bluuebunny/crossref_metadata_2025 huggingface dataset:
Malignant thymic carcinoid is not prevented by transcervical thymectomy in multiple endocrine neoplasia type 1
Authors: Burgess John R. , Giles Natalie , Shepherd Joseph J.
Published: March 2003

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant tumour syndrome. It is characterized by primary hyperparathyroidism, pituitary neoplasia and foregut lineage neuroendocrine neoplasia. Malignant thymic carcinoid tumours are an uncommon but important manifestation of MEN 1. Transcervical thymectomy is often advocated as prophylaxis against thymic carcinoids, although there is a paucity of evidence to support the efficacy of this procedure. This is the first report of a malignant thymic carcinoid occurring in an MEN 1 patient following prior parathyroidectomy and transcervical thymectomy. It is concluded that transcervical thymectomy does not reliably provide prophylaxis against thymic carcinoid.
Histocompatibility leucocyte antigens and closely linked immunomodulatory genes in autoimmune thyroid disease
Authors: Hunt P. J. , Marshall S. E. , Weetman A. P. , Bunce M. , Bell J. I. , Wass J. A. H. , Welsh K. I.
Published: March 2003

OBJECTIVES Associations between autoimmune thyroid disease and antigens of the major histocompatibility complex (MHC) have long been recognized. Graves' disease (GD) is associated with the histocompatibility leucocyte antigen (HLA) haplotype A*01‐B*0801‐DRB1*0301‐DQA1*0501‐DQB1*0201 (or B8/DR3) whereas autoimmune hypothyroidism (AIH) has been weakly associated with HLA DRB1*03, *04 and *11/*12 alleles (or DR3, DR4 and DR5). However, the presence of important immunoregulatory genes within the HLA Class II and III regions raises the possibility that these genes harbour the primary susceptibility locus. This study examines genetic variation across the MHC in UK Caucasoid subjects with autoimmune thyroid disease.

PATIENTS AND METHODS DNA extracted from venous blood samples from 215 patients with autoimmune thyroid disease (GD 135, AIH 77) and 267 control subjects was analysed. Genotyping was performed using polymerase chain reaction and sequence specific primers for HLA Class I and II alleles and polymorphisms within the TAP1, TAP2, tumour necrosis factor (TNF), lymphotoxin α (LTα), heat shock protein (HSP)70‐1, HSP70‐2 and HSP70‐Hom genes.

RESULTS For GD, the strongest association was with DRB1*03 [56% patients positive vs. 24% controls, P = 2 × 10−10, odds ratio (OR) 4·0]. Positive associations were also seen for DRB1*03 linked alleles, B*0801, DRB3*01/02, DQA1*05, DQB1*02 and DPB1*0101 (OR 2·3–3·4). Specific TNF and LTα alleles were strongly associated with GD (Pc = 3 × 10−5 and 0·001) and weak associations were seen for HSP70‐1 + 190C and HSP70‐2 + 1267G polymorphisms (Pc = 0·05 and 0·01). These associations were not significant when DRB1*03 status was considered. Patients with AIH showed only a weak association with DQB1*03 (P = 0·02).

CONCLUSIONS These results show that, of the polymorphisms tested within the MHC, GD is most strongly associated with DRB1*03, and associations with other immunoregulatory genes previously described in Caucasian subjects most likely reflect linkage disequilibrium. AIH differs from GD, being less influenced by the MHC region.
Is there an increase in second brain tumours after surgery and irradiation for a pituitary tumour?
Authors: Erfurth Eva Marie , Bülow Birgitta , Mikoczy Zoli , Svahn‐Tapper Gudrun , Hagmar Lars
Published: March 2003

OBJECTIVE To assess the incidence of second brain tumours in patients operated and irradiated for pituitary tumours.

DESIGN AND PATIENTS The study base consisted of a consecutive series of 325 patients operated and irradiated for pituitary tumours, excluding patients with acromegaly and Cushing's disease. Comparison was made with the general population from the same catchment area as the patients. The follow‐up period started in 1958 and on an individual basis patients were followed from the onset of postoperative irradiation until December 1995, or until date of death, emigration or a second brain tumour diagnosis, whichever occurred first.

RESULTS Three brain tumours (two astrocytomas and one meningioma) were observed, compared with 1·13 expected (standardized incidence ratios (SIR) 2·7; 95% confidence interval (CI) 0·6–7·8).

CONCLUSION The present study gives no firm support for an increased incidence of a second brain tumour in patients operated and irradiated for pituitary tumours. A crude meta‐analysis of the present and previously published cohort studies of patients with irradiated pituitary tumours gives an SIR of 6·1 (95% CI 3·16–10·69). Thus, the results of the meta‐analysis are in favour of an increased risk for second brain tumours. A genetic trait that predisposes to both pituitary tumours and brain tumours is an alternative causal factor. There is no definite proof that cranial irradiation per se is the causal factor. This question cannot be fully answered until sufficient cohort studies of nonirradiated pituitary tumour patients have been carried out.
Increased prevalence of heterozygous 21‐OH germline mutations in patients with adrenal incidentalomas
Authors: Baumgartner‐Parzer S. M. , Pauschenwein S. , Waldhäusl W. , Pölzler K. , Nowotny P. , Vierhapper H.
Published: March 2003

objective As a result of the widespread use and the enhanced quality of high‐resolution radiological techniques [computed tomography (CT), magnetic resonance imaging (MRI)] a high frequency (4–10%) of adrenal incidentalomas has been detected in the general population. It is still debated whether undiagnosed 21‐hydroxylase (21‐OH) deficiency, accounting for more than 90% of congenital adrenal hyperplasia (CAH) cases, predisposes for adrenal tumours. We therefore performed an analysis of the prevalence of 21‐OH germline mutations in patients with non‐functional adrenal incidentalomas.

