bluuebunny/crossref_metadata_2025 huggingface dataset:
Extradural Thoracic Arteriovenous Malformation in a Patient with Klippel-Trenaunay-Weber Syndrome: Case Report
Authors: Alexander Michael J. , Grossi Peter M. , Spetzler Robert F. , McDougall Cameron G.
Published: July 2004

OBJECTIVE AND IMPORTANCE

Spinal cord involvement in Klippel-Trenaunay-Weber (KTW) syndrome is rare. Cases of intradural spinal cord arteriovenous malformations (AVMs) have been associated with this syndrome. Likewise, cases of epidural hemangioma and angiomyolipoma have been reported to occur at the same segmental level as cutaneous hemangioma in KTW syndrome. This report details a rare case of an extradural thoracic AVM in a patient with KTW syndrome.

CLINICAL PRESENTATION

A 30-year-old man presented with a 10-month history of progressive myelopathy, bilateral lower-extremity weakness, and numbness, with the right side affected more than the left. His symptoms had progressed to the point that he was unable to walk. The patient had the characteristic manifestations of KTW syndrome, including numerous cutaneous angiomas and cavernomas, limb hypertrophy and syndactyly, and limb venous malformations. A magnetic resonance imaging scan and subsequent angiogram demonstrated a large extradural AVM causing cord compression at the T3–T4 levels.

INTERVENTION

The patient underwent two separate endovascular procedures, including embolization of upper thoracic and thyrocervical trunk feeders. Subsequently, he underwent T1–T4 laminectomy and microsurgical excision of the AVM. Clinically, the patient improved such that he could walk without assistance.

CONCLUSION

KTW syndrome represents a spectrum of clinical presentations. Although involvement of the spinal cord is uncommon, the manifestations of this syndrome may include both intradural and extradural AVMs in addition to various tumors.
Brainstem Infarction after Delayed Thrombosis of a Stented Vertebral Artery Fusiform Aneurysm: Case Report
Authors: Levy Elad I. , Boulos Alan S. , Bendok Bernard R. , Kim Stanley H. , Qureshi Adnan I. , Guterman Lee R. , Hopkins L. Nelson
Published: July 2004

OBJECTIVE AND IMPORTANCE

Recent technological advances have provided clinicians with stents that can be navigated throughout the tortuous proximal vessels of the posterior intracranial circulation. There have been few reports of fusiform and wide-necked aneurysms treated with stents. Of the known risks involved in stent placement in the intracranial circulation, delayed stent thrombosis has not been well described.

CLINICAL PRESENTATION

A 34-year-old man who experienced the sudden onset of a severe headache with increasing lethargy was found on computed tomographic imaging to have a subarachnoid hemorrhage. Angiography revealed a left vertebral artery fusiform aneurysm that incorporated the posteroinferior cerebellar artery origin.

INTERVENTION

A low-porosity Magic Wallstent (Boston Scientific, Natick, MA) was placed in the left vertebral artery across the aneurysm and the origin of the posteroinferior cerebellar artery. Angiography performed 9 days later revealed significant reduction in filling of the aneurysm. The patient returned 3 months after stent placement with severe neurological deterioration from a brainstem infarction caused by complete thrombotic occlusion of the left vertebral artery at the stented segment of the vessel.

CONCLUSION

Stenting of fusiform aneurysms has provided an alternative to surgical clipping or parent vessel reconstruction. With the increasing frequency of intracranial stent placement for various cerebrovascular disease entities, we must become aware of potential complications associated with these procedures. Such awareness may influence decision-making processes regarding treatment and follow-up care.
Necrotizing Neurosarcoidosis of the Cranial Base Resembling an en Plaque Sphenoid Wing Meningioma: Case Report
Authors: Tobias Samuel , Prayson Richard A. , Lee Joung H.
Published: July 2004

OBJECTIVE AND IMPORTANCE

Necrotizing sarcoid granuloma (NSG) has been recognized as a histological variant of sarcoidosis. Two cases of neurosarcoidosis (NS) with NSG with concomitant systemic disease have been described previously. We present an unusual case of primary NS-NSG that resembled an en plaque cranial base meningioma.

CLINICAL PRESENTATION

A 51-year-old man presented with a 3-month history of progressive left visual deterioration and proptosis. Brain magnetic resonance imaging demonstrated a large cranial base lesion occupying the left anterior clinoid process and sphenoid wing, extending to the left frontotemporal convexity. A second dura-based lesion was observed in the right parietal convexity. Both lesions enhanced homogeneously after administration of intravenous contrast medium. Magnetic resonance imaging characteristics were consistent with a typical clinoidal meningioma with an en plaque extension laterally.

INTERVENTION

A left frontotemporal craniotomy with extradural removal of the anterior clinoid process was performed. When the dura was opened, a red fibrous mass was identified. Intraoperative histological analysis revealed the presence of necrotizing and noncaseating granulomas. Postoperatively, cerebrospinal fluid, erythrocyte sedimentation rate, C-reactive protein, and serum and cerebrospinal fluid angiotensin-converting enzyme values were normal. The search for acid-fast bacilli or fungi was negative. A diagnosis of primary NS-NSG was made. The patient began long-term high-dose corticosteroid therapy. One and a half years after surgery, his vision had improved significantly and the lesions were stable as revealed by magnetic resonance imaging.

