bluuebunny/crossref_metadata_2025 huggingface dataset:
Pituitary tumours are multiclonal from the outset: evidence from a case with dural metastases
Authors: Buch H. , El‐Hadd T. , Bicknell J. , Simpson D. J. , Farrell W. E. , Clayton R. N.
Published: March 2003

In 1992 a 54‐year‐old man underwent transsphenoidal adenomectomy to remove a clinically nonfunctioning pituitary adenoma during which there was a transient cerebrospinal fluid (CSF) leak. He received radiotherapy to a small residual remnant. Follow‐up magnetic resonance imaging (MRI) scan in 1997 showed an increase in the tumour in the pituitary stalk region and an additional intradural lesion at C1 level. In the absence of neurological symptoms and signs, an observational policy was followed. By 1999 the cervical dural lesion had enlarged and laminectomy was performed, during which three intradural lesions were removed. Histology and immunohistochemistry of the metastases were identical to those of the initial pituitary adenoma. Follow‐up MRI scan showed extension of the pituitary remnant above the chiasma, requiring transfrontal surgery. Operation was complicated by secondary brain haemorrhage from which the patient died. Autopsy revealed a small amount of residual tumour at the top of the stalk and several small intradural tumour nodules at the level of the foramen magnum. Genetic analysis of the initial pituitary tumour identified significant allelic losses in keeping with its invasive nature, while that of the metastases indicated a separate clone as shown by retention of alleles lost in the primary tumour. The regrown pituitary tumour also appeared to be of a different clone to the initial tumour and the same as two of three of the first metastases (C1 level). The foramen magnum metastasis showed the same loss of heterozygosity (LOH) pattern as one of the original C1 metastases and the pituitary tumour tissue obtained at autopsy. We speculate that at the initial pituitary surgery, cells seeded into the CSF and grew in the dura. These cells were from a different clone, implying that the original pituitary tumour contained at least two clones, possibly three, providing evidence for the contemporaneous oligoclonality of the original pituitary tumour.
Knockout models are useful tools to dissect the pathophysiology and genetics of insulin resistance
Authors: Mauvais‐Jarvis Franck , Kulkarni Rohit N. , Kahn C. Ronald
Published: March 2003

objective The development of type 2 diabetes is linked to insulin resistance coupled with a failure of pancreatic β‐cells to compensate by adequate insulin secretion.

design Here, we review studies obtained from genetically engineered mice that provide novel insights into the pathophysiology of insulin resistance.

results Knockout models with monogenic impairment in insulin action have highlighted the potential role for insulin signalling molecules in insulin resistance at a tissue‐specific level. Polygenic models have strengthened the idea that minor defects in insulin secretion and insulin action, when combined, can lead to diabetes, emphasizing the importance of interactions of different genetic loci in the production of diabetes. Knockout models with tissue‐specific alterations in glucose or lipid metabolism have dissected the individual contributions of insulin‐responsive organs to glucose homeostasis. They have demonstrated the central role of fat as an endocrine tissue in the maintenance of insulin sensitivity and the development of insulin resistance. Finally, these models have shown the potential role of impaired insulin action in pancreatic β‐cells and brain in the development of insulin deficiency and obesity.
Low goitre prevalence among users of oral contraceptives in a population sample of 3712 women
Authors: Knudsen Nils , Bülow Inge , Laurberg Peter , Perrild Hans , Ovesen Lars , Jørgensen Torben
Published: March 2003

objective Goitre occurs primarily in women. As oestrogens may be an aetiologic factor, the use of oral contraceptives (OC) could be associated with an increased risk of goitre. This is supported by experimental data, but a recent population study suggested decreased thyroid volumes among users of OC.

design Cross‐sectional, observational study.

participants A random population sample of 3712 women from two Danish cities.

measurements Ultrasound and clinical examination of the thyroid, measurement of serum TSH, T3, T4 and thyroglobulin, and personal interviews with registration of use of OC or post‐menopausal oestrogen therapy. Data were analysed in linear models and logistic regression adjusting for age and iodine status.

results Thyroid volume was lower among users than non‐users of OC, 11·1 ml vs. 12·1 ml (P < 0·001). Use of OC was correspondingly associated with a reduced prevalence of thyroid enlargement on ultrasound (odds ratio 0·53, 95% confidence interval 0·37–0·74) and of palpable and visible goitre (OR 0·24, 95% CI 0·07–0·81). Serum TSH was 1·24 mU/l in non‐users of OC and 1·35 mU/l in users (P = 0·002). The percentage of goitre cases prevented by OC compared to a hypothetical population without use of OC was 29%. Post‐menopausal oestrogen therapy showed similar, but statistically non‐significant, associations.

conclusion Use of oral contraceptives was associated with a lower thyroid volume and reduced risk of goitre, and clinically evident goitre was four times more frequent among non‐users than among users of oral contraceptives.
Pitfalls in pituitary diagnosis: peculiarities of three cases
Authors: Glezer A. , D’Alva C. B. , Salgado L. R. , Musolino N. R. , Serafini P. , Vieira J. G. , Bronstein M. D.
Published: March 2003

