bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of noninvasively estimated microvascular O2 extraction during ramp exercise
Authors: Ferreira Leonardo F. , Koga Shunsaku , Barstow Thomas J.
Published: September 2007

Utilization of near-infrared spectroscopy (NIRS) in clinical exercise testing to detect microvascular abnormalities requires characterization of the responses in healthy individuals and theoretical foundation for data interpretation. We examined the profile of the deoxygenated hemoglobin signal from NIRS {deoxygenated hemoglobin + myoglobin [deoxy-(Hb+Mb)] ≈ O2 extraction} during ramp exercise to test the hypothesis that the increase in estimated O2 extraction would be close to hyperbolic, reflecting a linear relationship between muscle blood flow (Q̇m) and muscle oxygen uptake (V̇o2m) with a positive Q̇m intercept. Fifteen subjects (age 24 ± 5 yr) performed incremental ramp exercise to fatigue (15–35 W/min). The deoxy-(Hb+Mb) response, measured by NIRS, was fitted by a hyperbolic function [ f( x) = ax/( b + x), where a is the asymptotic value and b is the x value that yields 50% of the total amplitude] and sigmoidal function { f( x) = f0 + A/[1 + e−(− c+ dx)], where f0 is baseline, A is total amplitude, and c is a constant dependent on d, the slope of the sigmoid}, and the goodness of fit was determined by F test. Only one subject demonstrated a hyperbolic increase in deoxy-(Hb+Mb) ( a = 170%, b = 193 W), whereas 14 subjects displayed a sigmoidal increase in deoxy-(Hb+Mb) ( f0 = −7 ± 7%, A = 118 ± 16%, c = 3.25 ± 1.14, and d = 0.03 ± 0.01). Computer simulations revealed that sigmoidal increases in deoxy-(Hb+Mb) reflect a nonlinear relationship between microvascular Q̇m and V̇o2m during incremental ramp exercise. The mechanistic implications of our findings are that, in most healthy subjects, Q̇m increased at a faster rate than V̇o2m early in the exercise test and slowed progressively as maximal work rate was approached.
Long-Lasting NMDA Receptor-Mediated EPSCs in Mouse Striatal Medium Spiny Neurons
Authors: Logan Stephen M. , Partridge John G. , Matta Jose A. , Buonanno Andres , Vicini Stefano
Published: September 2007

Excitatory postsynaptic currents (EPSCs) from dorsolateral medium spiny neurons (MSNs) were recorded in cortico-striatal slice preparations from postnatal day 6–8 (P6-8) and >P12 wild-type mice and mice that were lacking either the NR2A or the NR2C subunit of the N-methyl-d-aspartate (NMDA) receptor. EPSCs were elicited by stimulation of the excitatory afferents and the NMDA and non-NMDA receptor-mediated components were pharmacologically isolated. The ratio of these components decreased with development and was significantly reduced only between age-matched +/+ and NR2A −/− neurons. In many MSNs, the NMDA-EPSC decay was characterized by the presence of a slow exponential component with a time constant lasting >1 s regardless of genotype or age. In the NR2A −/−, no developmental increase in the decay time (Tw) of the NMDA-EPSCs was observed although it was almost twofold longer than in +/+ MSNs. NR1/NR2B antagonists were ineffective in reducing the slow NMDA-EPSCs at all ages. Input-output studies revealed differences in stimulation threshold sensitivity of MSNs based on stimulus location. High-threshold responders were preferentially identified with stimulation from intracortical locations that produced considerably faster NMDA-EPSCs, whereas low-threshold responders were mainly elicited with stimulation more proximal to the striatum and exhibited slower NMDA-EPSCs. A low-affinity competitive antagonist of NMDA receptors failed to alter the decay of NMDA-EPSCs elicited from either location, suggesting that glutamate spillover is not responsible for the long-lasting NMDA-EPSCs. Our data are consistent with the expression of a unique NMDA receptor complex in MSNs with very slow deactivation kinetics.
Reversible Synaptic Depression in Developing Rat CA3–CA1 Synapses Explained by a Novel Cycle of AMPA Silencing-Unsilencing
Authors: Abrahamsson Therése , Gustafsson Bengt , Hanse Eric
Published: September 2007

In the developing hippocampus, experiments using whole cell recordings have shown that a small number of synaptic activations can convert many glutamate synapses to AMPA silent synapses. This depression of AMPA signaling is induced by low-frequency (0.05–0.2 Hz) activation, does not require N-methyl-d-aspartate or metabotropic glutamate receptor activation for its induction, and does not readily reverse after stimulus interruption. Here we show, using field recordings and perforated patch-clamp recordings of transmission in developing CA3–CA1 synapses, that this synaptic depression also can be observed under more noninvasive recording conditions. Moreover, under these conditions, the synaptic depression spontaneously recovers within 20 min by the absence of synaptic activation alone, with a time constant of ∼7 min as determined by field excitatory postsynaptic potential recordings. Thus as for the expression of long-term potentiation (LTP), recovery from this depression is susceptible to whole cell dialysis (“wash-out”). In contrast to LTP-induced unsilencing, the AMPA signaling after stimulus interruption was again labile, resumed stimulation resulted in renewed depression. The present study has thus identified a novel cycle for AMPA signaling in which the nascent glutamate synapse cycles between an AMPA silent state, induced by a small number of synaptic activations, and a labile AMPA signaling, induced by prolonged inactivity.
Different Learned Coordinate Frames for Planning Trajectories and Final Positions in Reaching
Authors: Ghez Claude , Scheidt Robert , Heijink Hank
Published: September 2007

