bluuebunny/crossref_metadata_2025 huggingface dataset:
Renography as a Measure of Renal and Neobladder Function in Patients with Ileal Bladder Substitution
Authors: Nishiyama Tsutomu , Terunuma Masahiro , Takeda Masayuki , Katayama Yasushi
Published: April 2003

Introduction: Using renography, we evaluated the function of both the kidneys and neobladder of 20 patients who underwent ileal bladder substitution. Methods: The patients were measured for renal and neobladder function with renography using 99mTc MAG3. Renal function was assayed in every renal unit using O’Reilly patterns. Voiding function was estimated using radioisotope counts for the reservoir. Results: Thirty-two of 37 renal units had normal renograms. Five renal units showed non-obstructive renograms. The percentage of total residual urine (RU) in the reservoir was 30% and more in 6 patients, 10–30% in 8, and <10% in 6. In 7 of 12 patients, the data on estimated RU correlated with the data on measured RU. However, in 5 patients, the data on estimated RU increased more in quantity than the data on RU measured at another time. Conclusions: In patients with bladder substitution the functions of both the kidneys and neobladder could be evaluated in a single renography.
Epidemiological Studies on the Prevalence of Upper Urinary Calculi in Taiwan
Authors: Lee Ying-Huei , Huang Wann-Chu , Tsai Jeng-Yu , Lu Chih-Ming , Chen Wei-Chuan , Lee Ming-Huei , Hsu Hueih-Shing , Huang Jong-Khing , Chang Luke S.
Published: April 2003

Introduction: A nationwide survey was conducted to investigate the prevalence of upper urinary calculi in Taiwan. Materials and Methods: A postal questionnaire was mailed to 27,758 people, 0.2% of the adults in Taiwan. Results: Of the 4,588 valid respondents, 440 had at least one episode of upper urinary calculus disease. The overall prevalence was 9.6% (14.5% in males and 4.3% in females). Men were more prone to nephrolithiasis than women (age-adjusted prevalence of 12.2% in men and 3.1% in women, p = 0). The ‘stone belt’ was localized in the Midwest region of Taiwan. A gender- and age-adjusted multivariate analysis revealed that alcohol consumption and family history of kidney stone were significant risk factors for stone occurrence. Compared with general population, the odds ratios for stone disease in inhabitants whose father, mother and both parents with stone history were 3.44 [95% confidence interval (CI), 2.33–5.07], 4.79 (95% CI, 2.85–8.07) and 10.40 (95% CI, 3.75–28.84), respectively. The subtropical temperature and gradually higher socioeconomic standards of living may contribute to the high prevalence. Inhabitants in the Midwest region have higher risk to develop stones. Conclusions: Further studies are needed to investigate the exact cause of these regional variations of stone prevalence. Nevertheless, the present study provides an additional piece of information on worldwide epidemiology of urolithiasis.
Renal Cell Carcinoma Presenting as Acute Pancreatitis
Authors: Nabi G. , Dogra P.N. , Chowdhary Ashmeet
Published: April 2003

We present a 50-year-old male with renal cell carcinoma and hypercalcemia presenting as acute pancreatitis. The sudden onset of epigastralgia, acute pancreatitis and hypercalcemia with raised parathyroid-like peptide levels in this patient could not be explained except for renal cell carcinoma. This is the first report of such a complication in renal cell carcinoma. The rare presentation and management with a review of the literature is described.
Familial Clustering of Intracerebral Hemorrhage: A Prospective Study in North Carolina
Authors: Alberts M.J. , McCarron M.O. , Hoffmann K.L. , Graffagnino C.
Published: April 2003

Few studies have assessed the frequency of familial clustering in intracerebral hemorrhage (ICH). Of 144 patients with ICH prospectively assessed, 14 (9.8%) had a positive family history of ICH (FH+). Four pedigrees had more than two affected family members. Comparisons between FH+ and FH– probands demonstrated no significant differences in race, age, sex, ICH type or location. An underlying genetic etiology may account for familial clustering in some ICH patients.
Severe Dysosmia Is Specifically Associated with Alzheimer-Like Memory Deficits in Nondemented Elderly Retirees
Authors: Royall Donald R. , Chiodo Laura K. , Polk Marsha J. , Jaramillo Carmen J.
Published: April 2003

Objectives: To determine whether or not (1) impaired olfactory function is associated with impaired memory on neuropsychological testing in healthy retirees, and if so then (2) whether memory impairment is most consistent with a mesiotemporal rather than frontal system disorder. Methods: 173 independent residents of a continuing care retirement community were studied. Subjects completed the University of Pennsylvania Smell Identification Test (UPSIT) and a battery of both general and specific cognitive measures that included the Mini-Mental State Examination (MMSE) and the Executive Interview (EXIT25). Subjects were examined twice over 3 years. Results: UPSIT performance was normal in 21% and in the ‘anosmic’ range in 25% of subjects. Anosmic UPSIT performance was associated with significantly worse performance on all cognitive tests. However, only short-term verbal memory was independently associated with UPSIT-defined anosmia. This association remained significant after adjusting for the other cognitive and sociodemographic variables. The memory deficits of anosmic subjects were qualitatively consistent with a cortical type (type 1) dementing illness such as Alzheimer’s disease (AD). Over time, UPSIT-defined ‘anosmic’ cases suffered significantly greater declines on both the MMSE and the EXIT25, independently of baseline age, gender and MMSE score. Conclusions: Impaired odor identification in individuals without overt dementia is associated with an AD-like memory impairment and an increased rate of cognitive decline. The comorbid association of these deficits is consistent with the known hierarchical spread of preclinical AD pathology and may be a specific indicator of future clinical AD dementia.
Irritable Bowel Syndrome: Update on Pathogenesis and Management
Authors: Alaradi Osama , Barkin Jamie S.
Published: April 2003