subjects and methods Fifty Austrian patients with non‐functional adrenal adenomas detected by CT for unrelated reasons were screened by PCR‐based sequencing for the most common point mutations and by Southern blot analysis for large gene deletion/conversion events of the 21‐OH gene.

results Heterozygosity for large gene conversions was shown in 5 (10%), for Q318 point mutations in 2 (4%) and for the Intron2splice mutation in 1 (2%) of the 50 patients with adrenal adenomas. One (2%) patient (70 years of age), identified to have a chimeric CYP21AB gene with a junction site before Intron 2 on one and a large (30 kb) deletion on the other allele, was diagnosed to be affected by CAH.

conclusion 21‐OH mutation screening indicates a higher frequency of classic CAH carriers (16%) and of manifest CAH (2%) due to 21‐OH‐deficiency among patients with adrenal adenomas than in the general population (1–2% carrier frequency for classic CAH).
The low‐dose ACTH test does not provide a useful assessment of the hypothalamic–pituitary–adrenal axis in secondary adrenal insufficiency
Authors: Suliman Abdulwahab M. , Smith Thomas P. , Labib Mourad , Fiad Tarek M. , McKenna T. Joseph
Published: March 2003

OBJECTIVE The 1 µg ACTH stimulation test has been introduced to improve the sensitivity of ACTH as a test of the integrity of hypothalamic–pituitary–adrenal axis (HPAA). This study aims to compare the sensitivity, specificity and diagnostic accuracy of the ‘low‐dose’ 1 µg ACTH (LDACTH) test and the ‘standard dose’ 250 µg ACTH (SDACTH) test, with the overnight metyrapone test (OMT) which assesses the entire HPAA.

DESIGN A prospective evaluation of the performance of SDACTH and LDACTH screening tests in a diverse cohort of patients with possible adrenal insufficiency as routinely encountered in clinical practice using the OMT as the reference method.

PATIENTS A total of 51 patients (26 with asthma on inhaled glucocorticoid, nine with hypopitutarism, three with hypothyroidism, one with hyponatraemia, one with Crohn’s disease, one with encephalitis and 10 with non‐specific symptoms) each underwent SDACTH, LDACTH and OMT tests in random sequence at least 1 week apart.

MEASUREMENTS Blood was sampled for plasma cortisol levels at 0 and 30 min after intravenous administration of 1 µg and 250 µg of ACTH. Metyrapone 30 mg/kg body weight was taken orally at midnight, and plasma samples were taken for measurement of 11‐deoxycortisol and cortisol next morning between 08·00 and 09·00 h. The OMT was deemed to be abnormal when both 11‐deoxycortisol and cortisol levels were less than 200 nmol/l.

RESULTS The sensitivity and specificity at an empirical ‘normal’ plasma cortisol threshold value of 500 nmol/l were 67% and 100% for the SDACTH test, and 73% and 81% for the LDACTH test, respectively. As the plasma cortisol cut‐off value was increased to 550 nmol/l and 600 nmol/l, the sensitivity of the SDACTH test was 67% and 80% and specificity was 97% and 92%, respectively. The sensitivity of the LDACTH test increased from 93% at plasma cortisol cut‐off value of 550 nmol/l to 100% at plasma cortisol cut‐off value of 600 nmol/l. However, the specificity of the LDACTH test fell from 72% to 56% as the plasma cortisol cut‐off value was increased from 550 nmol/l to 600 nmol/l. A receiver operating characteristic curve demonstrated that the specificity of the SDACTH test was higher than the specificity of the LDACTH test at any given level of sensitivity.

CONCLUSIONS Both the LDACTH and SDACTH tests fail to achieve acceptable levels of sensitivity and specificity to be useful as screening tests for secondary adrenal insufficiency. In this context the OMT can be safely used to assess the integrity of the entire HPAA.
The quantity of thyroid hormone in human milk is too low to influence plasma thyroid hormone levels in the very preterm infant
Authors: Van Wassenaer Aleid G. , Stulp Maykel R. , Valianpour Fredoen , Tamminga Pieter , Ris Stalpers Carrie , De Randamie Janine S. E. , Van Beusekom Christien , De Vijlder Jan J. M.
Published: March 2003

background Thyroid hormone is crucial for brain development during foetal and neonatal life. In very preterm infants, transient low levels of plasma T4 and T3 are commonly found, a phenomenon referred to as transient hypothyroxinaemia of prematurity. We investigated whether breast milk is a substantial resource of thyroid hormone for very preterm neonates and can alleviate transient hypothyroxinaemia. Both the influence of breast feeding on plasma thyroid hormone levels and the thyroid hormone concentration in preterm human milk were studied.

methods Two groups were formed from the placebo group of a randomized thyroxine supplementation trial in infants born at < 30 weeks’ gestational age on the basis of the mean breast milk intake during the third, fourth and fifth weeks of life. One group received more than 50% breast milk (mean breast milk intake 84%, n = 32) and the other group less than 25% breast milk (mean breast milk intake 3·3%, n = 25). Plasma thyroid hormone concentrations were compared between the two groups. Breast milk was collected from mothers of infants participating in the same trial and the thyroxine concentration in breast milk was measured with RIA after extraction.

