bluuebunny/crossref_metadata_2025 huggingface dataset:
Compliance, tone and sensitivity of the rectum in different subtypes of irritable bowel syndrome
Authors: Steens J. , Van Der Schaar P. J. , Penning C. , Brussee J. , Masclee A. A. M.
Published: March 2003

Abstract
 
Irritable bowel syndrome (IBS) consists of various subtypes. It is not known whether these subtypes share a common pathophysiology. Evaluation of motor and sensory function of the rectum using a barostat may help to explore a common pathophysiological background or differences in pathophysiology in subtypes of IBS. We have evaluated compliance, tone and sensitivity of the rectum, in both fasting state and postprandially, using a computerized barostat in 15 patients with diarrhoea‐predominant IBS (IBS‐D), 14 patients with constipation‐predominant IBS (IBS‐C) and compared the results with those obtained in 12 healthy controls. Rectal compliance as calculated over the steep part of the pressure–volume curve (17–23 mmHg) was decreased in both IBS groups (IBS‐D 8.0 ± 1.4 mL mmHg−1; IBS‐C 5.6 ± 1.1 mL mmHg−1) compared with controls (24.7 ± 3.5 mL mmHg−1). The perception of urge was increased only in IBS‐D patients, whereas pain perception was significantly increased in both IBS groups. Spontaneous adaptive relaxation was decreased in IBS‐D patients. Postprandially, rectal volume decreased significantly in the controls and in IBS‐D patients, but not in IBS‐C patients. In conclusion, both rectal motor and sensory characteristics are different between IBS‐D and IBS‐C patients. Therefore, testing of rectal visceroperception, adaptive relaxation and the rectal response to a meal may help distinguish groups of patients with different subtypes of irritable bowel syndrome.
Anisotropic propagation in the small intestine
Authors: Lammers W. J. E. P. , Stephen B. , Slack J. R. , Dhanasekaran S.
Published: March 2003

Abstract
 Measuring propagation anisotropy may help in determining the tissue layers involved in the propagation of electrical impulses in the intestine. We used 240 extracellular electrograms recorded from the isolated feline duodenum. The conduction velocities of slow waves and of individual spikes were measured from their site of origin into all directions. Both slow waves and spikes propagate anisotropically in the small intestine but in different directions and to a different degree. Slow waves propagated anisotropically faster in the circumferential (1.7 ± 0.8 cm s−1) than in the axial direction (1.3 ± 0.5 cm s−1; P < 0.001). Spikes, on the other hand, propagated faster in the longitudinal direction (7.8 ± 4.5 cm s−1) than in the circumferential direction (3.3 ± 4.3 cm s−1; P < 0.001). Furthermore, the average conduction velocity of spikes (6.3 ± 4.5 cm s−1) was significantly higher than that of slow waves (1.5 ± 1.1 cm s−1; P < 0.001). The anisotropic propagation of spikes supports the argument that these propagate in the longitudinal muscle layer. The anisotropic propagation of slow waves may be the result of the interaction between the myenteric layer of interstitial cells of Cajal and their electrotonic connection to both the longitudinal and the circular muscle layer.
Sensory neurone responses to mucosal noxae in the upper gut: relevance to mucosal integrity and gastrointestinal pain
Authors: Holzer P.
Published: March 2003

Abstract
 The digestive tract is supplied by extrinsic and intrinsic sensory neurones that, together with endocrine and immune cells, form a surveillance network that is essential to gut function. This article focuses on the responses of extrinsic afferent neurones to chemical insults of the gastrointestinal mucosa and their pathophysiological relevance to mucosal integrity and abdominal pain. Within the gastroduodenal region, spinal afferents subserve an emergency function because, in case of alarm by influxing acid, they stimulate mechanisms of mucosal protection via an efferent‐like release of transmitters. Other sensory neurones signal chemical noxae to the brain, a task that is not confined to spinal afferents because vagal afferents communicate gastric acid and peripheral immune challenges to the brainstem and in this way elicit autonomic, endocrine, affective and behavioural reactions. Emerging evidence indicates that hypersensitivity of extrinsic afferent pathways to mechanical and chemical stimuli makes an important contribution to the abdominal hyperalgesia seen in functional dyspepsia and irritable bowel syndrome. Sensitization may be brought about by inflammatory processes that lead to up‐regulation and functional alterations of receptors and ion channels on sensory neurones. Such sensory neurone‐specific molecules, which include vanilloid (capsaicin) receptors, may represent important targets for novel drugs to treat abdominal pain.
Effect of cholecystokinin‐A receptor blockade on postprandial insulinaemia and gastric emptying in humans
Authors: Hidalgo L. , Clavé P. , Estorch M. , Rodríguez‐Espinosa J. , Rovati L. , Greeley G. H. , Capellà G. , Lluís F.
Published: March 2003