We previously reported that the kinematics of reaching movements reflect the superimposition of two separate control mechanisms specifying the hand's spatial trajectory and its final equilibrium position. We now asked whether the brain maintains separate representations of the spatial goals for planning hand trajectory and final position. One group of subjects learned a 30° visuomotor rotation about the hand's starting point while performing a movement reversal task (“slicing”) in which they reversed direction at one target and terminated movement at another. This task required accuracy in acquiring a target mid-movement. A second group adapted while moving to—and stabilizing at—a single target (“reaching”). This task required accuracy in specifying an intended final position. We examined how learning in the two tasks generalized both to movements made from untrained initial positions and to movements directed toward untrained targets. Shifting initial hand position had differential effects on the location of reversals and final positions: Trajectory directions remained unchanged and reversal locations were displaced in slicing whereas final positions of both reaches and slices were relatively unchanged. Generalization across directions in slicing was consistent with a hand-centered representation of desired reversal point as demonstrated previously for this task whereas the distributions of final positions were consistent with an eye-centered representation as found previously in studies of pointing in three-dimensional space. Our findings indicate that the intended trajectory and final position are represented in different coordinate frames, reconciling previous conflicting claims of hand-centered (vectorial) and eye-centered representations in reach planning.
Candidate genes controlling pulmonary function in mice: transcript profiling and predicted protein structure
Authors: Ganguly Koustav , Stoeger Tobias , Wesselkamper Scott C. , Reinhard Claudia , Sartor Maureen A. , Medvedovic Mario , Tomlinson Craig R. , Bolle Ines , Mason John M. , Leikauf George D. , Schulz Holger
Published: September 2007

Impaired development and reduced lung capacity are risk factors of asthma and chronic obstructive pulmonary disease. Previously, our genomewide linkage analysis of C3H/HeJ (C3H) and JF1/Msf (JF1) mouse strains identified quantitative trait loci (QTLs) associated with the complex traits of dead space volume (Vd), total lung capacity (TLC), lung compliance (Cl), and diffusing capacity for CO (DCO). We assessed positional candidate genes by comparing C3H with JF1 lung transcript levels by microarray and by comparing C3H, BALB/cByJ, C57BL/6J, A/J, PWD/PhJ, and JF1 strains, using exon sequencing to predict protein structure. Microarray identified >900 transcripts differing in C3H and JF1 lungs related to lung development, function, and remodeling. Of these, three genes localized to QTLs associated with differences in lung function. C3H and JF1 strains differed in transcript and protein levels of superoxide dismutase 3, extracellular [SOD3; mouse chromosome (mCh) 5: Vd] and transcript of trefoil factor 2 (TFF2; mCh 17: TLC and DCO), and ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2; mCh 15: TLC and Cl). Nucleotide sequencing of Sod3, Tff2, and previously identified Relaxin 1 ( Rln1; mCh 19: Cl) uncovered polymorphisms that could lead to nonsynonymous amino acid changes and altered predicted protein structure. Gene-targeted Sod3−/−mice had increased conducting airway volume (Vd/TLC) compared with strain-matched control Sod3+/+mice, consistent with the QTL on mCh 5. Two novel genes ( Tff2 and Enpp2) have been identified and two suspected genes ( Sod3 and Rln1) have been supported as determinants of lung function in mice. Findings with gene-targeted mice suggest that SOD3 is a contributing factor defining the complex trait of conducting airway volume.
Treatment of Gastroesophageal Reflux Disease: Endoscopic Aspects
Authors: Špičák Julius
Published: September 2007

Gastroesophageal reflux disease (GERD) is a very common chronic disorder manifesting itself as heartburn, regurgitation, or dysphagia, possibly leading to esophagitis, Barrett’s esophagus and adenocarcinoma, and has a major impact on the patient’s quality of life. Both medical treatment and surgery are well-established methods with several limitations. Recently, three types of endoscopic methods in several modifications have been developed: (1) Radiofrequency therapy (Stretta procedure) is available both in Europe and USA and more than 5,000 patients have been treated to date. (2) Injection therapy requires the injection of bulking agents or implantation of bioprosthesis into the lower esophageal sphincter (LES) zone. Both Enteryx was withdrawn from the market in 2005, and Gatekeeper was suspended before FDA approval. (3) Suturing/plication therapy is based on the plication at the level of the LES, and most of all techniques resemble the principle of surgical treatment. Despite sophisticated technologies and promising short-term results, all these techniques are associated with inconsistencies, controversies, and relevant adverse affects. According to current practice, use of endoscopic methods is justifiable only as part of clinical trials. Many aspects, including commercial ones, will influence future developments in this area, which are difficult to predict.
How to Proceed in Helicobacter pylori-Positive Chronic Gastritis Refractory to First- and Second-Line Eradication Therapy
Authors: Vaira Dino , Ricci Chiara , Lanzini Alberto , Perna Federico , Romano Antonio , Corinaldesi Roberto
Published: September 2007

Helicobacter pylori is a widespread disease causing most of the peptic ulcer diseases and low-grade mucosa-associated lymphoreticular tissue (MALT) lymphoma. Moreover, H. pylori is a proven environmental risk factor for gastric carcinoma and it has been recognized as a type 1 carcinogen factor. A combination of drugs has been proposed, using a proton pump inhibitor (PPI), amoxicillin, clarithromycin, metronidazole and tetracycline to treat the infection. Since 1996, according to the European guidelines, the first-line approach using PPI, amoxicillin and clarithromycin or metronidazole has been suggested. Seven days of quadruple therapy with PPI (or ranitidine), tetracycline, bismuth salts and metronidazole has been reserved as second-line treatment. To improve the eradication rate of the triple therapy, a different combination of the available antibiotics has been proposed, consisting of a 10-day sequential regimen. A second-line levofloxacin-amoxicillin-based triple therapy given for 10 days has been proposed, obtaining a high eradication rate, suggesting this regimen to be a suitable retreatment option in eradication failure. A third-line treatment with rifabutin-based regimen has been proposed.
The Management of Complicated Celiac Disease
Authors: Al-toma A. , Verbeek W.H.M. , Mulder C.J.J.
Published: September 2007

