bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Footprints’ of Transient Ischemic Attacks: A Diffusion-Weighted MRI Study
Authors: Ay Hakan , Oliveira-Filho Jamary , Buonanno Ferdinando S. , Schaefer Pamela W. , Furie Karen L. , Chang Yuchiao , Rordorf Guy , Schwamm Lee H. , Gonzalez R. Gilberto , Koroshetz Walter J.
Published: April 2003

Objective: Diffusion-weighted imaging (DWI) conveys temporal as well as anatomic information about brain infarction, and is therefore well suited to identify ischemic injury that has occurred simultaneously, or closely linked in time, with a transient ischemic attack (TIA). We aimed to determine the proportion and clinical characteristics of patients with TIA who harbor infarction(s) on DWI. Methods: Using T2-weighted imaging (T2-WI), fast fluid attenuated inversion recovery (FLAIR), and DWI, we studied 57 consecutive patients presenting with acute focal neurologic symptoms lasting less than 24 h. Results: A hyperintense DWI lesion was identified in a vascular territory appropriate to the symptoms in 27 patients (47%). Lesions judged to be clinically appropriate on T2-WI and FLAIR overlapped with a DWI lesion in 41 and 48% of patients, respectively. Independent predictors of infarction on DWI were previous nonstereotypic TIAs, presentation with motor symptoms, and identified stroke mechanism. Conclusion: DWI establishes that recent infarction occurs in almost half of patients with the clinical syndrome of TIA and this subgroup is more likely to harbor an underlying cardiac or cerebrovascular abnormality.
Brain Iron Metabolism and Neurodegenerative Disorders
Authors: Sipe Jack C. , Lee Pauline , Beutler Ernest
Published: April 2003

Iron, an essential element for central nervous system (CNS) function, has frequently been found to accumulate in brain regions that undergo degeneration in neurological diseases such as Alzheimer disease, Parkinson disease, Friedreich ataxia and other disorders. However, the precise role of iron in the cause of many neurodegenerative diseases is unclear. To assist in understanding the potential importance of iron in CNS disease, this review summarizes the present knowledge in the areas of CNS iron metabolism, homeostasis and disregulation of iron balance caused by mutations in genes encoding proteins involved in iron transport, storage and metabolism. This review encompasses neurodegenerative disorders associated with both iron overload and deficiency to highlight areas where iron misregulation is likely to be important in the pathophysiology of several human brain diseases.
Pegylated Liposomal Doxorubicin with Vinorelbine in Metastatic Breast Carcinoma
Authors: Gebbia Vittorio , Mauceri Gaetano , Fallica Giuseppina , Borsellino Nicolò , Tirrito Maria Lina , Testa Antonio , Varvara Francesca , Colombo Alfredo , Ferrera Patrizia
Published: April 2003

A multicenter phase I-II trial was carried out with the aim of identifying the dose-limiting toxicity and the maximum tolerated dose of vinorelbine (VNR) in combination with pegylated liposomal doxorubicin at a dose of 20 mg/m2 every 15 days in patients with metastatic breast carcinoma. In the phase I part of the trial, VNR was given at a dose of 20 mg/m2 every 15 days to a group of 3 patients. In absence of unacceptable toxicity, VNR was escalated to 25, 30, and 35 mg/m2 for subsequent groups of 3 patients, until the dose-limiting toxicity was reached. No case of palmar-plantar erythrodysesthesia was recorded in these patients. Grade 4 neutropenia, grade 3 thrombocytopenia, and grade 3 mucositis were the dose-limiting toxicities recorded in patients treated with VNR 35 mg/m2. These side effects caused a substantial decrease in programmed dose intensity. Therefore 30 mg/m2 was considered the maximum tolerated dose of VNR in combination with pegylated liposomal doxorubicin 20 mg/m2, both given every 15 days. These dosages were employed for the treatment of further 18 patients included in phase II of the study. The overall response rate, calculated according to an intention to treat analysis, was 63% (95% CI: 44–80%), with 2 patients achieving a complete response. The median time to progression was 7.0 months or more (range 2–14 months). Median duration of objective responses was 8.4 months or more. The duration of the 2 complete responses was 9 and 14 months, respectively. Median duration of survival was 16.0 months or more (range from 4.0 to ≧24.0). Toxicity was generally mild and easily manageable. Neutropenia and mucositis were the most frequently recorded side effects. A case of palmar-plantar erythrodysesthesia was recorded in phase II of the study. In conclusion, the maximum tolerated dose of VNR in association with pegylated liposomal doxorubicin is 30 mg/m2 on a bimonthly schedule. Moreover, the combination of VNR and pegylated liposomal doxorubicin is active against metastatic breast carcinoma and is associated with a good toxicity profile. Further studies with this combination regimen are warranted.
Temozolomide in Patients with Glioblastoma at Second Relapse after First Line Nitrosourea-Procarbazine Failure: A Phase II Study
Authors: Brandes Alba A. , Ermani Mario , Basso Umberto , Paris Myriam K. , Lumachi Franco , Berti Franco , Amistà Pietro , Gardiman Marina , Iuzzolino Paolo , Turazzi Sergio , Monfardini Silvio
Published: April 2003

