bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical features, diagnosis, treatment and molecular studies in paediatric Cushing's syndrome due to primary nodular adrenocortical hyperplasia
Authors: Storr H. L. , Mitchell H. , Swords F. M. , Main K. M. , Hindmarsh P. C. , Betts P. R. , Shaw N. J. , Johnston D. I. , Clark A. J. L. , Reznek R. H. , Grossman A. B. , Savage M. O.
Published: November 2004

background  Primary nodular adrenocortical hyperplasia (PNAH) is a well recognized, but infrequently studied cause of paediatric Cushing's syndrome (CS).

objective  To assess presentation, diagnosis, radiological imaging, treatment and molecular analysis of patients with childhood‐onset CS due to PNAH.

patients  Four males and two females (median age 12·9 years, range 10·9–16·9 years) were studied.

results  All had growth failure (mean height SDS −1·2; range −2·5–0·0), weight gain [mean body mass index (BMI) SDS 3·5; range 2·5–4·6] and clinical virilization, while five had hypertension [mean systolic blood pressure (SBP) 130 mmHg, diastolic blood pressure (DBP) 83 mmHg]. One patient had generalized lentigines, one had a tibial chondromyxomatous cyst and two had facial freckling. One patient had a family history of primary nodular adrenocortical disease. The diagnosis of CS was based on elevation of sleeping midnight serum cortisol and urinary free cortisol excretion, and impaired suppression of cortisol on both low‐ and high‐dose dexamethasone suppression tests (DST). All patients had undetectable plasma ACTH with absent responses of both plasma ACTH and serum cortisol to an intravenous (i.v.) corticotrophin‐releasing hormone (CRH) test. Computed tomography or magnetic resonance imaging showed normal or small adrenals, with nodules in two patients. All patients underwent bilateral adrenalectomy, performed by open (n = 2) or laparoscopic surgery (n = 4) at a mean of 0·4 years (range 0·2–0·8 years) from diagnosis. Hypercortisolaemia was treated preoperatively by metyrapone alone 0·50–0·75 g/day (n = 4), metyrapone 0·75–1·50 g/day + o’p'DDD/mitotane 1–2 g/day (n = 1), or ketoconazole (n = 1). Adrenal histology showed nodular cortical hyperplasia with shrinkage of intervening cortical tissue and pigmentation, present in four patients. Molecular analysis of the type 1‐α regulatory subunit of protein kinase A (PRKAR1A) gene revealed a novel germline mutation in one patient. Postadrenalectomy, three patients, had catch‐up growth with height velocities increasing from 3·0, 3·9 and 2·5–8·9, 8·3 and 9·0 cm/years, respectively. All six are well at a follow‐up (mean 4·0 years; range 0·5–10·8 years).

conclusions  PNAH was associated with cushingoid features, virilization and hypertension with a lack of cortisol suppression on high DST, undetectable plasma ACTH and absent cortisol and ACTH responses to CRH. Adrenals were normal or small on imaging. PRKAR1A gene analysis may be helpful in the assessment of these patients.
Characterization of a promoter polymorphism in the glucocorticoid receptor gene and its relationship to three other polymorphisms
Authors: Van Rossum Elisabeth F. C. , Roks Petronella H. M. , De Jong Frank H. , Brinkmann Albert O. , Pols Huib A. P. , Koper Jan W. , Lamberts Steven W. J.
Published: November 2004

objective  Sensitivity to glucocorticoids within the normal population is highly variable and partly determined by polymorphisms in the glucocorticoid receptor (GR) gene (NR3C1). We investigated the exact sequence alteration of a TthIIII polymorphism in the GR gene, whether it is associated with glucocorticoid sensitivity, and its relationship to 3 polymorphisms of the GR gene (N363S, BclI, ER22/23EK).

design  Two dexamethasone (DEX) suppression tests were performed with 1 and 0·25 mg DEX, respectively.

patients  We genotyped a random subgroup of 209 participants of the Rotterdam Study, a population‐based study in the elderly.

measurements  Anthropometric parameters, cortisol, insulin and glucose levels, and lipid concentrations were measured.

results  We identified the TthIIII polymorphism as a C to T mutation, 3807 bp upstream from the mRNA start site. We found 39·7% CC‐carriers, 44·5% CT‐carriers, and 15·8 % TT‐carriers. No differences were found between TthIIII genotypes in sensitivity to DEX, baseline cortisol, insulin, glucose or cholesterol levels, or in anthropometric variables. However, all ER22/23EK‐carriers also carried the TthIIII T‐allele, and carriers of both these polymorphisms had a significantly smaller cortisol suppression after 1 mg DEX, lower fasting insulin levels, and lower total and low‐density lipoprotein (LDL) cholesterol levels than TthIIII T carriers without the ER22/23EK variant and noncarriers. No interaction was found between the TthIIII variant and N363S or BclI polymorphisms.

conclusions  The TthIIII polymorphism is not functional by itself. However, the ER22/23EK polymorphism is without exception linked to the TthIIII T polymorphism and this haplotype is associated with a relative resistance to glucocorticoids, and a healthy metabolic profile.
Associations of insulin‐like growth factors, insulin‐like growth factor binding proteins and acid‐labile subunit with coronary heart disease
Authors: Fischer Frank , Schulte Helmut , Mohan Subburaman , Tataru Mira‐Christine , Köhler Ekkehart , Assmann Gerd , Von Eckardstein Arnold
Published: November 2004

objective  IGFs and their binding proteins (IGFBPs) are produced both systemically and locally by cells of the cardiovascular system. As growth promoters, they may play a role in atherosclerosis.

