bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of 123I‐diagnostic imaging in the follow‐up of patients with differentiated thyroid carcinoma as compared to 131I‐scanning: avoidance of negative therapeutic uptake due to stunning
Authors: Siddiqi A. , Foley R. R. , Britton K. E. , Sibtain A. , Plowman P. N. , Grossman A. B. , Monson J. P. , Besser G. M.
Published: March 2003

OBJECTIVE Some patients with relapsed differentiated thyroid cancer may show rising thyroglobulin (Tg) levels despite a lack of 131I uptake on routine whole body imaging. A significant proportion of these patients, after therapy doses of 131I, may demonstrate positive 131I uptake with a subsequent fall in serum Tg, implying a therapeutic effect. Attempts to identify such patients by increasing the dose of the diagnostic 131I tracer may lead to inhibition of subsequent uptake after the therapy dose, an effect referred to as ‘stunning’ and associated with a reduction in therapeutic effect. 123I is a short half‐life γ‐emitter, thought to be unlikely to cause stunning, which may thus be more suitable than 131I for diagnostic imaging of thyroid cancer.

DESIGN AND PATIENTS The efficacy of the 123I radionuclide was determined in a longitudinal study of 12 patients who were selected only because they showed elevated serum Tg and a negative diagnostic 131I whole body study prior to therapy with 131I.

RESULTS There was almost complete concordance in uptake between 123I diagnostic imaging and the final scans carried out after 131I therapy (hereafter known as therapy studies) in 11 out of 12 patients at their first evaluation, in each of four patients receiving 123I at their second evaluation and in a single patient receiving 123I at a third evaluation. One patient had a positive 123I study but a negative 131I therapy study: following therapy Tg declined from 5·5 pg/l to undetectable levels, implying a therapeutic effect, and suggesting that the negative uptake was not the result of stunning. Two negative diagnostic 123I studies were followed by negative therapy studies, and thus there were no false negatives. 123I correctly identified disease in the nine patients with metastases in the lungs, mediastinum and bone at the first evaluation, in all four patients at the second evaluation and in the single patient at the third evaluation. At the end of the study, patients had received up to three 131I therapy doses, Tg had risen in four patients, fallen in eight and become undetectable in one patient.

CONCLUSIONS 123I is highly sensitive in diagnosing local recurrence and metastatic disease, and produces scintigraphic images which concord well with uptake following 131I therapy. It is proposed that 123I imaging, in combination with serum Tg measurements, should replace 131I tracer imaging as an indicator of the potential efficacy of 131I therapy. Stunning, with its detrimental effects on 131I therapy, may thus be avoided. The possibility of false negative images due to the stunning phenomenon must always be borne in mind if there is a discrepancy between positive 131I imaging studies and a surprisingly negative subsequent 131I therapy scan.
Adrenocorticotropin stimulation tests in patients with hypothalamic‐pituitary disease: low dose, standard high dose and 8‐h infusion tests
Authors: Nye Elisabeth J. , Grice Jeffrey E. , Hockings Gregory I. , Strakosch Christopher R. , Crosbie Georgina V. , Walters Margaret M. , Torpy David J. , Jackson Richard V.
Published: March 2003

OBJECTIVES Low doses of ACTH [1‐24] (0·1, 0·5 and 1·0 µg per 1·73 m2) may provide a more physiological level of adrenal stimulation than the standard 250 µg test, but not all studies have concluded that the 1·0 µg is a more sensitive screening test for central hypoadrenalism. Eight‐hour infusions of high dose ACTH [1‐24] have also been suggested as a means of assessing the adrenals' capacity for sustained cortisol secretion. In this study, we compared the diagnostic accuracy of three low dose ACTH tests (LDTs) and the 8‐h infusion with the standard 250 µg test (HDT) and the insulin hypoglycaemia test (IHT) in patients with hypothalamic‐pituitary disease.

SUBJECTS AND DESIGN Three groups of subjects were studied. A healthy control group (group 1, n = 9) and 33 patients with known hypothalamic or pituitary disease who were divided into group 2 (n = 12, underwent IHT) and group 3 (n = 21, IHT contraindicated). Six different tests were performed: a standard IHT (0·15 U/kg soluble insulin); a 60‐minute 250 µg HDT; three different LDTs using 0·1 µg, 0·5 µg and 1·0 µg (all per 1·73 m2); and an 8‐h infusion test (250 µg ACTH [1‐24] at a constant rate over 8 h).

RESULTS Nine out of the 12 patients in group 2 failed the IHT. Three out of 12 patients from group 2 who clearly passed the IHT, also passed all the ACTH [1‐24] stimulation tests. Seven of the 9 patients who failed the IHT, failed by a clear margin (peak cortisol < 85% of the lowest normal). Two of the 7 also failed all the ACTH [1‐24] tests. Five of the 7 patients had discordant results, four passed the 0·1 LDT, one (out of four) passed the 0·5 LDT, none (out of three) passed the 1·0 LDT, two passed the HDT and three passed the 8‐h test. Two patients were regarded as borderline fails in the IHT. Both passed the ACTH [1‐24] tests, although one was a borderline pass in the 8‐h test. Only five out of the 21 patients in group 3 showed discordance between the HDT and the LDTs. One patient passed the HDT and failed the 0·1 LDT, four patients failed the HDT but passed some of the different LDTS.

