bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal Subdural Empyema
Authors: Dacey Ralph G. , Winn Richard H. , Jane John A. , Butler Albert B.
Published: August 2004

Spinal subdural empyema (SSE) is a rare variety of intraspinal infection. SSE should be suspected in patients presenting with fever, back pain, and signs of cord or nerve root compression. Two patients with SSE are presented. The first patient complained of fever and back pain. She had no neurological deficit but was found to have SSE. The second patient, who presented with intracerebral hemorrhage in the fifth month of pregnancy and spontaneous abortion, was found to have SSE at lumbar puncture. The clinical manifestations and management are discussed.
Interdural Cyst of the Lumbosacral Region
Authors: Stephen L. Done , Anne L. Hayman , Paul F. J. New , Kenneth R. Davis , Paul H. Chapman
Published: August 2004

The purpose of this report is to call attention to the clinical, myelographic, and computed tomographic appearance of a very rare type of dural cyst within the lumbosacral spinal canal. We report this condition in three unrelated boys who presented with symptoms of cauda equina compression. Our experience suggests that these cysts are congenital in origin. Anatomically, the cyst wall consisted of a dura-like layer without arachnoid. There was a small ventral defect allowing incomplete communication with the compressed subarachnoid space. Cerebrospinal fluid-like fluid accumulated within the interdural cyst as a result of this communication. Treatment consisted of obliteration of the point of entry between cyst and subarachnoid space in all cases and partial cyst wall excision in one case. After operation, the two patients who had presented with long-standing sphincter disturbance had partial improvement in function and the child with a pain syndrome was completely relieved of symptoms.
Percutaneous Retrogasserian Glycerol Rhizotomy for Tic Douloureux: Part 1 Technique and Results in 112 Patients
Authors: Dade L. Lunsford , Marvin H. Bennett
Published: August 2004

The technique and results of treatment of tic douloureux by percutaneous retrogasserian glycerol rhizotomy (PRGR) were assessed in a series of 112 patients. All patients were refractory to or intolerant of medical therapy, Many of these patients had recurrent pain despite such surgical treatment as microvascular decompression (21%) or one or more percutaneous radiofrequency thermal rhizotomies (19%). The follow-up duration after glycerol rhizotomy ranged from 4 to 28 months. At the final assessment, 67% had complete pain relief; 23% were improved, with pain relieved by minimal drug therapy; and 10% had poor results with unsatisfactory pain relief even with medications. Before the final assessment, 19 patients required a second PRGR because of an initially suboptimal injection (10%) or recurrent pain (16.9%). Seventy-three per cent had no demonstrable change in facial sensation after operation. Hakanson's original procedure based on anatomic verification by cisternography provided precise localization. required no intraoperative stimulation or lesion generators, and allowed varied anesthetic options during operation. In contrast to thermal rhizotomy. PRGR offers patients relief of painful tic douloureux without altering facial sensation in most cases.
Intracarotid Chemotherapy with a Combination of 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU), cis-Diaminedichloroplatinum (Cisplatin), and 4'-O-Demethyl-1-O-(4,6-O-2-thenylidene-β-D-glucopyranosyl)epipodophyllotoxin (VM-26) in the Treatment of Primary and Metastatic Brain Tumors
Authors: David J.Stewart , Grahovac Zvonimir , Benoit Brien , Addison David , Richard Michael T. , Dennery Jean , Hugenholtz Herman , Russell Neville , Peterson Eric , Maroun Jean A. , Vandenberg Ted , Hopkins Harry S.
Published: August 2004

Thirty-seven patients with intracranial primary or metastatic tumors were treated with an intraarterial combination of BCNU, cisplatin, and VM-26 to determine the efficacy, toxicity, and maximal tolerated doses for the combination. A transfemoral fluoroscopic approach was used to catheterize temporarily the internal carotid or vertebral artery. Thirteen of 19 (68%) evaluable primary brain tumors and 9 of 16 (56%) evaluable brain metastases responded. The response rate was lower in patients previously treated with both cranial irradiation and i.v. chemotherapy than in patients less heavily pretreated (54% vs. 82%), although even patients previously treated i.v. with all three of the study drugs responded. All five patients with both extracranial and intracranial evaluable tumor deposits experienced a greater response of their intracranial than of their extracranial tumor. Ipsilateral retinal and neurological toxicity were dose-limiting, with major toxicity (permanent decreased vision or hemiparesis) occurring in five of nine (56%) patients receiving doses of BCNU ≥ 100 mg/m2, plus cisplatin, 60 mg/m2, plus VM-26, 175 mg/m2. Only 9% of the patients treated with a lower VM-26 dose developed permanent severe toxicity, and the doses that we now recommend are: BCNU, 100 mg/m2; cisplatin, 60 mg/m2; and VM-26, 150 mg/m2. The response rate was also dose-related (100% at the highest doses tested vs. 57% at the lower doses). Fully reversible toxicity was also seen, including transient decrease in ipsilateral visual acuity (11%), transient hemiparesis or hemianesthesia (5%), transient increased intracranial pressure (5%), mild ototoxicity (3%), mild to moderate vomiting (80%), severe periorbital pain and erythema during BCNU infusion (94%), and myelosuppression (30%). Vertebral artery infusion must be performed with great caution because infusions of BCNU and VM-26 (but not of cisplatin) were associated with marked but rapidly reversible somnolence and potentially life-threatening cardiac and respiratory depression. No cardiorespiratory depression was seen with carotid artery infusions. The intraarterial infusion of this three-drug regimen is quite effective in reducing the size of the tumor as seen on the computed tomographic scan in this poor prognosis group of patients, but is also potentially quite toxic. We are now initiating other studies adding i.v. drugs to our intracarotid combination.
Suprasellar Germ Cell Tumor with Extracranial Metastases
Authors: Jennings Darrell C. , Powell Deborah E. , Walsh John W. , Mortara Richard H.
Published: August 2004