CONCLUSION

The first case of primary NS-NSG in the absence of systemic sarcoidosis is reported. NS should be included in the differential diagnosis of dura-based lesions resembling meningioma.
Vertebroplasty for Osteoporotic Compression Fractures: Current Practice and Evolving Techniques
Authors: Peters Keith R. , Guiot Bernard H. , Martin Pamela A. , Fessler Richard G.
Published: July 2004

PERCUTANEOUS VERTEBROPLASTY WAS developed in France by Deramond et al., who provided initial reports of the procedure in 1987. This minimally invasive procedure uses a large-bore bone-cutting needle to percutaneously access a vertebral body, inject bone cement, and thereby stabilize and reinforce the remaining bone structure. The procedure was used initially to treat aggressive hemangiomas, but it then was extended to the treatment of osteolytic metastases and myeloma and currently osteoporotic compression fractures refractory to medical therapy. In this article, we review the current technique and its indications along with emerging devices and areas of current research.
Extracoelomic Mini Approach for Anterior Reconstructive Surgery of the Thoracolumbar Area
Authors: ElSaghir Hesham
Published: July 2004

OBJECTIVE

An extracoelomic mini approach is introduced as a less invasive technique for surgery of the thoracolumbar area performed via the anterior approach.

METHODS

Twenty-one patients with spinal pathological findings at the thoracolumbar junction were assessed. The reasons for surgery were as follows: burst fracture of the first lumbar vertebra (n = 5), degenerative disc at L1–L2 (n = 4), spondylodiscitis at L1–L2 (n = 8) and at T11–L1 (n = 1), pathological fracture of the first lumbar vertebra (n = 2), and pseudarthrosis at T11–L1 after failed reconstruction (n = 1). The anterior surgical procedure was performed via an extracoelomic mini approach. Intersomatic fusion was performed in 13 patients, corpectomy and bone grafting in 4, corpectomy and vertebral replacement with titanium cage packed with bone cement in 3, and removal of a cage in a failed fusion and bridging the defect with a strut bone graft in 1. Posterior instrumentation of the affected segment was performed in the same sitting.

RESULTS

The mean ± standard deviation of operative time of the anterior procedure was 101.2 ± 36.5 minutes. The mean blood loss during the anterior procedure was 724 ± 483.5 ml. The procedure was safe. No pseudarthrosis was encountered, and the reconstructed bone was stable in the three patients in whom bone cement was used.

CONCLUSION

The extracoelomic mini approach is less invasive; it results in less incisional morbidity, and it avoids opening the pleural and peritoneal cavities.
Current Concepts in Minimally Invasive Discectomy
Authors: Maroon Joseph C.
Published: July 2004

OBJECTIVE

The purpose of this study was to evaluate the various minimally invasive procedures available for the treatment of lumbar disc disease.

METHODS

A review of the literature, as well as my personal experience with minimally invasive approaches to the lumbar discs, was performed. This review included the percutaneous and open surgical approaches currently available and used for the treatment of lumbar disc disease.

RESULTS

The primary minimally invasive procedures for the treatment of lumbar disc disease include the following: 1) chemonucleolysis, introduced by Lyman Smith in 1964; 2) percutaneous manual nucleotomy, introduced by Hijikata in 1975; 3) microdiscectomy, first performed by Yaşargil in 1968; 4) automated percutaneous lumbar discectomy, introduced by Onik in 1984; 5) laser discectomy, first performed by Ascher and Choy in 1987; 6) endoscopic discectomy, first used by Schreiber and Suezawa in 1986 and improved by Mayer, Brock, and Mathews; 7) microendoscopic discectomy, introduced by Smith and Foley in 1995; and 8) intradiscal electrothermy, first reported by Saal and Saal in 2000.

CONCLUSION

Although all percutaneous techniques have been reported to yield high success rates, to date no studies have demonstrated any of these to be superior to microsurgical discectomy, which continues to be regarded as the standard with which all other techniques must be compared.
Protein Synthesis Inhibition Blocks Consolidation of an Acrobatic Motor Skill
Authors: Luft Andreas R. , Buitrago Manuel M. , Kaelin-Lang Alain , Dichgans Johannes , Schulz Jörg B.
Published: July 2004

To investigate whether motor skill learning depends on de novo protein
synthesis, adult rats were trained in an acrobatic locomotor task
(accelerating rotarod) for 7 d. Animals were systemically injected with
cycloheximide (CHX, 0.5 mg/kg, i.p.) 1 h before sessions 1 and 2 or sessions 2
and 3. Control rats received vehicle injections before sessions 1, 2, and 3.
Although CHX did not affect improvement of performance within session 1,
between-session improvement was impaired. In overtrained animals, comparable
injections of CHX had no effect on rotarod performance. These findings suggest
that consolidation of motor skills requires protein synthesis.
Providing Explicit Information Disrupts Implicit Motor Learning After Basal Ganglia Stroke
Authors: Boyd Lara A. , Winstein Carolee J.
Published: July 2004

