bluuebunny/crossref_metadata_2025 huggingface dataset:
Intralesional interferon in the treatment of Peyronie's disease: a pilot study
Authors: Judge J.S. , Wisniewski Z.S.
Published: November 2003

Objective  To investigate the effect of intralesional interferon on patients with severe Peyronie's disease.

Patients and methods  Thirteen patients with Peyronie's disease and associated penile deformity of greater than 12 months' duration were selected. Characteristics of the plaque and the degree of deformity were measured objectively. Ten patients received 1.5 MU of α2B‐interferon intralesionally three times a week for 3 weeks. Three patients received similar volumes of intralesional saline.

Results  Six of the 10 patients who received interferon reported the complete disappearance of pain on erection and an improvement in the penile deformity. Although the objective improvement in deformity was relatively small, with a mean improvement of 20°, patients with a small plaque (<4 cm) had a better response. All those receiving inferferon had predictable but brief side‐effects similar to the symptoms of influenza.

Conclusion  Intralesional interferon is safe and well tolerated and results in symptomatic and some objective improvement, especially in patients with smaller Peyronie's plaques.
Elective conservative surgery for renal carcinoma versus radical nephrectomy: a prospective study
Authors: D'Armiento M. , Damiano R. , Feleppa B. , Perdonà S. , Oriani G. , De Sio M.
Published: November 2003

Objective  To identify criteria with which to select candidates for conservative nephrectomy, and to compare the results of radical and conservative nephrectomy in two homogeneous groups of patients with renal carcinoma, in a prospective study.

Patients and methods  Forty patients (27 men and 13 women, mean age 49.9 years, range 23–76) with renal carcinoma (T1‐T2 N0M0,<4 cm in diameter) were enrolled in the study between 1988 and 1993 and followed for a maximum of 98 months (mean 70.1). The patients were divided into two groups: Group A comprised 19 patients (mean age 51.4, sd 13.7 years, mean tumour size 3.34, sd 0.64 cm) who underwent partial nephrectomy; Group B comprised 21 patients (mean age 48.7, sd 14.7 years, mean tumour size 3.21, sd 0.56 cm) who were selected for radical nephrectomy. The survival and progression of disease were assessed.

Results  Survival did not differ between the groups; one patient from each group died from distant metastases. There were no cases of local recurrence and multifocal neoplastic lesions were found in one patient during surgery.

Conclusion  This prospective study confirms the results of retrospective studies that conservative surgery is as effective as radical surgery for renal carcinoma; however, its clinical application is limited by the risk that the renal carcinoma is multifocal.
Out‐patient surgery for the correction of penile curvature
Authors: Hsu G‐L. , Chen S‐H. , Weng S‐S.
Published: November 2003

Objective  To evaluate an outpatient anaesthetic and surgical procedure for the correction of curvature of the penis.

Patients and methods  From February 1993 to December 1995, 128 patients (mean age 31 years, range 14–67) with penile curvature (120 with congenital curvature and eight with penile deformity from Peyronie's disease) were treated as out‐patients at our institution using a proximal dorsal nerve block and ventral infiltration of the penis as the method of anaesthesia. The degree of deformity, pain and sexual activity were assessed before and after surgery and all patients were followed post‐operatively using a questionnaire to determine the outcome and their satisfaction.

Results  All the patients were able to leave the hospital shortly after surgery. The follow‐up period ranged from 4 to 35 months (mean 17.3); 112 patients (87.5%) reported a satisfactory cosmetic and functional result, while the other 16 patients reported an improvement but had inadequate correction. There were no significant short‐ or long‐term complications; three patients with diabetes developed a hard lump over the operated tunica.

Conclusions  This unique operative method provided excellent correction of the deformities, was safe, cost‐efficient and durable and could be performed as an out‐patient procedure.
Transurethral vaporization of the prostate: a promising new technique
Authors: Thomas K.J. , Cornaby A.J. , Hammadeh M. , Philp T. , Matthews P.N.
Published: November 2003

Objective To evaluate the efficacy and safety of transurethral electrovaporization of the prostate (TUVP), using a grooved roller electrode, for the surgical treatment of symptomatic benign prostatic hypertrophy (BPH).