results No significant differences were found between both groups in plasma concentrations of T4, free T4, T3, TSH, rT3 and thyroxine‐binding globulin (TBG), which were measured once a week. Thyroxine concentration in breast milk ranged between 0·17 µg/l and 1·83 µg/l (mean 0·83, SD 0·3 µg/l) resulting in a maximum T4 supply of 0·3 µg/kg via ingested breast milk. In formula milk, the T4 concentration was equally low. Protease treatment did not influence the measured T4 concentrations.

conclusions No differences in plasma thyroid hormone between breast milk‐fed and formula‐fed infants were found. The amount of T4 present in human milk and formula milk is too low to alter the hypothyroxinaemic state of preterm infants.
Dysregulation of iodothyronine deiodinase enzyme expression and function in human pituitary tumours
Authors: Tannahill L. A. , Visser T. J. , McCabe C. J. , Kachilele S. , Boelaert K. , Sheppard M. C. , Franklyn J. A. , Gittoes N. J. L.
Published: March 2003

objective Thyroid hormones (THs) perform essential roles in pituitary function. They regulate anterior pituitary hormone secretion and are also key determinants of pituitary cell proliferation and differentiation. The critical role of deiodinase enzymes, which serve as prereceptor regulators of TH action, remains largely unexplored. Three deiodinase enzymes metabolize active and inactive THs and thereby determine tissue concentrations of the biologically active ligand, tri‐iodothyronine (T3). We hypothesized that aberrant expression of deiodinase enzymes and/or altered enzyme activity in pituitary tumours may change tissue concentrations of THs and influence their growth and secretory characteristics.

study design and patients We studied 105 pituitary tumours and 10 normal pituitaries for expression of deiodinase enzyme mRNAs encoding types 1 (D1), 2 (D2) and 3 (D3) using real‐time RT‐PCR. Enzyme activity data from 20 pituitary samples were also obtained.

results Pituitary tumours expressed significantly increased D3 mRNA (6·5‐fold, P < 0·0005) compared with normal pituitaries. D2 mRNA was also increased 2·6‐fold (P = 0·005) in pituitary tumours compared with normals. The rare TSH‐secreting pituitary tumour subtype expressed a 13·1‐fold excess of D3 mRNA and reduced D2 mRNA (0·1‐fold of normal pituitaries). D2 mRNA expression in ACTH‐secreting tumours was similarly reduced to 0·1‐fold that in normal pituitaries.

conclusions Pituitary adenomas express abnormal levels of deiodinase enzymes compared to normal pituitaries. These abnormalities may have functional consequences on pituitary tumour growth. In the case of TSH‐secreting pituitary adenomas, the observed pattern of deiodinase mRNA expression may explain the ‘resistance’ of this tumour type to TH feedback.
Does radioiodine therapy have disadvantageous effects in non‐iodine accumulating differentiated thyroid carcinoma?
Authors: Schaap Jeroen , Eustatia‐Rutten Carmen F. A. , Stokkel Marcel , Links Thera P. , Diamant Michaela , Van Der Velde Edo A. , Romijn Johannes A. , Smit Jan W. A.
Published: March 2003

background Although radioiodine therapy in differentiated thyroid carcinoma without radioiodine accumulation has not been considered harmful, increased thyrotrophin levels during thyroxine withdrawal without the benefit of radiotoxicity as well as the selection of de‐differentiated cells may have disadvantageous effects on tumour course.

objective We therefore analysed retrospectively the effects of radioiodine therapy on the course of serum thyroglobulin levels as a tumour marker in patients with progressive residual or metastatic differentiated thyroid carcinoma, with or without radioiodine accumulation on post‐therapeutic whole body scintigraphy.

patients and methods Patients who had undergone radioiodine therapies with sufficient pre‐ and post‐therapy thyroglobulin measurements to allow for regression analysis and not preceded or followed by other treatment modalities within a 1‐year interval were selected. All patients had undergone total thyroidectomy and ablative therapy. Thirty‐nine patients and radioiodine therapies were included (10 males, 29 females, mean age 57 years), and divided into a negative‐ (n = 17) and a positive post‐therapeutic whole body scintigraphy group (n = 22). Pre‐ and post‐therapeutic thyroglobulin course were analysed using non‐linear regression, comparing the difference in the thyroglobulin growth coefficient b1 post‐ and pre‐therapy (delta b1: b1post‐therapy‐b1pre‐therapy). In addition, absolute post‐ and pre‐therapeutic thyroglobulin levels, radiological follow‐up and clinical outcome were also analysed.

results The two groups were comparable with respect to age, sex, tumour stage, histology and prior therapies. Differences between post‐ and pre‐therapeutic b1 values differed significantly in the positive post‐therapeutic whole body scintigraphy group (delta b1: –0·65 µg/l−1 years−1, P < 0·001) but not in the negative post‐therapeutic whole body scintigraphy group (delta b1: –0·14). Absolute serum thyroglobulin levels and radiological follow‐up revealed a favourable response of radioiodine therapy in the positive whole body scintigraphy group but not in the negative group. Delta b1 was related significantly with clinical outcome as revealed by receiver operator curves (ROC): all patients with a positive delta b1 (n = 8) had an unfavourable outcome (progression or death), whereas from the 31 patients with negative delta b1, 61% had an unfavourable outcome.

conclusion We did not find disadvantageous effects of a single radioiodine therapy on serum thyroglobulin increments in patients with negative post‐therapeutic whole body scintigraphy. However, as we did not observe a beneficial effect either, we would not advise the continuation of radioiodine therapy in patients with negative post‐therapeutic whole‐body scintigraphy, unless a positive response is observed in individual cases.
Impact of GHBP interference on estimates of GH and GH pharmacokinetics
Authors: Hansen Troels Krarup , Fisker Sanne , Hansen Betina , Sørensen Hans Holmegaard , Christiansen Jens Sandahl , Jørgensen Jens Otto L. , Ørskov Hans
Published: March 2003

Objective Circulating GH‐binding protein (GHBP) may interfere with GH measurements in immunoassays by competing with the antibodies for ligands. The concentrations of circulating GHBP in humans are closely related to the amount of body fat, and subject to large interindividual differences.

