bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of loss of heterozygosity in large cell neuroendocrine carcinomas of the lung and small cell lung carcinomas
Authors: Takeuchi Tomoyo , Minami Yuko , Iijima Tatsuo , Kameya Toru , Asamura Hisao , Noguchi Masayuki
Published: July 2006

Large cell neuroendocrine carcinoma (LCNEC) of the lung is a new entity. Besides morphological characteristics, its molecular biological features have been investigated by many researchers and compared to those of other neuroendocrine carcinomas, small cell lung carcinoma (SCLC) and carcinoid tumor (CT). However, there are few reports that show the significantly different genetic characteristics between them. The purpose of the present paper was to study the frequency of loss of heterozygosity (LOH) at chromosome 3p (3p14.2) in 38 neuroendocrine carcinomas of the lung (13 LCNEC, 11 SCLC and 14 CT) and 10 large cell carcinomas (LCC). The frequencies of LOH at 3p14.2 were 69.2% in LCNEC, 81.8% in SCLC, 50.0% in LCC and 7.14% in CT. Those at 22q13.3 were 30.8% in LCNEC, 72.7% in SCLC, 45.5% in LCC and 7.14% in CT. In particular, the frequency of SCLC with LOH at both 3p14.2 and 22q13.3 (63.6%) was significantly higher than that of LCNEC (15.4%). LCNEC and SCLC had different characteristics of LOH patterns at 3p14.2 and 22q13.3. The combined analysis of the LOH at 3p14.2 and 22q13.3 is thought to be useful for differential diagnosis between LCNEC and SCLC.
Mantle cell lymphoma in Taiwan: Clinicopathological and molecular study of 21 cases including one cyclin D1‐negative tumor expressing cyclin D2
Authors: Chuang Shih‐Sung , Huang Wan‐Ting , Hsieh Pin‐Pen , Tseng Hui‐Hwa , Campo Elias , Colomer Dolors , Ye Hongtao , Lu Chin‐Li , Chang Hui‐Mei , Cho Chi‐Yi , Huang Shih‐Hung , Lu Yin‐Che , Wu Jiann‐Der
Published: July 2006

Mantle cell lymphoma (MCL) is a rare B‐cell lymphoma that has never been characterized in Taiwan. The purpose of the present paper was to retrospectively identify 21 cases in male patients, with a median age of 61, involving lymph node (91%), marrow (71%), and peripheral blood (23%). Eighteen (86%) were in stages III/IV with 1 and 5 year survival rates of 78% and 17%, respectively. Mixed nodular and diffuse pattern (45%) was most common while interstitial pattern (92%) predominated in marrow. Eighteen (86%) were of classical morphology, two were pleomorphic and one was blastic. The tumors expressed IgM and bcl‐2 (100%), cyclin D1 (95%), CD5 (86%), CD43 and IgD (62%), CD52 (60%), and bcl‐6 (5%). Ki‐67 index ≥30% (P = 0.1834) was associated with a trend toward poorer survival while p21, p27, or p53 expression was not statistically significant for survival. Real‐time polymerase chain reaction for cyclin D1 (CCND1) gene mRNA expression showed high levels in nine cyclin D1‐positive patients and a low level in the single cyclin D1‐negative patient. The latter patient was cyclin D2 positive and negative for immunoglubuin heavy chain gene and CCND1 gene translocation by locus‐specific interphase fluorescent in situ hybridization. In conclusion, it is confirmed that the usual morphological variants and aberrant immunophenotype of MCL in the West occur in Taiwan and that this disease carries a poor prognosis.
Lung carcinosarcoma with liposarcoma element: Autopsy case
Authors: Kitazawa Riko , Kitazawa Sohei , Nishimura Yoshihiro , Kondo Takeshi , Obayashi Chiho
Published: July 2006

Pulmonary carcinosarcoma, consisting of both carcinoma and sarcoma with a heterologous element, is a rare subtype, comprising approximately 0.3% of primary lung neoplasia. A 57‐year‐old man was admitted because of severe dyspnea. A tumor wholly occupying the right thorax was biopsied and diagnosed as pleomorphic sarcoma. The tumor did not respond to chemotherapy, and the patient died of respiratory failure and sepsis. At autopsy, pleomorphic sarcoma was histologically dominant and contained a liposarcoma element confirmed by histocytological and electron microscopic analysis. Adenocarcinoma component with papillary and tubular patterns was confined to the medial lesion of the right lower lobe (3 × 8 cm), which was found in the chest X‐ray 3 years before admission, and had continuously merged with the sarcomatous lesion through the histological transition of both components. Aggressive and rapid growth of the sarcoma derived from the earlier adenocarcinoma became prevalent and contributed to the severe clinical outcome. This is the first documented case of primary lung carcinosarcoma with a liposarcoma element.
Inverted ductal papilloma of minor salivary gland: Case report with immunohistochemical study and literature review
Authors: Kubota Nobuhisa , Suzuki Kenji , Kawai Yoshiaki , Mizunuma Hideyuki , Lee Ushaku , Konishi Hiroaki , Miyazaki Hiroyuki , Kubota Eiro , Watanabe Yoshihisa
Published: July 2006