Despite their purported neuroanatomic and functional isolation, empirical
evidence suggests that sometimes conscious explicit processes can influence
implicit motor skill learning. Our goal was to determine if the provision of
explicit information affected implicit motor-sequence learning after damage to
the basal ganglia. Individuals with stroke affecting the basal ganglia (BG)
and healthy controls (HC) practiced a continuous implicit motor-sequencing
task; half were provided with explicit information (EI) and half were not
(No-EI). The focus of brain damage for both BG groups was in the putamen. All
of the EI participants were at least explicitly aware of the repeating
sequence. Across three days of practice, explicit information had a
differential effect on the groups. Explicit information disrupted acquisition
performance in participants with basal ganglia stroke but not healthy
controls. By retention (day 4), a dissociation was apparent—explicit
information hindered implicit learning in participants with basal ganglia
lesions but aided healthy controls. It appears that after basal ganglia stroke
explicit information is less helpful in the development of the motor plan than
is discovering a motor solution using the implicit system alone. This may be
due to the increased demand placed on working memory by explicit information.
Thus, basal ganglia integrity may be a crucial factor in determining the
efficacy of explicit information for implicit motor-sequence learning.
Preserved Fronto-Striatal Plasticity and Enhanced Procedural Learning in a Transgenic Mouse Model of Alzheimer's Disease Overexpressing MutanthAPPswe
Authors: Middei Silvia , Geracitano Raffaella , Caprioli Antonio , Mercuri Nicola , Ammassari-Teule Martine
Published: July 2004

Mutations in the amyloid precursor protein (APP) gene inducing abnormal processing and deposition of β-amyloid protein in the brain have been implicated in the pathogenesis of Alzheimer's disease (AD). Although Tg2576 mice with the Swedish mutation (hAPPswe) exhibit age-related Aβ-plaque formation in brain regions like the hippocampus, the amygdala, and the cortex, these mice show a rather specific deficit in hippocampal-dependent learning and memory tasks. In view of recent findings showing that neural systems subserving different forms of learning are not simply independent but that depressing or enhancing one system affects learning in another system, we decided to investigate fronto-striatal synaptic plasticity and related procedural learning in these mutants. Fronto-striatal long-term depression (LTD) induced by tetanic stimulation of the cortico-striatal input was similar in Tg2576 and wild-type control mice. Behavioral data, however, pointed to an enhancement of procedural learning in the mutants that showed robust motor-based learning in the cross maze and higher active avoidance scores. Thus, in this mouse model of AD, an intact striatal function associated with an impaired hippocampal function seems to provide neural conditions favorable to procedural learning. Our results suggest that focusing on preserved or enhanced forms of learning in AD patients might be of interest to describe the functional reorganization of the brain when one memory system is selectively compromised by neurological disease.
Pseudoacne of the Nasal Crease: A New Entity?
Authors: Risma Kimberly A. , Lucky Anne W.
Published: July 2004

Abstract:  In this article we describe a clinical entity appearing in seven preadolescent patients who presented with chronic red papules within a prominent nasal crease. Milia were also noted in the nasal crease, but there was no evidence of acne vulgaris. The duration of symptoms was 4 months to 2 years, and lesions ranged from inflamed red papules, which were treated with topical antiinflammatory medications, to scarred white papules requiring excision. Histologic evaluation of two lesions revealed keratin granulomas that were likely derived from ruptured, inflamed milia. Due to its similarity in appearance to acne vulgaris, but different pathogenesis and clinical course, we suggest naming this newly described entity “pseudoacne of the nasal crease.”
Tinea Capitis in Kwa‐Zulu Natal, South Africa
Authors: Morar Nilesh , Dlova Ncoza C. , Gupta Aditya K. , Aboobaker Jamila
Published: July 2004

Abstract:  Tinea capitis is the most common dermatophyte infection in children. The hair involvement can be classified as endothrix, ectothrix, or favus, and the clinical appearance is variable. The goal of this study was to determine the demography, etiology, and clinical patterns of tinea capitis in South Africa. A prospective, cross‐sectional study was conducted over a 1‐year period. All cases were classified clinically and subject to Wood light examination, microscopy, and culture. One hundred patients were studied. The male:female ratio was 1.4:1. The mean age was 4.6 years (range 1–11 years). Trichophyton violaceum was isolated in 90% of positive cultures. Wood light was positive in one patient with Microsporum gypseum. The most common clinical variety was the “black dot” type, seen in 50% of patients. Twenty percent of the children presented with more than one clinical type simultaneously. We concluded that the most common cause of tinea capitis in South Africa is T. violaceum. The presentation is variable.
A Syndrome of Hemimaxillary Enlargement, Asymmetry of the Face, Tooth Abnormalities, and Skin Findings (HATS)
Authors: Welsch Michael Jude , Stein Sarah L.
Published: July 2004

Abstract: Hemimaxillofacial dysplasia and segmental odontomaxillary dysplasia appear to be the same syndrome, having the common features of unilateral abnormalities of bone, teeth, gums, and skin. Oral manifestations are the hallmark of this condition. Those affected are generally recognized in childhood and may have partial anodontia, abnormal spacing of the teeth, delayed eruption, and gingival thickening of the affected segment. Reported cutaneous manifestations include facial asymmetry, Becker's nevus, “hairy nevus,” lip hypopigmentation, discontinuity of the vermilion border, depression of the cheek, and erythema. The oral lesions do not appear to be progressive. We describe a child with features consistent with hemimaxillofacial dysplasia/segmental odontomaxillary dysplasia. Findings of a biopsy specimen from the cheek confirmed the presence of a Becker's nevus. Cutaneous findings reported in the previous 31 cases are reviewed and summarized. The acronym HATS (hemimaxillary enlargement, asymmetry of the face, tooth abnormalities, and skin findings) is introduced to reflect the spectrum of abnormalities in bone, teeth, and skin that may be seen in this developmental disorder.
Subungual Chondroblastoma in a 9‐Year‐Old Girl
Authors: Castanedo‐Cazares Juan Pablo , Lepe Verónica , Moncada Benjamín
Published: July 2004