Objectives: To investigate the efficacy of temozolomide (TMZ) in relationship to progression free survival at 6 months (PFS-6), median time to progression (TTP), response rate and toxicity, a phase II study was conducted in patients with recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a first-line regimen based on nitrosourea, procarbazine and vincristine. Methods: Forty-two patients with GBM were administered TMZ at the dose of 150 mg/m2/daily for 5 days every 4 weeks. Results: The PFS-6 and at 12 months (PFS-12) was 24% (95% Confidence Interval [CI] = 14–42%) and 8% (CI = 2–27%), respectively, with a median TTP of 11.7 weeks (CI = 9–22 weeks). The response was assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6 partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR = 19% (CI = 7–31%). Conclusion: TMZ as a second line regimen is a valid option in patients with heavily pretreated GBM.
DNA Aneuploidy in Relation to the Combination of Analysis of Estrogen Receptor, Progesterone Receptor, p53 Protein and Epidermal Growth Factor Receptor in 498 Breast Cancers
Authors: Tsutsui Shinichi , Ohno Shinji , Murakami Shigeru , Hachitanda Yoichi , Oda Shinya
Published: April 2003

Background: Various studies have analyzed the relationships between new biological parameters and DNA ploidy for human cancer. However, the biological significance of DNA ploidy remains unclear, since there have so far been few studies analyzing DNA ploidy in relation to the combination of multiple such biological parameters. Methods: Samples for the analysis of DNA ploidy, estrogen receptor (ER), progesterone receptor (PgR), p53 protein and epidermal growth factor receptor (EGFR) were prepared from the same frozen specimens of 498 primary breast cancers. DNA ploidy was determined by flow cytometry, while ER and PgR were determined by an enzyme immunoassay. Both p53 protein and EGFR were determined by immunohistochemical analyses. Results: Aneuploidy was significantly correlated with the absence of ER, the absence of PgR, the positivity of p53 protein and the positivity of EGFR, and it was also significantly correlated with the combination of the absence of ER and PgR and the combination of the positivity of p53 protein and EGFR. A deviation in the four parameters was defined as the absence of ER, the absence of PgR, the positivity of p53 protein or the positivity of EGFR. As the number of deviations of these four biological parameters increased, the incidence of aneuploidy increased significantly (p < 0.0001). Multivariate analysis also indicated that deviation of two, three or all four parameters were significant factors for DNA ploidy, while the p value decreased and the odds ratio increased as the number of deviations of the four biological parameters increased. Conclusions: DNA aneuploidy based on flow cytometric analysis reflects the accumulation of deviations in the four biological parameters investigated in the present study. The two facts that DNA aneuploidy reflects the accumulation of the aggressiveness of these biological parameters and that DNA aneuploidy consisted of heterogeneous characteristics which were represented by the deviation of each biological parameter should be taken into consideration when selecting treatment strategies for breast cancer.
Circulating Levels of Thrombopoietic and Inflammatory Cytokines in Patients with Acute Myeloblastic Leukemia and Myelodysplastic Syndrome
Authors: Hsu Hui-Chi , Lee Yuan-Ming , Tsai Wen-Hui , Jiang Mei-Lan , Ho Chau-Hung , Ho Chi-Kuan , Wang Sheng-Yuan
Published: April 2003

Background: The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. The regulatory mechanism of endogenous cytokines in circulating platelet counts of thrombocytopenic patients with acute myeloblastic leukemia (AML) and myelodysplastic syndrome (MDS) is still not clear. Methods: We measured the serum levels of both thrombopoietic and inflammatory cytokines in peripheral blood and bone marrow samples collected from 52 patients with either AML or MDS along with 35 normal control samples. The levels of thrombopoietin (TPO), interleukin (IL)-11, IL-6, IL-8 and stem cell factor (SCF) were determined by ELISA. Results: Platelet counts in the AML/MDS patients during initial diagnosis, chemotherapy and complete remission were 71.2 ± 11.6, 47.2 ± 6.1 and 181.4 ± 26.3 ×109/l, respectively. The median value of TPO in AML/MDS patients during diagnosis was 150.6 pg/ml and increased significantly during chemotherapy (median: 828 pg/ml; p < 0.05) but then decreased following complete remission (median: 221.4 pg/ml). However, these levels were all significantly higher in patients than in normal subjects (p < 0.05, p < 0.05 and p < 0.05; respectively), and no significant change was noted in the levels of IL-11 and SCF during treatment of patients or in normal controls. The level of IL-6 was not detectable in normal serum samples but was markedly increased in the AML/MDS patients (median level during diagnosis: 6.7 pg/ml; chemotherapy: 25 pg/ml; complete remission: 7 pg/ml). The level of IL-8 in patients with AML and MDS was markedly elevated during diagnosis (median: 27.5 pg/ml; range: 0–1,587 pg/ml), but decreased to the level of the normal controls when patients were under chemotherapy or in complete remission. Conclusions: The endogenous levels of TPO, IL-6 and IL-8 are elevated in the thrombocytopenic patients with AML and MDS. Our results are consistent with previous mechanistic studies and suggest that TPO and IL-6 may be active mediators of platelet production.
Balance between Cell Division and Cell Death as Predictor of Survival in Patients with Non-Small-Cell Lung Cancer
Authors: Puglisi Fabio , Minisini Alessandro Marco , Aprile Giuseppe , Barbone Fabio , Cataldi Palmina , Artico Daria , Damante Giuseppe , Beltrami Carlo Alberto , Di Loreto Carla
Published: April 2003

Objective: To evaluate the prognostic value of the balance between apoptosis and proliferation in non-small-cell lung cancer (NSCLC). Methods: Paraffin-embedded sections from a consecutive series of radically resected NSCLCs were scored for apoptosis (in situ DNA nick end labeling assay) and proliferation (immunohistochemistry for MIB-1). A total of 1,000 cells were counted per case, to obtain apoptotic (AI) and MIB-1 indices. Other potential prognostic indicators (pT, pN, pStage and histology) and p53 status were also evaluated. Results: Univariate analysis showed that adenocarcinomatous histotype (p = 0.03), nodal involvement (p = 0.04), higher pStage (p = 0.001) and the combination of low AI and high MIB-1 expression (p = 0.03) were associated with poorer outcome. The significant prognostic value of the combination ‘low AI/high MIB-1’ was also confirmed in a multivariate analysis after adjustment for other covariates. Conclusion: These results underline the importance of considering apoptosis and proliferation together to identify a subgroup of NSCLC associated with poor survival.
Inhibition of Eotaxin Expression in Human Corneal Fibroblasts by Interferon-γ
Authors: Fukuda Ken , Yamada Naoyuki , Fujitsu Youichiro , Kumagai Naoki , Nishida Teruo
Published: April 2003