design  Case–control, cross‐sectional.

patients  A total of 95 nondiabetic male patients with coronary heart disease (CHD) and 92 probands from the Prospective Cardiovascular Münster (PROCAM) who were below the age of 60 years and matched by age, body mass index (BMI) and smoking habits

measurements  We analysed the strength and independence of associations of angiographically assessed presence of CHD with BMI, systolic and diastolic blood pressure, total, high‐density lipoprotein (HDL) and LDL cholesterol, triglycerides, lipoprotein(a), apolipoproteins A‐I and B, total and free IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐3, IGFBP‐5, acid‐labile subunit (ALS), insulin, C‐peptide, testosterone, DHEAS and sex hormone binding globulin.

results  Using multivariate statistical analysis, the presence of CHD had significant positive associations with total IGF‐I, IGFBP‐5, ALS and IGFBP‐3. These associations were independent of each other as well as of traditional risk factors, insulin and sex hormones.

conclusion  These observations may indicate a pathogenetic role of the GH/IGF axis in coronary atherosclerosis.
Apolipoprotein E phenotype affects the malondialdehyde‐modified LDL concentration and forearm endothelial function in postmenopausal women
Authors: Tsuda Mikio , Sanada Mitsuhiro , Higashi Yukihito , Hara Yoshiko , Kodama Ichiro , Chayama Kazuaki , Yoshizumi Masao , Ohama Koso
Published: November 2004

objective  We investigated whether the apolipoprotein E (apo E) phenotype affects the serum concentration of malondialdehyde‐modified low‐density lipoprotein (MDA‐LDL) or forearm endothelial function in postmenopausal women.

patients and measurements  Individuals were divided into three groups according to their apo E phenotype: E2 (E2/2 and E2/3, n = 12); E3 (E3/3, n = 71); and E4 (E3/4 and E4/4, n = 27). The serum concentrations of lipids and MDA‐LDL were measured. Forearm blood flow during reactive hyperaemia and after sublingual nitroglycerin administration was measured by strain‐gauge plethysmography.

results  The serum concentrations of total and LDL cholesterol were significantly higher in the E4 group than in the E2 group (P < 0·05) or in the E3 group (P < 0·05). The serum apo B concentration was significantly higher in the E4 group than in the E2 group (P < 0·05). The serum concentrations of high density lipoprotein (HDL) cholesterol and nitrite/nitrate were significantly lower in the E4 group than in the E2 group (P < 0·05). Other lipid concentrations did not differ in the three groups. The serum MDA‐LDL concentration was highest in the E4 group, and was lowest in the E2 group (E2: 91·1 ± 6·9 IU/l, E3: 112·3 ± 5·9 IU/l, E4: 128·8 ± 9·9 IU/l; P < 0·05). The forearm blood flow response to reactive hyperaemia was lowest in the E4 group, and highest in the E2 group (E2: 52·2 ± 5·8 ml/min per 100 ml tissue, E3: 40·7 ± 1·7 ml/min per 100 ml tissue, E4: 33·4 ± 2·4 ml/min per 100 ml tissue; P < 0·05). The forearm blood flow changes in response to nitroglycerine were similar between all three groups.

conclusions  The apo E phenotype affects the serum MDA‐LDL concentration and forearm endothelial function in postmenopausal women.
A novel PROP1 gene mutation (157delA) in Japanese siblings with combined anterior pituitary hormone deficiency
Authors: Tatsumi Ke‐ita , Kikuchi Kiyoshi , Tsumura Kumi , Amino Nobuyuki
Published: November 2004

objective  The majority of cases of combined anterior pituitary hormone deficiency (CPHD) reported in Japanese patients have PIT1 abnormality. This study describes for the first time a homozygous mutation of the PROP1 gene in two Japanese siblings with CPHD born to consanguineous parents.

patients  Two siblings were growth retarded at 3 years of age and developed hypothyroidism. Pituitary function tests showed combined deficiency of GH, TSH, PRL and gonadotrophins. The size of their pituitary glands decreased with age, as demonstrated by magnetic resonance imaging (MRI).

results  The PROP1 gene was analysed by polymerase chain reaction (PCR) followed by direct sequencing. Both children were homozygous for a novel single base deletion at codon 53 (157delA), while their parents were heterozygous. This mutation, if translated, predicts the production of a protein lacking the paired‐like homeodomain required for DNA binding, suggesting that the mutation was the direct cause of CPHD in these patients.

conclusions  157delA is the first reported Japanese PROP1 gene mutation. In Japan, PROP1 abnormality appears to be a less frequent cause of CPHD than does PIT1 abnormality, whereas PROP1 abnormality predominates in CPHD patients of Caucasian and European origin.
Migration velocity analysis by depth image‐wave remigration: first results
Authors: Schleicher J. , Novais A. , Munerato F.P.
Published: November 2004

