bluuebunny/crossref_metadata_2025 huggingface dataset:
Extradural bupivacaine‐loaded microspheres and spinal cord bloodflow in the chronically instrumented rabbit
Authors: Malinovsky J.‐M. , Bernard J.‐M. , Corre P. Le , Faivre A. , Chatal J.‐F. , Pinaud M.
Published: November 2003

Thelocal anaesthetic agent bupivacaine decreases spinal cord blood flow. This study documents theeffect of bupivacaine‐loaded polylactic acid microspheres, a formulation allowing sustainedrelease, in the awake rabbit. Animals received at random extradural injection (1 ml) of either 5mg of plain bupivacaine (n=6)or 5 mg of bupivacaine‐loaded microspheres (n=6). Arterial blood pressure, cardiac output and spinal cord blood flow,using radioactive microspheres, and arterial blood gas tensions were measured before (T0) and30 (T30) and 120 (T120) min after the extradural injection. Motor blockade was assessed on afour‐point scale every 5 min until complete recovery. All rabbits experienced paralysis ofhindlimbs. Those receiving bupivacaine recovered completely before T120, and the blockduration was 86±23 min (mean±SD), whereas the block duration was210±60 min (P<0·05) in those receiving the microsphereformulation. Left renal blood flow baseline was 470±179 (mean±SD) and rightrenal blood flow was 464±177 ml min−1 100 g−1 and did not vary significantly throughout the experiment. Lumbar spinal cord bloodflow decreased in both groups, at T30 with bupivacaine (216±7%) and at T120with microspheres (212±8%). Arterial blood pressure decreased more rapidlywith bupivacaine (220±14% within 15 min) than with microspheres(219±11% within 30 min) and returned to baseline at T120 in both groups.Cardiac output and arterial blood gas tensions did not change significantly. We conclude thatpolylactic acid microspheres can prolong motor blockade from bupivacaine. Whatever itsformulation, and independently of systemic haemodynamic and blood gas variables, bupivacaineleads to a decrease in spinal cord blood flow, which persists for the duration of motorblockade. This suggests that motor block must be avoided in clinical practice when extraduralbupivacaine is used for pain relief.
Within‐subject variability in body composition using dual‐energy X‐rayabsorptiometry
Authors: De Lorenzo A. , Andreoli A. , Candeloro N.
Published: November 2003

The reproducibility of dual‐energy X‐ray absorptiometry (DXA)measure‐ments for total body composition and for segmental body composition wasinvestigated in 22 healthy male subjects who underwent six consecutive measurements in 90min. Body weight (mean±SD) and body height were72·3±8·8 kg and 1·75±0·04 m respectively,and body mass index was 23·5±2·5 kg m−2.Bone mineral content (BMC) was 3·30±0·36 kg, lean mass and fatmass as measured by DXA were 57·1±6·1 kg and11·8±6·5 kg respectively. For BMC, the reproducibility, expressed asthe coefficient of variation, was 1·2%, 1·5%,2·5%, 4·1% and 3·1% for total body, legs, arms,trunk and abdominal respectively. For lean tissue and for fat tissue, these values were1·5% and 5·0%; 1·8% and2·1%, 8·3% and 11·7%, 2·6%and 10·0%, 3·9% and 10·7% respectively. It isconcluded that the reproducibility for BMC is excellent, but that for lean tissue and for fattissue the variability is relatively high, especially in body segments.
Oral contraceptives elevate core temperature and heart rate duringexercise in the heat
Authors: Martin J. G. , Buono M. J.
Published: November 2003

It is generally believed that the elevated progesterone levels seen during the lutealphase of the menstrual cycle alter thermoregulatory function during exercise. We hypothesizedthat oral contraceptives (OCs) that contain synthetic progestogen would alter thermoregulationduring exercise in a manner similar to that seen during the luteal phase. To test this hypothesis10 healthy women currently taking OCs were recruited. Subjects performed a 1 h exercise boutin the heat (30 °C, 50% relative humidity; RH) at 60% of their maximumoxygen uptake on two occasions: once while on OCs and once during a control trial when thesubjects were off OCs. Core temperature, skin temperatures, heart rate, skin blood flow andsweat rate were measured at rest and every 20 min during both exercise bouts. OCssignificantly increased core temperature and heart rate over that seen during the controlcondition. Specifically, after 1 h of exercise, OCs caused a mean 0·3 °C and an 8‐bpm increase in core temperature and heart rate respectively. Additionally, the differences incore temperature and heart rate during the two trials became more exaggerated as exerciseduration increased, as evidenced by significant treatment‐by‐time interactions. These resultssuggest that OCs alter thermoregulatory and cardiovascular function during exercise in theheat. Furthermore, the changes in core temperature and heart rate seen during exercise whiletaking OCs are similar in direction and magnitude to those observed during the luteal phase ofthe menstrual cycle.
Muscle oxygen saturation during surgery in the lithotomy position
Authors: Svendsen L. B. , Flink P. , Wøjdemann M. , Riber C. , Mogensen T. , Secher N. H.
Published: November 2003

Surgeryin the lithotomy position canprovoke ischaemic lesions in the lower leg. We assessed lower leg oxygen saturation usingnear‐infrared spectroscopy (NIRS) in 42 patients undergoing urinary tract surgery. Lower legperfusion pressure was calculated as the difference of mean arterial pressure to pressure in an airbag supporting the lower leg and the hydrostatic pressure difference from the level of the lowerleg to the heart. During elevation of the lower leg for 25 (3–65) min (median and range),mean arterial pressure decreased from 100 (73–125) to 77 (53–112) mmHg and thelower leg perfusion pressure dropped from 103 (80–122) to 21 (−6–65)mmHg, corresponding to a reduction in oxygen saturation of the medial gastrocnemius musclefrom 68% (40–100%) to 58% (20–96%) (P<0·01). The results demonstrate significant desaturation of the calf muscles duringsurgery in the lithomy position.
Does long‐term smoking affect aortic stiffness more inwomen than in men?
Authors: Sonesson B. , Ahlgren Å. R. , Lazer L. , Länne T.
Published: November 2003

