bluuebunny/crossref_metadata_2025 huggingface dataset:
Hodgkin's disease masquerading as fibrous thyroiditis: potential role of cytokines in in vivo and in vitro studies
Authors: Bercovici Jean Pierre , Machelon Veronique , Gaudin‐Nome Françoise , Roudaut Nathalie , Conan‐Charlet Virginie , Leroy Jean Paul , Sensebe Luc , Kerlan Veronique
Published: March 2003

Hodgkin's disease appearing as, or associated with, fibrous thyroiditis has only been described rarely. We report the observation of a patient presenting with a goitre, fibrosis of the thyroid and adjacent structures, and hypothyroidism. The histological examination was compatible with fibrosclerotic thyroiditis. This diagnosis was reviewed 6 months later when the biopsy of a supraclavicular nodule that had subsequently appeared led to the diagnosis of a nodular‐sclerosis type of Hodgkin's disease. The plasmatic levels of interleukin 6 (IL‐6) and tumour necrosis factor alpha (TNF‐α) were very high compared to the levels in healthy subjects (12 and 40 IU/l vs. 0·05 and 2·0 IU/l, respectively). These cytokine levels decreased when the initial illness was treated, and their normalization was associated with the disappearance of the cervical and thyroidal fibroses. A parallel in vitro study of these cytokines and of TNF‐α receptors and IL‐13 was performed. The results suggest a possible cause‐and‐effect relationship between IL‐6 and IL‐13 produced locally by the tumoral tissue and the development of cervical fibrosis.
Final height outcome and value of height prediction in boys with constitutional delay in growth and adolescence treated with intramuscular testosterone 125 mg per month for 3 months
Authors: Kelly Brian P. , Paterson Wendy F. , Donaldson Malcolm D. C.
Published: March 2003

objectives Constitutional delay in growth and adolescence (CDGA) is common in boys, some of whom request treatment to accelerate growth and attainment of secondary sexual characteristics. The aims of this study were to confirm that a 3‐month course of intramuscular testosterone oenanthate does not impair final height in boys with CDGA, and to determine the accuracy of height prediction in this condition.

design and patients Boys with CDGA who had attended the growth clinic, who were now at or close to final height and who had received either testosterone or declined treatment, were identified by retrospective case note analysis. Bone age assessment was carried out by a single observer, using the RUS (TW2) method of Tanner and Whitehouse.

measurements The following auxological data were extracted from the case records: age, bone age, height, pubertal stage, parental heights and predicted final height. All subjects were then measured at age 19 years or greater. The main outcome measures were comparison of final height in treated and untreated boys; final height comparison with mid‐parental height and with height prediction [RUS (TW2) method] at initial assessment and at subsequent review.

results Sixty‐four boys met the inclusion criteria, of whom 41 subjects had received testosterone and 23 were untreated. There were no significant differences between the groups (treated mean/SD vs. untreated mean/SD; P‐value) in age (14·3/0·7 vs. 14·0/1·1; 0·13), height (144·7/6·2 vs. 144·2/6·2; 0·79), mid‐parental heights (170·4/5·5 vs. 171·1/4·5; 0·59), and bone age (12·0/1·2 vs. 12·3/1·3; 0·36). Final heights in both groups (168·9/6·0 vs. 168·2/3·5; 0·65) were closely related to predicted final heights (170·0/5·0 vs. 168·1/4·1; 0·15) and only slightly less than mid‐parental heights. Only three subjects had final heights below the initial height prediction range.

conclusions Our data support the hypothesis that this treatment regime does not adversely affect the final height achieved in constitutional delay of growth and adolescence and that height prediction, assessed by a single observer, is a useful and accurate tool.
Carriers for type II 3β‐hydroxysteroid dehydrogenase (HSD3B2) deficiency can only be identified by HSD3B2 genotype study and not by hormone test
Authors: Pang Songya , Carbunaru Goldy , Haider Anzar , Copeland Kenneth C. , Chang Ying Tai , Lutfallah Chantal , Mason J. Ian
Published: March 2003

objective We investigated adrenal steroidogenic function relevant to 3β‐hydroxysteroid dehydrogenase (HSD3B2) activity in vivo and HSD3B2 genotype in clinically normal family members of patients with HSD3B2 genotype‐proven HSD3B2 deficiency congenital adrenal hyperplasia (CAH) to determine whether genotype‐proven carriers for HSD3B2 deficiency exhibit decreased enzyme activity analogous to the mildly decreased adrenal 21‐hydroxylase activity in the carriers of CYP21 gene mutation.

design/patients Nineteen adult family members (ages median/range: 37/19–56 years) including 13 females and six males of six unrelated patients with HSD3B2 genotype‐proven HSD3B2 deficiency were studied.

measurements All family members had HSD3B2 DNA analysis and an ACTH stimulation test (Cortrosyn 0·25 mg IV bolus) for determination of adrenal HSD3B activity.

results Ten of 13 females and five of six males were carriers of a proven or predictably deleterious mutation in one allele of the HSD3B2 gene, which was identified in the probands. ACTH‐stimulated levels of 17‐hydroxypregnenolone (Δ5‐17P), 17‐hydroxyprogesterone (17‐OHP), cortisol (F), dehydroepiandrosterone (DHEA) and androstenedione (Δ4‐A) and ratios of Δ5‐17P to 17‐OHP, Δ5‐17P to F and DHEA to Δ4‐A, as well as increments of Δ5‐17P and DHEA values (ACTH‐stimulated − baseline) in the genotype‐proven female carriers (age, mean ± SD: 36 ± 6·7 years) and male carriers (age, mean ± SD: 37 ± 6·7 years) did not differ significantly from age‐matched normal females (35 ± 5·4 years, n = 20) and normal males (35 ± 6 years, n = 10), respectively. There were no significant differences in any of the ACTH‐stimulated hormonal levels or ratios between the female carriers with a seriously deleterious genotype (n = 5) and the female carriers with mildly deleterious genotypes (n = 5). These hormonal levels and ratios in three genotype‐normal females and one genotype‐normal male overlapped with those of the carriers.

