bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of glossopharyngeal nerve block on pain after elective adult tonsillectomy and uvulopalatoplasty
Authors: Bell K. R. , Cyna A. M. , Lawler K. M. , Sinclair C. , Kelly P. J. , Millar F. , Flood L. M.
Published: January 2004

This controlled, randomised, double blind study compared whether glossopharyngeal nerve block and intravenous morphine administered peri‐operatively, decreased pain following elective adult tonsillectomy and uvulopalatoplasty more than morphine alone. Sixteen of 30 patients undergoing uvulopalatoplasty and 38 of 78 patients having tonsillectomy received bilateral glossopharyngeal nerve blocks, using bupivacaine 0.5% and adrenaline 1:200 000, or no intervention. There were no differences in postoperative analgesic consumption between the two groups. Visual analogue pain scores measured during swallowing, in the recovery room and on the ward postoperatively, were significantly less overall in uvulopalatoplasty patients who had received a block (p = 0.004). This difference was not found for tonsillectomy. We found no significant differences between groups, in pain scores recorded during the first 5 days at home. We conclude that glossopharyngeal block does not improve analgesia following tonsillectomy although there is short‐lived benefit following uvulopalatoplasty.
Caesarean section in a parturient with respiratory failure caused by cystic fibrosis
Authors: Bose D. , Yentis S. M. , Fauvel N. J.
Published: January 2004

We describe a 27‐year‐old primigravida suffering from cystic fibrosis. Her chest was colonised with Burkholderia cepacia and she was in respiratory failure for which she required constant nasal intermittent positive pressure ventilation. In view of her rapid deterioration, Caesarean section was performed under epidural anaesthesia at 25 weeks gestation. A live 790‐g boy was delivered. Post‐operatively she made steady progress for 5 days although still requiring nasal ventilatory support. Thereafter she developed pneumonia and required tracheal intubation and ventilation on the eighth day. Her increasing hypoxaemia and pulmonary hypertension failed to respond to any therapy including inhaled nitric oxide and she died on the tenth postoperative day.
Trends in asthma, allergic rhinitis and eczema among Swedish conscripts from farming and non‐farming environments. A nationwide study over three decades
Authors: Bråbäck L. , Hjern A. , Rasmussen F.
Published: January 2004

Background
Asthma and allergies are less common in children who have been raised in farming environments.

Objectives
To assess whether children who grow up in a farming environment have been protected against the general increase in atopic disorders in Sweden and whether other rural environments could also be protective.

Method
Linkage at an individual level of three national registers in Sweden: The Swedish Military Service Conscription Register (MSCR), the Register of the Total Population (RTP) and the Population and Housing Censuses (PHC). Asthma, allergic rhinitis and eczema at conscription were analysed in relation to area of residence, parental occupation, maternal age, family size and being the first born for 1 309 652 male conscripts in three successive cohorts born between 1952 and 1981.

Results
Allergic rhinitis and eczema displayed a continuous increase throughout the study period, whereas the rise in asthma mainly occurred in conscripts born after 1961. Farming environments and rural living already provided protection from allergic rhinitis in conscripts born during the 1950s, but the protective effect was greater in later cohorts. An inverse association was observed between farm living and asthma, but mainly in conscripts born after 1970. The adjusted risk ratios for asthma in conscripts from farming vs. non‐farming families were 1.00 (95% CI 0.93–1.07), 0.94 (95% CI 0.88–1.01) and 0.85 (95% CI 0.79–0.91) in conscripts born in 1952–1961, 1962–1971 and 1972–1981, respectively. Rural living per se had no effect on the occurrence of asthma. Eczema was less common in rural areas, but the time trend was similar in urban and rural areas.

Conclusions
Our findings suggest that environmental changes affecting the whole of society have promoted an increase in asthma, allergic rhinitis and eczema in both farming and non‐farming environments. A lower risk of allergic rhinitis in conscripts whose parents were involved in farming was observed in all birth cohorts, whereas the protective effect of growing up on a farm on the risk of asthma appears to be a fairly recent phenomenon.
Eosinophilia in nasal polyposis: its objective quantification and clinical relevance
Authors: Gerstner A. O. H. , Gutsche M. , Bücheler M. , Machlitt J. , Emmrich F. , Sommerer F. , Tárnok A. , Bootz F.
Published: January 2004

Background
Eosinophilia within nasal polyps is often taken as a criterion for adjuvant medical treatment postoperatively such as topical steroids.

Objective
This study was performed in order to validate a new technique for objective quantification of eosinophilia by using laser scanning cytometry (LSC), to compare these results with manual scoring and routine histopathology, and to correlate them with the history of allergy or recurrence.

Methods
LSC was used for semi‐automated analysis of single‐cell preparations from representative ethmoidal polyps obtained during routine paranasal sinus surgery (n=41). This microscope‐based instrument scans the cells after immobilization of cells on a glass slide and after triple staining of cytokeratin, eosinophilic granula, and DNA. The location of each cell is stored with the fluorescence data. Therefore, the morphology of every cell can be documented by re‐staining with haemotoxylin and eosin and re‐localization on the slide. Subsequently, slides were subjected to manual scoring. The remaining polyps were analysed by routine histopathology.

Results
Data from LSC and manual scoring showed good correlation (r=0.81, P<0.001), whereas there were discrepancies with histopathology. Eosinophilia scored by LSC and histopathology was neither correlated with the history of allergy nor with recurrence as determined by Fisher's exact test independent of the definition of eosinophilia (2%, 3%, or 5% of all cells).