Smoking is a well‐known risk factor forcardiovascular disease, although understanding of the pathophysiological mechanism isincomplete. The effect of heavy smoking, for more than 20 years and of 20 cigarettes per day,on aortic stiffness was studied in women (n=23, age range 43–61years) and men (n=21, age range 43–61 years) who smoked but wereotherwise healthy and compared with a healthy reference population that did not smoke. Aorticstiffness (b) was calculated from the diameter and the pulsatile diameter change determinednon‐invasively using an ultrasonic echo‐tracking system and blood pressure obtained by theauscultatory method. The results showed that aortic diameter did not differ in smoking males (P=0·974) or in smoking females (P=0·361). Aortic stiffness was increased in the female (P=0·041) but not male smokers (P=0·222). Systolic,mean and diastolic blood pressure in the men and women who smoked did not differ fromthose in the healthy reference population. In conclusion, this investigation shows increasedaortic stiffness in female but not in male smokers. It indicates that the aorta of women might bemore vulnerable to smoking with regard to stiffening and degeneration than the aorta of men.
Release of atrial natriuretic peptide during pulmonary arteryclamping in man
Authors: Lindberg B. F. , Hambraeus G. , Wollmer P. , Andersson K.‐E.
Published: November 2003

The vasodilating hormone atrial natriuretic peptide (ANP) issecreted from the heart in response to atrial wall stretch, but knowledge of the time course ofANP secretion after acute releasing stimuli is limited. The time from stimulus to release ofimmunoreactive atrial natriuretic peptide (irANP) was investigated by unilaterally clamping thepulmonary artery in 12 patients undergoing pulmonary surgery. The second messenger toANP‐induced vascular relaxation, plasma cyclic guanosine mono‐phosphate (p‐cGMP), wasmeasured as an indirect marker of the vascular effects of ANP. Immediately after appliedclamping, p‐irANP (baseline level 15·4±2·9 pmol l−1) started to increase, reaching a significant, although moderate, increase(11±4%, P<0·05) after 2 min. This elevation of p‐irANPremained during the entire clamping period (+13±6%, P<0·05 vs. baseline). Within 1 min of declamping, p‐irANP returned to the baselinelevel. No conclusive alterations in p‐cGMP were observed. The prompt ANP response to theapplied stimulus, and the return to baseline after declamping, may indicate the presence of ashort time‐acting releasing mechanism of ANP.
Potassium and ventilation during positive and negative work inpatients with chronic obstructive pulmonary disease
Authors: Rooyackers J. M. , Dekhuijzen P. N. R. , Van Herwaarden C. L. A. , Folgering H. T. M.
Published: November 2003

In patients with chronic obstructive pulmonary disease (COPD),reduced ventilatory reserves limit exercise tolerance. In these patients, the ventilatoryrequirements of eccentric exercise (negative work, Wneg) are lower thanthose of concentric exercise (positive work, Wpos) at similar workloads.In this study, we investigated the relationship between plasma potassium levels and ventilationduring Wpos and Wneg in these patients. Twelvepatients with stable COPD [mean (SD) FEV1 46% (16) of predicted]performed Wpos and Wneg on a cycle ergometer(6 min of exercise; interval ≥1 h) in a randomized order at a constant workload of50% of the individual maximum (positive) work capacity. Minute ventilation (VE) and arterial plasma potassium concentration ([K+]a) were measured at rest, and at 1‐min intervals during exercise and during 3 min ofrecovery. VE increased less during Wneg thanduring Wpos [6 (range 3–26) vs. 18 (range 8–28) l min−1; P<0·01]. VE during Wneg was reduced in proportion to VCO2.The increase in [K+]a during Wpos and Wneg [0·45 (range 0·26–0·75) and0·34 (range 0·1–0·97) mM] did not differsignificantly. VE was closely correlated with VCO2 during both types of exercise. VE was also closelycorrelated with [K+]a, but the slope of the relationship between[K+]a and VE was steeper during Wpos than during Wneg [39·1 (range15·2–88·6) vs. 18·3 (range7·2–37·3) l min−1 mM−1; P=0·012]. In contrast, the slope of the relationship betweenVCO2 and VE was similar during bothtypes of exercise [27?8 (range 19·2–37·1) vs. 32·1 (range19·8–48·4)]. Thus, for a given increase in [K+]a, the increase in VE was significantly less during Wneg. In patients with COPD, potassium did not explain the difference inexercise ventilation between Wneg and Wpos, andmay not play a significant role in the control of breathing during low‐intensity exercise.
Mesenteric artery response to head‐up tilt‐induced centralhypovolaemia and hypotension
Authors: Perko M. J. , Madsen P. , Perko G. , Schroeder T. V. , Secher N. H.
Published: November 2003