Due to the increasing availability and sensitivity of diagnostic methods, biochemical and imaging abnormalities of pituitary function and anatomy are becoming more frequent. Hyperprolactinaemia was found in three women without any prolactin (PRL) related clinical features. All three patients had normal libido, regular menses with evidence of ovulation, no galactorrhoea, and normal FSH, LH, TSH and free T4 serum levels. Magnetic resonance imaging (MRI) of the sellar region showed images that were compatible with pituitary microadenomas in all three cases. Due to the discordance between laboratory and clinical features, we searched for the presence of PRL aggregates with high molecular weight and low biological activity (macroprolactinaemia). Initially, we screened with a polyethylene glycol precipitation method, and then confirmed the presence of macroprolactinaemia by chromatography. All three cases screened positive for the presence of macroprolactinaemia. MRI alterations, compatible with pituitary microadenomas, may be due to true microincidentalomas, normal anatomical variations or imaging artefacts. In conclusion, we have described the presence of double diagnostic pitfalls that might lead to unnecessary medical or surgical intervention.
Biochemical markers of growth hormone (GH) sensitivity in children with idiopathic short stature: individual capacity of IGF‐I generation after high‐dose GH treatment determines the growth response to GH
Authors: Kamp G. A. , Zwinderman A. H. , Van Doorn J. , Hackeng W. , Frölich M. , Schönau E. , Wit J. M.
Published: March 2003

objective and patients  To assess multiple dose–response relationships between three GH doses (1·5, 3·0 and 6·0 IU/m2) and nine different biochemical markers of GH sensitivity in a well‐defined group of 17 children with idiopathic short stature (ISS).

design and measurements  Serum levels of IGF‐I, IGF‐II and IGFBP‐3, and peripheral markers leptin, C‐terminal propeptide of type I collagen (PICP) and N‐terminal propeptide of type III collagen (PIIINP), alkaline phosphatase (AP) and osteocalcin (OC) were measured at the start and after 2 and 12 weeks of periods of no treatment, GH 1·5 IU/m2 and GH 3·0 IU/m2. Twelve‐week washout periods were applied between the 12‐week GH‐treatment periods. High‐dose GH treatment was given during the second year of study and all serum markers were measured at start, after 2 and 12 weeks and 1 year of GH 6·0 IU/m2. In 18 non‐GH‐treated children with ISS the same parameters were measured yearly. The bone resorption marker urinary deoxypyridinoline (DPD) was measured during 12‐h day and night periods at start and after 2 weeks GH 1·5, 3·0 and 6·0 IU/m2.

results  All markers were GH dependent, but the timing of maximal response varied among different markers. Height SDS at start, age at start and IGF‐II at baseline were inversely related to the first‐year growth response (r = −0·73, P = 0·001; r = −0·53, P = 0·03; and r = −0·53, P = 0·03, respectively). Some statistically significant correlations between biochemical responses on low GH doses (1·5 or 3·0 IU/m2) and second‐year growth response were found, but these showed no consistent pattern. However, all changes in IGF‐I SDS after GH 6·0 IU/m2 measured either after 2 or 12 weeks or 1 year correlated significantly with the second‐year growth response (r = 0·55, P = 0·02; r = 0·81, P = 0·001; and r = 0·86, P < 0·001, respectively). Baseline or GH‐stimulated levels of peripheral markers did not correlate with the growth response.

conclusion  The individual capacity of IGF‐I generation after high‐dose GH treatment (6·0 IU/m2) determines the growth response on high‐dose GH treatment. Peripheral markers do not seem to play a role in growth prediction of children with ISS.
Growth failure in a child showing characteristics of Seckel syndrome: possible effects of IGF‐I and endogenous IGFBP‐3
Authors: Schmidt A. , Chakravarty A. , Brommer E. , Fenne B. D. , Siebler T. , De Meyts P. , Kiess W.
Published: March 2003

Seckel syndrome is an autosomal‐recessive disorder with a frequency of less than 1/10 000 births in which there are multiple malformations including severe short stature. We report on a patient with Seckel syndrome with a current body height of −7·5 SDS. Laboratory investigations at the age of 19 months revealed high levels of IGF‐I, IGF‐II and IGFBP‐3. These data suggested the existence of IGF‐I resistance possibly caused by impairment of the IGF‐I receptor (IGF‐IR) or altered IGFBPs. The purpose of this investigation was to examine whether the growth retardation in a Seckel syndrome patient is related to an alteration in the IGF system. Analysis of IGF‐IR mRNA of patient's and control fibroblasts by solution hybridization/RNase protection assay did not show differences of IGF‐IR transcript expression or size. Affinity crosslinking studies using [125I]‐IGF‐I showed normal‐sized IGF‐IR–ligand complexes. Mutation analysis of the complete coding regions of the IGF‐I and IGF‐IR genes showed no evidence of genetic alterations. Ligand blot analysis of IGFBPs secreted by the patient's fibroblasts showed stronger signals than control cells. Quantitative measurement of IGFBP‐3 in cell‐conditioned media was performed by radioimmunoassay (RIA) and revealed a sixfold increase when compared to control fibroblasts. We conclude that in this patient with Seckel syndrome and severe growth impairment IGF‐I resistance is possibly related to altered production of IGFBP‐3.
Postpartum recurrence of Graves’ hyperthyroidism can be prevented by the continuation of antithyroid drugs during pregnancy
Authors: Nakagawa Yoshinori , Mori Kouki , Hoshikawa Saeko , Yamamoto Makiko , Ito Sadayoshi , Yoshida Katsumi
Published: March 2003

objective Previous studies recommend the discontinuation of antithyroid drug (ATD) therapy during pregnancy in women with well‐controlled Graves’ hyperthyroidism (GH). In this study, we investigated whether this termination of ATD therapy during pregnancy is beneficial in terms of postpartum GH recurrence.

design A nonrandomized, retrospective study.

patients Sixty‐five pregnant GH patients treated with maintenance doses of ATDs were assigned into two groups: ATD therapy was discontinued before delivery in Group 1, but continued during pregnancy and after delivery in Group 2.