Conclusion
Scoring eosinophilia by LSC in comparison with histopathology does not contribute to a more reliable basis for adjuvant medical therapy in nasal polyposis. Instead, functional parameters (cytokine production, apoptosis) may serve better.
C5a delays apoptosis of human neutrophils via an extracellular signal‐regulated kinase and Bad‐mediated signalling pathway
Authors: Perianayagam M. C. , Balakrishnan V. S. , Pereira B. J. G. , Jaber B. L.
Published: January 2004

Aims  We recently demonstrated that complement fragment C5a delays apoptosis of human neutrophils via induction of the phosphatidylinositol‐3 kinase (PI 3‐K) pathway. In the present study, we examined whether C5a modulates neutrophil survival through the extracellular signal‐regulated kinase (ERK) and Bad‐mediated signalling pathway.

Methods  Human neutrophils were isolated by percoll gradient and preincubated for 1 h with or without PD98059 (20 µM), a specific ERK inhibitor, followed by incubation with C5a (1 µg mL−1) for 24 h. Apoptosis was quantified by flow cytometry, using propidium iodide nuclear staining. Extracellular signal‐regulated kinase downstream signalling events were evaluated by measuring the expression of cytosolic total and phosphorylated p44/p42 proteins, and Bad phosphorylation using immunoblot analyses. These time‐dependent analyses were performed over a brief exposure to C5a (0–30 min). Modulation of cytosolic caspase‐9 and caspase‐3 activity was measured by Western blot analyses.

Results  C5a inhibited neutrophil apoptosis (P = 0·04), which was abrogated in the presence of PD98059 (P = 0·04). Time‐dependent effect of C5a on p44/p42 phosphorylation was rapid, peaked at 5 min, and was abrogated by the ERK inhibitor (P = 0·04). In addition, brief stimulation of neutrophils with C5a induced phosphorylation of Bad, which was inhibited by the ERK inhibitor (P = 0·03). Further, C5a suppressed the proteolytic cleavage of caspase‐9 and caspase‐3, which was reversed by ERK inhibition. Finally, blockade of both the ERK (with PD98059) and PI 3‐K (with wortmannin) pathways did not induce additive inhibition of neutrophil apoptosis by C5a.

Conclusion  This study demonstrates that in addition to the PI 3‐K pathway, C5a also inhibits neutrophil apoptosis via an ERK‐signalling pathway, resulting in phosphorylation of Bad and blockade of proteolytic cleavage of caspases. The activation of this additional survival‐signalling pathway may be another important cellular mechanism that enhances neutrophil survival in inflammatory states.
Metabolic effects of Troglitazone in patients with diet‐controlled type 2 diabetes
Authors: Robinson A. C. J. , Jeffs J. A. R. , Gray R. G. , Bannister P. A. , Mather H. , Gallagher J. J. , Robinson S. , Nattrass M. , Venkatesan S. , Halliday D. , Johnston D. G.
Published: January 2004

Background  In order to study the mechanisms of action of Troglitazone (TGZ) in vivo in Type 2 diabetes, its effects were studied on glucose metabolism, lipolysis and very low‐density lipoprotein (VLDL) apolipoprotein B100 (apoB) kinetics.

Materials and methods  A placebo‐controlled, double‐blind study was performed in 24 diet‐treated patients randomized to receive TGZ 600 mg day−1, TGZ 200 mg day−1 or placebo for 8 weeks. Glucose and glycerol turnover were assessed after an overnight fast, and during sequential low‐dose insulin infusions (0·01 U kg−1 h−1 followed by 0·015 U kg−1 h−1) using 6,6‐2H Glucose and 1,2,3‐2H Glycerol. Very low‐density lipoprotein apoB secretion was measured using l‐13C‐leucine, monitoring isotopic enrichment by gas chromatography‐mass spectrometry. Treatment effects were analyzed by analysis of covariance, adjusting for baseline.

Results  Therapy resulted in a significant group differences in fasting plasma glucose adjusting for baseline (P = 0·039). This was most evident at TGZ 600 mg daily [glucose decrease from (mean ± SD) 9·2 ± 2·7 to 6·6 ± 0·9 mmol L−1]. HbA1c and insulin levels did not change significantly. Plasma nonesterified fatty acid (NEFA) levels decreased (P = 0·045), most evidently at TGZ 200 mg daily, but glycerol was not significantly affected. Although no significant effects were observed on VLDL apoB or triglyceride concentrations, there were treatment differences in the absolute secretion rate of VLDL apoB of borderline (P = 0·056) statistical significance, with a decrease observed at TGZ 600 mg daily [geometric mean, SD range, 0·94 (0·41–2·15) to 0·40 (0·14–1·13 mg kg−1 h−1)]. Very low‐density lipoprotein apoB fractional secretion rate and pool size were unaffected. The VLDL triglyceride: apoB molar ratio differed between treatment groups (P = 0·013), being higher in the TGZ 600 mg group [5714 (4128–7741) to 8092 (5669–11552)]. Neither glucose nor glycerol rates of appearance were significantly altered by TGZ and nor did TGZ affect their suppression by insulin.

Discussion  The PPARγ agonist, troglitazone, decreases fasting glucose and NEFA levels in diet‐treated Type 2 diabetes. It may also decrease VLDL particle secretion. These effects would be considered beneficial. The biological importance of the increase in VLDL‐triglyceride enrichment warrants further study.
Global assessment for quality and safety of control in type 2 diabetic patients
Authors: Monnier L. , Colette C. , Lapinski H.
Published: January 2004

Background  HbA1c (glycated haemoglobin) suffers from obvious limitations in type 2 diabetic patients at risk of hypoglycaemia or requiring rapid therapeutic adjustments. This study was conducted to discern whether the monitoring of one particular plasma glucose (PG) value of the diurnal profile can be used in such situations.