Patients and methods TUVP was carried out using a grooved roller electrode, pure‐cutting diathermy and a standard irrigating resectoscope to rapidly heat prostatic tissue to >100°C, resulting in vaporization and cavitation of the prostatic adenoma. Over a 10 month period, 116 patients (mean age 69.8 years, range 51–93) with symptomatic BPH (confirmed by a symptom score, urinary flow rate and an ultrasonographic estimate of residual volume) were treated by TUVP. Patients with carcinoma of the prostate, an elevated level of prostate‐specific antigen or those in chronic urinary retention were excluded from the study. Each patient was followed up every 4 months during the first post‐operative year, assessing their flow rate, residual volume and symptom score.

Results Symptom scores improved by 67% and residual volumes by 72%; the mean maximal flow rate increased from 8.5 mL/s (range 3.5–14) before treatment to 20.5 mL/s (range 4.5–39.0) at the same 4 month review. The procedure was simple and safe, with a mean operative duration of 35 min (range 20–65), and no patients required a blood transfusion. Most patients had their catheters removed within 24 h and were discharged on the second day after treatment.

Conclusion The effectiveness of TUVP in improving symptoms and flow rates in patients with BPH was established. With minimal capital expenditure and a reduced in‐patient stay, TUVP appears to have several advantages over other surgical treatments for BPH, although continued follow‐up is needed to establish the long‐term results.
A new approach using tissue alkaline phosphatase activity to identify early testicular cancer
Authors: Dabare A.A.N.P.M. , Nouri A.M.E. , Reynard J.M. , Killala S. , Oliver R.T.D.
Published: November 2003

Objective To establish the specificity and sensitivity of alkaline phosphatase activity in testicular tumours for the early detection of testicular germ cell tumours (GCTs).

Materials and methods Samples from patients with GCTs of the testis were sectioned and stained using the nitroblue tetrazolium salt (NBT)/5 bromo‐4‐chloro‐3‐indolylphosphate (BCIP) Sigma Fast substrate technique (referred to as MEDC) and peroxidase anti‐peroxidase (PAP) assay. Additionally, several cell lines from GCTs and other tumours were cultured using standard techniques and stained using both methods, and lysates from all samples were stained after gel electrophoresis.

Results MEDC showed strong and specific staining of testicular tumours only. The activity on gel electrophoresis appeared as two bands, one at 75 and one at 95 kDa, which was a unique combination for testicular tumours and testis cell lines.

Conclusion The MEDC method has extreme sensitivity and intensityfor testicular tumour tissue and has potential use as a powerful tool for the early detection of testicular GCTs by analysing semen samples, particularly in patients with equivocal findings on testicular ultrasonography.
Determination of testicular function after torsion by DNA flow cytometry of serial fine‐needle aspirates
Authors: Carroll T.A. , Regan M.C. , Alyusuf R. , Greene D. , Curran B. , Kay E. , Leader M. , Fitzpatrick J.M.
Published: November 2003

Objective To determine the efficacy of DNA flow cytometric analysis of testicular percutaneous fine‐needle aspirates in the assessment and follow‐up of testicular function after torsion, and to determine the relationship between the duration of torsion and testicular injury.

Materials and methods Three groups of 15 adult rats underwent a 720° torsion, with fixation of the mesorchial ligament, for 1, 3 or 5 h. Bilateral aspirations, performed 7, 21 and 35 days after torsion were examined by flow cytometry. Testes were harvested and evaluated histologically using Johnsen's scoring.

Results Irreversible testicular injury occurred in all three groups of rats, with loss of function after 1 h and loss of viability after 3 and 5 h. The results from flow cytometry suggested significant contralateral testicular injury (P<0.025) but this was not supported by the histological evaluation. There was a strong correlation between the testicular function assessed by flow cytometry and by Johnsen's scoring of histological specimens (r2=0.95).

Conclusion The assessment of testicular aspirates by flow cytometry allows testicular function to be followed after torsion in rats, and potentially in humans. Using DNA flow cytometry, the temporal course of the twisted testis in the adult rat was determined; contralateral testicular injury following the reversal of torsion could not be excluded.
A randomized controlled trial of transurethral microwave thermotherapy
Authors: Nawrocki J.D. , Bell T.J. , Lawrence W.T. , Ward J.P.
Published: November 2003

Objective To establish the short term clinical and urodynamic effect of transurethral microwave thermotherapy (TUMT) in men with symptomatic uncomplicated benign prostatic hyperplasia (BPH) using a randomized controlled trial comparing the treatment with both ‘placebo‐like’ and untreated control groups.