measurements The prevalence of postpartum recurrence or exacerbation of GH within 1 year after delivery was examined. Serum T4, T3 TSH, and TSH receptor antibody levels were measured.

results In Group 1, 70·8% (17/24) of patients suffered a recurrence of GH within 1 year after delivery. In contrast, a postpartum exacerbation of GH was observed in only 29% (12/41) of patients in Group 2 (P < 0·01). Both exacerbations and recurrences of GH appeared primarily within 4–6 months after delivery. Apparent neonatal hypothyroidism and malformations were not observed in the offspring of either group.

conclusion Continuing antithyroid drug therapy throughout pregnancy prevents postpartum recurrence of Graves’ hyperthyroidism without resulting in neonatal hypothyroidism or malformations.
Increased incidence of parathyroid adenomas following X‐ray treatment of benign diseases in the cervical spine in adult patients
Authors: Rasmuson Torgny , Damber Lena , Johansson Lennart , Johansson Robert , Larsson Lars‐Gunnar
Published: March 2003

Objective To determine whether or not exposure to ionizing radiation as an adult increases the risk of developing parathyroid adenomas.

Design and Patients A cohort of 27 415 patients had received X‐ray treatment to palliate pain originating from arthrosis and spondylosis from 1950 to 1964. In a subcohort of 8144 patients the cervical spine was the target, or one of the targets for the treatment. With the technique used it could be assumed that, as a rule, the parathyroid glands had been included in the treated volume. Patients with parathyroid adenomas were obtained from the Swedish Cancer Register from 1958 to 1995. The standardized incidence ratio (SIR) was calculated.

Results The number of person‐years at risk was 180 492 in the cohort exposed at the cervical spine, and 412 994 in the control cohort irradiated only at other sites. The calculated dose in the parathyroid region in the study cohort was about 1 Gy. The observed number of parathyroid adenomas in the study cohort was 22, and 24 in the control cohort. Expected numbers based on population data were 12·0 and 24·7, respectively, giving an SIR of 1·83 (95% CI 1·14–2·76) and 0·97 (CI 0·62–1·45), respectively. Mean age at exposure was 48·9 years (SD 10·2) and at diagnosis 71·5 years (SD 8·3). The time from exposure to diagnosis varied from 2 to 34 years (median 26 years). The excess relative risk was about 0·8 per Gy.

Conclusion Exposure to ionizing radiation to the cervical spine in adult age seems to be associated with an increased risk of developing parathyroid adenomas.
CAG repeat length in the androgen receptor gene and gonadotrophin suppression influence the effectiveness of hormonal male contraception
Authors: Eckardstein Sigrid v. , Schmidt Anja , Kamischke Axel , Simoni Manuela , Gromoll Jörg , Nieschlag Eberhard
Published: March 2003

objective Nonuniformity in suppression of spermatogenesis induced by various hormones or hormone combinations has impeded the development of an effective hormonal male contraceptive. The basis for this heterogeneity in response remained unresolved to date; however, the presence of ethnic differences points to an involvement of genetic factors.

patients and measurements In a retrospective analysis we investigated the impact of a CAG repeat polymorphism in the androgen receptor and polymorphic sites in the oestrogen and FSH receptor genes on spermatogenic suppression in 85 Caucasian men treated with different regimens of hormonal contraception.

results Failure to reduce sperm concentrations below 3 million/ml was significantly associated with insufficient suppression of gonadotrophins. The extent of gonadotrophin suppression was not explained by any polymorphism but was primarily pharmacological, resulting from addition of gestagens to testosterone. When LH and FSH suppression was rapid and persistent none of the polymorphisms studied explained why some men failed to achieve azoospermia. In cases with incomplete gonadotrophin suppression the chances of becoming azoospermic were 2·5 times higher in men having more than 22 CAG repeats.

conclusions In summary, our analysis shows that in a subset of men, effective hormonal male contraception can be achieved even in the absence of complete gonadotrophin suppression.
Leptin measurement in urine in children and its relationship to other growth peptides in serum and urine
Authors: Zaman Nasra , Hall Catherine M. , Gill Matthew S. , Jones Julie , Tillmann Vallo , Westwood Melissa , Whatmore Andrew J. , Clayton Peter E.
Published: March 2003

objective Leptin has been implicated in the interaction between nutrition, energy balance and sexual maturation in humans. A non‐invasive method of measuring leptin would greatly facilitate longitudinal studies of changes in leptin in normal children. The aim of this study was to evaluate the use of urinary leptin as a surrogate for serum leptin measurements.

design We have modified and validated a serum immunoradiometric assay (IRMA) kit for the measurement of leptin in urine, and subsequently investigated the relationship between urinary leptin and other growth‐related proteins.

methods Cross‐sectional study: urinary leptin, measured in the first morning urine voided and expressed as ng excreted overnight, and serum concentrations of leptin, IGF‐I, IGF‐II, IGFBP‐3 and IGFBP‐1 were determined in a cohort of 188 healthy schoolchildren aged 5–19 years (88 males, 100 females). Height, weight and pubertal status were assessed in all children.