Background: The chemokine eotaxin is a potent and selective chemoattractant for eosinophils. The production of eotaxin by corneal fibroblasts likely contributes to eosinophil infiltration into the corneal stroma. The regulation of eotaxin synthesis in these cells was investigated by examining the effect of interferon-γ (IFN-γ), a T helper cell 1-derived cytokine, on eotaxin expression in cultured human corneal fibroblasts. Methods: The release of eotaxin from cultured corneal fibroblasts was measured by enzyme-linked immunosorbent assay, and the abundance of eotaxin mRNA in these cells was determined by reverse transcription combined with real-time polymerase chain reaction analysis. Results: IFN-γ inhibited in a dose-dependent manner the release of eotaxin induced by each of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and IL-1β in corneal fibroblasts. IFN-γ also inhibited the increase in the abundance of eotaxin mRNA induced by each of these cytokines. The synergistic increases in eotaxin release and in eotaxin mRNA abundance induced by the combination of TNF-α and the T helper cell 2-derived cytokine IL-4 were also both markedly inhibited by the treatment of cells with IFN-γ. Conclusions: IFN-γ inhibited eotaxin expression at both the protein and mRNA levels in cultured human corneal fibroblasts. This effect of IFN-γ may contribute to the inhibition of eosinophil infiltration into the cornea. Exogenous IFN-γ thus represents a potential new therapeutic agent for the treatment of corneal disorders associated with inflammatory ocular diseases such as vernal keratoconjunctivitis.
Alkaline Serine Proteinase from Aspergillus fumigatus Has Synergistic Effects on Asp-f-2-Induced Immune Response in Mice
Authors: Kurup Viswanath P. , Xia Jin-Qi , Shen Horng-Der , Rickaby David A. , Henderson Jr James D. , Fink Jordan N. , Chou Hong , Kelly Kevin J. , Dawson Christopher A.
Published: April 2003

Background: Exposure to Aspergillus fumigatus allergens results in the sensitization and the development of allergic bronchopulmonary aspergillosis in susceptible individuals. Aspergillus antigen consists of a number of chemically diverse components and their cumulative or synergistic effect may result in disease. When mice were challenged with individual recombinant allergens, there was only reduced inflammation and immunological responses compared to the whole antigen. Various enzymes identified from A. fumigatus have been thought to cause airway damage. In the present study, we evaluated the effect of exposure to Asp f 13, an alkaline serine proteinase, and Asp f 2 in mice. Methods: BALB/c mice were challenged intranasally with Asp f 2 and Asp f 13 alone and in combination. The antibody response, pulmonary inflammation, and airway hyperreactivity were studied. Results: Results demonstrated no major difference in antibody response and airway responses among the different groups. The inflammatory responses in the lungs, however, showed marked differences in the various groups. Conclusion: In spite of the similar immunological responses in the different groups of mice studied, the results demonstrate enhanced inflammation in the lungs of mice exposed to a combination of both allergens. Allergens with proteinase activity have been found to be involved in airway inflammation and remodeling, which may also apply for Aspergillus-induced allergy.
Neonatal Ovine Adrenal Cortical and Medullary Cell H+ Responses to ACTH and Prostaglandin E2
Authors: Zambrano E. , Nathanielsz P.W. , McDonald T.J.
Published: April 2003

The microphysiometric technique was used to evaluate 1- and 3-day-old lamb adrenal gland H+ production in response to ACTH or PGE2. ACTH stimulated cortical, but not medullary H+ production; maximal H+ by combined cortical and medullary cells was greater than by cortical cells alone (p < 0.05). In contrast, the magnitude of the H+ response to PGE2 was greater with medullary than with cortical cells alone or with cortical and medullary cells combined (p < 0.05). The H+ response to ACTH was greater in 3-day-old compared to 1-day-old lambs while the potency of PGE2 was not different at the ages studied. We conclude that in neonatal sheep: (1) ACTH and PGE2 are potentially important in adrenal regulation, and (2) paracrine communication appears to be functioning as has been shown for adults.
Cerebral Oxygenation Is Affected by Filling Mode and Perfluorochemical Volume in Partial Liquid Ventilation of Healthy Piglets
Authors: Burkhardt Wolfram , Proquitté Hans , Krause Susann , Wauer Roland R. , Rüdiger Mario
Published: April 2003

Intrapulmonary administration of perfluorochemicals (PFC) has been suggested for reasons other than respiratory insufficiency. PFC application has been described to affect cerebral Hb concentration, however, data for healthy lungs are missing. Newborn piglets were randomized into 3 groups (30-ml slow-filling, 10-ml slow-filling and 30-ml rapid-filling), orally intubated and mechanically ventilated. Partial liquid ventilation (PLV) was initiated by filling the lung with PF5080 (10 or 30 ml/kg) at a rate of 1.5 ml/min (slow filling) or within 45 s (rapid filling). Vital signs, blood gases, tidal volume (VT) and changes in the cerebral concentration of oxygenated hemoglobin (HbO2) and total Hb were determined for up to 20 min. Rapid administration of PFC caused an immediate drop in HbO2, PaO2 and VT. The concentration of oxygenated and total Hb increased thereafter and remained high. We found a slow increase in PaCO2, HbO2 and total Hb in the 30-ml slow-filling group, but almost no changes in the 10-ml slow filling group (except for a decrease in PaO2). According to our data, PLV with 10 ml/kg should be preferred since cerebral alterations are minimal. If complete filling of the lung is needed PFC should be administered slowly to minimize side effects.
Association between Nutrition and Gender during Lactation Influencing Glucose Homeostasis and Blood Pressure of the Adult Offspring
Authors: Moura Anibal Sanchez , Franco de Sá Cristiano Cosme Nascimento , Lopez da Costa Celia , Vicente Luciana Leão , Guerreiro Sabrina Mendonça , Pinto Alessandra Maria Silva
Published: April 2003