Design  Four diurnal PG concentrations (at 08:00, 11:00, 14:00 and 17:00 h) were measured in standardized conditions in 480 (246 men, 234 women) noninsulin‐using type 2 diabetic patients. Sensitivities for predicting treatment success, i.e. HbA1c < 7%, with a specificity ≥ 90% were calculated and compared using receiver‐operating characteristic (ROC) curves.

Results  The probabilities (areas under ROC curves) for predicting HbA1c < 7% were significantly higher at 11:00, 14:00 and 17:00 h than at 08:00 h. The optimal PG cut‐off values for predicting treatment success were, respectively, 6, 9, 7 and 6 mmol L−1 at 08:00 h, 11:00, 14:00 and 17:00 h. In most patients the lowest PG values of the diurnal profile were at 17:00 h, and 17·5% of the patients with HbA1c < 7% (54·5% of them treated with sulphonylureas) exhibited a PG value less than 4·4 mmol L−1 at 17:00 h (P = 0·0034 vs. the other timepoints).

Conclusions  Glucose monitoring at 17:00 h, i.e. during the extended postlunch period, appears as a global marker of control in noninsulin‐using type 2 diabetic patients both for detecting patients at risk of hypoglycaemia and for assessing the short‐term quality of diabetic control.
Cholesteryl ester transfer protein concentration is associated with progression of atherosclerosis and response to pravastatin in men with coronary artery disease (REGRESS)
Authors: Klerkx A. H. E. M. , De Grooth G. J. , Zwinderman A. H. , Jukema J. W. , Kuivenhoven J. A. , Kastelein J. J. P.
Published: January 2004

Background  The TaqIB polymorphism in the cholesteryl ester transfer protein (CETP) gene is associated with HDL‐C, progression of coronary artery disease (CAD) and response to pravastatin treatment in men with angiographically proven CAD (REGRESS). We hypothesized that differences in CETP concentration could explain these associations and now investigated whether CETP concentration is an independent determinant of these parameters.

Materials and methods  Plasma CETP concentrations at baseline and after 2 years’ treatment with pravastatin or placebo were measured (n = 674), and correlations with lipid and angiographic parameters (mean segment‐ and obstruction‐diameter; MSD and MOD), and TaqIB genotype were studied.

Results  After segregation into three groups (baseline CETP < 1·58, 1·58–2·21, > 2·21 mg L−1), subjects with the highest CETP had significantly higher baseline total cholesterol, LDL‐C and triglycerides (P < 0·01), while HDL‐C, MSD and MOD were not different among these groups. After 2 years of placebo, the MSD decreased threefold (P < 0·001) and the MOD decreased 2·4‐fold (P = 0·042) more in the highest compared with the lowest CETP quartile. Pravastatin treatment reduced total cholesterol LDL‐C and triglycerides significantly more in the highest CETP quartile. Moreover, only in the highest CETP quartile, pravastatin significantly reduced the MSD‐ (P = 0·003) and MOD‐decrease (P = 0·014) compared with placebo, and, notably, this was independent of baseline lipids and differential lipid changes in these quartiles. Strikingly, baseline associations and treatment responses according to baseline CETP were independent of TaqIB genotype.

Conclusions  High CETP concentration is associated with faster progression of coronary atherosclerosis in men with proven CAD. Second, pravastatin yielded the highest improvement of lipid and angiographic parameters in patients with high baseline CETP independent of baseline lipids, lipid changes and TaqIB genotype, indicating that the plasma CETP level itself is an important determinant of the response to statins.
Multiple effects of HIV‐1 trans‐activator protein on the pathogenesis of HIV‐1 infection
Authors: Huigen M. C. D. G. , Kamp W. , Nottet H. S. L. M.
Published: January 2004

The HIV‐1 trans‐activator (Tat) protein is proposed as an important factor in the complex HIV‐induced pathogenesis of AIDS. In this paper, multiple effects of this viral protein are described. Originally discovered as an intracellular activator of HIV‐1 transcription, Tat was found to regulate viral reverse transcription as well. Trans‐activator was found to be secreted by HIV‐infected cells and taken up by neighbouring cells. In this way, Tat is able to affect both infected and uninfected cells. Intracellularly, Tat can deregulate the expression of several heterologous cellular and viral genes. Extracellular Tat can contribute to the spreading of HIV‐1 and immunosuppression of uninfected cells. Finally, there is evidence that exogenous Tat is involved in AIDS‐associated pathologies such as Kaposi's sarcoma and HIV‐associated dementia. These capacities together accelerate the progression towards AIDS and make Tat an interesting candidate as a constituent of an anti‐AIDS vaccine.
Comparison of in vivo effects of nitroglycerin and insulin on the aortic pressure waveform
Authors: Westerbacka J. , Tamminen M. , Cockcroft J. , Yki‐Järvinen H.
Published: January 2004

Background  Individuals whose platelets are resistant to the antiaggregatory effects of insulin in vitro are also resistant to the antiaggregatory effects of nitroglycerin (GTN). We have previously shown that insulin acutely diminishes central wave reflection in large arteries and that this action of insulin is blunted in insulin‐resistant subjects. However, as yet, no studies have compared the haemodynamic effects of insulin and GTN on large arterial function in the same group of subjects. The aim of this study was to determine whether resistance to the haemodynamic effects of insulin is a defect specific to insulin or whether individuals resistant to the vascular actions of insulin are also resistant to GTN.