conclusion These data suggest that normal adrenal HSD3B2 activity is maintained in the genotype‐proven carriers because heterodimers of mutant and wild‐type HSD3B2 enzymes may be stable and exhibit similar activity compared to homodimers of wild‐type enzymes, possibly by a relatively rate‐unlimited effect of haplo‐wild‐type enzyme activity. However, we cannot preclude entirely the possibility of a limited expression of another HSD3B activity under ACTH stimulation contributing to the normal adrenal HSD3B activity in vivo in the HSD3B2 genotype‐proven heterozygotes. Which mechanism plays a role in maintaining normal enzyme activity in the heterozygotes remains to be elucidated. The hormone findings in the genotypic‐proven carriers for HSD3B2 deficiency also indicate that carriers for this disorder cannot be detected by a hormone test and can only be detected by HSD3B2 genotype study.
The role of quantitative ultrasound in the assessment of bone: a review
Authors: Prins  , Jørgensen  , Jørgensen  , Hassager
Published: March 2003

Quantitative ultrasound (QUS) bone measurement is a promising, relatively new technique for the diagnosis of osteoporosis. Unlike to the more established method of bone densitometry [measurement of bone mineral density (BMD) e.g. using dual X‐ray absorptiometry (DEXA)], QUS does not use ionizing radiation. It is cheaper, takes up less space and is easier to use than densitometry techniques. The two QUS parameters currently measured are broadband ultrasound attenuation (BUA) and speed of sound (SOS). The reported age‐related changes for healthy women range from −0·27% to −1·62% per year for BUA and from −0·06% to −0·19% per year for SOS. Precision ranges from 1·0 to 3·8% (CV) for BUA and from 0·19 to 0·30% (CV) for SOS. The new method of imaging ultrasound has improved the precision of QUS measurements. QUS is significantly correlated with BMD. Studies with the latest equipment have shown r‐values between 0·6 and 0·9 in site‐specific measurements, and QUS is thus believed to reflect mainly BMD. However, other studies indicate that QUS measures something other than the actual mineral content of bone, namely bone quality, e.g. in vitro studies have shown that QUS reflects trabecular orientation independently of BMD. In both cross‐sectional and prospective studies, QUS seems to be as good a predictor of osteoporotic fractures as BMD. In two large prospective studies, QUS also predicted fracture risk independently of BMD. QUS has just begun to be used systematically for monitoring the response to anti‐osteoporotic treatments in prospective trials. In the studies performed, QUS has been found to be useful in the follow‐up of patients. QUS is thus a promising new technique for bone assessment.
Arterial and venous plasma catecholamines during submaximal steady‐state exercise
Authors: Rostrup  , Westheim  , Refsum  , Holme  , Eide Ivar
Published: March 2003

Arterial and venous plasma catecholamine responses to 15 min of cycling at 60% of maximal oxygen uptake were examined 11 times during exercise and recovery in nine young men. Intra‐arterial blood pressure, heart rate and oxygen uptake were recorded continuously. All variables increased significantly during the initial 4 min, after which oxygen uptake, diastolic blood pressure and arterial plasma adrenaline showed no further increase. Heart rate and plasma noradrenaline, however, continued to increase, although significantly more slowly, and were closely correlated (r = 0·81, 95% CI 0·71–0·87), as were systolic blood pressure and heart rate (r = 0·78, 95% CI 0·71–0·87). Venous plasma adrenaline showed a steady increase during the whole exercise period and thus a different response pattern from arterial plasma adrenaline. In conclusion, arterial plasma catecholamines respond to steady‐state exercise by a two‐phase pattern paralleling the changes in arterial blood pressure and heart rate. Venous sampling does not reveal this association.
Analogue and digital electrocardiogram recordings in the assessment of heart rate variability
Authors: Simula  , Laitinen  , Hartikainen
Published: March 2003

We compared analogue and digital 24‐h electrocardiogram (ECG) recordings in the assessment of heart rate variability (HRV) in 41 patients with suspected coronary artery disease. The patients underwent ambulatory ECG recordings simultaneously with analogue (A) (Marquette 8500) and digital (D) (Oxford Medilog FD‐3) recorders. Digital ECG recordings were analysed with the Excel Medilog II system (DE) and analogue recordings were analysed with both Marquette (AM) and Excel Medilog II (AE) systems. SDNN, SDANN, rMSSD and pNN50 were calculated for the assessment of time domain measures of HRV, and powers of low (0·04–0·15 Hz) and high (0·15–0·40 Hz) spectral components of HRV for the assessment of frequency domain measures of HRV. Correlations between time domain measures of HRV derived from AM, AE and DE recording and analysis techniques were high (r = 0·803–0·999, P<0·001). SDANN and pNN50 assessed with AM and DE were equal, whereas SDNN and rMSSD values differed slightly but significantly from each other (P<0·01 for both). All time domain measures of HRV assessed with AE differed significantly from AM (P<0·001) and from DE (P<0·01). Correlations between frequency domain measures of HRV derived from AM, AE and DE were also high (r = 0·973–0·992, P<0·001). Despite this, frequency domain measures of HRV assessed with AM, AE and DE differed significantly from each other (P<0·001). In conclusion, when analysed with their own analysis systems, analogue and digital recordings provided almost identical time domain, but not frequency domain, measures of HRV. In addition, analysis of an ECG recording with an analysis system of different manufacturer should be avoided.
Divergent cardiac response to exercise in essential hypertension vs. normotension and the effect of enalapril
Authors: Gadsbøll  , Rasmussen  , Jensen  , Leth  , Giese  , Høilund‐Carlsen
Published: March 2003