Subjects and Methods To assess the influence of GHBP in a widely used commercial immunometric GH kit (DELFIA, Wallac, Finland) we systematically tested the effects of varying GHBP concentrations and assay incubation times on GH estimates over a broad range of GH concentrations. We subsequently investigated the impact of 24‐h vs. 2‐h incubation on estimates of GH pharmacokinetics obtained from two‐step primed‐constant infusions of GH in a group of 26 healthy nonobese men [mean age 37·3 years (range 22–55); body mass index (BMI) = 24·6 ± 0·4 kg/m2].

Results GHBP at physiological concentrations of 0·2, 0·5, 1·0, 2·0 nm reduced the GH estimates by as much as 40% at low GH concentrations. By increasing the incubation time from the recommended 2 h to 24 h the interference from GHBP was almost completely eliminated. The increase in measured GH using 24‐h vs. 2‐h incubation showed a strong positive correlation to the subjects’ GHBP levels (r = 0·66, P < 0·001). Consequently, the estimates of metabolic clearance rate (MCR) of GH at constant infusion rates of 1·5 µg/kg/h and 3·0 µg/kg/h were significantly reduced when using 24 h as opposed to 2 h incubation, and the changes were negatively correlated to the GHBP levels (r = −0·62, P < 0·001 and r =−0·54, P < 0·01, respectively). Furthermore, by reducing the interference of GHBP through 24‐h incubation, the previously observed positive correlations between MCR and not only the subjects’ GHBP levels but also with total body fat were reduced, while the positive correlation between baseline insulin concentrations and GH clearance was strengthened.

Conclusions We conclude that differences in GHBP concentrations significantly influence GH measurements in this commercial immunoassay, and that interindividual differences in GHBP concentrations may interfere with the results in studies involving between‐subject comparisons of GH concentrations and pharmacokinetics. We believe the extended incubation time allows for better ‘extraction’ of GH bound to serum GHBP, and that this effect should be investigated, and if relevant, be exploited in other GH immunoassays.
Pulmonary venous blood flow pattern in patients with univentricular hearts following total cavo‐pulmonary connection
Authors: Rydberg  , Teien  , Karp  , Vermilion  , Ludomirsky
Published: March 2003

The objective of the study was evaluation of the pulmonary venous blood flow (PVF) pattern and the influence of ventricular function and atrioventricular valve regurgitation on this flow in patients with univentricular hearts post total cavo‐pulmonary connection (TCPC). Transthoracic or transoesophageal echocardiographic studies were performed in 24 children with normal hearts (group A) and in 24 patients with univentricular hearts (group B). Ventricular function and atrioventricular valve regurgitation was semiquantitatively assessed. Systolic/diastolic maximal velocities and velocity time integrals (VTI) were measured from PVF tracings. Ejection fraction was measured by radionuclide angiography in 11 patients. Twelve patients underwent heart catheterization and angiography.

In group B the PVF showed a biphasic flow velocity curve. The systolic integrals were smaller and the diastolic integrals were larger than in group A (6·4 vs. 13·0 cm, P = 0·0001, and 13·9 vs. 10·0 cm, P = 0·005). The pulmonary venous systolic flow fraction in 13 patients with an open fenestration and/or atrioventricular valve regurgitation grade 2–3 was significantly lower than in those 11 patients without fenestration and none/small regurgitation (0·19 vs. 0·40, P = 0·05).

In conclusion, the PVF pattern in children with univentricular hearts palliated with TCPC is similar to the PVF pattern found in individuals with biventricular hearts showing a biphasic flow velocity curve despite the absence of pulsative pulmonary artery flow. The PVF in patients with TCPC‐palliated univentricular hearts is influenced by atrioventricular valve regurgitation and fenestration flow.
Quantitative digital evaluation of myocardial exercise thallium‐201 single‐photon emission tomography in post‐menopausal women
Authors: Janerot‐Sjöberg  , Ekberg  , Areskog  , Nylander  , Swahn
Published: March 2003

Quantitative computerized analysis of data from myocardial thallium‐201 (201Tl) single‐photon emission tomography (SPET) may improve the diagnostic accuracy of coronary heart disease. The reference ranges for post‐menopausal women are, however, limited and obtained mainly from patients. To compare reference values from healthy post‐menopausal women and to improve the quantitative analysis, 20 women (10 patients with coronary heart disease and previous infarction and 10 age‐matched healthy volunteers) were examined immediately post exercise and after a delay. A nine‐segment `bull's‐eye' model was used for analysis. At visual evaluation, reproducibility was high (93%), no false‐positive results were obtained and in 70% of the patients the SPET was interpreted as abnormal. Using reported reference values for quantitative analysis, all the healthy women had an abnormal result. New reference values based on three different methods of `normalization' were calculated: the relative activity of segment 3 set to 100%, the segment with the highest activity set to 100% and a least‐squares method. They all differed significantly from those that had previously been reported. The frequencies of agreement between visual and quantitative analysis were 84–92% and were highest when segment 3 was used as a reference, but in this case only 40% of the patients with coronary heart disease had an abnormal SPET. Using the least‐squares method for handling digital information, the SD of the normal values decreased and 90% of the patients with coronary heart disease were accurately diagnosed. These results provide quantitative digital reference values for healthy post‐menopausal women. They verify that quantitative analysis is in diagnostic agreement with visual evaluation, stress the need for local verification of reference ranges and suggest a least‐square normalization method for the analysis.
Amplitude variation in static‐charge‐sensitive bed signal increased in obstructive airways disease
Authors: Lindqvist Ari , Halme Maija , Tukiainen Pentti , Laitinen Lauri A.
Published: March 2003

