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Biomedical subjects

J M Hansen

Publications and source records attributed to J M Hansen.

At least 19 recordsLinked to original sources
PubMed1995

Consistent absorption of cyclosporine from a microemulsion formulation assessed in stable renal transplant recipients over a one-year study period.

To evaluate the pharmacokinetic properties of the new microemulsion formulation of cyclosporine (Sandimmun Neoral), a double-blind, prospective study in stable renal transplant recipients was performed. The patients were randomized on a 4:1 basis either to receive Sandimmun Neoral (n = 45) or continue on regular Sandimmun (n = 12). Before randomization, a steady-state pharmacokinetic profile study was performed in all patients while they were still on regular Sandimmun. Pharmacokinetic assessments were then performed after 8 and 12 weeks and after 1 year. A milligram-to-milligram dose conversion was shown to be adequate to maintain the patients within a predefined target therapeutic window. Changes in pharmacokinetic parameters after conversion to Sandimmun Neoral were consistent with an increased rate and extent of cyclosporine absorption from the Neoral formulation. This was reflected by a shorter time to reach peak concentration and also by a mean increase in peak concentration by 67%, and an overall mean increase in drug exposure (area under the curve) by 34%. These findings were also confirmed 1 year after conversion. Furthermore, significantly reduced intraindividual variability in pharmacokinetic parameters was found, as well as improvements in the correlation between trough concentrations and area under the curve after conversion to Sandimmun Neoral. In conclusion, our results indicate an improved and consistent absorption of cyclosporine from the Neoral formulation, which should make clinical management easier and safer.

Absorption↗
PubMed1995

[Cardiovascular effects of a calcium channel blocker in hypoxia caused by altitude].

OBJECTIVE: High altitude pulmonary oedema can be successfully treated and prevented by calcium channel blockers. Moreover, calcium entering in the cells could explain the congestive phenomena of acute mountain sickness (AMS). These findings led us to study the action of a calcium channel blocker, isradipine, in the prevention of non-complicated AMS. METHODS: In a double blind randomized study, 20 healthy volunteers received 5 mg of isradipine (n = 6) or placebo (n = 6) for 8 days. After 5 days of treatment in normoxia, the subjects were rapidly transported to an altitude of 4350 m. The efficiency of the treatment was then estimated by the AMS symptom score, haemodynamic parameters and renal function. RESULTS: The administration of isradipine did not significantly modify AMS symptom score nor most of other parameters measured in high altitude hypoxia. Heart rate was an average of 15 b/min lower in the isradipine group, probably because of a direct action of isradipine on the sinus node. Otherwise, the effects of hypoxia were similar in both groups and were in accordance with the literature. There was no clear explanation for the increase in cardiac output and stroke volume when the subjects moved from supine to standing position. Renal blood flow, measured by Doppler or para-aminohippuric acid clearance was not modified by hypoxia. Cerebral blood flow was elevated, due to the direct vasodilator effect of hypoxia. However this increase did not seem to be the main mechanism responsible for the congestive phenomena. On the other hand, the increase in capillary permeability (demonstrated by the increased transcapillary escape rate of albumin, and albuminuria) appeared to play a major role in the pathogenesis of AMS and high altitude cerebral oedema. Isradipine had no protective effect on these phenomena and its use should be restricted to the treatment of high altitude pulmonary oedema.

Adult↗
PubMed1995

[Survey of patients with upper gastrointestinal tract dyspepsia. A trial of H2 blocker therapy or endoscopy--a randomized trial of 2 management methods].

This study compared two strategies for the management of dyspepsia: therapy based on prompt endoscopy (group 1) vs an empirical treatment strategy with diagnostic endoscopy only in case of therapeutic failure or symptomatic relapse within one year (group 2). Patients without jaundice, bleeding, anaemia, or a previously diagnosed ulcer and with symptoms severe enough to justify empirical H2-blocker therapy were included. Symptoms, drug consumption, and sick-leave days were evaluated through monthly diaries. Patients with non-organic dyspepsia did not receive ulcer drugs. Of 414 patients randomized, 373 completed one year follow-up. In 68 (33%) of the 208 group 1 patients organic disease was found at endoscopy (ulcer in 45 patients). Endoscopy was eventually performed in 136 (66%) of 206 group 2 patients. Case selection for endoscopy was not improved by the empirical treatment strategy since the diagnostic profile was not altered and 40% of the presumed ulcer cases remained undiagnosed. After one year no differences in symptoms or quality of life measures were found. The empirical treatment strategy in dyspepsia was associated with higher costs, mainly due to increases in number of sick-leave days and in ulcer drug use. Prompt endoscopy is a cost-effective strategy in dyspeptic patients with symptoms severe enough to justify H2-blocker treatment.