The aim of this study was to evaluate the hypothesis that the association between nutritional status and gender of rat pups during the early postnatal period (lactation) induces changes in glucose homeostasis and blood pressure of the pups when becoming adults. The results indicate that undernourishment during lactation is associated with gender and affects glucose homeostasis and blood pressure of female adults. In our experiments, the blood glucose level at the end of a clamping was significantly different in the undernourished females (FU) compared with the female controls (FC) (FC: 11.2 ± 0.9 mmol/l; FU: 26.9 ± 2.1 mmol/l; p ≤0.001). On the other hand, the undernourished male (MU) group, when compared with the male control (MC) group, showed constant and similar glycemia during clamp-induced hyperglycemia, despite there being a significant reduction of plasma insulin (at the end of the clamping, MC: 595 ± 35 pmol/l and MU: 210 ± 4 pmol/l) in this group. In addition, in contrast to the control groups and the MU group, the systolic and diastolic (d) pressures at the end of the experimental period of the FU group were significantly lower than those of the FC group (FC: 15.3 ± 0.30 mm Hg and FU: 14.7 ± 0.25 mm Hg, p < 0.001; FCd: 7.7 ± 0.25 mm Hg and Fud: 6.8 ± 0.4 mm Hg, p≤0.001). Therefore, our results provide clear evidence that nutrition is associated with gender during the early postnatal period by inducing persistent changes in physiological outcomes.
Blood Transfusion in Anemic Infants with Apnea of Prematurity
Authors: Westkamp Eva , Soditt Volker , Adrian Sophie , Bohnhorst Bettina , Groneck Peter , Poets Christian F.
Published: April 2003

We found recently that blood transfusions had no effect on bradycardia and hypoxemia, the clinically important components of apnea of prematurity, in mildly anemic infants. Here, we wanted to know whether this also holds true for more severely anemic patients. Nineteen preterm infants, median gestational age at birth 25 (range 22–30) weeks, age at the time of study 5.5 (range 1–13) weeks, for whom a blood transfusion was ordered because of recurrent episodes of bradycardia and/or hypoxemia in conjunction with anemia (median hemoglobin level 78 g/l, range 63–98 g/l) were investigated. One infant received two transfusions and was thus studied twice. 4-hour recordings of pulse oximeter saturation (SpO2), pulse waveforms, electrocardiogram, breathing movements, and nasal airflow were performed immediately before transfusion of 20 ml/kg packed red blood cells and again 24 h later. The recordings were analyzed for baseline heart and respiratory rates and SpO2, all measured during regular breathing, as well as for apnea (≧20 s), bradycardia (heart rate <2/3 of baseline for ≧4 s), and episodic desaturation (SpO2 ≤80% for ≧4 s). There was no significant change in the combined frequency of bradycardia and desaturation, the primary study end point – median 6.4/h (range 3.0–13.5/h) before versus 4.6/h (range 0.6–15.7/h) after transfusion –, although there was slightly less bradycardia – 0.8/h (range 0.0–8.8/h) versus 0.7/h (range 0.0–5.1/h; p < 0.05). Baseline heart and respiratory rates decreased, respectively, from 163/min (range 140–182/min) and 58/min (range 34–98/min) to 152/min (range 134–172/min) and 55/min (range 36–82/min; p < 0.01). We conclude that blood transfusions significantly reduced heart and respiratory rates in these anemic infants, but had little effect on apnea of prematurity.
The Minicolumn and Evolution of the Brain
Authors: Buxhoeveden Daniel P. , Casanova Manuel F.
Published: April 2003

The minicolumn is generally considered an elementary unit of the neocortex in all mammalian brains. This essential building block has been affected by changes in the circuitry of the cortex during evolution. Researchers believe that enlargement of the cortical surface occurs through the addition of minicolumns rather than of single neurons. Therefore, minicolumns integrate cortical encephalization with organization. Despite these insights, few studies have analyzed the morphometry of the minicolumn to detect subtle but important differences among the brains of diverse mammals. The notion that minicolumns are essentially unchanged across species is challenged by strong evidence to the contrary. Because they are subject to species-specific variation, they can be used as a way to study evolutionary changes. Unfortunately, comparative studies are marred by a lack of standardized techniques, tissue preparation, cortical regions, or anatomical feature studied. However, recent advances in methodology enable standardized, quantified comparisons of minicolumn morphology.
Increased Expression of Tyrosine Hydroxylase Immunoreactivity in Paraventricular and Supraoptic Neurons in Illnesses with Prolonged Osmotic or Nonosmotic Stimulation of Vasopressin Release
Authors: Panayotacopoulou Maria T. , Malidelis Yiannis I. , Fliers Eric , Bouras Constantin , Ravid Rivka , Swaab Dick F.
Published: April 2003