A case of metastasizing suprasellar germ cell tumor is described. Serum tumor markers were measured and the immunochemistry of the tumor was studied. The rarity of extracranial metastasis from suprasellar germinomas is noted, and the relevance to mixed tumors is discussed. The difficulties associated with small biopsies and the importance of tumor marker studies in all cases of an intracranial germ cell tumor are emphasized by the case study. (Neurosurgery 16:9–12, 1985)
Ependymal Cyst of the Quadrigeminal Plate: Case Report
Authors: Davis Raphael P. , Sachdev Ved P. , Sachar Michael , Wood James H.
Published: August 2004

A patient with an ependymal cyst of the quadrigeminal plate is reported. The patient presented with headache, diplopia, and evidence of increased intracranial pressure. A nonenhancing cyst with hydrocephalus was demonstrated by computed tomographic scan. The cyst was subtotally resected using a transtentorial approach. The causes, clinical presentation, and treatment of quadrigeminal plate ependymal cysts are discussed, together with a review of the literature. (Neurosurgery 16:96–99, 1985)
Revascularization and Aneurysm Surgery: Current Status
Authors: Spetzler Robert F. , Carter Philip L.
Published: August 2004

Unclippable intracranial aneurysms are most effectively treated by hunterian ligation; however, the attendant risk of cerebral ischemia is significant. Many techniques have been used in an attempt to predict the safety of proximal vessel occlusion. Unfortunately, there is none that is risk-free and highly successful. A combination of stump pressure and cerebral blood flow measurements has been shown to be the most accurate in the acute assessment. In addition, recent studies have demonstrated that the long term risk of carotid ligation is significant. Extracranial-intracranial bypass grafting (EC-IC) has been shown to improve the safety of parent vessel ligation and is a low risk procedure. Whenever hunterian ligation is planned for the treatment of an intracranial aneurysm, EC-IC should be strongly considered. (Neurosurgery 16:111–116, 1985)
Intramedullary Spinal Neurofibroma Diagnosed with Computed Tomography: Report of a Case
Authors: Gonzalez Gelabert M. , Allut Garcia A. , Alonso Conde C. , Zabala Bollar A. , Rumbo Martinez R. , Oliveros Reyes F.
Published: August 2004

A case of intramedullary neurofibroma of the cervical spine in a patient with no signs of von Recklinghausen's disease is presented. Intramedullary neurofibroma is extremely rare, accounting for less than 1% of spinal cord neurofibromas. This case is the first diagnosed with computed tomography. (Neurosurgery 16: 543-545, 1985)
ATR couples FANCD2 monoubiquitination to the DNA-damage response
Authors: Andreassen Paul R. , D'Andrea Alan D. , Taniguchi Toshiyasu
Published: August 2004

Fanconi anemia (FA) is a multigenic autosomal recessive cancer susceptibility syndrome. The FA pathway regulates the monoubiquitination of FANCD2 and the assembly of damage-associated FANCD2 nuclear foci. How FANCD2 monoubiquitination is coupled to the DNA-damage response has remained undetermined. Here, we demonstrate that the ATR checkpoint kinase and RPA1 are required for efficient FANCD2 monoubiquitination. Deficiency of ATR function, either in Seckel syndrome, which clinically resembles Fanconi anemia, or by siRNA silencing, results in the formation of radial chromosomes in response to the DNA cross-linker, mitomycin C (MMC), thus mimicking the chromosome instability of FA cells.
Managerial process: the reflective practitioner
Authors: Greenall Paul
Published: August 2004

The successful management journey is replete with moments of truth. Recognizing those moments and their significance for successful managerial practice is both a reflective and a conscious practice. This article, written by a successful pharmacist who now manages a busy public service hospital pharmacy documents his management journey from starting position as a drug store pharmacist to his present position in the public service. The paper uses managerial process theory as a critical tool to assess the author's own managerial style. Starting off as an autocratic manager with micro management tendencies, he has now developed a different style of management built on a basic philosophy about the value of people. He sees a need for managers to build a work environment that supports the efforts of employees. This style has not only made him a more effective people manager and motivator, but he argues it has also made him a better pharmacist. The author concludes by advocating the value of reflective practice, particularly for healthcare administrators as a means of balancing the technical demands of their disciplines with the ongoing requirements of managing people.
A review of compliance studies in kidney transplanted adolescents
Authors: Mekechuk Joy
Published: August 2004

Strong evidence exists that compliance with the treatment regimen is a major problem for many transplant patients. Noncompliance with the treatment regimen is particularly evident among kidney‐transplanted adolescents. Research has not examined the adolescents' experience of living with a kidney transplant. Provides a review of the literature seeking to explain the causes of noncompliance in the population group. Although the studies referred to here provide insights into the situation, many lack reliability and validity because of methodological limitations. They also point to a gap in understanding the condition from the point of view of the adolescent. A more useful approach, therefore, is to use a qualitative research methodology. Such an approach has been shown to be useful in a study of diabetic adolescents, and offers promise for the greater understanding of kidney‐transplanted adolescents and the impact the medical regimen has on them. With improved understanding comes the ability of health practitioners to better meet their needs in terms of improving the quality of their post‐operative lives.
Modeling the structure of bound peptide ligands to major histocompatibility complex
Authors: Tong Joo Chuan , Tan Tin Wee , Ranganathan Shoba
Published: August 2004