Longitudinal study: urinary levels of leptin, IGF‐I and GH were measured daily in two adults (one male, one female) over a period of 6 weeks.

results The detection limit of this modified assay was 0·59 ng/L. The intra‐ and interassay coefficients of variation range was 4–8% and 4–9%, respectively. The recovery of recombinant leptin added to urine was 98–108%, and the assay had a recovery rate for serial dilution in the range of 106–112%. Urinary leptin correlated significantly with serum leptin (r = +0·65, P < 0·01). Urinary leptin showed similar changes through puberty to those of serum leptin, with levels rising in females throughout puberty, whereas in males levels peaked at G2/G3 then decreased. BMI SDS was the main determinant of urinary leptin, as it was for serum leptin. In the cross‐sectional study urinary leptin correlated significantly with serum IGF‐I (r = +0·41, P = 0·001), IGF‐II (r = +0·19, P = 0·05), IGFBP‐3 (r = +0·29, P = 0.001) and IGFBP‐1 (r = −0·25, P = 0·001). In the adult study, leptin was also detected in urine with similar night‐to‐night variability to that found for IGF‐I and GH.

conclusion Urinary leptin is a valid marker of serum leptin concentrations, and therefore this non‐invasive assay would be a useful tool for longitudinal assessment of changes in leptin in children.
The insulin‐like growth factor‐I generation test: peripheral responsiveness to growth hormone is not decreased with ageing
Authors: Lissett Catherine A. , Shalet Stephen M.
Published: March 2003

objective Ageing is accompanied by a reduction in GH secretion, and a decrease in circulating IGF‐I. Few data are available on whether the responsiveness of IGF‐I to GH stimulation changes with age.

subjects and methods Therefore we carried out multiple IGF‐I generation tests in 26 healthy volunteers (16 male) of normal body mass index (BMI); nine aged 20–40 years, six aged 41–60 years, and 11 aged > 61 years. Each subject received three single doses of GH: 0·8, 2·0 and 21 IU in random order at least 4 weeks apart. Serum samples were taken 0, 18, 24, 48, 72 and 120 h following each dose of GH.

results Basal serum levels of IGF‐I (P < 0·0001) and IGFBP‐3 (P < 0·01) declined with age, but serum acid‐labile subunit (ALS) levels did not (P = 0·2). Peak IGF‐I levels (P < 0·01 for 0·8 IU and P < 0·05 for the 2 IU dose) and area under curve (AUC) IGF‐I (P < 0·01 for the 0·8 IU and 2·0 IU doses of GH and P < 0·05 for the 21 IU dose) after GH administration continued to demonstrate a significant trend towards lower values with increasing age. However, the increment in IGF‐I, IGFBP‐3 and ALS in response to GH did not decline with age. Indeed, the increment in IGF‐I after 2 IU of GH, judged by the increase from basal to peak levels, increased with advancing age (P = 0·05), and a positive relationship was seen between the increment in the area under the IGF‐I curve following the 21 IU dose of GH and age (P < 0·02).

conclusion These data illustrate that although activity of the GH/IGF‐I axis declines with age, peripheral responsiveness to GH is not attenuated. This suggests that a decrease in GH responsiveness does not contribute to the age‐related fall in circulating GH‐dependent peptides. Thus, for those embarking on trials of GH therapy or GH secretagogues in the elderly, the capacity to generate IGF‐I will not limit potential efficacy. Furthermore, the dose of GH replacement required for patients with organic GH deficiency is likely to be lower in the elderly compared with young adults.
Inhomogeneity in planar ventilation scintigraphy of emphysematous patients
Authors: Xu J. H. , Moonen M. , Johansson Å. , Bake B.
Published: March 2003

The aim of this study was to develop and evaluate a method for the quantification of inhomogeneity in ventilation scintigraphy. Ten healthy volunteers and 10 emphysematous patients were investigated. Anteroposterior (AP) and posteroanterior (PA) images of planar ventilation scintigraphy were acquired. Lung regions of interest (ROI) were obtained by manual delineation of the lung contours and then divided into several 10‐pixel‐high horizontal‐stripe regions. By allowing for the statistical noise of the pixel count rate, the biological coefficient of variation (CVB) of the pixel counts in each stripe region was calculated. The apex‐to‐base distribution of the CVB in the emphysematous lungs dispersed largely and with higher values than the corresponding distribution in the healthy lungs. The mean values of the CVB (MCVB), the ranges of the CVB (RCVB) and the maximum values of the CVB (MAXCVB) in the stripe regions in emphysematous lungs were significantly higher than the corresponding ones in the healthy lungs (all P<0·001). The intraobserver variations of the MCVB, RCVB and MAXCVB (calculated using the standard deviations of the differences) were less than 2·3% units, 5·2% units and 3·9% units respectively. The corresponding values for interobserver variation were 5·7% units, 6·1% units and 6·4% units. A systematic decrease in lung ROI size, i.e. inclusion of successively less of the lung edge, resulted in a linear decrease of 1·7% units in the MCVB and MAXCVB of both emphysematous and normal lungs. In conclusion, the stripe‐region method is a reliable tool for the quantification of inhomogeneity in the planar ventilation scintigraphy.
Reproducibility of ultrasonic fetal volume blood flow measurements
Authors: Brodszki J. , Gardiner H. M. , Eriksson A. , Stale H. , Maršál K.
Published: March 2003