Refractory celiac disease (RCD) is being defined as persisting or recurring villous atrophy with crypt hyperplasia and increased intraepithelial lymphocytes (IELs) in spite of a strict gluten-free diet (GFD) for >12 months or when severe persisting symptoms necessitate intervention independent of the duration of the GFD. RCD may not respond primarily or secondarily to GFD. All other causes of malabsorption must be excluded and additional features supporting the diagnosis of CD must be looked for, including the presence of antibodies in the untreated state and the presence of celiac-related HLA-DQ markers. In contrast to patients with a high percentage of aberrant T-cells, patients with RCD I seem to profit from an immunosuppressive treatment. RCD II is usually resistant to medical therapies. Response to corticosteroid treatment does not exclude underlying enteropathy-associated T-cell lymphoma. Cladribine seems to have a role, although it is less than optimal in the treatment of these patients. It may be considered, however, as the only treatment thus far studied that showed significant reduction of aberrant T cells, seems to be well tolerated, and may have beneficial long-term effects in a subgroup of patients showing significant reduction of the aberrant T-cell population. Autologous stem cell transplantation (ASCT) seems promising in those patients with persisting high percentages of aberrant T cells. The first group of patients treated with ASCT showed improvement in the small intestinal histology, together with an impressive clinical improvement. However, it remains to be proven if this therapy delays or prevents lymphoma development.
Chronic Hepatitis in West and East
Authors: Kupcinskas Limas
Published: September 2007

The main etiologies of chronic hepatitis (CH) worldwide are viral B and C infections. Progression of CH to end-stage liver disease has a significant impact on mortality and need for liver transplantation worldwide. This review will focus on differences in etiology, prevalence, clinical outcomes of CH and impact on public health issues between developed Western and developing Eastern countries. Despite achievements in treatment and prevention of viral hepatitis in Western countries, processes of globalization contribute to further spread of the infections. Further efforts towards the elimination of hepatic B virus transmission throughout implementation of vaccination programs and primary prevention of hepatitis C infection are still of high importance, especially in developing world.
Anticytomegaloviral Activity of Esterified Milk Proteins and L-Polylysines
Authors: Chobert Jean-Marc , Sitohy Mahmoud , Billaudel Sylviane , Dalgalarrondo Michèle , Haertlé Thomas
Published: September 2007

MRC-5 fibroblasts infected with human cytomegalovirus (HCMV) reference strain AD 169 were treated with different concentrations of methylated α-lactalbumin (Met-ALA) or methylated β-lactoglobulin (Met-BLG), as well as with their peptic hydrolysates, and with the highly basic polypeptides such as are L-polylysines (4–15 kDa). The antiviral activity was calculated by comparing the number of infected cells in the presence and absence of the tested substances. Both Met-ALA and Met-BLG, as well as their peptic hydrolysates, decreased the infectious activity of cytomegalovirus in fibroblast cells. As expected, L-polylysines showed the highest antiviral activity. However, the tested basic proteins and polypeptides despite their lower antiviral activities might be potentially quite useful in fight of arising drug resistance activities and the persistence capacities of this virus.
Evolution and Extinction of Afro-Arabian Primates Near the Eocene-Oligocene Boundary
Authors: Seiffert Erik R.
Published: September 2007

Revised age estimates for the primate-bearing localities of the Jebel Qatrani Formation (Fayum area, northern Egypt) have provided a new perspective on primate response to early Oligocene climate change in North Africa. Environmental changes associated with early Oligocene cooling might have driven the local extinction of at least 4 strepsirrhine primate clades (adapids, djebelemurines, plesiopithecids and galagids). Contrary to previous suggestions, oligopithecid (and possibly proteopithecid) anthropoids persisted beyond the Eocene-Oligocene boundary (EOB) in the Fayum area, and the former group evidently continued to diversify through the early Oligocene at lower latitudes. Propliopithecids and parapithecine parapithecids first appear in the Jebel Qatrani Formation millions of years after the EOB, so their derived dental and gnathic features can no longer be interpreted as sudden adaptive morphological responses to earliest Oligocene climatic events. Evidence for latitudinal contraction of Afro-Arabian primate distribution through the early Oligocene suggests that the profound late Oligocene restructuring of Afro-Arabian primate communities is most likely to have occurred in equatorial and low-latitude tropical Africa.
Primate Visual Signals in Noisy Environments
Authors: Kingdon Jonathan
Published: September 2007

Most animals and plants need to send signals and rely on some sort of response. For an active receptor of signals, virtually all the signal transmissions that litter the environment, bar those that are functional at any given moment, can be described as ‘noise’. I concentrate here on some primate examples where loud calls combine with ‘loud’ colouring and patterns, to suggest that increasing the intensity of signals can help overcome the problem of ‘noise’. I also present evidence that certain ecological conditions favour use of the visual channel. I use some examples, drawn from African guenons, to suggest that visual patterns broadcast on this channel have evolved and have, effectively, been elaborated to conform with certain optical principles. These optical properties minimize ambiguity and enhance species-specific (or at least population-specific) distinctiveness. The abilities of ancestral forest primates to discriminate between functional signals and visual ‘noise’ may have played an important part in providing the basis for our own hominin ancestors’ visual proficiencies.
Perinatal Brain Damage Causation
Authors: Dammann Olaf , Leviton Alan
Published: September 2007