Irritable bowel syndrome (IBS) comprises a major proportion of gastrointestinal and primary care practice worldwide. The past several years have seen the rapid evolution of a new and comprehensive model of IBS based on alterations in brain-gut interactions. Alterations in the bidirectional communication between the enteric nervous system and the central nervous system are implicated in the pathogenesis of IBS. 5-Hydroxytryptamine (5-HT; serotonin), a major neurotransmitter in the gastrointestinal tract, and its receptors 5-HT3 and 5-HT4 are involved in the control of gastrointestinal function. A number of abnormal motor and sensory patterns have been reported in patients with IBS. However, it is not known whether these abnormalities are related to symptoms or have a role in establishing a diagnosis of functional gastrointestinal disorders. Visceral hyperalgesia in IBS patients can be secondary to altered receptor sensitivity at the viscus itself and altered central modulation of sensation involving psychological influences in the interpretation of these sensations. The development of diagnostic criteria for IBS helps to avoid unnecessary and costly investigations. A detailed history allows us to diagnose IBS and search for another cause if warning symptoms are present. The Rome criteria are presently used to define IBS and are currently the most widely applied criteria used in clinical diagnosis and research purposes. Abdominal pain or discomfort associated with chronic altered bowel habits are the mainstay in diagnosis, while the supportive criteria may be used to further classify IBS patients into diarrhea-predominant or constipation-predominant subgroups. Minimal diagnostic tests have been advocated in the initial diagnostic approach to patients with suspected IBS, depending on the predominant symptom. The therapeutic goals in IBS must focus on the overall well-being of the patient, including abdominal symptoms and the accompanying nonbowel symptoms and affective disorders. It is important to establish an effective physician-patient relationship and to reassure the patient once the diagnosis of IBS is made. Dietary modification may be of value in some patients with IBS. Dietary fiber is frequently recommended for patients with constipation-predominant IBS. Two novel serotonin agonists are currently under development for constipated IBS patients, tegaserod and prucalopride. Antidiarrheal agents, including loperamide and diphenoxylate, may help patients with diarrhea-predominant IBS. 5-HT3 receptor antagonists may play a role in the management of such patients in the future. Psychological treatment and antidepressants should be considered when IBS symptoms are severe or refractory or associated with psychological distress and impaired quality of life.
Increased [3H]Tiagabine Binding to GAT-1 in the Cingulate Cortex in Schizophrenia
Authors: Sundman-Eriksson Ingrid , Blennow Kaj , Davidsson Pia , Dandenell Anna-Karin , Marcusson Jan
Published: April 2003

Postmortem samples from individuals with schizophrenia (n = 13) and control subjects (n = 10) were investigated for binding of [3H]tiagabine to GABA transporter-1 GAT-1. The binding was analyzed in the cingulate cortex and the caudate nucleus. There were no differences in binding affinity between the groups in any of the investigated areas. The maximum number of binding sites (Bmax) was elevated in the schizophrenic cingulate cortex compared to controls (1,264 ± 96 vs. 860 ± 123 fmol/mg of protein). The Bmax in the caudate nucleus for schizophrenics (426 ± 40 fmol/mg of protein) was the same as for controls (495 ± 69 fmol/mg of protein). The increase in GAT-1 in schizophrenia could be explained by a modulatory upregulation in the cingulate cortex.
Effects of Intracerebroventricularly and Intraperitoneally Administered Growth Hormone on Body Weight and Food Intake in fa/fa Zucker Rats
Authors: Schulz Carla , Wieczorek Ingo , Reschke Kirsten , Lehnert Hendrik
Published: April 2003

Growth hormone (GH) possesses multiple metabolic effects, in particular with regard to glucose and lipid homeostasis. Studies on the effects of GH on body weight and food and water intake are scarce and have yielded controversial results. We investigated the effects of different modes of GH administration on the parameters of body weight and food intake as well as on insulin and leptin concentrations in fa/fa Zucker rats. In control experiments, aqua pro injectione was given. GH was administered over a time period of 11 days at a daily dose of 250 µg intraperitoneally (i.p.) and 25 µg intracerebroventricularly (i.c.v.). While both food intake and body weight were found to be unaltered in the four groups after this observation period, there was an enhanced food intake and consecutively an increase in body weight over the day period when compared to the night period in the groups of rats that received GH i.c.v. or i.p. This tendency was also shown for water intake. Insulin and leptin concentrations were similar in all groups. Thus, injection of GH appears to modify food intake-related behavior, since the periods of enhanced food and water intake were shifted from night- to daytime. Thus, while in general the metabolic parameters remained unchanged, the activity pattern was clearly modified.
Caloric and Rotational Testing: Merits, Pitfalls and Myths
Authors: Katsarkas Athanasios , Smith Heather , Galiana Henrietta
Published: April 2003