Design and results  Dose–response characteristics of insulin and GTN on the aortic waveform were determined using applanation tonometry and pulse wave analysis (PWA) in seven healthy men (age 26 ± 1 year, BMI 25 ± 2 kg m−2). Three doses of sublingual GTN (500 µg for 1, 3 or 5 min) and insulin (0·5, 1 or 2 mU kg−1 min−1 for 120 min) were administered on three separate occasions. Both agents dose‐dependently decreased central pulse pressure and the augmentation index (AIx) without changing brachial artery blood pressure. We next compared responses to insulin (2 mU kg−1 min−1 for 120 min) and sublingual GTN (500 µg for 5 min) in 20 nondiabetic subjects (age 50 ± 2 year, BMI 21·0–36·3 kg m−2). Again, both agents significantly decreased AIx. Although the vascular effects of insulin and GTN vascular were positively correlated [Spearman's r = 0·92 (95% confidence interval 0·81–0·97), P < 0·0001], the time‐course for the action GTN was faster than that of insulin. Brachial systolic blood pressure remained unchanged during the insulin infusion (122 ± 3 vs. 121 ± 3 mmHg, 0 vs. 120 min) but aortic systolic blood pressure decreased significantly by 30 min (111 ± 3 vs. 107 ± 3 mmHg, 0 vs. 30 min, P < 0·01). Similarly, GTN decreased aortic systolic blood pressure from 119 ± 4 to maximally 112 ± 3 mmHg (P < 0·001) without significantly decreasing systolic blood pressure in the brachial artery.

Conclusions  The effects of insulin and GTN on large arterial haemodynamics are dose‐dependent and significantly correlated. The exact mechanisms and sites of action of insulin and GTN in subjects with insulin resistance remain to be established.
Angiopoietin/tie‐2 as mediators of angiogenesis: a role in congestive heart failure?
Authors: Chong A. Y. , Caine G. J. , Lip G. Y. H.
Published: January 2004

Angiogenic factors, in particular vascular endothelial growth factor (VEGF) and the angiopoietins, Ang‐1 and ‐2, have recently generated significant interest, especially in oncology. The process of angiogenesis is also thought to occur in response to ischaemic conditions, which lie at the core of cardiovascular disease states such as coronary artery disease and congestive heart failure. However, current data do not conclusively show evidence of angiogenesis per se in these conditions, despite (for example) the presence of high levels of VEGF and Ang‐2. High levels of these angiogenic factors in heart disease also have not translated into clinically significant new vessel formation, as in accelerated cancer growth or proliferative retinopathy. Indeed, we would hypothesize that these angiogenic markers – especially the angiopoietins – do not necessarily translate into new vessel formation in congestive heart failure (CHF), but may well reflect disturbances of endothelial integrity in CHF.
Impaired neutrophil store‐mediated calcium entry in Type 2 diabetes
Authors: Advani A. , Marshall S. M. , Thomas T. H.
Published: January 2004

Background  In Type 2 diabetes impaired neutrophil function leads to increased bacterial infection and cardiovascular disease. Many neutrophil functions depend on calcium signalling, which involves release of calcium from intracellular stores and subsequently translocation of stores via the cytoskeleton to the plasma membrane, causing store‐mediated calcium entry (SMCE) into the cell. We hypothesized that in Type 2 diabetes there would be a defect in SMCE.

Materials and methods  Neutrophils were prepared from patients with Type 2 diabetes (DM, n = 15) and controls (NC, n = 15). Free cytosolic calcium [Ca2+]i was measured with Fura‐2 in resting cells and after stimulation of calcium release with fMLP and thapsigargin.

Results  Baseline [Ca2+]i was higher in neutrophils from the patients than the controls (NC 65 ± 5 nm, DM 80 ± 4 nm, P < 0·05). However, after fMLP‐treatment [Ca2+]i was significantly lower in the patients (NC 301 ± 28 nm, DM 210 ± 20 nm, P < 0·01). The greater increase in controls was not observed when cells were treated with fMLP in the absence of extracellular calcium (– fold increase NC 2·9 ± 0·5, DM 2·7 ± 0·3). Treatment of cells with thapsigargin caused a similar greater increase in [Ca2+]i in the controls than in the patients that was not seen in the absence of extracellular calcium (– fold increase with Ca2+ NC 5·2 ± 1·0, DM 3·0 ± 0·4, P < 0·05; fold increase without Ca2+ NC 2·5 ± 0·4, DM 2·2 ± 0·2).

Conclusions In Type 2 diabetes there is a defect in neutrophil calcium signalling which results in a lesser increase in free cytosolic calcium owing to impaired influx across the plasma membrane. Abnormal calcium signalling is likely to be important in the pathogenesis of diabetic complications.
Interaction between smoking and PON2 Ser311Cys polymorphism as a determinant of the risk of myocardial infarction
Authors: Martinelli N. , Girelli D. , Olivieri O. , Stranieri C. , Trabetti E. , Pizzolo F. , Friso S. , Tenuti I. , Cheng S. , Grow M. A. , Pignatti P. F. , Corrocher R.
Published: January 2004

Background  Increased oxidative stress is thought to play a role in the pathogenesis of the atherothrombotic process. Paraoxonases (PONs) are closely related antioxidant enzymes encoded by clustered genes on chromosome 7q. We evaluated three PON polymorphisms (PON1 Leu55Met and Gln192Arg; PON2 Ser311Cys) as possible risk factors for coronary atherosclerotic disease (CAD) and/or its main thrombotic complication, myocardial infarction (MI).

Materials and methods  We studied 890 subjects with angiographic documentation of coronary vessels (272 = CAD‐free; 618 = CAD). In the CAD group, 341 subjects had a previous MI.