The search for causes of perinatal brain damage needs a solid theoretical foundation. Current theory apparently does not offer a unanimously accepted view of what constitutes a cause, and how it can be identified. We discuss nine potential theoretical misconceptions: (1) too narrow a view of what is a cause (causal production vs. facilitation), (2) extrapolating from possibility to fact (potential vs. factual causation), (3) if X, then invariably Y (determinism vs. probabilism), (4) co-occurrence in individuals vs. association in populations, (5) one cause is all that is needed (single cause attribution vs. multicausal constellations), (6) drawing causal inferences from very small numbers of observations (the tendency to generalize), (7) unstated causal inferences, (8) ignoring heterogeneity, and (9) failing to consider alternative explanations for what is observed. We hope that our critical discussion will contribute to fruitful research and help reduce the burden of perinatal brain damage.
Delayed IGF-1 Administration Rescues Oligodendrocyte Progenitors from Glutamate-Induced Cell Death and Hypoxic-Ischemic Brain Damage
Authors: Wood Teresa L. , Loladze Vaho , Altieri Stefanie , Gangoli Nitish , Levison Steven W. , Brywe Katarina G. , Mallard Carina , Hagberg Henrik
Published: September 2007

We previously demonstrated that IGF-1 blocks glutamate-mediated death of late oligodendrocyte progenitors (OPs) by preventing Bax translocation, mitochondrial cytochrome c release and cleavage of caspases 9 and 3. Here, we demonstrate that IGF-1 prevents caspase 3 activation in late OPs when administered up to 16 h following exposure to glutamate. Moreover, late addition of IGF-1 to OPs previously exposed to toxic levels of glutamate promotes oligodendrocyte maturation as measured by myelin basic protein expression. We also demonstrate that intraventricularly administered IGF-1 retains OPs in the perinatal white matter after hypoxia-ischemia when given after insult. These results suggest that delayed administration of IGF-1 will rescue OPs in the immature white matter and promote myelination following hypoxia-ischemia.
Delayed Peripheral Administration of a GPE Analogue Induces Astrogliosis and Angiogenesis and Reduces Inflammation and Brain Injury following Hypoxia-Ischemia in the Neonatal Rat
Authors: Svedin Pernilla , Guan Jian , Mathai Sam , Zhang Rong , Wang Xiaoyang , Gustavsson Malin , Hagberg Henrik , Mallard Carina
Published: September 2007

Glycine 2-methyl proline glutamate (G-2mPE) is a proline-modified analogue to the naturally existing N-terminal tripeptide glycine-proline-glutamate that is a cleaved product from insulin-like growth factor-1. G-2mPE is designed to be more enzymatically resistant than glycine-proline-glutamate and to increase its bioavailability. The current study has investigated the protective effects of G-2mPE following hypoxic-ischemic brain injury in the neonatal brain. On postnatal day 7, Wistar rats were exposed to hypoxia-ischemia (HI). HI was induced by unilateral ligation of the left carotid artery followed by hypoxia (7.7% O2, 36°C) for 60 min. The drug treatment started 2 h after the insult, and the pups were given either 1.2 mg/kg (bolus), 1.2 mg/ml once a day for 7 days, or vehicle. The degree of brain damage was determined histochemically by thionin/acid fuchsin staining. G-2mPE’s anti-inflammatory properties were investigated by IL-1β, IL-6, and IL-18 ELISA, and effects on apoptosis by caspase 3 activity. Vascularization was determined immunohistochemically by the total length of isolectin-positive blood vessels. Effect on astrocytosis was also determined in the hippocampus. Animals treated with multiple doses of G-2mPE demonstrated reduced overall brain injury 7 days after HI, particularly in the hippocampus and thalamus compared to vehicle-treated rats. The expression of IL-6 was decreased in G-2mPE-treated animals compared to vehicle-treated pups, and both the capillary length and astrogliosis were increased in the drug-treated animals. There was no effect on caspase 3 activity. This study indicates that peripheral administration of G-2mPE, starting 2 h after a hypoxic-ischemic insult, reduces the degree of brain injury in the immature rat brain. The normalization of IL-6 levels and the promotion of both neovascularization and reactive astrocytosis may be potential mechanisms that underlie its protective effects.
Rising Prostate-Specific Antigen after Primary Treatment of Prostate Cancer: Sequential Hormone Manipulation
Authors: Schmid Hans-Peter , Keuler Franz U. , Altwein Jens E.
Published: September 2007

Objective: To evaluate systematically the current endocrine treatment options for patients with biochemical recurrence after radical prostatectomy or radiation therapy for localized prostate cancer. Methods: Literature search of PubMed documented publications and abstracts from international meetings. Key items included timing and type of salvage hormone therapy, length of its application and handling of side effects. Results: The majority of patients with isolated prostate-specific antigen (PSA) relapse are not candidates for salvage treatment with curative intent. The PSA threshold that triggers initiation of hormonal therapy is debatable and should be based also on pretreatment risk assessment. Intermittent androgen suppression is an emerging concept to circumvent the unresolved controversy of early versus deferred endocrine therapy. Since the tumor load at time of recurrence is low, peripheral androgen blockade with an antiandrogen and a 5α-reductase inhibitor is an acceptable first choice. In case of progression, addition of a LHRH analogue would be the next step. Antiandrogen withdrawal and second-line antiandrogens are clinically of limited value. Conclusions: Biochemical-only progression after definitive treatment in curative intent is different from objective or even symptomatic relapse and allows for sequential hormonal therapy with a variety of compounds.
Retroperitoneoscopic Nephrectomy for Autosomal Dominant Polycystic Kidney Disease: Initial Experience
Authors: Wyler Stephen F. , Bachmann Alexander , Ruszat Robin , Forster Thomas , Hudolin Tvrtko , Gasser Thomas C. , Sulser Tullio
Published: September 2007