Abstract
 Our aim was determine the relationship between cholecystokinin (CCK)‐A receptor blockade, glucose levels, insulin secretion and gastric emptying in humans, and to assess the effect of CCK‐A blockade on pancreatic polypeptide secretion. After a 12‐h fast, six healthy volunteers were given [99mTc]iminodiacetic acid monosodium salt (IDA) intravenously (5 mCi). One hour later they were offered a 577 kcal liquid meal containing [99mTc]diethylenetriaminepentaacetic acid (DTPA) (2 mCi) and glucose (105 g). Scintigraphic gastric and gallbladder activity, and plasma glucose, insulin and pancreatic polypeptide responses were monitored. In a second experiment, a continuous intravenous infusion of loxiglumide (7.5 mg kg h−1) was started 60 min before and continued until 120 min after test meal ingestion to block the CCK‐A receptors. Gallbladder emptying was blocked by loxiglumide. Loxiglumide accelerated gastric emptying, increased insulin secretion without alteration of glucose profiles, and abolished all phases of the postprandial pancreatic polypeptide response. Blockade of peripheral CCK‐A receptors accelerates gastric emptying of liquids with an increase in postprandial insulin levels. The lack of changes in glycaemia suggests that alternative homeostatic mechanisms also control postprandial glucose levels. Inhibition of pancreatic polypeptide release may reflect an independent effect of loxiglumide on vagal control involved in pancreatic polypeptide release.
Ligand‐gated ion channels in the enteric nervous system
Authors: Galligan J. J.
Published: March 2003

Abstract There are many cell surface receptors expressed by neurones in the enteric nervous system (ENS). These receptors respond to synaptically released neurotransmitters, circulating hormones and locally released substances. Cell surface receptors are also targets for many therapeutically used drugs. This review will focus on ligand‐gated ion channels, i.e. receptors in which the ligand binding site and the ion channel are parts of a single multimeric receptor. Ligand‐gated ion channels expressed by enteric nerves are: nicotinic acetylcholine receptors (nAChRs), P2X receptors, 5‐hydroxytryptamine3 (5‐HT3) receptors, γ‐aminobutyric acid (GABAA) receptors, N‐methyl‐d‐aspartate (NMDA) receptors,α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors and glycine receptors. P2X, 5‐HT3 and nAChRs participate in fast synaptic transmission in S‐type neurones in the ENS. Fast synaptic transmission occurs in some AH‐type neurones, and AH neurones express all the ligand‐gated ion channels listed above. Ligand‐gated ion channels may be localized at extra‐synaptic sites in some AH neurones and these extra‐synaptic receptors may be useful targets for drugs that can be used to treat disorders of gastrointestinal function.
The effect of glucagon‐induced gastric relaxation on TLOSR frequency
Authors: Chang H. Y. , Pandolfino J. E. , Shi G. , Boeckxstaens G. E. , Joehl R. J. , Kahrilas P. J.
Published: March 2003

Abstract This study aimed to determine the effect of glucagon‐induced gastric relaxation on the frequency of transient lower oesophageal sphincter relaxations (TLOSRs). Eight normal subjects (four male, age 18–52 y) were studied after a 6‐h fast using a combined manometric barostat assembly. The recording was divided into two 1‐h sessions: (1) a baseline period with the barostat set at minimal distending pressure (MDP) + 2 mmHg and (2) a period with continuous glucagon or placebo infusion with barostat set at MDP + 2 mmHg. Patients were studied on two different days and randomly received glucagon (4.8 μg kg−1 bolus followed by 9.6 μg kg−1 h−1 infusion) on 1 day and placebo (saline) on another. Lower oesophageal sphincter (LOS) pressure, frequency of TLOSRs, and barostat bag volumes were determined for both placebo and glucagon infusion. Glucagon induced significant fundal relaxation compared with placebo (P < 0.05) and significantly decreased baseline LEOS pressure (P < 0.05). The frequency of TLOSRs was not altered by glucagon infusion compared with placebo. Despite causing substantial proximal stomach relaxation, glucagon did not increase TLOSR frequency. This suggests that the relevant gastric mechanoreceptors responsible for triggering TLOSRs do not respond to passive elongation.
Acute, relapsing brain oedema with diffuse blood–brain barrier alteration and axonal damage in the acquired immunodeficiency syndrome
Authors: Gray  , Bélec  , Chrétien  , Dubreuil‐Lemaire  , Ricolfi  , Wingertsmann  , Poron  , Gherardi
Published: March 2003

A 38‐year‐old homosexual male with AIDS suffered four neurological episodes including headaches, confusion, visual impairment, memory disturbances, and dysarthria which resolved spontaneously in a few days. He was admitted to hospital during a fifth episode. Neurological examination revealed a cerebellar syndrome. General examination was normal. CD4 count was 90. CSF contained two WBCs/mm3 and 12.30 mg/dL protein. MRI revealed diffuse ill defined increased signal on T2‐weighted images in the white matter. His condition worsened rapidly with vomiting and he died 1 month after admission. Neuropathological examination revealed diffuse brain oedema with ventricular compression, central diencephalic herniation and bilateral tonsilar herniation in the absence of a focal lesion. Microscopical examination revealed predominant involvement of the white matter with diffuse myelin pallor and massive perivascular dilatation containing an exudate expressing serum proteins and occasional macrophages. The same exudate was also diffuse in the leptomeninges. Parenchymal damage predominated around the perivascular spaces and included loosening of tissue, axonal damage with spheroids and reactive astrocytosis. There was no evidence of productive HIV encephalitis, no multinucleated giant cells; p24 immunostaining and RT‐PCR for HIV genome were negative. There was neither significant inflammation nor microglial activation. In this illustrative case, the relapsing course of the neurological signs, the diffuse topography of the blood–brain barrier breakdown and the absence of local cause make it likely that the diffuse leak and axonal damage could be related to circulating factors.
Immunohistochemical analysis of cyclin A in astrocytic tumours
Authors: Chakrabarty  , Bridges
Published: March 2003