Abstract:  Chondroblastoma is an uncommon primary bone tumor, mainly found in the epiphyses of long bones. We describe a 9‐year‐old girl who presented with a chondroblastoma as a subungual mass in the fifth toe. Radiographs showed an expansive, calcified tumor of the distal phalanx. Histologic examination after excision revealed chondroid differentiation, active mitosis, multinucleated giant cells, calcification, and necrosis. There was no recurrence of the lesion after surgical excision. The purpose of this report is to document this unusual event that occurred in such a short bone as the distal phalanx of the fifth toe, mimicking a dermatologic entity.
A Subungual Nevus in a Filipino Child
Authors: Leung Alexander K. C. , Woo Tom Y.
Published: July 2004

Abstract:  A 2.5‐year‐old Filipino girl with a progressively growing, black, subungual lesion is described. A biopsy was performed because of the progressive increase in size of the lesion and its periungual involvement. Histologic examination revealed a junctional nevus. To our knowledge, this represents the first report of subungual nevus in a Filipino child. The need for histologic diagnosis prior to definitive surgery cannot be overemphasized.
Itraconazole in the Treatment of Tinea Capitis Caused by Microsporum canis: Experience in a Large Cohort
Authors: Ginter‐Hanselmayer Gabriele , Smolle Josef , Gupta Aditya
Published: July 2004

Abstract:  Mycotic scalp infection caused by Microsporum canis is one of the more recalcitrant disorders, with increasing incidence during the last decade. We report our experience with administration of itraconazole in 163 children (86 girls, 77 boys) with M. canis tinea capitis. Fifty‐five patients had previous treatment with terbinafine without success. In all children, the dosage of itraconazole was adjusted according to body weight, with 5 mg/kg/day given in a continuous regimen either as a capsule (116 patients) or an oral suspension (47 patients). In all children, there was both clinical and mycologic cure after a mean treatment period of 39 ± 12 days (range 10–77 days). Eleven children (6.7%) had side effects: diarrhea in five children, cutaneous eruption in four, and abdominal pain in two. Itraconazole was effective and safe for the treatment of M. canis tinea capitis.
Phenotypic and functional changes of circulating monocytes and polymorphonuclear leucocytes from elderly persons
Authors: De Martinis Massimo , Modesti Marco , Ginaldi Lia
Published: July 2004

The function and phenotype of monocytes and granulocytes in the elderly is consistently remodelled. Because leucocyte adhesion molecules play important roles in mediating a wide variety of leucocyte functions, age‐related changes in their expression on granulocyte and monocyte surfaces could be partially responsible for immune dysfunctions during senescence. Considering the central role of innate immunity in the process of immunosenescence and the involvement of cell adhesion molecules (CAM) in the great majority of leucocyte functions, we studied the expression of CD50 and CD62L adhesion molecules in peripheral blood granulocytes and monocytes from healthy elderly and young subjects. We show here that the percentage of granulocytes and monocytes expressing CD62L is decreased in the elderly, whereas its density expression is unchanged on both cell types. A downregulation of the density expression of CD50 at a per cell level characterizes granulocytes in the elderly, whereas CD50 expression on monocytes from old subjects shows a peculiar attitude: its density expression decreases whereas the number of positive cells is expanded. The downregulation of this receptor on granulocytes from aged people could determine a state of hyperactivation contributing to the proinflammatory status of the elderly, while the lower expression on monocytes could therefore contribute to the impaired antigen presentation in the elderly. On the other hand, the increased number of CD50 positive monocytes in the elderly, despite its decreased density expression at a per cell level, could be interpreted as an attempt to counteract the inability to mount strong immune responses. Both CD50 and CD62L changes in ageing polymorphonuclear (PMN) cells allow recognition as non‐self or senescent self to permit macrophages in the liver and spleen to remove them from the circulation. The increased proportion of granulocytes and monocytes lacking CD62L and the downregulation of CD50 intensity expression on both cell types may suggest a state of in vivo activation. Therefore, CD50 and CD62L shedding from the cell surface of activated granulocytes and monocytes could be interpreted as a tentative to counteract the dangerous effects of an excessive chronic inflammation in the elderly. However, the increased proportion of CD62L negative granulocytes in the elderly leads to an impairment in cell adhesion which is the first line of response to acute inflammatory stimuli. This phenomenon likely contributes to the increased susceptibility to acute infections of elderly people.
Bioassay detects soluble MAdCAM‐1 in body fluids
Authors: Leung Euphemia , Lehnert Klaus B , Kanwar Jagat R , Yang Yi , Mon Yu , McNeil H Patrick , Krissansen Geoffrey W
Published: July 2004