The aims of this study were to examine (1) the cardiac response to exercise in essential hypertension and (2) the effect of long‐term enalapril treatment on cardiac reserve. Ten normotensive control subjects and 15 patients with moderate, essential hypertension underwent radionuclide ventriculography during graded, supine exercise (0 W–50 W–100 W). The hypertensive patients were studied during monotherapy using hydrochlorothiazide and 3 and 12 months after supplementation with enalapril 10–40 mg o.d. During exercise, the control subjects demonstrated a 17% increase in left ventricular ejection fraction (LVEF) mediated by a 30% decrease in end‐systolic volume, a small increase in stroke volume and a minor biphasic (increase–decrease) change in end‐diastolic volume. In the hypertensive patients, both the end‐diastolic and the end‐systolic volume increased substantially with no increase in LVEF, although stroke volume increased by 33%. Long‐term therapy with enalapril induced only a minor change towards a more normal pattern of cardiac response to exercise. The hypertensive patients increased their stroke volume during exercise by recruiting preload reserve instead of increasing contractility. Long‐term treatment with enalapril had little, if any, effect on this abnormal cardiac response.
Renal prostanoids: physiological relevance in healthy salt‐depleted women
Authors: Agnoli  , Borgatti  , Cacciari  , Lenzi  , Marinelli  , Stipo
Published: March 2003

The effective role played by prostanoids in the control of renal function has been investigated in healthy women with salt depletion. Salt depletion (SD2 group, n = 6) was induced by low sodium chloride dietary intake (≤60 mmol per day) and combined treatment with natriuretic and potassium‐sparing drugs. At the end of the depletive treatment, the cumulative sodium deficit was 513 ± 56 mmol. The renal function and urinary excretions of prostaglandin (PG) E2, 6‐keto‐PGF1α (6KPGF) and thromboxane (Tx) B2 were evaluated during hypotonic polyuria. The basal values of plasma sodium and potassium concentrations, plasma renin activity (PRA) and urinary aldosterone excretion were determined before the induction of hypotonic polyuria. Paired studies were performed in the absence (control) and presence of indomethacin both in the SD2 group and in a previously studied group (N2, n = 6) of healthy women in normal sodium and potassium balance. Women in normal balance received 100 mg i.m. of indomethacin, salt‐depleted women received only 50 mg (because 100 mg of the drug produced a prolonged anuria). In the SD2 vs. N2 group in the absence of treatment the following significant differences were found: (a) higher basal values of PRA and urinary aldosterone excretion; (b) higher urinary excretions of 6KPGF and TxB2 but not of PGE2; (c) lower values of urinary flow rate, creatinine clearance, absolute and fractional excretions of sodium and chloride, plasma osmolality and plasma electrolyte concentrations. The effects of the indomethacin have been assessed as percentage variations by using paired data for each experimental group. In the SD2 vs. N2 group the reduction in urinary excretions of 6KPGF, TxB2 and potassium as well as in creatinine clearance were not significantly different. On the other hand, the following were significantly different: (a) the lower reduction in PGE2 excretion; (b) the higher reduction in urinary flow rate and in CH2O; (c) the reductions in absolute and fractional excretions of sodium and chloride, and the increase in plasma potassium concentration, significant in the SD2 group but not in the N2 group. The data suggest that: (1) when stimulated by salt depletion the renal biosynthetic pathways of PGI2 and TxA2 showed greater sensitivity to indomethacin inhibition; (2) the effects of the neurohormonal systems activated by salt depletion were either modulated or mediated by renal prostanoids.
Controlled oral glucose tolerance test: evaluation of insulin resistance with an insulin infusion algorithm that forces the OGTT glycaemic curve within the normal range. A feasibility study
Authors: Volpicelli  , Iannello  , Belfiore
Published: March 2003

This is a technical study to show the feasibility of a computer‐controlled oral glucose tolerance test (OGTT) using a specific algorithm, consisting of an OGTT carried out while insulin is infused as required to keep glycaemia within the normal range ( National Diabetes Data Group 1979 criteria). This technique allows (a) the amount of insulin (insulin area) required to maintain a normal glycaemic curve to be assessed, a parameter indicating the degree of insulin resistance; and (b) the unique parameter consisting of the insulin secretory response (C‐peptide) to a normal glycaemic curve under the inhibitory feedback exerted by the insulin levels required to maintain normal glycaemia to be obtained. Preliminary results confirmed the feasibility of this approach by showing that during the test while the glycaemic area was kept normal the insulinaemic area (endogenous + infused insulin) increased markedly in obese (n = 8) and obese diabetic (n = 5) subjects compared with normal subjects (n = 6), with values of 145·10 ± 26·71, 204·75 ± 20·77 and 68·25 ± 5·93 nmol l−1 min−1 respectively (P < 0·01 in both instances). In contrast, endogenous insulin secretion (C‐peptide levels) remained almost unchanged. Compared with data in normal subjects, free fatty acid (FFA) values were basally elevated in the obese and obese diabetic patients, and underwent a smaller decrease during the test. The FFA areas were greater than normal in both groups of patients, suggesting that FFAs were not fully suppressible despite the highest possible insulin levels (higher insulin levels would produce hypoglycaemia). The computer‐controlled OGTT might be useful for the metabolic study of patients in the clinical setting.
C‐type natriuretic peptide does not affect plasma and urinary adrenomedullin in man
Authors: Lazzeri  , Guerra C. Tosti , Vecchiarino  , Barletta  , Stefani  , Bandinelli  , Franchi  , Villa G. La
Published: March 2003