Superior mesenteric artery (SMA) blood flow and impedance were evaluated byduplex ultrasound during head‐up tilt (HUT)‐induced central hypovolaemia and hypotension ineight healthy volunteers. HUT induced a reduction in cardiac stroke volume from88·8±6·3 to 64·7±6·3 ml(mean±SEM; P<0·01) and an increase in thoracic electricimpedance from 38·6±2·1 to 42·6±2·1Ω (P<0·01) reflecting a reduced central blood volume. Maintainedtilt provoked a 30% reduction in mean arterial pressure (from 87·1±3·3to 63·4±3·6 mmHg; P<0·01) and the appearanceof presyncopal symptoms. During both the normotensive and the hypotensive phase of HUT, theSMA diameter (5·7±0·03 mm) and blood flow (514±75 ml min−1) did not change significantly, although the end‐diastolic velocity increasedfrom 9·7±4·8 to 39·7±4·0 cm s−1 (P<0·01). The increase in diastolic velocity, despite amaintained or reduced arterial pressure, supports a reduction in the SMA impedance as it wasreproduced during a meal test when a moderate reduction in mean arterial pressure (87±4to 80±4 mmHg; P=0·04) was accompanied by a ninefoldincrease in the end‐diastolic velocity (P<0·01). The results indicate areduction in the mesenteric vascular impedance to the extent that superior mesenteric artery bloodflow is maintained during HUT‐induced central hypovolaemia and hypotension.
Effects of adrenergic blockade on hepatic glucose production during ethanol administration
Authors: Delarue J. , Henry Ph. , Cayeux C. , Haesler E. , Jéquier E. , Tappy L.
Published: November 2003

Acute ethanol administration stimulates sympathetic nervous system activity. The present studywas designed to determine whether this sympathetic activation affects glycogenolysis and totalhepatic glucose production (HGP) during ethanol‐induced inhibition of gluconeogenesis. Nineteenvolunteers participated in four protocols. Two protocols aimed to study – using combinedinfusion of [6,6‐2H2]glucose and [U‐13C]glucose, VCO2 and 13CO2 measurements – theeffects of ethanol infusion alone (n=10) or with propranolol (n=6) or phentolamine infusion (n=4) on HGP, glucose disposal (Rd), glucose oxidation [13C]Glcox and non‐oxidativeglucose disposal (NOGD=Rd−[13C]Glcox). The fourth protocol assessed the effects of saline infusion alone on HGP. Usingethanol, HGP decreased by 23%, Rd by 20% and glycaemia by 9% (allP<0·001); heart rate increased by 10%, whereas blood pressureremained unchanged. The effects were not observed with saline, except a slight (10%)decrease in HGP (P<0·01 vs. ethanol). Ethanol did not affect[13C]Glcox but decreased NOGD by 73%(P<0·001). Propranolol or phentolamine did not alter any of the effects ofethanol on glucose metabolism, but decreased mean arterial pressure. Propranolol prevented theethanol‐induced increase in heart rate. In conclusion, ethanol decreased blood glucose bydecreasing HGP, presumably by inhibiting gluconeogenesis. Sympathetic activation prevented thedecrease in blood pressure produced by ethanol but did not stimulate glycogenolysis.
The twitch interpolation technique for the estimation of true quadricepsmuscle strength
Authors: Nørregaard J. , Lykkegaard J. J. , Bülow P. M. , Danneskiold‐Samsøe B.
Published: November 2003

The aim of this study was to examine the reliability of the twitchinterpolation technique when used to estimate the true isometric knee extensor muscle strength.This included an examination of whether submaximal activation causes any bias in the estimationof the true muscle strength and an examination of the precision of the method. Twenty healthysubjects completed three contraction series, in which the sub‐jects were told to perform as if theirvoluntary strength was 60%, 80% or 100% of that determined by a maximalvoluntary contraction (MVC). Electrical muscle stimulations were given at each of five differentcontraction levels in each series. At torque levels above 25% of MVC the relationshipbetween torque and twitch size could be approximated to be linear. The true muscle strength(TMS) could therefore be estimated using linear regression of the twitch–torquerelationship to the torque point of no twitch in each of the three series, termed TMS60, TMS80 and TMS100. The TMS80 was slightly lower (P<0·01), median 94% (IQ range 87–101%) of the TMS100. The TMS60 was median 99% (IQ range 83–125%)(NS) of TMS100, but a few severe outliers were ob‐served. In conclusion, we foundthe reliability of the method acceptable for many research purposes, if series with estimated centralactivation of below 40–50% were excluded. The only moderate precision and theslightly lower estimations in subjects applying submaximal does, however, limit its usefulness.
Inter‐ and intra‐observer variation in the reporting of cervical smears: specialist cytopathologists versus histopathologists
Authors: O'SULLIVAN J. P. , ISMAIL S. M. , BARNES W. S. F. , DEERY A. R. S. , GRADWELL E. , HARVEY J. A. , HUSAIN O. A. N. , KOCJAN G. , McKEE G. , OLAFSDOTTIR R. , RATCLIFFE N. A. , NEWCOMBE R. G.
Published: November 2003

One hundred and ten cervical smears were circulated to five specialist consultant cytopathologists and five consultant histopathologists. Of these smears, 100 were randomized and re‐circulated. The cytopathologists reported endocervical cells and wart virus infection more frequently than the histopathologists, although neither group showed good inter‐observer agreement for either assessment. Apart from smear adequacy and the presence of endocervical cells, both groups showed good intra‐observer agreement in all the parameters measured. This suggests that overall individuals were applying their own personal criteria with consistency over time, although a previous study had shown considerable lack of inter‐observer agreement among the histopathologists on the grade of dyskaryosis and the management recommendation. The results indicate that specialist cytopathologists bring a different viewpoint to the reporting of cervical smears than histopathologists. They also show a lack of standardization in the reporting of smears despite the guidelines issued by the British Society for Clinical Cytology.
Costs and benefits of cervical screening. III. Cost/benefit analysis of a call of previously unscreened women
Authors: WAUGH N. , SMITH I. , ROBERTSON A. , REID G. S. , HALKERSTON R. , GRANT A.
Published: November 2003

A population‐based cervical screening programme issued invitations to women with no record of a previous smear. This call was very good value, at £5780 per life saved or £159 per life‐year saved at 1991 prices. The first priority for the cervical screening service should be comprehensive coverage.
Sum variance—a most valuable parameter in computer‐assisted image analysis of voided urines
Authors: WIENER H. , VAN'T HOF‐GROOTENBOER A. E. , VOOIJS G. P.
Published: November 2003