Adult↗
PubMed1995

Is calculation of the dose in radioiodine therapy of hyperthyroidism worth while?

OBJECTIVE: The persistent controversy as to the best approach to radioiodine dose selection in the treatment of hyperthyroidism led us to perform a study in order to compare a fixed dose regime comprising doses of 185 370 or 555 MBq based on gland size assessment by palpation only, with a calculated 131I dose based on type of thyroid gland (diffuse, multinodular, solitary adenoma), an accurate thyroid volume measurement, and a 24-hour 131I uptake determination. DESIGN: Prospective randomized study. PATIENTS: Two hundred and twenty-one consecutive hyperthyroid patients referred for 131I treatment. Four Patients who died for reasons unrelated to hyperthyroidism, 7 lost to follow-up and 47 who did not receive antithyroid drugs after treatment, were excluded. The remaining 163 patients (143 women) were studied, divided into subgroups according to the type of gland. They all received antithyroid drugs prior to 131I treatment and this was resumed 7 days after treatment for a period of 3 weeks. MEASUREMENTS: Thyroid function variables were determined approximately 2 weeks before 131I treatment, and again 1, 2, 3, 6, 9 and 12 months after treatment. Prior to 131I therapy the size of the thyroid gland was determined by ultrasound and a 24-hour uptake of 131I was carried out. Thyroid volume was also estimated 12 months after 131I therapy in 78 of the 163 patients. Twelve months after the initial 131I dose patients could be classified as euthyroid, hyperthyroid or hypothyroid. RESULTS: Neither in the group of 163 patients nor within the three subgroups of hyperthyroidism could any significant difference in outcome between the two treatment regimes be demonstrated. Thirty-two of 78 patients (41%) in the calculated dose group and 30 of 85 patients (35%, NS) in the fixed group were classified as hyperthyroid. Seven of 78 (9%) in the calculated dose group and 6 out of 85 (7%, NS) in the fixed dose group were classified as permanently hypothyroid. Finally, 39 of 78 (50%) in the calculated dose group and 49 of 85 (58%, NS) in the fixed group were euthyroid at 12 months after 131I treatment. One year after 131I therapy thyroid volume was reduced from 59.3 +/- 9.2 (mean +/- SEM) to 36.2 +/- 6.6 ml (average reduction 39%) in the calculated dose group (P < 0.001). This reduction did not differ significantly from the fixed dose group where thyroid volume declined from 61.6 +/- 6.1 to 41.17 +/- 4.7 ml (average reduction 32%) (P < 0.001). CONCLUSIONS: A semiquantitative approach is probably as good as the more elaborately calculated radioiodine dose for treatment of hyperthyroidism. It is clearly more cost effective and allows the use of predetermined standard doses.

Adult↗
PubMed1995

Thyroid cytotoxic antibodies in atrophic and goitrous autoimmune thyroiditis.

It is unknown whether in chronic lymphocytic thyroiditis the goitrous (Hashimoto's thyroiditis) and atrophic forms (primary myxedema) are variants of the same disease or different pathogenic entities. Conventional thyroid-related autoimmune parameters are unable to separate both diseases serologically. It is assumed that cellular and humoral cytotoxic events induce gland atrophy and thus should be detectable more often in non-goitrous than goitrous autoimmune thyroiditis. We determined antibody-dependent cell-mediated cytotoxicity in 67 patients with autoimmune thyroiditis, using a 51chromium-release assay against human thyroid cells. Thyroid volume had been measured by ultrasonography. Other thyroid-specific antibodies, like TSH binding-inhibiting antibodies, TSH function-blocking antibodies, thyroglobulin antibodies and thyroid peroxidase antibodies, were determined. Cytotoxic antibody activity was 20.5% (median, range 0-54.5%) in patients with autoimmune thyroiditis and 8.3% (median, range 0-18.4%) in controls (p < 0.0001). Analysis of cytotoxicity regarding thyroid size showed a high incidence of cytotoxic antibodies in atrophic disease (median thyroid volume 6 ml), where cytotoxic antibodies were detectable in 80% versus 39% (x2 = 9.6; p < 0.0001) in goitrous disease (median thyroid volume 36 ml). The specific lysis of 30% (median; 95% confidence limit 23.9-32.9) in non-goitrous thyroiditis patients was significantly higher than in goitrous patients (16.9%; 95% confidence limit 13.2-20.4) (p = 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients.

Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.

Adult↗
PubMed1994

[Prevention of duodenal ulcer recurrence with penicillin].

The aim of this study was to test the hypothesis that infection with Helicobacter pylori is essential for recurrence of duodenal ulcer. We performed a randomized controlled trial of the relapse rate of duodenal ulcer during 12 weeks treatment with penicillin V or placebo in 170 out-patients from five centres. The relapse rate was 9% during treatment with penicillin and 50% with placebo, P < 0.0001. It is concluded that infection with penicillin-sensitive bacteria, i.e. H. pylori, plays an important role for recurrence of duodenal ulcer disease. Penicillin V suppresses this infection but does not eradicate it.

Adult↗
PubMed1994

Empirical H2-blocker therapy or prompt endoscopy in management of dyspepsia.

The recommended strategy for management of dyspepsia is empirical treatment with an H2-blocking drug, followed by endoscopy if the symptoms do not respond or recur. We compared two strategies for the management of dyspepsia--treatment based on the results of prompt endoscopy (group 1) and empirical H2-blocker treatment with diagnostic endoscopy only in cases of therapeutic failure or symptomatic relapse within 1 year (group 2). Eligible patients had symptoms severe enough to justify empirical H2-blocker therapy. Symptoms, drug consumption, and sick-leave days were assessed through monthly diaries. Patients with non-organic dyspepsia diagnosed by endoscopy did not receive ulcer drugs. Of 414 patients randomised, 373 completed 1-year follow-up. Organic disease was found at endoscopy in 68 (33%) of 208 group-1 patients (ulcer in 45). Endoscopy was done in 136 (66%) of 206 group-2 patients. Case selection for endoscopy was not improved by the empirical treatment strategy, since the diagnostic profile was the same as in group 1 and 40% of the expected ulcer cases remained undiagnosed. After 1 year there were no differences in symptoms or quality of life measures. The empirical treatment strategy in dyspepsia was associated with higher costs, due mainly to a higher number of sick-leave days and cost of ulcer drug use. Prompt endoscopy is a cost-effective strategy in dyspeptic patients with symptoms severe enough to justify the current practice of empirical H2-blocker treatment.

Adult↗
PubMed1994

The transplanted human kidney does not achieve functional reinnervation.

1. Previous histological studies have demonstrated partial reinnervation of the human transplanted kidney. However, it remains unknown whether this reinnervation is of any functional significance. 2. The effects of noradrenaline infusion (2 micrograms h-1kg-1) and lower body negative pressure (-27 mmHg) on renal haemodynamics, sodium excretion and tubular function were investigated in 25 renal transplant recipients and 10 normal subjects. Sixteen of the transplant recipients had all been transplanted for more than 27 months, and nine had all been transplanted for less than 2 months. 3. After an overnight fast, the subjects were water-loaded, and clearance studies were performed with a 1 h baseline period, a 1 h period with noradrenaline infusion, another 1 h baseline period, and a final 1 h period with lower body negative pressure. 4. During noradrenaline infusion the relative decrease in effective renal plasma flow, glomerular filtration rate and clearance of lithium and sodium was significantly more pronounced in the long-term transplanted patients than in the control subjects. 5. Lower body negative pressure only depressed the glomerular filtration rate significantly in the control subjects. Further, the relative decrease in effective renal plasma flow and clearance of lithium and sodium was significantly greater in the control subjects than in the two groups of transplanted patients. 6. The present study thus demonstrated that in short- and long-term transplanted kidneys in man, supersensitivity to circulating noradrenaline and an inadequate response to lower body negative pressure was present. This strongly suggests that the human transplanted kidney remains functionally denervated.

Adolescent↗
PubMed1994

Long-term follow-up of thyroid scintigraphies after 131I therapy of solitary autonomous thyroid nodules.

