bluuebunny/crossref_metadata_2025 huggingface dataset:
Avascular Necrosis of the Femoral Head in Adult Kuwaiti Sickle Cell Disease Patients
Authors: Marouf R. , Gupta R. , Haider M.Z. , Al-Wazzan H. , Adekile A.D.
Published: September 2003

While sickle cell disease (SCD) is generally mild in most Kuwaitis, because of their elevated fetal Hb levels, avascular necrosis of the femoral head (AVNFH) appears to be a common complication. It was recently documented in 26.7% of Kuwaiti children with SCD. There have, however, been no previous studies of adult patients. This is a 1-year study of consecutive, steady-state SCD patients seen in the hematology clinic of Mubarak Al-Kabeer Hospital. The patients’ charts were reviewed for frequency of hospitalizations, any documented complications and steady-state complete blood count (CBC). MRI was performed using T1- and T2-weighted FATSAT sequences in coronal and axial planes with 4-mm-thick slices on a 1.5-tesla GE super-conducting magnet. Thirty-five patients were studied, consisting of 25 SS and 10 Sβ⁰Thal patients aged between 17 and 44, with a mean age of 26.7 ± 9.3 years. Seventeen (48.6%) had varying degrees of AVNFH; among the 70 hips examined, 29 (41.1%) were affected. Of the 17 patients affected, 11 (64.7%) were SS, while 6 (35.3%) were Sβ⁰Thal. There were 14 (82.4%) males and 3 (17.6%) females (χ2 = 8.6, p < 0.01). The mean age of those affected, 27.5 ± 10.7 years, was not significantly higher than that of the unaffected (26.3 ± 8.0 years). Eleven (64.7%) of those affected had a history of frequent vaso-occlusive crisis. No significant differences could be demonstrated in the mean CBC and Hb F values of the two groups; coexistent α-thal trait was not a factor in the SS group. Male gender was the only significant predisposing factor identified. While more patients with frequent vaso-occlusive crises were affected, the difference was not significant. AVNFH is, indeed, quite common among Kuwaiti SCD patients and there is a need for early institution of preventive and therapeutic protocols.
The Molecular Mechanism of Arsenic Trioxide-Induced Apoptosis and Oncosis in Leukemia/Lymphoma Cell Lines
Authors: Zhu Jiebin , Okumura Hirokazu , Ohtake Shigeki , Nakamura Shinobu , Nakao Shinji
Published: September 2003

The mechanisms of As2O3-induced apoptosis are very complex. In the present study, we investigated the molecular mechanism of As2O3 in vitro at low concentration (0.25–2.0 µM) on three human leukemia/lymphoma cell lines: HL-60, RL and K562. As2O3 inhibited the growth of these cell lines significantly. During As2O3 treatment, two forms of cell death, apoptosis in HL-60 and RL and oncosis in K562, were found by morphological study. In HL-60 and RL, cell cycle analysis showed, at a distinct SubG1 region, that CD95 and CD95 ligand (CD95L) expression was upregulated, caspase 8 and caspase 3 were activated, and Bcl-2 protein expression was downregulated. On the other hand, in K562, the cell cycle was arrested at the G2+M phase, CD95/CD95L expression was upregulated, caspase 8 and caspase 3 were activated, but Bcl-2 expression was not changed as compared with untreated cells. These findings suggest that the CD95/CD95L pathway is involved in cell killing by As2O3. Using anti-CD95 IgG monoclonal antibody (anti-CD95 MoAb) or specific caspase inhibitor ZVAD-fmk to block the CD95 pathway, the cell death induced by As2O3 was partially blocked in each cell line. These results suggest that As2O3 inhibits the growth of these leukemia/lymphoma cell lines by inducing apoptosis or oncosis that is partially mediated by the CD95/CD95L pathway.
Elevated Levels of Serum Vascular Endothelial Growth Factor in Patients with Polycythaemia vera
Authors: Theodoridou Stamatia , Vyzantiadis Timoleon , Vakalopoulou Sofia , Perifanis Vassilios , Tziomalos Konstantinos , Vyzantiadis Athanassios , Garipidou Vassilia
Published: September 2003

Angiogenesis seems to be a prominent event of myeloproliferative diseases. There are few reported data on angiogenesis and the significance of its stimulator, the vascular endothelial growth factor (VEGF), in polycythaemia vera (PV). We report our observation of elevated serum VEGF levels in patients suffering from PV. Twenty patients with PV and 20 age-matched healthy subjects were enrolled. VEGF levels were measured by a quantitative sandwich enzyme immunoassay. Serum VEGF levels in PV were found to be very significantly higher than in healthy individuals (569.7 ± 101.2 vs. 164.7 ± 32.8 pg/ml, p = 0.001). We found no correlation between VEGF and haemoglobin, platelet or leucocyte counts in the patient group. Different therapeutic regimens had no influence on VEGF levels. However, in the control group, we observed a positive correlation between VEGF levels and platelet counts (r = 0.52, p = 0.02). Platelet counts did not differ between patients and healthy subjects. We also evaluated platelet-poor plasma VEGF levels in 10 patients and in all healthy individuals. We found very low levels of VEGF, approximately zero in most cases, in both groups and there was obviously no difference between the two groups. Our results indicate that VEGF is overproduced in PV. However, follow-up studies are needed to verify the role of this factor.
5- to 16-Year Follow-Up following Splenectomy in Chronic Immune Thrombocytopenic Purpura in Children
Authors: El-Alfy Mohsen S. , El-Tawil Mohamed M. , Shahein Naglaa
Published: September 2003