CONCLUSIONS We conclude that in the diagnosis of central hypoadrenalism, ACTH [1‐24] stimulation tests may give misleading results compared to the IHT. The use of low bolus doses of ACTH [1‐24] (1·0, 0·5 or 0·1 µg) or a high dose prolonged infusion does not greatly improve the sensitivity of ACTH [1‐24] testing. Dynamic tests that provide a central stimulus remain preferable in the assessment of patients with suspected ACTH deficiency.
Severe hypomagnesaemia‐induced hypocalcaemia in a patient with Gitelman’s syndrome
Authors: Pantanetti Paola , Arnaldi Giorgio , Balercia Giancarlo , Mantero Franco , Giacchetti Gilberta
Published: March 2003

Gitelman’s syndrome (GS) is characterized by hyperreninaemic hyperaldosteronism, hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria and is due to a defect of the Na–Cl cotransporter at the distal tubule, which may appear in a sporadic or in a familial form. It is an autosomal recessive disorder associated with normal or reduced blood pressure. We report a case of severe hypomagnesaemia‐induced hypocalcaemia in a 39‐year‐old Caucasian woman with GS. The patient had impaired parathormone (PTH) responsiveness to peripheral stimuli, as proved by the marked PTH increase and normalization of plasma calcium levels after acute and chronic administration of magnesium salts. Secondary normotensive hyperreninaemic hyperaldosteronism with hypokalaemia and metabolic alkalosis was also present. Normal plasma renin activity (PRA) and aldosterone levels were restored by administration of an inhibitor of prostaglandin synthesis. The electrolyte imbalance was successfully corrected with chronic treatment with magnesium and potassium salts. Genetic analysis identified a compound heterozygous mutation in the Na‐Cl cotransporter gene (NCCT), confirming the diagnosis of GS. The striking feature of this case of GS was impaired PTH responsiveness to peripheral stimuli determined by hypomagnesaemia and the resulting severe hypocalcaemia, which had not previously been described in this syndrome.
Long‐term follow‐up of patients with bone metastases from differentiated thyroid carcinoma – surgery or conventional therapy?
Authors: Zettinig Georg , Fueger Barbara J. , Passler Christian , Kaserer Klaus , Pirich Christian , Dudczak Robert , Niederle Bruno
Published: March 2003

objective Surgery of bone metastases from differentiated thyroid carcinoma seems indicated in individual patients. This study was performed (1) to analyse retrospectively patients with bone metastases from differentiated thyroid carcinoma and (2) to evaluate the impact of surgery of bone metastases on survival.

patients and design We analysed 41 consecutive patients with bone metastases from differentiated thyroid carcinoma who had undergone thyroid surgery at Vienna University Hospital since 1966. The median follow‐up time was 12 years. There were 24 females and 17 males with a mean age of 60 ± 12 years. Primary tumour histology was follicular in 35 and papillary in six patients. Radioiodine treatment was performed in 32 with a mean administered activity of 27 ± 24 GBq 131I. Metastases restricted to the skeleton were found in 22 whereas in 19 individuals additional extraskeletal distant metastases were seen. Twenty‐seven patients had multiple bone metastases. In 21 individuals, up to five bone metastases were surgically removed with the intention of cure.

results Univariate analysis identified total thyroidectomy (P = 0·003), lymph node surgery (P = 0·001), radioiodine therapy (P = 0·036), and the absence of extraskeletal distant metastases (P = 0·017) as significant predictors of survival. Multivariate analysis failed to identify significant prognostic factors. In the subgroup of patients with distant metastases limited to the bones, univariate analysis identified, in addition to thyroid and lymph node surgery, the surgical extirpation of the bone metastases as a significant prognostic factor associated with improved survival (P = 0·025).

conclusions These findings indicate that in patients without additional extraskeletal distant metastases, the radical surgical extirpation of bone metastases from differentiated thyroid carcinoma might be associated with improved survival.
Polysomnographic findings in five adult patients with pituitary insufficiency before and after cessation of human growth hormone replacement therapy
Authors: Nolte Wilhelm , Rädisch Carsten , Rodenbeck Andrea , Wiltfang Jens , Hüfner Michael
Published: March 2003

objective We observed the new onset of severe obstructive sleep apnoea syndrome (OSAS) in an adult male patient during human growth hormone (hGH) replacement therapy. This prompted us to evaluate the potential influence of hGH substitution therapy on sleep in middle‐aged men.

design A longitudinal study.

subjects Five male patients (aged 44–56 years, median age 54 years) with postoperative pituitary insufficiency given hGH replacement therapy for 1–2 years (median dose 2·0 U/day; median IGF‐I serum concentration 351 µg/l) and 6 months after cessation of hGH treatment (median IGF‐I level 77 µg/l – 1 µg/l = 0·131 nmol/l).

measurements Polysomnographic studies were performed, and the following parameters were determined: time in bed (TIB), sleep period time (SPT), total sleep time (TST), sleep efficiency (SE = TST/TIB), sleep stage 1 onset latency (SL), different sleep stages [W (wake), S1, S2, SWS (slow wave sleep = S3 + S4) and REM; % of SPT], stage shifts per hour of SPT (SS/h), stage shifts to W/h of SPT [A/h (awakening)], index of apnoea and hypopnoea events per hour of TST (AH/h), arousals from apnoea and hypopnoea per hour of TST (Ar/h), index of obstructive (OAH/h), central (CAH/h) and mixed (MAH/h) events of apnoea and hypopnoea per hour of TST and minimal desaturation (MD).

results Median baseline results were: TIB, 479 min; SPT, 465 min; TST, 405 min; SE, 77%; SL, 8·5 min; W, 18·9%; S1, 8·2%; S2, 52·7%; REM, 13·5%; SS/h, 17·7; A/h, 2·8; AH/h, 11·9; Ar/h, 4·4; MD, 80%. These parameters did not change significantly after cessation of hGH treatment. In contrast, median SWS decreased significantly from 33 min (7·1%) to 7·5 min (1·8%; P = 0·03). Median OAH/h decreased significantly from 4·4 to 0·1 (P = 0·03) whereas CAH/h increased from 6·3 to 14·6 (P = 0·03) after cessation of hGH. Correspondingly, one patient with OSAS improved markedly whereas another patient developed new and asymptomatic central SAS after cessation of hGH.

