bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Ketotifen on the Production of Reactive Oxygen Species from Human Eosinophils Primed by Eotaxin
Authors: Yamada Yoshiyuki , Sannohe Satoshi , Saito Norihiro , Cui Chang-Hao , Ueki Shigeharu , Oyamada Hajime , Kanda Akira , Yamaguchi Kazutoshi , Hamada Kazuyuki , Adachi Tetsuya , Kayaba Hiroyuki , Chihara Junichi
Published: September 2003

Ketotifen is an antiallergic drug and may have direct inhibitory effects on eosinophils. To investigate the anti-eosinophilic effect of ketotifen, we examined the effect of ketotifen on the production of reactive oxygen species (ROS) from eotaxin-primed human eosinophils. Ketotifen at 10–10–10–6 mol/l significantly reduced the production of ROS evoked by A23187 from eosinophils primed by eotaxin. In contrast, ketotifen at 10–5 mol/l significantly augmented the production in the absence of eotaxin. We demonstrated that appropriate concentrations of ketotifen may have direct inhibitory effects on eosinophil oxidative metabolism primed by eotaxin. Ketotifen may contribute to the treatment of allergic disease through its anti-eosinophilic effects.
Antagonism between the Anti-Inflammatory Activity of the Cannabinoid WIN 55212-2 and SR 141716A
Authors: Pozzi Ottorino , Misiano Paola , Clark Geoffrey D. , Visentin Luciano
Published: September 2003

The CB1/CB2 receptor agonist WIN 55212-2 (0.75 mg/kg, i.v.) caused a significant reduction in neurogenic plasma extravasation induced by electrical stimulation of the saphenous nerve in anesthetized rats; WIN 55212-2 at 2.5–10 mg/kg, s.c., also produced a significant reduction in the carrageenan-induced paw edema in conscious rats. The selective CB1 antagonist SR 141716A (0.075–0.75 mg/kg i.v.) antagonized the WIN 55212-2 effects in the plasma extravasation model and antagonized the WIN 55212-2 (2.5 mg/kg, s.c.)-induced decreases in rectal temperature and increases in tail-flick latencies. However, SR 141716A (10 mg/kg, p.o.) failed to antagonize the effects of Win 55212-2 (2.5 mg/kg, s.c.) in the carrageenan model, suggesting that cannabinoid receptors found in the periphery may be able to modulate inflammatory processes in rats.
Patch Urethroplasty Using a Fascia lata Autograft in Male Rabbits
Authors: Campodonico F. , Michelazzi A. , Ognio E. , Favre A. , Carmignani G.
Published: September 2003

Introduction: Urethral reconstruction is difficult when the genital skin is not available for surgery. We evaluate the feasibility of using the autologous fascia lata as a graft for urethral repair. Materials and Methods: 10 male rabbits underwent urethroplasty after creation of a ventral urethral defect. The defect was repaired using a graft harvested from the fascia lata. The animals were divided into three groups and sacrificed at 2, 4 and 12 weeks postoperatively. Radiologic control was performed after 10–12 days and before sacrifice. Results: In the 10 rabbits subjected to surgery, no case of death or wound infection was observed. During urethrography, a fistula was observed in 2 animals. In the remainder (n = 8), histological analysis showed the preservation of the original laminar structure without graft shrinkage or fibrosis. On the luminal side of the patch, a new line of urothelium appeared in the 2nd week after surgery. After 3 months, the new epithelium was multilayered and the graft edges were not detectable. No voiding dysfunction was detectable in 8 rabbits. Conclusions: Our study suggests the feasibility of using the autologous fascia lata for urethral patch repair.
Comparison of Two Methods – Mathieu and Snodgrass – in Hypospadias Repair
Authors: İmamoğlu M. Abdurrahim , Bakırtaş Hasan
Published: September 2003

Introduction: Perimeatal flap (Mathieu) and tubularized incised-plate (Snodgrass) methods were compared regarding success rate, postoperative complications, and cosmetic appearance in primary and recurrent distal hypospadias cases with normal urethral plates. Patients and Methods: Between 1995 and 2001 Snodgrass-type repair was done in 32 primary and in 24 recurrent hypospadias cases (total 56 patients; mean age 5.8, age range 3–17 years), and Mathieu-type repair was done in 33 primary and in 21 recurrent distal hypospadias cases (total 54 patients; mean age 5.2, age range 2–19 years). There was no statistically significant difference between groups regarding demographics. Patients with primary hypospadias either without or with minimal chordee and patients with recurrent hypospadias only with a normal urethral plate were included in the study. The mean postoperative follow-up period was 24 months. Results: Meatal stricture formation, fistula formation, wound dehiscence, and flap necrosis were seen in 2, 4, 4, and 2 patients, respectively, treated with the Mathieu technique and in 5, 4, 3, and 0 patients, respectively, treated with the Snodgrass technique. Wound dehiscence and flap necrosis were seen less frequently, whereas meatal stenosis was more common in the Snodgrass group (p < 0.05, p < 0.05, and p > 0.05, respectively; χ2 test). There was no difference between groups regarding fistula formation. Mean hospital stay, time to stent withdrawal, and urinary diversion period were shorter in the Mathieu group (7.5 ± 1.19 vs. 5.7 ± 1.38 days, 7.1 ± 0.67 vs. 5.4 ± 0.85 days, and 14.1 ± 1.17 vs. 10.2 ± 1.72 days, respectively; p < 0.001 for all). The total success rates were similar (78.6% in the Snodgrass group and 77.8% in the Mathieu group). Cosmetic appearance was highly satisfactory in the Snodgrass group. Conclusions: We believe that the Snodgrass method should be preferred for primary and recurrent hypospadias cases without chordee or with minimal chordee and with a normal urethral plate due to its lower complication rate and its satisfactory cosmetic appearance. However, when a healthy urethral plate is not available, Mathieu-type repair can be preferred.
Cystectomy and Orthotopic Ileal Neobladder Construction
Authors: Verleyen P. , Billiet I. , Mattelaer J. , Hardeman M. , Werbrouck P.
Published: September 2003