The long-term outcome after splenectomy in children with chronic immune thrombocytopenic purpura (ITP) has not been widely analyzed. We reviewed the medical records of 288 children and adolescents with chronic ITP between 1980 and 1996: 112 were splenectomized; 59 were steroid resistant and 42 were steroid dependent, and 11 were managed with repeated courses of intravenous immunoglobulin (IVIG). All had platelet counts (PCs) <30 × 109/l with frequent bleeding episodes or persistent thrombocytopenia <10 × 109/l. Ninety-eight patients (88%) were evaluated; 58 (60%) patients had never received immunotherapy for ITP following splenectomy. At 5 years, 44 (45%) remained in complete response (CR) and 34 (35%) in partial response (PR). In multivariate analysis, steroid-resistant patients were more likely to relapse after an initial CR (RR 5.2). Conclusion: The long-term CR was 45%; 60% had stable PCs >30 × 109/l not requiring therapy. Most postsplenectomy relapses occurred during the 1st year. Initial response to steroids and IVIG prior to splenectomy was a predictor of long-term response to splenectomy.
Vascular Endothelial Growth Factor Serum Levels Are Elevated in Patients with Hereditary Hemorrhagic Telangiectasia
Authors: Cirulli Anna , Liso Arcangelo , D’Ovidio Francesco , Mestice Anna , Pasculli Giovanna , Gallitelli Mauro , Rizzi Rita , Specchia Giorgina , Sabbà Carlo
Published: September 2003

Background: Hereditary hemorrhagic telangiectasia (HHT) is a genetic angiodysplasia affecting multiple organs. Two genes involved in the transduction of TGF-β signalling are responsible for HHT. An additional role for vascular endothelial growth factor (VEGF) has been proposed. Serum VEGF, which has been evaluated in several diseases characterized by aberrant angiogenesis, has never been measured in patients with HHT. Aims: To evaluate VEGF serum levels in HHT patients as compared to normal subjects. Materials and Methods: 32 HHT patients (age 47.7 ± 16.7 years) and a control group of 37 healthy subjects (age 48.2 ± 15.5 years) were entered in the study. Each patient underwent serum VEGF dosage using a commercial ELISA specific for the human molecule. Results: The serum level of VEGF in HHT patients was 196.3 ± 103.2 pg/ml, while it was 152.0 ± 84.1 pg/ml in the control group. Statistical analysis showed that serum VEGF was significantly higher in HHT patients than in the controls (p < 0.031). Conclusions: According to a study performed in a murine model, persistence of the activation phase of angiogenesis might be responsible for an increased production of several angiogenic factors, in particular VEGF, in HHT. Our work is the first to suggest an increased expression of VEGF in the serum of subjects with HHT in agreement with the stimulation of VEGF synthesis proposed in the murine model.
Synthesis, Structural Analysis and Antibacterial Activity of a Butyl Ester Derivative of Ampicillin
Authors: Bartzatt Ronald , Malesa Cynthia
Published: September 2003

Background: Ester groups placed on medicinal agents have been found to increase lipophilicity (more positive log p value). Alterations in a partition coefficient may affect medicinal activity. Formation of an ester group such as -C(O)OCH2CH2CH2CH3 from a carboxyl group [-C(O)OH] can be efficiently accomplished utilizing diazoalkanes and produces a prodrug-like structure of ampicillin (a bipartate drug carrier). Formation of an ester group may produce beneficial changes in medicinal parameters such as log P, log BB, and molecular polar surface area (TPSA). Methods: An ester of ampicillin was synthesized by replacing the carboxyl group with a butyl ester group. The ester formed was synthesized utilizing diazobutane, which is a gas at room temperature and reacts with the acidic hydrogen of the carboxylic acid. The ampicillin ester was dissolved into LB agarose media at levels of 0.228 and 0.180 mg/ml, and its antibacterial activity was compared to that of normal ampicillin. Medicinal parameters such as log P, solubility, polar surface area, log BB, molecular dipole, Clog P, intestinal absorption and the ‘Rule of 5’ were determined. Results: The ampicillin ester consisted of yellow crystals that were stable for >12 weeks at 0°C. The ester has reduced hydrogen bonding capacity and increased lipophilic character (by log P) compared to the parent structure. Each concentration of the ester tested induced 100% growth inhibition of ampicillin-susceptible but streptomycin-resistant Escherichia coli bacteria, and >30% growth inhibition of an ampicillin-resistant E. coli. This ester compound of ampicillin showed zero violations of the ‘Rule of 5’, which indicates good bioavailability and good bioactivity. Intestinal absorption indicated by TPSA value showed moderate absorption activity for both parent and ester compounds. The lipophilic substituent constant for the butyl ester is +0.941, which indicates increased lipophilicity. The ester group improves log BB and dermal permeability of ampicillin. Conclusion: The butyl ester of ampicillin inhibited the growth of susceptible and resistant E. coli. Favorable values for parameters such as TPSA, log P, log BB, and zero violations of the ‘Rule of 5’ suggest good bioavailability and good bioactivity.
Beta-Lactamase Stability of Faropenem
Authors: Dalhoff A. , Nasu T. , Okamoto K.
Published: September 2003