The relationship between oesophageal pressure variation and amplitude variation in the static‐charge‐sensitive bed (SCSB) ballistocardiogram suggests that changes in intrathoracic pressure can be detected using the SCSB method. We investigated whether amplitude variation in the static‐charge‐sensitive bed ballistocardiogram (SAV) is related to severity of airway obstruction in patients with asthma and chronic obstructive pulmonary disease. The ability of SAV to detect an increase in airway obstruction induced by histamine challenge was also tested. Twenty‐six patients suffering from asthma and 12 patients with chronic obstructive pulmonary disease (COPD) were enrolled in the study. SAV, amplitude from the SCSB ballistocardiogram, respiratory amplitude from the SCSB respiratory wave form and heart rate from the electrocardiogram (ECG) were computed using analysing software (Biorec, Helsinki, Finland) during a 7‐min supine rest. SAV was related to forced expiratory volume in one second (FEV1) immediately after signal recording. Asthma patients participated in a standardized histamine challenge test to reveal the effect of acute bronchoconstriction on SAV. An inverse relationship existed between baseline FEV1 and SAV in asthma and COPD. In the histamine inhalation test, FEV1 fell by 0·7 ± 0·3 l or 26% ± 11% (P<0·0001) and SAV increased by 12% ± 5% (P<0·0001) in 12 asthma patients. The fall in FEV1 induced by histamine followed regularly and correlated significantly with the rise in SAV (n = 24, r = −0·58, P = 0·002). Changes in respiratory amplitude or heart rate did not explain changes in SAV. SAV may not separate the upper airway obstruction from the bronchial obstruction but it is related to severity of airway obstruction. The clinically significant increase in airway obstruction induced by histamine inhalation increases amplitude variation in SCSB.
Effect of intraluminal temperature on human oesophageal motor function
Authors: Özdoğan  , Saadalla  , Emironal  , Yeğen  , Ulusoy
Published: March 2003

Oesophageal motor activity is altered by bolus temperature. The effects of sustained cold or warm intraluminal temperature on oesophageal motility have not been documented in detail. Oesophageal manometry was performed in 11 normal subjects after intraluminal room, cold‐ and warm‐water treatments. The intraluminal temperatures were 34·2 ± 0·8, 30·6 ± 1·7 and 39·7 ± 0·9°C respectively during room temperature, cold and warm applications. Low‐temperature treatment prolonged the duration of lower oesophageal sphincter relaxation and the duration of oesophageal peristaltic contraction wave compared with the room temperature and warm treatments. Low temperature also attenuated the mean pressure slope of oesophageal contraction waves and resulted in an increased percentage of non‐transmitted and simultaneous contractions. The effects of low‐temperature application persisted as long as the intraluminal temperature remained constant and there was no adaptation. Cooling oesophageal lumen temperature alters oesophageal motor activity, and this effect is not adaptive.
Does plasma L‐arginine level play a role in regulation of blood pressure during exercise and autonomic nervous function?
Authors: Penttinen Jyrki , Töyry Jari , Eerikäinen Sari , Litmanen Hannu , Rinkinen Tuija , Länsimies Esko
Published: March 2003

Little is known of L‐arginine's role in autonomic nervous regulation and physiological responses to dynamic exercise. We assessed heart rate and blood pressure during a maximal bicycle ergometer test and heart rate variability at rest in 15 healthy male volunteers, age 22–38 years. Venous blood samples for plasma
L‐arginine measurements were taken when subjects were sitting at rest before and at the end of exercise. The autonomic nervous function was assessed with time and frequency domain analysis of heart rate variability. Plasma
L‐arginine level decreased during maximal exercise from 71·4 μmol l−1 to 51·0 μmol l−1 (P < 0·0001) for all subjects studied. The systolic blood pressure during the maximal exercise test was inversely correlated with plasma
L‐arginine level at rest (r = −0·70, P < 0·01). Normalized low frequency band of power spectral analysis of heart rate variability correlated with
L‐arginine level at rest (r = 0·66, P < 0·01). In conclusion, plasma
L‐arginine level decreased in physical exercise, and plasma
L‐arginine level at rest was positively associated with the sympathetic component of power spectral analysis of heart rate variability at rest, and inversely with systolic blood pressure during physical exercise.
Cardiovascular response during head‐up tilt in chronic fatigue syndrome
Authors: LaManca  , Peckerman  , Walker  , Kesil  , Cook  , Taylor  , Natelson
Published: March 2003

This study examined the cardiovascular response to orthostatic challenge, and incidence and mechanisms of neurally mediated hypotension in chronic fatigue syndrome (CFS) during a head‐up tilt test. Stoke volume was obtained by a thoracic impedance cardiograph, and continuous heart rate and blood pressure were recorded during a 45‐min 70° head‐up tilt test. Thirty‐nine CFS patients and 31 healthy physically inactive control subjects were studied. A positive tilt, i.e. a drop in systolic blood pressure openface> 25 mmHg, no concurrent increase in heart rate and/or development of presyncopal symptoms, was seen in 11 CFS patients and 12 control subjects (P>0·05). During baseline and the first 5 min of head‐up tilt, CFS patients had higher heart rate and smaller pulsatile‐systolic area than control subjects (P<0·05). Among subjects who completed the test, those with CFS had higher heart rate and smaller stroke volume (P<0·05) than corresponding control subjects. When comparing those who had a positive test outcome in each group, CFS patients had higher heart rates and lower pulse pressure and pulsatile‐systolic areas during the last 4 min before being returned to supine (P<0·05). These data show that there are baseline differences in the cardiovascular profiles of CFS patients when compared with control subjects and that this profile is maintained during head‐up tilt. However, the frequency of positive tilts and the haemodynamic adjustments made to this orthostatic challenge are not different between groups.
Comparison of two methacholine challenge methods using Spira‐2 or Mefar dosimeter
Authors: Jõgi Rain , Janson Christer , Hedenström Hans
Published: March 2003