The aim of the present study was to assess thyroid scintigraphies after 131I treatment of autonomous thyroid nodules with respect to evolution of the hot nodules as well as the extranodular tissue. A 99mTc pertechnetate scintigraphy was carried out 1-16 years (median 8 years) after 131I treatment of a solitary autonomous nodule in 66 patients remaining euthyroid. At the time of diagnosis, 9 of the patients were euthyroid and 57 were hyperthyroid, of whom 27 received antithyroid drug therapy prior to 131I treatment. The scintigraphies were evaluated twice by 4 specialists (3 endocrinologists and 1 specialist in nuclear medicine). There was total agreement between the 4 observers in 50 and 52% in the first and second evaluation, respectively. The interobserver variation was evaluated by means of omega coefficients and omega ranged from 0.18 to 0.76 indicating poor to substantial agreement. A solitary autonomous nodule with suppression of the extranodular thyroid tissue persisted in 50% of the patients, whereas a solitary cold nodule, homogeneous uptake or inhomogeneous uptake was found in 15, 22, and 13%, respectively. We conclude that although euthyroidism is achieved by radioiodine treatment, a hot nodule suppressing the 99mTc pertechnetate in the extranodular tissue is still found in 50% of the patients even when serum TSH has been normal for years. Antithyroid drug therapy prior to 131I treatment was more frequent in this group of patients.

Adult↗
PubMed1994

Effects of acute beta-adrenoceptor blockade with metoprolol on the renal response to dopamine in normal humans.

The present study investigated the contribution of adrenergic beta 1-receptor stimulation to the cardiovascular and renal effects of low-dose dopamine in eight normal, water-loaded humans. Metoprolol (100 mg) or placebo was administered orally at 08.00 h in a randomized, double-blind fashion on two different days. Renal clearance studies were performed during a 1 h baseline period, two 1 h periods with dopamine infusion (3 micrograms kg-1 min-1), and a 1 h recovery period. Cardiac output was measured by an ultrasonic Doppler method, and lithium clearance (CLLi) was used to estimate proximal tubular outflow. Baseline values of heart rate, systolic pressure and mean arterial pressure decreased with metoprolol compared with placebo, but cardiac output, effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were not significantly changed. Metoprolol significantly decreased baseline CLLi and sodium clearance (CLNa) by 19% (P < 0.01) and 34% (P < 0.01), respectively. Metoprolol blunted the dopamine-induced increases in heart rate and systolic pressure, but cardiac output increased to the same extent on both study days by 26% (placebo, P < 0.05) and by 31% (metoprolol, P < 0.01), respectively. With and without metoprolol, dopamine did not significantly change GFR, and the percentage increases in ERPF were similar on the two study days (40% (P < 0.001) and 42% (P < 0.001), respectively). Dopamine increased CLLi and CLNa by 31% (P < 0.01) and 114% (P < 0.01), respectively, with placebo, and by 36% (P < 0.01) and 114% (P < 0.01), respectively, with metoprolol. Values during infusion remained significantly lower with metoprolol compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Albuminuria and overall capillary permeability of albumin in acute altitude hypoxia.

The mechanism of proteinuria at high altitude is unclear. Renal function and urinary excretion rate of albumin (Ualb) at rest and during submaximal exercise and transcapillary escape rate of 125I-labeled albumin (TERalb) were investigated in 12 normal volunteers at sea level and after rapid and passive ascent to 4,350 m. The calcium antagonist isradipine (5 mg/day; n = 6) or placebo (n = 6) was administered to abolish hypoxia-induced rises in blood pressure. Lithium clearance and urinary excretion of beta 2-microglobulin were used to evaluate renal tubular function. High altitude increased Ualb from 2.8 to > 5.0 micrograms/min in both groups (P < 0.05). In the placebo group, high altitude significantly increased filtration fraction (P < 0.05), but this response was abolished by isradipine. Lithium clearance and urinary excretion of beta 2-microglobulin remained unchanged by hypoxia in both groups. Exercise did not reveal any further renal dysfunction. In both groups, high altitude increased TERalb from 4.8 to > 6.7%/h (P < 0.05). In conclusion, acute altitude hypoxia increases Ualb despite unchanged tubular function and independent of effects of isradipine on filtration fraction. The elevated TERalb suggests an overall increase in capillary permeability, including the glomerular endothelium, as the critical factor in high-altitude induced albuminuria.

Adult↗
PubMed1993

Renal hemodynamics, tubular function, and response to low-dose dopamine during acute hypoxia in humans.

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.

Acute Disease↗
PubMed1993

Observer variation in ultrasound assessment of the thyroid gland.

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.

Adult↗
PubMed1992

[Health-economic aspects of newer anti-ulcer drugs].

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.

Cost Savings↗
PubMed1992

Subtle changes in serum thyrotrophin (TSH) and sex-hormone-binding globulin (SHBG) levels during long-term follow-up after radioactive iodine in multinodular non-toxic goitre.

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.

Adult↗