To investigate whether C‐type natriuretic peptide (CNP) at pathophysiological plasma levels stimulates the release of adrenomedullin (ADM) in man, six healthy subjects (three men and three women, mean age 35 ± 3 years, range 33–40 years) received an intravenous infusion of synthetic human CNP‐22 (2 pmol kg−1 min for 2 h), in a single‐blind, placebo‐controlled, random order, cross‐over study, with measurements of the plasma levels of cyclic guanosine monophosphate (cGMP), ADM, renin and atrial natriuretic peptide (ANP), arterial pressure, heart rate, renal blood flow (para‐aminohippurate clearance), glomerular filtration rate (creatinine clearance), and the urinary excretion rates of cGMP, ADM and sodium. Infusion of CNP induced increases in its own levels (from 1·17 ± 0·11 up to 21·13 ± 1·41 pmol l−1) without modifying the plasma levels of cGMP, ADM, renin and ANP, the urinary excretion rate of ADM and cGMP, renal haemodynamics and sodium excretion. These data indicate that circulating CNP is not involved in the regulation of ADM release, renal haemodynamics and sodium excretion in man.
Induction of acute metabolic acid/base changes in humans
Authors: Ven M. J. T. van de , Colier W. N. J. M. , Oeseburg  , Folgering
Published: March 2003

The aim of this study was to induce acute metabolic acid/base changes of ≥2 mequiv · l–1 change in base excess (BE) to aid future investigations of respiratory parameters under these conditions. Ammonium chloride (NH4Cl) was administered to induce acidification and furosemide was used to induce alkalization. Nine healthy volunteers (six men and three women aged 35 ± 18 years) ingested a calculated amount of NH4Cl at t=0 and a repeat dose after 60 min. Eight healthy volunteers (three men and five women aged 37 ± 16 years) consumed 40 mg of furosemide. Arterialized capillary blood gases were measured at t=0, 30, 60, 90, 120 and 180 min. In the case of acute metabolic acidosis, the target acidification of 2 mequiv · l–1 was attained after 30 min and the greatest change was achieved at 90 min: –4·9 (2·2) mequiv · l–1. In the case of acute metabolic alkalosis, the target alkalization of 2 mequiv · l–1 was reached between 120 and 180 min and the greatest change was seen at 180 min: +2·2 (1·4) mequiv · l–1. Significant (P<0·05) changes in acidification compared with baseline BE values were found between 60 and 180 min; significant (P<0·05) changes in alkalization were found between 120 and 150 min. Paco2 did not change significantly in either condition. We conclude that NH4Cl and furosemide induce a steady state of pure metabolic acid/base conditions in humans, which is buffered in an isocapnic manner.
Noise reduction of renograms: a new algorithm applied to simulated renograms for evaluation of the renal retention function
Authors: Ekman Mikael , Volkmann Reinhard , Carlsson Sten
Published: March 2003

Physiological information about an organ may be assessed from the retention function as derived by deconvolution analysis. However, noise in data may cause distortion of the retention curve and potentially induce methodological errors. To take full advantage of all parts of the retention function, i.e. even the vascular part, we have developed a non‐linear noise reduction algorithm. The algorithm is an adaptive polynomial fit (APF) in a sliding segment over the renogram to be deconvoluted. Each segment is modelled by the lowest polynomial resulting in a root of mean square error lower than a pre‐set value. APF was tested in comparison with conventional repetitive 1:2:1 smoothing and rectangular window smoothing, using a set of simulated retention functions and corresponding renograms with superimposed artificial noise. The outcome was evaluated by comparing the generated retention functions with the simulated ones. The conventional smoothing algorithms, as well as APF, induced some distortion of the retention function, but the deviation from the true retention function is essentially lower in the case of APF. In addition, APF seems to be more robust in cases of essentially reduced renal function and thereby relative high noise levels. APF reduces noise in data, leading to retention functions with reliable information in terms of a tracer’s first passage, uptake and outflow.
Scandinavian test of artificial neural network for classification of myocardial perfusion images
Authors: Lindahl  , Toft  , Hesse  , Palmer  , Ali  , Lundin  , Edenbrandt
Published: March 2003

Artificial neural networks are systems of elementary computing units capable of learning from examples. They have been applied to automated interpretation of myocardial perfusion images and have been shown to perform even better than experienced physicians. It has been shown that physicians interpreting myocardial perfusion images benefit from the advice of such networks. These networks have been developed and validated in the same hospital. However, widespread use of neural networks will only take place if the networks can maintain a high accuracy in other hospitals, i.e. hospitals using different gamma cameras, different acquisition techniques, different study protocols, etc. The purpose of this study was to develop a neural network in one hospital and test it in another. An artificial neural network was trained to detect coronary artery disease using myocardial perfusion scintigrams from 135 patients at a Swedish hospital. Thereafter, this network was tested using scintigrams from 68 patients at a Danish hospital and compared to six criteria based on expert physician analysis and quantitative analysis by the CEqual program. The sensitivity of the network was significantly higher than that of one of the physician criteria (0·92 versus 0·71) and two of the CEqual‐based criteria (0·94 versus 0·63 and 0·96 versus 0·65) compared at equal specificities. It was concluded that an artificial neural network can maintain high accuracy in a hospital other than the one where it was developed.
Anthracycline‐induced cardiomyopathy: long‐term effects on myocardial cell integrity, cardiac adrenergic innervation and fatty acid uptake
Authors: Nousiainen T. , Vanninen E. , Jantunen E. , Remes J. , Kuikka J. , Hartikainen J.
Published: March 2003