In this article, we present a new technique for the rapid and precise docking of peptides to MHC class I and class II receptors. Our docking procedure consists of three steps: (1) peptide residues near the ends of the binding groove are docked by using an efficient pseudo‐Brownian rigid body docking procedure followed by (2) loop closure of the intervening backbone structure by satisfaction of spatial constraints, and subsequently, (3) the refinement of the entire backbone and ligand interacting side chains and receptor side chains experiencing atomic clash at the MHC receptor–peptide interface. The method was tested by remodeling of 40 nonredundant complexes of at least 3.00 Å resolution for which three‐dimensional structural information is available and independently for docking peptides derived from 15 nonredundant complexes into a single template structure. In the first test, 33 out of 40 MHC class I and class II peptides and in the second test, 11 out of 15 MHC–peptide complexes were modeled with a Cα RMSD < 1.00 Å.
The HU–DNA binding interaction probed with UV resonance Raman spectroscopy: Structural elements of specificity
Authors: Wojtuszewski Kristi , Mukerji Ishita
Published: August 2004

The Escherichia coli protein HU functions as an architectural DNA‐binding protein by facilitating DNA looping or bending to form multiprotein complexes. Although HU does not recognize a specific DNA sequence, site‐specific binding to a number of discontinuous, looped, or bent DNA substrates has been observed. In this study UV resonance Raman (UVRR) spectroscopy is used to identify structural elements associated with low‐ and high‐affinity binding by examining three different HU–DNA complexes. UVRR spectra obtained with an excitation wavelength of 210 nm, which preferentially enhances protein backbone amide vibrations, indicate that HU secondary structure content increases and the protein structure becomes more rigid upon binding to DNA. The increase in α‐helical content is attributed to the C‐terminal helix, which interacts with the DNA and may play a role in binding affinity and specificity. UVRR spectra obtained with a 215 nm excitation wavelength demonstrate that Pro mode intensity at 1455 cm−1 decreases upon complex formation. This intensity decrease is attributed to the intercalation of Pro residues between DNA base pairs to induce a bend in the DNA, as has been observed previously in the IHF–DNA and HU–DNA cocrystal structures. DNA vibrational modes are also indicative of significant base unstacking and opening of the minor groove upon protein binding, consistent with bending and distortion of the DNA. In all three complexes, A‐DNA conformational features are indicated by deoxyribose‐phosphate backbone modes. These and other results suggest that protein‐induced bending plays an important role in HU site‐specific binding and supports a model of a mutually induced fit.
Conformational stability and thermodynamic characterization of the lipoic acid bearing domain of human mitochondrial branched chain α‐ketoacid dehydrogenase
Authors: Naik Mandar T. , Huang Tai‐Huang
Published: August 2004

The lipoic acid bearing domain (hbLBD) of human mitochondrial branched chain α‐ketoacid dehydrogenase (BCKD) plays important role of substrate channeling in oxidative decarboxylation of the branched chain α‐ketoacids. Recently hbLBD has been found to follow two‐step folding mechanism without detectable presence of stable or kinetic intermediates. The present study describes the conformational stability underlying the folding of this small β‐barrel domain. Thermal denaturation in presence of urea and isothermal urea denaturation titrations are used to evaluate various thermodynamic parameters defining the equilibrium unfolding. The linear extrapolation model successfully describes the two‐step; native state ↔denatured state unfolding transition of hbLBD. The average temperature of maximum stability of hbLBD is estimated as 295.6 ± 0.9 K. Cold denaturation of hbLBD is also predicted and discussed.
Long‐range allosteric transitions in carbamoyl phosphate synthetase
Authors: Thoden James B. , Huang Xinyi , Kim Jungwook , Raushel Frank M. , Holden Hazel M.
Published: August 2004

Carbamoyl phosphate synthetase plays a key role in both pyrimidine and arginine biosynthesis by catalyzing the production of carbamoyl phosphate from one molecule of bicarbonate, two molecules of MgATP, and one molecule of glutamine. The enzyme from Escherichia coli consists of two polypeptide chains referred to as the small and large subunits, which contain a total of three separate active sites that are connected by an intramolecular tunnel. The small subunit harbors one of these active sites and is responsible for the hydrolysis of glutamine to glutamate and ammonia. The large subunit binds the two required molecules of MgATP and is involved in assembling the final product. Compounds such as L‐ornithine, UMP, and IMP allosterically regulate the enzyme. Here, we report the three‐dimensional structure of a site‐directed mutant protein of carbamoyl phosphate synthetase from E. coli, where Cys 248 in the small subunit was changed to an aspartate. This residue was targeted for a structural investigation because previous studies demonstrated that the partial glutaminase activity of the C248D mutant protein was increased 40‐fold relative to the wild‐type enzyme, whereas the formation of carbamoyl phosphate using glutamine as a nitrogen source was completely abolished. Remarkably, although Cys 248 in the small subunit is located at ∼100 Å from the allosteric binding pocket in the large subunit, the electron density map clearly revealed the presence of UMP, although this ligand was never included in the purification or crystallization schemes. The manner in which UMP binds to carbamoyl phosphate synthetase is described.
Solution structure of the human Grb14–SH2 domain and comparison with the structures of the human Grb7–SH2/erbB2 peptide complex and human Grb10–SH2 domain
Authors: Scharf Paul J. , Witney Jill , Daly Roger , Lyons Barbara A.
Published: August 2004