Mucosal addressin cell adhesion molecule (MAdCAM‐1) is a key player in mediating the infiltration of leucocytes into chronically inflamed tissues. Five anti‐MAdCAM‐1 monoclonal antibodies (mAb), designated 17F5, 201F7, 314G8, 377D10 and 355G8, were generated by fusion of P3 × 63Ag8.653 myeloma cells with spleen cells from BALB/c mice immunized with recombinant human MAdCAM‐1‐Fc. The latter four mAb recognize the ligand‐binding first Ig domain, and block T ‐cell adhesion to MAdCAM‐1. The non‐blocking mAb 17F5 recognizes the mucin domain. Extensive analysis of a large panel of paraffin‐embedded human tissues revealed that the 314G8 mAb detected MAdCAM‐1 on venules in the spleen and small intestine. MAdCAM‐1 was strongly expressed in the synovium of osteoarthritis patients, predominantly on the endothelial lining of blood vessels, but also within the vessel lumen. An ELISA, based on mAb 377D10 and 355G8, was developed to determine whether soluble MAdCAM‐1 was present in body fluids, and to measure the levels present. The assay detected soluble MAdCAM‐1 in the serum and urine of healthy donors, at levels similar to those of soluble forms of the related CAM, ICAM‐1 and VCAM‐1. The anti‐MAdCAM‐1 antibodies and assay developed here may be useful therapeutically in the treatment of inflammation in humans. Similarly, they may be useful diagnostically to monitor the presence and levels of MAdCAM‐1.
Prostanoids and their receptors that modulate dendritic cell‐mediated immunity
Authors: Gualde Norbert , Harizi Hedi
Published: July 2004

Dendritic cells (DC) are essential for the initiation of immune responses by capturing, processing and presenting antigens to T cells. In addition to their important role as professional APC, they are able to produce immunosuppressive and pro‐inflammatory prostanoids from arachidonic acid (AA) by the action of cyclooxygenase (COX) enzymes. In an autocrine and paracrine fashion, the secreted lipid mediators subsequently modulate the maturation, cytokine production, Th‐cell polarizing ability, chemokine receptor expression, migration, and apoptosis of these extremely versatile APC. The biological actions of prostanoids, including their effects on APC‐mediated immunity and acute inflammatory responses, are exerted by G protein‐coupled receptors on plasma membrane. Some COX metabolites act as anti‐inflammatory lipid mediators by binding to nuclear receptors and modulating DC functions. Although the role of cytokines in DC function has been studied extensively, the effects of prostanoids on DC biology have only recently become the focus of investigation. This review summarizes the current knowledge about the role of prostanoids and their receptors in modulating DC function and the subsequent immune responses.
Investigation of the immunocompetent cells that bind early pregnancy factor and preliminary studies of the early pregnancy factor target molecule
Authors: Athanasas‐Platsis Stavrosia , Somodevilla‐Torres Maria J , Morton Halle , Cavanagh Alice C
Published: July 2004

Early pregnancy factor (EPF) is a secreted protein with immunosuppressive and growth factor properties. It has been shown to suppress the delayed‐type hypersensitivity response in mice as well as acute and chronic forms of experimental autoimmune encephalomyelitis in rats and mice, respectively. In previous studies, we have demonstrated that EPF binds to a population of lymphocytes and we hypothesized that it mediates its suppressive effects by binding to CD4+ T cells. In the present study, we isolated monocytes and subpopulations of lymphocytes and labelled them with fluoresceinated EPF in order to determine which populations bind EPF. We demonstrated that EPF binds specifically to CD4+, CD8+, CD14+ (monocytes) and CD56+ NK cells but not to CD19+ B cells. The identity of the molecule(s) on the cell surface that is targeted by EPF is unknown, but as EPF is an extracellular homologue of the intracellular protein chaperonin 10 (Cpn10), we examined the possibility that the EPF receptor is a membrane‐associated form of chaperonin 60 (Cpn60), the functional associate of Cpn10 within the cell. The EPF target molecule on lymphocytes was visualized by chemical cross‐linking of exogenous iodinated Cpn10 to cells and probed with anti‐Cpn60. The effect of anti‐Cpn60 on activity in the EPF bioassay, the rosette inhibition test, was also examined. In both instances, no specific interaction of this antibody and the putative receptor was observed. It was concluded that the cell surface molecule targeted by EPF is unlikely to be a homologue of Cpn60.
Changes in the immune functions and susceptibility to Listeria monocytogenes infection in mice fed dietary lipids
Authors: Puertollano María A , Puertollano Elena , Ruiz‐Bravo Alfonso , Jiménez‐Valera María , De Pablo Manuel A , Álvarez De Cienfuegos Gerardo
Published: July 2004

The direct examination of the effects that fish oil diets (composed of long‐chain n‐3 polyunsaturated fatty acids) exert on immune system function indicates a reduction of host natural resistance to infectious diseases mainly because of a suppression of immune function generated by the fatty acids contained in this diet. Here, we evaluated the concentration of IL‐12, IL‐4, prostaglandin E2 and leukotriene B4 in the serum from BALB/c mice receiving four different diets. Each group was fed a diet that differed only in the source of fat: a low‐fat diet (2.5% by weight), an olive oil diet (20% by weight), a fish oil diet (20% by weight) or a hydrogenated coconut oil diet (20% by weight). Mice were fed for 4 weeks and then infected with the intracellular pathogen Listeria monocytogenes. An initial reduction in the Th1‐type response as a result of a decrease in IL‐12p70 secretion, an inefficient action of IL‐4 (Th2‐type response) and no modification of pro‐inflammatory lipid‐mediator production could be, at least in part, the key events responsible for the inadequate elimination of L. monocytogenes from the spleens of mice fed a fish oil diet. Furthermore, our results suggest that the type of dietary lipids may affect the circulating concentration of IL‐12p70 and IL‐4, leading to a modulation in the protective cellular immune response to L. monocytogenes infection.
Evaluation of immunotherapy to reverse sequestration in the treatment of severe Plasmodium falciparum malaria
Authors: Goldring JP Dean
Published: July 2004