Cardiotoxicity of anthracyclines is a clinical challenge in cancer chemotherapy. Limited data is available on the physiological mechanisms responsible for anthracycline‐induced heart failure or its recovery. We studied four patients with a history of severe anthracycline‐induced heart failure manifested 2–116 months earlier by using radionuclide ventriculography for the measurement of left ventricular function, indium‐111‐antimyosin scintigraphy for the detection of myocardial cell injury and iodine‐123‐metaiodobenzylguanidine (MIBG) scintigraphy for the assessment of cardiac adrenergic innervation. Myocardial perfusion and fatty acid utilization were assessed with iodine‐123‐paraphenyl pentadecanoid acid (pPPA) and single photon emission computed tomography (SPECT). Symptoms of congestive heart failure (CHF) were still present in two patients whereas the others were asymptomatic at the time of the study. The patients who showed complete clinical recovery had normal or near normal left ventricular ejection fraction (LVEF) (47 and 52%), whereas the patients with symptoms of heart failure had low ejection fractions (21 and 31%). All patients presented with abnormal antimyosin uptake and decreased myocardial MIBG uptake. Patients with low ejection fraction tended to have higher antimyosin uptake suggesting more severe, persistent myocyte injury. All but one patient showed normal fatty acid utilization. These data suggest that patients with a history of severe anthracycline‐induced cardiomyopathy have persistent myocardial cell injury and adrenergic dysfunction up to 10 years after the development of heart failure. These findings seem to be present regardless of recovery of left ventricular function.
Leg uptake of calcitonin gene‐related peptide during exercise in spinal cord injured humans
Authors: Kjær Michael , Mohr Thomas , Dela Flemming , Secher Niels , Galbo Henrik , Olesen Hanne Lis , Sørensen Fin Biering , Schifter Søren
Published: March 2003

Exercise‐induced increases in cardiac output (CO) and oxygen uptake (VO2) are tightly coupled, as also in absence of central motor activity and neural feedback from skeletal muscle. Neuromodulators of vascular tone and cardiac function – such as calcitonin gene related peptide (CGRP) – may be of importance. Spinal cord injured individuals (six tetraplegic and four paraplegic) performed electrically induced cycling (FES) with their paralyzed lower limbs for 29 ± 2 min to fatigue. Voluntary cycling performed both at VO2 similar to FES and at maximal exercise in six healthy subjects served as control. In healthy subjects, CGRP in plasma increased only during maximal exercise (33·8 ± 3·1 pmol l−1 (rest) to 39·5 ± 4·3 (14%, P<0·05)) with a mean extraction over the working leg of 10% (P<0·05). Spinal cord injured individuals had more pronounced increase in plasma CGRP (33·2 ± 3·8 to 46·9 ± 3·6 pmol l−1, P<0·05), and paraplegic and tetraplegic individuals increased in average by 23% and 52%, respectively, with a 10% leg extraction in both groups (P<0·05). The exercise induced increase in leg blood flow was 10–12 fold in both spinal cord injured and controls at similar VO2 (P<0·05), whereas CO increased more in the controls than in spinal man. Heart rate (HR) increased more in paraplegic subjects (67 ± 7 to 132 ± 15 bpm) compared with controls and tetraplegics (P<0·05). Mean arterial pressure (MAP) was unchanged during submaximal exercise and increased during maximal exercise in healthy subjects, but decreased during the last 15 min of exercise in the tetraplegics. It is concluded that plasma CGRP increases during exercise, and that it is taken up by contracting skeletal muscle. The study did not allow for a demonstration of the origin of the CGRP, but its release does not require activation of motor centres. Finally, the more marked increase in plasma CGRP and the decrease in blood pressure during exercise in tetraplegic humans may indicate a role of CGRP in regulation of vascular tone during exercise.
Excessive exercise ventilation in moderate left heart dysfunction. Influence of postural changes in central haemodynamics and blood gases
Authors: Refsum H. E. , Eritsland J. , Müller O. K.
Published: March 2003

To evaluate the relative importance of pulmonary congestion and peripheral hypoxia as causes for the excessive exercise ventilation in left heart dysfunction, seven patients with excessive ventilation and distinct left heart dysfunction during moderate exercise (LHD), and seven control patients with essentially normal exertional functions (CTR), had ventilation, central haemodynamics, arterial and mixed venous blood gases examined at rest and exercise, 32 W (25–40) in the LHD group and 44 W (33–49) in the CTR group, in lying and sitting positions. Change from lying to sitting exercise, led to fall in pulmonary artery wedge pressure (PAWP) from 31·0 ± 5·5 to 8·8 ± 5·0 mmHg in the LHD group, compared with from 13·7 ± 1·0 to 2·1 ± 2·4 mmHg in the controls, while ventilation/O2 intake ratio (V˙/V˙O2) and physiological dead space/tidal volume ratio (VD/VT) showed a tendency to rise, from 36·3 ± 8·8 to 39·2 ± 7·4, and from 0·35 ± 0·11 to 0·39 ± 0·09, respectively, in the LHD group, and from 27·5 ± 3·1 to 28·7 ± 5·3, and from 0·19 ± 0·09 to 0·21 ± 0·12 in the controls. Mixed venous O2 tension (PvO2) showed a marked decline from 3·60 ± 0·33 to 3·26 ± 0·36 kPa in the LHD group, as compared with from 3·94 ± 0·28 to 3·71 ± 0·29 kPa in the controls, while the calculated physiologic shunt (Q˙s/Q˙t) suggested improved alveolo‐arterial gas exchange. The data fit in with recent studies ascribing the excessive exercise ventilation to a combination of signals from hypoxia‐induced changes, particularly in the exercising muscles, and augmented ergoreflex and central and peripheral chemoreceptor activity, partly to changes in the integrated control of ventilation and circulation, not to mechanisms related to pulmonary congestion.
Effects of a high‐fat meal on resistance vessel reactivity and on indicators of oxidative stress in healthy volunteers
Authors: Schinkovitz Andreas , Dittrich Peter , Wascher Thomas C.
Published: March 2003