Results  Frequencies of various genotypes were not significantly different between CAD‐free subjects and the entire CAD population. In the latter group, there were more carriers of the PON2 311Cys variation among those who had suffered a MI than among those who had not (P < 0·01 by χ2). The adjusted OR for MI among PON2 311Cys carriers was 1·5 (95%CI, 1·03–2·19). A gene–environmental interaction was found between PON2 Ser311Cys and smoking. Smoking by itself was associated with an increased MI risk. Among smokers, however, the MI risk was related to PON2 genotype: Cys/Cys homozygotes (OR = 5·3; 95%CI, 1·7–16·4) and Ser/Cys heterozygotes (OR = 2·1; 95%CI, 1·3–3·6) were at greater risk than Ser/Ser subjects (OR = 1·2; 95%CI, 0·8–1·8). The PON2 polymorphism did not influence the MI risk among nonsmokers.

Conclusions  In CAD subjects, a proportion of the risk of MI may be influenced by the interaction between smoking and a polymorphism in the antioxidant enzyme PON2.
Delayed genomic and acute nongenomic action of glucocorticosteroids in seasonal allergic rhinitis
Authors: Tillmann H.‐C. , Stuck B. A. , Feuring M. , Rossol‐Haseroth K. , Tran B. M. , Lösel R. , Schmidt B. M. , Hörmann K. , Wehling M. , Schultz A.
Published: January 2004

Background  Glucocorticosteroids are effective in the treatment of allergic rhinitis, a disease characterized by a variety of symptoms, e.g. rhinorrhea and itching. The time course of symptomatic relief for allergic rhinitis by steroids has not been examined in detail to date, although the onset of steroid action is one of the main discriminations between genomic and nongenomic actions of steroids. We therefore investigated the time course of subjective and objective measures of nasal affection after steroid administration in patients with allergic rhinitis following specific allergen challenge.

Methods  Six female and 18 male volunteers (median age 26 years) with a history of allergic rhinitis but currently free of symptoms were included in this randomized, placebo‐controlled, double‐blind, three‐period crossover study. A single dose of either betamethasone (60 mg), methylprednisolone (400 mg) or placebo was given intravenously, 5 min after intranasal allergen provocation. After 10, 20, 60, 150 and 240 min, nasal itching and nasal obstruction were assessed using a standardized visual analogue scale. In addition, nasal airflow was measured by anterior rhinomanometry.

Results  Nasal itching was markedly reduced following either of the two steroids within 10 min after administration of study drug. Itching was depressed by 38% following betamethasone (P < 0·05) and by 18% following methylprednisolone (P = 0·07) compared with placebo. Nasal airflow and nasal obstruction were not significantly altered by steroids during the first 2 h of the study. However, after 150 min, nasal airflow was 21% rsp. 19% higher after methylprednisolone and betamethasone (P < 0·05) compared with placebo. After 240 min, nasal airflow was increased by 20% following betamethasone (P < 0·05) and by 19% following methylprednisolone. Nasal obstruction was also beneficially affected by both steroids 150 and 240 min after administration compared with placebo (P < 0·05 for both time points following betamethasone).

Conclusion  This study for the first time shows rapid in vivo effects of external glucocorticosteroids in humans. Itching, a pathophysiologically complex sensation, is favourably influenced by steroids within 10 min, therefore presumably via nongenomic mechanisms. Though no detailed mechanisms can be derived from this study, steroid interaction with receptors in the central nervous system may play an important role in mediating this effect.
Extensive vascular invasion is a marker of risk of relapse in encapsulated non‐Hürthle cell follicular carcinoma of the thyroid gland: a clinicopathological study of 18 consecutive cases from a single institution with a 11‐year median follow‐up
Authors: Collini P , Sampietro G , Pilotti S
Published: January 2004

Aims : To determine the prognostic value of certain clinicopathological features in a series of 18 consecutive cases of encapsulated follicular carcinoma (EFC) of the thyroid gland with long follow‐up.

Methods and results : Eighteen consecutive cases of EFC were retrieved from 1975 to 1993. Gender, age at onset, type of surgery, presence of capsular and/or vascular invasion, number of involved vessels, tumour size, and TNM/pTNM classification were evaluated and correlated with disease outcome. None of the cases presented with distant metastases. Extensive vascular invasion (defined as more than four capsular vessels involved) was present in two cases. After a median follow‐up of 133 months, all patients were alive. Three cases had relapsed in lung and bone. In two out of these three cases, extensive vascular invasion was present. Radioiodine therapy was curative in two of three of the relapsed cases.

Conclusions : EFC is a low‐risk carcinoma, with no patients' deaths after a median follow‐up of 11 years. Extensive vascular invasion should be considered as a risk factor for relapse. A conservative surgical approach is recommended. Since relapses may occur up to 14 years after the initial surgery, life‐long follow‐up is advisable.
Pyothorax‐associated lymphoma (PAL): a western case with marked angiocentricity and review of the literature
Authors: Androulaki A , Drakos E , Hatzianastassiou D , Vgenopoulou S , Gazouli M , Korkolopoulou P , Patsouris E , Dosios T
Published: January 2004

Aims : To report a case of pyothorax‐associated lymphoma in a non‐immunocompromised 78‐year‐old man with a 45‐year history of tuberculous pleuritis and left pleural effusion. Pyothorax‐associated lymphoma is a high‐grade non‐Hodgkin's lymphoma occurring in 2% of patients with long‐standing tuberculous pleuritis and pyothorax. Pyothorax‐associated lymphoma is frequently Epstein–Barr virus (EBV)‐associated, mainly reported in Japan but exceedingly rare in western countries.

Methods and results : Histology revealed a high‐grade, diffuse large B‐cell lymphoma with immunoblastic and plasmacytoid features and marked angiocentricity with focal destruction of the vessel walls. Immunohistochemistry revealed a post germinal B‐cell phenotype. RNA in‐situ hybridization and molecular analysis showed a latent EBV infection and absence of human herpes virus‐8 (HHV‐8).