Patients and methods The study comprised 120 symptomatic patients with BPH who were candidates for transurethral resection and TUMT. They were randomized to one of three groups: group 1 underwent a standard TUMT, group 2 underwent a simulated treatment identical to group 1 but with no emission of microwaves and group 3 received no treatment. The treatment of the first two groups was ‘double‐blind’ and the heat experienced by the patients during treatment was simulated in both. Patients were assessed on entry to the study and 6 months after treatment using an identical protocol to measure the American Urological Association (AUA) symptom score, maximum urinary flow rate (Qmax ), post‐void residual urine volume (PVR), minimum urethral opening pressure ( pmuo ) and maximum detrusor pressure ( pdet max ).

Results In the untreated group there were no clinically or statistically significant changes in the median AUA symptom score, Qmax , PVR, pmuo and pdet max . In group 1 the AUA score changed significantly, from 19 to 9.5, but the Qmax , PVR, pmuo and pdet max did not. In group 2, the AUA score also changed significantly, from 17.5 to 9.5, but Qmax , PVR, pmuo and pdet max did not.

Conclusion The untreated control group showed no clinically relevant deterioration or improvement. The standard and simulated TUMT groups showed little clinically relevant improvement in ‘objective’ variables, while the clinically significant symptom improvement was of a similar magnitude in both groups.
Evaluation of primary standard cisplatin‐based chemotherapy for clinical stage II non‐seminomatous germ cell tumours of the testis
Authors: Culine S. , Théodore C. , Court B.H. , Perrin J.‐L. , Droz J.‐P.
Published: November 2003

Objective To evaluate the use of primary cisplatin‐based chemotherapy before retroperitoneal lymph node dissection (RPLND) in patients with clinical stage II non‐seminomatous germ cell tumours of the testis.

Patients and methods Between 1984 and 1992, 55 patients with clinical stage II testicular cancer (12 with stage IIA, 33 stage IIB and 10 stage IIC disease) were treated at Institut Gustave Roussy with primary chemotherapy using three conventional regimens including cisplatin. Patients were assessed 4 weeks after the end of chemotherapy and, depending on the response, underwent RPLND; the overall survival and disease progression were monitored.

Results Sixteen (29%) patients achieved a sustained complete remission after chemotherapy only, while 30 (55%) patients required subsequent RPLND for persistent residual tumour masses; nine other patients obtained a clinical partial remission. Six patients who initially had achieved either a clinical complete response (three) or a surgical complete response (one) or a clinical partial response (two) subsequently relapsed. Overall, 52 of 55 (95%) patients remained free of disease 33 to 111 months after the end of treatment.

Conclusion These results show that primary cisplatin‐based chemotherapy can effect a cure of the tumour in all subgroups of patients with stage II disease.
Natural erection induced by prostaglandin‐E1 in the diagnosis and treatment of congenital penile anomalies
Authors: Perovic S. , Djordjevic M. , Djakovic N.
Published: November 2003

Objective  To report the use of a natural erection induced by prostaglandin E1 (PGE1) in the diagnosis and therapy of congenital penile anomalies as an alternative to artificial erection.

Patients and methods  From February 1991 to December 1995 a natural erection was induced in 672 patients (mean age 5.7 years, range 12 months–47 years) to diagnose and treat congenital anomalies, e.g. simple penile curvature, chordee with and without hypospadias, epispadias, micropenis, cripple penis, etc. The dose injected intracavernosally was dependent on the patient's age, penile size and response, and ranged from 0.5 to 15 μg.

Results  A natural dilatation of erectile tissue was achieved in all forms of penile anomalies except in seven patients who did not respond. The mean duration of erection was 80 min, but a prolonged erection, for up to 6 h, occurred in two patients.