High fat meals postprandially impair macrovascular endothelial function and a link to increased oxidative stress is suggested. Few information, on the other hand, exists on the effect of postprandial hyperlipidaemia on resistance vessel function. Under normal circumstances this vascular bed regulates tissue perfusion and, by controlling flow, impacts on macrovascular nitric oxide formation. The impact of a high fat meal (1200 kcal, 90 g fat, 46 g protein and 47 g carbohydrates) on postprandial resistance vessel reactivity and on indicators of oxidative stress was studied in 11 healthy subjects by venous‐occlusion plethysmography using another six subjects as time control group. Ingestion of the test meal resulted in a pronounced increase of serum triglycerides from 1·05 ± 0·61 mmol l−1 in the fasting state to peak postprandial values of 1·94 ± 0·41 mmol l−1 (P < 0·001) reached after 4 h and a return to baseline after 8 h. Fasting peak reactive hyperaemia (RH) was 19·6 ± 2·4 ml min−1 (100 ml)−1. Two hours after ingestion of the test meal peak RH was transiently reduced to 16·8 ± 2·2 ml min−1 (100 ml)−1 (P < 0·05). No alteration of resting forearm perfusion was observed. The time course of peak RH suggested a potential biphasic effect of the test meal with an early impairment and a late increase of RH. Ingestion of a lipid rich test meal did not exert any influence on either total plasma antioxidant capacity given in trolox equivalents (513 ± 26 μmol l−1 at baseline) or on plasma peroxides measured as H2O2 equivalents (469 ± 117 μmol l−1). Our results suggest that ingestion of a meal containing 90 g of fat results in a transient impairment of reactive hyperaemia in healthy subjects but these vascular alterations are not accompanied by signs of systemically increased oxidative stress.
Spirometric reference values in Estonian schoolchildren
Authors: Kivastik Jana , Kingisepp Peet‐Henn
Published: March 2003

This study was conducted to describe the relationship between anthropometric parameters and lung function in Estonian children, to determine the reference values for spirometry, and to compare these results with other data sets. The results are based on 1170 healthy non‐smoking children (643 girls and 527 boys), aged 6–18 years. The spiroanalyser Pneumoscreen II (Jaeger) was used to register dynamic lung parameters. Natural logarithmic values of lung volumes, standing or sitting height and age were used in the final regression model. Prediction equations for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow, forced expiratory flows when 50 and 75% of FVC has been exhaled, and mean forced expiratory flow over the middle 50% of the FVC for both sexes are presented. In comparison with recent data from European children the reference values were close for FVC, the differences were bigger for FEV1 and forced expiratory flows, especially in taller children.
Human G protein β3 subunit variant does not alter hypercarbic or hypoxic ventilatory response
Authors: Exner Hans Juha , Groeben Harald , Rosskopf Dieter , Siffert Winfried , Peters Jürgen
Published: March 2003

Hypercarbic respiratory drive is mainly determined by PCO2 and pH with activity of the intracellular Na+/H+ exchanger (NHE) playing an important role in maintaining intracellular pH and respiratory drive. Because NHE activity varies with genetically different G‐protein β3 subunits (GNB3) (C/T polymorphism at nucleotide position 825) different genotypes might alter respiratory regulation. To test the hypothesis that short‐term ventilatory responses vary with different GNB3 healthy volunteers with different genotypes (CC, TC, TT) were exposed to either hyperoxic hypercarbia (n=33) or to isocapnic hypoxia (n=31), respectively. There was no difference between CC, TC, and TT genotypes in hypercarbic and hypoxic respiratory drive when assessed as the ratio of minute ventilation over endexpiratory PCO2 changes (ΔV˙E/ΔPETCO2), maximal tolerable PETCO2, and ratio of changes in ventilation over arterial haemoglobin desaturation (ΔV˙E/ΔSO2), respectively. Thus, short‐term hypercarbic and hypoxic ventilatory drive do not differ between individuals with genotypes encoding different GNB3. Whilst respiratory control may still be influenced by G‐protein aberration, other mechanisms seem to have a more important role in controlling ventilation.
A new method to quantify postexercise ST‐deviation – the ST‐deficit. A study in men at high and low‐risk for coronary heart disease
Authors: Suurküla Madis , Arvidsson Anders , Fagerberg Björn , Bjurö Thorvald , Wikstrand John
Published: March 2003

Background Quantitative heart rate adjusted exercise ST criteria like μV/beats per minute (bpm) improve the diagnostic accuracy of the exercise ECG. However, there are few quantitative HR adjusted postexercise variables available. The aim of the present exercise study was to evaluate a new such variable from computerized averaging of the postexercise ECG.