The intraobserver reproducibility of ultrasonic volume blood flow measurements in the human fetus was evaluated in this study. A new approach, simultaneous measurement of the vessel diameter and the flow velocity with a pulsed‐wave Doppler ultrasound synchronized with a real‐time ultrasound phase‐locked echo‐tracking system, was used to estimate volume blood flow (VBF) in the fetal descending aorta. Measurements were performed in a longitudinal study on 20 normally grown fetuses. Intraobserver reproducibility of repeated estimations of mean blood flow velocities throughout gestation was very good, with high values of intraclass correlation coefficient (IntraCC 0·80–0·91) and low values of coefficient of variation (CV 4–11%). The IntraCC of repeated vessel diameter measurements throughout gestation was low (0·30–0·68), whereas the values of CV were acceptable (< 12%), with the exception of the period between 140 and 167 gestational days (CV > 12%). The lower reproducibility of vessel diameter measurement contributed directly to the relatively low reproducibility of VBF estimations overall (IntraCC 0·25–0·70; CV 17–28%), as these are calculated from a formula using both flow velocity and vessel diameter. Nevertheless, the synchronized approach gives absolute values of vessel diameter, flow velocity and VBF comparable with values reported in the human fetus previously. The new method provides, by taking the vessel wall pulsations into consideration and by measuring diameter and velocity simultaneously, a more complete information on fetal haemodynamics and fetal physiology.
One‐year reproducibility and stability of the signal amplitude ratio and other variables of the electromyogram: test–retest of a shoulder forward flexion test in female workers with neck and shoulder problems
Authors: Elert Jessica , Karlsson Stefan , Gerdle Björn
Published: March 2003

We have studied 23 women with neck and shoulder problems in a car factory with a 1‐year interval. Our main aim was to investigate the reproducibility and stability of the tension pattern. In addition, the mean frequency (MNF) of the power spectrum and the signal amplitude (RMS) of the surface electromyograph (EMG) of the trapezius, deltoid and infraspinatus muscles and mechanical output were determined throughout 100 maximal isokinetic shoulder forward flexions. The signal amplitude ratio (SAR) was calculated as the ratio between the signal amplitude of the EMG of the passive relaxation and the active flexion part of each contraction cycle. The SAR variable can be reproduced (r = 0·47−0·76) with a 1‐year interval. There was a significantly lower SAR of the trapezius at the second test, which might have been due to lower work pace at the factory. The longitudinal patterns of SAR throughout the two tests were similar at both tests. There were significant correlations between tests for 18 out of 22 EMG variables, even though the correlations were generally lower than for SAR (initial MNF: r = 0·39−0·48; MNF endurance level: r = 0·55−0·83; RMS (%): r = 0·08− 0·46). Peak torque had better reproducibility than work. In conclusion, SAR has a long‐term reproducibility equal to or better than other EMG and biomechanical variables. The present results indicate that SAR has potential to measure unnecessary muscle tension in intervention studies and to identify individual movement patterns.
Myocardial sestamibi uptake in healthy subjects is related to age, gender and habitus
Authors: Bouvier  , Bevegård  , Nejat  , Jensen‐Urstad
Published: March 2003

The object of this study was to evaluate the effect of gender, age and anthropometric data on regional isotope uptake in myocardial perfusion scintigraphy using 99mTc‐MIBI‐SPECT (myocardial sestamibi single‐photon emission technique). Seventy‐one healthy, non‐smoking subjects, 42 men and 29 women between 40 and 80 years of age, with less than 5% likelihood of having coronary artery disease were studied. All subjects underwent a maximal exercise and rest MIBI‐SPECT using a 2‐day protocol and a 180° anterior circular rotation. No correction for scatter or attenuation was made. Normalized regional activity was different in men and women in the anterior and inferior regions, with higher values anteriorly in men and inferiorly in women. Regional activity also differed with age in both women and men with higher relative activity in the anterior regions in the oldest age groups. Higher activities were seen in the basal parts of the left ventricle at rest compared with stress in both men and women. Regional isotope uptake was significantly affected by habitus expressed as body mass index (BMI) and thoracic circumference. Different protocols for stress and rest seem to be needed for men and women in different age groups, and for stress and rest when performing semiquantitative MIBI‐SPECT and comparing data with a normal file of healthy subjects. Furthermore, such anthropometric data as BMI and/or thoracic circumference should be considered in order to minimize the risk for false‐positive or false‐negative scintigraphic results.
Effect of beta blockade with and without sympathomimetic activity (ISA) on sympathovagal balance and baroreflex sensitivity
Authors: Haberthür  , Schächinger  , Langewitz  , Ritz
Published: March 2003

Beta blockers increase heart rate variability (HRV) and improve survival in coronary artery disease (CAD). The benefit of beta blockers with intrinsic sympathomimetic activity (ISA) in CAD still remains a matter of debate, and their effect on HRV has not yet been investigated. Therefore, we measured HRV, systolic blood pressure variability (BPV) and baroreflex sensitivity (BRS) under propranolol (PROP, without ISA, 160 mg q.d.), pindolol (PIN, with potent ISA, 15 mg q.d.) and placebo (PLA, q.d.) in 30 healthy subjects, aged 21–39 years, during controlled frequency breathing (0·30 Hz) in supine and tilt positions. PROP increased HRV in the high‐frequency (0·15–0·40 Hz) band (PROP 7·4 ± 1·0; PLA 6·9 ± 1·4; PIN 6·8 ± 1·0 ln MI2; P = 0·003), decreased BPV in the low‐frequency band (at 0·1 Hz, Mayer waves) (PROP 0·6 ± 0·7; PLA 1·3 ± 1·1; PIN 1·2 ± 1·2 ln mmHg2; P = 0·001) and enhanced BRS (PROP 14·6 ± 9·5; PLA 8·0 ± 6·8; PIN 8·7 ± 6·8 ms  mmHg−1; P = 0·001) in the supine position. After passive tilt, PROP decreased HRV in the low‐frequency band (PROP 6·1 ± 0·9; PLA 6·5 ± 1·1; PIN 6·9 ± 0·7 ln MI2; P<0·001) and decreased Mayer waves (PROP 1·8 ± 0·8; PLA 2·4 ± 1·0; PIN 2·7 ± 0·8 ln mm Hg2; P<0·001). PIN increased the low‐frequency HRV response, which is induced by passive tilt (PIN + 0·9 ± 1·0; PLA + 0·3 ± 1·3, PROP + 0·3 ± 1·0  ln MI2; P = 0·026). Our results prove that beta‐adrenergic blockade with potent ISA does not increase HRV, has no beneficial effect on autonomic balance and even exaggerates sympathetic responses to passive tilt.
Non‐invasive cardiac output assessment during moderate exercise: pulse contour compared with CO2 rebreathing
Authors: Houtman Sibrand , Oeseburg Berend , Hopman Maria T. E.
Published: March 2003