Grb14 is an adapter protein that is known to be overexpressed in estrogen receptor positive breast cancers, and in a number of prostate cancer cell lines. Grb14 has been demonstrated to bind to a number of activated receptor tyrosine kinases (RTKs) and to modulate signals transduced through these receptors. The RTKs to which Grb14 binds include the insulin receptor (IR), the fibroblast growth factor receptor (FGFR), the platelet‐derived growth factor receptor (PDGFR), and the tunica endothelial kinase (Tek/Tie2) receptor. Grb14 has been shown to bind to these activated RTKs through its Src homology 2 (SH2) domain, with the exception of the insulin receptor, where the primary binding interaction is via a small domain adjacent to the SH2 domain (the BPS or PIR domain). Grb14 is a member of the Grb7 family of proteins, which also includes Grb7 and Grb10. We have solved the solution structure of the human Grb14–SH2 domain and compared it with the recently determined Grb7–SH2 and Grb10–SH2 domain structures.
Changes in Sexual Function in Middle‐Aged and Older Men: Longitudinal Data from the Massachusetts Male Aging Study
Authors: Araujo Andre B. , Mohr Beth A. , McKinlay John B.
Published: August 2004

Objectives: To describe within‐individual change in sexual function over a 9‐year period and to determine whether the amount of change differs by age group.

Design: Cohort study; participants interviewed at baseline (1987–89) and follow‐up (1995–97).

Setting: Population‐based; communities surrounding Boston, Massachusetts.

Participants: One thousand eighty‐five men aged 40 to 70 at baseline (born between 1917 and 1947) with complete baseline and follow‐up sexual function data.

Measurements: Within‐person change (follow‐up minus baseline) in the following sexual function variables: sexual intercourse, erection frequency, sexual desire, ejaculation with masturbation, satisfaction with sex, and difficulty with orgasm.

Results: Unadjusted analyses showed significant longitudinal changes over the 9‐year period in all domains of sexual function except frequency of ejaculation with masturbation, which showed no change between baseline and follow‐up. Adjusted for baseline sexual function, within‐person change in all outcomes was strongly related to age, with decline in sexual function becoming more pronounced with increasing age. For example, over the 9‐year study period, sexual intercourse or activity frequency decreased by less than once per month, two times per month, and three times per month in men in their 40s, 50s, and 60s, respectively. Number of erections per month declined by 3, 9, and 13 in men in their 40s, 50s, and 60s, respectively.

Conclusion: This research fills a major gap in the literature by providing age‐specific estimates of change in sexual functioning over a 9‐year period in a cohort of unselected men.
Family cancer histories predictive of a high risk of hereditary non‐polyposis colorectal cancer associate significantly with a genomic rearrangement in hMSH2 or hMLH1
Authors: Ainsworth PJ , Koscinski D. , Fraser BP , Stuart JA
Published: August 2004

Hereditary non‐polyposis colorectal cancer (HNPCC) results from inactivating germline mutations in a set of DNA‐mismatch‐repair genes, of which the most clinically relevant are hMSH2 and hMLH1. Computer‐assisted pedigree risk assessment tools are available to assist in the calculation of an individual's likelihood of bearing such a deleterious mutation. One such tool, cancergene version 3.4 (http://www3.utsouthwestern.edu/cancergene) was used to assess the risk of a deleterious mutation in the genes hMSH2 and/or hMLH1 in a series of probands selected from a panel of 67 South‐western Ontario kindred previously identified as likely candidates for HNPCC by established clinical criteria. A DNA sample isolated from peripheral blood leukocytes obtained from each of these probands was examined for genomic rearrangement using the multiplex ligation‐dependent probe amplification (MLPA) method. Of the individuals calculated to have a risk of >50% of a hMSH2 or hMLH1 gene mutation by the CancerGene risk assessment tool, 69% (9/13) were shown to have a genomic rearrangement resulting in the deletion of one or more exons of one of these two genes. Family cancer histories predictive of a high risk of HNPCC significantly associate with a genomic rearrangement in hMSH2 or hMLH1.
In Defence of a Dogma: Davidson, Languages, and Conceptual Schemes
Authors: Nevo Isaac
Published: August 2004

In this paper I draw on Davidson's work to generate counter examples to his claim that since there are no untranslatable languages there are also no alternative conceptual schemes. I argue that Davidson's argument to that effect is based upon an equivocation.
Aberrant IgG2 Antibody Response to Neisseria Meningitidis Polysaccharide A After Vaccination in Frequently Infected Compared to Healthy IgA‐Deficient Individuals
Authors: Friman V. , Hahn‐Zoric M. , Björkander J. , Oxelius V.‐A. , Hanson L. Å.
Published: August 2004

In search for a possible explanation of the phenotypic heterogeneity in selective immunoglobulin (Ig)A deficiency, we studied the IgG2 antibody response to meningococcal polysaccharide A (PSA) in IgA‐deficient (IgAd) individuals after vaccination with meningococcal A + C polysaccharide vaccine. Two groups of IgAd individuals, one frequently infected and one clinically apparently healthy, as well as healthy controls, were studied. In response to meningococcal A + C polysaccharide vaccine, a significant titre increase of specific IgG2 anti‐PSA was found in 71% of the control individuals, in 50% of the healthy and in 42% of the infection‐prone IgAd individuals. The specific IgG2 response against meningococcal PSA was significantly lower in the infection‐prone IgAd individuals compared to the controls (P < 0.05). Among the IgAd individuals who responded with a significant IgG2 antibody increase, the IgG2 antibody response was significantly lower in the infection‐prone than in the healthy IgAd individuals (P < 0.05). Thus, a limited capacity to mount a specific IgG2 response may suggest a more profound antibody maturation defect in infection‐prone IgAd patients compared to healthy IgAd individuals.
Interactions Between Lipoxin A4, the Stable Analogue 16‐phenoxy‐lipoxin A4 and Leukotriene B4 in Cytokine Generation by Human Monocytes
Authors: Andersson P. , Serhan C. N. , Petasis N. A. , Palmblad J.
Published: August 2004