Inverted ductal papilloma (IDP) is a type of ductal papilloma arising in ducts of minor salivary glands. Very few cases, and no cases in Japan, have been reported. Reported herein is a case of IDP with a review of the literature. The patient was a 49‐year‐old man presenting with a lump in the right buccal mucosa of the premolar area of the mandible. The tumor was excised en bloc after a biopsy diagnosis of IDP. On the surface of the covering epithelium, an opening was seen to be filled with mucinous material. On cut surface the opening led to the tumor cavity. The major portion of the tumor parenchyma was made up of papillary proliferation of basaloid squamous cells. Some crypts, microcysts, and mucous cells were seen. There were no findings suggestive of a malignant tumor. The patient’s postoperative course was uneventful and there has been no recurrence after 1 year’s follow up. Immunohistochemical analysis of the present case supports the hypothesis that IDP originates from squamous metaplasia and proliferation of minor salivary gland duct cells.
Lingual subgemmal neurogenous plaques with pseudoepitheliomatous hyperplasia: Incidental pseudomalignant condition
Authors: Val‐Bernal J. Fernando , Rivadulla Isidro , Garijo M. Francisca
Published: July 2006

Pseudoepitheliomatous hyperplasia is a reactive proliferation of benign squamous epithelium that can mimic squamous cell carcinoma. Herein is a report on this type of reaction on two subgemmal neurogenous plaques in a lingual circumvallate papilla. To the authors’ knowledge this is the first report on this combination of lesions. A 66‐year‐old man died with disseminated squamous cell carcinoma of the lung. At autopsy the tongue was found to have an incidental pseudoepitheliomatous hyperplasia on two subgemmal neurogenous plaques with ganglion cells. Subgemmal neurogenous plaque should be included in the differential diagnosis of causes of lingual pseudoepitheliomatous hyperplasia. Awareness of the morphological spectrum of subgemmal neurogenous plaques can avoid the overdiagnosis of these lesions as neural tumors or squamous cell carcinoma.
Diode laser cycloablation in adult glaucoma: long‐term results of a standard protocol and review of current literature
Authors: Vernon Stephen A , Koppens Joanne M , Menon G Jayakrishna , Negi Anil K
Published: July 2006

Abstract

Background:  To study the long‐term efficacy and safety of diode laser cycloablation under a standard protocol in refractory glaucoma.

Methods:  A retrospective study involving 42 eyes (39 patients), observed for 36–84 (mean 65.7) months after cycloablation involving 14 burns of 2‐W power and 2‐s duration, over 270° of the ciliary body.

Results:  By final review, mean intraocular pressure (IOP) had dropped by 50.3% from 31.4 ± 8.8 mmHg before treatment to 15.6 ± 6.3 mmHg (P < 0.0001). Thirty‐seven of the 42 eyes (88.1%) achieved IOP < 22 mmHg. Thirty‐five of the 42 eyes (83.3%) eyes achieved IOP reduction ≥ 30% from baseline levels. The mean number of antiglaucoma medications per eye dropped from 2.55 ± 0.83 to 1.71 ± 1.44 (P = 0.0004). The percentage of eyes requiring oral acetazolamide dropped from 92.9% to 11.9% (P < 0.0001). About 59.6% of eyes required multiple treatment sessions (mean 2.17). Twenty‐seven (64.3%) eyes suffered deterioration, 11 (26.2%) maintained stability and 4 (9.5%) exhibited improvement of visual acuity. No relationship between the number of treatment sessions and visual outcome was evident.

Conclusions:  This conservative repeatable protocol affords delivery of the minimum dose of photocoagulation necessary to achieve a safe, long‐term ocular hypotensive response, while minimizing the risk of serious adverse effects, and is valuable in the difficult treatment of refractory glaucoma.
Comparative evaluation of oral fluorescein angiography using the confocal scanning laser ophthalmoscope and digital fundus camera with intravenous fluorescein angiography using the digital fundus camera
Authors: Azad Raj Vardhan , Baishya Bipul , Pal Nikhil , Sharma Yog Raj , Kumar Atul , Vohra Rajpal
Published: July 2006

Abstract

Background:  To study the efficacy of oral fluorescein angiography (FA) with confocal scanning laser ophthalmoscope (CSLO).

Methods:  Ten patients each of choroidal neovascular membrane, central serous retinopathy, diabetic retinopathy and five normal subjects were evaluated with group 1 – intravenous FA using digital fundus camera (DFC); group 2 – oral FA using DFC; and group 3 – oral FA using CSLO.

Results:  Third‐order branch vessels were identified in 85.7% eyes in group 3 versus 51.4% in group 2 (P = 0.004), image quality was comparable to intravenous FA in 77.1% in group 3 versus 48.5% in group 2 (P = 0.02) and margin delineation was better in 80% eyes in group 3 versus 35% in group 2 (P = 0.01). The foveal avascular zone was clear and intact in 54.2% eyes in group 3 versus 37.1% in group 2 (P = 0.14) and 57.1% in group 1 (P = 0.8).

Conclusion:  Oral FA using CSLO is superior to oral FA using DFC and comparable to intravenous FA using DFC in terms of image quality, branch retinal vessel identification and margin delineation.
Histopathology of explanted AlphaCor due to keratoprosthesis extrusion
Authors: Caporossi Aldo , Mazzotta Cosimo , Balestrazzi Angelo , Occhini Rossella , Toti Paolo , Traversi Claudio
Published: July 2006

Abstract

AlphaCor keratoprosthesis (KPro) is a new‐concept poly (2‐hydroxyethyl methacrylate) one‐piece KPro that makes possible a two‐step implantation technique easy to perform with a short learning curve. In literature an 18% incidence of AlphaCor removal due to melting complications is reported. The histopathology of corneal tissue removed during a re‐operation while bearing an AlphaCor KPro has previously been described in the literature only in one report. Herein, the first histological features of an AlphaCor–corneal complex explanted because of KPro extrusion is described. The histopathology of the AlphaCor–corneal complex is characterized by mild inflammation in the corneal tissues, limited to the region surrounding the anteriorized and extruded part of the KPro. It is not possible to fully understand the mechanisms that trigger the device extrusion. One possible explanation could be a dislocation of the prosthesis in the corneal pocket due to the untied fixation stitch. Another explanation could be a foreign body reaction induced by KPro.
Facts on fats
Authors: Chong Elaine W‐T , Sinclair Andrew J , Guymer Robyn H
Published: July 2006