The chromatin pattern of retrospectively Feulgen–Schiff‐stained exfoliative urothelial cells was determined by computer‐assisted analysis for 12 detailed texture image parameters. These were compared with density parameters and geometric parameters for their ability to discriminate between benign and malignant samples. The discriminatory power of the mean variable of the texture parameter sum variance was found to equal that of densitometric parameters which reflect the nuclear DNA content of the cell. The results suggest that determination of the texture parameter sum variance is valuable in distinguishing nuclei of specimens negative from those positive for malignancy.
Fine needle aspiration (FNA) cytology of the breast: the influence of unsatisfactory samples on patient management
Authors: LAZDA E. J. , KOCJAN G. , SAMS V. R. , WOTHERSPOON A. C. , TAYLOR I.
Published: November 2003

FNA continues to play an important role in the management of patients with breast lesions. However, the reliability and efficiency of the FNA service depends heavily on the quality of the specimens. We have audited the rate of ‘inadequate FNAs’ at intervals over the last 5 years and related our findings to the clinical expertise of the aspirator. We have also correlated the rate of inadequate FNAs with the percentage of patients who had an FNA preceding a definitive diagnosis of cancer. We report trends in the rate of inadequate samples, and subsequent diagnosis of cancer, over a 5‐year period. The percentage of breast FNA samples reported as inadequate was 46.8% in 1988–89, falling to 20% in 1991–92 with the introduction of an FNA clinic, and rising to 30.6% in 1993. The rates of cancer following inadequate FNA were 15.7%, 16.1% and 4.2%, respectively, and the percentage of patients with cancer having a preceding inadequate FNA were 37.5%, 13.2% and 7.1%. Possible explanations for the apparent paradox between increasing numbers of inadequate FNA specimens and a falling breast cancer rate are discussed.
A study to determine the underlying reason for abnormal glandular cytology and the formulation of a management protocol
Authors: LEESON S. C. , INGLIS T. C. M. , SALMAN W. D.
Published: November 2003

A retrospective review is presented of 89 patients with glandular dyskaryosis in order to formulate a management protocol. Fifteen patients had cervical intraepithelial neoplasia (CIN) without glandular abnormality (17%). One patient had adenocarcinoma in situ of the cervix and one patient had vaginal intraepithelial neoplasia (VAIN) grade III. Twenty‐two patients had endometrial carcinoma (24.5%) and 11 patients had cervical carcinoma (12.5%). Of the patients presenting with post‐menopausal bleeding as well as having glandular dyskaryosis, 69% had a gynaecological malignancy. In conclusion, colposcopy and out‐patient endometrial sampling are recommended in all cases. Patients with abnormal endometrial sampling require hysteroscopy. Cone biopsy is necessary to exclude occult glandular disease if cytology remains abnormal despite negative colposcopy and sampling.
Fine needle aspiration (FNA) cytology of adenoid cystic carcinoma and adenomyoepithelioma of breast: two lesions rich in myoepithelial cells
Authors: McCLUGGAGE W. G. , McMANUS D. I. , CAUGHLEY L. M.
Published: November 2003

Adenoid cystic carcinoma and adenomyoepithelioma are relatively rare, but well described, breast lesions. The FNA cytology features in two cases of mammary adenoid cystic carcinoma and two cases of adenomyoepithelioma are described. In both cases of adenoid cystic carcinoma, aspirates consisted of tightly cohesive clusters of cells arranged around spheres and interconnecting cylinders of acellular material. The two aspirates of adenomyoepithelioma were composed of large tightly cohesive clusters of cells associated with small amounts of stromal material. In all four aspirates a dual population of epithelial and myoepithelial cells could be identified within cellular aggregates, and numerous bare nuclei were present. Histology revealed the characteristic features of adenoid cystic carcinoma and adenomyoepithelioma. Immunohistochemical staining of histological sections for S‐100 protein and alpha‐smooth muscle actin confirmed the presence of large numbers of myoepithelial cells within all four lesions, providing indirect evidence that bare nuclei in breast aspirates represent myoepithelial cells. The presence of a dual population of epithelial and myoepithelial cells and of numerous bare nuclei within a breast aspirate is generally indicative of a benign lesion. This is not always the case, as adenoid cystic carcinoma is a malignant tumour, and adenomyoepithelioma, while generally exhibiting benign behaviour, is capable of local recurrence and distant metastasis.
Evaluation of HMFG2 and thyroglobulin in the diagnosis of thyroid fine needle aspiration (FNA)
Authors: VENETI S. , ATHANASSIADOU P. , KANDARAKI C. , KYRKOU K.
Published: November 2003

In order to appraise the usefulness of HMFG2 and thyroglobulin (Tg) as specific markers for the diagnosis of thyroid disease, we studied 63 FNA smears. Cases tested included 30 benign (nine colloid goitres, six cases of Hashimoto's thyroiditis, six Hürthle cell adenomas, nine follicular adenomas) and 33 malignant lesions (nine follicular carcinomas, 12 papillary carcinomas, nine anaplastic carcinomas, three medullary carcinomas). All cases with malignant lesions except the anaplastic carcinomas were positive for HMFG2. Immunoreactive cells to HMFG2 were also found in 15 adenomas out of 30 benign cases. Positive Tg reaction was found in benign and malignant thyroid lesions, except six cases of Hashimoto's thyroiditis, nine anaplastic and three medullary carcinomas. The results obtained indicate that morphology paired with immunocytochemistry can usually depict a more specific profile of thyroid lesions for better evaluation of the pathology.
Audit of 6 years' experience of breast fine needle aspiration (FNA) cytology using the cytospin method; improvement through multidisciplinary clinical audit
Authors: DUNDAS S. A. C. , MANSOUR P. , ZEIDERMAN M. , HARRISON I. , SKIPWORTH P. , DUTTON J.
Published: November 2003