Lipoxins display both stimulatory and inhibitory actions with leucocytes that are cell‐type dependent. We tested whether lipoxin A4 (LXA4) and its stable synthetic analogue 16‐phenoxy‐17‐18,19,20‐tetranor‐lipoxin‐A4 (16‐phe‐LXA4) modulated the ability of human blood monocytes (MO) to express mRNA and proteins for interleukin‐1β (IL‐1β), IL‐6 and IL‐1 receptor antagonist (IL‐1Ra) in vitro and compared their actions with lipopolysaccharide (LPS) and leukotriene B4 (LTB4). 16‐phe‐LXA4, LPS and LTB4, but not LXA4, induced gene expression of IL‐1β in MO. IL‐1β protein synthesis increased by LPS (1500‐fold), LTB4 (280‐fold) and 16‐phe‐LXA4 (30‐fold). Although the IL‐1Ra gene was constitutively activated, mRNA concentration not affected by any of the stimulants, IL‐Ra protein synthesis was increased by LPS (with 74%), 16‐phe‐LXA4 (35%) and LTB4 (20%), but not by LXA4. Each of these stimuli upregulated the IL‐6 gene. Increases of IL‐6 protein were 3000‐fold for LPS, threefold for 16‐phe‐LXA4, eightfold for LXA4 and twofold for LTB4. Prior exposure of MO to 16‐phe‐LXA4, but not LXA4, reduced LTB4 induced synthesis of IL‐1β with 66%, IL‐6 with 20% and IL‐1Ra with 29%. Thus, a stable LXA analogue, that resists rapid inactivation by monocytes, displays novel actions in cytokine generation, intimately involved in the regulation of inflammation.
Protective Responses in Tuberculosis: Induction of Genes for Interferon‐γ and Cytotoxicity by Mycobacterium tuberculosis and During Human Tuberculosis
Authors: Toossi Z. , Mayanja‐Kizza H. , Kanost A. , Edmonds K. , McHugh M. , Hirsch C.
Published: August 2004

The host effector mechanisms against Mycobacterium tuberculosis infection are not well understood, and this remains a problem in the development of new vaccines and immunotherapies in tuberculosis (TB). Here, we studied the expression of genes for interferon gamma (IFN‐γ) and molecules involved in lymphocyte‐mediated cytotoxicity [granzyme B (grzB), perforin, granulysin and Fas ligand (FasL)] against M. tuberculosis‐infected macrophages. The kinetics of expression of these molecules were first established in peripheral blood mononuclear cells (PBMC) of healthy donors, and then investigated in TB patients with and without HIV‐1 coinfection and appropriate control groups. We found that only IFN‐γ and grzB were induced by M. tuberculosis in PBMC from healthy purified protein derivative skin test reactive subjects. However, expression of neither gene nor IFN‐γ protein correlated with intracellular M. tuberculosis growth containment by macrophages. Mycobacterium tuberculosis induction of IFN‐γ, but not grzB, mRNA expression was significantly lower (P < 0.03) in TB patients as compared with healthy subjects.
Mesenchymal Stem Cells Inhibit the Expression of CD25 (Interleukin‐2 Receptor) and CD38 on Phytohaemagglutinin‐Activated Lymphocytes
Authors: Le Blanc K. , Rasmusson I. , Götherström C. , Seidel C. , Sundberg B. , Sundin M. , Rosendahl K. , Tammik C. , Ringdén O.
Published: August 2004

Mesenchymal stem cells (MSC) are immunomodulatory and inhibit lymphocyte proliferation. We studied surface expression of lymphocyte activation markers and secreted cytokines, when lymphocytes were activated in the presence of MSC. MSC suppressed the proliferation of phytohaemagglutinin (PHA)‐stimulated CD3+, CD4+ and CD8+ lymphocytes. MSC significantly reduced the expression of activation markers CD25, CD38 and CD69 on PHA‐stimulated lymphocytes. Mixed lymphocyte culture (MLC) supernatants containing MSC suppressed proliferation of MLC and PHA‐stimulated lymphocytes dose‐dependently. MSC secrete osteoprotegerin (OPG), but not hepatocyte growth factor (HGF) or transforming growth factor‐β (TGF‐β). Stromal‐cell‐derived factor‐1 (SDF‐1) is not expressed on the cell surface. A recent report suggested that T‐cell suppression by MSC is mediated by HGF and TGF‐β. MSC suppression was not restored by the addition of neutralizing antibodies against SDF‐1, OPG, HGF or TGF‐β, alone or in combination. Addition of guanosine to PHA‐stimulated lymphocyte cultures containing MSC did not affect lymphocyte proliferation. The immunosuppressive effects of cyclosporine and MSC did not interfere, when present in the cultures of PHA‐activated lymphocytes. In summary, human MSC suppress proliferation of both CD4+ and CD8+ lymphocyte and decrease the expression of activation markers.
Perception of the Climate for Creativity in the Workplace: the Role of the Level in the Organization and Gender
Authors: Kwaśniewska Joanna , Nȩcka Edward
Published: August 2004