Abstract

Cardiovascular disease and age‐related macular degeneration (AMD) may share common risk factors in their causal pathways. Decades of research from the cardiovascular sciences on fats have led investigators to focus on specific types of fats rather than total fat as a whole. They have established that saturated and trans‐unsaturated fats (trans fats) are damaging to cardiovascular health while polyunsaturated fats, particularly the marine omega 3 fatty acids appear protective. This has led to a number of studies investigating the associations of fat and AMD. Though the causal relationship between fats and AMD remain unproven, some studies suggest that an association may be present. To be able to understand and interpret the study results and their implications, an understanding of the fats in the diet is important. This review aims to give an overview of fatty acids, particularly the trans‐unsaturated fatty acids, and the relevant food groups.
Iris melanoma in 12‐year‐old boy
Authors: Tran Tu A , Hirst Lawrence W , Axelsen Roy A , Welch Roger
Published: July 2006

Abstract

A 12‐year‐old boy presented with an incidental finding of an iris lesion after blunt injury. Ocular examination revealed a large atypical brown vascular nodule in the nasal iris, extending to the pupillary margin. There were smaller scattered nodules scattered within the iris and anterior chamber. Ultrasound biomicroscopy examination revealed no tumour behind the iris. Fundal examination findings were normal. Sector iridectomy revealed mixed spindle and epitheliod melanoma. The eye was enucleated. Histopathologic examination confirmed malignant melanoma confined to the iridocorneal angle, iris, ciliary body and inner layer of the anterior sclera. Iris melanomas are very rare in the prepubertal age group.
Effect of mitomycin C on ostium in dacryocystorhinostomy
Authors: Deka Amarendra , Bhattacharjee Kasturi , Bhuyan Saurabh Kr , Barua Chiranjib Kumar , Bhattacharjee Harsha , Khaund Gautom
Published: July 2006

Abstract

Background:  To observe the effect of intraoperative mitomycin C of varying concentration on postoperative ostium size after external dacryocystorhinostomy (DCR).

Methods:  In this prospective controlled study, 60 cases of DCR were taken up irrespective of age and sex. Cases were divided into three groups. Group 1 was taken as a control group and operated without mitomycin C; in experimental group 2 and group 3, mitomycin C at a concentration of 0.05 mg/mL and 0.4 mg/mL was applied, respectively, for 2 min. Each group consisted of 20 cases. Half of the cases in each group underwent single‐flap DCR (SFDCR) and half underwent double‐flap DCR (DFDCR) surgery. Nasal endoscopic evaluation was performed on the first postoperative day, at 2 weeks and at 6 months after surgery. A Student’s t‐test was used to compare the osteotomy size of each group.

Results:  At the end of the final follow up, average size of the ostium in group 1 was 3.6 ± 2.36 mm2 in SFDCR and 4.5 ± 3.59 mm2 in DFDCR, in group 2 was 4.8 ± 4.82 mm2 in SFDCR and 4.9 ± 4.12 mm2 in DFDCR, and in group 3 was 16.6 ± 6.80 mm2 in SFDCR and 17.5 ± 9.07 mm2 in DFDCR. The ostium size in group 3 was found to be significantly bigger in comparison with group 1 (P = 0.0001 in SFDCR, P = 0.001 in DFDCR) and with group 2 (P = 0.0009 in SFDCR, P = 0.001 in DFDCR). No statistically significant difference of ostium size was found in SFDCR and DFDCR.

Conclusion:  Mitomycin C in appropriate dose minimizes postoperative fibrosis and granulations, thereby maintaining a bigger postoperative ostium throughout the postoperative observation period.
Complex genetics of complex traits: the case of primary open‐angle glaucoma
Authors: Hewitt Alex W , Craig Jamie E , Mackey David A
Published: July 2006

Abstract

Glaucoma, which is a complex heterogeneous disease, presents an ideal case for genetic investigation. Primary open‐angle glaucoma (POAG) is the commonest subtype and will be the focus of this review. When detected early, POAG is amenable to therapeutic intervention. Unfortunately, current population‐based clinical screening lacks efficacy. If individuals with a genetic predisposition for developing POAG can be identified, then efficient and cost‐effective population‐based screening programs could be designed. Although considerable inroads have been made in understanding the natural history of POAG caused by mutations in the myocilin and optineurin genes, other POAG genes accounting for most cases remain to be identified. This review explores the genetic mechanisms that have been unequivocally linked to the glaucomatous process and then discusses potential avenues for future breakthroughs.
Taurine potentiates presynaptic NMDA receptors in hippocampal Schaffer collateral axons
Authors: Suárez Luz M. , Solís José M.
Published: July 2006