Conclusions : Pyothorax‐associated lymphoma represents a rare but distinctive type of diffuse large B‐cell lymphoma, with characteristic clinico‐epidemiological, immunohistological, and biological features.
Assessment of apoptosis by M30 immunoreactivity and the correlation with morphological criteria in normal colorectal mucosa, adenomas and carcinomas
Authors: Koornstra J J , Rijcken F E M , De Jong S , Hollema H , De Vries E G E , Kleibeuker J H
Published: January 2004

Aims : To investigate the monoclonal antibody M30 for the assessment of apoptosis in colorectal tissues. Although Terminal deoxyribonucleotidyl transferase mediated nick end labelling (TUNEL) and in‐situ end labelling (ISEL) are the methods most often used to demonstrate and quantify apoptosis in histological tissue sections, the interpretation and specificity of these techniques have been controversial. Immunohistochemistry using the monoclonal antibody M30 that recognizes caspase‐cleaved cytokeratin 18 is considered to be a promising alternative but has yet to be validated against a generally accepted standard.

Methods and results : Paraffin sections of normal colonic mucosa (n = 30), normal mucosa obtained from resection margins from carcinomas (n = 30), colorectal adenomas (n = 84) and carcinomas (n = 40) were studied. Apoptosis of epithelial cells was assessed by M30 immunoreactivity and morphological criteria and expressed as a proportion of the total number of cells counted (apoptotic index). Mean apoptotic indices using M30 were 0.18 ± 0.04% in normal mucosa, 0.42 ± 0.04% in adenomas and 1.97 ± 0.24% in carcinomas. Using morphological criteria, these indices were 0.23 ± 0.03%, 0.62 ± 0.06% and 1.78 ± 0.19%, respectively. Apoptotic counts were higher in normal mucosa obtained from resection margins than in genuinely normal mucosa using the M30 antibody. Apoptotic indices obtained by M30 immunoreactivity and morphological criteria were positively correlated (r = 0.71, P < 0.01).

Conclusion : Assessment of apoptotic cells by M30 immunoreactivity correlates well with morphological criteria. Apoptotic indices increase in the course of the adenoma–carcinoma sequence. Apoptosis in normal mucosa obtained from resection margins differs from genuinely normal mucosa necessitating caution when interpreting studies of apoptosis in normal colonic mucosa. Our findings support the use of the M30 method in the study of apoptosis in colorectal tissues.
Towards reasonable workload in diagnosis of sentinel lymph nodes: comparison of two frozen section methods
Authors: Krogerus L A , Leidenius M H K , Toivonen T S , Von Smitten K J A
Published: January 2004

Aims : To compare two methods of histological assessment with intraoperative diagnosis of sentinel node metastases in breast cancer.

Methods and results : A total of 204 consecutive breast cancer cases with lymphatic mapping, sentinel node biopsy and intraoperative diagnosis were included. The sentinel nodes in the first 102 cases (method A) were bisected and serially sectioned. In the other 102 cases (method B) the nodes were sliced thinly with a razor blade. All 1–1.5 mm thick slices were mounted on prechilled mounting medium on frozen section buttons. Cytological imprints were also made of the attached tissue slices. Postoperative diagnosis of sentinel lymph node metatases was taken as gold standard. Sentinel node metastases were found in 28 (27%) cases in group A and in 42 (40%) cases in group B (P = 0.05). The median size of the sentinel node metastases was 4.3 mm in group A and 3.3 mm in group B (P < 0.05).

Conclusion : Method B finds more and smaller metastases and takes less time and effort in the laboratory. When using method A, many small metastases are not detected at all.
Ki67 expression in bronchial preneoplastic lesions and carcinoma in situ defined according to the new 1999 WHO/IASLC criteria: a preliminary study
Authors: Meert A‐P , Feoli F , Martin B , Verdebout J‐M , Mascaux C , Verhest A , Ninane V , Sculier J‐P
Published: January 2004

Aims : The World Health Organization classification of bronchial intraepithelial neoplastic lesions has been shown to be reproducible. However little is known about its biological value. The aim of this study was to assess the proliferative activity of mild (MiD), moderate (MoD), severe (SD) dysplasia and carcinoma in situ (CIS) by the expression of Ki67 on biopsy specimens obtained during fluorescence bronchoscopy.

Methods and results : The percentage of Ki67+ lesional nuclei was calculated in each lesion. In addition, the presence of Ki67 clusters (defined as a group of at least two strongly Ki67+ nuclei located in the upper third of the epithelium) and a Ki67 score were evaluated. The Ki67 score depended on the proportion of the stained nuclei and on the intensity of staining. MiD, MoD, SD and CIS showed increased Ki67 staining (respectively, 10%, 20%, 30% and 40% median values of positive cells). Thirty‐one percent MiD, 77% MoD, 91% SD and 100% CIS showed one or more positive clusters. When only multiple clusters were considered the difference between high‐ and low‐grade lesions was accentuated. Ki67+ clusters were more frequent in SD (91%) and CIS (94%) compared with MiD (15%) and MoD (22%). This difference was statistically significant (P < 0.01). Evaluation of the Ki67 score was in line with the above results: high grade lesions (SD and CIS) more often showed scores >4 (P = 0.05 between MiD plus MoD versus SD plus CIS).

