bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypospadias: Incidence and Effects on Psychosexual Development as Evaluated with the Minnesota Multiphasic Personality Inventory Test in a Sample of 11,649 Young Italian Men
Authors: Mondaini Nicola , Ponchietti Roberto , Bonafè Massimiliano , Biscioni Stefano , Di Loro Filippo , Agostini Paolo , Salvestrini Francesco , Rizzo Michelangelo
Published: April 2003

Purpose: We evaluated the incidence of hypospadias and its effects on psychosexual development in a sample of 11,649 young Italian males. Over the last 30 years only about 30 major publications have addressed these issues and the results of many studies have been contrasting. Some defects in methodology, such as low response rates, heterogeneity of age ranges and the choice of controls, have been the main limitations. Our study was designed to take these problems into account. Materials and Methods: Forty-two hypospadic subjects and a random sample of 500 nonaffected males selected from the large sample of 11,649 young men (>90% of the 18-year-old males living in the Italian region of Tuscany) were screened by the Minnesota Multiphasic Personality Inventory (MMPI) test, psychological interview and clinical evaluation. Results: The incidence of hypospadias in this representative group of Italian men is 3.6/1,000. No difference was noted in the percentage with altered MMPI compared with the control group. The age at surgical corrections and the number of operations are not related to an abnormal global psychological adjustment. Severity of disease influences a more negative genital appraisal and the number of operations is correlated only with more difficulty in initiating contact with the opposite sex. Conclusions: Surgery for hypospadias has to be strongly pursued in as many cases as possible. In addition, we strongly recommend following up all hypospadics, independently of the severity of their genital malformations, through adolescence to early adulthood, to ensure early detection of subjects with impaired psychological profiles.
Detection of LOH of the RB1 Gene in Bladder Cancers by PCR-RFLP
Authors: Açikbas I. , Keser I. , Kiliç S. , Bağci H. , Karpuzoğlu G. , Lüleci G.
Published: April 2003

Objectives: Retinoblastoma (RB1) gene involves in retinoblastoma, osteosarcoma, bladder, prostate, lung, breast carcinomas, and soft tissue sarcomas. Loss of heterozygosity (LOH) is the most common mutation of the gene. Methods: Xba I polymorphism in intron 17 of the gene was used to detect LOH in 20 bladder cancer patients. A cystitis and an osteosarcoma were used as control. LOH was investigated in three different kinds of samples (blood, paraffin-embedded tissue and fresh tissue) belonging to the same patients, and 20 blood samples, 20 paraffin-embedded tissue samples and 16 fresh tissue samples were obtained from 20 cancer patients. Results: None of the 20 blood samples showed LOH. Eleven out of 20 paraffin-embedded bladder tissues were amplified, 3 of them homozygous and all 8 informative paraffin-embedded tissues showed LOH. Five out of 16 fresh tumor tissues obtained were amplified, in 1 the fresh tissue was normal, 1 fresh tissue showed LOH and 3 were not digested by Xba I. Conclusion: The results of the study have suggested that detection of LOH of the RB1 gene by PCR-RFLP can be a good adjunctive test for evaluation of the bladder cancer.
Strangulation of the Penis by a Self-Circumcision Device
Authors: Kim Se J. , Chung Han , Ahn Hyun S. , Chung Do Y. , Kim Young S.
Published: April 2003

Penile strangulation caused by wearing metallic or non-metallic objects is unusual but potentially serious. We report the case of a 33-year-old man who presented with penile strangulation after applying a self-circumcision device. The device was removed, and after conservative treatment conventional circumcision was performed. It is stressed that circumcision should be performed by urologists or medically trained personnel.
Comparison of Cefepime versus Ceftriaxone-Amikacin as Empirical Regimens for the Treatment of Febrile Neutropenia in Acute Leukemia Patients
Authors: Borbolla José R. , López-Hernández Manuel A. , González-Avante Mauricio , DeDiego José , Trueba Elvira , Alvarado Martha L. , Jiménez Rosa M.
Published: April 2003

Background: High-intensity regimes of chemotherapy have led to longer and more severe episodes of neutropenia with a resulting increase in morbidity and mortality due to infections. Which empiric antibiotic regimen to use in these cases is still under debate. Methods: We performed a randomized comparative study to evaluate the efficacy of cefepime versus ceftriaxone plus amikacin as the initial treatment in an escalating, empirical, antibiotic therapy regimen in febrile neutropenic patients. Both adults and children were included. All patients had less than 500 neutrophils/µl at the time of infection. Patients were randomized to receive either cefepime or ceftriaxone plus amikacin. If infection continued 72 h later, patients in both groups received vancomycin, and if infection had not disappeared 7 days after starting antibiotics, amphotericin B was started. Results: Twenty patients were included in each group. Both treatment and control groups were comparable for age and sex, among other factors. There were 18 cures in the cefepime group and 17 in the ceftriaxone plus amikacin group (p = 0.9). No patient discontinued therapy because of toxicity. Conclusions: Cefepime is a safe and very effective therapy for patients with acute leukemia and febrile neutropenia; in addition, it is a cheaper regimen in our country, and lacks the potential toxicity of the aminoglycosides.
Cross-Sectional Analysis of Neurological Findings among Healthy Elderly: Study in a Remote Island in Kagoshima, Japan
Authors: Kodama Tomoko , Nakagawa Masanori , Arimura Kimiyoshi , Koriyama Chihaya , Akiba Suminori , Osame Mitsuhiro
Published: April 2003