The image‐wave equation for depth remigration is a partial differential equation that is similar to the acoustic wave equation. In this work, we study its finite‐difference solution and possible applications. The conditions for stability, dispersion and dissipation exhibit a strong wavenumber dependence. Where higher horizontal than vertical wavenumbers are present in the data to be remigrated, stability may be difficult to achieve. Grid dispersion and dissipation can only be reduced to acceptable levels by the choice of very small grid intervals. Numerical tests demonstrate that, upon reaching the true medium velocity, remigrated images of curved reflectors propagate to the correct depth and those of diffractions collapse to single points. The latter property points towards the method's potential for use as a tool for migration velocity analysis. A first application to inhomogeneous media shows that in a horizontally layered medium, the reflector images reach their true depth when the remigration velocity equals the inverse of the mean medium slowness.
Velocity modelling and prestack depth imaging below complex salt structures: a case history from on‐shore Germany
Authors: Oezsen R.
Published: November 2004

In recent years, the advances in velocity model building and depth imaging have provided a better understanding of complex subsalt plays. The tomographic approach to subsurface velocity modelling, using interpretive processes, has led to significant progress in solving subsalt imaging problems, which were once considered to be impenetrable barriers. We show how gravity data, as an alternative data source, can be integrated into iterative velocity–depth model building to constrain the overburden velocity model and delineate the shape of the salt body above the target reflector. In this way, a structurally accurate image of subsalt reflectors is achieved.
Wave‐equation migration velocity analysis. I. Theory
Authors: Sava P. , Biondi B.
Published: November 2004

We present a migration velocity analysis (MVA) method based on wavefield extrapolation. Similarly to conventional MVA, our method aims at iteratively improving the quality of the migrated image, as measured by the flatness of angle‐domain common‐image gathers (ADCIGs) over the aperture‐angle axis. However, instead of inverting the depth errors measured in ADCIGs using ray‐based tomography, we invert ‘image perturbations’ using a linearized wave‐equation operator. This operator relates perturbations of the migrated image to perturbations of the migration velocity. We use prestack Stolt residual migration to define the image perturbations that maximize the focusing and flatness of ADCIGs.

Our linearized operator relates slowness perturbations to image perturbations, based on a truncation of the Born scattering series to the first‐order term. To avoid divergence of the inversion procedure when the velocity perturbations are too large for Born linearization of the wave equation, we do not invert directly the image perturbations obtained by residual migration, but a linearized version of the image perturbations. The linearized image perturbations are computed by a linearized prestack residual migration operator applied to the background image. We use numerical examples to illustrate how the backprojection of the linearized image perturbations, i.e. the gradient of our objective function, is well behaved, even in cases when backprojection of the original image perturbations would mislead the inversion and take it in the wrong direction.

We demonstrate with simple synthetic examples that our method converges even when the initial velocity model is far from correct. In a companion paper, we illustrate the full potential of our method for estimating velocity anomalies under complex salt bodies.
Wave‐equation migration velocity analysis. II. Subsalt imaging examples
Authors: Sava P. , Biondi B.
Published: November 2004

Subsalt imaging is strongly dependent on the quality of the velocity model. However, rugose salt bodies complicate wavefield propagation and lead to subsalt multipathing, illumination gaps and shadow zones, which cannot be handled correctly by conventional traveltime‐based migration velocity analysis (MVA). We overcome these limitations by the wave‐equation MVA technique, introduced in a companion paper, and demonstrate the methodology on a realistic synthetic data set simulating a salt‐dome environment and a Gulf of Mexico data set. We model subsalt propagation using wave paths created by one‐way wavefield extrapolation. Those wave paths are much more accurate and robust than broadband rays, since they inherit the frequency dependence and multipathing of the underlying wavefield. We formulate an objective function for optimization in the image space by relating an image perturbation to a perturbation of the velocity model. The image perturbations are defined using linearized prestack residual migration, thus ensuring stability, relative to the first‐order Born approximation assumptions. Synthetic and real data examples demonstrate that wave‐equation MVA is an effective tool for subsalt velocity analysis, even when shadows and illumination gaps are present.
3D tomographic velocity model estimation with kinematic wavefield attributes
Authors: Duveneck E.
Published: November 2004

A tomographic inversion method is presented that uses kinematic information in the form of zero‐offset traveltimes and kinematic wavefield attributes (first and second spatial traveltime derivatives) to determine smooth, laterally inhomogeneous 3D subsurface velocity models for depth imaging. The kinematic wavefield attributes can be extracted from the seismic prestack data by means of the common reflection surface (CRS) stack. The input for the tomography is then taken from the resulting attribute volumes at a number of pick locations in the CRS stacked zero‐offset volume. As a smooth model description based on B‐splines is used and reflection points are treated independently of each other, only locally coherent events in the stacked volume are required and very few picks are needed. Thus, picking is considerably simplified.

During the iterative inversion process, the required forward‐modelled quantities are obtained by dynamic ray tracing along normal rays pertaining to the input data points. Fréchet derivatives for the tomographic matrix are calculated with ray perturbation theory. The inversion algorithm is demonstrated on a 3D synthetic data example, where the kinematic wavefield attributes have directly been obtained by forward modelling.
Changing professional practice in tuberculosis care: an educational intervention
Authors: Dick Judy , Lewin Simon , Rose Elizabeth , Zwarenstein Merrick , van der Walt Hester
Published: November 2004

Aim.  This paper describes the development and implementation of an experiential, participatory in‐service education programme focusing on patient‐centeredness, problem‐solving and critical reflection for primary providers delivering care to tuberculosis patients in South Africa.