Our previous studies indicated that in the human paraventricular (PVN) and supraoptic (SON) nuclei, tyrosine hydroxylase (TH) – the first and rate-limiting enzyme in catecholamine synthesis – is localized mainly in magnocellular neurons and that antemortem factors regulate its expression. The purpose of the present study was to investigate the distribution of TH-immunoreactive (TH-IR) perikarya of the hypothalami of a large sample of well-documented adult subjects without neurological, psychiatric or endocrinological disease in order to identify factors that could regulate the expression of TH in the human neurosecretory neurons. Our material consisted of the hypothalami of 38 subjects studied immunohistochemically for TH using the peroxidase-antiperoxidase method. Striking individual differences were observed among the subjects studied concerning the number and distribution of TH-IR perikarya within the PVN and SON. These differences were evident throughout the entire rostrocaudal length of the hypothalamus and appeared to be related neither to the age or sex of the subjects nor to the postmortem interval or staining procedures. In the sample studied, a large number of TH-IR perikarya were observed specifically in all subjects that had suffered from right-sided heart failure due to pulmonary hypertension, liver cirrhosis or dehydration. In all the above illnesses, increased production and secretion of vasopressin (VP) are reported to occur due to a decrease in ‘effective’ blood volume or to osmotic stimulation. We conclude that somatic illnesses leading to prolonged osmotic or nonosmotic stimulation of VP release may induce increased expression of TH immunoreactivity in the human neurosecretory neurons related to neuronal activation.
Estrogenic Properties of Raloxifene, but Not Tamoxifen, on D2 and D3 Dopamine Receptors in the Rat Forebrain
Authors: Landry Michelle , Lévesque Daniel , Di Paolo Thérèse
Published: April 2003

The present study investigated the estrogenic specificity of the modulation of dopamine D2 and D3 receptors by comparing the effects of estradiol with tamoxifen or raloxifene. These compounds have estrogenic and/or antiestrogenic activity depending on the target tissue. Two weeks after ovariectomy of female rats, we observed a 60% decrease in the uterine weight, which was prevented by a replacement therapy of 2 weeks with 17β-estradiol. A tamoxifen or raloxifene treatment of 2 weeks increased uterine weights by 35 and 15%, respectively, but significantly less than estradiol treatment. Ovariectomy decreased dopamine D2 receptor specific binding (20%) in the dorsolateral part of the anterior striatum and these receptors were left unchanged in the other parts of the striatum as well as in the olfactory tubercle and the nucleus accumbens. 17β-Estradiol and raloxifene, but not tamoxifen treatment prevented this decrease. Ovariectomy left dopamine D3 receptor specific binding unchanged. However, estradiol and raloxifene treatment decreased dopamine D3 receptor binding in the islands of Calleja, the core and shell of the nucleus accumbens and the dorsal part of the anterior striatum, compared with ovariectomized rats. Our results show that raloxifene, but not tamoxifen, has an agonist estrogenic activity on dopamine receptors. Furthermore, estradiol and raloxifene have opposite effects on specific binding to dopamine D2 and D3 receptors.
Effect of Glycolic Acid on UVB-Induced Skin Damage and Inflammation in Guinea Pigs
Authors: Park K.S. , Kim H.J. , Kim E.J. , Nam K.T. , Oh J.H. , Song C.W. , Jung H.K. , Kim D.J. , Yun Y.W. , Kim H.S. , Chung S.Y. , Cho D.H. , Kim B.Y. , Hong J.T.
Published: April 2003

Objectives: Recently the use of glycolic-acid-containing cosmetics has received increased public interest in their supposed ability to reduce wrinkles, roughness, age spots and other skin damage. However, the safety of such products when used excessively or chronically, especially by photosensitive people, is being questioned. The purpose of this study was to examine the effects of glycolic acid alone or in combination with UVB on skin damage and inflammatory response. Method: Guinea pigs were treated with glycolic acid (from 1 to 7 mg/cm2) alone or in combination with UVB (0.4 or 3 J/cm2) for 14 days. Skin damage was evaluated by scoring the skin irritation value by the method of Draize and by histopathological observations. Cyclooxygenase 2 (COX-2) expression and prostaglandin E2 (PGE2) production were also assessed. Results: Glycolic acid caused an increase in the level of skin damage in a dose- and time-dependent manner. Lower doses (1 and 3 mg/cm2) of glycolic acid mostly caused erythema and eschar, and these consequently formed scales, whereas higher doses (5 and 7 mg/cm2) of glycolic acid caused redness, edema and necrotic ulceration. Glycolic acid also increased the thickness of the epidermal layer, reduced the organization of the stratum corneum and eventually destroyed some parts of the epidermal layer at 7 mg/cm2. UVB (0.4 and 3 J/cm2) caused redness and edema as well as reduced the integrity of the stratum corneum. Glycolic acid enhanced the UVB-induced skin damage. The magnitude of the damage caused by combined UVB and glycolic acid treatment was much greater than that caused by glycolic acid or UVB alone. Moreover, partial destruction of the epidermal layer was observed in skin treated with 3 J/cm2 UVB and 3 mg/cm2 glycolic acid. However, glycolic acid did not change the basal and UVB-induced PGE2 production and COX-2 protein expression. Conclusion: These results show that glycolic acid causes skin damage in a dose- and time-dependent manner and that it enhances UVB-induced skin damage without accompanying PGE2 production or COX-2 protein expression. Therefore, caution should be exercised by those using glycolic acid on a chronic basis or excessively. Moreover, those with photosensitive skins and those more exposed to the sun should be particularly careful.
Effects upon Bone Metabolism following Total Hip and Total Knee Arthroplasty
Authors: Schneider Ulrich , Schmidt-Rohlfing Bernhard , Knopf Udo , Breusch Steffen J.
Published: April 2003