Audit of 6 years' experience of breast fine needle aspiration (FNA) cytology using the cytospin method; improvement through multidisciplinary clinical audit

A breast FNA cytology service for palpable breast lumps was commenced in 1989 using the cytospin method. Over the following 6 years 2314 aspirates were received. The results were audited in detail in 1990, 1991/1992 and 1994. Multidisciplinary clinical audit meetings followed each audit cycle. Practice change was agreed after each audit. Each audit cycle was followed by demonstrable improvement in the complete sensitivity of the technique, being respectively 79%, 88% and 96%. The cytospin method is a viable alternative to the conventional smear method.
Immunocytochemical staining of effusions; an external quality control study in The Netherlands
Authors: KUENEN‐BOUMEESTER V. , DE BRUIJN E. M. C. A. , HENZEN‐LOGMANS S. C.
Published: November 2003

Immunocytochemical staining of effusions; an external quality control study in The Netherlands

In The Netherlands an external quality control study of immunocytochemical (IC) staining of effusions was initiated, consisting of three test rounds. The 12 participating laboratories received samples of malignant effusions (runs 1, 2 and 3), and five unstained control specimens prepared from the same material in runs 2 and 3. The laboratories used their own protocols to prepare and stain the samples (‘in‐house’ specimens). Two persons viewed and scored the slides following preset criteria concerning number and morphology of diagnostic cells, background staining and staining specificity. Better scoring results were found for control specimens, compared with ‘in‐house’ specimens, primarily caused by cell loss in the latter. This finding underlines the view that high quality IC needs well organized processing and staining procedures, and warrants external quality control systems.
The value of lymph node imprint cytodiagnosis: an assessment of interobserver agreement and diagnostic accuracy
Authors: MOLYNEUX A. , ATTANOOS R. , COGHILL S.
Published: November 2003

The value of lymph node imprint cytodiagnosis: an assessment of interobserver agreement and diagnostic accuracy

The aim of this study was to assess the reliability of cytodiagnosis of lymph node imprints without fixed tissue sections. One hundred randomly selected archival cases were used in the study. These air‐dried May–Grünwald–Giemsa imprint slides were assessed independently and blind by three pathologists. Cases were assigned to one of four diagnostic categories: reactive changes, non‐Hodgkin's lymphoma (NHL), Hodgkin's disease (HD) and secondary malignancy. Each broad diagnosis was compared with the ‘correct’ reviewed histological diagnosis to calculate interobserver agreement and diagnostic accuracy. The overall κ score (+0.59) was indicative of moderate agreement. The mean pathologist diagnostic accuracy was 78%, with complete agreement with the histological diagnosis in 61% of cases. The main diagnostic difficulties were in the distinction between reactive changes and NHL and distinguishing NHL from HD. Further diagnostic classification, e.g. typing of lymphomas and subclassification of Hodgkin's disease, was not found to be reliable using the imprints alone. With these limitations in mind, pathologists should be able to use lymph node imprints for cytodiagnosis in selected cases. The study also emphasized the utility of imprints as a corollary to the histology and as a tool for cytology training and continuing education.
Routine audit of breast fine needle aspiration (FNA) cytology specimens and aspirator inadequate rates
Authors: SNEAD D. R. J. , VRYENHOEF P. , PINDER S. E. , EVANS A. , WILSON A. R. M. , BLAMEY R. W. , ELSTON C. W. , ELLIS I. O.
Published: November 2003

Routine audit of breast fine needle aspiration (FNA) cytology specimens and aspirator inadequate rates

In an attempt to improve the quality of the breast FNA specimens we instigated a continuing audit of this procedure in this hospital. All FNAs since 1990 have had the following recorded: mode of aspiration, e.g. freehand or image guided, patient presentation (screening or symptomatic), patient diagnostic category, cytological diagnosis and final histological diagnosis. Aspirator performance was assessed by means of the inadequate aspiration rate (IR) of FNAs performed on patients with a final diagnosis of cancer (FDC) and diagnostic category A patients (clinically or radiologically malignant lesions). An ongoing annual review of the performance of all the aspirators was undertaken, all of whom received individual feedback. Counselling and further training were offered where indicated by poor performance. Over the period 1990–1995 a total of 13 537 FNAs were performed by 27 aspirators. The IR on category A and FDC cases over this period was 16.0% and 18.1%. The best performance achieved by an aspirator in a calendar year was an IR of 3.6% with no inadequate specimens in either FDC or category A lesions, and the best performance over the entire period was an average IR of 11.75% and 14.25% for FDC and category A groups, respectively. The overall IR on category A patients ranged from 15.9% to 23.8% and on FDC cases from 12.2% to 21.7%. There was a significant improvement in individual junior aspirator performance when their first year was compared with their last year on the unit. In some cases a deterioration in intra‐aspirator performance was observed, from an IR of 6% to 33%. The overall IR rate of the unit remained stable for FDC patients, 15.5% in 1990 compared with 15.1% in 1995. This appeared to be largely due to a high proportion of the aspirations being performed by experienced personnel with consistent IRs. However, concealed within the overall rate there were some poor performers who benefited from counselling and/or further training. These results indicate an important role for audit in identifying poor aspirators who benefit from targeted training and advice, thereby improving the quality of FNA specimens, and ultimately patient care.
Comparative analysis of techniques for detection of grapevine and citrus viroids in Tunisia
Authors: Elleuch A. , Fakhfakh H. , Jendoubi L. , Bessaies N. , Marrakchi M.
Published: November 2003