We have conducted annual health checkup surveys of elderly subjects aged 60 years or older in a remote island of southwestern Japan. After excluding patients with neurological diseases and the subjects who needed help in activities of daily living, a cross-sectional analysis of the data obtained from 348 elderly people aged 60–89 years was made. We examined the age and sex distributions of abnormal neurological findings, including the scores of the Mini-Mental State Examination (MMSE). In this study, aging was associated with muscle weakness in the lower limbs, cerebellar dysfunction, hand tremor, decrease in handgrip, abnormality of deep sensation and a decrease in the MMSE score. These findings suggest a characteristic pattern of nervous system deterioration with age. We discuss the possible pathogenesis and significance of these findings that should contribute to a better understanding of normal aging in the nervous system.
Evaluation and Correction for a ‘Training Effect’ in the Cognitive Assessment of Older Adults
Authors: Di Bari Mauro , Pahor Marco , Barnard Marie , Gades Naomi , Graney Marshall , Franse Lonneke V. , Penninx Brenda W.J.H. , Marchionni Niccolò , Applegate William B.
Published: April 2003

Background: Repeated administration of psychometric instruments frequently results in a higher score on retesting, the so-called training effect. Yet, a training effect has been poorly considered in longitudinal studies of cognitive changes in older persons. Methods: We investigated the presence, magnitude and potential adjustments for training effect in the older participants of the Systolic Hypertension in the Elderly Program (SHEP). SHEP evaluated the cognitive status effects of a diuretic-based treatment of isolated systolic hypertension versus placebo. Changes in the short Comprehensive Assessment and Referral Evaluation (short-CARE) questionnaire score, from baseline through 4 years of follow-up, were assessed in 4,718 participants. In this study, we used two regression techniques to adjust data for the training effect. Results: In both study groups, a training effect was evident as a progressive improvement in the short-CARE score throughout year 1. Thereafter, cognitive scores tended to deteriorate, more in the placebo than in the active treatment group (p = 0.055). When follow-up scores were adjusted based upon baseline data, the difference between the study groups reached statistical significance (p = 0.019), but the apparent overall trend towards deterioration in cognitive score was no longer observed. Adjustment of baseline data preserved this apparent temporal course, but did not improve the discrimination between the two study groups (p = 0.165). Conclusions: In SHEP, repeated cognitive assessments were likely biased by a training effect which could be only partially corrected by statistical techniques. Studies of changes in the cognitive status of older persons should be designed appropriately to estimate and minimize the consequences of a training effect in follow-up data.
Association Analysis for the Genetic Variants of the NMDA Receptor Subunit 2b and Alzheimer’s Disease
Authors: Tsai Shih-Jen , Liu Hsiu-Chih , Liu Tsung-Yun , Cheng Chih-Ya , Hong Chen-Jee
Published: April 2003

N-methyl-D-aspartate (NMDA) receptor dysfunction has been implicated in the pathogenesis of Alzheimer’s disease (AD). The NMDA receptor is composed of several subunits, of which the receptor 2b subunit (NR2b) is of particular significance for AD. Abundant in the hippocampus of normal subjects, reductions in NR2b have been demonstrated in the hippocampus and entorhinal cortex of AD patients. In this study, we tested the hypothesis that the allelic variant (C2664T) of the NR2b confers susceptibility to AD using a sample population of 132 AD patients and 114 normal controls. The distribution of the NR2b genotypes (p = 0.600) and alleles (p = 0.652) did not differ significantly between AD patients and controls, however, suggesting that it is unlikely that the NR2b C2664T polymorphism plays a substantial role in conferring susceptibility to AD. We propose that other genetic variations of the NMDA subunits, relating either to AD or to the therapeutic response for NMDA partial agonists, may need further investigation.
Cognitive Impairment and Mortality among Nonagenarians: The Danish 1905 Cohort Survey
Authors: Andersen Kjeld , Nybo Hanne , Gaist David , Petersen Hans Chr. , McGue Matt , Jeune Bernard , Vaupel James W. , Christensen Kaare
Published: April 2003

Cognitive impairment has been associated with increased mortality. Most studies, however, have only included small numbers, if at all, of the very old. In a large nationwide survey of all Danes born in 1905 and still alive in 1998, where the baseline examination was conducted, we examined the impact of cognitive impairment on mortality over a 2-year period. No cognitive impairment was defined as a score of 24–30 points on the Mini Mental State Examination, mild cognitive impairment was defined as a score of 18–23 points, and severe impairment was defined as a score of 0–17 points. Cox regression analysis was applied to adjust for a number of known and suspected factors known or suspected of being associated with cognition and mortality (e.g. sociodemographic factors, sex, smoking, alcohol consumption, depressive symptoms, and physical abilities), and yielded hazard ratios (95% confidence interval) of 1.24 (1.00–1.55) for mildly impaired and 1.73 (1.37–2.20) for severely impaired Danes compared to individuals with no impairment. Cognitive impairment predicts mortality among the very old, even after controlling for most known predictors of mortality.
Leigh’s Disease in 3 Sibs of a Kuwaiti Family
Authors: Abdul-Rasoul Majedah , Al-Qatan Hanan , Habeeb Hessa , Al-Adwani Muneera , Al-Bouloshi Maliha , Habeeb Yousif , Mousa Ali
Published: April 2003