conclusion This study showed that hGH replacement therapy influenced sleep reaction in a complex way in middle‐aged men; cessation of treatment was associated with a significant decrease in slow wave sleep and a shift from obstructive to central apnoea and hypopnoea.
Effects of glucose, free fatty acids or arginine load on the GH‐releasing activity of ghrelin in humans
Authors: Broglio Fabio , Benso Andrea , Gottero Cristina , Prodam Flavia , Grottoli Silvia , Tassone Francesco , Maccario Mauro , Casanueva Felipe F. , Dieguez Carlos , Deghenghi Romano , Ghigo Ezio , Arvat Emanuela
Published: March 2003

objective Ghrelin, a 28 amino acid peptide purified from the stomach and showing a unique structure with an n‐octanoyl ester in serine‐3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS‐R) and strongly stimulates GH secretion. In humans, ghrelin is more potent than growth hormone‐releasing hormone (GHRH) and non‐natural GHS such as hexarelin. Moreover, ghrelin shows a true synergism with GHRH, has no interaction with hexarelin and, similarly to non‐natural GHS, is partially refractory to the inhibitory effect of exogenous somatostatin (SS). Despite this evidence, the mechanisms underlying the GH‐releasing effect of ghrelin in humans have not been fully clarified.

subjects To this aim we enrolled six normal young volunteers [age (mean ± SEM) 28·9 ± 3·1 year; body mass index 22·3 ± 1·0 kg/m2).

design and measurements In all subjects we studied the effects of glucose (OGTT, 100 g oral glucose at −45 min) or free fatty acids (FFA) load [lipid–heparin emulsion, Li–He, Intralipid 10% 250 ml + heparin 2500 U i.v. from −30 to +120 min] as well as of arginine (ARG, 0·5 g/kg infused from 0 to +30 min) on the GH response to human ghrelin (1·0 µg/kg i.v. at 0 min) administration. These results were compared with those obtained by studying the effects of OGTT, Li–He and ARG on the GH response to GHRH‐29 (1·0 µg/kg i.v. at 0 min).

results The GH response to ghrelin (auc 5452·4 ± 991·3 µg/l/h) was higher (P < 0·05) than that after GHRH (1519·4 ± 93·3 µg/l/h). The GH response to GHRH was inhibited by OGTT (450·7 ± 81·1 µg/l/h, P < 0·05) and almost abolished by Li–He (230·0 ± 63·6 µg/l/h, P < 0·05) while was markedly potentiated by ARG (2520·4 ± 425·8 µg/l/h, P < 0·05). The GH response to GHRH + ARG, however, was lower (P < 0·05) than that to ghrelin alone. The GH response to ghrelin was blunted by OGTT (2153·1 ± 781·9 µg/l/h, P < 0·05) as well as by Li–He (3158·8 ± 426·7 µg/l/h, P < 0·05) but these responses remained higher (P < 0·05) than that to GHRH alone. On the other hand, ARG did not modify the GH response to ghrelin (6324·3 ± 1275·5 µg/l/h). For GH 1 µg/l = 2 mU/l.

conclusions In humans, ghrelin exerts a strong stimulatory effect on GH secretion which is partially refractory to the inhibitory effect of both glucose and FFA load and is not enhanced by ARG. These factors almost abolish and potentiate, respectively, the GH response to GHRH, at least partially, via modulation of hypothalamic SS release. Thus, our findings agree with the hypothesis that ghrelin as well as non‐natural GHS acts, at least partially, by antagonizing SS activity.
Localization of gastrinomas by selective intra‐arterial calcium injection
Authors: Turner J. J. O. , Wren A. M. , Jackson J. E. , Thakker R.V. , Meeran K.
Published: March 2003

Background Preoperative localisation is important for successful surgical treatment of gastrinomas. However, a satisfactory method that achieves this has not been defined, and at present somatostatin receptor scintigraphy and selective intra‐arterial stimulation testing with secretin have the greatest sensitivities. As secretin is now difficult to obtain, we decided to explore the use of calcium gluconate as a secretagogue. High extracellular calcium concentrations cause degranulation of neuroendocrine cells and subsequent release of hormone.

Methods Two patients with biochemically proven gastrinomas were investigated pre‐operatively. Under angiographic control calcium gluconate was injected into the arteries supplying the pancreas and duodenum, gastrin levels were then determined in hepatic vein samples obtained before and 30, 60, 90, 120 and 180 seconds after each injection. One of the patients had also previously undergone selective intra‐arterial stimulation testing with secretin.

Results Calcium gluconate produced sharp peaks of gastrin which unequivocally localised the tumour to a specific vascular territory in each case. Furthermore, surgery confirmed the localisations of the gastrinomas. Calcium injection, unlike secretin, into vascular territories without gastrinomas caused no rise in gastrin, thereby demonstrating calcium's greater specificity.