The arterial pulse contour method called Modelflow 2·1 calculates stroke volume continuously, beat to beat, from the non‐invasive blood pressure signal measured by Finapres or Portapres. Portapres is the portable version of Finapres. The purpose of this study was to compare cardiac output (CO) calculated using Modelflow 2·1 (COmf) with CO obtained by the CO2 rebreathing method (COre) during steady state at moderate exercise levels. Twelve subjects visited the laboratory twice and performed submaximal exercise on a bicycle ergometer at 20%, 40% and 60% of their individual peak power output (POpeak). The averaged correlation between COmf and COre gives an r‐value of 0·69, whereas the slope and intercept of the regression line were 1·06 and 1·65 respectively. The averaged difference between COmf and COre was 2·27 ± 3·9 l min–1 (mean ± standard deviation). However, the test–retest difference between COmf and COre was 2·5 ± 3·1 and 0·5 ± 1·3 l min–1 respectively. These results suggest that Modelflow 2·1 is not an accurate method for estimating CO from non‐invasive blood pressure data collected by Portapres during exercise at up to 60% of the individual POpeak corresponding with daily life activity.
Clearance and renal extraction of technetium‐99m‐ L,	L‐ethylenedicysteine, I‐131‐ortho‐iodohippurate and I‐125‐iothalamate in pigs
Authors: Nielsen Søren S. , Poulsen Ejvind U. , Marqversen Jørgen , Nielsen Lene E. , Bacher Theis , Rehling Michael
Published: March 2003

99mTc‐ L,
L‐ethylenedicysteine (99mTc‐EC) has been proposed as a 99mTc‐labelled alternative to radio‐iodinated ortho‐iodohippurate (OIH) for renal imaging and evaluation of renal function. The kinetics of this new renal function agent were studied by a single‐injection plasma clearance technique in pigs. 99mTc‐EC, 131I‐OIH and 125I‐iothalamate were injected and the plasma concentration of the three tracers was followed for 240 min. Renal, hepatic and total plasma clearance were calculated. There was no difference between the renal plasma clearance of 99mTc‐EC and 131I‐OIH (175 ± 9 versus 178 ± 8 ml min−1, P=0·43), whereas the difference between the total plasma clearance of 99mTc‐EC and 131I‐OIH was highly significant (268 ± 16 versus 185 ± 9 ml min−1, P=0·0001). 99mTc‐EC had a significant hepatic clearance of 83 ± 10 ml min−1 whereas the hepatic clearance of 131I‐OIH was negligible. Renal plasma extraction of both 99mTc‐EC and 131I‐OIH decreased significantly between 2 and 240 min post‐injection from 0·85 to 0·45% for 99mTc‐EC and from 0·93 to 0·57% for 131I‐OIH. Red blood cell binding of 99mTc‐EC and 131I‐OIH was 6·1% and 20%, respectively. The protein binding of 99mTc‐EC and 131I‐OIH was 32% for both tracers. We conclude that 99mTc‐EC is not a suitable tracer for measuring renal function by the single‐injection plasma clearance technique in pigs. This is due to a decreasing renal extraction and a significant hepatic clearance.
Short‐term variations in oscillatory and spirometric lung function parameters of non‐asthmatic adults
Authors: Randell  , Salonen  , Pekkarinen  , Tukiainen
Published: March 2003

Oscillatory respiratory resistance (Rrsfo) at 8 Hz was compared to flow‐volume spirometry with regard to immediate, within‐day, day‐to‐day and week‐to‐week variations in seven female and four male non‐smoking, non‐asthmatic volunteers. The lung functions were measured at 08:00, 12:00, 16:00 and 20:00 h on each of the four study days, i.e. two consecutive days in two consecutive weeks. During each visit there were three immediately repeated measurements of Rrsfo, followed by three spirometric recordings. The intra‐subject coefficient of variation (Coeffvar) for the immediately repeated measurements was largest for Rrsfo (11·8%). When a simple reliability index (±2 SD of the differences between the repeated measurements) was applied to the Rrsfo data, the Coeffvar reduced to 7·5%. In spirometry, the airflow parameters at defined lung volumes showed larger immediate variations (MEF50=5·6%, MEF25=8·3%, MMEF=4·4%) than FEV1 (1·5%) and PEF (3·2%). The within‐day variations were larger than the day‐to‐day or week‐to‐week variations, and the variations were largest in Rrsfo. A significant diurnal pattern was shown in spirometric parameters but not in Rrsfo. About 38% of the total variance in Rrsfo was due to variation within subjects, while the corresponding proportions in spirometric parameters were 1·8–18·4%. In conclusion, Rrsfo showed larger intra‐subject variations than the spirometric parameters at all time intervals. Application of a simple reliability index and standardization of the time of day of the measurement reduced the variations and improved the quality of the Rrsfo data.
Determinants of post‐ischaemic reactive hyperaemia in patients with diabetes mellitus type II
Authors: Francesconi  , Koizar  , Wascher
Published: March 2003