We have previously shown that activation of presynaptic N‐methyl‐d‐aspartate (NMDA) receptors (NMDAR) enhances the amplitude of the presynaptic fibre volley (FV) evoked in Schaffer collateral axons of rat hippocampal slices, by a mechanism independent of extracellular Ca2+. Here we compared the pharmacological characteristics of presynaptic NMDARs affecting axon excitability (activated by 10–300 µm NMDA for 10 min), with those mediating field excitatory postsynaptic potentials (NMDA‐fEPSP). We found that NMDA‐induced potentiation was completely inhibited by NVP‐AAM077, an antagonist of NR2A‐containing NMDAR, but not by ifenprodil, an NR2B‐selective antagonist. The inhibitor of the glycine‐binding site in NMDARs, 7‐clorokynurenic acid (7‐CK), was more potent against NMDA‐fEPSP (IC50 = 6.3 ± 1.3 µm) than against the NMDA‐induced FV potentiation (IC50 = 26.5 ± 1.3 µm). Moreover, both post‐ and presynaptic NMDAR‐mediated phenomena were enhanced by glycine and d‐serine, but taurine, an endogenous analogue of glycine, only enhanced the latter (EC50 = 19 µm). Taurine was able to block the inhibitory effect of low doses of 7‐CK on NMDA‐induced FV potentiation, while glycine and d‐serine only reduced the effects of higher concentrations of this drug. Surprisingly, the enhancing effect of taurine on NMDA‐induced FV potentiation was blocked when it was co‐applied with glycine. Furthermore, the glutamate released synaptically with a train of stimuli also increased FV amplitude by a mechanism dependent on NMDARs; this was potentiated by taurine but not by co‐application of taurine and glycine. These results reveal that presynaptic NMDARs have unique properties that mediate the facilitation of axon excitability.
Estrogen controls PKCε‐dependent mechanical hyperalgesia through direct action on nociceptive neurons
Authors: Hucho Tim B. , Dina Olayinka A. , Kuhn Julia , Levine Jon D.
Published: July 2006

Protein kinase C epsilon (PKCε) is an important intracellular signaling molecule in primary afferent nociceptors, implicated in acute and chronic inflammatory as well as neuropathic pain. In behavioral experiments inflammatory mediators produce PKCε‐dependent hyperalgesia only in male rats. The mechanism underlying this sexual dimorphism is unknown. We show that the hormone environment of female rats changes the nociceptive signaling in the peripheral sensory neuron. This change is maintained in culture also in the absence of a gender‐simulating environment. Stimulation of β2‐adrenergic receptors (β2‐AR) leads to PKCε activation in cultured dorsal root ganglia (DRG) neurons derived from male but not from female rats. Addition of estrogen to male DRG neurons produces a switch to the female phenotype, namely abrogation of β2‐AR‐initiated activation of PKCε. Estrogen interferes downstream of the β2‐AR with the signaling pathway leading from exchange protein activated by cAMP (Epac) to PKCε. The interfering action is fast indicating a transcriptional‐independent mechanism. Estrogen has a dual effect on PKCε. If applied before β2‐AR or Epac stimulation, estrogen abrogates the activation of PKCε. In contrast, estrogen applied alone leads to a brief translocation of PKCε. Alsoin vivothe activity of estrogen depends on the stimulation context. In male rats, intradermal injection of an Epac activator or estrogen alone induces mechanical hyperalgesia through a PKCε‐dependent mechanism. In contrast, injection of estrogen preceding the activation of Epac completely abrogates the Epac‐induced mechanical hyperalgesia. Our results suggest that gender differences in nociception do not reflect the use of generally different mechanisms. Instead, a common set of signaling pathways can be modulated by hormones.
On the postnatal development of the striate cortex (V1) in the tree shrew (Tupaia belangeri)
Authors: Drenhaus Ulrich , Rager Günter , Eggli Peter , Kretz Robert
Published: July 2006

Histological serial sections, three‐dimensional reconstructions and morphometry served to study the postnatal development of V1 in tree shrews. The main objectives were to evaluate the expansion of V1, the implications of its growth on the occipital cortex and, vice versa, the effects of the expanding neocortex on the topography of V1. The future V1 was identified on postnatal day 1 by its granular layer IV, covering the superior surface of the occipital cortices including the poles. A subdivision of layer IV, distinctive for the binocular part, was evident in the central region. V1 expanded continuously with age into all directions succeeded by the maturation of layering. The monocular part was recognized from day 15 onward, after the binocular part had reached its medial border. In reference to the retinotopic map of V1, regions emerged in a coherent temporo‐spatial sequence delineating the retinal topography in a central to peripheral gradient beginning with the visual streak representation. The growth of V1 was greatest until tree shrews open their eyes, culminated during adolescence, and completed after a subsequent decrease in the young adult. Simultaneous expansion of the neocortex induced a shifting of V1. Translation and elongation of V1 entailed that the occipital cortex covered the superior colliculi along with a downward rotation of the poles. The enlargement of the occipital part of the hemispheres was in addition associated with the formation of a small occipital horn in the lateral ventricles, indicating an incipient ‘true’ occipital lobe harbouring mainly cortices involved in visual functions.
Contribution of spinal 5‐HT1Aand 5‐HT7receptors to locomotor‐like movement induced by 8‐OH‐DPAT in spinal cord‐transected mice
Authors: Landry Eric S. , Lapointe Nicolas P. , Rouillard Claude , Levesque Daniel , Hedlund Peter B. , Guertin Pierre A.
Published: July 2006

Growing evidence fromin vitrostudies suggests that spinal serotonin (5‐HT) receptor subtypes 5‐HTR1Aand 5‐HTR7are associated with an induction of central pattern generator activity. However, the possibility of a specific role for these receptor subtypes in locomotor rhythmogenesisin vivoremains unclear. Here, we studied the effects of a single dose (1 mg/kg, i.p.) of 8‐hydroxy‐2‐(di‐N‐propylamino)‐tetralin (8‐OH‐DPAT), a potent and selective 5‐HTR1A/7agonist, in mice spinal cord transected at the low‐thoracic level (Th9/10). The results show that 8‐OH‐DPAT acutely induced, within 15 min, hindlimb movements that share some characteristics with normal locomotion. Paraplegic mice pretreated with the selective 5‐HTR1Aantagonists, WAY100,135 or WAY100,635, displayed significantly less 8‐OH‐DPAT‐induced movement. A similar reduction of 8‐OH‐DPAT‐induced movements was found in animals pretreated with SB269970, a selective 5‐HTR7antagonist. Moreover, a near complete blockade of 8‐OH‐DPAT‐induced movement was obtained in wild‐type mice pretreated with 5‐HTR1Aand 5‐HTR7antagonists, and in 5‐HTR7–/– mice pretreated with 5‐HTR1Aantagonists. Overall, these results clearly demonstrate that 8‐OH‐DPAT potently induces locomotor‐like movement in the previously paralysed hindlimbs of low‐thoracic‐transected mice. The results, with selective antagonists and knockout animals, provide compelling evidence of a specific contribution of both receptor subtypes to spinal locomotor rhythmogenesisin vivo.
Persistent cerebrovascular effects of MDMA and acute responses to the drug
Authors: Ferrington Linda , Kirilly Eszter , McBean Douglas E. , Olverman Henry J. , Bagdy György , Kelly Paul A. T.
Published: July 2006