Sequestration and the attachment of Plasmodium falciparum malaria‐infected RBC to venous endothelial cells involves parasite‐encoded ligands interacting with up to nine host receptors. Antisequestration immunotherapy as an adjunct to quinine did not alter the dynamics of parasite clearance or prove beneficial for the patient. Estimated concentrations of antibody likely to reverse adherence in patients were based on the concentrations of parasite ligands, host receptors and patient equivalents derived from in vitro observations. Calculations presented here indicate that concentrations in excess of a fivefold increase in antibody concentrations used in the immunotherapy trial and equivalent to doubling normal peripheral blood antibody concentrations are anticipated for the successful reversal of sequestration to occur. It is suggested that immunotherapy aimed at either parasite ligands or host receptors to reverse sequestration in the treatment of severe malaria infections is unlikely to be successful given the complexity and number of receptors and ligands and the calculated concentrations of antibodies required.
Using patient‐identifiable data for epidemiological research
Authors: Malfroy M. , Llewelyn C. A. , Johnson T. , Williamson L. M.
Published: July 2004

Summary.  The use of patient‐identifiable data in epidemiological research is subject to increasingly complex regulation. This article reports the experience of a research team in setting up the Epidemiology and Survival of Transfusion Recipients (EASTR) study in which patient‐identifiable information was needed in order to link data from two sources for analysis and obtain long‐term survival patterns of transfusion recipients. The process of establishing the study involved obtaining separate ethical, research and development and data protection approval, including application to the newly formed Patient Information Advisory Group, set up under Section 60 of the Health and Social Care Act, 2001. We describe the high cost in administrative procedures and time now necessary to gain statutory approval before such a study can begin, which has been the result of recent legislation. Issues arising from our experience are discussed.
A simple automatized audit system for following and managing practices of platelet and plasma transfusions in a neonatal intensive care unit
Authors: Petäjä J. , Andersson S. , Syrjälä M.
Published: July 2004

Summary.  During neonatal intensive care, blood components are often used in clinical situations where both their efficacy and safety lack solid justification. A practical system to continuously analyse actual transfusion practices is a prerequisite for improvements of quality in transfusion therapy. We hypothesized that such a system would reveal inappropriate variations in clinical decission making and offer a means for staff education and quality improvement and assurance.

The study consisted of three 120–152‐day periods (P I, P II and P III) between January 2000 and October 2001 and involved 543 new patient admissions (141 patients with birth weight < 1501 g) and 6227 days of patient care at a single tertiary level NICU. P I was a control with no intervention, P II was after technically introducing the computer system and, the last period, P III was after presenting and discussing the results of P I and P II at a staff meeting. Upon an order of platelet or fresh frozen plasma (FFP) unit from the blood bank, a computer‐based audit system compared the last platelet count or prothrombin time [expressed as percentage of normal clotting activity, prothrombin time (PT‐%)] to predefined criteria. In the case of exceeding the preset thresholds, the system required additional information and recorded the pretransfusion laboratory values for later analysis.

Thirty‐two per cent of platelet transfusions were given with pretransfusion platelet count >49 × 109 L−1, and 60% of these transfusions (19% of all platelet transfusions) could not be clinically justified in retrospective chart review. There was no significant change in this practice from P II to P III. FFP transfusions were given with significantly different pretransfusion PT‐% values during P II and P III. The proportions of FFP transfusions with pretransfusion PT‐% > 49% were 7·8% and 0·9% during P II and P III, respectively (P < 0·0001). In chart review, none of the FFP transfusions with pretransfusion PT‐% > 49% could be justified by clinical grounds.

Inappropriate transfusions of both platelets and plasma remain a significant challenge for quality assurance of neonatal intensive care. Automated recording of pretransfusion platelet count and prothrombin time reliably identified the poorly justified transfusions and thus offered a practical resource‐saving tool for quality assurance of transfusion in the NICU. A significant shift towards more appropriate use of plasma was demonstrated after implementation of the audit system.
Soluble urokinase plasminogen activator receptor in blood transfusion components
Authors: Riisbro R. , Brünner N. , Christensen I. J. , Nielsen H. J.
Published: July 2004

Summary.  Post‐transfusion infectious complications associated with allogeneic blood components may depend on storage time and may be related to extracellular accumulation of bioactive substances during storage. The glycoprotein, soluble urokinase plasminogen activator receptor (suPAR), which is located in specific granules of neutrophils, plays a role in inflammation and remodelling of the extracellular matrix. Using enzyme‐linked immunosorbent assay, suPAR was determined in serum, plasma and blood cell lysates. In addition, suPAR was measured in whole blood (WB), buffy‐coat‐depleted saline‐adenine‐glucose‐mannitol (SAGM) blood, platelet‐rich plasma (PRP) and buffy‐coat‐derived platelet (BCP) pools with and without pre‐storage leucofiltration, and in non‐filtered WB, SAGM blood and platelet concentrates prepared using apheresis (APC) at different time points during storage. Mean suPAR concentration was significantly higher in cell lysates, compared to that in a corresponding serum (P = 0·007) and in plasma samples (P = 0·004). Mean suPAR levels in WB, BCP and SAGM were significantly reduced using leucofiltration (WB: 3·4 versus 2·0 ng mL−1; BCP: 1·6 versus 1·1 ng mL−1; SAGM: 2·8 versus 0·19 ng mL−1), whereas no difference was observed in PRP. In non‐filtered WB, SAGM and APC, extracellular suPAR accumulated significantly in a storage‐time‐dependent manner (WB: P < 0·01; SAGM: P < 0·001; APC: P < 0·001). The present study demonstrates that cell lysates contain significantly more suPAR, compared to both serum and plasma. This can be explained by the release of suPAR from intracellular granules during cell lysis. The amount of suPAR is significantly increased during storage of blood transfusion components, an accumulation that is reduced using pre‐storage leucofiltration.
Plasma renin in mice with one or two renin genes
Authors: Hansen P. B. , Yang T. , Huang Y. , Mizel D. , Briggs J. , Schnermann J.
Published: July 2004

Aim:  In the present study we have investigated whether the presence of a second renin gene exerts an overriding influence on plasma renin such that mice with two renin genes have consistently higher renin levels than mice with only one renin gene.