Objective: In a prospective study we evaluated the course of markers for bone formation and bone resorption in patients undergoing elective total hip and total knee arthroplasty due to osteoarthritis. The aim was to evaluate which changes in bone metabolism take place in the immediate postoperative course following arthroplasty. Methods: Serum and urine samples were obtained preoperatively and in the postoperative course from patients undergoing total arthroplasty over a 90- or 180-day period. The study included a total of 63 patients with cemented hip prostheses (n = 20), uncemented hip prostheses (n = 23) and cemented knee prostheses (n = 20). Different biochemical markers of bone metabolism were assessed including the serum markers bone-specific alkaline phosphatase, and carboxyterminal propeptide of type I procollagen, and the urine markers n-telopeptide (NTx) and deoxypyridinoline (DPD). Results: For all four markers, there were changes over time which were statistically significant. Markers indicating bone formation were slightly elevated after a 3-month period. In contrast, the two markers indicating bone resorption were back to normal after a 6-month period. There were differences between the groups with cemented and uncemented total hip arthroplasty in the postoperative course with higher values of the markers indicating bone resorption in the cemented group. However, these differences were not statistically significant. Conclusions: Our results indicate that the two markers of bone resorption, NTx and DPD, are elevated during the first 6 months after hip and knee arthroplasty. Therefore, during this period they cannot be used as a marker for aseptic loosening. However, if these two markers are still elevated after this period, they may reflect an impaired bone metabolism. Further studies are required to assess the potential value of these markers for the diagnosis of aseptic loosening.
Induction of hRAD9 Is Required for G2/M Checkpoint Signal Transduction in Gastric Cancer Cells
Authors: Hayashi Ken , Kuniyasu Hiroki , Oue Naohide , Shigeishi Hideo , Kuraoka Kazuya , Nakayama Hirofumi , Yasui Wataru
Published: April 2003

DNA damage triggers the activation of checkpoints that delay cell cycle progression to allow for DNA repair. Loss of G2 checkpoints provides a growth advantage for tumor cells undergoing aberrant mitosis. However, the precise mechanisms of G2 checkpoints acting in gastric cancer are unknown. Here, we analyzed the G2 checkpoint function in two gastric cancer cells, MKN-28 cells containing a mutant p53 gene and MKN-45 cells which have wild-type p53. Two agents damaging DNA, camptothecin (CPT) or ultraviolet light (UV), were utilized to trigger a G2 phase cell cycle checkpoint response in these tumor cells. Both CPT and UV inhibited the growth of MKN-45 cells, whereas they did not affect the growth of MKN-28 cells. CPT induced cell cycle arrest at the G2/M phase and enhanced the expression of human RAD9 (hRAD9) in MKN-45 cells. In addition, hRAD9 showed perinuclear staining and similar localization with Bcl-2 in MKN-45 cells but not in MKN-28 cells after having applied CPT or UV light. These results suggest that besides p53 activity, the induction of hRAD9 is required for G2/M checkpoint signal transduction in gastric cancer cells.
Cutoff Scores of the Cognitive Abilities Screening Instrument, Chinese Version in Screening of Dementia
Authors: Lin Ker-Neng , Wang Pei-Ning , Liu Chia-Yih , Chen Wei-Ta , Lee Yi-Chung , Liu Hsiu-Chih
Published: April 2003

The purpose of this study of dementia screening was to obtain different cutoff scores of the Cognitive Abilities Screening Instrument, Chinese versions (CASI C-2.0) for subjects with different educational backgrounds. The diagnosis of dementia was based on the Diagnostic and Statistical Manual of Mental Disorders, ed 3 revised or ed 4 criteria. To diagnose Alzheimer’s disease, the guidelines of the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association was followed. The severity of dementia was determined on the Clinical Dementia Rating scale. Altogether 2,096 subjects, aged 65 years and more, were included. Of them, 1,178 were normal and 918 were demented. Their performance on CASI C-2.0 was influenced by their education and age. Gender difference on CASI C-2.0 scores was only significant in the illiterate, but not in the literate group. We recommend that the population be divided into three levels, namely those who (1) had no formal education (Edu = 0); (2) received 1–5 years of schooling (Edu = 1–5), and (3) received 6 or more years of education (Edu ≧6). The cutoff scores of CASI C-2.0 in the diagnosis of dementia in these three educational groups were as follows: Edu = 0: 49/50 (sensitivity = 0.83; specificity = 0.85); Edu = 1–5: 67/68 (sensitivity = 0.83; specificity = 0.91), and Edu ≧6: 79/80 (sensitivity = 0.89; specificity = 0.90).
Role of Transtympanic Endoscopy of the Middle Ear in the Diagnosis of Perilymphatic Fistula in Patients with Sensorineural Hearing Loss or Vertigo
Authors: Selmani Z. , Pyykkö I. , Ishizaki H. , Marttila T.I.
Published: April 2003

Background: The diagnosis of perilymphatic fistula (PLF) is often difficult, and therefore the condition can be overlooked. Tympanoscopy presents an alternative procedure for visualising the middle ear anatomy, and it may help to diagnose PLF. Aim: The aim of this study was to evaluate the use of middle ear endoscopy in establishing the diagnosis of PLF and in defining its incidence in patients with sensorineural hearing loss and/or vertigo and tinnitus. Subjects and Methods: Two hundred and sixty-five patients (22–80 years of age, mean 48 years) were prospectively and consecutively referred for middle ear examination with tympanoscopy. Tympanoscopy was performed using endoscopes with visual angles of 5 and 25° and an outer diameter of 1.7 mm. The round window niche (with its secondary membrane), the oval window with a stapes superstructure, a part of the facial recess and the area in the fissula ante fenestram were examined and video-recorded. Results: For 1 patient, tympanoscopy revealed fistula in the round window membrane that was covered with a fibrinous layer. In 4 cases abnormal mucosal shining appeared in the round window, but no PLF was present. In 7 cases the tympanic cavity could not be visualised because of the adhesive tympanic membrane, abnormal anatomy or the prominent exostoses of the external ear canal. In 6 cases a postendoscopic middle ear infection was found. No permanent tympanic membrane perforation occurred in any of the patients in this study. Conclusions: Tympanoscopy is a rapid examination tool with which to verify certain areas of the middle ear anatomy, but it is of limited value for ruling out the presence of PLF.
Severe Hearing Loss in Pallister-Killian Syndrome
Authors: Schuster M. , Hoppe U. , Eysholdt U. , Rosanowski F.
Published: April 2003