Conclusions : Ki67 expression increases from MiD to CIS with a statistically significant difference between MiD plus MoD and SD plus CIS. These results suggest that, in terms of Ki67 positivity, SD behaves like CIS rather than like MiD or MoD.
Prognostic value of immunohistochemical expression of p53, bax, Bcl‐2 and Bcl‐xL in resected non‐small‐cell lung cancers
Authors: Groeger A M , Esposito V , De Luca A , Cassandro R , Tonini G , Ambrogi V , Baldi F , Goldfarb R , Mineo T C , Baldi A , Wolner E
Published: January 2004

Aims : Some experimental evidence suggests that in lung cancer, development, progression and an increased proliferation rate can be linked to apoptosis‐related factors. In this study we evaluated the possible role of p53 and Bcl‐2 gene family members as prognostic factors for non‐small‐cell lung cancer.

Methods and results : We investigated the immunohistochemical expression of p53 and Bcl‐2 gene family members (bax, Bcl‐2 and Bcl‐xL) in 94 non‐small‐cell lung cancer specimens to establish the role of these genes in lung cancer pathogenesis, and to evaluate their prognostic importance. The expression of Bcl‐2 was correlated with a shorter patient survival time and with the nodal status of the neoplasm. We also found frequent over‐expression of bax and Bcl‐xL to be of no prognostic significance. Finally, we found no correlation between frequent detection of aberrant p53 protein and expression of either Bcl‐2, bax or Bcl‐xL or with patient survival time.

Conclusions : This study confirms a relevant role for apoptosis‐regulatory proteins in the pathogenesis of lung cancer, and highlights the possible role of Bcl‐2 as a prognostic factor for this tumour.
Invasive micropapillary carcinoma of the breast: high incidence of lymph node metastasis with extranodal extension and its immunohistochemical profile compared with invasive ductal carcinoma
Authors: Zekioglu O , Erhan Y , Çiris M , Bayramoglu H , Özdemir N
Published: January 2004

Aims : Invasive micropapillary carcinoma of the breast is an aggressive and distinctive variant of breast cancer. These tumours have a characteristic histological appearance and have been associated with a high incidence of axillary lymph node metastases and a poor clinical outcome. The aims of this study were to investigate the immunohistochemical profile of invasive micropapillary carcinoma of the breast, to compare it with invasive ductal carcinoma, and to identify the morphological parameters which predict its poor outcome.

Methods and results : Fifty‐three (2.6%) invasive micropapillary carcinomas of the breast from 2022 cases of infiltrating breast carcinomas were identified by retrospective review. The patient age at presentation ranged from 33 to 78 years (mean 52.5 years). The tumour size ranged from 5 to 70 mm (mean 27 mm). Eighty‐two percent (43 of 53) were of high histological grade; 69% (33 of 48) of cases with axillary lymph node dissections had positive lymph nodes; and 75.5% (40 of 53) had lymphatic invasion: 46% (22 of 48) of cases had extranodal extension. Of lymph node‐positive cases, 61% had four or more metastatic lymph nodes. Of tumours with tumour size >10 mm, 77% had positive lymph nodes. The percentages of cases positive for oestrogen receptor (ER) and progesterone receptor (PR) were 68% and 61%, respectively. These values were significantly higher than the values for invasive ductal carcinomas. p53 and c‐erbB‐2 were detected in 48% and 54% of cases, respectively. The mean value of Ki67 was 26%. Follow‐up was available in 36 patients. Eight patients had local recurrences, nine patients had distant metastases, and 10 patients died of disease within a follow‐up period of 9 years.

Conclusion : Lymphotropism and an unfavourable prognosis are the hallmarks of this distinct entity. Prognostic markers such as ER, PR, p53, and c‐erbB‐2 failed to provide new criteria to allow discrimination of these tumours from other breast cancers.
Morphological variants of plasma cell tumours
Authors: Banerjee S S , Verma S , Shanks J H
Published: January 2004

Banerjee S S, Verma S & Shanks J H  (2004) Histopathology44, 2–8
 Morphological variants of plasma cell tumours
Carcinomas arising in multilocular thymic cysts of the neck: a clinicopathological study of three cases
Authors: Moran C A , Suster S , El‐Naggar A , Luna M A
Published: January 2004

Aims : To report three cases of primary carcinoma of the neck arising in multilocular thymic cysts (MTC).

Methods and results : The patients were three men aged 47, 50 and 52 years who presented with a painless neck mass of several weeks' duration. The patients had no history of previous surgical procedures or of malignancy elsewhere. The tumours in all three patients were located on the right lateral side of the neck; all patients underwent complete surgical resection of the mass. Grossly, the tumours were cystic and measured between 20 and 30 mm in greatest diameter. Histologically, the tumours showed cyst walls lined by squamous epithelium. The cyst walls contained prominent germinal centres with lymphoid hyperplasia, cholesterol cleft granulomas, and scattered keratinized structures reminiscent of Hassall's corpuscles. In addition, a neoplastic cellular proliferation composed of round to oval cells arranged in sheets and originating from the lining of the cystic structures was present. The neoplastic cells showed moderate amounts of eosinophilic cytoplasm, round nuclei, and, in some areas, prominent nucleoli. Mitotic figures were easily found, and cellular pleomorphism was present in several areas. In two cases the tumours showed features of basaloid carcinoma of the thymus, while in one case the pattern was that of squamous cell carcinoma. Immunohistochemical studies for keratin showed a strong positive reaction in the tumour cells, while leucocyte common antigen strongly stained the lymphoid background. Follow‐up information obtained in two patients showed them to be alive 6 months after initial diagnosis. One patient was lost to follow‐up.

Conclusion : The cases described here represent an unusual variant of carcinoma arising in multilocular thymic cyst in the neck region.
Epithelioid haemangiosarcoma of the thyroid gland. Report of six cases from a non‐Alpine region
Authors: Ryška A , Ludvíková M , Szépe P , Böör A
Published: January 2004

Aim : To report a series of six cases of thyroid haemangiosarcoma (HAS) from a non‐Alpine region.