Methods:  Plasma renin was determined as the rate of angiotensin I generation using a radioimmunoassay (RIA) kit with (plasma renin concentration, PRC) or without (plasma renin activity, PRA) the addition of purified rat angiotensinogen as substrate.

Results:  In male 129SvJ, DBA/2 and Swiss Webster mice, strains possessing both Ren‐1 and Ren‐2, PRC (ng Ang I mL−1 h−1) averaged 178 ± 36, 563 ± 57 and 550 ± 43 while PRA was 2.9 ± 0.5, 3.6 ± 0.8 and 7.8 ± 1.2. In male C57BL/6, C3H and BALB/c mice that express only Ren‐1, PRC averaged 426 ± 133, 917 ± 105 and 315 ± 72, and PRA was 3.4 ± 1.0, 6.9 ± 1.7 and 4.5 ± 1.2. In the two renin gene A1AR−/− mice compared with the one renin gene A1AR+/+, PRC averaged 538 ± 321 and 415 ± 159 while PRA averaged 3.2 ± 1.1 and 4.4 ± 1.4 ng Ang I mL−1 h−1. Aldosterone levels showed no significant differences between one renin (C57BL/6, C3H and BALB/c) and two renin (129SvJ, DBA/2 and Swiss Webster) gene mice. Furthermore, by quantitative real‐time polymerase chain reaction (RT‐PCR) we found no correlation between the number of renin genes and whole kidney renin mRNA levels from one and two renin gene mice.

Conclusion:  Our data show that baseline plasma renin is not systematically higher in mice with two renin genes than in one renin gene mice. Thus, the presence of a second renin gene does not seem to be a major determinant of differences in PRC between different mouse strains.
Mechanisms for macula densa cell release of renin
Authors: Persson A. E. G. , Ollerstam A. , Liu R. , Brown R.
Published: July 2004

The juxtaglomerular apparatus in the kidney is important in controlling extracellular fluid volume and renin release. The fluid load to the distal tubule is first sensed at the macula densa site via the entry of NaCl, through a Na, K, 2Cl co‐transport mechanism. The next step is unclear, but there is recent evidence of an increased macula densa cell calcium concentration with a reduction in fluid load to the macula densa. An increase in macula densa cell calcium could activate phospholipase A2 to release arachidonic acid, the rate‐limiting step in the formation of prostaglandins. Recent evidence suggests that the prostaglandin formed is PGE2, a potent stimulator for renin release. Recent evidence has also shown that adenosine has an important function in the juxtaglomerular apparatus. It stimulates calcium release in afferent arteriolar smooth muscle cells, leading to contraction of the afferent arteriole as part of the tubuloglomerular feedback mechanism, and inhibits renin release. Thus, renin release from the afferent arteriole is mediated partly through formation of PGE2, and partly through the reduction of adenosine formation that inhibits renin production.
Mechanisms underlying the antihypertensive functions of the renal medulla
Authors: Bergström G. , Evans R. G.
Published: July 2004

There is good evidence that the renal medulla plays a pivotal role in long‐term regulation of blood pressure. ‘Renal medullary’ blood pressure regulating systems have been postulated to involve both exocrine (pressure natriuresis/diuresis) and endocrine [renal medullary depressor hormone (RMDH)] functions. However, recent studies indicate that pressure diuresis/natriuresis dominates the antihypertensive renal response to increased renal perfusion pressure, suggesting little physiological role for a putative RMDH in compensatory responses to acutely increased blood pressure. The medullary circulation appears to play a key role in mediating pressure diuresis, although the precise mechanisms involved remain controversial. Counter‐regulatory vasodilator mechanisms (e.g. nitric oxide), at least partly mediated through cross‐talk between the vasculature and the tubular epithelium, protect the medullary circulation from the vasoconstrictor effects of hormonal factors such as angiotensin II. These mechanisms also appear to contribute to compensatory responses to increased salt intake in salt‐resistant individuals. Failure of these mechanisms predisposes the organism towards the development of hypertension, appears to underlie the development of some forms of experimental hypertension, and may even contribute to the pathogenesis of essential hypertension.
Volume natriuresis vs. pressure natriuresis
Authors: Bie P. , Wamberg S. , Kjolby M.
Published: July 2004

Body fluid regulation depends on regulation of renal excretion. This includes a fast vasopressin‐mediated water‐retaining mechanism, and slower, complex sodium‐retaining systems dominated by the renin–angiotensin aldosterone cascade. The sensory mechanisms of sodium control are not identified; effectors may include renal arterial pressure, renal reflexes, extrarenal hormones and other regulatory factors. Since the pioneering work of Guyton more than three decades ago, pressure natriuresis has been in focus. Dissociations between sodium excretion and blood pressure are explained as conditions where regulatory performance exceeds the precision of the measurements. It is inherent to the concept, however, that sudden transition from low to high sodium intake elicits an arterial pressure increase, which is reversed by the pressure natriuresis mechanism. However, such transitions elicit parallel changes in extracellular fluid volume thereby activating volume receptors.