Introduction: This study evaluates the outcome of orthotopic neobladder construction in a regional hospital setting. Material and Methods: Orthotopic ileal neobladders were constructed in 51 patients between 1990 and 2001. All complications were reported systematically and continence was evaluated in a standardized manner. Results: One patient died perioperatively (2%). Early complications occurred in 56.9%. They were related to the neobladder in 21.6% and unrelated to the neobladder in 47.1%. 31.4% experienced complications in the late postoperative period. In 25.5%, these complications were neobladder related and in 11.8% they were not. After 1 year, daytime continence was 91.7% and nighttime continence 80.6%. Our results are comparable to those reported by others. Conclusion: We conclude that the construction of a Hautmann neobladder can be performed with acceptable results in a regional hospital. The democratization of recent bladder replacement techniques may offer more patients a better quality of life and prevent the formation of waiting lists. Radical treatment may then be opted for sooner and thus improve cancer-related survival.
Increased Formation of 8-Hydroxy-2’-Deoxyguanosine in Peripheral Blood Leukocytes in Bladder Cancer
Authors: Akçay Tülay , Saygılı Ilker , Andican Gülnur , Yalçın Veli
Published: September 2003

Introduction: Reactive oxygen species-induced damage to DNA plays a major role in carcinogenesis. Methods: In order to estimate the level of oxidative damage in bladder cancer, 8-hydroxy-2′-deoxyguanosine (8-OHdG) was determined in DNA isolated from peripheral blood leukocytes of healthy adults and patients with superficial transitional cell carcinoma. Patients with transitional cell carcinoma of the bladder and control individuals were similar in age. In this study, the level of 8-OHdG in DNA in male subjects was measured by the high-performance liquid chromatography-electrochemical detector method. Results: The 8-OHdG levels in DNA from leukocytes of bladder cancer patients were significantly higher than those in controls. Conclusion: Reduction of oxidative stress is thought to be a very important measure for primary prevention of bladder cancer.
Relationship between Febrile Urinary Tract Infection and Urodynamics in Myelodysplastic Children with Vesicoureteral Reflux
Authors: Seki Narihito , Masuda Katsuaki , Tanaka Masatoshi , Kinukawa Naoko , Senoh Kouhei , Naito Seiji
Published: September 2003

Objective: We conducted a retrospective study in order to identify factors that may predict the incidence of febrile urinary tract infection (UTI) in myelodysplastic children with vesicoureteral reflux (VUR). Methods: A total of 23 myelodysplastic children with persistent VUR who were managed by clean intermittent catheterization (CIC) were eligible for this study. Any factors, including urodynamic parameters and urinary tract abnormalities, that may have been associated with the incidence of febrile UTI were evaluated using both univariate analysis and multiple logistic regression analysis. Results: Of 23 patients, 10 (43%) had had one or more episodes of febrile UTI. Both univariate and multivariate analyses showed a statistically significant relationship between low bladder compliance (<10 ml/cm H2O) and episodes of febrile UTI. Conclusion: These results demonstrated that the urodynamics linked to bladder function disorder in the filling phase appear to be correlated with the incidence of febrile UTI in myelodysplastic children with VUR who are managed by CIC.
Eosinophilic Cystitis
Authors: Kiliç Süleyman , Erguvan Rezzan , Ipek Deniz , Gökçe Hasan , Güneş Ali , Aydin N. Engin , Baydinç Can
Published: September 2003

Purpose: We present a large series of eosinophilic cystitis including 8 cases; 3 of them had tumor-like lesions. Materials and Methods: The archives of pathology clinic of Inonu University Medical Faculty were reviewed from 1988 to 2002. The characteristics of patients and their diseases were recorded. Data obtained from 180 cases (172 from the literature and 8 from the present series) was assessed. Results: Seven cases had symptoms such as dysuria, frequency, hematuria, suprapubic pain, and difficulty in voiding. One asymptomatic case with history of bladder carcinoma was diagnosed during routine cystoscopy. The findings were microhematuria in 6 cases, macrohematuria in 2, pyuria in 3, urinary infection in 1, eosinophilia in 1, hyperazotemia in 1, and bladder masses in 3. Cystoscopies detected edematous and erythematous areas in 5 cases and lesions mimicking bladder carcinoma in 3. One case did not take further treatment after cystoscopy and biopsy and completely recovered. Four cases underwent medical therapy with nonsteroidal anti-inflammatory drugs and antihistaminics. They became asymptomatic and control cystoscopies showed no abnormal finding. Two of three patients with mass lesions recovered after steroid therapy following transurethral resection. The lesion in the third recurred and he improved after a second course of steroid therapy. Conclusions: Eosinophilic cystitis is a rare pathology. Sometimes, it may simulate bladder malignancies. Biopsy is mandatory at diagnosis. Usually, it has a benign course and may be treated with fulguration, analgesics, antihistaminics and steroids, although recurrence is possible.
Pharmacological Effects of KRP-197 on the Human Isolated Urinary Bladder
Authors: Murakami Shigetaka , Yoshida Masaki , Iwashita Hitoshi , Otani Masayuki , Miyamae Koichi , Masunaga Koichi , Miyamoto Yutaka , Inadome Akito , Ueda Shoichi
Published: September 2003