Background.  Tuberculosis is a major contributor to the disease burden in developing countries. In South Africa, approximately 90% of tuberculosis patients are managed by nurses at the primary level. Despite efforts to improve quality of care for these patients, many fail to complete their treatment as prescribed. Poor rapport between health care providers and patients with tuberculosis is a major reason for non‐adherence to treatment. Methods of improving the quality of care delivery and communication between health care providers and patients with tuberculosis is therefore a priority.

Discussion.  The paper outlines the stages of developing and implementing the education programme and reflects on this process. Data is drawn from an in‐depth qualitative evaluation of the delivery and impacts of the intervention. The approach was acceptable to health care providers and adaptable to the needs of specific clinics. Participants evaluated the educational intervention positively, noting that it facilitated critical reflection on their work; encouraged problem‐solving; and heightened their awareness of communication with patients and with colleagues. However, important structural barriers to practice change were identified, including conditions of service, relations with colleagues and support from management.

Conclusions.  Experiential, participatory in‐service education can be implemented on a large scale in primary care settings. However, the process is resource intensive and the impacts of such education may be limited by barriers at other levels of the health system.
Comparison of the tensile bond strengths of cast metal crowns luted with resin cements
Authors: Fonseca R. G. , Dos Santos Cruz C. A. , Adabo G. L. , Vaz L. G.
Published: November 2004

summary  The limitation of photoactivation of dual‐polymerized resin cements along the margins of metal restorations may adversely affect the mechanical properties of these cements, thus impairing the retention of restorations. The aim of this study was to assess the bond strength of cast metal crowns cemented with three dual‐polymerized resin cements, using a chemically‐activated resin cement and zinc phosphate as controls. Fifty nickel–chromium alloy crowns were cast and randomly assigned to five groups of equal size. Castings were cemented on their corresponding metal dies with one of the tested luting agents: Scotchbond Resin Cement, Enforce and Panavia F (dual‐polymerized resin cements), Cement‐It (chemically‐activated resin cement) and Zinc Phosphate Cement (zinc phosphate cement). Specimens were stored in distilled water at 37 °C for 24 h and then loaded in tension until failure. Panavia F and Zinc Phosphate Cement provided the highest and lowest bond strength means, respectively. Scotchbond Resin Cement, Enforce and Cement‐It cements exhibited similar intermediate values, but with statistically significant difference compared to the other materials (P < 0·05). Even with the restriction or absence of light activation, all tested dual‐polymerized resin cements produced significantly higher bond strength than did the zinc phosphate cement and yielded similar or better results than the chemically activated cement. It should be pointed out that the findings of this study relate to a test scenario which does not mimic clinical circumstances and that further work is required to identify the clinical significance of the reported tensile bond strength differences between the different luting materials.
Chronic telogen effluvium or early androgenetic alopecia?
Authors: Sinclair Rodney
Published: November 2004

A 16‐year‐old girl presented with a 12‐month history of generalized hair shedding from the scalp. The onset of shedding coincided with the development of Hashimoto's thyroiditis and iron deficiency. At the time of initial presentation, the Hashimoto's thyroiditis had been treated with Neo‐Mercazole and she was euthyroid. Her iron stores were low, with a ferritin level of 13 µg/L. As she was vegetarian, oral iron replacement therapy was commenced without further investigation. On follow‐up 6 months later, her iron stores were normal (ferritin, 36 µg/L), but the hair shedding had continued. On examination, there was a positive hair pull test from both the vertex of the scalp and the occipital scalp. There was mild bitemporal recession, but no widening of the central part, and she appeared to have a full, thick head of hair (Fig. 1). Additional investigations at that time revealed normal thyroid function and negative antinuclear antibody (ANA) and syphilis serology. She was on no medication other than Neo‐Mercazole. Serum testosterone, dihydroepiandosterone sulphate (DHEAS) and sex hormone binding globulin (SHBG) were normal. Two 4‐mm punch biopsies were taken from the vertex of the scalp; one was sectioned horizontally and the other vertically. The vertical section was unremarkable. On the horizontal section, there were 32 hair follicles in total, 30 of which were terminal hairs and two of which were vellus hairs. One hair was in telogen. The ratio of terminal to vellus hairs was 15 : 1.

Initial presentation

image

A diagnosis of chronic telogen effluvium was made. The condition was explained to the patient and she was reassured that chronic telogen effluvium is not a progressive condition and does not lead to baldness. No treatment was recommended.

At follow‐up 12 months later, the hair loss had obviously progressed and the patient was assessed as having Ludwig Stage 1 androgenetic alopecia with widening of the central part (Fig. 2). Repeat blood tests showed normal iron studies, thyroid function, and hormone parameters. Three 4‐mm punch biopsies were taken from the vertex of the scalp and all were sectioned horizontally. The terminal to vellus hair ratios were 1 : 1, 2.6 : 1, and 1.9 : 1. A diagnosis of androgenetic alopecia was made and she was commenced on oral spironolactone, 200 mg/day.