Objectives: The evaluation of the caloric and the rotational tests in the light of contemporary data on the function and dysfunction of the vestibular system. This is attempted by using novel engineering system notions. Material and Patients: Our work in mathematical modeling of the vestibuloocular reflex. In addition, our data from thousands of patients submitted to caloric testing and more than one hundred patients submitted to rotational testing. Methods: Analysis of results in light of system engineering notions. Results and Conclusions: The caloric test, corresponding to low head velocity and movement frequency, is an excellent test in defining the degree of excitability of one side versus the other. If there is a bilateral loss of vestibular function both, right and left, caloric responses will be compromised. However, the definition of the dynamic condition of the system and the detection of nonlinearities, especially in the presence of pathology, require rotational tests, which will yield such information if data are appropriately processed. Present day knowledge is insufficient on: (1) the functional contribution of the fast phase of nystagmus, (2) the synergistic effects of semicircular canals and otoliths, and (3) the synergistic effects of vestibular and other sensory modalities.
On the Value of Components in the Vestibular Examination
Authors: Gacek Richard R.
Published: April 2003

Several techniques are used to evaluate the dizzy patient. The use of these methods is dependent upon the value of information forthcoming and cost. Accordingly, in order of value per unit of cost, these components in the examination are history, physical examination, tests of auditory and vestibular function, and finally special tests (neuroimaging, rotation tests, and posturography). An accurate diagnosis and effective treatment program can be formulated in the majority of dizzy patients using these techniques.
A partial BRCA1 sequence homology mapping to 4q28
Authors: Stec I. , van Vliet M. , van Eijk R. , Meijers H. , Kroeze K.H.G. , Dauwerse J.G. , van Ommen G.-J.B. , Cornelisse C.J. , den Dunnen J.T. , Devilee P.
Published: April 2003

Using a BRCA1 cDNA probe in Southern analysis, we detected a sequence of 348 bp on 4q28 that is homologous to the 3′ end of BRCA1. A 28-kb sequence contig has been assembled spanning the homologous region, which we designated BRCA1-h. An open reading frame was identified encoding a sequence of 82 amino acids; 22 of the last 23 amino acids are identical to the last 23 residues of BRCA1. BLAST-searches, RT-PCR and RACE-experiments have been unable to provide evidence that BRCA1-h is part of an expressed gene.
Isolation of novel mouse genes associated with ectopic ossification by differential display method using ttw, a mouse model for ectopic ossification
Authors: Koshizuka Y. , Ikegawa S. , Sano M. , Nakamura K. , Nakamura Y.
Published: April 2003

Mouse mutant ttw (tiptoe walking) is an excellent model for ectopic ossification. This mutant exhibits ossification in various soft tissues, which is histologically similar to human OPLL (ossification of posterior longitudinal ligament of the spine). We previously reported that ttw is caused by a nonsense mutation of the nucleotide pyrophosphatase (ENPP1) gene, and that a polymorphism of the human ENPP1 gene is associated with OPLL. These facts indicate that ENPP1 regulates ectopic ossification in vivo; however, the mechanism is unclear. ENPP1 is an ectoenzyme that generates phosphate (Pi) and pyrophosphate (PPi). PPi is a strong inhibitor of ossification. Abnormal Pi metabolism is observed in patients with OPLL, and diseases with abnormal Pi metabolism such as hypophosphatemic rickets are frequently complicated by ectopic ossification. These lines of evidence suggest Pi-PPi metabolism associated with ENPP1 may play an important role in regulation of ectopic ossification. To clarify the molecular mechanism of ectopic ossification in ttw, we examined the effect of dietary phosphate and calcium on the ttw phenotype and found a high dietary phosphate-accelerated ectopic ossification. Then we examined genes associated with the enhanced ossification in ttw on a high phosphate diet by a differential display method. We identified nine mouse genes; six genes were up-regulated by the high phosphate diet, and three were down-regulated. Six of the nine genes were novel and we cloned and characterized them. Two of the genes were highly specific to cartilage, suggesting their specific role in enchondral ossification. Our identification of the novel genes would give novel insight into the mechanism of ectopic ossification and etiology of OPLL.
Syrian hamster 5S rRNA genes are assigned to 6q2 with PNA-FISH by an R-banded karyotype
Authors: Lomholt B. , Christensen K. , Frederiksen S.
Published: April 2003

A karyotype for the Syrian hamster is proposed based on an R-banding pattern. R-bands were obtained by BrdU incorporation into the cells followed by a combined DAPI and propidium iodide staining of the fixed metaphase spreads. In situ hybridisation was performed with two biotinylated 18-mer PNA (peptide nucleic acid) probes complementary to sequences within the 5S rRNA gene. The 5S rRNA gene repeats map to chromosome 6q2. The present PNA-FISH procedure is an abbreviated and simpler version of that previously published.
Molecular characterization and chromosome assignment of the porcine gene COX7A1 coding for the muscle specific cytochrome c oxidase subunit VIIa-M
Authors: Drögemüller C. , Kuiper H. , Voß-Nemitz R. , Brenig B. , Distl O. , Leeb T.
Published: April 2003

The COX7A1 gene encodes a heart- and muscle-specific isoform of the subunit VIIA of cytochrome c oxidase, which is the last component of the mitochondrial electron transfer chain. Cloning and characterization of the porcine COX7A1 gene revealed a highly conserved organization with respect to other mammalian COX7A1 orthologs. The porcine gene consists of four exons spanning approximately 1.5 kb and codes for a peptide of 80 amino acids. The COX7A1 gene showed no variation between pigs from different breeds. The gene was assigned by FISH and RH-mapping to SSC 6q1.1→q1.2 which is in agreement with previously established comparative maps.
Molecular cytotaxonomy of New World monkeys (Platyrrhini) – comparative analysis of five species by multi-color chromosome painting gives evidence for a classification of Callimico goeldii within the family of Callitrichidae
Authors: Neusser M. , Stanyon R. , Bigoni F. , Wienberg J. , Müller S.
Published: April 2003