KRP-197, 4-(2-methylimidazol-l-yl)-2,2-diphenylbutyramide, is a newly synthesized antimuscarinic drug, developed for the treatment for overactive bladder. For evaluation of pharmacological characteristics of KRP-197, we investigated whether it influenced both prejunctional and postjunctional muscarinic receptors on the isolated human detrusor smooth muscles as compared with the effects of atropine, oxybutynin, and propiverine. Using the muscle bath technique, we investigated the effects of various antimuscarinic drugs on the contractions induced by carbachol, KCl, CaCl2, and electrical field stimulation. Furthermore, using high-performance liquid chromatography with a microdialysis technique, we measured the acetylcholine release from the muscle strips during electrical field stimulation. The effects of various antimuscarinic drugs on acetylcholine releases were also evaluated. Pretreatment with various antimuscarinic drugs caused parallel shifts to the right in carbachol-induced concentration-response curves. The rank order of pA2 values was KRP-197 ≧ atropine > oxybutynin > propiverine. Atropine and KRP-197 did not cause significant inhibition of KCl- and CaCl2-induced contractions. All drugs caused concentration-dependent inhibitions in electrical field stimulation-induced contractions. Pretreatment with atropine and propiverine did not cause significant changes in electrical field stimulation-induced acetylcholine release. However, KRP-197, and oxybutynin caused significant decreases in acetylcholine release. The present study demonstrates that KRP-197 has an inhibitory effect on postjunctional muscarinic receptors as well as on prejunctional muscarinic receptors to modulate acetylcholine release in human detrusor smooth muscles. The findings suggest the usefulness of KRP-197 as a therapeutic drug for an overactive bladder with symptoms of frequency, urgency, and urge incontinence.
Comparison of Double Vertical Incision with Various Tubularization Techniques and Its Clinical Application
Authors: Yazici Mesut , Copcu Eray , Etensel Barlas , Culhaci Nil , Balkaya Muharrem , Özkisacik Sezen , Gürsoy Harun
Published: September 2003

Introduction: Tubularization is one of the indispensable practices of reconstructive surgery, especially in the repair of hypospadias. In all procedures of forming a tube, the desired diameter should be reached without any complication. Materials and Methods: We used as a new technique, ‘double vertical incision’, in 8 rabbits and compared it with free skin graft, local flap and single vertical incision. We formed 32 tubes randomly around an 8-french catheter using 7/0 PDS suture. Twenty-one days after the operation, the tubes were taken, randomized to staining with hematoxylin and eosin and with Masson’s trichrome and then subjected to histopathological examination. Inflammation, fibrosis and lumen diameter were statistically evaluated. Results: Widest lumen diameters were found in the double incision group and this result was statistically different when compared with the results of the other groups (p < 0.001). Conclusions: Double vertical incision is promising in that it is easier to perform, provides a desired amount of tissue in cases in which the urethral bed is narrow, and causes no scar. Based on the results we obtained, we applied double vertical incision, a modification of tubularized incised plate urethroplasty popularized by Snodgrass, in 4 patients. The tubes were not distended, their long-term follow-up showed no complication and a urethra of the desired diameter was obtained.
Emphysematous Perinephric Abscess without Diabetes or Urinary Obstruction
Authors: Pandey S. , Kumar S. , Dorairajan L.N. , Agarwal A. , Elangovan S.
Published: September 2003

Emphysematous pyelonephritis is a rare disease seen usually in patients with diabetes mellitus or obstructive uropathy. We report a case of emphysematous pyelonephritis in a male who had no evidence of diabetes or obstructive uropathy. Such an occurrence of emphysematous pyelonephritis without diabetes or obstructive uropathy is very rare. The patient was managed with antibiotics, supportive measures and surgical drainage and he recovered completely.
Cavernous Hemangioma of the Renal Hilum Presenting as an Avascularized Solid Mass
Authors: Virgili Guido , Di Stasi Savino Mauro , Bove Pierluigi , Orlandi Augusto , Preziosi Paolo , Vespasiani Giuseppe
Published: September 2003

Hemangiomas are slowly growing benign vascular tumours which rarely involve the kidney. They usually occur in the mucosa or subepithelial tissue of the pelvis, in the pyramid of the kidney and in the cortex. We report a case of cavernous hemangioma presenting as a solid, paradoxically avascular mass of the right renal hilum.
Vesicoureteral Junction Obstruction Associated with Unilateral Renal Agenesis
Authors: Matsukura Hiro , Toyoshima Shinichiro , Inaba Susumu , Miyanaki Toshio , Miyamoto Masatoshi
Published: September 2003

A 7-month-old boy with a solitary kidney showed recurrent urinary tract infection. Magnetic resonance urography helps in the identification of vesicoureteral junction obstruction associated with unilateral renal agenesis.
Extrarenal Calyces: A Rarity
Authors: Garg Pradeep , Godara Rajesh , Karwasra R.K.
Published: September 2003

Extrarenal calyces are an extremely rare entity and only a few cases have been reported worldwide. We report a case with extrarenal calyces and give a brief review of the literature. Awareness of this rare entity can prevent inadvertent injury to the pelvicalyceal system during surgery.
A Culture Device Demonstrates that Hydrostatic Pressure Increases mRNA of RGS5 in Neuroblastoma and CHC1-L in Lymphocytic Cells
Authors: Manome Yoshinobu , Saeki Natsumi , Yoshinaga Hisao , Watanabe Michiko , Mizuno Shuichi
Published: September 2003