This paper reports a study conducted to examine differences between employees in managerial and non‐managerial positions, as well as between men and women, in their perception of climate for creativity in the workplace. It was hypothesized that, in general, managers would perceive the climate as more favourable than non‐managers, and this discrepancy should be modulated by gender. The questionnaire used in the study, conceptually grounded in Amabile's empirical and theoretical work on creativity and innovation, was administered to 388 respondents: 229 female and 159 male participants drawn from a wide range of Polish work organizations. The results show that managers perceive the climate as significantly more conducive to creativity than non‐managers do. Female employees perceive the climate less favourably than male employees, although these differences appeared smaller and less frequent as compared to the managers/non‐managers comparisons. Moreover, higher positions of female participants in the organization do not improve their perception of the climate to the same extent as it does in the case of male participants. Implications and areas for future research are explored.
How is money spent on children's services?
Authors: Thalange N. , Gardner C. , Reading R.
Published: August 2004

Finance and activity data for the year 1999–2000 were used to identify the money spent on children's services in health and social care in a county with a population of 790 000. Total costs were almost £80m. Considerable amounts were spent on high cost, low volume activity. Local health and social care commissioners require this information to implement and monitor changes in children's services, particularly in light of the UK government proposals for children's trusts.
The measure of processes of care (MPOC): validation of the Dutch translation
Authors: Van Schie P. E. M. , Siebes R. C. , Ketelaar M. , Vermeer A.
Published: August 2004

Aim  The objective was to validate the Dutch translation of the Canadian measure of processes of care (MPOC) questionnaire for use in children's rehabilitation centres in the Netherlands. MPOC consists of 56 items (assessing five domains) and was designed to find out what parents of children with chronic health problems think of the services they and their child receive and to measure the extent to which these services are family‐centred.

Methods  The Canadian validation procedures were followed, consisting of construct and concurrent validation and reliability analyses. Participants were parents of 427 children aged 1–18 years recruited through nine children's rehabilitation centres in the Netherlands.

Results  The construct validity of the Dutch version of MPOC (MPOC‐NL) was examined with confirmative analyses of the scale structure. These analyses all supported the construct validity of MPOC‐NL. MPOC‐NL showed adequate internal consistency, with Cronbach's α ranging from 0.80 to 0.95. The intraclass correlation coefficients (ICCs) ranged from 0.79 to 0.94, which demonstrated good stability of MPOC‐NL. The Spearman correlations between MPOC‐NL scores and satisfaction questions ranged from 0.39 to 0.73, and thus supported the construct validity of MPOC‐NL. Correlations between MPOC‐NL scores and a question about parents’ stress in relation to services received were moderately negative (rs = −0.28 to −0.39).

Conclusion  The construct and concurrent validity of MPOC‐NL was shown by confirmative analyses of the original Canadian scale structure, and by modest Spearman correlations between MPOC‐NL scores and satisfaction and stress variables. MPOC‐NL is internally consistent and reliable.
CD8α+ dendritic cells and immune protection from experimental allergic encephalomyelitis
Authors: PETTERSSON Å , WU X-C , CIUMAS C , LIAN H , CHIRSKY V , HUANG Y-M , BJELKE B , LINK H , XIAO B-G
Published: August 2004

Dendritic cells (DC) represent a phenotypically heterogeneous population endowed with two important biological functions, immunity and tolerance. Here we report that the injection of splenic CD8α+ DC, derived from rats with experimental allergic encephalomyelitis (EAE), delayed the onset and suppressed the severity of EAE in Lewis rats. This was accompanied by the lack of magnetic resonance imaging (MRI) lesions in the brain and spinal cord and by reduced numbers of inflammatory cells within the central nervous system. Injection of CD8α+ DC inhibited T cell proliferation that may relate to increased interferon (IFN)-γ and nitric oxide production. Although CD8+CD28– suppressor T cells, apoptotic cells and co-stimulatory molecules were not altered, CD4+ T cells expressing interleukin (IL)-10 were augmented in rats receiving CD8α+ DC compared to rats receiving total DC or medium. These results demonstrate that rat splenic CD8α+ DC could provide a cellular basis for a novel, individualized immunotherapy using autologous DC as a complement to conventional therapy in diseases with an autoimmune background such as multiple sclerosis.
Development of granulomatous common variable immunodeficiency subsequent to infection withToxoplasma gondii
Authors: MRUSEK S , MARX A , KÜMMERLE-DESCHNER J , TZARIBACHEV N , ENDERS A , RIEDE U-N , WARNATZ K , DANNECKER G E , EHL S
Published: August 2004

Common variable immunodeficiency (CVID) is a heterogeneous immunodeficiency that is accompanied by granulomatous lesions in 5–10% of cases. Why some patients develop granulomatous disease remains unclear. Here we describe a 12-year-old previously healthy girl who presented with pancytopenia and granulomatous lymphoproliferation subsequent to infection with Toxoplasma gondii. Loosely arranged non-fibrosing granulomas were observed in the liver, lymph nodes and lung, but no Toxoplasma tachyzoites could be demonstrated and polymerase chain reaction (PCR) and culture were negative for Toxoplasma and a wide range of other pathogens. While the patient had a normal peripheral B cell status at presentation, the development of CVID could be observed during the following months, leading to a loss of memory B cells. This was accompanied by an increasingly activated CD4+ T cell compartment and high serum levels of angiotensin-converting enzyme (ACE), tumour necrosis factor (TNF) and sCD25. Steroid therapy reduced pancytopenia, granulomatous lymphoproliferation and cytokine elevations, but did not improve the B cell status. This is the first report of an association of Toxoplasma infection with granulomatous CVID and provides one of the rare examples where the onset of CVID could be documented subsequent to an infectious disease.
CCTTT-repeat polymorphism of the inducible nitric oxide synthase is not associated with HIV pathogenesis
Authors:   THE SWISS HIV COHORT STUDY, HERSBERGER M , BONHOEFFER S , RAMPINI S K , OPRAVIL M , MARTI-JAUN J , TELENTI A , HÄNSELER E , LEDERGERBER B , SPECK R F
Published: August 2004