Pallister-Killian syndrome is a rare disorder characterised by a specific combination of anatomic anomalies, mental retardation and lack of speech acquisition due to tetrasomy 12p. Hearing loss does not seem to be characteristic for this syndrome, although it was reported in several cases. We present the case of a girl first seen in our department at the age of 6 months. A severe sensory hearing loss was confirmed by subjective and objective audiometry. The child was successfully equipped with hearing aids. In the literature almost all children with Pallister-Killian syndrome are described as not developing verbal speech. Surprisingly their hearing abilities were not examined systematically. We advise audiological testing of children with Pallister-Killian syndrome.
Long-Term Results of a New Stapedotomy Prosthesis
Authors: Velegrakis George A. , Prokopakis Emmanuel P. , Karatzanis Alexander D. , Hatziioannou Jannis K. , Kyrmizakis Dionysios A. , Helidonis Emmanuel S.
Published: April 2003

The long-term results of a new, home-made stapedotomy prosthesis are presented. The innovations of this prosthesis concern both portions, design for attachment to the incus and shaft. Our series include a total number of 42 individuals with stapes fixation, operated using the new prosthesis, with a medical follow-up period between eighteen months and five years. Our innovations offer a proper and safe insertion of the prosthesis into the oval window associated with excellent manipulation and handling. These advantages could be of major importance for younger surgeons and trainees. Postoperative hearing results are similar to those achieved with other commercially available pistons.
Heroin Use in Slovenia – A Consequence or a Vehicle of Social Changes
Authors: Flaker Vito
Published: April 2003

Slovenia is a country in transition with a relatively successful record both in the economic and social spheres. It has not escaped all the adverse consequences of transition (high unemployment, especially among youths, changes in values). Massive heroin use has also started in the 90s, and there are approximately 450 intravenous drug users or 900 regular users per 100,000 inhabitants. Those groups that were uprooted in the process of transition (young people, males, immigrants) are vulnerable to problematic use. The HIV prevalence is extremely low, while that of hepatitis C is relatively substantial. Difficulties with employment, housing shortage and severed social ties are all the result of problematic heroin use as well as the factor that promotes it along with the changes in youth culture and social values. Poverty is probably one of the most important vectors towards destructive outcomes while postindustrial hedonistic individualism is an important cultural vehicle toward the increase in drug use.
Midterm Visual Outcome and Progression of Diabetic Retinopathy following Cataract Surgery
Authors: Schrey S. , Krepler K. , Biowski R. , Wedrich A.
Published: April 2003

Objective: To assess the influence of cataract surgery on progression of diabetic retinopathy and visual acuity. Methods: 37 patient eyes with mild to moderate diabetic retinopathy at baseline underwent phacoemulsification and intraocular posterior chamber lens implantation. They were examined 3.3 ± (SD) 0.7 years after surgery. Results: 83.8% of the eyes showed a better final visual acuity, and 67.6% achieved a final visual acuity of 0.5 or better. The retinopathy remained unchanged in 83.8% and progressed in 16.2% of the eyes. No eye progressed to proliferative retinopathy. Conclusion: Phacoemulsification and implantation of a posterior chamber intraocular lens is a safe procedure for patients with mild to moderate diabetic retinopathy.
Influence of Latanoprost on the Corneal Epithelial Barrier Function in Glaucoma Patients
Authors: Ishibashi Takeshi , Yokoi Norihiko , Ohtsuki Masanori , Mori Kazuhiko , Komuro Aoi , Kinoshita Shigeru
Published: April 2003

Aim: To evaluate the influence of topically administered latanoprost, a prostaglandin F2α analog, on the corneal epithelial barrier function. Patients and Methods: Twenty-four patients suffering from a glaucoma were enrolled. Ten patients without prior topical antiglaucoma medication received topical latanoprost (0.005%, once daily) for 30 days (monotherapy group); 14 patients receiving topical antiglaucoma medication also received latanoprost (0.005%, once daily) for 180 days (combination treatment group). Before and 30 days after treatment (monotherapy group) and before and 30 and 180 days after treatment (combination group), the corneal epithelial barrier function was measured by a fluorophotometric technique. Results: The fluorescein uptakes in the monotherapy group were 54.6 ± (SE) 7.5 and 57.1 ± 11.0 ng/ml before and 30 days after treatment, respectively (p = 0.81). In the combination group, the uptakes were 101.0 ± 18.3 and 118.9 ± 25.9 ng/ml (p = 0.38) and 93.4 ± 17.5 ng/ml (p = 0.58) before and 30 and 180 days after treatment, respectively. Conclusion: The corneal epithelial barrier function remained intact following the instillation of latanoprost in both groups.
Simple Dacryops: A Case Series and Review of the Literature
Authors: Betharia S.M. , Pushker Neelam , Sharma Vidushi , Sen Seema
Published: April 2003