Previous studies demonstrated that mechanical forces affect a wide range of cellular behaviors. These forces regulate important cellular responses in the human body and consist of gravity, hydrostatic pressure, stretch, and shear stress, which is exerted on the vascular system by the passage of blood flow. We reasoned that these forces might be significant and dynamic regulators of cellular functions within the human body. While cellular effects of stretch and shear stress have been studied particularly with endothelial cells, little is known about the effects of gravity and hydrostatic pressure to cells. To examine the direct effect of hydrostatic pressure, we developed a culture device to confer hydrostatic pressures to cells ranging from 0 to 1,000 psi. We subjected human neuroblastoma cells and rIL-2-activated lymphocytes to a constant pressure of 20 or 100 psi for 48 h and attempted to identify genes regulated by hydrostatic pressure. Genes of regulator of G-protein signaling 5 in neuroblastoma cells and CHC1-L in lymphocytes increased after exposure to hydrostatic pressure. The results demonstrated that hydrostatic pressure directly regulates the expression of specific genes in mammalian cells. Moreover, there may be some underlying mechanisms that have common effects in altered physical environments. Our in vitro culture system may provide some insight into the mechanisms through the intracellular processes affected by mechanical forces.
Blood-Tissue Barriers in the Male Reproductive Tract of the Dog: A Morphological Study Using Lanthanum Nitrate as an Electron-Opaque Tracer
Authors: Cambrosio Mann Mireille , Friess Armin E. , Stoffel Michael H.
Published: September 2003

Blood-tissue barriers preventing an uncontrolled exchange of larger molecules between adjacent but metabolically separate compartments have been demonstrated in various organs. One prominent example is the blood-testis barrier which has been investigated in a number of species. A key function of this barrier is to shield developing germ cells from the immune system in order to avoid autoimmune reactions. This requirement also applies to the male excurrent duct system. Yet, very few investigations have addressed the morphology of the blood-epididymal barrier. The goal of the present study, therefore, was to revisit the blood-testis barrier in the dog and to identify the structures constituting the blood-epididymal barrier in this species. Lanthanum nitrate was used as a tracer for electron microscopy. In the testis, lanthanum had free access to the intercellular space of the seminiferous epithelium up to the Sertoli cell junctions. Similarly, epithelial tight junctions were found to represent the permeability barrier in the epididymis. The present study highlights species differences with respect to the blood-testis barrier and extends the knowledge of the blood-epididymal barrier by providing morphofunctional data in this domestic species.
Collagen Types I, III and IV in the Placentome and Interplacentomal Maternal and Fetal Tissues in Normal Cows and in Cattle with Retention of Fetal Membranes
Authors: Boos A. , Stelljes A. , Kohtes J.
Published: September 2003

The increase in uterine mass during pregnancy requires the establishment of sufficient blood supply to and strong supportive elements within the uterus. These needs are correlated with the remodelling and production of ECM materials. Therefore, placentomes and interplacentomal parts of the uterine walls and adherent allantochorion were collected from 45 cows at slaughter. Additional placentomes were obtained from 5 cows at premature cesarean section and at term in 5 cows releasing their fetal membranes in time or in 5 animals with retention of the fetal membranes, i.e. in total 60 pregnancies. Unfixed cryostat sections from 4 animals per month of pregnancy and 5 animals per peripartal group (in total 51 pregnancies) were used to immunolocalize collagen types I, III, and IV by an indirect FITC method. Collagen types I and III co-localize within the uterus. The tensile strength of the pregnant uterus is mainly represented by high contents of collagen type I within the allantochorion and subepithelial endometrial and subserosal meshes. Chorionic villi are fixed within caruncular crypts by two mechanisms: crypt openings are narrow and supplied with thick edges containing collagen types I and III. Collagen type IV contributes to all basement membranes and encloses connective tissue cells within the maternal crypt stroma, the stratum compactum and the perimetrial connective tissue. At term, fetal membranes and placentomes are edematous and at the light-microscopic level no distinct differences are visible between connective tissue fibers of placentomes from animals retaining the fetal membranes and those releasing them in time. In conclusion, collagen types I, III and IV exhibit type- and location-specific distribution patterns within the uterus of the pregnant cow. These may additionally be influenced by the stage of pregnancy, thus reflecting the dynamic processes at the stromal level.
Hypercholesterolemia-Induced Long-Term Increase of Macrophages in the Myocardium of New Zealand White Rabbits
Authors: Kinscherf Ralf , Kamencic Huse , Deigner Hans-Peter , Metz Jürgen
Published: September 2003