Cyclins are important regulators of the cell cycle; there is increasing evidence that some cyclins are positively involved in carcinogenesis. Amplification and translocation of the cyclin genes and overexpression of their mRNAs and proteins have been observed in a variety of tumours. We studied cyclin A protein in astrocytic tumours by immunohistochemical analysis. Immunohistochemistry with microwave antigen retrieval was carried out on formalin fixed, paraffin embedded material from 15 glioblastomas (WHO grade IV), 10 anaplastic astrocytomas (WHO grade III), seven diffuse low grade astrocytomas (WHO grade II) and nine pilocytic astrocytomas (WHO grade I) using antibodies against cyclin A and a proliferation marker MIB1. Staining for these antibodies was seen mainly in the tumour cell nuclei; 66% of all cases showing staining for cyclin A and 95% of all cases staining for MIB1. Mean labelling indices (LI) for cyclin A were higher in glioblastoma (mean LI‐6.7) and anaplastic astrocytoma (mean LI‐5.9) than low grade diffuse astrocytoma (mean LI‐1.7) and pilocytic astrocytoma (mean LI −0.12), although there was no clear cut off point between the various tumour types. A good correlation was seen between labelling indices of cyclin A and MIB1 (Pearson correlation coefficient r=0.59, P<0.0001). Cyclin A is variably expressed in astrocytic tumours, either reflecting increased tumour proliferation (cyclin A being an integral component of the cell cycle), an alteration of its gene, protein upregulation or regulation of apoptosis. The genetic basis of expression of cyclin A in astrocytic tumours remains to be determined.
Expression of neuronal markers in oligodendrogliomas: an immunohistochemical study
Authors: Wharton  , Chan  , Hamilton  , Anderson
Published: March 2003

The oligodendroglioma has been considered to be a tumour showing oligodendrocyte differentiation, but studies of the expression of oligodendrocyte markers have not conclusively demonstrated this and the pattern of differentiation of this tumour remains uncertain. Recent studies have suggested that some oligodendrogliomas may show neuronal differentiation. The aim of this study was to determine whether there was evidence of neuronal differentiation in a series of oligodendrogliomas, and, if so, to determine whether this identified a biologically or clinically distinct group. Immunohistochemistry was carried out on paraffin sections using antibodies to synaptophysin, phosphorylated and non‐phosphorylated neurofilament proteins. An archival series of 32 oligodendrogliomas had been previously characterized for histological features, histological grade, Ki‐67 labelling index, apoptosis index and prognosis. Six per cent of tumours showed expression of synaptophysin. Thirty‐one per cent of cases showed expression of neurofilament proteins with an antibody to non‐phosphorylated epitopes, but no cases were positive with antibodies to phosphorylated neurofilament epitopes. Tumours showing expression of neuronal markers did not show a difference in the distribution of histological grade or GFAP expression from those which did not express these markers, and there was no difference in labelling indices or prognosis between the two groups. In conclusion, a subset of oligodendrogliomas showed expression of neuronal lineage markers; this is discussed in relation to histogenesis and differential diagnosis. The expression of such markers did not identify a biologically or clinically distinct subgroup.
Laminar specific loss of isocortical presenilin 1 immunoreactivity in Alzheimer's disease. Correlations with the amyloid load and the density of tau‐positive neurofibrillary tangles
Authors: Colle M. ‐A. , Duyckaerts C. , Laquerrière A. , Pradier L. , Czech C. , Checler F. , Hauw J. ‐J.
Published: March 2003

Presenilin 1 has been shown to be mutated in a high proportion of cases of familial Alzheimer's disease. Immunoreactive epitopes of the protein have been found mainly in neurones devoid of neurofibrillary tangles – an observation that has led to the conclusion that presenilin 1 could have a protective role. In this study, the relationship between deposits of Aβ peptide (both the 40 and 42 isoforms), tau positive neurofibrillary tangles and presenilin 1‐positive neuronal profiles were analysed in three cases of presenilin 1 mutation, four cases of sporadic Alzheimer's disease and five controls. Immunohistochemistry was performed in a sample from the supramarginal gyrus. The proportion of volume occupied by the Aβ1–40 and Aβ1–42 deposits (amyloid load) was evaluated by a point‐counting technique. Tau‐positive neurofibrillary tangles, and presenilin 1‐positive neuronal profiles were directly counted. The location of the lesions in the thickness of the cortex was recorded. The density of PS1‐positive neuronal profiles in Alzheimer's disease cases was lower than in the controls. The deficit was significant only in the upper layers of the cortex. The density of presenilin 1 neuronal profiles was negatively correlated with Aβ1–40 and Aβ1–42 loads, and with the density of tau‐positive neurofibrillary tangles. Multivariate analysis showed that the Aβ1–42 load was the best determinant of the decrease in presenilin 1‐positive neuronal profiles. Presenilin 1‐positive neurones appear to be lost rather than protected in the course of Alzheimer disease.
The ubiquitin protein catabolic disorders
Authors: Layfield Robert , Alban Andrew , Mayer R. John , Lowe James
Published: March 2003