Introduction: Nephrectomy for autosomal dominant polycystic kidney disease (ADPKD) has been reported to have significant morbidity and mortality. Because of the large kidney size, laparoscopic nephrectomy is technically demanding and there have been only few reports on this subject. We describe our retroperitoneoscopic technique and review the literature. Methods: Retroperitoneoscopic nephrectomy was performed in 2 patients. A four-port retroperitoneal access was used, after hilar control the kidney was freed and extracted. Results: The mean operative time was 155 min, the mean intraoperative blood loss was 125 ml. There were no intraoperative complications. A postoperative retroperitoneal hematoma in 1 of the patients was managed conservatively with transfusion. Conclusion: Retroperitoneoscopic nephrectomy for ADPKD is feasible. The main advantages of this technique compared to transperitoneal laparoscopy are the quick and easy access to the hilar vessels even in large polycystic kidneys and the strict extraperitoneal route.
Metastasectomy without Systemic Therapy in Metastatic Renal Cell Carcinoma: Comparison with Conservative Treatment
Authors: Kwak Cheol , Park Yong Hyun , Jeong Chang Wook , Lee Sang Eun , Ku Ja Hyeon
Published: September 2007

Aim: The objective of this study was to evaluate the efficacy of metastasectomy after nephrectomy in patients with metastatic renal cell carcinoma who had not received systemic therapy. Patients and Methods: A total of 62 patients were included in the study. The patients were categorized according to their surgical treatment: the metastasectomy group (n = 21) and the nonmetastasectomy group (n = 41). Results: In the metastasectomy group, the median overall survival was 36.5 (range 4.0–182.7) months, whereas the patients of the nonmetastasectomy group reached a median overall survival of 8.4 (range 0.9–63.7) months (p < 0.001). The 1-, 3-, and 5-year overall survival rates were calculated at 71.4 and 34.1%, 47.6 and 9.8%, and 9.8 and 2.4%, respectively (p < 0.001). When the patients were stratified according to their characteristics, the overall survival was lower in the nonmetastasectomy group than in the metastasectomy group in the younger patients (p = 0.002), in both male (p = 0.001) and female (p = 0.030) patients, in patients with a poor performance status (p = 0.027), in patients with a shorter time between diagnosis of the primary tumor and development of metastases (p < 0.001), and in patients with a solitary metastasis (p = 0.005). Multivariate analysis using the Cox proportional hazards model showed that only the metastasectomy status was an independent predictor of the overall survival (Hazard ratio 2.57, 95% confidence interval 1.21–5.44; p = 0.014). Conclusion: Our findings suggest that for the management of metastatic renal cell carcinoma, complete surgical resection of the metastatic lesions may prolong survival even in patients with some poor prognostic factors who cannot or are not willing to receive systemic therapy.
Elucidation of the Mechanism of Crystal-Cell Interaction Using Fibronectin-Overexpressing Madin-Darby Canine Kidney Cells
Authors: Tsujikawa Kozo , Tsujihata Masao , Tei Norihide , Yoshimura Kazuhiro , Nonomura Norio , Okuyama Akihiko
Published: September 2007

Introduction: Attachment of newly formed crystals to renal epithelial cells is considered to be a critical step in stone formation. Previously, we reported that exogenous fibronectin (FN; 220–240 kDa) had an inhibitory effect against renal tubular cell injury in Madin-Darby canine kidney (MDCK) cells. However, the exact mechanism of FN is not fully understood. To examine the role of FN in crystal-cell interaction, we generated stably transfected MDCK cells that overexpress FN. Materials and Methods: MDCK cells were transfected with rat FN cDNA. First, we assessed cell injury by addition of calcium oxalate monohydrate (COM) crystals. Next, we examined the effect of FN on the adhesion of COM crystals. Finally, we studied the association of COM crystals by scanning electron microscopy. Results: Cell injury was significantly reduced in the transfected cells relative to control MDCK cells. In the inhibitory assay, crystal adhesion decreased markedly as compared with control MDCK cells. Morphological study showed that few crystals were attached to the surface of the transfected cells. Conclusions: We elucidated the relationship between crystal-cell interaction and FN by using FN-overexpressing MDCK cells. We suppose that FN inhibits the adhesion of crystals to cells by coating the renal tubular epithelial cells.
Heterogeneous p27Kip1 Expression within Primary Renal Cell Cancers, Their Invasive Margins and Peritumoral Renal Parenchyma Correlation with Pathological and Prognostic Features
Authors: Merseburger A.S. , Serth J. , von der Heyde E. , Kobierski A. , Wegener U. , Mengel M. , Jonas U. , Kuczyk M.
Published: September 2007