Chromosome rearrangements are considered as “rare genomic changes” and can provide useful markers and even landmarks for reconstructing phylogenies complementary to DNA sequence data and bio-morphological comparisons. Here, we applied multi-directional chromosome painting to reconstruct the chromosome phylogeny and evolutionary relationships among the New World monkey (Platyrrhini) species Callithrix argentata, Cebuella pygmaea, Saguinus oedipus, Callithrix jacchus and Callimico goeldii. The results clarified several aspects of New Wold monkey phylogeny. In particular the phylogenetic position of C. goeldii was elucidated, which has been controversially discussed and variously classified in the family Callitrichidae, in the family Cebidae or in its own family Callimiconidae. Comparative genome maps were established by multi-color fluorescence in situ hybridization (FISH) with human, S. oedipus and Lagothrix lagothricha chromosome- specific DNA probes. From these data we reconstructed the putative ancestral karyotype of all Callitrichidae. Various derived chromosomal syntenies are shared by all five species and cytogenetically define Callitrichidae – including Callimico goeldii – as a distinctive group within the Platyrrhini. C. pygmaea and C. argentata share identical chromosomal syntenies from which S. oedipus and C. jacchus differ by single independent translocations. A common derived chromosomal change links Callimico with the marmosets to the exclusion of the tamarins, however, it has further diverged from an ancestral marmoset karyotype by at least four apomorphic rearrangements. Saimiri sciureus, representing the Cebinae, exclusively shares a derived syntenic association with all Callithrichidae, defining the genus Saimiri as a sister group.
Alignment of VIM, MRC1, GAD2, and IL2RA genes on swine chromosome 10q by in situ hybridization and RH mapping
Authors: Hiraiwa H. , Uenishi H. , Yasue H.
Published: April 2003

Since the distal half of swine chromosome (SSC) 10q was shown to contain a quantitative trait locus (QTL) influencing swine growth, the precise correspondence between this chromosome region and the orthologous human chromosome region (HSA10p) was investigated using chromosomal fluorescence in situ hybridization and RH mapping of type I loci spanning the growth QTL. The goal was to align this critical region of swine with the corresponding region in human for the purpose of identifying candidate genes. The HSA10p type I loci mapped in swine were VIM, MRC1, GAD2, and IL2RA. Locus order on SSC10q was shown to be centromere–VIM–MRC1–GAD2–IL2RA, while in human the order is centromere–GAD2–MRC1–VIM–IL2RA, indicating that the chromosome segment marked by VIM, MRC1 and GAD2 has been inverted relative to the centromere and IL2RA.
Screening for Autoantibodies to Tissue Transglutaminase Reveals a Low Prevalence of Celiac Disease in Blood Donors with Cryptogenic Hypertransaminasemia
Authors: Soresi M. , Amplo M. , Agliastro R. , Sesti R. , Di Giovanni G. , Magliarisi C. , Belvedere M. , Carroccio A. , Montalto G.
Published: April 2003

Patients with chronic cryptogenic hypertransaminasemia are at high risk of developing celiac disease (CD). In fact, among the various serological disorders, CD patients at onset frequently present hypertransaminasemia. In this study, we evaluated usefulness and reliability of the new test for antitissue transglutaminase (tTG) in screening for CD as well as in estimating the prevalence of CD in a population of blood donors presenting unexplained hypertransaminasemia at donation. Controls were 180 consecutive healthy donors without hypertransaminasemia and 20 CD patients with known antiendomysial antibody (EmA) positivity. Out of 22,204 blood donors over a period of 2 years, we found 258 subjects (1.2%) with cryptogenic hypertransaminasemia. Four of these subjects (1.5%) were positive for anti-tTG, but only 3 of them were positive for EmA. EmA were negative in all the remaining hypertransaminasemia subjects. In the control groups, anti-tTG antibodies were negative in all the 180 healthy donors without hypertransaminasemia, but positive in all the CD patients known to be EmA positive. 3 of the 4 subjects positive for anti-tTG, including 2 who were also EmA positive, underwent biopsy of the distal duodenal mucosa which showed a picture compatible with CD only in the 2 patients with concomitant EmA positivity. After 3 months of gluten-free diet, the serum transaminase values normalized in these 2 patients. In conclusion, the prevalence of CD in our blood bank population was lower than that reported in other similar studies, but the new test for anti-tTG showed a good sensitivity and reliability, and, therefore, it can be proposed as a first-level test in screening for CD in selected populations such as subjects with hypertransaminasemia.
Potent and Long-Lasting Action of Lafutidine on the Human Histamine H2 Receptor
Authors: Fukushima Yasushi , Otsuka Hiroko , Ishikawa Minako , Asano Tomoichiro , Anai Motonobu , Katsube Takao , Ogawa Kenji , Kajiwara Tetsuro , Ohkawa Shinichiro , Ishikawa Takashi , Omata Masao , Saitoh Toshihito
Published: April 2003