Conclusion  The natural erection achieved by injecting PGE1 into the corpora cavernosa is a useful alternative to artificial erection in the diagnosis and treatment of congenital penile anomalies.
A potential autocrine loop between heregulin‐alpha and erbB‐3 receptor in human prostatic adenocarcinoma
Authors: Leung H.Y. , Weston J. , Gullick W.J. , Williams G.
Published: November 2003

Objective To examine the expression of heregulin‐alpha (a new member of the epidermal growth factor family) and its receptor erbB‐3 in human prostate cancer by immunohistochemistry, and to analyse their implication for clinical outcome.

Patients and method Using specific anti‐peptide antibodies, tumour samples from 50 consecutive patients with newly diagnosed prostate cancer (18 well, 15 moderately and 17 poorly differentiated) and four patients with benign prostatic hyperplasia (BPH) were immunostained for heregulin‐alpha (an isoform of heregulin) and erbB‐3 proteins. Representative areas from each case were used to assess immunoreactivity.

Results Heregulin‐alpha was expressed (i.e. ≥10% of tumour cells positive) in 36 (72%) and erbB‐3 in 27 (54%) of the 50 cases. High levels of expression of heregulin‐alpha (>90% of tumour cells stained) appeared to be related to high‐grade tumours, but the association did not reach statistical significance. There was no correlation between the levels of expression of erbB‐3 and tumour grade. All four samples from BPH stained negatively for heregulin‐alpha and erbB‐3. Fourteen patients had bony metastases identified by bone scintigraphy and all received androgen ablation after undergoing transurethral resection of the prostate. Immunoreactivity for heregulin‐alpha and erbB‐3 were absent in five cases, all of whom responded to hormone manipulation and remained symptom‐free at the time of review (mean follow up 3 years, range 2–4). Despite hormone manipulation, the nine patients overexpressing heregulin‐alpha and/or erbB‐3 died during a mean follow up of 2.5 years (range 0.5–4).

Conclusion The overexpression of heregulin‐alpha and erbB‐3 in prostate cancer is detectable by immunostaining. Activation of the type 1 growth‐factor receptor system by heregulin‐alpha and/or the erbB‐3 receptor appears to be associated with a less favourable prognosis in advanced disease.
The infusion trial of micturition
Authors: Lyth D.R. , Braslis K. , Iacovou J.W.
Published: November 2003

Objective  To compare three methods for a trial of micturition (TOM) (the midnight removal of the catheter, dawn removal, and a new infusion method) in a randomized prospective study.

Patients and methods  A total of 118 consecutive patients who had undergone transurethral resection of the prostate (TURP) or bladder neck incision (BNI) underwent TOM by one of the three methods. In the infusion method, the bladder was filled at a fast‐drip rate via the catheter from a bag of normal saline connected by an intravenous supply set. The catheter was then removed, the patient voided and the volume was measured. From the volume of saline remaining, it was possible to calculate the residual volume in the patient.

Results  The infusion TOM took a mean 13 h less than the other two methods, which were statistically indistinguishable.

Conclusion  The infusion TOM is safe and simple, is quick to carry out and can be performed at any time. It establishes the completeness of bladder emptying, which helps in the assessment of voiding.
Morphological changes in the basement membrane during progression from non‐invasive to invasive rat bladder cancer induced by N‐butyl‐N‐(4‐hydoxybutyl) nitrosamine
Authors: Zhang X.H. , Takenaka I.
Published: November 2003

Objective To investigate the ultrastructural changes in the basement membrane (BM) in the rat model of bladder cancer when progressing from non‐invasive to invasive disease.

Materials and methods
N‐butyl‐N‐(4‐hydoxybutyl) nitrosamine (BBN) was administered to 50 rats (7 weeks old) in their drinking water (0.05% BBN) for 28 weeks. At between 20 and 28 weeks, 10 rats were killed every 2 weeks and morphological changes of the BM were investigated by transmission electron microscopy and histological changes by light microscopy.

Results At between 20 and 28 weeks, the transitional cell carcinoma (TCC) of the rat bladder induced by BBN progressed from non‐invasive (stage Ta) to invasive (stage T1–2) disease. Focal thinning and discontinuity of the BM occurred in five of 26 rats with non‐invasive TCC and in all 24 rats with invasive TCC.