Faropenem (FAR) is an orally available member of the penem class unique among carbapenems and other available β-lactams. This study compared FAR to cephalosporins and imipenem with respect to β-Iactamase (BLA) stability and emergence of resistance to Staphylococcus aureus and Escherichia coli. BLA stability was studied using enzyme preparations from sonicated/centrifuged 24-hour cultures of E. coli, Enterobacter cloacae, Proteus vulgaris, Providencia rettgeri, Klebsiella pneumoniae, S. aureus, and Bacteroides fragilis grown in the presence of 20 mg/l ampicillin or cephaloridine to induce penicillinase or cephalosporinase, respectively. Substrate hydrolysis was quantitated spectrophotometrically. Multistep acquisition of resistance was promoted by growing bacteria in broth containing 2-fold dilutions of antibiotic over 10 cycles. Aliquots from test tubes with visible growth provided the inoculum for the next series of dilutions. FAR as well as other cephalosporins tested were highly stable to penicillinase derived from S. aureus and E. coli. However, E. coli- and P. vulgaris-derived cephalosporinase hydrolyzed cephaloridine, cefaclor and cefotiam considerably, whereas FAR was highly stable. FAR was highly stable against hydrolysis by various BLAs prepared from four B. fragilis strains and the rate of FAR hydrolysis by metallo-BLA was 5 times lower than that for imipenem. Additionally, the acquisition of resistant S. aureus strains was less pronounced for FAR compared to other agents tested. MICs rose 8-fold after the 10th sub-MIC exposure, while MICs rose 16-, 31- and 512-fold for cefixime, cefazolin and cefaclor, respectively. E. coli shifts in MICs were moderate for all the agents tested. In conclusion, FAR is characterized by pronounced BLA stability compared to other cephalosporins and imipenem. Furthermore, a lower propensity for resistance development with FAR as compared to cephalosporins was observed.
Brief Exposure to Antimycotics Reduces the Extracellular Phospholipase Activity of Candida albicans and Candida tropicalis
Authors: Anil S. , Samaranayake L.P.
Published: September 2003

Background: Although the phospholipase activity is considered a potential virulence determinant of the pathogenic Candida species, the effect of antimycotics on this attribute is not known. Hence we evaluated the phospholipase activity in 10 isolates each of Candida albicans and Candida tropicalis, after their exposure to antifungals. Methods: The impact of antimycotics on phospholipase activity was also assessed after exposure of the isolates to sub-minimum inhibitory concentrations of nystatin, amphotericin B and fluconazole. Results: All Candida isolates investigated exhibited phospholipase activity (Pz). In general C. albicans showed relatively higher Pz activity than C. tropicalis, and exposure of the isolates to antimycotics led to a significant (p < 0.05) reduction in the phospholipase activity. Nystatin and amphotericin B, but not fluconazole, significantly reduced the phospholipase activity of both Candida species. Conclusion: These observations, while confirming the higher virulence of C. albicans relative to C. tropicalis, demonstrate for the first time the effect of antifungal agents on extracellular phospholipases of these common opportunistic pathogens.
Histone H1 Modulates Immune Status in Experimental Breast Cancer
Authors: Vani G. , Devipriya S. , Shyamaladevi C.S.
Published: September 2003

Background: Breast cancer chemotherapy aims at employing cytotoxic agents that swing the balance between tumor cell invasion and host immune cells in favor of the latter. This study aimed at assessing the effect of exogenous histone H1 in maintaining the immune status of animals in experimental breast cancer taking advantage of its tumor-suppressive activity. Methods: Histone H1 was injected intratumorally as a single injection in tumor-bearing animals. Tumor response was assessed from changes in tumor volume, survival time and the immune status of animals from total and differential blood cell counts, levels of circulating immune complexes, thromboxane B2 and IgA in serum. Immune response was assessed from the macrophage count in the tumor and peritoneal exudates after activation. Results: Histone H1 treatment significantly inhibited tumor growth, enhanced mean survival time and significantly improved the immune response and status. Conclusion: These results indicate that histone H1 plays a vital role in maintaining the immune status.
Concomitant Mycobacterium tuberculosisand Aspergillus niger Infection in a Patient with Acute Myeloid Leukemia
Authors: Aksoy Duygu Yazgan , Turker Alev , Altundag M. Kadri , Abali Huseyin , Durusu Mine , Erman Mustafa , Uner Aysegul , Sungur Ayse Arzu , Unal Serhat , Uzun Omrum
Published: September 2003

Primary cutaneous infection by Aspergillus spp. is an uncommon form of aspergillosis in patients with severe immunosuppression, e.g. patients with HIV infection or hematological malignancies. Disruption of the dermal integrity by trauma or maceration, followed by colonization of the wound by Aspergillus spp. creates a suitable environment for cutaneous infection. Despite aggressive therapy with amphotericin, primary cutaneous aspergillosis can lead to disseminated disease with fatal consequences. Tuberculosis is another rare infection in patients with hematological malignancies, but when present it is usually disseminated. We present a 46-year-old woman with acute myeloid leukemia who developed concomitantly Mycobacterium tuberculosis and Aspergillus niger infection. Cutaneous aspergillosis was diagnosed during neutropenia after induction therapy, which later became disseminated disease during antifungal therapy. Tuberculosis infection was diagnosed in a scalene lymph node biopsy specimen. The patient achieved remission of her underlying disease and responded very well to antituberculous and antifungal therapy.
Regulation of Endothelin-Converting Enzyme 1 in Nephrotic Syndrome in Rats
Authors: Ikebe Mika , Nonoguchi Hiroshi , Nakayama Yushi , Tashima Yuka , Shimada Kohei , Tanzawa Kazuhiko , Tomita Kimio
Published: September 2003