Methods The presence of possible myocardial ischaemia in a population based sample of 74 elderly male hypertensives at high‐risk of coronary heart disease, and in 42 age‐matched clinically healthy males (reference group) at low‐risk was assessed by exercise ECG. All men had a normal resting ECG without signs of ischaemia. Variables studied: standard ST‐criteria, ST/HR slope ≤–2·4 μV · bpm–1, shape of the rate‐recovery loop, the latter also with a new quantitative variable, the ST‐deficit.

Results In spite of a normal resting ECG many subjects showed an abnormal ST/HR slope during exercise, 43% in the hypertension group and 26% in the reference group. An abnormal rate‐recovery loop (ST‐deficit) also contributed substantially to identify patients with possible myocardial ischaemia, 30 vs. 10%, respectively (P<0·02); cumulatively for the two HR adjusted criteria 53% vs. 29%, respectively (P<0·02). Mean ST‐deficit was significantly lower in the high‐risk group.

Conclusions Effort‐related myocardial ischaemia is frequently silent in elderly high‐risk hypertensives and necessitates testing, preferably with computerized exercise ECG and heart rate adjusted ST criteria. A new quantitative variable to assess the postexercise rate‐recovery loop in the time domain, the ST‐deficit is described. This variable seems to effectively discriminate between subjects with low and high‐risk for coronary heart disease and thus provides new information. Further studies are warranted to validate this variable against myocardial perfusion scintigraphy and coronary angiography.
Endothelin‐1: increased plasma clearance, pulmonary affinity and renal vasoconstriction in young smokers
Authors: Ahlborg G. , Lundberg J. M.
Published: March 2003

Pulmonary and renal haemodynamics and elimination of endothelin‐1 (ET‐1) were studied in six young smokers in response to 20 min intravenous infusion of ET‐1 (4 pmol kg–1 min–1) after smoking. At 20 min of ET‐1 infusion fractional ET‐1 extractions in the lungs and kidneys were 60 ± 2 and 60 ± 7%, respectively. Cardiac output and renal blood flow (RBF) fell by 18 ± 4% (P<0·05) and 34 ± 5% (P<0·01). Mean systemic arterial pressure increased (P<0·05) whereas pulmonary pressures were unchanged. Compared with previously published data in non‐smokers (Weitzberg et al., 1991, 1993) basal arterial ET‐1 and ET‐1‐values during ET‐1 infusion were lower with a more rapid return to basal value. Smokers had higher pulmonary extraction of ET‐1 at the same pulmonary arterial concentration (P<0·05). RBF reduction was more pronounced (P<0·05). Systemic vascular resistance increased while pulmonary vascular resistance did not increase as in non‐smokers. Increased plasma clearance and more efficient pulmonary elimination of ET‐1 lowers the arterial level in young smokers. In addition ET‐1 evokes more pronounced renal vasoconstriction in these individuals.
Fine needle aspiration (FNA) biopsy of primary cutaneous meningioma: report of two cases
Authors: KALFA M. , DASKALOPOULOU D. , MARKIDOU S.
Published: March 2003

Fine needle aspiration (FNA) biopsy of primary cutaneous meningioma: report of two cases

Two cases of primary cutaneous meningioma are described. A male and a female patient, aged 56 and 61 years, respectively, presented each with a solitary subepidermal nodule. The initial diagnosis was established in both patients by application of FNA biopsy. The subsequent histologic examination confirmed the cytologic diagnosis. Extensive investigation of the patients by computed tomography (CT) and nuclear magnetic resonance imaging (MRI) scans failed to reveal any primary meningioma of the neuraxis. Neurologic examination and routine laboratory test results were all normal. The microscopic features, immunocytological study and histology, which all gave a similar pattern to that seen in intracranial meningiomas, are discussed. Distinction from other cutaneous lesions that may be considered in the differential diagnosis is made. A brief review of the literature is also presented.
Fine needle cytology of palpable head and neck lesions: a comparison of sampling methods with and without suction
Authors: Allen S. M. , Boon A. P. , Brownridge D. M. , Chadwick C. H. , Buckley J. G.
Published: March 2003

Fine needle cytology of palpable head and neck lesions: a comparison of sampling methods with and without suction

Patients attending the ear, nose and throat (ENT) department at St James's University Hospital, Leeds, UK, for evaluation of palpable head and neck lesions have a fine needle cytology (FNC) specimen taken and receive the result at the same out‐patient visit. This study was designed to discover if there is a significant difference in the efficiency of the methods with and without suction. The method was chosen randomly on each occasion and the adequacy or otherwise of the specimen was determined taking into account the site and nature of the lesion and the total cellularity of the sample. The level of blood contamination was also compared by each method. When benign and malignant lesions from all sites were analysed together the method with suction produced a significantly higher number of adequate samples than the method without suction. The exception was in the case of samples from lymph node lesions measuring < 1 cm, where adequate specimens were only obtained without suction. The non‐suction technique was particularly poor at sampling salivary gland lesions in the 1–1.5 cm category. There was no significant difference in the level of blood contamination between the two methods at any site. These results are at variance with most other similar studies and possible reasons for this are discussed.
Cytologic findings of metastatic mucin‐secreting adenocarcinoma of brain from parotid gland primary
Authors: Horn K. D. , Richert C. A. , Rajan P. B. , Bastacky S. I. , Peterson A. B. , Barnes E. L.
Published: March 2003

Introduction
Fine needle aspiration cytology (FNAC) of mammary granular cell tumour: a report of three cases
Authors: McCluggage W. G. , Sloan S. , Kenny B. D. , Alderdice J. M. , Kirk S. J. , Anderson N. H.
Published: March 2003