Acutely, 3,4,‐methylenedioxymethamphetamine (MDMA) induces cerebrovascular dysfunction [Quate et al., (2004)Psychopharmacol., 173, 287–295]. In the longer term the same single dose results in depletion of 5‐hydroxytrptamine (5‐HT) nerve terminals. In this study we examined the cerebrovascular consequences of this persistent neurodegeneration, and the acute effects of subsequent MDMA exposure, upon the relationship that normally exists between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu). Dark agouti (DA) rats were pre‐treated with 15 mg/kg i.p. MDMA or saline. Three weeks later, rats from each pre‐treatment group were treated with an acute dose of MDMA (15 mg/kg i.p.) or saline. Quantitative autoradiographic imaging was used to measure LCBF or LCMRglu with [14C]‐iodoantipyrine and [14C]‐2‐deoxyglucose, respectively. Serotonergic terminal depletion was assessed using radioligand binding with [3H]‐paroxetine and immunohistochemistry. Three weeks after MDMA pre‐treatment there were significant reductions in densities of 5‐HT transporter (SERT)‐positive fibres (−46%) and [3H]‐paroxetine binding (−47%). In animals pre‐treated with MDMA there were widespread significant decreases in LCMRglu, but no change in LCBF indicating a persistent loss of cerebrovascular constrictor tone. In both pre‐treatment groups, acute MDMA produced significant increases in LCMRglu, while LCBF was significantly decreased. In 50% of MDMA‐pre‐treated rats, random areas of focal hyperaemia indicated a loss of autoregulatory capacity in response to MDMA‐induced hypertension. These results suggest that cerebrovascular regulatory dysfunction resulting from acute exposure to MDMA is not diminished by previous exposure, despite a significant depletion in 5‐HT terminals. However, there may be a sub‐population, or individual circumstances, in which this dysfunction develops into a condition that might predispose to stroke.
Mapping macroecology
Authors: Ruggiero Adriana , Hawkins Bradford A.
Published: July 2006

Although macroecology arose from geographical ecology, it has diverted from a geographical perspective. At present, most macroecological studies use a statistical approach that adopts an ‘individual species focus’ and relies on comparisons between species to test for broad‐scale ecological patterns. Sometimes, space is included as part of the analysis, but almost always in a single dimension. In both situations, observed relationships are depicted using bivariate scatter‐plots. We argue that current macroecological approaches may interfere with our perception of patterns and have important implications for their biological interpretation. We use the literature concerned with spatial variation in the range sizes of species (Rapoport's rule) to illustrate our point of view. Given the current lack of maps actually showing the patterns we are trying to explain, we contend that macroecology could benefit greatly by returning to its geographical roots, at least when data contain spatial structure.
Species richness, area and climate correlates
Authors: Nogués‐Bravo David , Araújo Miguel B.
Published: July 2006

Aim  Species richness–area theory predicts that more species should be found if one samples a larger area. To avoid biases from comparing species richness in areas of very different sizes, area is often controlled by counting the numbers of co‐occupying species in near‐equal area grid cells. The assumption is that variation in grid cell size accrued from working in a three‐dimensional world is negligible. Here we provide a first test of this idea. We measure the surface area of c. 50 × 50 km and c. 220 × 220 km grid cells across western Europe. We then ask how variation in the area of grid cells affects: (1) the selection of climate variables entering a species richness model; and (2) the accuracy of models in predicting species richness in unsampled grid cells.

Location  Western Europe.

Methods  Models are developed for European plant, breeding bird, mammal and herptile species richness using seven climate variables. Generalized additive models are used to relate species richness, climate and area.

Results  We found that variation in the grid cell area was large (50 × 50 km: 8–3311 km2; 220 × 220: 193–55,100 km2), but this did not affect the selection of variables in the models. Similarly, the predictive accuracy was affected only marginally by exclusion of area within models developed at the c. 50 × 50 km grid cells, although predictive accuracy suffered greater reductions when area was not included as a covariate in models developed for c. 220 × 220 km grid cells.

Main conclusions  Our results support the assumption that variation in near‐equal area cells may be of second‐order importance for models explaining or predicting species richness in relation to climate, although there is a possibility that drops in accuracy might increase with grid cell size. The results are, however, contingent on this particular data set, grain and extent of the analyses, and more empirical work is required.
Don't Screw the Crew: Exploring the Rules of Engagement in Organizational Romance
Authors: Riach Kathleen , Wilson Fiona
Published: July 2006