Background: Nephrotic syndrome is characterized by severe proteinuria and sodium and water retention. Although endothelin (ET) 1 can cause natriuresis or antinatriuresis, the role played by ET-1 in proteinuria and in sodium retention due to nephrotic syndrome remains unclear. Methods: We investigated the role played by the ET-1 system in sodium and water retention and in proteinuria in puromycin aminonucleoside induced nephrotic syndrome in rats using microdissected nephron segments, competitive polymerase chain reaction, and Western blot. Results: The expression of prepro ET-1, ET-converting enzyme 1 (ECE-1), and ET A receptor mRNAs, but not ET B receptor mRNA, in the glomeruli was increased in rats with nephrotic syndrome. The cGMP generation in the glomeruli induced by atrial natriuretic peptide and ET-1 was decreased, whereas the ET-3-induced cGMP generation was increased in rats with nephrotic syndrome. ECE-1 mRNA expression was increased not only in the glomeruli, but also in the thick ascending limbs and collecting ducts. The protein expression of ECE-1 was increased in the membrane fraction of the cortex and in the outer and the inner medulla of nephrotic rats. Blockade of ET A and B receptors by bosentan did not inhibit the occurrence of nephrotic syndrome. However, the administration of bosentan increased the urinary sodium excretion. Conclusion: These data suggest that an activated ET-1-ET A receptor pathway in glomeruli and/or an increased ECE-1 mRNA expression in distal segments may participate in sodium and water retention, but not in the occurrence of nephrotic syndrome.
Expression of Hepatocyte Growth Factor Is Induced by the Interaction between Human Mesangial Cells and Monocytes
Authors: Koyama Takayuki , Hora Kazuhiko , Ako Shinji , Kamijo Yuji , Higuchi Makoto
Published: September 2003

Background: In pathological states various cytokines are produced by mesangial cells (MC) and contribute to disease progression. It is likely that interactions between monocytes and MC partially regulate these cytokines, including hepatocyte growth factor (HGF). Because HGF might have a potent therapeutic effect on the kidney, it is believed to play a critical role in the pathogenesis and development of glomerulonephritis. However, there is little knowledge about HGF production by MC or infiltrated monocytes in glomerulonephritis. Methods: To investigate HGF expression in pathological states, we cultured human MC (hMC) with a human monocytoid cell line and assessed HGF mRNA expression and protein production. Next, we performed immunohistochemical staining to explore which types of cell in the co-culture system expressed HGF. Because several humoral factors that can induce HGF production have been reported, we also performed noncontact co-culture to explore the contribution of humoral factors. Results: The HGF concentration of the co-culture system showed a time-dependent increase, and was fourfold greater than that of hMC alone. Expression of HGF mRNA was also increased. Both THP-1 cells and hMC in the co-culture demonstrated staining of HGF. The HGF concentration in the noncontact co-cultures was smaller than in the ordinary ones, but was greater than hMC alone. Conclusion: Direct cell-to-cell interaction between hMC and monocytes induced HGF production of both types of cells, indicating that local HGF production induced by cell-to-cell interaction plays an important role in the pathogenesis of glomerulonephritis. While direct cell-to-cell contact was important for HGF production, it is considered that some humoral factors might contribute.
Urinary Nephrocalcin Excretion in Children with Urolithiasis
Authors: Noyan A. , Yaşar H. , Bayazit A.K. , Anarat R. , Bayazit Y. , Anarat A.
Published: September 2003

The aim of this study was to investigate the role of nephrocalcin in childhood urolithiasis. Forty-one patients with urinary stones and 25 age- and sex-matched healthy controls were admitted to the study. Blood and timed urine samples were taken from both patient and control groups for biochemical analysis. Serum and urine creatinine (Cr) and urinary nephrocalcin (NC) were measured. NC excretion was expressed as a NC/Cr (mg/g) ratio. NC-PreA/Cr and NC-D/Cr ratios were found to be significantly higher in patients than in the control group. No statistically significant differences were found in NC-A/Cr, NC-B/Cr, NC-C/Cr ratios between the patient and control groups. The high NC-PreA/Cr ratio (p = 0.012) observed in stone-forming patients indicates that this ratio may also be an important stimulatory factor for urinary stone disease.
Intensive Early Physiotherapy Combined with Dexamphetamine Treatment in Severe Stroke: A Randomized, Controlled Pilot Study
Authors: Martinsson Louise , Eksborg Staffan , Wahlgren Nils Gunnar
Published: September 2003

Background: The most severely disabled stroke patients are often excluded from studies evaluating effects of physiotherapy. This study intended to investigate the effect of an increased intensity of physiotherapy in combination with dexamphetamine the first week after ischemic stroke in patients with an impaired level of consciousness and severe motor dysfunction. Methods: Thirty patients were enrolled within 96 h after onset of symptoms. Patients were randomized to 30–45 min of physiotherapy twice daily or to maximally 15 min per day for 5 days. All patients received dexamphetamine to achieve alertness. Functional outcome measures were assessed at baseline, the day after treatment discontinuation, and 3 and 12 months after stroke onset. Residence of living was registered at long-term follow-ups. Results: No statistically significant differences were seen between groups in the outcomes measured at any time point. However, both groups improved over time in all outcomes at 3 and 12 months (p < 0.05), except for sensory functions at 3 months and motor functions at 12 months. The number of patients needed to treat (NNT) to achieve the desired improvement in Lindmark motor score was 8, with the 95% CI being NNT(harm) 10 to NNT(beneficial) 3. The fraction of patients who died was the same in both treatment groups, 47% (95% CI 28–65%). Conclusions: An increased intensity of physiotherapy in combination with dexamphetamine during the first week after stroke onset did not affect short- or long-term outcome in this limited sample of patients with severe stroke.
Consequences of Mild Stroke in Persons <75 Years – A 1-Year Follow-Up
Authors: Carlsson Gunnel E. , Möller Anders , Blomstrand Christian
Published: September 2003