The effect of hypercholesterolemia on the number, immunological phenotype and oxidative stress-dependent processes of macrophages (MΦ) and dendritic cells (DC) was studied in New Zealand White rabbits. The left ventricular myocardium was immunohistochemically analyzed in group I (control), which was on standard chow, and groups II and III, which both received a 0.5% cholesterol-enriched diet for 96 days, but thereafter, only group III was fed standard chow for 4 months. In the myocardial interstitium of group I, (1) significantly less RAM-11-immunoreactive (ir) MΦ than S-100-ir DC were found; (2) both, MΦ and DC, were similar major histocompatibility complex (MHC) class II molecules LN3-, ISCR3-, and 2.06-ir; (3) all MΦ and most DC were manganese superoxide dismutase (MnSOD)-ir and homing receptor CD44-ir. In group II, only MΦ increased about 10-fold in the myocardium in parallel to the about 40-fold increase of the serum cholesterol levels. In group III, the elevated serum cholesterol levels significantly decreased (about 90%), while the MΦ still remained significantly increased (about 8-fold). The cellular immunoreactivities of MHC class II molecules, as well as MnSOD and CD44 did not change in groups II and III in comparison to group I. We suggest that mainly the MΦ, which increase within the myocardium of rabbits after elevation of serum cholesterol levels and remain significantly increased for a long time after decrease of the blood lipid levels, might initiate or aggravate eventual complications such as coronary atherosclerosis and myocardial fibrosis.
The Intrinsic Organization of the Nucleus lentiformis mesencephali magnocellularis: A Light- and Electron-Microscopic Examination
Authors: Zayats N. , Eyre M.D. , Némeh A. , Tömböl T.
Published: September 2003

The nucleus lentiformis mesencephali magnocellularis (nLMmc) is an essential part of the accessory optic nuclei and is responsible for stabilization of the horizontal eye movement. The morphology of this nucleus and its intrinsic structural connectivity were studied with Golgi, biotinylated dextran amine anterograde immunotracer and GABA immunostaining methods by light and electron microscopy. In the Golgi preparations neurons of large, medium-large, medium and small sizes were distinguished. The small neurons are GABA-immunopositive local circuit neurons, the others are proposed to be partly projection, partly local circuit neurons. The large and medium-large projection neurons are located in a tight topographical relationship observed in the Golgi preparations. The dendrites of the large and medium-large cells are also observed to be in close proximity with each other, and also with retinal fibre terminals. The morphological arrangement suggests that the retinal fibres make synaptic contacts with dendrites from both types of cell, and this is confirmed by the examination of retinal fibre terminals using electron microscopy. The optic fibre terminals establish synaptic contacts with small dendritic branches, dendritic processes and dendritic spines of large and medium-large neurons in the nLMmc. This arrangement allows the two types of nLMmc neuron access to very similar, if not identical, inputs, which may facilitate some of the different aspects of visual processing. Optic transmission by these cells may be modulated by the GABA-immunopositive terminals from various local circuit neurons, and very probably from GABAergic myelinated fibres as well, which may originate from the contralateral nLMmc and/or the visual Wulst.
The Roots of Empathy: The Shared Manifold Hypothesis and the Neural Basis of Intersubjectivity
Authors: Gallese Vittorio
Published: September 2003

Starting from a neurobiological standpoint, I will propose that our capacity to understand others as intentional agents, far from being exclusively dependent upon mentalistic/linguistic abilities, be deeply grounded in the relational nature of our interactions with the world. According to this hypothesis, an implicit, prereflexive form of understanding of other individuals is based on the strong sense of identity binding us to them. We share with our conspecifics a multiplicity of states that include actions, sensations and emotions. A new conceptual tool able to capture the richness of the experiences we share with others will be introduced: the shared manifold of intersubjectivity. I will posit that it is through this shared manifold that it is possible for us to recognize other human beings as similar to us. It is just because of this shared manifold that intersubjective communication and ascription of intentionality become possible. It will be argued that the same neural structures that are involved in processing and controlling executed actions, felt sensations and emotions are also active when the same actions, sensations and emotions are to be detected in others. It therefore appears that a whole range of different ‘mirror matching mechanisms’ may be present in our brain. This matching mechanism, constituted by mirror neurons originally discovered and described in the domain of action, could well be a basic organizational feature of our brain, enabling our rich and diversified intersubjective experiences. This perspective is in a position to offer a global approach to the understanding of the vulnerability to major psychoses such as schizophrenia.
Subtypes and Factors of Schizophrenia in an Acutely Ill Nigerian Sample
Authors: Ohaeri Jude U. , Otote David I.
Published: September 2003

The objectives of the study were to assess the factors that would emerge from combining the ratings based on the Brief Psychiatric Rating Scale, Scale for Assessment of Negative Symptoms and ICD-10 diagnostic criteria for research, and examine the stability of these factors at the third month of treatment; to highlight the correlates of these factors, and to compare the factors yielded with those of previous reports. Principal component analysis with varimax rotation was performed on the ratings of 65 males and 37 females, aged 33.7 ± 8.4 years (SD), with a duration of illness of 7.3 ± 6.6 years. Five conceptually meaningful factors emerged, accounting for 61% of the variance. The first 2 factors (diminished expression or psychomotor poverty, and social dysfunction or disordered relating) are negative syndromes, followed by disorganization, catatonic and excitement syndromes. These factors did not endure at the third month. The disorganization syndrome was significantly correlated with duration of illness, while age was inversely correlated with the catatonic syndrome; however, the score on a measure of soft signs of neurological dysfunction was not significantly correlated with the negative syndromes. In spite of hallucinations and delusions not loading significantly on any factor, the individual factors were highly similar to those of previous studies. But the instability of the negative syndromes, coupled with the results of previous Nigerian short-term outcome studies, casts doubt on the validity of the concept of deficit schizophrenia in this and other treated noninstitutionalized schizophrenics in Nigeria.
Psychopathological Dimensions in Childhood and Adolescent Psychoses: A Confirmatory Factor Analytical Study
Authors: Thakur Anupam , Jagadheesan K. , Sinha Vinod K.
Published: September 2003