Conclusions Calcium gluconate is a highly sensitive and specific alternative secretagogue to secretin for localisation of pancreatic and duodenal gastrinomas. Furthermore calcium gluconate was found to demonstrate the territory of the tumour more accurately than secretin.
Gender‐related differences in erythrocyte glutathione peroxidase activity in healthy subjects
Authors: Massafra Cosimo , Gioia Dino , De Felice Claudio , Muscettola Michela , Longini Mariangela , Buonocore Giuseppe
Published: March 2003

objective The antioxidant property of oestrogens may partly explain the gender differences in atherosclerotic heart disease and a reduction in the incidence of coronary heart disease, as well as mortality from cardiovascular disease in women undergoing postmenopausal oestrogen therapy. In the present study, we tested the hypothesis that the antioxidant glutathione peroxidase (GSH‐Px) erythrocyte activity is gender related and is correlated with oestradiol serum levels.

patients One hundred and fifty healthy women (90 premenopausal; 60 postmenopausal) and 150 age‐matched healthy men were recruited during routine health screening.

design and measurements Serum was analysed for oestradiol (E2), progesterone and testosterone concentrations, and erythrocytes for GSH‐Px enzyme activity. Thirty of the 60 postmenopausal women were treated with transdermal therapy for 30 days with 8‐mg E2 patches (nominal daily dose 100 µg), while the remaining 30 acted as controls.

results Erythrocyte GSH‐Px activity was significantly higher in premenopausal than in postmenopausal women (P = 0·0014), and higher in premenopausal women than in age‐matched men (P = 0·025). By contrast, no significant differences were observed between postmenopausal women and the age‐matched male population. In postmenopausal women, E2 replacement therapy induced a significant increase in erythrocyte GSH‐Px activity (P < 0·001). GSH‐Px was positively correlated with serum E2 levels in both premenopausal (r = 0·26, P = 0·011) and postmenopausal women treated with oestrogen replacement therapy (r = 0·42, P = 0·022). No significant correlations in the female population were found between GSH‐Px erythrocyte activity and the other sex steroid hormones examined (r2 ≤ 0·10, P ≥ 0·45). No statistically significant correlations were found between GSH‐Px and E2, progesterone and testosterone in the male population (r2 ≤ 0·15, P ≥ 0·30).

conclusions Our findings support the hypothesis that oestrogens are responsible for the sex‐related differences in glutathione peroxidase activity. The hypothesis generated from the present study can be tested directly in experimental models involving specific bone marrow cells by analysis of specific glutathione peroxidase transcriptional changes.
Thyroid stimulating hormone (TSH) concentrations and menopausal status in women at the mid‐life: SWAN
Authors: Sowers MaryFran , Luborsky Judy , Perdue Craig , Araujo Katy L. B. , Goldman Marlene B. , Harlow Siobán D.
Published: March 2003

objective We evaluated menopausal symptoms, menstrual cycle bleeding characteristics and reproductive hormones for their associations with thyroid stimulating hormone (TSH) concentrations in women at the mid‐life from five ethnic groups.

methods This report is from the baseline evaluation of the Study of Women's Health Across the Nation (SWAN), a community‐based multiethnic study of the natural history of the menopausal transition. Enrollees were 42–52 years old (pre‐ and early perimenopausal) African American, Caucasian, Chinese, Hispanic and Japanese women (n = 3242). Enrollees were interviewed about self‐reported diagnosed hypo‐ and hyperthyroidism or thyroid treatment, menopausal symptoms and menstrual cycle bleeding characteristics. Serum was assayed for TSH, oestradiol, testosterone, FSH and SHBG.

results There were 6·2% of women with TSH > 5·0 mIU/ml and 3·2% with TSH < 0·5 IU/ml, cutpoints that have been used to encompass clinical and subclinical hypo‐ and hyperthyroidism, respectively. African American women had significantly lower mean TSH concentrations than Caucasian, Hispanic and Chinese women. Of the more than 15 menopause symptoms evaluated, only fearfulness was associated with having a TSH value > 5·0 mIU/ml (P < 0·008) or < 0·5 mIU/ml (P < 0·02). Women with TSH values outside the range of 0·5–5·0 mIU/ml were more likely to report shorter or longer menstrual periods (P = 0·004 for both) than women within that range. FSH, SHBG, dehydroepiandrosterone sulphate (DHEA‐S), testosterone, and oestradiol concentrations were not associated with TSH concentrations.

conclusion In mid‐aged women, there was a 9·6% prevalence of TSH values outside the euthyroid range of 0·5–5·0 mIU/ml. Although TSH was associated with bleeding length and self‐reported fearfulness, it was not associated with indicators of the menopausal transition, including menopausal stage defined by bleeding regularity, menopausal symptoms or reproductive hormone concentrations.
The outcome in Australian children with hyperinsulinism of infancy: early extensive surgery in severe cases lowers risk of diabetes
Authors: Jack Michelle M. , Greer Ristan M. , Thomsett Michael J. , Walker Rosslyn M. , Bell John R. , Choong Catherine , Cowley David M. , Herington Adrian C. , Cotterill Andrew M.
Published: March 2003

aimsHyperinsulinism of infancy (HI) is characterized by unregulated insulin secretion in the presence of hypoglycaemia, often resulting in brain damage. Pancreatic resection for control of hypoglycaemia is frequently resisted because of the risk of diabetes mellitus (DM). We investigated retrospectively 62 children with HI from nine Australian treatment centres born between 1972 and 1998, comparing endocrine and neurological outcome in 28 patients receiving medical therapy alone with 34 who required pancreatic resection to control their hypoglycaemia.

methodsHistory, treatment and clinical course were ascertained from file audit and interview. Risk of DM (hazard ratio) attributable to age at surgery (< vs. ≥ 100 days at last pancreatectomy) and extent of resection (< vs. ≥ 95%) were calculated using Cox proportional hazards regression and categorical variables compared by the χ2‐test. Neurological outcome (normal, mild deficit or severe deficit) was derived from the most authoritative source.