Objective and Importance: To describe Leigh’s disease in 3 sibs of a Kuwaiti family. Case Presentation: Two brothers presented in early infancy with progressive neurological symptoms of hypotonia, delayed milestones and brisk reflexes. Investigations revealed metabolic acidosis, high serum and cerebrospinal fluid lactate. Magnetic resonance imaging (MRI) showed characteristic changes of Leigh’s disease. The 3rd brother, who was asymptomatic initially, was investigated because of his family history and was found to have similar changes. Intervention: All children developed progressive neurological deterioration and persistent metabolic lactic acidosis, which was treated with sodium bicarbonate, and the 1st patient needed renal dialysis to control the acidosis. The 2nd child was placed on vitamins and carnitine. Conclusion: The neurological deterioration was progressive in all 3 sibs, and they eventually died of respiratory failure despite ventilatory support. Since MRI changes are characteristic, MRI should be done to confirm the diagnosis.
Cognitive Dysfunction in Recovered Depressive Patients with Silent Cerebral Infarction
Authors: Yamashita H. , Fujikawa T. , Yanai I. , Morinobu S. , Yamawaki S.
Published: April 2003

In this study, we characterized cognitive functioning in patients with major depression and silent cerebral infarction (SCI), as detected by magnetic resonance imaging (MRI), after they had recovered from depression. Thirty-five patients with unipolar depression who experienced the onset of depression after the age of 50 underwent MRI and were classified as SCI(+) (n = 17) or SCI(–) (n = 18). The Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Uchida-Kraepelin psychodiagnostic test were administered after the patients had recovered from depression. In addition, the intelligence quotient (IQ) and mental speed of the patients in the two groups were compared. The total, verbal and performance IQ scores, as determined by the WAIS-R, were significantly lower in the SCI(+) group than in the SCI(–) group. The mental speed of patients in the SCI(+) group, as assessed by the Uchida-Kraepelin psychodiagnostic test, was almost half that of the SCI(–) group. Our findings provide further evidence that a comprehensive impairment of cognitive functioning, especially a severe reduction in mental speed, remains after recovery from depression in patients with major depression and SCI.
Opioid Addiction Changes Cerebral Blood Flow Symmetry
Authors: Pezawas Lukas , Fischer Gabriele , Podreka Ivo , Schindler Shird , Brücke Thomas , Jagsch Reinhold , Thurnher Maida , Kasper Siegfried
Published: April 2003

Changes in regional cerebral blood flow (rCBF) due to long-term abuse of opioids such as heroin or morphine are not yet fully understood in humans. The goal of the present study was to investigate rCBF alterations in a large sample of long-term opioid addicts in comparison to healthy controls. We investigated 21 opioid-dependent subjects, who were currently abusing heroin or were enrolled in a methadone or morphine maintenance program, and 36 healthy controls with 99mTc-HMPAO single photon emission computed tomography. We found a decrease in rCBF in most regions of interest in patients in comparison to controls. Long-term opioid dependence seems to decrease prefrontal CBF in particular. A right-greater-than-left CBF asymmetry in healthy subjects was reversed in patients. This change in CBF symmetry could reflect the different emotional status of opioid-dependent patients. Our findings are in line with neuropsychological investigations indicating a correlation of mood states with lateralization of hemispheric activation patterns.
Effect of the Noncompetitive NMDA Antagonists MK-801 and Ketamine on the Spastic Han-Wistar Mutant: A Rat Model of Excitotoxicity
Authors: Brunson Kristen L. , Khanna Aparna , Cromwell Howard C. , Cohen Randy W.
Published: April 2003

The neuroprotective effects of the NMDA antagonists MK-801 and ketamine were analyzed in a mutant strain of Han-Wistar rats which develop neurodegeneration in the hippocampus and cerebellum. Previous experiments have shown that the progressive neuronal degeneration observed in this mutant may be the result of a dysfunctional glutamatergic system. For MK-801 studies, mutants were injected in a chronic paradigm with (+)MK-801 or its weaker acting isomer (–)MK-801 at a dose of 1 mg/kg. Ketamine studies consisted of both acute (50 mg/kg once) and chronic (10 mg/kg multiple times) injection paradigms. MK-801-treated mutants exhibited longer life spans (8–23%) compared to saline-injected mutants. Ketamine-injected mutants in both paradigms also lived slightly longer (6–9%) than the saline mutants. Motor skill deterioration was monitored in an open-field test, and after 50 days of age the MK-801 and ketamine mutants displayed over 20% greater motor skill activity than the saline mutants. In the cerebellum, mutants treated with ketamine and both forms of MK-801 had 10–20% more Purkinje cells surviving at 55 days than the saline mutants. Further, the density of CA3c pyramidal hippocampal neurons in ketamine and MK-801-treated mutants as compared to saline mutants appeared to be greater upon qualitative analysis. This study shows that these mutants derive some protective effects from the NMDA antagonists MK-801 and ketamine, confirming glutamate-induced excitotoxicity as a possible cause of neuronal degeneration in this mutant strain of rat.
Maternal Choline Availability Alters the Localization of p15Ink4B and p27Kip1 Cyclin-Dependent Kinase Inhibitors in the Developing Fetal Rat Brain Hippocampus
Authors: Albright Craig D. , Mar Mei-Heng , Friedrich Claudia B. , Brown Elliott C. , Zeisel Steven H.
Published: April 2003