Dysfunction of resistance arteries is thought to be an early reversible stage in the development of atherosclerosis. Dynamics of post‐ischaemic reactive hyperaemia are believed to constitute a useful tool for monitoring resistance vessel function. Patient characteristics influencing reactive hyperaemia, however, need to be defined more precisely. Since reactive hyperaemia is a dynamic process, yielding submaximal peak values after 5 min of ischaemia, this period was chosen to investigate the determinants of reactive hyperaemia in 100 type II diabetic patients as well as in 61 control subjects. Reactive hyperaemia was measured by venous‐occlusion plethysmography; clinical and laboratory data were acquired by routine methods. Statistical comparison was performed with SYSTAT 5·0 for Apple Macintosh. Overall, no significant differences between diabetic patients and controls were observed by group comparison. In control subjects, only gender showed an influence on peak reactive hyperaemia (females 40·5 ± 15·3; males 51·8 ± 17·7 ml min–1 100 ml–1, P<0·01). In diabetic patients, in addition to gender, actual blood glucose (r=0·377, P<0·05) and meal intake (non‐fasting 42·8 ± 19·2; fasting 51·2 ± 19·5 ml min–1 100 ml–1, P<0·05) were found to influence reactive hyperaemia. Further investigation revealed a loss of the correlation between peak reactive hyperaemia and actual blood glucose observed in the fasting state (P<0·001) in non‐fasting diabetic patients, indicating an influence of meal intake on resistance vessel reactivity. Our results suggest that, in diabetic subjects, in addition to gender actual blood glucose and the postprandial situation impacts on peak reactive hyperaemia.
Delayed respiratory response to exercise of short duration in patients with severe intermittent claudication due to bilateral atherosclerotic vascular disease: normalization after aorto‐bifemoral bypass operation
Authors: Refsum Harald E.
Published: March 2003

To investigate the respiratory response to exercise in patients with severe intermittent claudication, eight male patients, aged 57 years (range 43–73), with bilateral multi‐segment atherosclerotic vascular disease, median maximum walking distance 50 m (range 20–200) and ankle‐to‐arm pressure index 0·4 (range 0·3–0·6), were studied before and after aorto‐bifemoral bypass operation. Ventilation, CO2 output and O2 intake were recorded in the sitting position during 20 min of rest, 1 min of leg exercise on a bicycle ergometer [4·9 kJ (500 kpm)], and 20 min of recovery and rest. Before operation, maximal ventilation and CO2 output per minute were observed 2–4 min after cessation of work, while afterwards peak values were found during the work or the first minute of recovery. Pre‐operatively, the extra ventilation and CO2 output during the work and recovery period and the recovery times of the ventilation and CO2 output per minute were markedly increased. Afterwards these values were clearly reduced towards normal. It is concluded that patients with severe intermittent claudication show a characteristic delay and prolonged rise in the respiratory response to exercise of short duration, which closely corresponds to the previously described pattern of outflow of hypoxia‐generated metabolites from the exercising muscles. The pattern of respiratory response after operation reflects the fact that these patients also suffer from atherosclerotic heart dysfunction.
Measurement of lung density by photon transmission for monitoring intravascular and extravascular fluid volume changes in the lungs
Authors: Bergström Petra , Jacobsson Lars , Lomsky Milan
Published: March 2003

Left ventricular (LV) heart failure increases pulmonary blood volume (PBV) and interstitial fluid volume. Continuous measurements of lung density may be a simple non‐invasive method for monitoring of the LV function as the lung density should reflect the changes in the PBV and extravascular lung water. The purpose of the study was to optimize transmission measurements of the lung with a gamma camera and a planar source. Another aim was to assess the possibility of transmission monitoring in normal subjects at rest and during exercise and to compare the results with simultaneous measurements of PBV changes. Transmission measurements were made in a water‐filled phantom containing lungs of different density. A gamma camera and a planar 57Co source were used. The coefficient of variation in density determination owing to counting statistics in a lung area was calculated for different energy windows, acquisition times and collimation. Dynamic measurements in normal subjects were carried out in a sitting and a supine position at rest and during exercise. Pulmonary blood volume was monitored simultaneously using 99mTc‐labelled red blood cells and the registered blood pool activity was corrected for attenuation. Highest precision in relative density determination was obtained with large energy window and uncollimated source. A precision of 1·0% was obtained with 1 min measuring time. About 10% change in transmission corresponding to a 15% change in density was observed during exercise. Changes in blood pool and lung density covariated. We conclude that lung density changes can be monitored with a high degree of statistical precision in a few minutes and with a low radiation dose of radiation using a gamma camera and a planar source.
Wide‐band spectral analysis of blood pressure and RR interval variability in borderline and mild hypertension
Authors: Takalo Reijo , Korhonen Ilkka , Sorsa Heli , Majahalme Silja , Tuomisto Martti , Turjanmaa Väinö
Published: March 2003