The present study explored psychopathological dimensions in psychoses of children and adolescents and the distribution of demographic and clinical variables across different psychopathological domains. This study included 101 consecutive patients aged 6–18 years who had a DSM-IV psychotic disorder (schizophrenia and related disorders or mood disorders). Exclusion criteria included presence of organicity, substance use disorders, and any other childhood disorder. Psychopathology was assessed with Scales for Assessment of Positive and Negative Symptoms. Analysis revealed a four-factor model comprising primary negative, secondary negative, manic and paranoid factors. Patients were regrouped into one of the four factors based on their symptomatology. Patients in these four groups differed in education and age of onset and duration of illness. This study confirmed the existence of a factor structure in psychoses of children and adolescents.
The Role of Gender in Depressive Mixed State
Authors: Benazzi Franco
Published: September 2003

Background: Gender is an important variable in the study of mood disorders. Study aims were to find the prevalence of women, and to study gender differences in depressive mixed state (DMX), a major depressive episode (MDE) with few concurrent hypomanic symptoms. Sampling and Methods: Consecutive 173 unipolar and 260 bipolar II MDE outpatients were interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders – Clinician Version. The variables studied were gender, age, age at onset of the first MDE, number of MDEs, MDE chronicity, atypical, melancholic, and psychotic features, axis I comorbidity, MDE severity, hypomanic symptoms, and DMX3 (DMX defined as MDE plus 3 or more concurrent hypomanic symptoms). Results: Significantly more females than males had DMX3 vs. non-DMX3 (73.6 vs. 57.8%, p = 0.0006). Females were significantly associated with atypical features and psychomotor agitation in the DMX3 sample. Conclusions: Findings suggest that females may be more likely than males to have DMX (as defined in the present study), opening the way to speculations about the biological relationship between female gender and DMX. Limitations of the study were a single interviewer and a nonblind assessment.
Gender Differences and Hormonal Modulation of G Proteins Gαq/11 Expression in Lymphoid Organs
Authors: Morton Terri L. , Ansari Mansoor A. , Jacobson Jill D.
Published: September 2003

Androgens and estrogens exert potent divergent feedback effects on gonadotropin-releasing hormone (GnRH) production at the level of the hypothalamus and GnRH action at the level of the pituitary. Androgens exert generally suppressive effects on GnRH production and action, whereas rising levels of estradiol increase both GnRH release and action. In addition to its known endocrine actions, GnRH possesses immunomodulatory effects. We have previously demonstrated gender differences in immune responsiveness to GnRH that parallel gender differences in endocrine responsiveness: females appear to be more immunologically responsive to GnRH than males. GnRH exerts its actions via the stimulatory G protein Gαq and Gα11 (referred to collectively as Gαq/11) as well as via Gαs. We have recently demonstrated that the heightened immune responsiveness to GnRH in lupus-prone female mice correlated with increased expression of Gαq/11 in lymphoid cells from females compared to males. We hypothesize that the hormonal milieu of females may contribute to increased expression of stimulatory G proteins and to the heightened immune and endocrine responsiveness to GnRH. In this report, we document gender differences in expression of Gαq/11 protein in lymphoid organs in non-autoimmune DBA/2 mice. In an effort to address the mechanisms for the gender differences in G-protein expression, we used competitive reverse transcription PCR to quantitate mRNA for stimulatory G proteins in immune cells under various hormonal conditions. We quantitated the expression of Gαq/11 mRNA and protein under physiologic hormonal alterations, i.e. throughout the estrous cycle in female mice. We demonstrate that expression of Gαq/11 mRNA and protein in lymphoid organs is significantly increased on the afternoon of proestrus compared to metestrus. Additional studies demonstrate that exposure to GnRH or to estrogens significantly increases the expression of Gαq/11 mRNA in immune cells. These findings support an active role for hormonal modulation of G proteins in the gender differences in endocrinologic and immunologic responsiveness to GnRH.
Treatment-Seeking Inpatient Cocaine Abusers Show Hypothalamic Dysregulation of Both Basal Prolactin and Cortisol Secretion
Authors: Contoreggi Carlo , Herning Ronald I. , Koeppl Bonnie , Simpson Pippa M. , Negro Jr. Paulo J. , Fortner-Burton Carolyn , Hess Judith
Published: September 2003

Cocaine causes neuroendocrine aberrations in cocaine abusers with pituitary stress hormone secretion providing a window to the stress system in the brain. Substance abusers and control participants were hormonally profiled for 3 weeks. Abusers showed significant basal elevations in prolactin in week 1 with normalization over the 3 weeks. No differences in prolactin secretion were seen with either thyrotropin-releasing hormone stimulation or L-dopa suppression testing. Basal afternoon cortisol secretion was significantly elevated during weeks 1 and 2 comparing abusers to controls. Elevated afternoon cortisol secretion is a sensitive indicator of central stress activation. These results point to the hypothalamus, not the pituitary gland, as being primarily altered in cocaine withdrawal. The data demonstrate that both the dopamine-prolactin and hypothalamic-pituitary-adrenal (HPA) axes are affected during cocaine cessation. As medications are developed to modulate activation of a dysfunctional stress system, future therapeutic studies of substance abuse, withdrawal, craving and relapse should employ more sophisticated tests of hypothalamic pituitary function, especially the HPA axis, as this information may be a guide in the diagnosis and predict clinical responses.
Role of Glucocorticoids in the Regulation of Pituitary Somatostatin Receptor Subtype (sst1–sst5) mRNA Levels: Evidence for Direct and Somatostatin-Mediated Effects
Authors: Park Seungjoon , Kamegai Jun , Kineman Rhonda D.
Published: September 2003