Previously we have shown that changes in maternal dietary choline are associated with permanent behavioral changes in offspring. Importantly, in adult male rats, feeding a choline-deficient diet increases the localization of cyclin-dependent kinase inhibitors (CDKIs) in the liver, whereas young adult CDKI knockout mice (p15Ink4B or p27Kip1) exhibit behavioral abnormalities. Thus, maternal dietary choline-CDKI interactions could underlie the changes we observe in fetal hippocampal development and cognitive function in offspring. Here, timed-pregnant rats on embryonic day E12 were fed the AIN-76 diet with varying levels of dietary choline for 6 days, and, on E18, fetal brain sections were collected, and the localization of CDKI proteins was studied using immunohistochemistry and an unbiased image analysis method. In choline-supplemented animals compared to controls, the number of cells with nuclear immunoreactivity for p15Ink4b CDKI protein was decreased 2- to 3-fold in neuroepithelial ventricular zones and adjacent subventricular zones corresponding to the fimbria, primordial dentate gyrus and Ammon’s horn regions in the fetal hippocampus. In contrast, maternal dietary choline deficiency significantly decreased nuclear p15Ink4b immunoreactivity in the neuroepithelial layer of the dentate gyrus. Unlike p15Ink4b, the CDKI protein p27Kip1 was observed almost exclusively in the cytoplasm, though the protein was distributed throughout the proliferating and postmitotic zones in the E18 fetal hippocampus. Maternal dietary choline supplementation decreased the cytoplasmic staining intensity for p27Kip1 throughout the fetal hippocampus compared to control animals. Choline deficiency increased the staining intensity of p27Kip1 throughout the hippocampus in association with increased expression of MAP-1 and vimentin proteins. These results link maternal dietary choline availability to CDKI protein immunoreactivity and commitment to differentiation during fetal hippocampal development.
Inhibition of α(1–6)-Linked Fucose Decreases Inner Retinal Cells and Increases Photoreceptors in Chicken Retinal Reaggregates
Authors: Willbold Elmar , Rothermel Andrée , Huhn Jutta , Stelck Simone , Layer Paul G.
Published: April 2003

We investigated the developmental role of α(1–6)-linked fucose, applying Aleuria aurantia lectin to a specific retinal regeneration system. Thereby, dissociated retinal cells of chicken embryos reaggregate, proliferate, and differentiate in vitro into histotypical spheres, so-called retinospheroids. Under the influence of A. aurantia lectin, processes of proliferation, differentiation and histogenesis of retinospheroids were disturbed. Extending these in vitro studies, we here show that A. aurantia lectin treatment decreases cells of the inner half retina and their processes into inner plexiform layer areas, as revealed by quantitative enzyme histochemistry for butyryl- and acetylcholinesterase, and immunohistochemistry using antibodies to acetylcholinesterase, Pax-6, calbindin-D, and F11. Concomitantly, the number of rod and red/green photoreceptors dramatically increases, using the antibodies rho4D2 and CERN901 (both specific for rods) and CERN906 (specific for red/green cones). These findings show that glycoproteins exhibiting fucose in α(1–6)-linkage are involved in processes determining retinal cell fate, strongly shifting the relative ratio of cells of the inner towards cells of the outer retina.
Evaluation of the Statolith Function by Measurement of Ocular Counterrolling?
Authors: Kingma H. , Kavelaars J. , van Tienen N. , Caris R.
Published: April 2003

Ocular counterrolling (OCR) induced by lateroflexion, whole body roll, eccentric rotation or translational acceleration has been explored and promoted as an indicator of the vestibular statolith function. Quantification of eye torsion induced by stimulation of the statolith organ has recently become available for broad clinical application thanks to the development of video nystagmography. The most simple way and maybe clinically the most attractive procedure to induce OCR could have been by changing the orientation of the statolith system relative to the gravitation vector, i.e. by lateroflexion of the head. However, irrespective of the visual condition, irrespective of the type of head roll, static or dynamic, OCR showed considerable inter- and intravariability. Findings in healthy subjects and patients indicate that according to our current insight, measurement of OCR induced by lateroflexion or whole body roll has a limited sensitivity and specificity. The normal range of OCR in healthy subjects is large (4.5–9.0% and could be interpreted as a functional asymmetry in statolith function that does not really exist. At present there are insufficient clinical data available to judge the clinical relevance of this test. OCR induced by sideward translations has the advantage over the previously described techniques that it allows an evaluation of the frequency characteristics of the statolith function. Major problems with this technique are that the equipment required is complex and expensive, that a appropriate head fixation is difficult and that responses are quite small. So far, the scarce clinical data do not yet point to a clear clinical relevance of this approach.
Immunological Hyperresponsiveness in HTLV-I LTR-env-pX Transgenic Rats: A Prototype Animal Model for Collagen Vascular and HTLV-I-Related Inflammatory Diseases
Authors: Nakamaru Yuji , Ishizu Akihiro , Ikeda Hitoshi , Sugaya Toshiaki , Fugo Kazunori , Higuchi Masato , Yamazaki Hidetoshi , Yoshiki Takashi
Published: April 2003