Two bronchial challenge protocols with breath‐actuated dosimeters, Spira Elektro‐2 and Mefar, with similar cumulative dose steps were compared in 28 patients with mild to moderate asthma. Methacholine challenges were performed after two different protocols at the same time of day in random order 3 or 4 days apart. The provocative dose of methacholine producing a 20% fall in forced expiratory volume in 1 second (PD20) was lower when determined by Spira than with the Mefar dosimeter (P<0·05). Transition equations calculated by linear regression analysis were: PD20mefar=exp10[0·897 + 0·678(logPD20spira)] (P<0·05; r=0·62)  and PD20spira=exp10[0·759 + 0·559 (log PD20mefar)] (P<0·05; r=0·62). The slopes were calculated by regressing the percentage fall in FEV1 on log10 (dose) and transformed as slope=100/(regression coefficient + 10). The mean slope (95% CI) for Spira was 3·1 (2·6–3·7) and for Mefar 4·4 (3·6–5·1) (P<0·005). Regression equations calculated by linear regression analysis were: slopemefar=2·126 + 0·712 slopespira (P<0·05; r=0·51) and slopespira=1·551 + 0·365 slopemefar (P<0·05; r=0·51). In conclusion, PD20 was smaller and the decline in FEV1/log(dose) curve steeper using the Spira compared with the Mefar protocol. The dose–response curves should be validated and transition equations calculated when bronchial reactivity to inhaled agents is compared, even while using apparently similar well‐standardized dosimeter methods.
Simple forced oscillatory technique and spirometry in assessment of bronchial responsiveness in non‐asthmatic and asthmatic subjects
Authors: Randell  , Salonen  , Tukiainen
Published: March 2003

Simple validity controlled forced oscillatory respiratory resistance (Rrsfo) at 8 Hz frequency was compared with flow‐volume spirometry in detection of bronchial changes during induced broncho‐constriction. The methacholine provocation test was performed in subjects with mild asthma (n = 18) and in non‐asthmatic subjects (n = 61) of which 44 were classified as responders (ΔFEV1 ≥ 15% in methacholine test). According to the index of maximal response/coefficient of variation for immediately repeated measurements (Δmax/Coeffvar), Rrsfo was shown to be at least as sensitive indicator of bronchoconstriction as FEV1, and better than MMEF and FVC. The shape of the dose–response curves were similar for all parameters. In the non‐asthmatic group, there were similar plateaux in Rrsfo, FEV1, and FVC at the same methacholine concentrations. In the asthmatic group, the provocative concentrations for Rrsfo and spirometric parameters correlated significantly (PC60‐Rrsfo versus PC10‐FEV1, P<0·05; PC60‐Rrsfo versus PC25‐MMEF, P<0·01). In the non‐asthmatic responsive subjects, the correlations between PC60‐Rrsfo and PC25‐MMEF were significant (P<0·05). Thus, Rrsfo at a fixed 8 Hz frequency and built‐in validity control was shown to be at least as sensitive an indicator for changes in lung function in asthmatic and non‐asthmatic responsive subjects as spirometry. Compared to spirometry, it may give additional information with fewer confounding factors during performance.
Is routine echocardiography useful in patients hospitalized for chest pain? Evidence of areal myocardial dysfunction detected only by echocardiography
Authors: Luotolahti Matti , Hänninen Kai‐Petri , Saraste Markku , Porela Pekka , Peltonen Jari‐Matti , Pulkki Kari , Hartiala Jaakko , Voipio‐Pulkki Liisa‐Maria
Published: March 2003

To assess the diagnostic value of routine two‐dimensional echocardiography in the coronary care unit setting, we studied 81 unselected patients admitted for acute chest pain. Using electrocardiography (ECG), clinical history and serum markers of myocardial injury, the patients were retrospectively diagnosed as having had definite acute myocardial infarction (AMI) with (n=13) or without (n=31) previous infarction, possible AMI with (n=14) or without (n=15) previous infarction, and non‐coronary cardiac or other causes of chest pain (n=8). Abnormal wall motion was observed in 75/77 patients with a cardiac origin of symptoms (sensitivity 97%), and there were no false‐positive wall motion findings. In the 73 patients who were finally diagnosed with coronary artery disease (CAD), echocardiography showed wall motion abnormality in at least one additional coronary territory area in which there were no diagnostic ECG changes for 56% of patients with CAD (41/73) (P<0·001). These areas were considered to be indicative of the presence of myocardium at risk for future cardiac events. We conclude that in addition to being a sensitive and accurate tool for detection of ischaemic wall motion abnormalities, two‐dimensional echocardiography can give valuable information about the area of myocardium at risk. Therefore, therapeutic decisions can be affected by the findings of the routine echocardiographic examination, which is recommended even in unselected coronary care unit patients.
Forearm metabolism during infusion of adrenaline: comparison of the dominant and non‐dominant arm
Authors: Simonsen Lene , Stefl Bohumir , Bülow Jens
Published: March 2003

Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain‐gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured by the local133Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a‐v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0·3 nmol kg−1 min−1. No difference in the metabolic information obtained in the fasting state could be demonstrated. During infusion of adrenaline, blood flow and lactate output increased significantly more in the non‐dominant arm (8·12 ± 1·24 versus 6·45 ± 1·19 ml 100 g−1 min−1) and (2·99 ± 0·60 versus 1·83 ± 0·43 μmol 100 g−1 min−1). Adrenaline induced a significant increase in oxygen uptake in the non‐dominant forearm (baseline period: 4·98 ± 0·72 μmol 100 g−1 min−1; adrenaline period: 6·63 ± 0·62 μmol 100 g−1 min−1) while there was no increase in the dominant forearm (baseline period: 5·69 ± 1·03 μmol 100 g−1 min−1; adrenaline period: 4·94 ± 0·84 μmol 100 g−1 min−1). It is concluded that the two forearms do not respond equally to adrenaline stimulation. Thus, when comparing results from different studies, it is necessary to know which arm was examined.
Isotonic dynamometry for the assessment of power and fatigue in the knee extensor muscles of females
Authors: Stauber  , Barill  , Stauber  , Miller
Published: March 2003

Impairments in muscle power production and recovery following short‐duration intense activity could lead to decreased performance and risk of injury. We developed a power test for the knee extensor muscles using torque–velocity testing and moderate isotonic loads. Twenty‐eight female volunteers performed three maximal efforts at each of four isotonic loads (27·1, 40·6, 54·2 and 67·8 N · m). If the calculated regression line for the torque–velocity data had an r2 ≥ 0·95 (i.e. an acceptable test), maximal power (408 ± 56 W) was computed from the data. Immediately after torque–velocity testing, the subjects repeated maximal effort knee extensions with 33·9 N · m for three bouts of 15 repetitions with 15 s of rest to produce muscle fatigue, defined as a decrease in power output during isotonic exercise. After a 4 min rest, the torque–velocity test was repeated and power calculated (345 ± 48 W). For the group, the recovery of maximal power after the fatigue protocol was 85%. The extremes were represented by one subject who recovered only 70% of her maximal power and another who recovered completely (>98%). Physiological differences in muscle power following repeated exercise could have an impact on the outcome of therapeutic interventions for sports injuries, fatigue syndromes and occupational over‐use conditions.
Cerebral haemodynamics during the Mueller manoeuvre in humans
Authors: Reinhard  , Hetzel  , Hinkov  , Lücking
Published: March 2003

Voluntary negative intra‐thoracic pressure (Mueller manoeuvre) is known to reduce arterial blood pressure (ABP). To investigate changes in cerebral blood flow velocity (CBFV) during 15 s Mueller manoeuvres at –30 mmHg intra‐thoracic pressure, 27 young (aged 21–31 years, group A) and 11 older (52–64 years, group B) healthy adults were studied using transcranial Doppler and non‐invasive ABP measurement (Finapres). After closely following the initial ABP drop, CBFV showed an overshoot during temporary recovery of ABP. Then ABP and CBFV decreased significantly to below baseline. While ABP declined further until the end of the manoeuvre, CBFV increased in group A 4·7 s (2·4–8·5) (median and range) and in group B 5·7 s (4·1–7·2) after the onset of the CBFV decrease. Critical closing pressure (CCP), calculated for each cardiac cycle from the dynamic pressure–flow relationship (DPFR), indicated a reduction of intra‐cranial pressure during the first half of the strain. DPFR‐related estimation of cerebrovascular resistance provided a more physiological response than the conventional cerebrovascular resistance quotient ABP/CBFV, and decreased about 1·5 s before the observed CBFV increase. A modification of the previously described dynamic auto‐regulation index ROR correlated significantly with CO2 reactivity values (r=0·61, P=0·001). In conclusion, changes in CBFV during Mueller manoeuvres are likely to reflect dynamic cerebral auto‐regulation and may provide an estimate of dynamic cerebral auto‐regulation capacity. In older adults, the maximal dynamic auto‐regulatory response seems to be unchanged, but the onset of reaction is slightly delayed.
Capnography in spontaneously breathing preterm and term infants
Authors: Tirosh E. , Bilker A. , Bader D. , Cohen A.
Published: March 2003

Objective: To investigate sidestream EtCO2 wave patterns as related to prematurity. Design: The EtCO2 wave pattern was analyzed longitudinally in 20 sequential preterm, 32–37 weeks of gestation and 39 fullterm controls. Infants with a cardiorespiratory disease, neurological deficit or a metabolic disorder were not included in the study. Sidestream EtCO2 was employed. Wave patterns were identified and baseline expiratory/inspiratory length and wave amplitude were measured. Results: Two predominant (about 75%) wave patterns were identified: (i) (with plateau) significantly more prevalent among infants born at term as compared with preterm infants across their postconceptional ages (PCA) (P=0·005–0·04), (ii) (plateau free) significantly more prevalent among the youngest preterm infants as compared with the fullterm controls. Expiratory length was significantly correlated with respiratory rate (RR) across ages (P=0·01–0·001) whereas inspiratory length was correlated with RR among the two youngest groups of infants only (P=0·002 and 0·004). Wave patterns were not found to be affected by environmental temperatures, blood pressure, body weight, haemoglobin level, aminophylline or O2 supplementation. Conclusion: These findings suggest that EtCO2 wave pattern distribution among preterm infants is distinctly different from that of term controls, regardless of PCA, while inspiration is related to the degree of maturity. Alveolar pathology could probably be missed by sidestream capnography.
Effects of exogenous melatonin on pituitary hormones in humans
Authors: Ninomiya Tosirou , Iwatani Noritaka , Tomoda Akemi , Miike Teruhisa
Published: March 2003