Glucocorticoids can differentially regulate somatostatin (SRIH) receptor subtype expression depending on the duration of treatment, dose used and tissue type examined. In order to determine if glucocorticoids are critical regulators of pituitary SRIH receptor synthesis in vivo, we examined the effect of adrenalectomy (ADX), with and without dexamethasone (DEX; 200 µg/day for 8 days) treatment, on the relative expression levels of the SRIH receptor subtypes, sst1–sst5, by multiplex RT-PCR. ADX increased pituitary sst2 mRNA levels, but did not significantly alter mRNA levels of the other SRIH receptor subtypes. These findings indicate that pituitary sst2 synthesis is normally under inhibitory control of endogenous glucocorticoids. High-dose DEX resulted in a decrease in sst1–sst4 mRNA and an increase in sst5 mRNA, independent of adrenal status. DEX also decreased sst2, sst3 and sst4 mRNA levels and increased sst5 mRNA levels by short-term in vitro application (10 nM, 4 h) in primary rat pituitary cell cultures, indicating DEX regulation of sst2–sst5 in vivo is at least in part due to a direct action at the level of the pituitary. However, the inhibitory actions of DEX on sst1 mRNA levels observed in vivo were not consistently replicated in vitro. In order to determine if the somatotrope population of the pituitary would display a similar response to DEX, fluorescent-activated cell sorting was used to obtain somatotrope-enriched cultures (>95% growth hormone immunopositive cells). DEX treatment (10 nM, 4 h) of somatotropes decreased sst2 and sst3, but did not alter sst5 mRNA levels. These results indicate that the effects of DEX on sst5 mRNA levels observed in unsorted pituitary cell cultures might be due to changes in sst5 expression in pituitary cell types other than somatotropes. Since excess glucocorticoids are thought to enhance SRIH tone, we also tested if ligand activation of SRIH receptor subtypes in vitro could mimic any of the actions of DEX on SRIH receptor mRNA levels observed in vivo. To this end, unsorted pituitary cell cultures and somatotrope-enriched cultures were treated with SRIH (1 and 100 nM) for 4 h. SRIH increased sst3 and sst5 mRNA levels, in both culture systems. These results suggest that the DEX-induced increase in endogenous SRIH tone may contribute to enhanced sst5 mRNA levels observed in vivo. However, the stimulatory actions of SRIH on sst3 mRNA levels observed in vitro might be overridden by direct inhibitory actions of DEX.
Adrenal Enucleation in MSG-Damaged Hyperleptinemic Male Rats Transiently Restores Adrenal Sensitivity to Leptin
Authors: Perelló Mario , Gaillard Rolf C. , Chisari Andrea , Spinedi Eduardo
Published: September 2003

It is known that the neonatal treatment of rats with monosodium L-glutamate (MSG) induces several metabolic abnormalities, resulting in enhanced adiposity and hyperleptinemia. Our study was designed to explore the consequences of MSG-induced chronic hyperleptinemia on adrenal sensitivity to the inhibitory effect of exogenous leptin. Neonatal male rats treated with MSG or vehicle (controls, CTR) were followed during 150 days in order to study changes observed over development in body weight, food consumption as well as in vivo hypothalamo-pituitary-adrenal (HPA) axis and adipocyte functions. During adulthood, adrenal response to adrenocorticotropin (ACTH) was evaluated both in vitro and in vivo in order to determine the adrenal sensitivity to the inhibitory effect of leptin. For this purpose, sham-operated as well as CTR and MSG rats with bilateral adrenal enucleation (AE) were used. Our results indicate that: (1) between 30 and 150 days of age, MSG animals developed hypophagia, accompanied by arrest in body weight gain, and concomitant enhanced basal levels of all HPA axis components and of leptin; (2) adrenals from of 150-day- old MSG rats displayed an in vitro adrenocortical hyperresponse to ACTH stimulation as well as an adrenal refractoriness to the physiological inhibitory effect of leptin on ACTH-stimulated glucocorticoid output, and (3) bilateral AE in adult MSG-treated rats transiently reversed the MSG-induced hyperleptinemia, restoring normal leptin levels as well as a normal adrenal sensitivity to the inhibitory effect of leptin. Our data indicate that adrenal exposure to the chronically high plasma leptin levels observed in MSG rats is involved in the loss of the inhibitory regulatory effect of leptin at the adrenal level, being therefore, at least in part, responsible for the increased total and free glucocorticoid production measured in MSG adult rats. Furthermore, this study strongly suggests that the adrenal overfunction, frequently associated with different phenotypes of obesity, could be due to an adrenal resistance to the leptin-negative regulation.
A 6-Year Study of Cognition and Spatial Function in the Demented and Non-Demented Elderly: The Sydney Older Persons Study
Authors: Bennett Hayley P. , Piguet Olivier , Grayson David A. , Creasey Helen , Waite L.M. , Broe G.A. , Halliday G.M.
Published: September 2003