We have earlier reported that diverse collagen vascular diseases, including arthritis, arteritis, thrombosis, myocarditis, myositis, sialo-/dacryoadenitis and dermatitis develop with the advent of autoantibodies in transgenic rats carrying the LTR-env-pX gene of human T lymphocyte virus type I (LTR-env-pX rats). To clarify the pathogenesis of these collagen vascular diseases, immunological features of LTR-env-pX rats were examined. In LTR-env-pX rats affected with these diseases, expression of CD80/86 on both tissue-infiltrating and peripheral T cells increased, compared with findings in non-transgenic rats with experimental inflammatory diseases. CD80/86 was also upregulated on peripheral T cells in LTR-env-pX rats prior to the development of diseases. Lymphocytes from LTR-env-pX rats showed an increase in autologous proliferation and were hyperreactive against several mitogens, including concanavalin A, immobilized anti-CD3 antibodies, and superantigens in vitro. Antigen-specific immune response was also enhanced in LTR-env-pX rats. The collective evidence indicates that lymphocytes of LTR-env-pX rats constitutively express surface molecules related to T cell activation and are immunologically hyperresponsive. Bone marrow cell transfer from LTR-env-pX rats to lethally irradiated non-transgenic rats revealed that these immunologically pre-activated and hyperresponsive lymphocytes play a critical role in the pathogenesis of several collagen vascular diseases, especially of dermatitis in LTR-env-pX rats.
Genomic organization and chromosome mapping of the human homeobox gene HHEX
Authors: Morgutti M. , Demori E. , Pecile V. , Amoroso A. , Rustighi A. , Manfioletti G.
Published: April 2003

In the present study, we report the genomic reconstruction of the human homeobox-containing gene HHEX by the use of the data available in public databases. This analysis allowed characterization of the gene organization showing that it is very similar to the mouse gene. Moreover the gene was mapped using FISH to 10q24.
Molecular and cytogenetic characterisation of a small interstitial de novo 20p13→p12.3 deletion in a patient with severe growth deficit
Authors: Leprêtre F. , Montpellier C. , Delannoy V. , Froguel P. , Vasseur F.
Published: April 2003

We report on a small de novo interstitial deletion of the short arm of chromosome 20, 46,XY,del(20)(p12.3p13), in a young boy with hypotonia, moderate development delay, mild facial dysmorphism and severe growth failure. This patient did not show major features of Alagille-Watson Syndrome (AWS) which are common in more proximal 20p deletions. Standard and high resolution chromosome banding analysis revealed an apparent terminal deletion. Nevertheless, using chromosomal fluorescent in situ hybridization (FISH) and molecular analysis with polymorphic markers, we demonstrated that the abnormal chromosome resulted from a de novo interstitial deletion of paternal origin spanning from D20S842 to D20S900 and covering approximately 6 Mb. These findings indicate that a karyotype can lead to insufficient characterization of an apparently terminal deletion, and that one or a few genes in 20p13→p12.3 bands are important for normal growth.
Genomic structures of the human angiopoietins show polymorphism in angiopoietin-2
Authors: Ward E.G. , Grosios K. , Markham A.F. , Jones P.F.
Published: April 2003

The family of human angiopoietins comprises factors with important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to the endothelial cell-specific receptor, Tie2. The mechanism by which they contribute to angiogenesis is thought to involve regulation of endothelial cell interactions with supporting perivascular cells. In this study the genomic structures of all three human angiopoietins were characterised by direct sequencing of human genomic DNA from the appropriate P1 artificial chromosome (PAC) clones. The exact positions at the intron/exon boundaries and the lengths of all eight introns were determined. As would be expected from the homology of these three proteins, the positions of the introns in the three genes are highly conserved. The putative RNA transcription start site for each angiopoietin gene was also determined. Intron-specific primers were used to amplify each exon of angiopoietin-1 and angiopoietin-2 from individual genomic DNAs. Although no polymorphism has been detected in the coding region of angiopoietin-1, three independent polymorphisms have been identified for angiopoietin-2.
Comparative mapping of the human 9q34 region in Fugu rubripes
Authors: Bouchireb N. , Grützner F. , Haaf T. , Stephens R.J. , Elgar G. , Green A.J. , Clark M.S.
Published: April 2003

Twenty-seven genes have been cloned and mapped in Fugu which have orthologues within the human chromosome 9q34 region. The genes are arranged into five cosmid and BAC contigs which physically map to two different Fugu chromosomes. Considering the gene content of these contigs, it is more probable that a translocation event took place early in the Fugu lineage to split the ancestral 9q34 region onto two chromosomes rather than the alternative hypothesis of a large-scale duplication of the region into two chromosomes with subsequent rapid and dramatic gene loss. There are considerable differences in gene order between the two species, which would appear to be the result of a series of complex chromosome inversions; thus suggesting that there have been no positional constraints on this particular gene set.
Comparative FISH mapping of 32 loci reveals new homologous regions between donkey and horse karyotypes
Authors: Raudsepp T. , Mariat D. , Guérin G. , Chowdhary B.P.
Published: April 2003

A total of 32 loci comprising specific genes, microsatellites and anonymous BAC clones from horse and cattle were mapped on donkey chromosomes. Of these, 13 markers were also mapped for the first time in the horse. This information, together with that previously available in donkey and horse updates the comparative status of the karyotypes of the two species. The findings of the present study for the first time show correlation between eleven equine acrocentric autosomes and the donkey chromosomes and in part enable detection of rearrangements between them. There are still 7–8 pairs of chromosomes/arms for which no correspondence is known. At least 20 chromosome rearrangements (inversions, fusions and fissions) are already identified that differentiate the two karyotypes. More will be known once complete correspondence is deduced between them. These observations match similar differences observed between human-gibbon and mouse-rat karyotypes that show considerable rearrangements in relation to each other. How donkey and horse karyotypes gathered these differences within a short period of 5–10 Myr since divergence from a common ancestor will be known only after an ancestral equid karyotype is deduced, and the direction of change leading to chromosome rearrangements is clearly understood.
What Diseases of the Eyes Affected Biblical Men?
Authors: Ben-Noun Liubov (Louba)
Published: April 2003