Introduction: The expression of the negative cell cycle regulator p27Kip1 is frequently found to be deregulated in various human cancer types. Whether expression of p27Kip1 can be used as prognostically relevant biological variables for renal cell cancer patients still remains to be clarified. Therefore, in the present investigation the expression within different tissue areas obtained from renal cell carcinomas was determined. Patients and Methods: For analysis of p27Kip1 in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising of 1,260 tissue samples each obtained from the tumor itself, the invasive front as well as non-malignant surrounding parenchyma. A sufficient follow-up after surgical therapy was available in 251 cases. Results: In univariate survival analysis, decreased expression of p27Kip1 within tissue cores obtained from the invasion front was significantly correlated with the patients’ disease-specific long-term survival (p = 0.02, log-rank test). In contrast, expression of p27Kip1 protein within the primary tumors was not identified to reveal any prognostically important information. In Cox regression analysis, histological stage and grade (p < 0.01), the presence of regional lymph node (p < 0.01) or distant metastases at the time of surgery (p < 0.01) as well as decreased expression of p27Kip1 (p = 0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery. Conclusion: Our analysis demonstrated that p27Kip1 is heterogeneously expressed in renal cell carcinomas. Moreover, the result of the present study supports the prognostic value of p27Kip1 protein expression for patients diagnosed with renal cell carcinoma.
Altered Regulation of Renin-Angiotensin, Endothelin and Natriuretic Peptide Systems in Rat Kidney with Chronic Unilateral Ureteral Obstruction
Authors: Bae Eun Hui , Kim In Jin , Park Jeong Woo , Ma Seong Kwon , Choi Ki Chul , Lee Jong Un , Kim Soo Wan
Published: September 2007

Background: The present study was designed to investigate the role of the local renin-angiotensin-aldosterone system (RAAS), endothelin (ET) and the natriuretic peptide system (NPS) for the development of renal fibrosis and progressive renal disease in experimental unilateral ureteral obstructed (UUO) rats. Methods: Male Sprague-Dawley rats (180–200 g) were unilaterally obstructed by ligation of the proximal ureters for 14 days. Control rats were treated in the same way, except that no ligature was made. The mRNA expressions of local renin-angiotensin system, aldosterone synthase (CYP11B2), ET-1 and NPS was determined in the cortex by real-time polymerase chain reaction. Results: Following the unilateral ureteral obstruction, the mRNA expressions of angiotensin-converting enzyme 1, ET-1 and transforming growth factor-β1 (TGF-β1) were increased, while angiotensin-converting enzyme 2 was decreased in the obstructed kidney compared with the controls. Angiotensin II type 1 receptor was decreased and TGF-β1 was not changed in contralateral kidney compared with the controls. Atrial natriuretic peptide, brain natriuretic peptide, and C-type natri- uretic peptide expressions were increased in UUO kidneys compared with the controls, while natriuretic peptide receptor-A was decreased in UUO kidneys. Conclusion: The local RAAS and ET-1 was upregulated which may play a role in the progressive renal fibrosis in obstructed kidneys in rats with UUO. The enhanced activity of NPS in UUO kidney may play a role to compensate against progressive renal fibrosis in chronic obstructive uropathy.
Bladder Stone Formation after a Tension-Free Vaginal Tape Procedure: Report on Two Cases
Authors: Tzortzis Vassilios , Mitsogiannis Iraklis C. , Moutzouris George , Aravantinos Evangelos , Anagnostou Theodoros , Gravas Stavros , Melekos Michael D.
Published: September 2007

We present 2 cases of large bladder stones formed on a tension-free vaginal tape (TVT) which was inadvertently passed through the bladder during the continence procedure. The stones together with the intravesical portion of the slings were removed using a suprapubic approach. High clinical suspicion of bladder complications is necessary when evaluating patients with urinary symptoms after a TVT operation.
Squamous Cell Carcinoma of the Descending Colon: Report of a Case and Literature Review
Authors: Miyamoto Hidenori , Nishioka Masanori , Kurita Nobuhiro , Honda Junko , Yoshikawa Kouzou , Higashijima Jun , Miyatani Tomohiko , Bandou Yoshimi , Shimada Mitsuo
Published: September 2007

It is very rare that squamous cell carcinoma (SCC) arises from colorectal epithelium. An 89-year-old man was treated in 2001 with chief complaints of anorexia, abdominal pain, and low grade fever. The histological diagnosis as SCC was determined by biopsy during a colonoscopy. We diagnosed primary SCC of the colon because except in the colon no malignant lesions were found by systemic CT. Surgical complete resection was performed. However, he died three months after surgical resection because of hepatic metastasis and cachexia. The prognosis of this disease seems to be worse than that of adenocarcinoma.
The Roles of Intrarenal 20-Hydroxyeicosatetraenoic and Epoxyeicosatrienoic Acids in the Regulation of Renal Function in Hypertensive Ren-2 Transgenic Rats
Authors: Čertíková Chábová Věra , Kramer Herbert J. , Vaněčková Ivana , Thumová Monika , Škaroupková Petra , Tesař Vladimír , Falck John R. , Imig John D. , Červenka Luděk
Published: September 2007