Background/Aim: Based on animal models, lafutidine, a novel histamine H2 receptor (H2R) antagonist, is reported to show potent and long-lasting antagonisms of histamine H2R-mediated effects. However, no reports have been published concerning its direct interaction with the human H2R. This study aims at characterizing its interaction with human H2R. Methods: Chinese hamster ovary cell lines stably expressing human H2Rs were obtained. The dose-dependent effects of lafutidine and famotidine on [3H]tiotidine binding and histamine-stimulated cAMP production were analyzed. The effects of preincubation with 2.78 × 10–7M of lafutidine or famotidine for 30 min on histamine-dependent cAMP production and [3H]tiotidine binding were also examined after 0, 1, 2, 4, and 12 h. This concentration is below the Cmax of lafutidine (10 mg p.o.) and above the Cmax of famotidine (20 mg p.o.). Results: Lafutidine inhibited [3H]tiotidine binding and histamine-stimulated cAMP production as or more potently than famotidine. At higher concentrations lafutidine was more potent than famotidine. In addition, preincubation with 2.78 × 10–7M lafutidine, but not with 10–5M famotidine, had marked inhibitory effects which persisted as long as after extensive washing. Conclusion: Lafutidine shows a potent and long-lasting antagonism on the human H2R.
Effects of Very Long (up to 10 Years) Proton Pump Blockade on Human Gastric Mucosa
Authors: Lamberts Regina , Brunner Gorig , Solcia Enrico
Published: April 2003

Background: Long-term use of proton pump inhibitors (PPI) has been reported to worsen oxyntic mucosa gastritis and the resulting gland atrophy has been considered a potential risk factor for neoplastic changes in the gastric mucosa. Aims: The present study examines the effect of extended continuous PPI treatment for up to 10 years on the exocrine and endocrine stomach of patients with acid-related diseases of the upper GI tract. Methods: Biopsies from the antral and oxyntic mucosa taken at regular time intervals were examined for gastritis, atrophy, intestinal metaplasia, Helicobacter pylori and argyrophil cells and correlated to serum gastrin levels. Results: A general amelioration of antral gastritis without relevant changes of atrophy or intestinal metaplasia, contrasted with the worsening of gastritis and gland atrophy seen in the oxyntic mucosa of reflux esophagitis (but not gastric or duodenal ulcer) patients in the presence of H. pylori infection. In association with PPI- induced hypergastrinemia, argyrophil cell hyperplasia (but not dysplasia or neoplasia) developed in the oxyntic mucosa. Conclusion: The present results outline the milder pretreatment pattern and higher proneness to PPI-related, H. pylori-restricted worsening of oxyntic mucosa gastritis in reflux esophagitis compared to gastric ulcer or duodenal ulcer patients. In addition, they confirm a substantial safety of long-term PPI therapy as concerns neoplastic changes in the exocrine and endocrine human stomach.
Quality of Life in Animals as a New Outcome for Surgical Research: G-CSF as a Quality of Life Improving Factor
Authors: Bauhofer Artur , Witte Klaus , Lemmer Björn , Middeke Martin , Lorenz Wilfried , Celik Ilhan
Published: April 2003

Sepsis is still a major problem in human medicine with a high mortality rate. Nearly all attempts to improve the outcome of septic patients with immune modulators failed. In most of these trials only mechanistic endpoints such as mortality rate, complication rate, cytokine levels and physiological parameters were assessed. Only in a very few trials quality of life had been chosen as primary endpoint. In basic research and especially in animal experiments in the field of sepsis and oncology, only molecular investigations which explain drug and treatment interactions were in the focus of the scientific community. Animal models simulating clinical complexity and investigating outcomes like quality of life were very rare. The aim of this study was to demonstrate alterations in sickness behaviour – the animal equivalent to quality of life in man – in rats as a response to sepsis after prophylaxis with G-CSF and antibiotics. Sickness behaviour was assessed by measurement of core body temperature, food and water intake, locomotor activity and circadian rhythm of these parameters. Complex animal experiments in rats were performed including anaesthesia, antibiotic and cytokine (G-CSF) prophylaxis, volume substitution, laparotomy, contamination and infection with human faecal suspension and postoperative analgesia. In group A (sham) and D (antibiotic + G-CSF) the mortality rate was 0% , but in group B (no prophylaxis) 33% (3/9) and in group C (antibiotic prophylaxis) 11% (1/9) of the animals died. Before infection all rats showed clear circadian patterns of locomotor activity and body temperature with physiologically higher values during the night-time. Immediately after operation and infection temperature increased, water and food intake, locomotor activity decreased and circadian rhythms were lost. Body temperature and water consumption were already normalised at day 2 after infection in all groups. Normal food intake was re-established in group C and D at day 3 while one more day was needed for recovery in Group C. Restoration of locomotor activity occurred in group D at day 5, in group C at day 7. In group B locomotor activity remained suppressed during the whole observation period of 8 days postoperatively. In conclusion, in septic rats sickness behaviour, an equivalent to quality of life in humans, is improved rapidly by a prophylaxis with G-CSF in combination with antibiotics and can be used as a new outcome in preclinical surgical research.
Hyperoxia in Extreme Hemodilution
Authors: Habler O. , Kleen M. , Kemming G. , Zwissler B.
Published: April 2003