Nitric oxide (NO) produced by the inducible form of nitric oxide synthase (iNOS) has bactericidal and virocidal effects. Although NO synthesis and iNOS expression in macrophages affect several aspects of human immunodeficiency virus (HIV) type-1 pathogenesis, their role in HIV disease remains largely unknown. In humans, the expression of iNOS is influenced by a functional CCTTT-repeat polymorphism in the promoter region of the gene. We investigated the association of this polymorphism with HIV pathogenesis in naive HIV-infected patients before the initiation of antiretroviral therapy. The allele frequencies of the iNOS CCTTT-repeat polymorphism were assessed by PCR in 857 patients from the Swiss HIV Cohort Study, including rapid progressors and long-term nonprogressors, and in 240 healthy volunteers. In HIV-infected patients, the initial viral load and the decline in total CD4 cells was calculated to estimate disease progression. Allele frequencies of the iNOS CCTTT-repeat polymorphism were similar between the HIV-infected and noninfected blood donors. In treatment-naive HIV-positive patients, there was no association of the iNOS polymorphism with viral load or with the course of CD4 cells. Regulation of iNOS expression by the functional CCTTT-polymorphism does not modify HIV pathogenesis.
Importance of FNAC in the detection of tumours within multinodular goitre of the thyroid
Authors: Kojić Katović S. , Halbauer M. , Tomić‐Brzac H.
Published: August 2004

The primary challenge in the management of a multinodular thyroid gland is to rule out malignancy. The present study was undertaken to assess the value of preoperative ultrasound‐guided fine needle aspiration cytology (FNAC) in diagnosing tumours of the thyroid gland. Of the 80 patients operated for multinodular lesions, malignant tumours were found in 29 and benign tumours in 36 patients (81%) and non‐tumorous lesions in 15 (19%) patients. Compared with the histopathological postoperative diagnosis, the overall sensitivity of FNAC was 85% and specificity 88%. Current morphological diagnosis of the nodules in multinodular goitre requires thorough preoperative examination, including ultrasound‐guided FNAC in order to establish the appropriate management.
Follicular variant of papillary thyroid carcinoma – a cytological study
Authors: Jogai S. , Adesina A. O. , Temmim L. , Al‐Jassar A. , Amir T. , Amanguno H. G.
Published: August 2004

The cytological diagnosis of classical papillary carcinoma is easily established based on the characteristic architectural and nuclear features. However, the follicular variant of papillary thyroid carcinoma(FVPTC) poses a diagnostic challenge. In this study we analysed the cytological features of 14 histopathologically proven cases of FVPTC. We inferred that a combination of architectural features such as follicles and syncytial clusters and nuclear features, viz grooves, pseudoinclusions and enlarged nuclei with fine chromatin, were helpful in establishing the diagnosis. It is hence suggested that based on the combination of the aforesaid features a diagnosis of FVPTC be offered whenever it is possible. This helps in patient management, obviating the need for a second surgical intervention.
Optimization of sub‐band coding method for seismic data compression
Authors: Røsten Tage , Ramstad Tor A. , Amundsen Lasse
Published: August 2004

Seismic data volumes, which require huge transmission capacities and massive storage media, continue to increase rapidly due to acquisition of 3D and 4D multiple streamer surveys, multicomponent data sets, reprocessing of prestack seismic data, calculation of post‐stack seismic data attributes, etc. We consider lossy compression as an important tool for efficient handling of large seismic data sets. We present a 2D lossy seismic data compression algorithm, based on sub‐band coding, and we focus on adaptation and optimization of the method for common‐offset gathers. The sub‐band coding algorithm consists of five stages: first, a preprocessing phase using an automatic gain control to decrease the non‐stationary behaviour of seismic data; second, a decorrelation stage using a uniform analysis filter bank to concentrate the energy of seismic data into a minimum number of sub‐bands; third, an iterative classification algorithm, based on an estimation of variances of blocks of sub‐band samples, to classify the sub‐band samples into a fixed number of classes with approximately the same statistics; fourth, a quantization step using a uniform scalar quantizer, which gives an approximation of the sub‐band samples to allow for high compression ratios; and fifth, an entropy coding stage using a fixed number of arithmetic encoders matched to the corresponding statistics of the classified and quantized sub‐band samples to achieve compression. Decompression basically performs the opposite operations in reverse order. We compare the proposed algorithm with three other seismic data compression algorithms. The high performance of our optimized sub‐band coding method is supported by objective and subjective results.
Multiple cognitive deficits during the transition to Alzheimer's disease
Authors: Bäckman L. , Jones S. , Berger A.‐K. , Laukka E. J. , Small B. J.
Published: August 2004