Methods and results : The patients were four females and two males, aged 54–81 years (average 68 years). The tumours presented as large haemorrhagic masses (diameter 40–70 mm, average 56 mm) with extensive necrosis. Histologically, they were composed of polymorphous epithelioid cells with vesicular nuclei and abundant eosinophilic cytoplasm with occasional intracytoplasmic lumina. Mitotic activity was high. Tumor cells expressed vimentin (6/6), CD31 (6/6), FVIII (5/6), CD34 (2/6), and cytokeratins (5/6). One tumour (1/6) over‐expressed p53 protein in more than 20% of cells. Ultrastructurally, Weibel–Palade bodies were present (4/6). Clinical follow‐up of four patients (range 3–24 months, median 9 months) showed that two of them have died of the disease 0.5 and 3 months after diagnosis, one died of unrelated causes (with 24 months' uneventful follow‐up) and one is alive 21 months after operation with no evidence of disease.

Conclusions : Although thyroid HAS is usually regarded as an extremely aggressive neoplasm with a dismal prognosis similar to anaplastic carcinoma, one of our cases suggests that HAS can behave in a less aggressive way. The morphological, immunohistochemical and ultrastructural findings support the hypothesis that thyroid HAS is a distinct entity, unrelated to other thyroid malignancies.
Cyclooxygenase‐2 expression: a potential prognostic and predictive marker for high‐grade ductal carcinoma in situ of the breast
Authors: Tan K‐B , Yong W‐P , Putti T C
Published: January 2004

Aims : To study cyclooxygenase‐2 (COX‐2) expression in ductal carcinoma in situ (DCIS) of the breast and its association with histological features. COX‐2, an inducible prostaglandin synthase, has been shown to be important in mammary carcinogenesis, being associated with increased tumour size and unfavourable outcome in breast cancer. Animal studies indicate that COX‐2 inhibition is effective in the prevention and treatment of mammary cancers.

Methods and results : Fifty‐one cases of DCIS diagnosed during 1990–2000 were reviewed. Immunohistochemistry for COX‐2 was performed and the COX‐2 staining scores were correlated with histological features. The majority of cases [41 of 51 (80%)] had positive COX‐2 staining, of which 13 cases (25%) had strong staining. High nuclear grade DCIS was significantly associated with increased COX‐2 staining (P = 0.04).

Conclusions : High‐grade lesions are known to be associated with a higher recurrence rate following excision and are often oestrogen receptor negative, and as such, may be less responsive to adjuvant tamoxifen therapy. There is a need to examine further the role of COX‐2 expression in DCIS, as both a prognostic and predictive factor.
Academic underachievement by people with Prader–Willi syndrome
Authors: Whittington J. , Holland A. , Webb T. , Butler J. , Clarke D. , Boer H.
Published: January 2004

Background  Prader–Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder that is associated with the under‐expression of maternally imprinted genes at the 15q11–q13 chromosomal locus. In addition to a characteristic physical and behavioural phenotype, those with the syndrome have impaired social cognition, literal mindedness and inflexibility. The present authors investigated the relationship between the PWS cognitive and behavioural phenotype, educational experience, and levels of attainment in reading, writing and arithmetic.

Methods  All subjects from a population‐based sample of people with PWS, augmented by those with PWS living in other regions together with a contrast group of people with learning disability (LD) of other aetiologies, are included in the present study. Those children over 3 years of age whose families consented or adults who themselves consented were assessed for ability and attainment (over 7 years of age), and information on functional ability was also obtained from an informant. Underachievement was defined as the difference between the score predicted from full‐scale IQ and the actual achievement score.

Results  Commonly, levels of achievement were lower than would have been predicted on the basis of IQ among those in the groups with PWS and LD. In the group with PWS, underachievement across academic domains was positively correlated with the percentage of time in education in a special school and negatively correlated with Vineland Socialization domain standard score. There were no across‐domain significant correlations in the group with LD. When using multiple regression analysis, the percentage of time in special school was the only predictor of underachievement and only in the group with PWS. However, some children with PWS in special schools did achieve as expected in at least one academic domain.

Conclusions  Children with PWS may be placed in special schools largely because of their behavioural problems or physical disabilities, or expectations based on their PWS status. Their intellectual abilities may well be masked by their immature social behaviour. The present authors propose that a failure to recognize and address the specific educational needs which follow from this combination of poor socialization skills and complex maladaptive behaviours, in the context of relatively mild LD, may explain their findings.
People with intellectual disability and their health problems: a review of comparative studies
Authors: Jansen D. E. M. C. , Krol B. , Groothoff J. W. , Post D.
Published: January 2004

Background  The transition of people with intellectual disability (ID) from care institutions to the community – according to Western policy – results in a shift of responsibility towards primary health care services. In order to provide optimal care to people with ID living in the community, general practitioners need to be aware of the specific health problems of this patient category. The aim of this paper is to present an overview of recent studies on the specific health problems of people with ID, in particular on health problems of people with ID in the community, compared to those of the general population.

Method  To reliably compare health problems of individuals with and without ID, this review is limited to comparative research using a control group of individuals without ID. The focus of the review concentrates on international literature, published between 1995 and 2002.

Results  Most comparative research among people with ID presents higher prevalence rates for epilepsy, diseases of the skin, sensory loss and (increased risk of) fractures. These health problems are specific for people with ID, both in general and living in the community in particular.

Conclusions  there are only few studies focusing on health problems in people with ID in which a control group of individuals without ID is included. Most comparative studies on health problems in people with ID are based on comparison with reported prevalence rates of general health surveys.