Background: The present study was performed in hypertensive Ren-2 transgenic rats (TGR) and in normotensive Hannover Sprague-Dawley (HanSD) rats. First, the intrarenal protein expression of CYP4A, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of CYP2C23, the enzyme responsible for epoxyeicosatrienoic acid (EET) production, was evaluated. Second, the renal functional responses to inhibition of the intrarenal formation of 20-HETE and EETs were investigated. Methods: Renal hemodynamics and electrolyte excretion were evaluated in response to the administration of inhibitors of 20-HETE and EET formation into the renal artery. In renal cortical tissue, CYP4A and CYP2C23 protein expression was assessed by Western blot analysis. Urinary concentrations of 20-HETE and EETs were measured using a fluorescent HPLC assay. Results: TGR have higher kidney CYP4A protein expression and urinary 20-HETE excretion but significantly lower CYP2C23 protein expression and urinary EET excretion than HanSD. Intrarenal inhibition of 20-HETE and EET formation decreased sodium excretion in HanSD, whereas inhibition of 20-HETE increased urinary excretion of sodium in TGR without altering renal hemodynamics. Conclusions: Our data suggest that in TGR, deficient intrarenal synthesis of EETs combined with increased synthesis of 20-HETE with its stimulation of tubular sodium absorption may contribute to the development of hypertension in TGR.
Outcome after Emergency Surgery for Acute Perforated Diverticulitis in 200 Cases
Authors: Vermeulen Jefrey , Akkersdijk George P. , Gosselink Martijn P. , Hop Wim C.J. , Mannaerts Guido H. , van der Harst Erwin , Coene Peter-Paul L.O. , Weidema Wibo F. , Lange Johan F.
Published: September 2007

Background: Mortality and morbidity rates of acute perforated diverticulitis remain high. The ideal treatment is still controversial. The object of this study was to compare patients with perforated diverticulitis treated either by resection with primary anastomosis (PA) or Hartmann’s procedure (HP). Methods: A multicenter study was carried out on 200 consecutive patients with acute perforated diverticulitis who were presented in the surgical units of four affiliated teaching hospitals in Rotterdam, The Netherlands, between 1995 and 2005. Mortality and morbidity were compared in relation to type of surgery, ASA classification, age, gender, Mannheim Peritonitis Index (MPI), Hinchey score, surgeon’s experience, and the time of operation. Results: There was a tendency for more severely affected patients (Hinchey, MPI, ASA and age) to undergo HP. Multivariate logistic regression analysis showed no significant difference in mortality between HP and PA. After HP, more patients needed one or more reinterventions to treat postoperative complications compared to PA. Besides, HP resulted in a longer total hospital and intensive care unit stay. Specialist colorectal surgeons performed significantly more frequently a PA instead of a HP and had fewer postoperative complications than general surgeons. The time of operation did not influence the choice of surgical procedure. Conclusion: Selected patients with perforated diverticulitis can be managed well by PA, as it does not seem to be inferior to HP in terms of severe postoperative complications that need surgical or radiological reintervention and mortality. This decision should be made while taking into account the patient’s concomitant diseases, response on preoperative resuscitation and the availability of a surgeon experienced in colorectal surgery.
Chronic Liver Abnormalities in Sickle Cell Disease: A Clinicopathological Study in 70 Living Patients
Authors: Traina Fabiola , Jorge Stefano Gonçalves , Yamanaka Ademar , de Meirelles Luciana R. , Costa Fernando Ferreira , Saad Sara T.O.
Published: September 2007

Background and Aim: The present study aimed to evaluate the incidence and etiology of chronic liver abnormalities in 70 living patients with sickle cell disease from the Hematology and Hemotherapy Center of the State University of Campinas. Methods: Clinical and laboratory investigations, including liver function tests, serological tests for viral hepatitis and abdominal ultrasound, were performed in all patients. Additionally, liver biopsies were taken from 20 patients. Results: Sixty-seven (96%) patients had some liver abnormality; these included abnormal liver function tests, viral hepatitis, liver ultrasonographic changes or cholelithiasis. The sickling process was the only explanation for the abnormal liver function tests or liver ultrasonographic changes in 24% of these patients. One or more defined reasons, including viral hepatitis, cholelithiasis, clinical hemosiderosis, alcoholism or diabetes, justified the liver abnormalities in 76% of the patients. Nineteen of the 20 liver biopsies presented some degree of vascular lesion; other histological findings were associated with hemosiderosis, viral hepatitis or cholestasis. Conclusions: In patients with sickle cell disease, chronic liver abnormalities are frequent and seem to be a multifactorial phenomenon, depending on overlapping factors such as cholelithiasis, viral damage, iron overload and also the primary disease itself.
Impact of Upward Lymph Node Dissection on Survival Rates in Advanced Lower Rectal Carcinoma
Authors: Uehara Keisuke , Yamamoto Seiichiro , Fujita Shin , Akasu Takayuki , Moriya Yoshihiro
Published: September 2007

Background/Aims: This study investigated appropriate level of upward lymph node (LN) dissection in advanced lower rectal carcinoma. Methods: A total of 285 consecutive patients with stage II/III lower rectal carcinoma were analyzed. LN dissection was classified as follows: division of the root of the superior rectal artery (UD2), division of the root of the inferior mesenteric artery (UD3) and UD3 with para-aortic LN dissection (UD4). Results: LN metastases at the root of the inferior mesenteric artery were found in 4 patients. Their prognoses were worse than those of the other stage III patients (p = 0.011). On the other hand, LN metastases along the superior rectal artery were discovered in 14 patients, whose 5-year overall survival rate was 61.2%. By removing the LNs either UD2 or UD3/4, a similar survival rate was achieved in stage III patients with LN metastases along the superior rectal artery. Conclusion: Survival of a minority with metastatic LNs at the root of the inferior mesenteric artery was poor. Additionally, survival is no worse in patients with positive LN along the superior rectal artery as long as these positive nodes are resected by either UD2 or UD3/4. Low ligation is adequate for advanced lower rectal carcinoma.
Prospective, Randomized Trial Comparing a 3- versus 6-Stitch Purse-String Suture in Stapled Hemorrhoidopexy
Authors: Inoue Yasuhiro , Kobayashi Minako , Yoshiyama Shigeyuki , Hiro Junichiro , Ohi Masaki , Miki Chikao , Kusunoki Masato
Published: September 2007