The aim of this study was firstly to investigate whether indices of wide‐band spectral analysis in borderline hypertensive (BHT) or mildly hypertensive (HT) subjects differ from those in normotensive (NT) subjects, and secondly to assess the predictive value of these indices for future hypertension. Electrocardiogram and intra‐arterial 24 h ambulatory blood pressure (BP) were recorded in 32 NT, 29 BHT and 30 HT middle‐aged men. From the recordings, a 16 h period was extracted for wide‐band spectral analysis. A single spectrum of BP and RR interval (RRI) variability was computed for each period by the fast Fourier transform method. The slopes of the spectra were assessed on a log–log scale by linear fitting of the spectral values. Power spectral densities were calculated over regions of 0–0·003, 0·003–0·04, 0·04–0·15, 0·15–0·40 and 0–0·4 Hz. No between‐group differences were found in the slopes of BP and RRI spectra. The between‐group differences in spectral powers for BP variability were almost invariably significant. The spectral powers for RRI variability did not show between‐group differences. Five years later, 22 NT, 22 BHT and 18 HT subjects were re‐assessed using casual BP measurements. In a logistic regression model for the combined group of NT and BHT subjects who became HT (22 of 44) during the five‐year period, none of the parameters of wide‐band spectrum predicted the development of hypertension. In conclusion, parameters of wide‐band spectral analysis may not be useful in predicting future hypertension in NT and BHT subjects. Because the BP level is a major factor influencing BP variability, the between‐group differences in wide‐band spectral powers in BP may be due to differences in BP level rather than differences in cardiovascular regulatory mechanisms.
The relation between mitral annulus motion and left ventricular ejection fraction in atrial fibrillation
Authors: Emilsson Kent , Wandt Birger
Published: March 2003

Mitral annulus motion (MAM) has recently been introduced as an index of left ventricular function. Previous studies have shown a good agreement between MAM (mm) × 5 and ejection fraction in middle‐aged and elderly patients. These studies only included patients with sinus rhythm, while patients with atrial fibrillation were excluded. In the present study, MAM was reduced in patients with atrial fibrillation while ejection fraction (EF) did not differ from age‐matched control patients with sinus rhythm. The ‘conversion factor’ (EF/MAM) was 7·2 in the group with atrial fibrillation and 5·1 in controls with sinus rhythm. This difference must be taken into account when MAM is used to estimate left ventricular function in patients with atrial fibrillation. Patients with atrial fibrillation had lower stroke volume and higher heart rate than patients with sinus rhythm. A decreased systolic long‐axis shortening was found (P<0·005) compared to patients with sinus rhythm, but no difference in short‐axis diameter shortening.
Electrocardiographic ST‐segment depression in children with Fontan circulation
Authors: Rydberg Annika , Teien Dag E. , Rask Peter , Hörnsten Rolf
Published: March 2003

Despite successful operation, many patients palliated with a Fontan‐type procedure continue to show effort limitation. We previously observed that these children showed electrocardiographic ST depression during exercise tests. The purpose of the study was to investigate whether electrocardiographic ST depression is a common finding in children with Fontan circulation. Forty‐two children in two groups were examined: group A consisted of 14 patients who had all undergone a modified Fontan procedure, and group B consisted of 28 children with a structurally normal heart, matched for length, weight and gender to group A. Complete echocardiographic examinations were performed in all patients and controls. All 14 patients and all 28 healthy children underwent standard 24 h ambulatory electrocardiographic monitoring. All the recordings were analysed by a PC‐based Holter system where an analysis of ST changes was performed. Seven patients and 14 matched healthy children were exercised on bicycle ergometers. Four patients and eight matched healthy children underwent exercise testing by walking/running a treadmill. Ten of 13 patients analysed had significant ST depressions on ambulatory electrocardiogram (>0·20 mV). Three of the 10 patients with ST depression were on digoxin. Three patients showed depressions of the ST segment in the electrocardiogram during exercise, with a maximal depression of 0·20–0·35 mV. None of the 28 matched healthy children showed electrocardiographic ST depression on the ambulatory 24 h ECG. These findings indicate that ST depression in daily activity is a common finding in children with Fontan circulation.
Segmental composition of whole‐body impedance cardiogram estimated by computer simulations and clinical experiments
Authors: Kauppinen  , Kööbi  , Hyttinen  , Malmivuo
Published: March 2003

Whole‐body impedance cardiography (ICGWB) has been proposed as a feasible means of measuring cardiac output (CO). However, the source distribution of heart‐related impedance variations in the whole body is not known. To establish how much of a signal originates in each segment of the body and what the contribution of each is to stroke volume (SV) in ICGWB, impedance in the extremities and trunk were investigated in 15 healthy volunteers. In addition, the theoretical measurement properties of ICGWB were studied using a computer model of the whole‐body anatomy as a volume conductor. The model confirmed the expected result that most of the basal impedance originates from the extremities. Clinical experiments revealed that the heart‐related amplitude variations in the ICGWB signal originate more evenly from various body segments, the trunk slightly more than the arms or legs. The heart‐related ICGWB signal represents a weighted sum of segmental pulsatile events in the body yielding physiologically meaningful data on almost the whole circulatory system.
Effect of nasal air temperature on FEV1 and specific airways conductance
Authors: Millqvist  , Johansson  , Bende  , Bake
Published: March 2003

We investigated whether changes in nasal air temperature affect specific airway conductance (SGaw) and one second forced expiratory volume (FEV1) in 10 asthmatic patients with a history of cold‐sensitive asthma and eight healthy subjects. An air‐stream (0·6 l s–1) of –15°C, +22°C or +37°C was blown into both nostrils during a Valsalva manoeuvre. Each provocation consisted of 10 puffs of air, each of 15 s duration, at 1 min intervals. Before and at regular intervals after the provocations, SGaw and FEV1 were determined. In asthmatics, after cold air provocation, SGaw fell 23% (P<0·01) and FEV1 8% (P<0·01). After the warm air provocations, SGaw rose 15% (P<0·01) and FEV1 6% (P<0·01). After the ambient air provocations, no significant changes occurred in SGaw or FEV1. In the healthy subjects, the nasal provocations caused no significant changes in lung function. The present study shows that cold air in the nose causes a slight obstruction and warm air possibly a slight dilatation of the lower airways in patients with a history of cold‐sensitive asthma but not in healthy subjects.