Reverse transcription polymerase chain reaction (RT‐PCR) was used for the detection of Citrus exocortis viroid (CEVd) in total nucleic acids from infected citrus indicator hosts or directly from field trees. Grapevine yellow speckle viroid‐1 (GYSVd‐1) and Australian grapevine viroid (AGVd) were also detected by this technique in total nucleic acids from infected grapevine plants. Three protocols for nucleic acid extraction were tested: a phenol‐based method, a protocol using a commercial reagent (Trizol) and a method in which extraction with a high‐salt buffer was combined with partial purification using non‐ionic cellulose. The third protocol, coupled to RT‐PCR, seems to be the most suitable, allowing detection of the three viroids in Tunisian citrus and grapevine samples. This method should be used in a testing programme to produce certified viroid‐free planting material.
Emergence en Tunisie d’un nouveau pathotype de Verticillium alboatrum pouvant attaquer les cultivars de tomate possédant le gène de résistance Ve
Authors: Hajlaoui M. R. , Gargouri S. , Guermech A. , Hamza N.
Published: November 2003

Au cours du printemps 2002, une grave maladie s’est manifestée dans une culture de tomate (cv. Collibri) de primeur sous abris‐serres dans une exploitation située à Chott Mariem (120 km au sud de Tunis). Les plantes attaquées montrent les symptômes caractéristiques d’une maladie vasculaire. L’isolement de l’agent pathogène à partir des vaisseaux à différents niveaux de la tige des plantes malades a révélé systématiquement la présence de Verticillium alboatrum. La virulence de ce nouveau pathotype de V. alboatrum a été vérifiée sur quatre cultivars de tomate portant le gène de résistance Ve et comparée à un témoin sensible. Ce nouveau pathotype a montré une virulence accrue aussi bien chez les cultivars résistants que chez le témoin sensible entraînant une réduction de la croissance de 18%à 34%, le dessèchement des feuilles et le brunissement des vaisseaux. Ces résultats confirment la présence pour la première fois en Tunisie d’un nouveau pathotype de V. alboatrum pouvant attaquer les cultivars de tomate pourvus du gène de résistance Ve.
Cyclosporine induces high bone turnover and may contribute to bone loss after heart transplantation
Authors: THI ÉBAUD D. , KRIEG M. A. , GILLARD‐BERGUER D. , JACQUET A. F. , GOY J. J. , BURCKHARDT P.
Published: November 2003

Cardiac transplantation has become a successful therapy for end‐stage heart disease. However, increased bone loss has been observed in heart transplant recipients, sometimes being responsible for osteoporotic fractures. Glucocorticoids cause dose‐related bone loss, particularly in the first 6–12 months of use, but cyclosporine might play a role as well. The evolution of bone mineral density (BMD) and biochemical parameters was prospectively assessed in 24 patients (mean age 52 years) from cardiac transplantation. All patients received cyclosporin A (CsA) and prednisone, the latter at decreasing dosage. The mean current daily dose of CsA was 321 mg and serum levels of CsA were constant. All patients received calcium (500 mg day−1) and vitamin D (1000 U day−1) for prevention of bone loss. BMD (g cm−2) was measured in 17 patients at the lumbar spine, femoral neck and total hip with dual energy X‐ray absorptiometry every 6 months. Spinal BMD as well as neck and total hip BMD decreased at 6 and 12 months after transplantation, being statistically significant at the three sites: −5.6 and −3.4% for the lumbar spine, −9.3 and−8.5% for the femoral neck, −4.8% and −6.0% for the total hip respectively. Parathyroid hormone (PTH) and osteocalcin (BGP) increased by 90% and 800% respectively between pretransplantation values and 18 months after transplantation. BGP levels measured every 2 months from transplantation increased continuously from 8.7 μg L−1 (mean ± SEM) before transplantation to 31.3 ± 10.1 (P<0.05) at 4 months, to 59.1 ± 8.8 (P<0.01) at 6 months and to 72.2 ± 9.9 (P<0.01) at 18 months (Kruskal–Wallis analysis: P<0.0001). PTH showed a biphasic pattern with an initial decrease from 39.3 ± 4.1 ng L−1 at baseline to 22.0 ± 2.8 ng L−1 at 2 months, but increasing thereafter to 45.9 ± 5.7 at 6 months and 74.2 ± 8.9 at 18 months (Kruskal–Wallis analysis: P<0.001). These variations represent a biochemical profile remarkably different from that of glucocorticoid‐induced osteoporosis. In summary, cardiac transplant patients lose bone immediately after transplantation at the spine and the hip. Later on, the loss in BMD discontinues at all sites of the skeleton, but predominantly at the spine, and a few patients still lose bone at the hip. This is probably a result of the high bone turnover either due to secondary hyperparathyroidism or induced by cyclosporin A.
Renal and hormonal actions of atrial natriuretic peptide during angiotensin II or noradrenaline infusion in man
Authors: EISKJÆR H. , NIELSEN C. B. , SØRENSEN S. S. , PEDERSEN E. B.
Published: November 2003