resultsSurgically treated patients had a greater birthweight, earlier presentation and higher plasma insulin levels. Of 18 infants < 100 days and 16 ≥ 100 days of age at surgery, four (all ≥ 100 days) became diabetic as an immediate consequence of surgery and five (two < 100 days and three ≥ 100 days) became diabetic 7–18 years later. Surgery ≥ 100 days and pancreatectomy ≥ 95% were associated with development of diabetes (HR = 12·61, CI 1·53–104·07 and HR = 7·03, CI 1·43–34·58, respectively). Neurodevelopmental outcome was no different between the surgical and medical groups with 44% overall with neurological deficits. Patients euglycaemic within 35 days of the first symptom of hypoglycaemia (Group A) had a better neurodevelopmental outcome than those still hypoglycaemic > 35 days from first presentation (Group B) (P = 0·007). Prolonged hypoglycaemia in Group B was due either to delayed diagnosis or to need for repeat surgery because of continued hypoglycaemia. Within Group A, medically treated patients (who presented later with apparently milder disease) had a higher incidence of neurodevelopmental deficit (n = 15, four mild, three severe deficit) compared with surgically treated patients (n = 18, two mild, none severe deficit) (P < 0·025).

conclusionsPoor neurodevelopmental outcome remains a major problem in hyperinsulinism of infancy. Risk of diabetes mellitus with pancreatectomy varies according to age at surgery and extent of resection. Patients presenting early with severe disease have a better neurodevelopmental outcome and lower risk of diabetes if they are treated with early extensive surgery.
Thoracoabdominal asynchrony in small children with lung disease – methodological aspects and the relationship to lung mechanics
Authors: Strömberg N. O. T. , Nelson N.
Published: March 2003

Thoracoabdominal asynchrony (TAA) has been regarded as a clinical sign of lung disease. A measure of TAA is the phase angle (φ) between ribcage (RC) and abdominal (ABD) respiratory motion. The aim of this study was to assess the effect of the points chosen for φ calculation. The influence of correct respiratory timing was assessed by calculating TAA indices using a pneumotachometer (PTM) as timing reference and using the calibrated respiratory inductive plethysmograph (RIP) signal for respiratory timing. The relationship between TAA and lung mechanics was studied in 15 young children 9 months to 2·5 years of age with a wide span of restrictive and/or obstructive lung disease. φ as calculated from mid‐RC points was poorly related to φ as calculated from the top RC and ABD positions, indicating non‐sinusoidal respiratory motions. The estimation of the TAA indices depended on correct respiratory timing, which in the case of severe asynchrony cannot be inferred from the RIP signals alone. An external source for respiratory timing, such as the airway flow measured by a PTM, is needed. The degree of asynchronous chest wall movement was only a weak indicator of pathological lung mechanics. We conclude that the usefulness of TAA indices as indicators of impaired lung mechanics is limited by the sensitivity to the points used for their calculation (φ) and the need of an external source for respiratory timing. It was therefore not surprising that a rather weak relationship was seen between TAA indices and lung mechanics.
Endurance training, overtraining and baroreflex sensitivity in female athletes
Authors: Uusitalo
Published: March 2003

We examined heavy training‐induced changes in baroreflex sensitivity, plasma volume and resting heart rate and blood pressure variability in female endurance athletes. Nine athletes (experimental training group, ETG) increased intense training (70–90% VO2max) volume by 130% and low‐intensity training (<70% VO2max) volume by 100% during 6–9 weeks, whereas the corresponding increases in six control athletes (CG) were 5% and 10% respectively. Maximal oxygen uptake (VO2max) in the ETG and CG did not change, but in five ETG athletes VO2max decreased from 53·0 ± 2·2 (mean ± SEM) (CI 46·8–59·2) ml kg–1 min–1 to 50·2 ± 2·3 (43·8–56·6) ml kg–1 min–1 (P<0·01), indicating overtraining. Baroreflex sensitivity (BRS) measured using the phenylephrine technique and blood pressure variability (BPV) did not change, but the low‐frequency power of the R–R interval variability increased in the ETG (P<0·05). The relative change in plasma volume was 7% in the ETG and 3% in the CG. The changes in BRS did not correlate with the changes in plasma volume, heart rate variability and BPV. We conclude that heavy endurance training and overtraining did not change baroreflex sensitivity or BPV but significantly increased the low‐frequency power of the R–R interval variability during supine rest in female athletes as a marker of increased cardiac sympathetic modulation.
Hypoglycaemia leads to an increased QT interval in normal men
Authors: Eckert Bodil , Agardh Carl‐David
Published: March 2003

Hypoglycaemia is presumed to be the cause of death in about 3% of insulin‐treated diabetic patients. Some of these patients suffer from hypoglycaemic brain damage, but the majority have no evident brain damage and are supposed to have died from other causes such as a cardiac arrhythmia. The putative mechanism is a hypoglycaemia‐induced prolongation of the QT interval which increases the risk of malignant ventricular tachycardia. The aim of the present study was to examine the electrocardiogram during and after hypoglycaemia in healthy men. To that end, hypoglycaemia was induced by an intravenous infusion of insulin (2·5 mU kg−1 min−1) in 10 healthy men to reach a venous blood glucose level of 2·1 ± 0·3 mmol l−1 for 65 ± 9 min. Before hypoglycaemia, after 20 and 50 min of hypoglycaemia and 20 and 45 min after normalization of the blood glucose, the QT interval was measured by a ruler and corrected for the heart rate. Results are given as mean ± SD and comparisons were made with an
ANOVA, except for symptom scores and plasma adrenaline where non‐parametric tests were used. When this indicated significance, further analysis was performed with a two‐tailed t‐test. During hypoglycaemia the corrected QT interval increased from 380 ± 20 ms½ to 440 ± 30 ms½ (P<0·001), and the amplitude of the T wave decreased (P = 0·002). The serum potassium level decreased from 4·3 ± 0·3 mmol l−1 to 3·5 ± 0·2 mmol l−1 (P<0·001) and the plasma adrenaline concentration increased from 0·20 ± 0·04 nmol l−1 to 2·46 ± 2·58 nmol l−1 (P<0·01). The results of this study confirm that a prolongation of the QT interval occurs during hypoglycaemia, but the significance of this finding still has to be proven.
Study of the effects of various transcutaneous electrical nerve stimulation (TENS) parameters upon the RIII nociceptive and H‐reflexes in humans
Authors: Walsh  , Noble  , Baxter  , Allen
Published: March 2003