Background and Purpose: Mild strokes can be neglected regarding subtle sequels as fatigue, and cognitive and emotional changes. We have addressed this topic by exploring late consequences of an initially mild stroke (Barthel score ≧50). Accordingly, we assayed impairment, disability and handicap data 1 year after the first-ever stroke in persons <75 years, focusing on symptoms as fatigue, concentration difficulties, memory disturbances, emotional lability, stress resistance, anxiety and uneasiness, symptoms comprised in the astheno-emotional disorder (AED), and its relation to life satisfaction. Results: The mean value of the Barthel Index was 99.5 (SD 0.5) and 25% scored 0–1 on the Oxford Handicap Scale. AED was diagnosed in 71% of the patients, and fatigue was experienced by 72%. AED correlated significantly with life satisfaction, handicap and depression. Life satisfaction was significantly below that of norm values according to satisfaction with life as a whole, sex life and ability to manage selfcare. Conclusions: Our findings emphasize that ‘hidden dysfunctions’ not so easily discovered within the hospital context are common consequences of mild stroke. The concept of mild stroke as principally founded in motor function or ability in P-ADL therefore seems to be insufficient with respect to the patient long-term perspective.
Improvement of Cerebral Blood Flow by Olprinone, a Phosphodiesterase-3 Inhibitor, in Mild Heart Failure
Authors: Ueda Takashi , Mizushige Katsufumi , Yukiiri Kazushi , Takahashi Tsutomu , Kohno Masakazu
Published: September 2003

Cerebral blood flow (CBF) is reduced in heart failure (HF). For the treatment of acute HF, a phosphodiesterase-3 inhibitor, olprinone (OL), yields an increase in myocardial contractility and a decrease in arterial afterload. During a 15-min intravenous infusion of OL (0.2 µg/kg/min), regional CBF at 6 sites of each cerebral cortex was examined using technetium-99m-ethylcysteinate dimer brain SPECT in 18 HF patients and 7 age-matched normal subjects. The baseline CBF was significantly reduced in HF (43.0 ± 3.9 ml/min/100 g) compared to that in normal subjects (48.0 ± 4.6 ml/min/100 g, p < 0.01). The baseline CBF showed a significant negative correlation with the increase in CBF during the OL infusion in HF (r = –0.38, p < 0.01) and normal subjects (r = –0.65, p < 0.01). The percent increase in CBF was significantly greater in HF (13.7%) than in normal subjects (9.8%, p < 0.046). In patients with HF, the CBF of the cerebral cortex was decreased, but was increased by OL infusion.
A Prospective Community-Based Study of Stroke in Southern Italy: The Vibo Valentia Incidence of Stroke Study (VISS)
Authors: Di Carlo Antonio , Inzitari Domenico , Galati Franco , Baldereschi Marzia , Giunta Vincenzo , Grillo Gaetano , Furchì Alfonso , Manno Valerio , Naso Francesco , Vecchio Antonino , Consoli Domenico
Published: September 2003

Background and Purpose: Data on stroke morbidity are lacking in southern Italy, an area with about 20 million inhabitants and a mean income lower than the rest of the country. Therefore a population-based stroke register was established to determine incidence and case fatality in the Province of Vibo Valentia, Calabria. Methods: The survey was conducted among the 179,186 residents. Standard definitions and multiple case-finding procedures were employed. All identified cases of first-ever stroke were followed at 28 days, 3 and 12 months. The registration started on January 1, 1996, and ended on December 31, 1996. Results: A total of 321 first-ever-in-a-lifetime strokes were identified. The crude annual incidence rate was 1.79 (95% CI 1.60–1.99) per 1,000 inhabitants. Rates age-standardized to the 1996 Italian population and to the standard European population were, respectively, 1.99 (95% CI 1.79–2.20) and 1.36 (95% CI 1.19–1.53) per 1,000 inhabitants. A subtype diagnosis was reached in 96% of patients. The crude annual incidence rates per 1,000 inhabitants were 1.31 for cerebral infarction, 0.35 for intracerebral hemorrhage, 0.06 for subarachnoid hemorrhage, and 0.07 for unspecified stroke. Overall case fatality was 23.7% at 28 days, 27.4% at 3 months and 40.2% at 12 months. Conclusions: This is the first prospective population-based stroke register established in southern Italy. Incidence and case fatality were comparable to those previously reported in northern and central Italy and other industrialized countries. Our estimates are useful for developing management services and allocating resources.
Paradoxical Effects of Opioid Antagonist Naloxone on SSRI-Induced Analgesia and Tolerance in Mice
Authors: Singh Vijay Pal , Patil Chandrashekhar S. , Jain Naveen K. , Singh Amarjit , Kulkarni Shrinivas K.
Published: September 2003

Selective serotonin reuptake inhibitors (SSRIs) have been used clinically as co-analgesics in various devastating painful conditions. Upon chronic treatment tolerance develops to their analgesic effect, which is often refractory to increasing dose. Although modulation of serotonergic pathways considerably explains their clinical efficacy, numerous reports nevertheless indicate the direct/indirect role of the opioidergic pathway in SSRI-induced analgesia. The present study was designed to investigate the effect, if any, of the opioid antagonist naloxone on SSRIs-induced analgesia and tolerance employing acetic acid-induced writhing assay. Two SSRIs, fluoxetine (FLX), and citalopram (CTP) were used in the study. Acute systemic (5–40 mg kg–1 i.p.), or intrathecal (5–40 µg per mouse, i.t.) administration of fluoxetine or citalopram exhibited a dose-dependent and significant (p < 0.05) antinociceptive effect. Single systemic (2–5 mg kg–1 i.p.) or intrathecal (1 µg per mouse, i.t.) administration of opioid antagonist naloxone blocked where as systemic ultra-low dose (10 ng/kg) or intrathecal (0.05 ng) naloxone potentiated the acute antinociceptive effect of both SSRIs (10 mg kg–1 i.p. and 10 µg i.t.). Animals treated chronically over a 7-day period with SSRIs developed tolerance to their antinociceptive effect. Further, chronic administration of ultra-low dose of naloxone intrathecal (0.05 ng per mouse, i.t.) or systemic (10 ng kg–1 i.p.) with fluoxetine or citalopram (10 µg i.t.; 5 mg kg–1 i.p.) over a 7-day period reversed the tolerance to the antinociceptive effect of SSRIs. Thus, in ultra-low doses, naloxone paradoxically enhances SSRIs-induced analgesia and reverse tolerance through spinal and peripheral action. These effects of opioid antagonist naloxone on SSRIs-induced antinociception may have an implication in refractory cases upon chronic use of SSRIs as co-analgesics.
Threshold for Antiproliferative and Proapoptotic Activity of Taxol in HepG2 Cells Expressing Human CYP3A4: Effect of P-Glycoprotein Transporters
Authors: Holownia Adam , Cederbaum Arthur I.
Published: September 2003