In order to study the renal and hormonal actions of atrial natriuretic peptide (ANP) during background infusions with angiotensin II (ANG II) or noradrenaline (NA), 69 healthy subjects were examined in three main groups receiving a 90‐min infusion with either placebo, ANG II (1.5 ng kg−1 min−1), or NA (25 ng kg−1 min−1). Each of these three main groups were subdivided into two groups receiving an infusion with either placebo or ANP (10 ng kg−1 min−1) for the last 60 min of the background infusion. Lithium clearance was used to evaluate segmental tubular reabsorption. ANG II alone caused a decrease in glomerular filtration rate (GFR), renal plasma flow, urinary absolute and fractional excretion of sodium, both proximal and distal fractional tubular sodium reabsorption, and urinary flow. NA alone caused a decrease in renal plasma flow. ANP alone caused a decrease in renal plasma flow. Urinary absolute and fractional excretion of sodium were increased and the distal fractional tubular reabsorption of sodium decreased, whereas the proximal fractional tubular reabsorption was unchanged by ANP. ANG II + ANP: during a background ANG II infusion, ANP still increased fractional excretion of sodium. Proximal fractional reabsorption was decreased, whereas distal fractional reabsorption of sodium was unchanged by ANP during ANG II infusion. The ANP‐induced decreases in proximal absolute (−147 vs. +714 μmol min−1 1.73 m−2P = 0.05) and fractional (−1.7% vs. +0.6%, P<0.01) tubular sodium reabsorption were more pronounced, and the decrease in distal fractional tubular reabsorption of sodium (−0.1% vs. −1.4%, P<0.05) less pronounced compared with when ANP was given alone. NA + ANP: during a background NA infusion, ANP still increased urinary sodium excretion and decreased distal fractional reabsorption. None of the ANP‐induced absolute changes seen during background infusion with NA were significantly different from the ANP‐induced changes seen during placebo background infusion. It is concluded that the natriuretic action of low‐dose ANP seems to be preserved during background infusions with ANG II and NA in man. Net sodium excretion during the combined infusion with ANG II and ANP seems to reflect the sum of the opposing influences of each peptide. Low‐dose ANP had a very modest but significant inhibitory effect on proximal tubular sodium reabsorption prestimulated by ANG II infusion.
Sex differences in initial clearance of palmitate by human hepatocytes
Authors: POND S. M. , GORDON R. A. , BASS L.
Published: November 2003

To determine if the sex differences in clearance of long chain fatty acids by the liver observed in the rat are relevant to humans, the authors isolated hepatocytes from human adult males and females (five per group) and measured the initial (unidirectional) clearance of [3H]‐palmitate from buffer containing albumin. The clearance was significantly higher (about twofold) in hepatocytes from females because of a higher permeability of the plasma membrane to the fatty acid. The livers had been perfused with University of Wisconsin (UW) solution and stored for 12–16 h before isolation of the cells. The magnitudes of the clearances in humans were similar to those in the rat when the livers were stored similarly, but lower than in cells isolated from fresh rat liver. When hepatocytes isolated from fresh rat liver were stored in UW solution, clearance of [3H]‐palmitate was unaffected. Thus, hepatocytes prepared from intact liver stored for several hours in UW solution do not have as good preservation of function as hepatocytes isolated from fresh liver and then stored in UW solution.
The Jak–STAT pathway: specific signal transduction from the cell membrane to the nucleus
Authors: HEIM M. H.
Published: November 2003

The Jak–STAT pathway is a newly discovered intracellular signal transduction pathway that is used by a growing number of extracellular signalling proteins (ESPs) for transciptional activation of target genes. Binding of ligands to their transmembrane receptors leads to activation of members of the Jak tyrosine kinase family. The activated receptor–kinase complexes recruit members of the STAT family and activate them by phosphorylation. As a consequence, the phosphorylated STAT proteins dimerize, translocate into the nucleus, bind response elements in the promoter of target genes and stimulate the transcription of these genes. Their dual role as signalling molecules and transcription factors is reflected in the name: STAT stands for signal transducers and activators of transcription. Different ligands specifically activate different members of the Jak and STAT families. Signal transduction through the Jak–STAT pathway contributes to the specificity and diversity of cellular responses to peptide hormones, growth factors, cytokines and interleukins.
Defective interferon‐gamma production by T‐lymphocytes from patients with acute brucellosis
Authors: RODRIGUEZ‐ZAPATA M. , SALMERON I. , MANZANO L. , SALMERON O. J. , PRIETO A. , ALVAREZ‐MON M.
Published: November 2003

The authors investigated the production of interleukin‐2 (IL‐2) and interferon‐gamma (IFN‐γ) by phytohaemagglutinin (PHA)‐stimulated T‐lymphocytes from 21 untreated patients with acute brucellosis. PHA‐stimulated T‐lymphocytes from acute brucellosis patients showed normal IL‐2 production but defective IFN‐γ production (brucellosis patients 531 ± 103 pg mL−1 vs. healthy controls 1024 ± 212 pg mL−1) after 72 h of culture. This altered pattern of IL‐2 and IFN‐γ production by T‐lymphocytes was observed in seven brucellosis patients whose T‐lymphocytes exhibited a normal proliferative response to PHA (61 612 ± 18 422 cpm) as well as in the 14 patients with a defective T‐lymphocyte proliferative response to the PHA after 5 days of culture (19 479 ± 4409 cpm). After antibiotic therapy, production of the two lymphokines by the PHA‐stimulated T‐lymphocytes from acute brucellosis patients was similar to that of T‐lymphocytes from healthy control subjects. The authors conclude that PHA‐stimulated T‐lymphocytes from untreated patients with acute brucellosis have defective INF‐γ production but normal IL‐2 production.
Assay of human erythrocyte sodium‐dependent lithium efflux: the importance of timing of blood sampling
Authors: ADEBAYO G. I. , GAFFNEY P. , SINNOTT M. , FEELY J.
Published: November 2003

The activity of the human erythrocyte sodium–lithium countertransport (SLC) is stable over long periods in individuals. However, it is becoming increasingly evident that the transport system is susceptible to modulation, both acutely and chronically, by various factors. In this study, the authors observed temporal variation in SLC over a period of 10 h (08.00–18.00 hours) in healthy volunteers. SLC Vmax was maximum (0.354 ± 0.051 mmol L−1 cell−1 h−1; mean ± SE) at ‘mid‐day’ and significantly higher than in the morning (0.291 ± 0.035 mmol L−1 cell, h; P < 0.010). Its value in the evening (0.316 ± 0.042 mmol L−1 cell−1 h−1) was lower than at ‘mid‐day’ (P < 0.045) but higher than in the morning (P < 0.037). These changes were not accompanied by any significant change in the affinity of the transporter for external sodium, Km. Changes in SLC Vmax did not correlate with the corresponding ones in either plasma cortisol or aldosterone. However, they correlated well with those in plasma renin activity, the correlation between mid‐day and a.m. sets of values (r = 0.718; P = 0.019) being better than that between mid‐day and p.m. (r = 0.688; P = 0.028). The authors conclude that changes in SLC occur during the day, and this need be taken into account in the planning and execution of studies involving determination of the activity of this transport system.
Erythropoietic protoporphyria: two populations of reticulocytes, with and without protoporphyrin
Authors: BRUN A. , STEEN H. , SANDBERG S.
Published: November 2003