The ubiquitin–proteasome system of intracellular proteolysis is essential for cell viability. We propose the concept that neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as other conditions including some types of cancer, collectively represent a raft of ‘ubiquitin protein catabolic disorders’ in which altered function of the ubiquitin–proteasome system can cause or directly contribute to disease pathogenesis. Genetic abnormalities within the ubiquitin pathway, either in ubiquitin‐ligase (E3) enzymes or in deubiquitinating enzymes, cause disease because of problems associated with substrate recognition or supply of free ubiquitin, respectively. In some cases, mutations in protein substrates of the ubiquitin–proteasome system may directly contribute to disease progression because of inefficient substrate recognition. Mutations in transcripts for the ubiquitin protein itself (as a result of ‘molecular misreading’) also affect ubiquitin‐dependent proteolysis with catastrophic consequences. This has been shown in Alzheimer's disease and could apply to other age‐associated neurodegenerative conditions. Within the nervous system, accumulation of unwanted proteins as a result of defective ubiquitin‐dependent proteolysis may contribute to aggregation events, which underlie the pathogenesis of several major human neurodegenerative diseases.
Childhood meningiomas associated with meningioangiomatosis: report of five cases and literature review
Authors: Kim N. R. , Choe G. , Shin S.‐H. , Wang K.‐C. , Cho B.‐K. , Choi K. S. , Chi J. G.
Published: March 2003

Meningioangiomatosis is a unique, rare hamartomatous lesion. Meningiomas arising in the background of meningioangiomatosis are rare conditions which pathologically and radiologically mimic invasive meningiomas, but have a benign clinical course in children and young adults. In this study, five such cases are reported. To our knowledge, this is the largest reported collection of meningiomas associated with meningioangiomatosis. Less immunoreactivity for progesterone receptor and high Ki‐67 labelling index are generally known to be associated with invasive meningiomas. However, high expression of progesterone receptor and low Ki‐67 labelling index in the present cases supports the idea that brain invasion is not an indicator of malignancy but an independent finding associated with meningiomas which have arisen from meningioangiomatosis. We emphasize the good prognosis of such tumours and discuss pathogenesis of meningiomas with meningioangiomatosis.
Cytokines and neurotrophic factors fail to affect Nogo‐A mRNA expression in differentiated human neurones: implications for inflammation‐related axonal regeneration in the central nervous system
Authors: Satoh J.‐I. , Kuroda Y.
Published: March 2003

Nogo is a novel myelin‐associated inhibitor of neurite outgrowth which regulates stable neuronal connections during axonal regeneration following injury in the adult mammalian central nervous system (CNS). Because cytokines and neurotrophic factors play a key role in inflammation‐related axonal regeneration, we investigated: (i) the constitutive expression of Nogo and the Nogo receptor (NgR) mRNA in human neural cell lines; (ii) Nogo and NgR mRNA levels in the NTera2 human teratocarcinoma cell line during retinoic acid (RA)‐induced neuronal differentiation; and (iii) their regulation in NTera2‐derived differentiated neurones (NTera2‐N) after exposure to a battery of cytokines and growth factors potentially produced by activated glial cells at post‐traumatic inflammatory lesions in the CNS. By reverse transcriptase‐polymerase chain reaction analysis, the constitutive expression of Nogo‐A, the longest isoform of three distinct Nogo transcripts and NgR mRNA was identified in a wide variety of human neural and non‐neural cell lines. By Northern blot analysis, the levels of Nogo‐A mRNA were elevated markedly in NTera2 cells following RA‐induced neuronal differentiation, accompanied by an increased expression of the neurite growth‐associated protein GAP‐43 mRNA. In contrast, Nogo‐A, Nogo‐B, NgR and GAP‐43 mRNA levels were unaltered in NTera2‐N cells by exposure to basic fibroblast growth factor, brain‐derived neurotrophic factor, glia‐derived neurotrophic factor, tumour necrosis factor‐α, interleukin‐1β, dibutyryl cyclic AMP or phorbol 12‐myristate 13‐acetate. These results indicate that both Nogo‐A and NgR mRNA are coexpressed in various human cell types, including differentiated neurones, where their expression is unaffected by exposure to a panel of cytokines and neurotrophic factors which might be involved in inflammation‐related axonal regeneration in the CNS.
Glycosphingolipid lysosomal storage diseases: therapy and pathogenesis
Authors: Jeyakumar M. , Butters T. D. , Dwek R. A. , Platt F. M.
Published: March 2003

Paediatric neurodegenerative diseases are frequently caused by inborn errors in glycosphingolipid (GSL) catabolism and are collectively termed the glycosphingolipidoses. GSL catabolism occurs in the lysosome and a defect in an enzyme involved in GSL degradation leads to the lysosomal storage of its substrate(s). GSLs are abundantly expressed in the central nervous system (CNS) and the disorders frequently have a progressive neurodegenerative course. Our understanding of pathogenesis in these diseases is incomplete and currently few options exist for therapy.

In this review we discuss how mouse models of these disorders are providing insights into pathogenesis and also leading to progress in evaluating experimental therapies.
The age‐related decrease in CNS remyelination efficiency is caused by an impairment of both oligodendrocyte progenitor recruitment and differentiation
Authors: Zhao C. , Sim F. J. , Penderis J. , Franklin R. J. M.
Published: March 2003

Developing strategies to reverse the age‐associated decline in CNS remyelination requires the identification of how the regenerative process is impaired. We have addressed whether remyelination becomes slower because of an impairment of recruitment of oligodendrocyte progenitors (OPs) or, an impairment of OP differentiation into remyelinating oligodendrocytes. The OP response during remyelination of focal, toxin‐induced CNS demyelination in young and old rats was compared by in situ hybridization using probes to PGDF‐αR, and the OP transcription factor, MyT1. The expression patterns for both OP markers are very similar and reveal a delay in the colonization of the demyelinated focus with OPs in the old animals compared to young. By comparing the mRNA expression pattern MyT1 with that of the myelin proteins MBP and Gtx, we have found that in the old animals there is also a delay in OP differentiation, which increases with longer survival times. These results indicate that the age‐associated decrease in remyelination efficiency occurs because of an impairment of OP recruitment and their subsequent differentiation into remyelinating oligodendrocytes, and that strategies aimed at ameliorating the age‐associated decline in remyelination efficiency will therefore need to promote both components of the regenerative process.
Factors influencing tumour cell and vascular proliferation in glioblastoma
Authors: Chan P. T. H. , Weller R. O.
Published: March 2003

Introduction:  This project examines the factors that influence tumour cell and vascular proliferation in glioblastomas.