Taxol treatment froze the cell cycle in the G2/M phase, induced morphological changes characteristic of apoptotic/necrotic cell death and increased CYP3A4 enzymatic activity, CYP3A4 mRNA and protein levels in HepG2 cells overexpressing CYP3A4. Apoptosis was associated with cytochrome c release to the cytosol; however, at higher Taxol levels, cells became relatively resistant to the drug-induced freezing of the cell cycle and saturation thresholds for both antiproliferative and proapoptotic activity of Taxol were observed. P-Glycoprotein expression was only slightly increased by Taxol, however, P-glycoprotein-mediated pumping efficiency was significantly increased. Preincubation of cells with an anti-MDR1 monoclonal antibody prior to the drug treatment, coincubation of cells with a potent CYP3A4 inhibitor – ketoconazole – or with both compounds increased Taxol toxicity and proapoptotic activity, indicating that the P-glycoprotein system has a major role in Taxol disposition in hepatoblastoma cells.
Nicotinamide Offers Multiple Protective Mechanisms in Stroke as a Precursor for NAD+, as a PARP Inhibitor and by Partial Restoration of Mitochondrial Function
Authors: Klaidman Lori , Morales Maria , Kem Seyha , Yang Jun , Chang Mei-Ling , Adams Jr. James D.
Published: September 2003

The purpose of the current study was to investigate aspects of improved bioenergetic function using nicotinamide during stroke. Using a global ischemia-reperfusion mouse model, ATP was depleted by 50% in the brain. The use of nicotinamide to provide a large reserve of brain NAD+ restored ATP levels to 61% of control levels. Alternatively, using nicotinamide as a PARP inhibitor restored ATP levels up to 72%. However, using a large reserve of NAD+ in the brain together with PARP inhibition proved to be additive, restoring ATP to 85% of control levels during the first critical 5 min of reperfusion. NAD+ and ATP levels correlated almost exactly. Brain mitochondrial function was also examined after cerebral ischemia-reperfusion. State 3 respiration of complex I was found to be abolished. However, this was a non-permanent inhibition of activity in vitro, since (NADH ubiquinone oxideroductase) complex I activity in these mitochondria was restored upon the addition of NADH. In vivo, the use of increased brain NAD+ and PARP inhibition was able to partially restore mitochondrial respiration. Taken together, the results show that nicotinamide offers a substantial protective role in terms of preservation of cellular ATP and mitochondrial NAD-linked respiration.
Augmented Pulmonary Vascular and Venous Constrictions to NG-Nitro-L-Arginine Methyl Ester in Rats with Monocrotaline-Induced Pulmonary Hypertension
Authors: Leung Susan W.S. , Cheng Xing , Lim Su Lin , Pang Catherine C.Y.
Published: September 2003

The hemodynamic effects of NG-nitro-L-arginine methyl ester (L-NAME, inhibitor of nitric oxide (NO) synthase) were examined in thiobutabarbital-anesthetized controlrats and rats with monocrotaline-induced pulmonary hypertension. L-NAME (1–16 mg/kg i.v.) increased mean arterial pressure, systemic vascular resistance, venous resistance and pulmonary vascular resistance, and decreased cardiac output in both the control and pulmonary hypertensive rats. Relative to the controls, L-NAME (16 mg/kg) caused a smaller increase (≈50% of control) in mean arterial pressure in the pulmonary hypertensive rats, but greater increases in venous (≈200%) as well as pulmonary vascular (≈400%) resistances and a greater decrease in cardiac output (≈140%). The results show that NO is an important dilator within the arterial, venous and pulmonary circulation; its pulmonary and venous dilator roles are augmented in pulmonary hypertension.
The Use of Transversely Tubularized Bowel Segment for Segmental Ureteral Replacement
Authors: Çetinel Bülent , Demirkesen Oktay , Çetinel Şule , Gül Ümit , Kiliç Nurten , Solok Vural
Published: September 2003

The aim of the present study was to evaluate the results of the use of a new technique, i.e. transversely tubularized bowel segment (TTBS) for segmental ureteral replacement in pigs. Eight pigs had segmental left ureteral replacement with the TTBS technique, via midline incision in 5 and flank incision in 3. The right ureters were left untouched and used as controls. The pigs were evaluated by excretory urography approximately 3 months after surgery and then sacrificed thereafter, harvesting the kidneys, ureters, and the bladders en bloc for macroscopic and histologic examination. Three pigs died in the early postoperative period. The remaining 5 pigs were followed for 82–112 days. Postoperative intravenous urograms revealed moderate ureterohydronephrosis in 2, mild ureteral dilation in 1, and normal upper tracts in 2. The 2 pigs with moderate ureterohydronephrosis had had midline incisions, and examination after having sacrificed these pigs revealed many intestinal adhesions to the anastomotic region. Easy catheterization of each left ureter through ileal ureteral segment and histologic examination thereafter demonstrated that all ileal ureteral segments including anastomotic sites were patent. Adjacent to the junctional area, metaplastic transitional epithelium covered atrophic villi and in some regions crypts as well. Ureteral replacement by the TTBS technique seems to be a safe and effective surgical treatment option in segmental ureteral defects in short term. However, long-term follow-up studies are needed.
Prognostic Values of p53 and HER-2/neu Coexpression in Invasive Bladder Cancer in Taiwan
Authors: Tsai Yuh-Shyan , Tzai Tzong-Shin , Chow Nan-Hua , Yang Wen-Horng , Tong Yat-Ching , Lin Johnny S.N. , Chang Chien-Chen , Cheng Hong-Lin , Lin Yung-Ming
Published: September 2003