Thirty years ago sociological research began to discover what workplace romance might mean for the participants. Since then management research has tended to adopt a functionalist approach, using survey methods, or third‐party approaches to ask about company policy and negative consequences of workplace romance, warning of the dangers and consequences of romance and offering solutions for managers on how to deal with this potential problem. Drawing on the sexuality of organization and critical literature, and adopting a position of constructivist structuralism with a qualitative research method, this research looks at how the concept of workplace romance is defined and negotiated within a public‐house setting. It examines the ‘rules of engagement’, the personal experiences and views of both managers and workers, as well as first‐hand stories of workplace romance. Romance was conceptualized as ‘natural’ and something that could not be legislated for, where unwritten rules were defined but often ignored. However, the ‘rules of engagement’ emerged as favouring particular groups depending on gender, position in the hierarchy and sexual identity. Subjective value judgements are made, often resting on gendered assumptions of male and female behaviour.
Fairness and the Political Economy of Trade
Authors: Davidson Carl , Matusz Steve , Nelson Doug
Published: July 2006

This paper argues that, as a matter of positive political economy, fairness plays a non‐trivial role in the politics of trade policy. Specifically, we first argue that, as a matter of fact, widely held notions of fairness, that are empirically identifiable on the micro level, have macro effects not only in the social and political spheres of life, but even in the economy. Furthermore, as we argue in the second section, these notions systematically constrain public officials in the construction and pursuit of trade policy.
A Gravity Model Forecast of the Potential Trade Effects of EU Enlargement: Lessons from 2004 and Path‐dependency in Integration
Authors: Papazoglou Christos , Pentecost Eric J. , Marques Helena
Published: July 2006

This paper uses a gravity model to forecast the potential impact on trade balances and trade patterns of the 2004 EU enlargement. The results suggest that gross trade creation for the accession economies is about 25 per cent of their 2003 trade. Although membership of the EU creates trade it also results in trade diversion; that is, a declining share of accession country exports and imports with non‐EU15 countries. Overall, the trade balances of the accession countries suffer larger trade deficits after accession due to import growth surpassing export growth. The extent of increase in the trade deficit due to accession is inversely related to the level of integration and income of the new members. Hence integration is path‐dependent and the EU should take this into account when preparing for further enlargements to the Balkans and Southeast Europe.
The Natural History of Headache: Predictors of Onset and Recovery
Authors: Boardman HF , Thomas E , Millson DS , Croft PR
Published: July 2006

The objective of this study was to determine predictors of onset of new headache episodes and recovery from headache over one year. A population-based cohort study was conducted, comprising a baseline postal survey to a random sample of adults aged ≥18 years, with follow-up survey after 1 year. Risk factor data at baseline were compared with headache status at follow-up in two groups: (i) those free of recent headache at baseline and (ii) those with a recent headache at baseline. In respondents free of recent headache at baseline, previous headache [risk ratio (RR) 4.15], the presence of other pain at baseline (RR 1.43), severe sleep problems (RR 1.67) and drinking caffeine (RR 1.99) increased the risk of a new headache episode during the follow-up year. In respondents with recent headache at baseline, less severe headaches at baseline predicted recovery during the follow-up year, as did the absence of anxiety [recovery ratio (ReR) 2.84] and of sleep problems (ReR 2.77). Risks for increased headache-related disability reflected those for onset of a new episode and these risks increased in strength for large increases in disability. Sleep problems and caffeine consumption increase the risk of developing headache and thus provide targets for prevention. Low levels of anxiety, sleep problems and the absence of other pain improve the likelihood of recovering and remaining free from headache.
Fluid flow in shear zones: insights from the geometry and evolution of ore bodies at Renco gold mine, Zimbabwe
Authors: BLENKINSOP T. G. , KADZVITI S.
Published: July 2006

The geometry of mineral deposits can give insights into fluid flow in shear zones. Lode gold ore bodies at Renco Mine, in the Limpopo Belt, Zimbabwe, occur as siliceous breccias and mylonites within amphibolite facies shear zones that dip either gently or steeply. The two sets of ore bodies formed synchronously from hydrothermal fluids. The ore bodies are oblate, but have well‐defined long axes. Larger ore bodies are more oblate. High‐grade gold ore shoots have long axes that plunge down dip; this direction is perpendicular to the long axes of the low‐grade ore bodies. The centres of the high‐grade ore bodies align within the low‐grade ore bodies along strike in both gently and steeply dipping groups. The range of sizes and shapes of the ore bodies are interpreted as a growth sequence. Geometrical models are proposed for the gently and steeply dipping ore bodies, in which individual ore bodies grow with long axes plunging down dip, and merge to form larger, more oblate ore bodies. The models show that when three or more ore bodies coalesce, the long axis of the merged ore body is perpendicular to the component ore bodies, and that ore bodies in the deposit may have a range of shapes due to both growth of individual ore bodies, and their coalescence. The long axes of the high‐grade ore bodies are parallel to the shear directions of both the gently and steeply dipping dip slip shear zones, which were the directions of greatest permeability and fluid flow. The larger, lower grade bodies, which may have formed by coalescence, are elongate perpendicular to these directions.
Infliximab (Remicade®): from bench to clinical practice. A paradigm shift in rheumatology practice
Authors: HSIA Elizabeth C. , RULEY Kristin M. , RAHMAN Mahboob U.
Published: July 2006

Infliximab (Remicade®) is a chimeric monoclonal antibody that binds tumour necrosis factor–alpha (TNF‐α) and inhibits its biologic activity. Infliximab has been approved by the FDA for the treatment of a variety of immune‐mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis (RA), Crohn's disease (CD), ankylosing spondylitis (AS), ulcerative colitis (UC), and psoriatic arthritis (PsA). This is a brief review of the development of infliximab primarily in RA and CD; the pathogenesis of RA and CD as applicable to TNF‐α activity; conventional therapies available for RA and CD; early clinical trials and those leading to approval for RA, CD and other indications; coadministration with methotrexate (MTX), and the safety of infliximab as a therapeutic agent for IMIDs.
Effectiveness of a modified dosing regimen with a lower maintenance dose of infliximab in the treatment of patients with ankylosing spondylitis and spondyloarthropathy
Authors: CHAN K. Y. , LEE K. L. , HSU E. , MA K. Y. , LEE K. W.
Published: July 2006

Objective:  Anti‐tumour necrosis factor therapy offers hope to patients with ankylosing spondylitis (AS) and spondyloarthropathy (SpA) refractory to conventional disease‐modifying antirheumatic drugs (DMARDs). However, it is expensive with the standard recommended dosing (5 mg/kg) every 6–8 weeks. We assess the effectiveness of treating AS and SpA with a modified lower maintenance dosing regimen of infliximab.