Despite over two decades of clinical use, the neurophysiological and anti‐nociceptive effects of transcutaneous electrical nerve stimulation (TENS) have yet to be definitively described. The current study was designed to examine the effect of TENS on the RIII nociceptive reflex elicited in healthy human subjects; the H‐reflex was measured concomitantly to monitor changes in α‐motoneuron excitability. Following approval from the university’s ethical committee, 50 healthy human volunteers (25 male and 25 female) participated in the study. The subjects ranged in age from 18 to 30 years (mean 22, SD 3). Subjects were randomly allocated equally to a control group or one of four TENS groups. In the TENS groups, stimulation was applied for a total of 15 min over the sural nerve in the left leg. Ipsilateral RIII and H‐reflexes were recorded five times during the 45 min experimental period. In addition, subjects also rated pain associated with the RIII reflex using a computerized visual analogue scale (VAS). Statistical analysis using two‐way repeated‐measures ANOVA showed no differences between groups for H‐reflex, RIII reflex nor VAS data. These results suggest that TENS does not significantly affect either of the two reflexes, at least using the parameters and application time in the current study.
Effect of somatostatin on postprandial gallbladder relaxation
Authors: Vu M. K. , Van Oostayen J. A. , Biemond I. , Masclee A. A. M.
Published: March 2003

Although the inhibitory effect of somatostatin (SST) on gallbladder contraction is well known, the influence of SST on gallbladder motility during the late postprandial or relaxation phase has not been studied. We therefore investigated the effect of SST on gallbladder relaxation and gut hormone release during the late postprandial phase. Eight healthy volunteers participated in two experiments performed in random order during continuous infusion of either SST or saline (placebo) starting 2 h after meal ingestion. At regular intervals, gallbladder volumes were measured (ultrasonography) and blood samples were taken for determination of plasma cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY) and neurotensin levels (radioimmunoassay). Postprandial gallbladder contraction was similar in both experiments: 68 ± 4% vs. 66 ± 4%. During SST infusion, postprandial gallbladder contraction was significantly (P<0·01) reduced (2874 ± 813% *240 min) compared with saline (9391 ± 1595% *240 min). Plasma CCK, PP, PYY and neurotensin levels were in the same range in the early postprandial phase but were significantly reduced during SST infusion compared with placebo (late postprandial phase). Plasma levels of CCK correlated with gallbladder volumes during both the contraction and relaxation phase (r=0·68, P=0·01 and r=0·61, P=0·008, respectively). SST enhances gallbladder relaxation and reduces hormone secretion in the late postprandial phase. The results point to an association between CCK and gallbladder volume not only during the postprandial contraction phase but also during the relaxation phase.
Decreased reuptake of serotonin in human platelets after surgery
Authors: Naesh Ole , Hindberg Inge , Bruun Aase B.
Published: March 2003

We have documented earlier a decrease in platelet serotonin and a concurrent increase in plasma serotonin, 5‐hydroxytryptamin (5‐HT) after various forms of stress, suggesting a disturbed platelet 5‐HT reuptake mechanism following stress. In order to further elucidate these findings, we have studied platelet 5‐HT reuptake kinetics (Vmax and Km) in nine patients before and 4 days after major, uncomplicated abdominal surgery. We found a significant decrease in the maximal 5‐HT reuptake velocity (Vmax) after surgery and changes in Km, verifying alterations in the affinity of the platelet 5‐HT transport system. The present results thus confirm the hypothesis that 5‐HT reuptake kinetics are altered following adrenergic hyperactivity. A decrease in platelet 5‐HT reuptake may bear implications for our understanding of poststress adaptive changes in the cardiovascular system as well as in the central nervous system (CNS) serotonergic neurones following stressful stimulation.
Day‐to‐day variation in oxygen consumption at submaximal loads during ergometer cycling by adolescents
Authors: Wergel‐Kolmert Ulla , Ågehäll Anna , Rosenberg Nils , Wohlfart Björn
Published: March 2003

The day‐to‐day variation in oxygen consumption (V˙O2) during ergometer cycling by 20 healthy adolescents, 10 females and 10 males, was measured using indirect calorimetry. The two sets of measurements were performed on two consecutive days. Great care was taken to minimize possible disturbing factors. Cycling started at 50 and 100 W for female and male adolescents, respectively. The load was increased at a rate of 5 W 30 s−1. In order to reach steady state, the load was kept constant for 3·5 min twice during the cycling session, at 100 and 130 W for the females and at 130 and 160 W for the males. Cycling continued until exhaustion. The maximal loads were 196 W (mean) and 271 W (mean) for females and males, respectively. At the maximal loads the day‐to‐day variation (±2 SD) in oxygen consumption (V˙O2) was ±330 ml min−1 for females and 390 ml min−1 for males. At the submaximal loads the day‐to‐day variation in heart rate (HR) was 9·3 beats min−1 (±2 SD) (coefficient of variation, CV=3·4% at 130 W) for both sexes. The day‐to‐day variation in oxygen consumption (V˙O2) was ±199 ml min−1 (±2 SD) at the different submaximal loads and did not differ between female and male adolescents (CV=5·7% at 130 W). This natural day‐to‐day variation must be taken into consideration when using a submaximal ergometer cycling test for the evaluation of physical capacity in the two sexes.
Changes of heart rate and blood pressure in registration of forced respiration flow‐volume loop
Authors: Kingisepp P.–H. , Jagomägi K. , Raamat R.
Published: March 2003