Fine needle aspiration cytology (FNAC) of mammary granular cell tumour: a report of three cases

This report describes the FNAC findings in three cases of granular cell tumour of the breast. The patients comprised two females aged 59 and 62 years and one male aged 28 years. All patients presented with a breast lump which was clinically and radiologically suspicious of malignancy. FNAs yielded moderately cellular specimens which on cytologic examination consisted of groups of cells and single cells with small regular nuclei and abundant granular cytoplasm. Bare nuclei were also present but these did not have the characteristic bipolar appearance of myoepithelial cells. In two cases there was a granularity to the background. The aspirates were reported as equivocal or atypical, probably benign, and surgical biopsy was performed. Histological examination showed typical benign granular cell tumours with strong positive staining for S‐100 protein. Pathologists should be aware that granular cell tumour may occur in or around the breast and should consider this diagnosis in aspirates containing a population of cells with regular nuclei and abundant granular cytoplasm. The main cytologic differential diagnoses are likely to be apocrine cells and histiocytes. The suspicion of a granular cell tumour should be heightened when these features are present in an aspirate from a clinically and radiologically suspicious mass. These cases highlight the role of the triple approach encompassing clinical, radiological and cytological features in the assessment of a breast lesion.
Cervical cytology EQA – the Northern experience
Authors: Cross P. , Shiell A.
Published: March 2003

Cervical cytology EQA – the Northern experience

The experience of the Northern region using the 1995 draft National Gynaecological Cervical Cytology External Quality Assurance (EQA) Scheme is given. Over three rounds, 390 staff reporting Cervical Cytology took part, and using a cumulative non‐numeric marking scheme, five participants were deemed ‘unacceptable’ at the end of three rounds. A total of 3450 responses were given to the 40 test slides used, with an overall false‐positive rate of 5.9% and a false‐negative rate of 1.4%. Grading was assessed for pathologists, and many appeared to perform badly by accumulating discrepancies for non‐clinically‐significant grading differences. The problems of slide selection/staining and grading consistency/accuracy are highlighted. This EQA scheme serves its dual function of education and identifying poor performance. It must be seen as a viable EQA scheme, although other options must be considered, given advances in technology.
Diagnosis of skeletal lymphoma and myeloma by radiology and fine needle aspiration cytology
Authors: Söderlund V. , Tani E. , Skoog L. , Bauer H. C. F. , Kreicbergs A.
Published: March 2003

Diagnosis of skeletal lymphoma and myeloma by radiology and fine needle aspiration cytology

From 1986 to 1998, all patients referred to Karolinska Hospital because of a skeletal destruction of unknown origin routinely underwent radiographic examination and fine needle aspiration cytology (FNAC). Among these, there were 83 patients with solitary lesions of the bone diagnosed and treated for myeloma (plasmacytoma) or non‐Hodgkin’s lymphoma. Review of the series showed that myeloma could not be distinguished radiographically from lymphoma. Nor could low and high grade lymphoma lesions be discriminated by radiographic appearance. The diagnostic utility of plain radiography in the two conditions seems to be confined to the mere detection of a destructive bone lesion and visual guidance for FNAC. The latter aspect, however, is crucial for the application of FNAC to bone lesions. Review of the cytologic specimens obtained by FNAC showed that they allowed a conclusive diagnosis in all 40 myeloma cases and in 41 of 43 lymphoma cases. In 32 of the 40 myeloma cases, the FNAC material could be used for immunocytochemistry, which disclosed κ or λ light chain restriction, corroborating the cytomorphological diagnosis. Thirty‐eight lymphomas were characterized immunologically and in 35, a light chain restriction could be demonstrated. Our results show that the use of FNAC in the diagnosis of primary myeloma and lymphoma of bone obviates the need for other diagnostic modalities, including open biopsy. A combined approach based on radiology and FNAC, performed as an out‐patient procedure, offers rapid and accurate diagnosis of myeloma and lymphoma among patients with radiographically unclassified destructive bone lesions.
The use of cytospin monolayer technique in the cytological diagnosis of vulval and anal disease
Authors: Levine T. S. , Rolfe K. J. , Crow J. , Styles S. , Perrett C. W. , Maclean A. B. , Reid W. M. N.
Published: March 2003

The use of cytospin monolayer technique in the cytological diagnosis of vulval and anal disease

This pilot study investigated the use of the non‐invasive cytospin monolayer technique in the diagnosis and screening of neoplastic and non‐neoplastic vulval disease. Twenty‐three patients (age range 34–86 years) attending a vulval disease clinic had brush cytology performed. The samples were prepared with a cytospin monolayer technique and the slides Papanicolaou‐stained. Subsequent cytological interpretation and diagnosis were performed without knowledge of the clinical history and correlated with follow‐up biopsy histopathology from each patient. Twenty‐eight cytospin samples were analysed in total, of which 11 (39%) contained dyskaryotic cells which were assessed and a predicted VIN/AIN grade given. Ten of 11 samples (91%) reported as dyskaryotic had VIN/AIN on biopsy histology. One of 11 samples (9%) was reported as containing occasional squamous cells with borderline nuclear features and, although the corresponding biopsy did not show VIN, basal atypia was reported. One patient had features suggesting invasive carcinoma on cytology which was verified on subsequent biopsy. The 15 cases in which no dyskaryotic cells were identified did not show VIN or AIN on subsequent histology. Two cases were acellular and considered inadequate for cytological interpretation. The cytospin monolayer technique allows the diagnosis of neoplastic from non‐neoplastic vulval disease. It is a quick, inexpensive and non‐invasive method that may have a role in diagnosis, screening and surveillance of patients.