Background/Objective: The elderly have suffered from visual impairment for thousands of years. This report evaluates the first documented cases of visual disability in the elderly as described in the Bible. Results: Three old men suffered from a gradual loss of vision. It is more likely that either mature cataract, or age-related macular degeneration, or asymptomatic open-angle glaucoma, or ischemic optic neuropathy or optic nerve atrophy were associated with visual loss. Corneal ulceration or scarring can also be considered. Hereditary causes of optic nerve atrophy and retinal degeneration can be excluded. Conclusion: This report demonstrates that the roots of contemporary modern gerontology lead back to biblical times.
Comprehension of Written Health Care Information in an Affluent Geriatric Retirement Community: Use of the Test of Functional Health Literacy
Authors: Gausman Benson Jennifer , Forman Walter B.
Published: April 2003

Background: The comprehension of written health care information, e.g. prescription bottle labels or an informed consent form, impacts on communication with patients and their ability to understand medical procedures, as well as goals of therapy. Objective: To determine if the problem of literacy was present in a population of affluent Albuquerque retirement community dwellers. Methods: We administered the Test of Functional Health Literacy in Adults (TOFHL) to 93 residents (71 women and 22 men), using a one-on-one directed examination conducted by one of the authors (J.G.B.). Results: The group studied had a mean age of >70 years, were not acutely ill, had no known loss of mental function, were better educated and had a high standard of living compared to national standards. However, 30% (95% confidence level) of our group were unable to adequately comprehend written information as measured by the TOFHL. The subgroup with poor comprehension (21 women and 7 men) had a mean age of 85 years (versus 82 years in the group with good comprehension) and a mean of 13 years (versus 15 years in the group with good comprehension) of formal education. Multivariate analysis was consistent with a negative effect of age (p = 0.04), a positive effect of years of formal education (p = 0.0005) and no effect of gender on the TOFHL score. Conclusion: Two recent studies, one in an emergency room setting and the other among Medicare enrollees, demonstrated similar results to ours. The high prevalence of poor comprehension in these groups should alert providers to the need to develop additional or different communication skills that can address the problem of poor reading comprehension across at least three diverse groups of people, with particular attention to those over the age of 65.
Trial of Invasive versus Medical Therapy in the Elderly (TIME)
Authors: Pfisterer M.
Published: April 2003

Background: The risk associated with revascularization (coronary artery bypass-graft surgery and percutaneous coronary interventions) is increased in elderly patients with chronic symptomatic coronary artery disease (CAD) and may outweigh the benefit compared to optimal medical management in this patient group. Patients and Methods: Patients aged ≧75 years with angina Canadian Cardiac Society class ≧II despite at least two antiangial drugs are prospectively enrolled in 14 Swiss centers. They are randomized to coronary angiography and revascularization if possible or to optimized medical therapy and followed up for 6 and 12 months. The primary endpoint is quality of life, assessed by a self-administered structured questionnaire at baseline and after 6 months and occurrence of a composite endpoint of: death, myocardial infarction or hospitalization for acute coronary syndrome/need for revascularization. Results and Relevance: Preliminary data show that included patients meet the goals of the trial. Results will define the role of revascularization in these patients with significant management and cost implications.
Method Comparison in Cardiovascular Trials Using the Difference Plot Method
Authors: Engelmann Mads D.M.
Published: April 2003

In cardiovascular trials investigators often want to compare two different measuring methods and decide on the equivalence of the two measurements. The differences between association and agreement are emphasised and the plot of difference against the average, ‘the difference plot method’, is demonstrated using a practical example. In addition, the interpretation of bias and limits of agreement are discussed and logarithmic transformation is suggested if the difference between the measurements by the two methods is related to the magnitude of the measurement. Finally, it is emphasised that no method will be appropriate in all circumstances and that care should be taken to ensure sufficiently large samples, to pre-specify the meaning of agreement and to avoid systematic variation, that can be caused by observer, time of day, position of subject etc. These are precautions valid to all method comparison studies irrespective of the statistical methods used in the final analyses.
Microalbuminuria Is Associated with Increased Risk of Death in Patients with Myocardial Infarction
Authors: Taskiran Mustafa , Klausen Klaus , Kornerup Karen , Feldt-Rasmussen Bo , Jensen Gorm B. , Jensen Jan Skov
Published: April 2003