In this prospective, small case series, 3 patients with simple dacryops were analyzed along with a review of literature. All 3 patients in this series had classical clinical features of simple dacryops. All of them underwent complete cyst removal with the aid of a cryoprobe. Histopathology was compatible with dacryops. In 2 of the 3 patients, the cyst revealed calcification, which to the best of our knowledge has not been reported. None of the patients developed a recurrence. In conclusion, simple dacryops is an easily recognized clinical entity. This entity has been infrequently reviewed in the older literature, and in the last decade only 6 cases have been reported. Most of the patients underwent complete excision of the cyst with no recurrences.
Significant Variation of the Elevated Nitric Oxide Levels in Aqueous Humor from Patients with Different Types of Glaucoma
Authors: Tsai Der-Chong , Hsu Wen-Ming , Chou Ching-Kuang , Chen Shih-Jen , Peng Chi-Hsien , Chi Chin-Wen , Ho Larry L.-T. , Liu Jorn-Hon , Chiou Shih-Hwa
Published: April 2003

Though several studies have shown that the biochemical function of nitric oxide (NO) in the eye might play an important role in the regulation of intraocular pressure (IOP), local control of ocular blood flow and loss of retinal ganglion cells by apoptosis, it is unclear whether the role of NO is similar in the pathogenesis of different kinds of glaucoma: primary open-angle glaucoma (POAG), chronic closed-angle glaucoma (CCAG) and neovascular glaucoma (NVG). To further explore this issue, we measured the concentrations of NO in aqueous humor and plasma samples from patients with POAG (n = 31), CCAG (n = 76), NVG (n = 8) and cataract (n = 30). All of the NVG patients suffered from severe proliferative diabetic retinopathy, while other patients were free of any other systemic disease. The NO levels in both aqueous humor and plasma samples were assessed by chemiluminescence assay. We found that the NO levels in aqueous humor samples were greatly varied in patients with POAG (36.2 ± 3.3 µM), CCAG (47.7 ± 3.4 µM) and NVG (65.8 ± 5.4 µM), and all of them were significantly higher than in cataract patients (27.0 ± 2.9 µM; p < 0.05). Except NVG patients whose NO levels in plasma samples were highest (24.1 ± 3.5 µM) among all groups, the plasma NO levels were not significantly different between the other glaucoma patients and the cataract patients. We therefore concluded that significant variation of the elevated NO levels in aqueous humor samples from the patients with different types of glaucoma may reflect their differences in the pathogenesis.
The Distribution of Long Range Admixture Linkage Disequilibrium in an African-American Population
Authors: Rybicki Benjamin A. , Iyengar Sudha K. , Harris Trent , Liptak Rachel , Elston Robert C. , Sheffer Roberta , Chen Kang Mei , Major Marcie , Maliarik Mary J. , Iannuzzi Michael C.
Published: April 2003

Objectives: To better understand the effect of admixture on long range linkage disequilibrium (LD), we characterized extended LD in gene-rich regions of an African-American population. Methods: Approximately 290 cM of chromosomes 1, 3, 6, 11–17, 20 and 22 were scanned using 109 polymorphic microsatellite markers spaced an average of 3 cM apart. Disequilibrium between loci (D′) was based on maximum-likelihood estimates of haplotype frequencies computed for 200 unrelated African Americans. Results: Mean D′ values were highest on chromosomes 6p23–p21.3 (D′ = 0.33) and 15p22.2–p25.3 (D′ = 0.34), and lowest on chromosome 12p11.2–q14 (D′ = 0.21). Overall, the variance in LD among chromosomes accounted for approximately two-thirds of the total LD variance. Of the 434 locus pairs spaced between 0.3 and 38.7 cM apart, there was no detectable correlation between LD and recombination distance and a weak negative correlation between LD and physical distance (rs = –0.12; p = 0.031). For the 192 intrachromosomal locus pairs where allele frequency data were available from the Centre d’Etude du Polymorphisme humain (CEPH), we found a statistically significant positive correlation between LD and the allelic frequency differences (δ) between the African-American study population and Caucasian reference CEPH population (rs = 0.53; p < 0.0001). The correlation between LD and both recombination and physical distance was markedly increased for locus pairs with high δ levels. Conclusions: Our results suggest that recent Caucasian admixture maintains a high level of long range LD in African Americans on a genomic scale, and selected markers with large African American/Caucasian δ levels may be useful in association studies.
Backward Haplotype Transmission Association (BHTA) Algorithm – A Fast Multiple-Marker Screening Method
Authors: Lo Shaw-Hwa , Zheng Tian
Published: April 2003

The mapping of complex traits is one of the most important and central areas of human genetics today. Recent attention has been focused on genome scans using a large number of marker loci. Because complex traits are typically caused by multiple genes, the common approaches of mapping them by testing markers one after another fail to capture the substantial information of interactions among disease loci. Here we propose a backward haplotype transmission association (BHTA) algorithm to address this problem. The algorithm can administer a screening on any disease model when case-parent trio data are available. It identifies the important subset of an original larger marker set by eliminating the markers of least significance, one at a time, after a complete evaluation of its importance. In contrast with the existing methods, three major advantages emerge from this approach. First, it can be applied flexibly to arbitrary markers, regardless of their locations. Second, it takes into account haplotype information; it is more powerful in detecting the multifactorial traits in the presence of haplotypic association. Finally, the proposed method can potentially prove to be more efficient in future genomewide scans, in terms of greater accuracy of gene detection and substantially reduced number of tests required in scans. We illustrate the performance of the algorithm with several examples, including one real data set with 31 markers for a study on the Gilles de la Tourette syndrome. Detailed theoretical justifications are also included, which explains why the algorithm is likely to select the ‘correct’ markers.