Intraoperative surgical blood loss is initially replaced by infusion of red cell-free, cristalloidal or colloidal solutions. When normovolemia is maintained the ensuing dilutional anemia is compensated by an increase of cardiac output and of arterial oxygen extraction. In the ideal case, a surgical blood loss can entirely be ‘bridged’ without transfusion by intraoperative normovolemic hemodilution. However major blood loss results in extreme hemodilution and the transfusion of red blood cells may finally become necessary to increase arterial oxygen content and to preserve tissue oxygenation. When transfusion has to be started before surgical control of bleeding has been achieved, parts of the red blood cells transfused will get lost, thereby increasing intraoperative transfusion needs. Beside red blood cell transfusion, arterial oxygen content can be rapidly increased by ventilating the patient with 100% oxygen (hyperoxic ventilation), thus enhancing the amount of physically dissolved oxygen in plasma (hyperoxia). In experimental and clinical studies hyperoxic ventilation has emerged as a simple, safe and effective intervention to enlarge the margin of safety for hemodynamic compensation and tissue oxygenation in hemodiluted subjects experiencing major bleeding. The hyperoxia-associated microcirculatory dysregulation and impaired tissue oxygenation known to take place in the presence of a physiologic hemoglobin concentration are not encountered in hemodiluted subjects. Hyperoxic hemodilution i.e. the combination of intraoperative extreme hemodilution and hyperoxic ventilation may therefore be considered a cost-effective, safe and efficient supplement to reduce allogeneic transfusion during surgical interventions associated with high blood losses. The vast majority of the experimental and clinical investigations this new concept is based on was initiated and performed under the guidance of Prof. Konrad Messmer.
An Examination of the Hofer and Sliwinski Evaluation
Authors: Salthouse Timothy A. , Nesselroade John R.
Published: April 2003

Although we fully endorse the thesis of Hofer and Sliwinski that all research designs and analytical procedures should be critically examined before accepting conclusions based upon them, in this commentary we question whether their critical examination is complete. In particular, we suggest that they neglected some disadvantages of longitudinal and narrow age range cross-sectional designs and that they may have been overly pessimistic with respect to the potential usefulness of cross-sectional designs for certain research questions.
A Strategy for the Management of Elderly Women with Primary Hyperparathyroidism: A Comparison of Etidronate Therapy with Parathyroidectomy
Authors: Horiuchi T. , Onouchi T. , Inoue J. , Shionoiri A. , Hosoi T. , Orimo H.
Published: April 2003

Objective: To evaluate the efficacy of etidronate (EHDP) on lumbar spine bone mineral density (LSBMD) and total bone mineral density (TBMD) in elderly women with primary hyperparathyroidism (PHPT), we compared changes in LSBMD and TBMD between patients treated by EHDP therapy and parathyroidectomy (PTX). Subjects and Methods: Twenty-two PHPT patients were enrolled and randomized into two groups; 9 received EHDP and 13 underwent PTX. All patients were followed up for 1 year by measuring LSBMD, TBMD, serum calcium, inorganic phosphate, parathyroid hormone, 1,25-dihydroxyvitamin D, serum alkaline phosphatase, intact osteocalcin, urinary pyridinoline (Upyd) and urinary deoxypyridinoline (Udpd). The presence of spinal fractures was evaluated by X-ray photography before and after treatment. Results: EHDP treatment produced a significant increase in LSBMD of 10% compared with pretreatment levels after 1 year (p < 0.03, compared to baseline), while PTX produced a significant increase in LSBMD of 20% compared to pretreatment levels (p < 0.01). However, TBMD remained unchanged for 1 year after both EHDP administration and PTX. Among biochemical bone turnover markers, EHDP administration resulted in significant decreases in alkaline phosphatase by 78%, Upyd by 64% and Udpd by 37% after 12 months compared with the pretreatment levels (p < 0.05) and intact osteocalcin by 67% after 6 months (p < 0.05). There were no differences in the fracture rate between the EHDP and PTX groups during 1 year. Conclusion: EHDP administration results in a somewhat lower increase in LSBMD than that following PTX and suppresses bone formation and resorption in elderly PHPT patients for 1 year. We conclude that PTX is preferable to EHDP therapy for the management of elderly PHPT patients; however, EHDP administration should also be considered for elderly patients with many complications or who are unfit for surgery.
Effect of ‘Drug Holiday’ on Blood Pressure Control: A Randomized Double-Blind Comparative Trial of Amlodipine versus Felodipine Extended Release in Chinese Patients with Mild to Moderate Essential Hypertension
Authors: Hu Dayi , Zhao Xiuli , He Xin , Tao Daning , Wang Shoulan , Wei Guojing , Qiu Zhiyong , Li Wanyi , Liu Yin , Li Zhaoxia , Zhang Giulan
Published: April 2003

Objective: To compare the antihypertensive effect and safety of amlodipine and felodipine extended release (ER). Methods: Seventy-six patients with mild to moderate hypertension were randomized to two groups in a double-blind manner. One group was treated with amlodipine 5.0–10.0 mg/day (group 1), and the other group with felodipine ER 5.0–10.0 mg/day (group 2), for 12 weeks. Twenty-four-hour ambulatory blood pressure (ABP) monitoring at baseline and after treatment was used to evaluate drug efficacy and blood pressure (BP) changes during a ‘drug holiday’ (48 h). Results: Diastolic BP was reduced in the amlodipine group by 15.1 mm Hg (to a final BP of 84.8 mm Hg) and in the felodipine ER group by 15.3 mm Hg (to a final BP of 85.0 mm Hg). Efficacy was considered to be achieved in 83.8% of patients in group 1 and in 87.9% of patients in group 2 (not significant). The number of patients controlled at the starting dose was 28 in group 1 and 19 in group 2 (p < 0.01). In group 1, BP remained below 140/90 mm Hg 24–48 h after the missed dose, and 24-hour ABP was not significantly different from that before the missed doses. In group 2, BP was above 140/90 mm Hg after the missed dose, and both BP and 24-hour ABP were statistically significantly higher than those before the missed doses. Adverse reactions were infrequent in both groups. Conclusions: Both amlodipine and felodipine ER are effective, safe, reliable and well tolerated in the treatment of mild to moderate essential hypertension. BP was well controlled in group 1 24–48 h after the missed dose. The fluctuation of BP in group 2, however, was significantly worse than that in group 1.
Beyond Traditional Risk Factors: Homocysteine and Atherosclerosis
Authors: Spieker Lukas E. , Lüscher Thomas F. , Noll Georg
Published: April 2003