Changes in heart rate (HR) and finger mean blood pressure (MBP) during registration of the flow‐volume loop of forced respiration in healthy young subjects were studied. Breathing patterns of performing the flow‐volume loop of forced respiration (forced respiratory manoeuvre, FRM) as well as the related responses of cardiovascular parameters in different subjects were found to vary to a large extent. FRM has a remarkable influence on the cardiovascular system: during FRM the peak values of MBP were 19 ± 9 mmHg higher than baseline values and the peak values of HR were 30 ± 11 beats min–1higher. We conclude that it is essential to pay attention to a remarkable elevation of blood pressure in functional breathing tests in patients with high blood pressure.
Interindividual variability of surface EMG changes during cycling exercise in healthy humans
Authors: Jammes Y. , Arbogast S. , Faucher M. , Montmayeur A. , Tagliarini F. , Robinet C.
Published: March 2003

We studied surface electromyogram (SEMG) changes during 1‐h endurance cycling in 12 healthy subjects of whom five were involved in mountain bike training programme. The work load was set at 50% of the predicted maximal heart rate. The surface EMG and the compound evoked muscle action potential (M‐wave) from the vastus lateralis muscle were recorded at rest, during the 1‐h cycling period, and the 20‐min recovery period. The root mean square (RMS) and the median frequency (MF) of SEMG power spectrum were computed. In all subjects, there was no shift in the median frequency throughout the cycling period and the increase in RMS remained stable. In subjects untrained to endurance cyclism, the M‐wave duration increased at the end of the cycling period and these changes persisted for a consecutive 15‐min period during recovery of exercise. By contrast, in trained mountain bikers the M‐wave duration decreased after 2 min of exercise – the effect persisting for 2 min during recovery. These data suggest that the interpretation of M‐wave changes during cycling must take into consideration the sport practices of the subjects and also that SEMG power spectrum and M‐wave explore different electrophysiological events.
Diagnostic value of qualitative and quantitative variables in thyroid lesions
Authors: Rout P. , Shariff S.
Published: March 2003

Diagnostic value of qualitative and quantitative variables in thyroid lesions

Two hundred and thirty‐three thyroid lesions were studied by fine needle aspiration (FNA) cytology using standard cytologic criteria available in the literature. These included 114 cases of nodular colloid goitre (NCG), 47 cases of Hashimoto's thyroiditis (HT), 12 follicular adenomas (FAd), five cases of subacute thyroiditis and three cases of thyrotoxicosis among the benign lesions. The malignant lesions seen were 30 cases of papillary carcinoma (PCa), 16 follicular carcinomas (FCa), three cases with double lesions, e.g. papillary carcinoma with coexisting NCG, and three of papillary carcinoma with HT. Emphasis was given to eight qualitative and quantitative (morphometric) variables in these various thyroid lesions. Cell measurements were done using a Visopan Lux projection microscope. The three qualitative variables included type of nuclear membrane (regular/irregular), type of nuclear chromatin and the presence or absence of conspicuous nucleoli. The quantitative variables studied were nuclear diameter, nuclear area, cytoplasmic diameter, cytoplasmic area & N/C ratio. Statistical analysis was performed in order to know whether the standard cytologic criteria used at FNA cytology in the literature (increased cellularity, microfollicles, increased N/C ratio, absence of significant haemosiderin‐laden macrophages and scanty colloid) could differentiate a follicular adenoma from a follicular carcinoma. A statistical analysis was also performed to establish the utility of the qualitative and quantitative variables. The results showed that none of the standard cytologic criteria applied could differentiate follicular adenoma from a follicular carcinoma. With regard to qualitative variables, irregularity of nuclear membrane and presence of conspicuous nucleoli were most significant in papillary carcinoma, followed by follicular carcinoma, then by follicular adenoma; these features being hardly evident in nodular colloid goitre and Hashimoto's thyroiditis. A coarse nuclear chromatin was most significant in follicular carcinomas followed by follicular adenomas. It was less obvious in the benign conditions, but more prominent in Hashimoto's thyroiditis compared with a goitre. It was also not obvious in a papillary carcinoma. Of the quantitative variables, all measurements were greatest in PCa > FCa > FAd > NCG = HT. When differentiating follicular adenoma from follicular carcinoma the qualitative variables of significance were the presence or absence of nucleoli, the chromatin pattern and regularity/irregularity of nuclear membrane; the nuclear area was the most important feature among quantitative variables.
Radial scar/complex sclerosing lesion—a problem in the diagnostic work‐up of screen‐detected breast lesions
Authors: Orell S. R.
Published: March 2003

Radial scar/complex sclerosing lesion—a problem in the diagnostic work‐up of screen‐detected breast lesions

During the first 7.5 years of breast cancer screening in South Australia, 88 radial scar/complex sclerosing lesions were among the mammographically detected abnormalities. A false‐positive cytological diagnosis by fine needle biopsy was given in three of 69 such cases with satisfactory smears, a false‐positive rate of 4.3% in this particular group. A review of the smears suggested that the false‐positive diagnoses could have been avoided if a total or near total absence of a benign epithelial component had been included among the criteria for a malignant diagnosis. However, even after review, atypia was considered sufficiently worrying to be reported as a suspicion of malignancy in 7% of cases.
Training in cervical cytology, past, present and future
Authors: Denton K. J.
Published: March 2003