Recently we studied the orchestration of sodium homeostasis by chronic and acute sodium loading in normal humans and trained dogs. Small increases in arterial blood pressure are easily generated by acute sodium loading, and dogs appear more sensitive than humans. However, with suitable loading procedures it is possible – also acutely – to augment renal sodium excretion by at least one order of magnitude without any change in arterial pressure whatsoever. Although pressure natriuresis is a powerful mechanism capable of overriding any other controller, it seems possible that it is not operative under normal conditions. Consequently, it is suggested that physiological control of sodium excretion is neurohumoral based on extracellular volume with neural control of renin system activity as an essential component.
Pharmacotyping of hypokalaemic salt‐losing tubular disorders
Authors: Reinalter S. C. , Jeck N. , Peters M. , Seyberth H. W.
Published: July 2004

Long standing confusion exists in the terminology of hypokalaemic salt‐losing tubulopathies (SLTs). SLTs are autosomal recessively transmitted and characterized by normotensive secondary hyperreninism/hyperaldosteronism with hypokalaemic metabolic alkalosis. Historically, four phenotypical variants have been described: (1) the (classic) Bartter syndrome (cBS), (2) the hypomagnesaemic hypocalciuric Gitelman syndrome (GS), (3) the hypercalciuric hyperprostaglandin‐E‐syndrome (HPS) or antenatal Bartter syndrome (aBS) and (4) the hyperprostaglandin‐E‐syndrome with sensorineural deafness (HPS + SND). The latter two syndromes are the most severe variants with antenatal manifestation with polyhydramnios and life‐threatening course of salt‐ and water‐loss. Defects in five renal membrane proteins involved in electrolyte reabsorption have been identified: In HPS‐patients mutations in (1) either the furosemide‐sensitive sodium–potassium–chloride cotransporter NKCC2, or (2) in the potassium channel ROMK have been identified, and (3) HPS + SND is caused by mutations in the β‐subunit of the chloride channels ClC‐Kb and –Ka (named barttin), all mimicking the major pharmacological effects of furosemide with minor potassium‐wasting in ROMK‐patients as seen in patients treated with simultaneous furosemide and amiloride, and minor calcium‐wasting in Barttin‐patients resembling the combination of furosemide and thiazides. (4) cBS is caused by mutations in the chloride channel ClC‐Kb with similar clinical characteristics as seen under combination of thiazides and furosemide, (5) GS is caused by mutations in the thiazide‐sensitive sodium‐chloride cotransporter NCCT resembling the effect of long‐term thiazide administration.

Conclusion:  The combination of pharmacology and genetics suggests a new terminology for the above described SLTs: Furosemide‐like‐SLT for HPS caused by NKCC2‐mutations, furosemide/amiloride‐like‐SLT for HPS caused by ROMK‐mutations, furosemide/thiazide‐like‐SLT for HPS + SND, thiazide/furosemide‐like‐SLT for cBS, and thiazide‐like‐SLT for GS.
The role of cyclooxygenases and prostanoid receptorsin furosemide‐like salt losing tubulopathy:the hyperprostaglandin E syndrome
Authors: Nüsing R. M. , Seyberth H. W.
Published: July 2004

Hyperprostaglandin E syndrome/antenatal Bartter syndrome is characterized by NaCl wasting and volume depletion, juxtaglomerula hypertrophy, hyper‐reninism and secondary hyperaldosteronism. Primary causes are mutations in the gene for Na‐K‐2Cl‐cotransporter, NKCC2, or for potassium channel, ROMK, responsible for medullary NaCl malabsorption. Most intriguing aspect of the syndrome is the association with a massively increased renal prostaglandin production which contributes substantially to the clinical picture of the patients. Therefore the term hyperprostaglandin E syndrome has been introduced. It is unclear how prostaglandins aggravate the NaCl transport deficiency. Aspects to prostaglandin synthesis and receptor‐mediated function within the kidney in patients suffering from hyperprostaglandin E syndrome/antenatal Bartter syndrome will be discussed.
The renin–angiotensin system in kidney development
Authors: Chen Y. , Lasaitiene D. , Friberg P.
Published: July 2004

All components of the renin–angiotensin system (RAS) are highly expressed in the developing kidney in a pattern suggesting a role for angiotensin II in renal development. In support of this notion, pharmacological interruption of angiotensin II type‐1 (AT1) receptor signalling in animals with an ongoing nephrogenesis produces specific renal abnormalities characterized by papillary atrophy, abnormal wall thickening of intrarenal arterioles, tubular atrophy associated with expansion of the interstitium, and a marked impairment in urinary concentrating ability. Similar changes in renal morphology and function develop also in mice with targeted inactivation of genes encoding renin, angiotensinogen, angiotensin‐converting enzyme, or both AT1 receptor isoforms simultaneously. Taken together, these results clearly indicate that an intact signalling through AT1 receptors is a prerequisite for normal renal development. The present report mainly reviews the renal abnormalities induced by blocking the RAS pharmacologically in experimental animal models. In addition, pathogenetic mechanisms are discussed.