Normal fasting homocysteine plasma levels average 5–15 µmol/l. Elevated homocysteine plasma levels are caused by genetic variants, malnutrition, drugs or renal failure, among other causes. A relatively frequent point mutation of the N5,N10-methylenetetrahydrofolate-reductase (MTHFR) gene codes for a thermolabile variant of MTHFR with reduced enzymatic activity. The prevalence of mild hyperhomocysteinemia in the general population is 5–7%; severe hyperhomocysteinemia is rare. In contrast to severe hyperhomocysteinemia, mild hyperhomocysteinemia often remains asymptomatic until the fourth decade, then causing premature atherosclerotic vascular disease. So far, several studies have shown that the association between coronary artery disease and hyperhomocysteinemia is not confined to the rare inborn homocystinuria but also exists in the general population. In fact, there is a positive correlation between homocysteine plasma levels above 10 µmol/l and mortality. Homocysteine plasma levels can be lowered by intake of folic acid and vitamins B6 and B12. However, until the results of randomized controlled studies investigating the effects of homocysteine-lowering therapy are available, general screening for hyperhomocysteinemia is not recommended. In patients with hyperhomocysteinemia and a high risk for cardiovascular events (i.e. patients with multiple risk factors or established atherosclerotic vascular disease), the dietary intake of folic acid and vitamins B6 and B12 should be optimized. Persistently elevated homocysteine plasma levels may be treated with dietary supplementation of these vitamins, i.e. folic acid 0.4 mg/day, vitamin B6 2 mg, and vitamin B12 6 µg/day.
Intramyocardial Injection of Genes with a Novel Percutaneous Technique: Initial Safety Data of the Euroinject One Study
Authors: Kastrup Jens , Jørgensen Erik , Drvota Viktor , Thuesen Leif , Bøtker Hans Erik , Gyöngyösi Marian , Glogar Dietmar , Rück Andreas , Bin Islam Khalid , Sylvén Christer
Published: April 2003

Therapeutic angiogenesis with vascular endothelial growth factor proteins or genes encoding for the proteins is a new potential treatment for patients who cannot be treated with conventional coronary bypass surgery or balloon angioplasty. The Euroinject One study is a multicenter noncommercial randomized double-blind placebo-controlled study of the therapy with the gene encoding for VEGF-A165. The study is designed to include 80 patients with severe coronary artery disease and a reversible defect on myocardial stress scintigraphy. It is planned that 40 patients will receive the VEGF-A165 plasmid and 40 patients the placebo plasmid without the gene encoding for VEGF-A165. The injection catheter is entered percutaneously into the left ventricle. Guided by electromechanical mapping with a NOGA system 10 intramyocardial injections of plasmid are given around and within the tissue area with reversible ischemia. The injections are monitored carefully regarding predefined variables to ensure injections of the genes into the ischemic myocardium. The primary endpoint are changes of reversible myocardial ischemia on stress myocardial scintigraphy. The safety data from the first 10 patients demonstrated that the percutaneous intracardial injection of genes seems safe and can be performed without complications.
Correlation of Pulmonary Arterial Smooth Muscle Structure and Reactivity during Adaptation to Extrauterine Life
Authors: Kelly David A. , Hislop Alison A. , Hall Susan M. , Haworth Sheila G.
Published: April 2003

Peripheral pulmonary arteries remodel immediately after birth as pulmonary vascular resistance falls. We hypothesised that there is a link between the response to agonist stimulation and wall structure in early postnatal life. Arteries from fetal, newborn and 14-day-old piglets were mounted on a perfusion myograph. Lumen diameter and smooth muscle cell nuclear positions were recorded after sequential addition of KCl, U46619 and bradykinin. Subsequently, vessels were studied by confocal and transmission electron microscopy. Contractile agonist stimulation caused a greater and faster reduction in lumen diameter in the newborn than at 14 days (p < 0.02) and the distance between cells decreased more in the newborn (p < 0.05). Unstimulated smooth muscle cells changed shape from being rounded in the fetus to fusiform by 14 days, with increasing length/width ratio (p < 0.01). On contraction, length/width ratio decreased most at 14 days (p < 0.01). Extracellular matrix, collagen and elastin, sparse at birth, increased by 14 days. Thus a greater change in lumen diameter in relation to cellular contraction was observed in the newborn than at 14 days and the amount of extracellular matrix within the vessel wall may affect the overall change in lumen diameter.
Met-RANTES Inhibition of Mucosal Perfusion Failure in Acute Intestinal Transplant Rejection – Role of Endothelial Cell-Leukocyte Interaction
Authors: Stojanovic Tomislav , Bedke Jens , Gröne Hermann-Josef , Proudfoot Amanda E.I. , Becker Heinz , Markus Peter , Hecker Markus
Published: April 2003