In order to study the long-term effect of microalbuminuria on mortality among patients hospitalized with acute myocardial infarction, we followed 125 patients from 1996 to 2000. Exclusion criteria at baseline were renal or urinary tract disease, diabetes mellitus and acute coronary revascularization. At inclusion, urinary albumin/creatinine concentration ratio, height, weight, blood pressure, left ventricle ejection fraction by echocardiography, smoking status, medication, number of acute myocardial infarctions, age and sex were recorded. Deaths were traced in 2000 by means of the Danish Personal Identification Register. Microalbuminuria, defined as a urinary albumin/creatinine concentration ratio above 0.65 mg/mmol, occurred in 52% of the patients and was associated with increased all-cause mortality. Thus, 39% of the patients with microalbuminuria versus only 20% with normoalbuminuria had died within 4 years (p = 0.04). In logistic regression analyses, the odds ratio for death associated with microalbuminuria was 2.5 (1.2–5.6) (p = 0.03), whereas the age-adjusted odds ratio was 1.8 (0.8– 4.2) (p = 0.18). We conclude that the presence of microalbuminuria might be associated with an increased 4-year risk of death among hospitalized patients with myocardial infarction. This hypothesis should be tested in a major population of patients in order to verify the independence from other risk factors including age. Furthermore, we recommend microalbuminuria to be included in future trials in patients with myocardial infarction.
Fever, Cancer Incidence and Spontaneous Remissions
Authors: Kleef Ralf , Jonas Wayne B. , Knogler Wolfgang , Stenzinger Werner
Published: April 2003

Objective: Accumulating evidence exists for (1) an inverse correlation between the incidence of infectious diseases and cancer risk and (2) an inverse correlation between febrile infections and remissions of malignancies. This review is part of an effort of the Office of Alternative Medicine at the National Institutes of Health to examine this evidence. Methods: A review of the literature to a key word search was undertaken, using the following key words: fever, infectious diseases, neoplasm, cancer incidence and spontaneous remission. Results: The data reviewed in this article support earlier observations on the topic, i.e. that the occurrence of fever in childhood or adulthood may protect against the later onset of malignant disease and that spontaneous remissions are often preceded by feverish infections. Conclusion: Pyrogenic substances and the more recent use of whole-body hyperthermia to mimic the physiologic response to fever have successfully been administered in palliative and curative treatment protocols for metastatic cancer. Further research in this area is warranted.
Hemodialysis Is as Effective as Hemoperfusion for Drug Removal in Carbamazepine Poisoning
Authors: Tapolyai Mihály , Campbell Maureen , Dailey Kathleen , Udvari-Nagy Szilvia
Published: April 2003

Although most authors recommend charcoal hemoperfusion (CHP) for the removal of carbamazepine (CBZ) in acute CBZ poisoning, we present a case where we had the chance to compare CHP with hemodialysis (HD). A 50-year-old white man with normal renal function ingested an unkown quantity of CBZ with lithium. He was dialyzed for 3 h and his serum CBZ level was reduced by 27.7%. Four hours later he also had a 3-hour CHP which further reduced his CBZ level by 25.3%. Therefore we conclude that HD with high-flux dialyzers is at least as effective as CHP for the removal of CBZ from the blood after CBZ intoxication.
A Hemodialysis Patient with Trazodone-Induced Parkinsonism
Authors: Fukunishi Isao , Kitaoka Tateki , Shirai Tetsuo , Kino Kyoko , Kanematsu Emiko , Sato Yoshikazu
Published: April 2003

A hemodialysis male patient exhibited depressive symptoms and trazodone was prescribed orally. Although his depressive symptoms disappeared, he gradually presented with parkinsonism. His parkinsonism improved within a week after stopping trazodone. The clinical course strongly suggested that it was induced by trazodone. However, there is no report on antidopaminergic side effects of parkinsonism. This case suggests that antidopaminergic effects leading to parkinsonism need to be considered in patients on hemodialysis that are taking trazodone.
Experimental Nephropathy Induced by Haemophilus parainfluenzae Antigens
Authors: Yamamoto C. , Suzuki S. , Kimura H. , Yoshida H. , Gejyo F.
Published: April 2003

Background: We have demonstrated that outer membrane antigens of Haemophilus parainfluenzae (OMHP) are potentially involved in IgA nephropathy (IgAN). In this study, we established an experimental model of IgAN using OMHP antigens and investigated the nephritogenicity of OMHP antigens. Methods: One hundred and twenty C3H/HeN mice were administered OMHP antigens orally (PO group) or intraperitoneally (IP group). Mice were sacrificed at 10, 20, 30, 40, and 50 weeks of age to examine sequential glomerular changes and to measure levels of IgG, IgA, and IgM antibody against OMHP by ELISA. Results: Glomerular deposition of IgA and increases in the amount of mesangial matrix were observed in the PO group and the IP group from 40 and 30 weeks of age, respectively. Mice in both groups showed glomerular deposition of OMHP antigens from 30 or 40 weeks of age. Levels of IgA antibodies against OMHP were significantly increased in the PO and IP groups compared with controls. There was a significant correlation between mesangial proliferation and glomerular deposition of IgA. Conclusions: Administration of OMHP antigens to mice may induce glomerular deposition of IgA and mesangial proliferation, resembling the changes seen in IgAN, with increases in IgA antibodies against OMHP antigens. This is the first use of OMHP antigens to establish an active model of IgAN.
Stomach Phytobezoars in Two Uremic Anorexic Patients
Authors: Catalano C. , Leone L. , Fabbian F. , Conz P.A.
Published: April 2003