Presentation after 12 months

image
Isolated hepatic tuberculosis in a transplanted liver
Authors: Alothman A. , Al Abdulkareem A. , Al Hemsi B. , Issa S. , Al Sarraj I. , Masoud F.
Published: November 2004

Abstract: Background. The incidence of tuberculosis (TB) has been increasing, especially in immunocompromised patients. It was reported that the overall incidence of TB in solid‐organ transplant recipients is 0.8%. Hepatic graft TB was reported once before in a child, who underwent living‐related hepatic graft transplantation.

Case report. A 43‐year‐old man underwent orthotropic liver transplantation (OLT) in October 1999. His pre‐transplant work‐up was negative for TB (history and PPD skin test). He developed an episode of acute rejection which responded to steroids. He was discharged home on December 1999 with normal liver function tests (LFT). His LFT remained normal during January 2000, but his serum transaminases were found elevated on February 2000 (aspartate aminotransferase [AST] 206, alanine aminotransferase [ALT] 266). A liver biopsy then showed no evidence of TB or cytomegalovirus disease. The patient continued to have stable elevation of his serum AST and ALT until late March 2000 when a repeat liver biopsy showed caseating granuloma. The patient was started on anti‐TB medications, with which he was compliant. By mid‐May 2000 he was doing well, with significant reduction in his transaminase levels (AST 72, ALT 79). A retrospective inquiry about the donor revealed that he was a healthy young man from India, who died in a road traffic accident.

Conclusion. To our knowledge our patient appears to be the first case reported of isolated hepatic TB in the OLT patient population. It is likely that the allograft was infected prior to transplantation and the disease was reactivated nearly 3 months after the procedure.
Cytomegalovirus‐associated bleeding diathesis in renal transplant recipients
Authors: Kazory A. , Ducloux D. , Chalopin J.‐M.
Published: November 2004

Abstract: Cytomegalovirus (CMV) infection is reported to be capable of modifying endothelial surface with subsequent increased risk of thromboembolic complications. Nevertheless, there are only sparse reports on its role in the development of bleeding diathesis. Here we report two renal transplant recipients who manifested severe coagulation disorders associated with acute CMV infection. Antiviral therapy was followed by consistent correction of coagulation abnormalities.
A case of arthritis caused by cytomegalovirus after kidney transplantation
Authors: Contamin C. , Brion J.P. , Bayle F. , Morand P. , Peo'ch M. , Vialtel P.
Published: November 2004

Abstract: Cytomegalovirus (CMV) is the leading cause of infectious complications after organ transplantation. We report the case of a 55‐year‐old renal transplant recipient who presented with CMV infection 2 months after transplantation. During oral ganciclovir treatment (5 weeks after interruption of intravenous ganciclovir), he experienced a sharp pain in the right shoulder. Examination was normal, but CMV antigenemia remained positive with 30 cells/300,000. He underwent a shoulder puncture, which confirmed the presence of CMV in the articular fluid after evaluation by polymerase chain reaction gene amplification. The patient recovered from his arthritis of the shoulder, and antigenemia became negative after 3 weeks of parenteral ganciclovir. We describe a CMV arthritis that occurred despite a curative treatment for CMV disease, and comment on the pathogenesis of this infection, the pharmalogical failure, and dosing or treatment duration.
Sequential cytomegalovirus antigenemia monitoring in kidney transplant patients treated with antilymphocyte antibodies
Authors: Ozaki K.S. , Pestana J.O.M. , Granato C.F.H. , Pacheco‐Silva A. , Camargo L.F.A.
Published: November 2004

Abstract: Background: Antilymphocyte antibodies (ALA) use is related to disseminated cytomegalovirus (CMV) disease after kidney transplantation. Strict surveillance of CMV infection, preemptive antiviral treatment or concomitant ganciclovir and ALA use are proposed as an attempt to prevent related clinical complications. Our objective was to describe the pattern of CMV infection, based on sequential antigenemia detection, after ALA treatment.

Patients and methods: Thirty renal transplant patients were prospectively screened for CMV infection after ALA treatment. CMV antigenemia (pp65 antigen detection) was monitored twice a week in the first month and weekly until 60 days after the beginning of ALA therapy. Any positive value of antigenemia was considered CMV infection.

Results: Twenty‐eight (93.3%) patients were CMV positive (IgG) before transplantation. The mean duration of ALA treatment was 12.1±2.4 days. Positive antigenemia was detected in 24 (80%) patients, a mean of 52.5±15 days after transplant and 44.7±14 days after the beginning of ALA treatment. The median antigenemia count was 7 positive cells/300,000 neutrophils (range: 1–227). Antigenemia preceded clinical symptoms by 5.8 days (0–28 days). Eighteen (75%) of 24 positive patients received ganciclovir treatment: 8 patients (26.7%) for viral syndrome, 2 patients (33.3%) for invasive disease, and 8 patients (26.7%) as part of preemptive therapy, asymptomatic with high antigenemia values. Six pp65‐positive patients with low counts were followed up until a negative result and remained asymptomatic without any specific treatment.