Hypothesis:  Necrosis is a major factor inducing tumour cell and vascular proliferation in glioblastomas.

Material and methods:  5 µm paraffin sections from 10 cases of glioblastoma containing areas of normal brain, viable tumour and necrosis were stained with H&E, reticulin and by immunocytochemistry for GFAP, Ki‐67, CD34 for blood vessel endothelium, a combined Ki‐67/CD34, and CD68 for macrophages and microglia. Tumour cell proliferation in Ki‐67 preparations was measured in relation to (a) distance from necrosis and (b) proximity to blood vessels. The density of blood vessels was related to the distance from necrosis, and the presence of macrophages was related to the distance from necrosis and to the proximity to blood vessels. These measurements were effected by an automated computer quantification algorithm and by field‐specific ocular quantification.

Results:  The mean tumour proliferation index (PI) was 6.49% (±4.95), with a two‐fold increase in tumour cell PI to 12.36% ± 5.82 (P ≤ 0.001) in the vicinity of blood vessels. The density of blood vessels was increased in the vicinity of areas of necrosis. Macrophages were distributed throughout the tumour, but were increased around areas of necrosis and around blood vessels. No relationship between tumour cell proliferation and necrosis was detected.

Conclusions:  Tumour cell proliferation is concentrated around blood vessels in glioblastomas. Blood vessel proliferation, but not tumour cell proliferation, is related to areas of necrosis and the presence of macrophages in glioblastomas. Targeting of blood vessel proliferation and macrophages within glioblastoma may present a therapeutic strategy for treatment of these devastating tumours.
Familial hemi‐polymicrogyria and neurofibromatosis type 1
Authors: McLellan A. , Harding B. , Cross H.
Published: March 2003

Background:  There have been rare reports of cerebral cortical malformations occurring in individuals with neurofibromatosis type 1 (NF1) but, to our knowledge, none with polymicrogyria. This communication concerns two brothers with right unilateral hemipolymicrogyria, one of who clinically has NF1.

Observations:  The index case, a boy, presented at 22 months of age with macrocephaly and developmental delay, cutaneous stigmata of NF1 and a mild left hemiplegia. He developed drug resistant epilepsy, which led to focal resective surgery. Full‐scale IQ was 64 with poor memory performance. MRI demonstrated right hemisphere polymicrogyria, while functional imaging involving passive movement of the left hand showed activation in the dysplastic right sensorimotor cortex. Neuropathological examination of the focal resection confirmed polymicrogyria. His older brother showed mild learning difficulties at school but does not have cutaneous signs of NF1 or epilepsy. Psychometry revealed IQ of 87 with difficulties in working memory. Structural and functional MRI studies were similar to his brother.

Comment:  Both brothers show extensive hemipolymicrogyria, with similar functional imaging and neuropsychological profiles, but only one brother has signs of NF1. Several maternal relatives also have NF1, and presently genetic studies are being undertaken to determine possible causal links or an independent mutation.
Third ventricular chordoid glioma: clinicopathological features of two cases
Authors: Kurian K. M. , Statham P. F. X. , Smith C. , Bell J. E. , Ironside J. W.
Published: March 2003

Introduction:  Primary brain tumours occupying the third ventricle form a heterogenous group of uncommon lesions including colloid cysts, choroid plexus tumours, ependymoma, pilocytic astrocytoma, germinoma and pineal parenchymal tumours. Recently Brat et al. (J Neuropathol Exp Neurol 1998; 57: 238) described a tumour of the third ventricle composed of epithelioid cells with eosinophilic cytoplasm, extracellular mucin as well as a lymphoplasmacytic infiltrate. Although they resembled chordoma and chordoid meningioma histologically, immunohistochemistry demonstrated that these tumours were in fact glial in nature. These tumours have therefore been termed third ventricular chordoid glioma. They characteristically lack the chromosomal and genetic alterations commonly found in other types of gliomas or meningiomas (Reifenberger et al. Brain Pathol 1999; 9: 617). We describe the clinicopathological features of two recent cases of chordoid glioma that presented to the Department of Neuropathology, Western General Hospital, Edinburgh.

Results:

Case 1 (238/01)

Case 2 (474/01)

Sex
Female

Female

Age
32 years

37 years

Presentation
Mild but progressive
Acute hydrocephalus

 visual failure, weight

  increase of 25.5 kg

  over 4 years
 headache, memory

  problems, collapse

Imaging
Lower lateral third
Third ventricular

 ventricle/ Hypothalamic

  lesion
 lesion

Immuno.
Ki67
<1%
<1%

GFAP
+++
+++

VIM
+++
+++

EMA
++
++

Conclusions:  The two cases of chordoid glioma we describe have slightly different clinical presentations and different appearances on histology. Understanding these variations will aid diagnosis of this unusual tumour.
Selective loss of inhibitory neurons in the cerebral cortex in motor neuron disease
Authors: Maekawa S. , Cotter D. , Leigh N. , Al‐Sarraj S.
Published: March 2003

Introduction:  Motor neuron disease (MND) is characterized by selective loss of upper and lower motor neurons, although other CNS regions may also be affected (Abrahams et al. Brain 1996; 119: 2105; Lloyd et al. Brain 2000; 123: 2289). We previously demonstrated reduced neuronal density within extra‐motor cortical areas associated with astrocytic and microglial activation. We have now explored whether selective loss of inhibitory (GABAergic) neurones occurs in MND.