Methods:  An open‐labelled, prospective trial with subjects recruited from a local tertiary hospital. Patients either fulfilled the modified New York criteria for classification of ankylosing spondylitis (AS) or European Spondyloarthropathy Study Group (ESSG) classification criteria for SpA with active disease. After induction with infliximab at 5 mg/kg at week 0 and 2 (induction period), patients were given 3 mg/kg at week 6 and then 8‐weekly (maintenance period) to 22 weeks. The patients were assessed with a standard protocol to 30 weeks. Erythrocyte sedimentation rate, c‐reactive protein, Visual Analogue Scale (VAS) pain score, VAS global health score (GH), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were recorded. The Ankylosing Spondylitis Assessment (ASAS) 20, ASAS 40 and ASAS 5/6 were determined at the end of the study.

Results:  Eighteen Chinese patients were recruited (16 AS, 2 SpA; M : F 8 : 10), with the mean age of 38.2 years and mean disease duration of 8 years. Nine patients had extra‐articular manifestations (9 uveitis, 1 aortic valve insufficiency, 1 colitis). Thirteen of these were on concurrent DMARDs. When comparing baseline with 6, 14, 22 or 30 weeks, erythrocyte sedimentation rate, c‐reactive protein, VAS pain, VAS GH, BASDAI and BASFI all achieved a statistical significant reduction. Half of the patients (9/18) achieved ASAS20 and ASAS40, whereas 61.1% (11/18) achieved ASAS5/6 at the end of the study. Partial remission was achieved in 22.2% (4/18) of subjects studied. Improvement in VAS pain score, VAS GH and BASFI after the induction period was sustained during the maintenance period.

Conclusion:  The modified dosing regimen with a lower maintenance dosage of infliximab was feasible and effective in the treatment of spondyloarthropathy. This would allow more patients to access and afford the therapy. A larger cohort with longer follow‐up would be useful to assess structural changes as well as confirmation of our current findings.
Experience with anti‐tumor necrosis factor‐α therapy in India
Authors: KUMAR Ashok
Published: July 2006

Aims:  To review the Indian experience with anti‐tumor necrosis factor (TNF)‐α therapy.

Methods:  ‘PubMed’ and ‘IndMED’ were searched for Indian studies on anti‐TNF‐α therapy. Data were compiled and analysed.

Results:  Data on infliximab from 176 patients from five different series were collated. One hundred and forty‐seven had ankylosing spondylitis (AS), nine had polyarticular juvenile idiopathic arthritis (JIA), 12 had rheumatoid arthritis (RA), six had undifferentiated spondyloarthropathy, one had inflammatory bowel disease‐related spondyloarthritis and one had psoriatic arthritis. Thus, 155/176. (88%) had spondyloarthropathy (SpA). No screening for latent tuberculosis was done in any of the studies. One series comprising 108 cases of AS, used 3 mg/kg infliximab infusions (instead of 5 mg/kg) at 8‐weekly intervals with omission of the 2‐week and 6‐week doses. All others with SpA (n = 47) followed the standard protocol: 171/176 patients had a significant improvement. Reactivation tuberculosis developed in 5/47 (10.6%) SpA patients treated with standard doses of infliximab. This amounted to 56 times increased risk compared to baseline (0.187%). None of the 129 patients treated with 3 mg/kg infusions of infliximab developed reactivation tuberculosis (AS −108, RA −12, JIA −9). The lone study on etanercept showed good efficacy in 40 patients with RA. However, seven serious adverse events occurred.

Conclusions:  Infliximab showed expected efficacy in SpA, RA and JIA. Reactivation tuberculosis developed in 10.6% of the SpA group treated with standard regimen. Patients treated with lower doses of infliximab which included a large subgroup of SpA patients and those with RA or JIA did not develop tuberculosis.
Clinical experience with infliximab among Filipino patients with rheumatic diseases
Authors: NAVARRA Sandra V. , RASO Anne‐Annette , LICHAUCO Juan Javier , TAN Perry P.
Published: July 2006

Aim:  To describe the clinical experience with infliximab among Filipino patients with rheumatic diseases, specifically disease indications, dose regimens, clinical response, and adverse events.

Methods:  We reviewed the data on Filipino patients who were given infliximab by rheumatologists for a rheumatic disease indication. The case report form included demographic profile, underlying rheumatic disease, comorbidities, concurrent medications, dose and frequency of infliximab, physicians’ assessment of clinical response, and adverse events. The frequency of doses, intervals between doses, and discontinuation status were recorded.

Results:  Included were 64 patients (35 females), with a mean age of 44 years. Most (41%) had rheumatoid arthritis, followed by psoriasis/psoriatic arthritis (31.2%) and ankylosing spondylitis (17.2%). Average disease duration from diagnosis to initiation of infliximab therapy was 7.6 years ± 6.7 SD. Among 35 patients, the interval between maintenance infusions ranged from 6 to 13.6 weeks, with a mean of 8.27 weeks. Clinical response was good to excellent in more than 80% of patients. Discontinuation rate was 10.9% and 28.1% at 3 and 12 months, respectively. Infusion‐related adverse events were mild and transient, and 14 (21.8%) cases of infection resolved with appropriate therapy. Infliximab was temporarily withheld in five (7.8%) patients with active tuberculosis.