Conclusion: CMV infection was frequent after ALA treatment in this group and generally occurred late after completion of treatment. Antigenemia was a reliable tool to guide preemptive treatment in these patients, and such strategy is an alternative option compared to the prophylactic use of ganciclovir with ALA treatment.
The pp67 mRNA assay in treatment and monitoring of cytomegalovirus disease in renal transplant patients in India
Authors: Wattal C. , Joshi S. , Gupta A. , Sharma A. , Oberoi J.K. , Prasad K.J. , Rana D.S. , Bhalla A. , Khullar D.
Published: November 2004

Abstract: The present report describes use of nucleic acid sequence‐based amplification (NASBA) technology to detect pp67 mRNA of cytomegalovirus (CMV) in transplant patients in India. In our experience, pp67 mRNA assay was an accurate, rapid, and effective diagnostic tool to detect active CMV disease in 40.7% (50/123) of symptomatic transplant cases. This assay also allowed us to monitor CMV therapy. As part of the immunosuppressive regimen mycophenolate mofetil was found to increase the risk of developing CMV disease. All positive cases with this assay were subjected to antiviral therapy, with complete remission of the disease. At our center CMV NASBA assay has become the gold standard for the diagnosis of CMV disease in transplant patients.
Familial Occurrence of Bovine Dilated Cardiomyopathy in Denmark
Authors: Leifsson P. S. , Agerholm J. S.
Published: November 2004

Bovine dilated cardiomyopathy (BDCM) is a hereditary disease genetically related to the Canadian Holstein sire Montwick Red Apple Sovereign (MRAS). The occurrence of this disorder in the Red Danish Dairy breed, Holsteins, and Red Holsteins in Denmark is reported. Fourteen cases were diagnosed during a 13‐year period. All suffered from congestive heart failure because of progressive myocardial fibrosis. Pedigree information was available in 12 cases revealing both maternal and paternal relationship to MRAS. Several sires were identified as carriers of BDCM. These sires originated from breeding lines used to upgrade Danish cattle populations. The findings indicate that BDCM is a potential health problem for Danish cattle.
Two Cases of Spontaneous Pseudohermaphroditism in Cynomolgus Monkeys (Macaca fascicularis)
Authors: Pasello‐Legrand F. , Mowat V.
Published: November 2004

Disorders of genital development occur in all mammals. Hermaphroditism is a condition where the subject has genital organs of both sexes. True hermaphrodites have both ovarian and testicular tissue. Pseudohermaphrodites have only one type of gonadal tissue according to which they are classified as male or female pseudohermaphrodites. Two cases of spontaneously occurring pseudohermaphroditism in Cynomolgus monkeys (Macaca fascicularis) were seen here during 1999–2001. Both animals had female external genitalia, but each was found to have testicular tissue.
Obstructive, Granulomatous Tracheitis caused byOnchocercasp. in a Dog
Authors: Papaioannou N. , Psalla D. , Papadopoulos E. , Adamama‐Moraitou K. K. , Petanidis T. , Rallis T. , Vlemmas I.
Published: November 2004

A 3‐year‐old spayed female dog was admitted with a history of episodes of dyspnoea and coughing. Severe tracheal stenosis was found on radiography. The dog died during an episode of refractory dyspnoea. Necropsy revealed an obstruction of the thoracic part of the trachea because of a chronic granulomatous inflammation protruding into the tracheal lumen. Histological examination revealed nematodes, which were identified asOnchocercasp. according to their morphological characteristics. In contrast to the common ocular manifestation in dogs, obstructive tracheitis caused byOnchocercainfection has not been reported before.
Neospora‐associated Abortion Episode over a 1‐Year Period in a Dairy Herd in North‐east Spain
Authors: López‐Gatius F. , López‐Béjar M. , Murugavel K. , Pabón M. , Ferrer D. , Almería S.
Published: November 2004

This report describes a retrospective study based on serological screening, performed on aNeospora‐associated abortion episode over a 12‐month period in a dairy herd in north‐east Spain. During the 1‐year study period, the overall abortion rate for the herd was 23.2% (38 abortions of 164 diagnosed pregnancies). The data analysed were those derived from blood samples collected from the whole herd (n = 237) and from diagnosed pregnancies. Antibodies toNeospora caninumwere found in 35.4% of the cattle with 44% of seropositive pregnant animals aborting over 1‐year period. Based on the odds ratio, the risk of abortion was 12.2 times higher (P < 0.0001) in theNeospora‐seropositive animals than in seronegative animals and significantly higher during the second term of gestation (P < 0.01) than during the first and third terms. Abortions were not found to be associated with parity status or season of pregnancy, and the common risk factors associated with pregnancy loss in the geographical area of the study. Age‐related differences inN. caninumseroprevalence were not statistically significant, indicating vertical transmission as the main route of infection. Indeed, a high percentage of congenitally infected offspring was observed (90.6%) and the farm had been free of dogs for the last 7 years. Our results suggest that, when a dairy herd shows an increased incidence of abortions due to Neosporosis, maternal serology can be a good indicator of the abortion risk in individual cows, and that the effects of factors normally related to abortion, such as parity and pregnancy season, may be masked.
Developing New Regulatory Approaches to Antimicrobial Safety
Authors: Tollefson L.
Published: November 2004