Material and methods:  The density of inhibitory interneurons immunoreactive for the calcium‐binding proteins calbindin‐D28K (CB), calretinin (CR), and parvalbumin (PV) was determined via quantitative image analysis in the primary motor cortex (PMC; Brodmann's area 4) and dorsolateral prefrontal cortex (DLPFC; Brodmann's area 9) from 13 MND and eight control cases, matched for age and postmortem interval.

Results:  There was a significant reduction in CB‐+ve densities within lamina II of both area 4 and 9 in MND (Wilk's lambda multivariate test: P = 0.003). However, post hoc comparisons of individual regions showed that these changes were only significant in area 9 (P = 0.046). PV‐+ve densities within cortical layer VI were significantly reduced in MND in both regions (P = 0.015), whereas the multivariate test showed no significant difference within the two regions (P = 0.951).

Conclusions:  These findings reveal a selective loss in the density of subpopulations of GABAergic neurons in PMC and DLPFC in MND.
Concerning Kuru plaques alias ‘cactus’, ‘stellate’, ‘hairy’ or ‘asteroid’ bodies
Authors: Duckett S.
Published: March 2003

Klatzo, Gadusek and Zigas described nodular swellings of dendrites of Purkinje cells in their study of the neuropathology of Kuru as ‘the presence of remarkable plaque‐like structures’ (Laboratory Invest 1959; 8: 799). Henceforth these structures were named ‘Kuru plaques’ and were considered to be specific or nearly specific for Kuru. However, this is not quite the case. Such plaques or bodies had been described and profusely illustrated in animal and human neurological diseases by Cajal (1907, 1911, 1926), Nageotte and Leon‐Kindberg (1908, 1910), Hechst (1929), Von Santha (1930), Norman (1940), Hunter and Russell (1954) and Fowler and Robertson (also in 1959), among others. They were variously named as cactus, stellate, asteroid or hairy bodies. In 1963, Friede referred to these bodies and axonal torpedoes as ‘nonspecific injury responses’. This presentation is a review of the literature concerning these bodies. Their history illustrates Raymond Garcin's observation: ‘Tout àétéécrit mais pas tout àété lu’ (everything has been written but not everything has been read).
Epidemiological issues in perinatal outcomes research
Authors: Jackson  , Lang  , Ganiats
Published: March 2003

Outcomes research takes an expansive view of health and seeks to improve the science of evaluating the quality of health care by refining traditional clinical measures and including measures of overall patient well‐being. This broader view of health (rather than disease) is especially appropriate in perinatal research. Attention to the perinatal period requires recognition that pregnancy is in most cases a healthy life event, that there is a predictable progression and time course with a key definable outcome (delivery) and that there are two patients, mother and infant. Two issues stand out as methodological challenges in the design and conduct of perinatal outcomes studies. The first is to establish baseline comparability across study groups with regard to case‐mix or perinatal risk, and also comparability of services other than the one under study. The second is the refinement of traditional perinatal outcomes, such as low birthweight and Caesarean section, and the inclusion of patient‐based health status measures, such as health‐related quality of life, for the peripartum woman and her newborn.
Stillbirths and neonatal encephalopathy in Kathmandu, Nepal: an estimate of the contribution of birth asphyxia to perinatal mortality in a low‐income urban population
Authors: Ellis  , Manandhar  , Manandhar  , Wyatt  , Bolam  , Costello
Published: March 2003

We describe a prospective cross‐sectional survey over a 12‐month period in the principal maternity hospital of Kathmandu, Nepal, where over 50% of the local population deliver. The study aim was to estimate the contribution of birth asphyxia to perinatal mortality in this setting. During 1995, there were 14 371 livebirths and 400 stillbirths, a total stillbirth rate of 27 per 1000 total births. The fresh term (2000 g or more) stillbirth rate was 8.5 per 1000 total births [95% CI 7.1, 10.1]. Ninety‐two cases of neonatal encephalopathy (NE) affecting term infants were detected (excluding those due to congenital malformations, hypoglycaemia and early neonatal sepsis). The birth prevalence of NE was 6.4 per 1000 livebirths [95% CI 5.2, 7.8]. There was evidence of intrapartum compromise in 63 (68%) of the cases of NE and 65 (76%) of the stillbirths, but only in 12 (12%) of controls. The cause‐specific early neonatal mortality rate for NE was 2.1 per 1000 livebirths [95% CI 1.4, 3.0]. Combining the NE deaths and fresh stillbirths gives an upper estimate for term birth asphyxia perinatal mortality rate of 10.8 per 1000 total births [95% CI 9.2, 12.6], 24% of all perinatal deaths before hospital discharge. This study suggests that birth asphyxia remains an important cause of perinatal mortality in developing countries. The paper discusses the pros and cons of different strategies to reduce birth asphyxia in low‐income countries.
Stress and pregnancy among African‐American women
Authors: Renae Stancil Tonya , Hertz‐Picciotto Irva , Schramm Margaret , Watt‐Morse Margaret
Published: March 2003