Aim: The purse-string suture is the most important part of the procedure in stapled hemorrhoidopexy affecting resection of an ideal mucosal rectal ring. We designed a prospective, randomized study to evaluate the safety and clinical outcome of a 6-stitch purse-string suture compared with a more simple 3-stitch purse-string suture intended to achieve certain interruption of the hemorrhoidal artery. Methods: Ninety patients were randomly assigned to undergo stapled hemorrhoidopexy with either a 6-stitch (n = 45) or a 3-stitch (n = 45) purse-string suture. Operative data and postoperative complications were compared between the 2 groups. The ring of excised rectal mucosa was examined histologically. Anal physiology was also assessed. Results: Although there were no statistically significant differences in postoperative complication rates, histological analysis of the excised mucosa, or anorectal function between the 2 groups, the 3-stitch procedure was significantly superior to the 6-stitch procedure in terms of intraoperative hemostasis and operative time, especially in advanced surgery. Conclusion: Once the learning curve has been completed, a 3-stitch purse-string suture in stapled hemorrhoidopexy could be an alternative to the 6-stitch suture, with effective hemostasis and a shorter operative time.
Impact of Valvular Thickness on Stroke Recurrence in Medically Treated Patients with Stroke
Authors: Okajima K. , Abe Y. , Suzuki K. , Salameh M.J. , Di Tullio M.R. , Jin Z. , Sacco R.L. , Mohr J.P. , Homma S.
Published: September 2007

Background: It remains controversial whether left-sided valvular thickening (VaT) is a risk factor for ischemic stroke. Little is known about the relationship between VaT and the recurrent adverse event rate in medically treated patients with stroke. Methods: We examined the outcomes of 627 noncardioembolic stroke patients who were double-blindly assigned to either warfarin or aspirin therapy and assessed VaT using transesophageal echocardiography. Endpoints were recurrent ischemic stroke or death from any cause. The Cox proportional hazards model was used to adjust for covariates. Results: VaT was present in 57.3% of the patients (359/627), 34.6% (271/627) involving the aortic valve and 46.4% (291/627) involving the mitral valve. There was no difference in the time to primary endpoints between those with and without VaT of the aortic valve (p = 0.49; hazard ratio, HR: 1.17; 95% CI: 0.74–1.85; 2-year event rates: 18.9 vs. 13.2%) or mitral valve (p = 0.66; HR: 0.91; 95% CI: 0.60–1.38; 2-year event rates: 16.9 vs. 14.7%). Among the patients with VaT, there was no significant difference in the time to primary endpoints between those treated with warfarin and those with aspirin (p = 0.13, HR: 0.65, 95% CI: 0.37–1.14, 2-year event rates: 15.2 vs. 22.7% for the aortic valve; p = 0.22, HR: 0.70, 95% CI: 0.40–1.23, 2-year event rates: 14.2 vs. 19.6% for the mitral valve). Conclusions: VaT does not appear to increase recurrent adverse event rates in medically treated patients with ischemic stroke, regardless of warfarin or aspirin therapy.
Chances and Battles in Stroke Research
Authors: Warlow Charles P.
Published: September 2007

Here I have reviewed how good luck, bad luck and barriers determined my research directions in stroke over the last 30 or so years. Good luck should be exploited, and very often barriers can be not just overcome but put to good use as well. It is crucial for the young researcher to find mentors as good as I have had, and to move around to gain a broad experience, and for the experienced researchers to bring on the younger generation as I have tried to do.
Fluoride Intake by Children at Risk for the Development of Dental Fluorosis: Comparison of Regular Dentifrices and Flavoured Dentifrices for Children
Authors: Oliveira M.J.L. , Paiva S.M. , Martins L.H.P.M. , Ramos-Jorge M.L. , Lima Y.B.O. , Cury J.A.
Published: September 2007

The aim of the present study was to determine fluoride intake by children at risk of dental fluorosis according to the type of dentifrice used. Forty-two volunteers aged between 20 and 30 months, from 2 kindergartens, were supervised while brushing their teeth with regular dentifrices (nominally 1,500 ppm F) and dentifrices flavoured for children (nominally 1,100 ppm F), brushing 3 times with each type in random order to minimize bias. The amount of fluoride ingested was determined by subtracting the weight of dentifrice recovered from the weight used and calculating the mean of the 3 brushings. Fluoride was analyzed with specific electrodes. Parents were asked how often the children brushed their teeth and the daily tooth brushing frequency was used to calculate the daily fluoride intake. The average fluoride intake using regular dentifrices and those flavoured for children was 0.567 ± 0.300 and 0.630 ± 0.320 mg F/day, respectively, corresponding to doses of 0.046 ± 0.023 and 0.051 ± 0.026 mg F/kg/day (p > 0.05). Fluoride intake was slightly higher with the use of dentifrices flavoured for children. Moreover, the dose to which children were exposed with either type of dentifrice was very close to that which is considered the limit (0.05–0.07 mg F/kg/day).
Growth Hormone Therapy for Short Children Born Small for Gestational Age
Authors: Chatelain P. , Carrascosa A. , Bona G. , Ferrandez-Longas A. , Sippell W.
Published: September 2007

Children born small for gestational age may demonstrate continued growth retardation, resulting in persistent short stature. In the majority of the cases, this is linked with abnormal growth hormone secretion and also abnormal insulin-like growth factor levels. This review discusses the treatment of such children with recombinant human growth hormone. It illustrates the importance of starting therapy early, the dose-dependent response, and the advantages of continuous therapy and describes safety considerations.