Resistance to antimicrobial agents is of concern to public health officials worldwide. In industrialized countries, a significant source of antimicrobial‐resistant food‐borne infections in humans is the acquisition of resistant bacteria originating from animals. The US Food and Drug Administration (FDA) is committed to resolving the public health impact arising from the use of antimicrobial drugs in food‐producing animals. The FDAs goal is to ensure that significant human antimicrobial therapies are not compromised or lost while providing for the safe use of antimicrobials in food animals. Recently the FDA published a guidance document titled ‘Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern’ (US Food and Drug Administration, Center for Veterinary Medicine, 2003). This document outlines a pathway drug sponsors can use to address concerns about antimicrobial resistance prior to approval of their drug. The process uses a qualitative risk assessment approach to assess the potential of the intended use of a product to develop resistance in bacteria that may harm humans. The level of risk determines the level of risk management that is required for the drug to be used. The Food and Drug Administration (FDA) always has the option of not approving a drug if the risk of a public health consequence is too high.
Monitoring adverse drug reactions: scales, profiles, and checklists
Authors: Jordan S. , Knight J. , Pointon D.
Published: November 2004

Background:  Globally, adverse drug reactions (ADRs) make a substantial contribution to ill health. Introducing a systematic approach to patient surveillance could mitigate these problems. Formalized medication monitoring schedules have been proposed as one strategy to diagnose and action side‐effects and the problems emanating from adverse drug reactions. To date, most developments have been linked to antipsychotic medications. Several scales, checklists, and side‐effect profiles are available, including the West Wales ADR (adverse drug reaction) profile. However, relatively little work has been undertaken on the clinical validity, reliability, and sensitivity of these instruments.

Aim:  This paper describes the development of the monitoring schedule approach to medication management. It also reviews and compares the instruments available for monitoring the adverse drug reactions of antipsychotic medications. The UKU (Udvalg for Kliniske Undersogelser) scale and the West Wales ADR profile assess a broader range of physiological parameters and potential problems than other instruments. However, to be adopted in practice, such instruments must achieve a balance between clinical gain and practical cost, including the time spent in administration.

Conclusion:  Further work is needed to explore the translation of formalized ADR surveillance programmes into clinical gains and improved outcomes for clients.
The People's Budget? Politics, Participation and Pro‐poor Policy
Authors: Bräutigam Deborah
Published: November 2004

Recent moves towards ‘participatory’ budgeting have raised hopes and expectations that spending and revenue generation can be made more pro‐poor if informed citizens and their non‐traditional political organizations participate directly in budgeting decisions. This article reviews experiences of participatory budgeting and pro‐poor policy‐making in Brazil, Ireland, Chile, Mauritius, and Costa Rica. It draws attention to several important issues: Who participates? What kind of institutional framework is necessary? What happened to the revenue‐generation side of pro‐poor budgeting? It points out that making spending and taxation more ‘pro‐poor’ has historically depended on pro‐poor political parties gaining power.
The Rise of Kenyan Supermarkets and the Evolution of their Horticulture Product Procurement Systems
Authors: Neven David , Reardon Thomas
Published: November 2004

Supermarkets are rapidly penetrating urban food retail in Kenya and spreading well beyond their initially tiny market niche among the urban middle class into the food markets of lower‐income groups. Having penetrated processed and staple food markets much earlier and faster than fresh foods, they have recently begun to make inroads into the fresh fruits and vegetables category. Supermarkets in Kenya already buy about half the volume of produce exported, and thus represent a significant new ‘dynamic market’ opportunity for farmers. The important changes in their procurement systems bring significant opportunities and challenges for small farmers, and have implications for agricultural diversification and rural development programmes and policies.
Trends in real wages during the industrial revolution: a view from across the Irish Sea
Authors: GEARY FRANK , STARK TOM
Published: November 2004

This article calculates cost of living indices for Ireland between 1785 and 1870 and real wage indices for agricultural labourers, textile workers, and building workers. These indices show gains in real wages which are not consistent with current hypotheses about widespread pre‐Famine immiseration, though textile workers did experience a reduction in earning power. Before the Famine, wages proved sticky downwards in the face of falling prices; after the Famine, money wages rose faster than prices. A revised UK index suggests that real wages began their increase earlier, in the 1820s, and increased by around an additional 10 percentage points by 1870.
Rituximab‐responsive CIDP
Authors: Briani C. , Zara G. , Zambello R. , Trentin L. , Rana M. , Zaja F.
Published: November 2004

Chemotherapy has been used for treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with incosistent results. Chemotheraphy has been used for treating with inconsistent results. Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen, used to treat B‐cell lymphoma and reported to be effective in some neuropathies with IgM autoreactivity. We saw a 72‐year‐old man with CIDP refractory to steroids, plasma exchange, IV Ig, and cyclosporin. He was unable to walk; severe impairment was present also at the upper limbs. Electrodiagnostic studies revealed slowing of motor and sensory conduction velocities, and prolonged distal motor latencies. Immunoelectrophoresis evidence an IgM/k monoclonal gammopathy. Antibodies to Myelin Associated Glycoprotein (MAG) and other peripheral nerve antigens were negative. Bone marrow biopsy documented a small lymphocytic B‐cell lymphoma (CD20+). Treated with Rituximab (375 mg/m2 for 4 weeks), the patient presented at follow‐up evaluations (3, 6 and 8 months later) a progressive improvement. Eventually, he was able to walk, and regained full strength at upper limbs. Consistently, electrophysiological studies improved. We suggest considering treatment with Rituximab in CIDP resistant to conventional therapy, at least in cases associated with IgM lymphoproliferative diseases.
Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients
Authors: Pantoni L. , Sarti C. , Pescini F. , Bianchi S. , Bartolini L. , Nencini P. , Basile A. M. , Lamassa M. , Kalaria R. N. , Dotti M. T. , Federico A. , Inzitari D.
Published: November 2004