Research on stress tends to support an adverse effect on pregnancy outcomes, and suggests that the impact of these stressors is modified by social class and/or race. This study explicitly examined social factors such as experiences of discrimination, either racial or sexual, and neighbourhood crime as predictors of stress. We also examined cortisol and stress as predictors of blood pressure. A subsample of 94 African‐American pregnant women, aged 18–39 years, who were enrolled in a longitudinal study of pregnancy and exposure to lead in the environment were used in this analysis. The women were patients at an obstetrics clinic at Magee Women’s Hospital in Pittsburgh, PA, USA. Younger age, higher income, lower education and experiences of discrimination, both racial and sexual, were related to greater perceived stress; however, life events were not related to perceived stress. Higher income and urinary cortisol adjusted for creatinine were related to systolic blood pressure after the 36th week. As a body of evidence suggests that stress can have deleterious effects in both pregnant and non‐pregnant women, future research should examine these forms of discrimination, especially racial discrimination, as a possible reason for the disparity in adverse pregnancy outcomes between African‐American and white women.
Central nervous system tumours in children in Costa Rica, 1981–96
Authors: Reutfors Johan , Kramárová Eva , Weiderpass Elisabete , Monge Patricia , Wesseling Catharina , Ahlbom Anders
Published: March 2003

Incidence rates of malignant central nervous system (CNS) tumours in children in Costa Rica are presented in an international perspective. For the 16‐year period 1981–96, a total of 256 CNS tumours were registered in children below age 15 years by the National Tumour Registry of Costa Rica. The age‐standardised incidence rate was 15.2 per million person–years, with a male‐to‐female ratio of 1.4. The median age‐standardised incidence rates of selected registries in other Latin American countries were 19.3, in other developing countries 12.0 and in industrialised countries 29.6 per million person–years. The comparatively low incidence rates in Costa Rica were evident in all diagnostic subgroups, most notably in the youngest age group and for tumours in the brain stem. In the Central Valley, where the capital and the only specialised paediatric hospital are situated, the crude incidence rate was 18.1 [95% CI 15.1, 21.1] compared with 10.5 [95% CI 8.3, 12.8] per million person–years in the rest of the country (RR = 1.7, 95% CI 1.3, 2.3). There was no evidence of any increase over time. The data in this study cannot exclude under‐diagnosis and, to a lesser degree, under‐registration as a partial explanation of the low incidence rates of malignant CNS tumours in children in Costa Rica.
Epidemiology of neonatal necrotising enterocolitis: a population‐based study
Authors: Llanos Adolfo R. , Moss Mark E. , Pinzòn Maria C. , Dye Timothy , Sinkin Robert A. , Kendig James W.
Published: March 2003

We examined the birthweight‐, gender‐ and race‐specific incidence as well as the biodemographic and clinical correlates of necrotising enterocolitis (NEC) in a well‐defined six‐county perinatal region in upstate New York. We conducted a retrospective, 8‐year population‐based survey to identify all cases of proven NEC (modified Bell stage II and above) in the area's regional neonatal intensive care unit (NICU). The denominator used to calculate the incidence was obtained from the Statewide Planning Research Cooperative System. Incidence was expressed as cases per 1000 live births. A total of 85 documented cases of proven NEC was identified in a six‐county perinatal region that experienced 117 892 live births during the 8‐year period. The average annual incidence was 0.72 cases per 1000 live births [95% CI 0.57, 0.87 per 1000 live births]. The highest incidence of NEC occurred among infants weighing 750–1000 g at birth and declined with increasing birthweight. The urban county had a 1.53 times higher risk of NEC than rural counties [95% CI 0.9, 2.6]. The overall incidence of NEC for non‐Hispanic blacks was significantly greater than that for non‐ Hispanic whites (2.2 vs. 0.5 cases per 1000 live births, P = 0.00). The differences remained statistically significant even after correction for birthweight. Most cases (93%) in this series were preterm (gestational age <37 weeks). Only two patients were never fed before the diagnosis of NEC was confirmed. Positive blood cultures were documented in 27% of the cases with a predominance of Gram‐negative enteric micro‐organisms. NEC remains an important health problem especially for preterm infants and the non‐Hispanic black population.
Cytokine mRNA levels in the hearts of inbred mice that develop different degrees of cardiomyopathy during infection with Trypanosoma cruzi
Authors: POWELL MALCOLM R. , MORGAN JULIETTE , GUARNER JEANNETTE , COLLEY DANIEL G.
Published: March 2003

Profiles of cytokine mRNA expression were examined by semiquantitative RT‐PCR in the hearts of DBA/2 (pathopermissive) and B10.D2 (pathoresistant) mice during infection with the Brazil strain of Trypanosoma cruzi. The levels and time‐course profiles of IFNγ, IL‐1β and IL‐10 mRNA expression were similar in each strain. TNFα, iNOs, and IL‐13 mRNA expression peaked at comparable levels and times after infection in each strain, but declined more rapidly in B10.D2 than in DBA/2 mice. Peak IL‐2 mRNA levels were also similar between the two strains, but occurred earlier in DBA/2 than in B10.D2 mice. Levels of IL‐4, IL‐6 and IL‐12 mRNA were significantly higher in DBA/2 than in B10.D2 mice from day 10 through day 50 of infection. With the exception of IL‐1β, which was expressed constitutively in both strains, the levels of mRNA of all other cytokines examined reached their peak no later than day 20 and declined significantly by day 50 after infection. The inflammatory infiltrate paralleled the latter cytokines; starting at day 10 in DBA/2 mice and at day 15 in the B10.D2 s, peaking between days 20 and 30 in both strains, decreasing to minimal levels by day 50 in the pathoresistant mice, but maintaining a mild amount through day 70 in the pathopermissive strain. The inflammation was composed mostly of lymphocytes and histiocytes throughout the entire process. These data demonstrate differences in the profiles of cytokine mRNA that may be related to the differential degree of cardiac pathology that develops in these two strains of mice upon infection with T. cruzi.
Comparison of antibody and protective immune responses against Trypanosoma cruzi infection elicited by immunization with a parasite antigen delivered as naked DNA or recombinant protein
Authors: LÚCIA PEREIRA‐CHIOCCOLA VERA , COSTA FABIO , RIBEIRÃO MARCELO , SOARES IRENE S. , ARENA FERNANDA , SCHENKMAN SERGIO , RODRIGUES MAURICIO M.
Published: March 2003