Background: Spatial function has been suggested to be disproportionately worse in people with dementia with Lewy bodies (DLB) than other dementia groups, and poor performance on the Mini-Mental State Examination pentagon copying (PC) task has been proposed as adequate for assessing this. We aimed to establish the prevalence of poor PC in the non-demented elderly; determine the validity of the use of PC as a spatial function test, and determine if poor PC is more common in DLB than non-DLB dementias. Methods: In a population-based sample of 299 participants, 126 were rated as being cognitively normal (clinical rating scale [CDR] = 0), 95 mildly cognitively impaired (CDR = 0.5), and 78 met criteria for dementia, 19 of whom met criteria for probable DLB (pDLB) and 25 with none of the core features of DLB (non-DLB). The accuracy of PC performance was determined across CDR groups, and the relationship of PC to performance on a broad range of cognitive tests was evaluated. The dementia groups were compared cross-sectionally to determine differences in PC and other cognitive test performance, as well as 3 and 6 years earlier to determine cognitive differences at initial stages of cognitive decline. Results: Poor PC was common in the non-demented elderly (39% CDR = 0; 43% CDR = 0.5). In this non-demented group, PC was selectively related to tests of spatial function. Poor PC was not significantly different in the pDLB and non-DLB groups at any assessment time, however it became more prevalent as dementia severity increased. Memory function and verbal fluency were more impaired in the pDLB group in the early stages of the disorder. Comment: PC appears to be a good measure of spatial function in the elderly. However, in contrast to other findings of poor spatial skills in DLB when dementia is in the mild to moderate stages, poor PC performance has not been shown to be a good early marker of DLB and its clinical correlates are yet to be determined.
Neocortical Glial Cell Numbers in Alzheimer’s Disease
Authors: Pelvig Dorte P. , Pakkenberg Henning , Regeur Lisbeth , Oster Solveig , Pakkenberg Bente
Published: September 2003

Most studies agree that specific regions of the hippocampus and specific subcortical regions show neuronal loss in Alzheimer’s disease (AD). The aim of the study was to use design-based stereological methods to obtain an estimate of the total glial cell population in 14 AD cases and 20 controls to determine whether brains from AD patients have a different number of neocortical glial cells than controls. The mean total number of neocortical glial cells was 25.9 × 109 for the AD group and 29.1 × 109 for the control group, 2p = 0.18. The mean total number of neocortical neurons was 18.9 × 109 for the AD group and 21.2 × 109 for the control group, 2p = 0.059. Estimates of the sum of all glial cells and neurons in the neocortex were in the order of 50 billion cells with a glia to neuron ratio of 1.37 in both groups.
Life Situation, Coping and Quality of Life in People with High and Low Risk of Developing Alzheimer’s Disease
Authors: Axelman Karin , Lannfelt Lars , Almkvist Ove , Carlsson Marianne
Published: September 2003

The psychosocial consequences of being at different risk for inheriting Alzheimer’s disease (AD) were investigated in a high-risk group (n = 106) and a low-risk group (n = 37). Non-affected individuals from families with AD in two or more generations answered questions about their life situation, quality of life and coping. Their answers were compared with a population sample (n = 408). The high-risk group assessed the quality of their personal relationships and everyday life higher than did the population sample. They also used less emotive and supportive coping strategies compared with the population sample. Nearly 90% in the high-risk group felt anxiety concerning their own risk or the risk of their children and grandchildren of developing AD. About 50% of the respondents complained about a lack of information. The pieces of information they asked for were early signs of the disease, treatment, and practical information on how to handle everyday life with an affected relative.
Systematic Review and Meta-Analysis Show that Dementia with Lewy Bodies Is a Visual-Perceptual and Attentional-Executive Dementia
Authors: Collerton Daniel , Burn David , McKeith Ian , O’Brien John
Published: September 2003

To resolve differences in the literature, we have systematically reviewed 21 controlled comparisons of the cognitive performance of patients with dementia with Lewy bodies (DLB) These were identified by end May 2002 by Medline and PsycInfo searches, checking reference lists and contacting authors. Nine had comparisons between DLB patients (total n = 180) and age-matched controls (n = 172). Sixteen had comparisons between DLB (n = 312) and Alzheimer’s disease (AD, n = 380). Three compared DLB (n = 48) with Parkinson’s disease (PD, n = 65). Two raters independently scored the methodological quality. This was variable with a lack of high-quality studies (median rating 3 on a 0–7 scale, Kw = 0.41). There was a significant heterogeneity in results with marked discrepancies between studies. In a meta-analysis, DLB patients were more cognitively impaired than were AD or PD patients (95% CI of inverse variance weighted average of effect size relative to controls DLB 2.0–2.2; AD 1.4–1.6; PD 0.7–1.0). To permit an analysis of impairments in specific cognitive areas, the cognitive abilities underpinning the wide variety of tasks used were classified by a group of experienced neuropsychologists. Reducing overlapping task classifications using factor analysis showed large effect sizes relative to controls, AD and PD on two factors (combined variance 30%): attentional/executive impairment (effect sizes 1.1–2.9) and visual-perceptual impairment (0.7–3.6). There were small differences on two other factors (combined variance 39%): general verbal/non-verbal impairment (–0.12 to –0.5) and relative verbal memory impairment (–0.33 to 0.21). The cognitive performance is also more variable in DLB than in controls or in AD, but not PD (ratio of DLB to comparator standard deviations estimated from linear regression: DLB/controls 2.5–3.6; DLB/AD 2.1–2.6; DLB/PD 0.8–1.0). The greater variability of patients with DLB is seen only on tasks needing timed or motor responses, visual learning, executive or attentional abilities, or with visual content. Further stratification indicated that recent consensus diagnostic criteria, clinical diagnoses, and milder dementia were all associated with a more distinctive cognitive profile. The uniquely profound visual-perceptual and attentional-executive impairments that characterize DLB are consistent with the most frequent locations of Lewy bodies in frontal, cingulate, and inferior temporal cortex and may be related to the characteristic visual hallucinations and clinical fluctuations of this disease. These findings need to be confirmed in prospective, longitudinal, clinicopathological studies.