In recent years every aspect of the practice of cytology has come under close scrutiny. It is perhaps surprising therefore that very little has been published on the subject of training in cytology. Whilst training is an issue in all aspects of diagnostic cytology, this review will concentrate on cervical cytology.
Personal commentaryExternal quality assessment (EQA) in gynaecological cytology: radical rethinking required?
Authors: Slater D. N.
Published: March 2003

Accepted for publication 19 February 1999

THE PAST

The value of EQA in pathology, including proficiency testing in gynaecological cytology, has been the subject of much recent lively debate1–6. In summary, the proven role of EQA in the monitoring of personal performance and ability is still uncertain. Furthermore, its potential to prevent critical incidents remains purely speculative. Also, whether EQA would be better replaced, for some or all professional groups, by other methods of quality assurance is unknown. Similarly, whether EQA can justify the considerable professional time, effort and expense involved has not been resolved.

THE PRESENT

Not surprisingly, events at Kent & Canterbury Hospitals abruptly halted much of the debate about the foregoing issues7. Indeed, as a direct consequence of this and other incidents, the NHS Executive stipulated unilaterally that EQA is now mandatory within the NHS Cervical Screening Programme (CSP)8 and reinforced the necessity for all qualified laboratory staff to participate8–10. A surprise, however, was the Executive's enlightened comments on EQA. First, and of greatest significance, that the principal function of EQA in pathology is to improve standards and advance quality through personal education. Second, that EQA should be seen to complement other QA systems for the early identification of potential problems which might affect patient care. Third, that the identification of individual poor performance through EQA will be exceptional and in essence is a by‐product of the basic educational exercise. The latter conclusion was drawn, as far as one can judge, from previous experience with the NHS Breast Screening Programme (NHSBSP) EQA.

THE FUTURE—PERSONAL SUGGESTIONS FOR OPEN DEBATE
Analysis of proliferating cell fraction determined by monoclonal antibody to M1‐subunit ribonucleotide reductase and Ki‐67 in relation to p53 protein expression in fine‐needle aspirates from non‐Hodgkin's lymphomas
Authors: Sviatoha V. , Tani E. , Rassidakis G. , Tribukait B. , Kleina R. , Skoog L.
Published: March 2003

Analysis of proliferating cell fraction determined by monoclonal antibody to M1‐subunit ribonucleotide reductase and Ki‐67 in relation to p53 protein expression in fine‐needle aspirates from non Hodgkin's lymphomas

The purpose of this study was to analyse the proliferative fraction with the monoclonal antibody M1‐R‐R to M1‐subunit ribonucleotide reductase and with MIB‐1 to Ki‐67 antigen in relation to p53 protein expression in fine needle aspirates from B‐cell non‐Hodgkin's lymphomas.

One hundred and thirty‐seven cases, previously diagnosed and sub‐typed according to the Kiel classification and characterized by immunophenotyping, were included in the study. The M‐1 subunit ribonucleotide reductase (M1‐R‐R), Ki‐67 and p53 antigens were detected using monoclonal antibodies on stored cytospin preparations.

There was a good correlation (r = 0.72) between Ki‐67 and M1‐R‐R positive cell fraction in both high and low grade lymphomas. High‐grade lymphomas had a median percentage of M1‐R‐R/MIB‐1 positive cells of 53.0/73.0 for lymphoblastic, 61.0/52.0 for immunoblastic and 33.5/41.0 for centroblastic lymphomas, respectively. In low grade lymphomas figures of median percentage of M1‐R‐R/MIB‐1 were 9.0/15.0 for centroblastic/centrocytic, 11.0/9.5 for chronic lymphocytic leukaemia, 16.0/27.0 for centrocytic and 12.0/9.0 for immunocytomas, respectively. The median percentages of M1‐R‐R/MIB‐1 for high and low grade lymphomas were 37.0/50.5 and 11.0/12.0, respectively. In the p53 positive cases the proliferation rate as measured by staining for M1‐R‐R and MIB‐1 was higher than in p53 negative cases, but the difference was not statistically significant.

The results show that cytospin material obtained by fine needle aspiration and stored at −70 °C for years can be used reliably for both peroxidase‐avidin‐biotin and three‐step alkaline phosphatase immunocytochemical staining. In addition, proliferation fraction determined by M1‐R‐R monoclonal antibody staining correlates well with that measured by an established marker for cell proliferation, the Ki‐67 antibody.

However, the proliferation fraction as measured by the two antibodies differs in the various subtypes of non‐Hodgkin's lymphoma which indicates that they may contribute different prognostic information.
How predictive is a cervical smear suggesting invasive squamous cell carcinoma?
Authors: Johnson S. J. , Wadehra V.
Published: March 2003

How predictive is a cervical smear suggesting invasive squamous cell carcinoma?

Features have been described in severely dyskaryotic cervical smears that suggest frankly invasive or microinvasive squamous cell carcinoma. These are reported in three separate categories in our department. The aim of the current study was to assess the positive predictive value of these categories for invasive disease on histology. All smears reported in these categories over a five year period were correlated with the histology results. 527 smears were assessed. The positive predictive value of a smear suggesting frank invasion was 55.7% for all invasive squamous carcinomas and 40% for stage IB or above. Smears suspicious of invasion or microinvasion predicted invasive disease in 22.3% and 17.2%, respectively, most carcinomas being stage IA. Invasive squamous cell carcinoma may be predicted to a limited degree by cervical cytology especially when the smear suggests frank invasion.