The literature on cognitive markers in preclinical AD is reviewed. The findings demonstrate that impairment in multiple cognitive domains is typically observed several years before clinical diagnosis. Measures of executive functioning, episodic memory and perceptual speed appear to be most effective at identifying at‐risk individuals. The fact that these cognitive domains are most implicated in normal cognitive aging suggests that the cognitive deficit observed preclinically is not qualitatively different from that observed in normal aging. The degree of cognitive impairment prior to the diagnosis of Alzheimer's disease (AD) appears to generalize relatively well across major study characteristics, including sample ascertainment procedures, age and cognitive status of participants, as well as time to diagnosis of dementia. In episodic memory, there is evidence that the size of the preclinical deficit increases with increasing cognitive demands. The global cognitive impairment observed is highly consistent with observations that multiple brain structures and functions are affected long before the diagnosis of AD. However, there is substantial overlap in the distribution of cognitive scores between those who will and those who will not be diagnosed with AD, hence limiting the clinical utility of cognitive markers for early identification of cases. Future research should consider combining cognitive indicators with other types of markers (i.e. social, somatic, genetic, brain‐based) in order to increase prediction accuracy.
P‐75  Development of an in vitro test to evaluate cerumen‐dissolving properties of veterinary ear cleansing solutions
Authors: Nielloud F. , Reme C. A. , Fortune R. , Laget J. P. , Mestres G. , Gatto H.
Published: August 2004

This study aimed to evaluate objectively the cleansing properties of four veterinary ear care solutions. An in vitro test was developed, based on dissolution of synthetic dog cerumen in test tubes. Artificial cerumen was produced, based on literature data, with a melting point and consistency very close to natural canine cerumen. One millilitre of test solution was poured into haemolysis tubes containing 100 mg of synthetic cerumen. Contact time was 10 min at 37°C. Moderate agitation was then applied for 10 s to mimic in vivo application. Solutions were vacuum‐filtered on filter paper and cerumen remaining in the tube or on the paper was weighed after drying. The experiment was repeated five times for each formulation. One‐way ANOVA was performed to detect differences between formulations. In order to validate the test, measurement of the solution wetting power was performed in parallel using the reference ISO 8022 method. Mean quantities of cerumen dissolved were 4.7, 6.5, 7.7, 14.7 and 23.2 mg for Cerulane®, Otolane®, distilled water (control), Otoclean® and Physiological Ear Cleanser®, respectively. The latter was the only solution that demonstrated greater ability for cerumen dissolution as compared to water (P < 0.05). Macroscopically, Physiological Ear Cleanser® solution became white and opaque in test tubes, reflecting the formation of an emulsion. Other solutions remained clear or only partially turbid. This cerumen dissolution test proved a practical and valuable model to assess the cleansing power of ear solutions before in vivo trials.

Funding: Virbac SA.
FC‐41  A prospective pilot study on the use of cyclosporin on feline allergic diseases
Authors: Noli C. , Scarampella F.
Published: August 2004

The efficacy of cyclosporin in canine atopic dermatitis has been well documented, but reports on its use in feline allergic dermatoses are scarce. The aim of this study was to evaluate the efficacy of cyclosporin in cats affected by pruritus and eosinophilic dermatoses. Ten otherwise healthy cats were selected. All cats had no response to a hypoallergenic diet trial, had not been treated with short‐acting corticosteroids or antihistamines for at least 2 weeks, had not been treated with long‐acting steroids for 2 months, and had been treated with endo‐ and ectoparasiticidal drugs with no improvement 2 weeks before entering the study. All cats were pruritic and had erythema, seven had alopecia, five had an eosinophilic plaque, three had facial pruritus, one had miliary dermatitis, and one had an eosinophilic granuloma. Cyclosporin was administered daily at the dosage of 5 mg/kg for 1 month. Owners assessed pruritus by means of a visual analogue scale, and veterinarians evaluated cutaneous lesions on days 0 and 30 by a newly developed index called Feline Eosinophilic Granuloma, Eosinophilic Plaque, Extension and Severity Index (FEGEPESI), similar to the Canine Atopic Dermatitis Extension and Severity Index (CADESI). Fifty percent of the cats had a reduction of pruritus ≥ 50%, and in 50% of the animals, the lesions improved or disappeared completely. However, overall pruritus and FEGEPESI scores did not improve significantly. In conclusion, cyclosporin was helpful in symptomatically treating about half of the cases of feline pruritus and eosinophilic dermatitides.

Funding: Novartis.
Functioning of family nursing in transition: an example of a small town in Poland. Are there any benefits for patients?
Authors: Marcinowicz Ludmiła , Chlabicz Sławomir
Published: August 2004

Objective  To evaluate whether organizational changes in the Polish health care system affected patients’ opinions about selected aspects of the quality of care provided by family nurses.

Design  Two independent surveys conducted in 1998 and 2002 using face‐to‐face interviews with structured questionnaires.

Setting and participants  The study was performed in a small town in Poland, where family physicians were introduced in 1995. The study groups consisted of two samples of patients randomly selected from those registered on the patient list. Altogether 1000 interviews were obtained in survey I (in 1998) and 1000 from another sample in survey II (in 2002). In 1998, family nurses were employed by family physicians, but in 2002 they had established their own practices and held direct contracts with the National Health Fund.

Results  The surveys carried out at a 4‐year interval showed a significant increase in the percentage of patients reporting home visits by family nurses, both at the request of physicians and on the nurses’ own initiative (from 16.3 to 45.8%, P < 0.05). Comparative analysis showed that in survey II the percentage of the respondents who were satisfied with nursing care increased from 35.8 to 53.6% (P < 0.05).

Conclusion  Care provided by independent nurses was available to a larger group of patients. Patients were more satisfied with the services of family nurses working as independent contractors. The investigations in the present study should be supplemented by a qualitative study.