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.
The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia‐ischemia as potently as erythropoietin
Authors: Wang Xiaoyang , Zhu Changlian , Wang Xinhua , Gerwien Jens Gammeltoft , Schrattenholz Andre , Sandberg Mats , Leist Marcel , Blomgren Klas
Published: November 2004

Recently, erythropoietin (EPO) and the nonerythropoietic derivative asialoEPO have been linked to tissue protection in the nervous system. In this study, we tested their effects in a model of neonatal hypoxia‐ischemia (HI) in 7‐day‐old rats (unilateral carotid ligation and exposure to 7.7% O2 for 50 min). EPO (10 U/g body weight = 80 ng/g; n = 24), asialoEPO (80 ng/g; n = 23) or vehicle (phosphate‐buffered saline with 0.1% human serum albumin; n = 24) was injected intraperitoneally 4 h before HI. Both drugs were protective, as judged by measuring the infarct volumes, neuropathological score and gross morphological score. The infarct volumes were significantly reduced by both EPO (52%) and asialoEPO (55%) treatment, even though the plasma levels of asialoEPO had dropped below the detection limit (1 pm) at the onset of HI, while those of EPO were in the nanomolar range. Thus, a brief trigger by asialoEPO before the insult appears to be sufficient for protection. Proteomics analysis after asialoEPO treatment alone (no HI) revealed at least one differentially up‐regulated protein, synaptosome‐associated protein of 25 kDa (SNAP‐25). Activation (phosphorylation) of ERK was significantly reduced in asialoEPO‐treated animals after HI. EPO and the nonerythropoietic asialoEPO both provided significant and equal neuroprotection when administered 4 h prior to HI in 7‐day‐old rats. The protection might be related to reduced ERK activation and up‐regulation of SNAP‐25.
An NCAM‐derived FGF‐receptor agonist, the FGL‐peptide, induces neurite outgrowth and neuronal survival in primary rat neurons
Authors: Neiiendam Johanne Louise , Køhler Lene Boding , Christensen Claus , Li Shizhong , Pedersen Martin Volmer , Ditlevsen Dorte Kornerup , Kornum Martin Kirkegaard , Kiselyov Vladislav V. , Berezin Vladimir , Bock Elisabeth
Published: November 2004

The Neural Cell Adhesion Molecule (NCAM) plays a crucial role in development of the central nervous system regulating cell migration, differentiation and synaptogenesis. NCAM mediates cell–cell adhesion through homophilic NCAM binding, subsequently resulting in activation of the fibroblast growth factor receptor (FGFR). NCAM‐mediated adhesion leads to activation of various intracellular signal transduction pathways, including the Ras‐mitogen activated protein kinase (MAPK) and the phosphatidylinositol‐3‐kinase (PI3K)‐Akt pathways. A synthetic peptide derived from the second fibronectin type III module of NCAM, the FGL peptide, binds to and induces phosphorylation of FGFR without prior homophilic NCAM binding. We here present evidence that this peptide is able to mimic NCAM heterophilic binding to the FGFR by inducing neuronal differentiation as reflected by neurite outgrowth through a direct interaction with FGFR in primary cultures of three different neuronal cell types all expressing FGFR subtype 1: dopaminergic, hippocampal and cerebellar granule neurons. Moreover, we show that the FGL peptide promotes neuronal survival upon induction of cell death in the same three cell types. The effects of the FGL peptide are shown to depend on activation of FGFR and the MAPK and PI3K intracellular signalling pathways, all three kinases being necessary for the effects of FGL on neurite outgrowth and neuronal survival.
Expression of damage‐induced neuronal endopeptidase (DINE) mRNA in peri‐infarct cortical and thalamic neurons following middle cerebral artery occlusion
Authors: Ohba Norihiro , Kiryu‐Seo Sumiko , Maeda Mitsuyo , Muraoka Michinari , Ishii Masamitsu , Kiyama Hiroshi
Published: November 2004

Damage‐induced neuronal endopeptidase (DINE) is a unique nerve‐injury associated molecule, which was recently identified in a peripheral nerve injury model. The aim of this study was to determine the expression profiles and distribution of DINE in adult rats after middle cerebral artery (MCA) occlusion. Focal cerebral ischemia induced late‐onset and prolonged expression of DINE mRNA in the peri‐infarct cortex and specific nuclei of thalamus. Double labeling using immunohistochemistry and in situ hybridization revealed that DINE mRNA was exclusively expressed in cells that were positive to a neuronal marker NeuN. Previously established knowledge on neuroanatomical fiber connection suggests that DINE mRNA was expressed in areas projecting their axons to or through the core region of the infarction. This unique expression profile was similar to that of activating transcription factor‐3 (ATF‐3), which is a marker of nerve‐injured neuron. More than 98% of ATF‐3 immunoreactive neurons simultaneously expressed DINE mRNA, suggesting that DINE expression is observed in injured neurons of CNS as well as PNS. Since DINE expression promotes antioxidant activity, our results suggest that DINE may act as a neuroprotective molecule in neurons under ischemic insult.