Immunization with naked DNA represents an attractive strategy for development of vaccines against a variety of infections including those caused by protozoan parasites. Recently, we have described that immunization with a plasmid containing the trans‐sialidase (TS) gene induced protective immunity against Trypanosoma cruzi infection in BALB/c mice. The present study was aimed at examining and comparing the effectiveness of immunization using either plasmid or recombinant delivered antigens in a mouse strain highly susceptible to infection (A/Sn). Two plasmids were generated containing the coding region for the catalytic domain of TS. TS gene was inserted into pcDNA3 vector with or without the coding region for TS signal peptide. These two plasmids were found to be equally immunogenic at inducing antibodies to TS or inhibition of T. cruzi infection. A third plasmid, in which the TS gene was inserted into the vector VR1012, was as immunogenic as the two others. Immunization with a TS recombinant protein in alum generated a significantly higher antibody response as measured by ELISA or inhibition of TS enzymatic activity. Most relevant, this immunization reduced the mortality due to acute infection.
Leishmania major infection in interleukin‐4 and interferon‐γ depleted mice
Authors: Chatelain René , Mauze Smita , Varkila Kari , Coffman Robert L.
Published: March 2003

The outcome of experimental Leishmania major infection in mice is closely correlated with the type of CD4+ helper T cell (Th) response. Whereas a Th1 response is host protective, a Th2 response leads to a disseminated, fatal course of disease. Previous studies in this murine model have shown, that the two prominent Th1 and Th2 cytokines, interferon (IFN)‐γ and interleukin (IL)‐4, themselves play a major role in the determination of the resulting Th response. Treatment of susceptible mouse strains (BALB/c) with anti‐IL‐4 induces a Th1 response, allowing the animals to cure the infection. Treatment of resistant strains (e.g. C3H/HeN) with anti‐IFN‐γ induces a Th2 response with dissemination of the disease. In this report, we investigated the course of infection and Th response in susceptible and resistant mice treated with anti‐IL‐4 and anti‐IFN‐γ simultaneously. Both mouse strains showed an initial exacerbation of the disease and an overall reduced cytokine response early after infection. Later during infection both strains had a strong Th1 response that was resulting in cure of disease in C3H/HeN mice. BALB/c mice however, could not control the spread of infection despite the strong Th1 response.
Differentially enhanced cytokine gene expression in CD4+ and CD8+ T cells in mesenteric lymph nodes in rats infected with Nippostrongylus brasiliensis
Authors: Matsuda Shinji , Uchikawa Ryuichi , Yamada Minoru , Arizono Naoki
Published: March 2003

Infection with the nematode Nippostrongylus brasiliensis upregulates the expression of type 2 cytokine genes in rat mesenteric lymph node (MLN) cells, as we reported previously. Here, we compared the spectrum of cytokine gene expression in CD4+ and CD8+ T cells in MLN. After infection, CD4+ T cells showed high levels of expression of interleukin (IL)‐3, IL‐4, IL‐5, and IL‐13 genes, expression of which was scarcely detected before infection. In CD8+ T cells, IL‐3, IL‐5, and IL‐13 mRNAs increased greatly, but IL‐4 mRNA was not detected at all after infection. IL‐10 message was strongly enhanced in CD8+ T cells after infection, while detected at high levels before and after infection in CD4+ T cells. Nematode infection induced CD8+ T cells to express the inhibitory cytokines IL‐10 and IL‐13, but not IL‐4. The role of CD8+ T cells in nematode infection is discussed.
Reversal in microfilarial density and T cell responses in human lymphatic filariasis
Authors: Sartono Erliyani , Lopriore Cristina , Kruize Yvonne C.M. , Kurniawan‐Atmadja Agnes , Maizels Rick M. , Yazdanbakhsh Maria
Published: March 2003

This study reports reversals in microfilarial density and the accompanying changes in cellular immune responses to filarial antigens of 39 individuals (11 microfilaria‐positives, 22 microfilaria‐negatives and six converters) living in an area endemic for brugian filariasis. Microfilarial counts decreased from April, the end of the rainy season to July, middle of the dry season (g.m. 88 mf/ml and 38 mf/ml, respectively; P = 0.001) and subsequently increased in November, the beginning of the rainy season (P = 0.088). Whereas the proliferative responses remained low throughout the study period in microfilaraemic individuals, in amicrofilaraemics these responses changed in the opposite direction to that of microfilarial densities. In three converters, proliferation changed in the opposite direction to the presence or absence of microfilariae. Cytokine analysis in the converters revealed that interferon‐γ was most affected by the shifts in microfilarial densities. In contrast, interleukin‐4 responses showed little correlation with changes in parasite densities.