Conglomerates of food and mucus or phytobezoars composed of vegetable matter are sometimes found in the stomach in the general population. Reports of phytobezoars in uremic patients are, however, scarce. Here we describe 2 uremic patients in which esophagogastroduodenoscopy was performed due to dyspepsia associated with weight loss and in which stomach phytobezoars were discovered. Theoretically, uremic patients should be at risk for producing bezoars. In fact, these patients frequently present predisposing conditions such as autonomic neuropathy, diabetes mellitus and delayed gastric emptying. Gastric bezoars cause anorexia. Anorexia is a frequent symptom in dialysis patients and is associated with malnutrition. In these patients, malnutrition is strongly associated with mortality and is quite difficult to reverse. Similarly, phytobezoars cause chronic anorexia. We suggest that clinicians working in dialysis units should consider the possibility of a gastric bezoar when evaluating anorexic uremic patients.
A Comparison of Selected Antihypertensives and the Use of Conventional vs Ambulatory Blood Pressure in the Detection and Treatment of Hypertension
Authors: Ebbs David
Published: April 2003

This multicenter, randomized, double-blind, parallel group study was undertaken to determine the effectiveness of selected antihypertensives (doxazosin, amlodipine, enalapril, and bendrofluazide) in maintaining 24-hour control of blood pressure (BP). The predictive value of ambulatory (A)BP versus clinic (C)BP measurements as a method for detecting patients with hypertension was also evaluated. A total of 204 patients were screened and of these 110 were diagnosed as mild to moderately hypertensive with clinic diastolic BP 100–110 mm Hg (≧95 mm Hg in patients with coronary heart disease risk factors). The 4 antihypertensives were all equally effective at controlling BP over 24 h, as shown by 24-hour ABP measurements. The incidence of adverse events was similar for all 4 treatment groups; headache was the most common event, being reported by 22 patients (20%). There was a clinically relevant reduction in total cholesterol for the doxazosin (–15.4 mg/dl) and amlodipine (–11.6 mg/dl) treatment groups in comparison with enalapril and bendrofluazide. Our results from ABP measurements suggest that the antihypertensives studied are effective first-line therapy in the regulation of hypertension and that ABP is a reproducible measure. ABP may also be useful in identifying patients with various types of high BP, for instance those with ‘white coat’ hypertension, enabling more accurate screening and diagnosis.
Is the Fluoride Concentration Limit of 1,500 ppm in Cosmetics (EU Guideline) Still Up-to-Date?
Authors: Bloch-Zupan A.
Published: April 2003

The 1,500 ppm fluoride (F–) concentration limit set up for European cosmetic toothpaste needs to be considered in terms of effectiveness and toxicity. There is clear evidence for a dose-response relationship between F– concentration and caries-preventive effect (25–30% caries reduction achieved with a 1,000 ppm F– dentifrice). Clinical significance of higher F– concentration has not been totally proven. Low F– toothpastes (<500 ppm F–) have been marketed to reduce F– ingestion by young children in order to minimize the risk of dental fluorosis. Their effectiveness is, however, unclear. Fluoride intake and caries risk assessment should be performed by dental professionals and prescription of topical fluoride should be adjusted individually.
Erosive Potential of Oral Care Products
Authors: Lussi A. , Hellwig E.
Published: April 2003

Seven oral care products and orange juice as a positive control were tested for the erosive potential by immersing each enamel specimen (10 per group) into solutions of the various products for 10 and 20 min. Before and after the experiment Knoop surface hardness (SMH) was measured. The enamel microstructure before and after immersion was assessed by scanning electron microscopy and confocal laser scanning microscopy. Orange juice produced the most marked losses of hardness after 10 and 20 min. Among the dental hygiene products only the fluoride-free toothpaste produced a significant reduction of hardness after 10 as well as after 20 min. With the exception of Elmex gel, all tested oral care products led to a significant (p < 0.05) increase of enamel hardness. The results of the hardness measurements corresponded with the microstructure findings. It may, therefore, be concluded that the tested fluoride-containing oral care products do not exhibit any erosive potential, which could be picked up with the methodologies under study.
CT and MRI Rating of White Matter Lesions
Authors: Fazekas Franz , Barkhof F. , Wahlund L.O. , Pantoni L. , Erkinjuntti T. , Scheltens P. , Schmidt R.
Published: April 2003

Rating scales play an important role in the evaluation of computed tomography (CT) or magnetic resonance-detected white matter lesions (WML). Unfortunately, this type of visual semiquantitative assessment is not yet an optimal tool because commonly agreed concepts regarding its use are lacking. To generate a discussion platform for further improvement of CT and MRI rating, we will provide some basic definitions, summarize the advantages and disadvantages of scoring schemes and review current efforts towards the improvement of this tool. Future research will have to concentrate on deepening our understanding of the histopathologic substrates of WML and on strategies to document their progression.
Cerebral Amyloid Angiopathy and Vessel Dysfunction
Authors: Greenberg Steven M.
Published: April 2003

Cerebral amyloid angiopathy (CAA), defined by deposition of the β-amyloid peptide in medium and small cortical and meningeal vessels, is a well-recognized cause of hemorrhagic stroke. This paper reviews the accumulating evidence supporting an additional role for CAA in producing vessel dysfunction, reduced cerebral blood flow and ischemia. Ischemic lesions are characteristic of several hereditary CAA syndromes, including a recently described mutation of the amyloid precursor protein associated with dementia (but not hemorrhagic stroke) in an Iowa family. Ischemic lesions are seen in some sporadic CAA patients as well, and recent data from transgenic mice suggest potential mechanisms by which β-amyloid may alter vessel physiology. Future studies will seek to define the clinical importance of vascular β-amyloid as a potential target for drug therapy in dementia.