Summary:  These findings substantiate the superior clinical efficacy of infliximab and manageable adverse events among Filipinos with rheumatic diseases. It also demonstrates dose regimens in clinical practice in a third world setting with limited resources.
The use of anti‐tumour necrosis factor‐α therapies for rheumatoid arthritis in Singapore
Authors: THONG B. Y. H. , VASOO S. , KOH E. T.
Published: July 2006

Anti‐tumour necrosis factor‐α (anti‐TNF‐α) agents are biologic disease‐modifying antirheumatic drugs (DMARDs) used in the treatment of moderate to severe rheumatoid arthritis (RA). We describe the demographic and therapeutic profiles of 22 patients who received anti‐TNF‐α therapy for RA in two hospitals in Singapore. The majority of patients were female, middle‐aged, full‐time working adults with limitation in their social or vocational activities. The mean RA disease duration was 101.4 ± 101.6 months (3.4–401.3). All received conventional DMARDs for a mean of almost 7 years before starting anti‐TNF‐α, with the majority having failed two or more DMARDs. The most commonly used anti‐TNF‐α therapies were infliximab (90.9%), etanercept (18.2%) and adalimumab (4.5%). Only one patient developed a major infection, while three developed minor infections requiring temporary cessation of anti‐TNF‐α therapy. There were no cases of malignancy, drug‐induced lupus, demyelinating disease or congestive heart failure during an average of 36.9 ± 21.9 months (3.9–63.0) from initiation of therapy.
Adverse effects of tumour necrosis factor‐α blocking agents
Authors: PARK Kyung‐Su , PARK Sung‐Hwan
Published: July 2006

Tumor necrosis factor α (TNF‐α) blocking agents have been proved to be very effective in the treatment of various inflammatory rheumatic diseases which are refractory to conventional disease‐modifying antirheumatic drugs. However, anti‐TNF‐α therapy may have adverse effects on host defence against infectious agents in which TNF‐α plays a pivotal role. In addition, there are reports about neurologic, autoimmune, cardiac, and malignant diseases associated with TNF‐α blocking agents. This article summarizes the adverse effects and safety of these agents.
Extended indications for anti‐tumor necrosis factor‐α therapy
Authors: YOON Chong‐Hyeon , KIM Ho‐Youn
Published: July 2006

Tumour necrosis factor‐α is a pleiotropic cytokine which has a broad range of actions in inflammation, infection and immunity. TNF‐α is supposed to play a crucial role in the pathogenesis of various autoimmune diseases. TNF‐α blocking agents have been demonstrated to be highly effective in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and juvenile rheumatoid arthritis. TNF‐α inhibitors also have been tried with other rheumatic diseases and have emerged as promising treatments. We here review the current evidences of effectiveness of the anti‐TNF‐α therapy in various autoimmune diseases.
Anti‐tumor necrosis factor therapy: the Australian experience
Authors: NASH Peter
Published: July 2006

Anti‐tumor necrosis factor (TNF) therapy for the management of rheumatic diseases has been reimbursed in Australia progressively per agent and disease indication since 2003. Initial projections of uptake were grossly overestimated. In this article the anti‐TNF experience in Australia is reviewed, including results of an eligibility study, Australian Rheumatology Association guidelines, anti‐TNF registry, and a report of adverse effects. These observations may assist APLAR countries currently coming to terms with anti‐TNF drug registration and funding.
Implications of Clinical Subtypes of Migraine With Aura
Authors: Eriksen Malene Kirchmann , Thomsen Lise Lykke , Olesen Jes
Published: July 2006

Objective.—To compare the clinical characteristics of familial hemiplegic migraine (FHM), sporadic hemiplegic migraine (SHM), and nonhemiplegic migraine with aura (NHMA) and further, to compare subtypes of NHMA.

Background.—To discover distinct underlying genetic and pathophysiological mechanisms it is crucial to drive clinical subdivision of migraine with aura as far as possible. The documentation of subtypes of migraine with aura depends on the clinical characteristics as the genetic mechanisms are unknown except for the dominantly inherited FHM.

Methods.—Patients with FHM, SHM, or familial NHMA were recruited from specialist practice and diagnosed according to the International Classification of Headache Disorders (ICHD) in a validated interview by a physician. Patients with hemiplegic migraine had a physical and neurological examination. Patients with population‐based NHMA from a previous Danish study were used for comparison.

Results.—We recruited 147 patients with FHM, 105 with SHM, and 362 with familial NHMA. FHM and SHM had similar aura and headache characteristics. Patients with FHM and SHM were more likely to experience two or more aura symptoms (100% vs. 31%, P < .0001), they more often had prolonged aura symptoms, they almost always had a headache associated with the aura (93% vs. 58%, P < .0001), and they more frequently had basilar‐type symptoms (69% vs. 10%, P < .0001) than patients with population‐based NHMA. Patients with familial NHMA were more likely to experience two or more aura symptoms than patients with population‐based NHMA (61% vs. 32%, P < .0001). Within the subtypes of NHMA, patients with typical aura with migraine headache had an earlier age at onset (20 ± 10 vs. 23 ± 13 years, P= .044) and a higher co‐occurrence of migraine without aura (43% vs. 22%, P= .002) than patients with typical aura with nonmigraine headache.

Conclusions.—The present study proves that distinct subtypes of migraine with aura exist. It further underlines the phenotypic differences between the different subtypes of migraine with aura which likely are caused by different etiological mechanisms. In future studies FHM, SHM, and NHMA therefore should be analyzed as separate entities and patients with NHMA may be stratified by ICHD‐2 subtype of NHMA.