Erythrocytes from patients with erythropoietic protoporphyria contain large amounts of protoporphyrin. The photosensitivity experienced by these patients is assumed to be due to a leakage of protoporphyrin from the erythrocytes and transfer to the skin, where protoporphyrin acts as a photosensitizer. The leakage of protoporphyrin from the erythrocytes has been offered as an explanation for the great variety in protoporphyrin content observed among erythrocytes in this disease. Based on density gradient separation of red cells, it has been concluded that all reticulocytes and young erythrocytes contain large amounts of protoporphyrin. From our results, density gradient centrifugation is not suitable for age separation of red cells from patients with erythropoietic protoporphyria. By developing a new method for isolation of reticulocytes and applying flow cytometry to determine protoporphyrin content in individual cells, it was observed that two populations of reticulocytes were present in patients with erythropoietic protoporphyria, one with and the other without protoporphyrin. The half‐life of protoporphyrin in red cells was found to be 12–14 days, in contrast to 1–2 days described previously, suggesting a slower release of protoporphyrin from the red cells than previously anticipated.
Synergistic stimulatory effects of tumour necrosis factor α and interferon γ on replication of human immunodeficiency virus type 1 and on apoptosis of HIV‐1‐infected host cells
Authors: HAN X. , BECKER K. , DEGEN H. J. , JABLONOWSKI H. , STROHMEYER G.
Published: November 2003

Differential and sometimes contradictory effects have been described for tumour necrosis factor α (TNF‐α) and interferon γ (IFN‐γ) on replication of human immunodeficiency virus type 1 (HIV‐1). The authors examined individual and co‐ordinate action of these cytokines on HIV‐1 expression, and on apoptosis of HIV‐1‐infected host cells by determination of reverse transcriptase activity in cell culture supernatant, expression of HIV‐1‐RNA and production of p24 antigen in the promonocytic cell line U937 and its persistently HIV‐1‐infected clone U1. Apoptosis was demonstrated by typical cleavage of cellular DNA at internucleosomal regions in promonocytic and T‐lymphocytic cell lines. TNF‐α alone markedly stimulated HIV‐1 replication in U1 cells at the transcriptional and on the translational level. Exclusive application of IFN‐γ only slightly enhanced HIV‐1 expression, whereas it synergistically potentiated stimulatory effects of TNF‐α. Both cytokines also synergistically induced apoptosis in HIV‐1‐infected host cells. Co‐ordinate action of TNF‐α and IFN‐γ is suggested to represent an important mechanism for disease progression in HIV infection. These findings demonstrate that cytokine effects on viral expression may vary depending on their single or combined application.
Influences of lipid and non‐lipid nutritional parameters on factor VII coagulant activity in normal subjects: the Nove Study
Authors: GIRELLI D. , OLIVIERI O. , ARIGLIANO P. L. , GUARINI P. , BASSI A. , CORROCHER R.
Published: November 2003

Community‐based studies have suggested that the dietary intake of total fat influences factor VII coagulant activity (FVIIc), a predictor of fatal events from coronary heart disease (CHD). Nevertheless, the question whether the quality of dietary fats, with special reference to fatty acids (FAs), influences FVIIc is unsolved. The authors investigated in 90 healthy volunteers living in Nove, a village near Vicenza (northern Italy), the relationships between FVIIc and the plasma concentration of individual FAs. Several indices of other nutritional factors that have recently received increasing attention as determinants of CHD risk (antioxidant vitamins A and E, oligoelements) were also included in the multivariate analysis. The stepwise multiple linear regression analysis revealed body mass index (BMI), and the concentrations of plasma stearic acid (C18 : 0) and serum copper as significant independent predictors of a substantial proportion of FVIIc variability (R = 0.52; R 2 = 0.27; P < 0.001). This study substantially supports the role of the plasma concentration of stearic acid as an important factor in modulating FVIIc
Cytokine profiles in bronchoalveolar lavage fluid and blood in HIV‐seronegative patients with Pneumocystis carinii pneumonia
Authors: PERENBOOM R. M. , VAN SCHIJNDEL A. C. H. W. , BECKERS P. , SAUERWEIN R. , VAN HAMERSVELT H. W. , FESTEN J. , GALLATI H. , VAN DER MEER J. W. M.
Published: November 2003

Concentrations and ex vivo production of interleukin‐1β (IL‐1β), tumour necrosis factor‐α (TNF), interleukin‐6 (IL‐6), interleukin‐1 receptor antagonist (IL‐1RA) and TNF soluble receptors were followed in bronchoalveolar lavage (BAL) fluid and blood from 10 HIV‐seronegative patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy volunteers. During the acute phase of PCP, TNF but not IL‐6 or IL‐1β was detectable in BAL fluid. At that time, plasma concentrations of the proinflammatory cytokines were low, whereas plasma concentrations of the anti‐inflammatory cytokines were high. The ex vivo production capacity of proinflammatory cytokines was suppressed in the acute phase, in the blood as well as at the site of infection. During convalescence the production capacity of the blood cells normalized. The IL‐1RA production capacity of the alveolar cells was also suppressed in the acute phase, but preserved in blood cells.