, therefore, be followed up for a more prolonged period.
OBJECTIVE: It has been postulated that a decrease in thyroid size can be achieved by thyroxine treatment in patients with goitrous Hashimoto's thyroiditis but no objective data are available. We have therefore investigated the influence of thyroxine treatment on ultrasonically determined thyroid size. We also measured serum antithyroid peroxidase antibodies. DESIGN: Consecutive patients with goitrous Hashimoto's thyroiditis was studied. PATIENTS: Thirteen women participated; all had goitrous thyroiditis. TREATMENT: To render them euthyroid thyroxine was given for 24 months. MEASUREMENTS: Thyroid size was measured ultrasonically and antithyroid peroxidase antibodies were measured using a commercial radioimmunological method. RESULT: Concomitant with the gradual increase in serum free thyroxine and free triiodothyronine index values and a fall in serum thyrotrophin level, a gradual decrease in thyroid volume from 50.4 +/- 6.8 ml (mean +/- SEM) to 34.1 +/- 5.7 ml (32%), P less than 0.001 was demonstrated. Antithyroid peroxidase antibodies were present in high concentrations in all subjects but the mean serum level was not significantly changed at 24 months after initiation of treatment. CONCLUSION: A clinically significant reduction in thyroid volume related to normalization of thyroid function but unrelated to changes in antithyroid peroxidase antibody can be achieved during L-thyroxine treatment of hypothyroid goitrous Hashimoto's thyroiditis.
In order to evaluate the reliability of clinical assessment of the thyroid gland, two specialists in endocrinology and two younger doctors independently examined 53 patients twice, and assessed whether they had a diffuse goitre, a multinodular goitre, a solitary nodule or a normal gland. In 30% of the patients all four observers were in agreement, whereas in 47% and 23% of the patients, two and three different diagnoses were given, respectively. Inter-observer variation was determined and kappa values between -0.04 and 0.54 were found. Intra-observer variation was smaller, revealing kappa values between 0.44 and 1.00. The present study suggests that clinical assessment of the thyroid gland may lead to misclassification of the type of thyroid disease, and thereby to a less than optimal choice of therapy.
In a retrospective questionnaire-study, we have attempted to elucidate how open access endoscopy influences management of dyspeptic patients, with special focus on young patients (less than 40 year), since the proportion of examinations with findings not requiring medical treatment are consistently reported higher in this age group. During a one-year period, 436 patients referred for open access endoscopy and their general practitioners completed questionnaires giving details of medical treatment, consultation rate for dyspepsia and global assessment before and 6-18 months after the endoscopy. Relevant changes in medical treatment (stopped in patients with no or minor abnormalities or started in patients with major abnormalities) was found for 27% of the patients, irrespective of age group. The result of the endoscopy provided reassurance for 70% of the patients with no or minor abnormalities. Reassurance was coupled with a lower consultation rate and with fewer symptoms. Altogether, 83% of the young patients with no or minor abnormalities had a positive outcome of the endoscopy. As the endoscopy service introduced relevant and lasting prescription habits and reduced consultation rates at general practitioners, also for younger dyspeptic patients with no or minor abnormalities, the strategy generally proposed of a trial with H2-receptor antagonists before considering referral for endoscopy should be subjected to formal clinical trial evaluating all relevant levels of efficacy.
1. Amino acids have been used to test renal reserve filtration capacity. Previous studies suggest that amino acids increase glomerular filtration rate (GFR) by reducing distal tubular flow and tubuloglomerular feedback activity. 2. Glomerular function and the renal tubular handling of sodium during infusion of amino acids was studied in 12 normal volunteers. 3. Clearance of sodium (CNa) was unchanged. Effective renal plasma flow increased slightly, but significantly, by 9% (P less than 0.05). GFR was increased by 13% (P less than 0.001). Clearance of lithium (CLi) (used as an index of proximal tubular outflow) increased by 38% (P less than 0.001). Calculated absolute proximal reabsorption (GFR-CLi) remained unchanged. Fractional proximal reabsorption [1-(CLi/GFR)] was decreased by 10% (P less than 0.001). Calculated absolute distal sodium reabsorption [(CLi-CNa) x PNa, where PNa is plasma sodium concentration] increased by 40% (P less than 0.001). Plasma renin concentration did not change significantly. 4. The results suggest that amino acids increase GFR by a primary effect on renal haemodynamics or, less likely, by reducing the signal to the tubuloglomerular feedback mechanism. The increase in proximal tubular outflow was compensated for in the distal tubules, so that the sodium excretion rate remained unchanged.
1. Using the renal clearance of lithium (CLi) as an index of proximal tubular outflow of sodium and water, together with simultaneous measurements of effective renal plasma flow, glomerular filtration rate (GFR) and sodium clearance (CNa), renal function and the tubular segmental reabsorption rates of sodium and water during dopamine infusion (3 micrograms min-1 kg-1) were estimated in 12 normal volunteers. 2. CNa increased by 128% (P less than 0.001). Effective renal plasma flow and GFR increased by 43% (P less than 0.001) and 9% (P less than 0.01), respectively. CLi increased in all subjects by, on average, 44% (P less than 0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P less than 0.001), and estimated absolute proximal reabsorption rate (GFR-CLi) decreased by 8% (P less than 0.01). Absolute distal sodium reabsorption rate [(CLi-CNa) x PNa, where PNa is plasma sodium concentration] increased (P less than 0.001), and fractional distal sodium reabsorption [(CLi-CNa)/CLi] decreased (P less than 0.001). 3. It is concluded that natriuresis during low-dose dopamine infusion is caused by an increased outflow of sodium from the proximal tubules that is not fully compensated for in the distal tubules.
1. The effect of severe hypothyroidism on the pharmacokinetics and pharmacodynamics of oxazepam 15 mg given orally (n = 10) and the metabolism of paracetamol 750 mg given intravenously (n = 8) was investigated before and after treatment with levothyroxine. 2. The median total and unbound clearance of oxazepam increased significantly during the study period from 0.78 ml min-1 kg-1 (0.40-1.25) to 1.22 ml min-1 kg-1 (0.66-1.94) and from 9.3 ml min-1 kg-1 (5.2-14.2) to 15.9 ml min-1 kg-1 (7.8-21.8), respectively (P less than 0.01). 3. The elimination half-life of oxazepam was prolonged by hypothyroidism to a median (range) value of 9.3 h (5.4-21.9) compared with 7.5 h (4.8-10.5) in the euthyroid state (P less than 0.05). 4. Hypothyroidism did not affect the protein binding of oxazepam; median values of the free percentage being 8.2% as compared with 7.7% when euthyroid. 5. The median (range) clearance of paracetamol under hypothyroid conditions was 3.12 ml min-1 kg-1 (1.64-4.40) and 4.70 ml min-1 kg-1 (3.18-5.70) following replacement therapy (P less than 0.01). This increase was associated with a comparable increase in the partial clearance to the glucuronide metabolite: 1.86 ml min-1 kg-1 to 2.70 ml min-1 kg-1. 6. Hypothyroidism was associated with decreased performance in a finger tapping test that was exacerbated by oxazepam. When the patients were euthyroid oxazepam did not produce any effect.