Objectives: To explore the clinical significance of p53 and HER-2/neu coexpression by immunohistochemistry in patients with invasive bladder cancer in Taiwan. Methods: Paraffin-embedded tumor blocks were obtained from 67 patients with invasive bladder cancer subjected to radical cystectomy, bilateral lymph node dissection, and urinary diversion with or without systemic chemotherapy. Two observers (N.H.C. and T.S.T.), blinded to clinical outcome, reviewed the immunohistochemical staining for p53 (PAb1801) and HER-2/neu (Ab-17). The results were analyzed for progression-free survival and patient survival. Results: Positive staining for p53 and HER-2/neu was found in 30 (44.8%) and 39 (58.2%) patients. In contrast to HER-2/neu, p53 expression was significantly associated with tumor grade and pathologic stage (p = 0.040 and 0.004, respectively), and tended to be related to the nodal status (p = 0.080). Most importantly, coexpression of p53 and HER-2/neu significantly correlated with nodal metastases (p = 0.020). Univariate and multivariate analysis revealed p53 and nodal status as two independent prognostic factors. Additionally, patients with p53 and HER-2/neu coexpression had the shortest time to relapse and overall survival, irrespective of whether adjuvant chemotherapy was given or not (p = 0.005 and 0.030). Conclusions: In invasive bladder cancer, p53 was an important prognostic factor since its expression correlated with tumor grade and stage, even nodal status, whereas HER-2/neu did not show prognostic significance. Tumors with p53 and HER-2/neu coexpression were associated with nodal metastases, probably resulting in decreased progression-free survival. Although some basic studies provide some important supports, studies including larger patient cohorts would still be required to prove the hypothesis that p53 and HER-2/neu-coexpressing tumors have a worse prognosis and are more resistant to a cisplatin-based multidrug regimen.
Urinary Diversion in Infants with Primary High-Grade Vesicoureteric Reflux, Urinary Sepsis and Renal Function Impairment
Authors: Mattioli G. , Buffa P. , Torre M. , Carlini C. , Pini Prato A. , Castagnetti M. , Betti E. , Manzara A. , Piaggio G. , Perfumo F. , Jasonni V.
Published: September 2003

Introduction: General consensus on the optimal treatment of septic infants with primary high-grade vesicoureteric reflux (VUR) and renal function impairment has not been reached. Our study aims at evaluating the role of temporary urinary diversion. Materials and Methods: Twenty male infants, affected by sepsis and primary high-grade VUR, underwent urinary diversion in 1996–2001 because of estimated risk of renal function deterioration, due to non-compliance with the antibiotic treatment. Plasmatic creatinine clearance, ultrasonography, micturition cystography and scintigraphy were evaluated. Results: Creatinine clearance was abnormal in 13 infants on admission, in 10 after urinary diversion and in 6 after second surgery. Renal damage (focal or diffuse) was evident in 16 patients, without modifications after surgery. No patient developed urinary tract infections (UTI). Vesicostomy was done in 12 cases, ureterostomy in 8. Nephrectomy was performed in 3 cases with poor renal function, and ureteroneocystostomy in 17. Conclusions: Urinary diversion in septic infants with high-grade VUR can represent an alternative approach to the conservative or surgical treatment in selected patients presenting risk of renal function impairment. This procedure allowed an easy management of UTI without worsening of renal function while waiting for a better anatomical status to perform reconstructive surgery.
Differentiating Solitary Pulmonary Metastases in Patients with Renal Cell Carcinomas by 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography – A Preliminary Report
Authors: Chang Chao-Hsiang , Shiau Yu-Chien , Shen Yeh-You , Kao Albert , Lin Cheng-Chieh , Lee Cheng-Chun
Published: September 2003

Objective: This preliminary study was to evaluate the characteristics of indeterminate solitary pulmonary lesions in patients with renal cell carcinomas (RCC) using 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Material and Methods: Fifteen patients with RCC were found to have solitary pulmonary lesions with indeterminate chest X-ray and CT findings. Pulmonary metastases were suspected in all cases so whole body surveys with FDG-PET were performed. Results: FDG-PET correctly identified 9 true-positive and 4 true-negative cases. However, FDG-PET failed to interpret 1 false-positive and 1 false-negative case. Standard uptake values (SUV) were used as parameters to differentiate the solitary pulmonary lesions. Using SUV >2.5 as the cutoff to diagnose malignancy, the sensitivity, specificity, and accuracy of FDG-PET were 90, 80, and 87%, respectively. Conclusion: We conclude that FDG-PET is an accurate modality to differentiate solitary pulmonary lesions in patients with RCC.
Cadaveric versus Porcine Models in Urological Laparoscopic Training
Authors: Katz Ran , Hoznek András , Antiphon Patrick , van Velthoven Roland , Delmas Vincent , Abbou Clément-Claude
Published: September 2003