Acute rejection-induced microvascular injury results in graft dysfunction, ultimately leading to graft loss. Infiltration of T cells and monocytes as a consequence of an enhanced endothelial cell-leukocyte interaction appears to play an important role in this deleterious process. Recruitment of these pro-inflammatory cells to the vessel wall is mediated by chemokines such as RANTES. Heterotopic small bowel transplantation was performed in rats with the fully allogeneic Brown Norway-Lewis strain combination and, as a control, the syngeneic Lewis-Lewis strain combination. Intravital microscopy was performed from postoperative day 1–7 in both groups. The percentages of perfused villi and villus stasis, mucosal and muscular functional capillary densities, red blood cell velocities, and finally, firm adherence of leukocytes in postcapillary submucosal venules were assessed. Syngeneic small bowel transplantation revealed homogeneous perfusion of villi and muscle layers over the whole study period. Allogeneic small bowel transplantation showed a decline in perfusion from postoperative day 1 until complete failure on postoperative day 7. This was accompanied by a continuous increase in endothelial cell-leukocyte interaction which reached a plateau on postoperative day 5. Met-RANTES treatment at 200 µg/day for 5 days markedly attenuated both the decrease in functional capillary density and the increased endothelial cell-leukocyte interaction in rats following allogeneic small bowel transplantation. We conclude that blocking chemokine receptors, thereby limiting endothelial cell-leukocyte interaction, may constitute a useful therapeutic approach to the prevention of microcirculatory perfusion failure in acute transplant rejection.
Effects of Sex on Renal Structure
Authors: Neugarten Joel , Kasiske Bertram , Silbiger Sharon R. , Nyengaard Jens R.
Published: April 2003

Aims: There are few data examining differences in renal structure between the sexes. Elucidation of the mechanisms responsible for the observed effects of sex on the progression of chronic renal disease requires knowledge of the effects of sex on renal structure. Results: Although we found that male kidneys weigh more than female kidneys, sex is not an independent determinant of kidney weight. The increased kidney weight seen in men is solely dependent on their greater body surface area. We found no difference in glomerular number between men and women. Although men had larger glomeruli than women, sex is not an independent determinant of glomerular volume. The occurrence of larger glomeruli in men is solely dependent on their greater body surface area. Similarly, the greater total glomerular volume seen in men as compared to women reflects increased kidney weight in men. Sex is not an independent determinant of total glomerular volume. Conclusions: These findings do not support the hypothesis that renal structural differences contribute to sex-related differences in the rate of progression of chronic renal disease.
Relationship between Renal Size and Hypertension in Patients with Chronic Renal Failure
Authors: Zümrütdal Ayşegül Örs , Turan Can , Çetin Faruk , Adanalı Süreyya
Published: April 2003

Background/Aims: The aim of this study was to compare renal size, shape and volume in hypertensive and nonhypertensive patients with end-stage renal failure. Methods: Patients with volume overload and diabetes mellitus, myeloma, amyloidosis, or polycystic renal disease were all excluded. Fifty patients undergoing hemodialysis for the first time were grouped as normotensive (23/50) and hypertensive (27/50). Hypertensive patients were then divided into subgroups having slight (4/27), medium (13/27), or high (10/27) hypertension. Using ultrasonographic methods, absolute renal size, relative renal size (renal length/body length), renal volume (length × width × depth × 0.52), and renal shape (width/length) were calculated. Results: In hypertensive patients, right and left relative and absolute renal lengths and left renal volume were found to be significantly less than in normotensive patients. Within the hypertensive group, no significant differences were found in the parameters. There was no relationship between age, sex, height, weight, body mass index, creatinine, creatinine clearance, sodium, calcium levels, renal shape and hypertension. Conclusion: In this study, etiopathogenesis of the renal disease, individual and multifactorial effects, residual renal function and nephron numbers may be involved in the results. Further investigations are needed to evaluate multifactorial effects on blood pressure and kidney size in chronic renal failure patients.
Affinity Binding of Glycosaminoglycans with β2-Microglobulin
Authors: Ohashi Kenichi , Kisilevsky Robert , Yanagishita Masaki
Published: April 2003

Background: A constant finding in β2-microglobulin (β2m) amyloidosis is an increase in tissue heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PGs) at sites of amyloid deposits. However, the binding characteristics of PGs with β2m have not been elucidated yet. Methods: Using affinity retardation chromatography, β2m- and glycosaminoglycan (GAG)-anchored columns, an affinity between β2m and GAGs was analyzed. Five peptides which spanned the entire β2m amino acid sequence were prepared, and an affinity between these peptides and heparin (HP) was examined. Furthermore, the specific binding of biotinylated β2m peptide for AA amyloid deposits via GAGs was examined on tissue sections. Results: Using β2m-anchored column, HP showed the smallest dissociation constant (Kd), i.e. the strongest affinity, among the GAGs examined. At 0.4 M NaCl, the Kds of β2m relative to BSA-anchored columns for HP, HS, CS-A, CS-B, and CS-C were 94, 620, 130, 660 and 190 µM, respectively. Using GAG-anchored columns, at 0.15 M NaCl, pH 7.4, β2m also showed an affinity for HP, with the Kd relative to a reference column being 370 µM. Under the latter conditions, no β2m affinity for CSA was demonstrated. Among the five peptides, peptide-1, which is composed of residues 1–24, showed the highest affinity for HP, the Kd being 190 µM. Peptides analogous to peptide-1, in which each basic amino acid was individually replaced by alanine, showed a remarkable decrease in affinity for HP. The specific binding of biotinylated β2m peptide for AA amyloid deposits via HS and CS was confirmed in situ by pretreatment with heparitinase and chondroitinase ABC. Conclusion: The present data indicate that HP/HS is effective in the binding of the β2m monomer, and the anatomic localization of β2m amyloid precursor protein.