The effects of melatonin on physiological function remain unclear, although the therapeutic potential of melatonin is being increasingly recognized. The aim of the present study is to investigate the effects of exogenous melatonin on the spontaneous release of pituitary hormone in humans. A double blind placebo‐controlled protocol was designed to examine 12 adult healthy volunteers and 12 sleep disorder patients who have been treating with low doses of melatonin for 1 year. Either exogenous melatonin or placebo of 1 mg was given at 09:00 hours, followed by the collection of blood samples every 20 min for 4 h. Each blood sample was examined for levels of serum melatonin, PRL, LH, FSH, GH and TSH. LH levels were higher in sleep disorder patients compared with the healthy volunteers. In other pituitary hormones, there were no significant difference between healthy adults and sleep disorder patients. In all subjects, PRL levels were stimulated by acute administration of 1 mg of exogenous melatonin, while the levels of other pituitary hormones were not affected. These results suggested that exogenous melatonin can affect the spontaneous release of LH and PRL in humans. In addition, we demonstrated that 1‐year oral melatonin treatment did not affect the responses to the acute administration of melatonin.
Forearm blood flow measurements using computerized R‐wave triggered strain‐gauge venous occlusion plethysmography: unilateral vs. bilateral measurements
Authors: Kamper Adriaan M. , De Craen Anton J. M. , Blauw Gerard J.
Published: March 2003

The human forearm is a well established model to study local vascular reactivity in humans in vivo, using strain‐gauge venous occlusion plethysmography to measure blood flow and changes in blood flow in the forearm. To reduce the intra‐individual variability of the forearm blood flow (FBF), it has been advocated that simultaneous measurements of contralateral forearm blood flow is obligatory. Therefore, the use of the calculated forearm ratio (FR) is recommended instead of using the actual FBF. In the present study we compared the intra‐individual variability of forearm blood flow measurements and the forearm ratio, by using computerized R‐wave triggered strain‐gauge venous occlusion plethysmography, to test if bilateral expression of measurements is better than unilateral. Results were obtained in eight volunteers. Intra‐arterial infused sodium nitroprusside induced a dose dependent increase in forearm blood flow and a dose dependent increase in the calculated forearm ratio. Intra‐arterial infused norepinephrine induced a dose dependent decrease in forearm blood flow and a dose dependent decrease in the calculated forearm ratio. The differences between the variation coefficients of the forearm blood flow measurements and the calculated forearm ratio were different. These results support our hypothesis that by using a computerized, R‐wave triggered system for unilateral forearm blood flow measurement is a more reliable outcome than the calculated forearm ratio derived from bilateral measurements.
Standardized submaximal exercise testing in never smokers: a normative study
Authors: Gulsvik Amund , Beckett Laurel A. , Bakke Per , Humerfelt Sjur , Omenaas Ernst , Speizer Frank E.
Published: March 2003

In a population survey on the south‐western coast of Norway, 373 never smokers aged 18–73 years (230 women) without respiratory symptoms performed a standardized, progressive, incremental submaximal bicycle exercise test. All individuals were able to do an exercise involving oxygen uptake of 1·0 l min–1, 80% of the subjects reached 1·5 l min–1 and 50% of the subjects reached 2·0 l min–1. The respiratory frequency (RF), ventilation (VE) and heart rate (HR) for a given oxygen uptake were all higher in women than in men. Significant predictors of failure to reach oxygen uptake of 1·5 and 2·0 l min–1 were sex, age, body height and weight. Prediction equations are given for respiratory frequency, heart rate and ventilation for an oxygen uptake of 1·0 l min–1 in women and 1·5 l min–1 in men; and body height is a strong predictor for all dependent variables. A multiple linear regression analysis in women showed that age was a significant predictor of respiratory frequency (P<0·05), ventilation (P<0·001) and heart rate (P<0·001), while in men age was a significant predictor only of ventilation (P<0·001) during the bicycle exercise protocol.
Expiratory and inspiratory forced vital capacity and one‐second forced volume in asymptomatic never‐smokers in Norway
Authors: Gulsvik A. , Tosteson T. , Bakke P. , Humerfelt S. , Weiss S. T. , Speizer F. E.
Published: March 2003

The objectives of this study were to examine within and between individual variation detected during forced expiratory (FE) and forced inspiratory (FI) manoeuvers in a general population and to investigate the dependence of these variables on age, body size, and gender. A random sample of asymptomatic never smokers who had never been exposed occupationally to quartz or asbestos and who were living on the south‐western coast of Norway were examined by spirometry; 81% of the individuals invited to attend did so. Of the 488 subjects between 18 and 73 years of age, 98% contributed three acceptable recordings for forced expiratory vital capacity (FVC) and one‐second forced expiratory volume (FEV1), 94% contributed three acceptable recordings for forced inspiratory vital capacity (FIVC) and 85% contributed three acceptable recordings for one‐second forced inspiratory volume (FIV1). The within‐subject variation increased with body height and was considerably larger for FIV1 than for FVC, FEV1 or FIVC. A four‐parameter model of pulmonary function measurement divided by height squared, including a gender term and a linear and quadratic term of age, fit the median of the observed values well. The residuals had a close‐to‐normal distribution, and the fifth‐percentile values were estimated as the lower limit of normal. The peak value of dynamic lung volumes was observed into the middle of the fourth decade of life, and the decline thereafter did not differ greatly between the genders or among the different indices. The forced inspiratory volumes are the first reported in any reference population.