Introduction: Laparoscopy performed on anesthetized pigs is an established training model. In this pilot study, we performed laparoscopy on cadavers as a training modality for urologists participating in a laparoscopic seminar. Materials and Methods: We compared data from two consecutive laparoscopy seminars performed at our institution. The first included a laparoscopy session performed on pigs. The second was in the same setup, yet laparoscopy was performed on fresh cadavers. We analyzed and compared the trainees’ perspectives regarding the 2 modalities using a 5-scale satisfaction questionnaire. Results: Seven trainees attended the cadaveric and 9 the porcine laparoscopy session. The two groups were similar in terms of age and previous laparoscopic and urological experience. The general satisfaction of the two training modalities was high in the two groups, as well as their will for another session of the same kind. Yet the trainees ranked their understanding of the surgical anatomy, laparoscopic technique and use of instruments significantly higher in the cadaveric laparoscopy group (p values were 0.007, 0.006 and 0.032, respectively). Conclusions: Cadaveric laparoscopy may offer an ideal surgical environment allowing dissection and performance of complete procedures. In this pilot study, we conducted the first reported cadaveric laparoscopy training seminar in urology. The trainees preferred the cadaveric laparoscopy and found it superior to porcine laparoscopy. We believe that cadaveric laparoscopy is an important training tool, which may be added to the armamentarium of urological laparoscopy training courses.
Incidental Bilateral Leydig Cell Tumor of the Testes
Authors: Akman Haluk , Ege Gurkan , Yildiz Sacit , Cakiroglu Gokhan
Published: September 2003

Testis tumors are extremely rare tumors, especially if they are bilateral, interstitial tumors. We present a case with bilateral Leydig cell tumors, which were detected incidentally. First, radical left orchiectomy was performed and pathologic diagnosis was Leydig cell tumor. One week later, partial right orchiectomy was done. The diagnosis was the same. After the 12-month follow-up, no recurrence or metastasis was detected. We suggest organ-sparing surgery as an alternative in the treatment of bilateral Leydig cell tumors especially for young males, since this surgical approach prevents hormonal replacement therapy and maintains fertility and potency.
Findings and Clinical Course of a Localized Primitive Peripheral Neuroectodermal Tumor of the Kidney
Authors: Habermann Helga , Benesch Martin , Schips Luigi , Pummer Karl , Ratschek Manfred , Uggowitzer Martin M. , Urban Christian , Hubmer Gerhart
Published: September 2003

Primitive neuroectodermal tumor (PNET) is a very aggressive neoplasm, considered to have an unfavorable prognosis, and renal location is extremely rare. We present the findings and clinical course of a patient with localized disease who is free of disease more than 3 years after first presentation. In suspicious cases we recommend to surgically explore renal masses as early as possible.
Giant Stone in a Complete Duplex Ureter with Ureterocele
Authors: Dominici A. , Travaglini F. , Maleci M. , di Cello V. , Rizzo M.
Published: September 2003

We describe a case of a monolateral duplex system and a ureterocele containing a gigantic stone in a 65-year-old woman who presented with pyelonephritis without any previous history of urinary tract infections or stone disease. Stone removal and double left ureteroneocystostomy with plastic widening of a narrowed obstructive side were performed. The ureteral stone measured 10.5 cm in greatest diameter, weighed 85 g and contained calcium oxalates and phosphates. Three months after surgery, radiology (intravenous urography and cystography) showed left unobstructed upper and lower urinary tracts and the absence of vesicoureteral reflux. Urine culture was negative 3, 6 and 9 months after surgery.
Rupture of an Aortic Anastomotic Aneurysm into a Ureter
Authors: Georgopoulos S.E. , Arvanitis D.P. , Tekerlekis P. , Chronopoulos A. , Kostakopoulos A.
Published: September 2003

A case of rupture of a false aneurysm of the distal aorta into the left ureter is reported. The patient presented with purulent hydronephrosis and hematuria. A left aorto-femoral graft had been inserted 3 years earlier, which became infected and was then removed. After 2 years a false distal aortic aneurysm developed, and in the last 6 months recurrent episodes of hematuria have occurred. An aorto-ureteric fistula was confirmed at surgery, and a left nephrostomy was performed with proximal and distal ligation of the ureter and then aneurysmectomy followed by aorto-bifemoral bypass.
Rare Case of Primary Lymphoma of the Prostate: Giving the Patient the Benefit of the Doubt
Authors: Wazait H.D. , Al-Buheissi S.Z. , Dudderidge T. , Patel H.R.H. , Jarmulowicz M. , Pigott K. , Miller R.A.
Published: September 2003

One third of non-Hodgkin lymphomas are extranodal, however it is uncommon for the lower urinary tract to be involved. We present an unusual case of a low-grade primary lymphoma affecting the prostate, which responded well to radical radiotherapy.
Somatosensory Organization and Behavior in Naked Mole-Rats I: Vibrissa-Like Body Hairs Comprise a Sensory Array That Mediates Orientation to Tactile Stimuli
Authors: Crish Samuel D. , Rice Frank L. , Park Thomas J. , Comer Christopher M.
Published: September 2003

Orientation guided by mechanosensory stimuli is a fundamental behavior that has been analyzed most effectively in simple systems, but has been difficult to assess in mammals. This study demonstrates that sparsely distributed sensory ‘hairs’ on the body of naked mole-rats provide an ideal detector array for the assessment of touch guided orienting behavior. Naked mole-rats are fully subterranean rodents that are functionally blind and lack fur. About 40 tactile hairs (resembling facial vibrissae) are found on each side of the body, and they are systematically organized in a grid-like pattern from head to tail. Deflection of a single body hair triggered a highly accurate orientation of the snout toward the point of stimulation, thus topographically organized motor behavior can be elicited from this sensory array. This orienting behavior is specific to the body hair system: touch of intervening skin evoked responses less reliably, and observed responses were not topographically organized. Orientation elicited from this array was accurate regardless of the head-to-body position at the time of hair stimulation indicating that the orienting motor score takes relative head position into account. The consistent pattern of these hairs coupled with robust orienting behavior indicates that this mammalian model provides an appropriately simple system for analyzing the neuronal basis of sensorimotor integration involved in tactile orienting behavior.