Conclusions Stage Ta bladder cancer in the rat model may be associated with degradative changes in the BM and can be divided into two types, Ta1 where there is no degradation of the BM and Ta2, where the BM is degraded.
Testis‐preserving surgery in bilateral testicular germ cell tumours
Authors: Heidenreich A. , Höltl W. , Albrecht W. , Pont J. , Engelmann U.H.
Published: November 2003

Objective To evaluate the indications, techniques and outcome of organ‐preserving tumour enucleation in patients with bilateral testicular germ cell tumours (BTGCT) rather than standard bilateral radical orchidectomy which results in loss of fertility and a lifelong requirement for androgen replacement.

Patients and methods In 13 patients with BTGCT of 6–30 mm in diameter, the tumours were enucleated under cold ischaemia after inguinal testicular exploration, and biopsies of the tumour bed and the peripheral parenchyma were taken. Histology of the orchidectomy specimen revealed a seminoma in four cases, an embryonal carcinoma in three, a teratocarcinoma and a mixed‐germ cell tumour in two each, and a mature teratoma in one. Histology of the enucleated tumours showed a seminoma in seven cases, an embryonal carcinoma in five and a mature teratoma in one. Six of the 13 patients underwent testicular radiation (20 Gy) for carcinoma in situ (CIS) and five patients had adjuvant local therapy. Six months post‐operatively, a testicular biopsy was taken to determine the success of therapy.

Results The median follow‐up was 62 months (range 14–163) and the 13 patients are currently free of disease; one patient had local recurrence 9 months after tumour enucleation but after orchidectomy the patient is free of disease after a follow‐up of 156 months. Serum concentrations of luteinizing hormone and testosterone were within the normal range in all patients and no androgen substitution was necessary. A testicular biopsy taken 6 months post‐operatively revealed Sertoli cells only in all patients who had received radiation therapy.

Conclusions These results suggest that organ‐sparing surgery in patients with BTGCT represents a new therapeutic approach with endocrinological and psychological advantages. In our experience, enucleation resection of testicular tumours is possible with certain prerequisites, i.e. the tumour is organ‐confined with no infiltration of the rete testis, multiple biopsies of the tumour bed and peripheral parenchyma should be taken, any associated CIS treated by radiation therapy, and patients must be followed closely.
Impact of early orchidopexy on testicular growth
Authors: NAGAR H. , HADDAD R.
Published: November 2003

Objective

 To assess the impact of early orchidopexy on post‐operative testicular growth.

Patients and methods

 One‐hundred and ninety boys (age range 1 week to 15 years at the time of initial diagnosis) underwent surgery for the repair of unilateral cryptorchidism, and the relative testicular size was assessed before and after operation.

Results

 When compared with the size of the uninvolved testis, testicular size increased after surgery in 11.6% of cases and decreased in 2.6%. Testicular growth was more common among children operated when younger than 18 months (P=0.016) than when older.

Conclusion

 The testicle may grow when orchidopexy is performed in children younger than 18 months.
A multicentric, placebo‐controlled, double‐blind clinical trial of β‐sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia
Authors: KLIPPEL K.F. , HILTL D.M. , SCHIPP B. ,   for the German BPH‐Phyto study group‡
Published: November 2003

Objective

 To report the results of a double‐blind, placebo‐controlled trial to evaluate Azuprostat® , a β‐sitosterol, in patients with symptoms of outlet obstruction caused by benign prostatic hyperplasia (BPH).

Patients and methods

 A randomized, double‐blind and placebo‐controlled clinical trial was conducted to assess the efficacy and safety of 130 mg free β‐sitosterol (phytosterol) daily, using the international prostate symptom score (IPSS) as the primary outcome variable. In total, 177 patients with BPH were recruited for 6 months of treatment in 13 study centres. In addition to the relative difference in the IPSS, changes in quality of life, peak urinary flow rate (Qmax ) and post‐void residual urinary volume (PVR) were recorded. The drug used in the trial consisted of a chemically defined extract of phytosterols, derived for example from species of Pinus, Picea or Hypoxis, with β‐sitosterol as the main component.

Results

 There were significant (P<0.01) improvements over placebo in those treated with β‐sitosterol; the mean difference in the IPSS between placebo and β‐sitosterol, adjusted for the initial values, was 5.4 and in the quality‐of‐life index was 0.9. There were also significant improvements in the secondary outcome variables, with an increase in Qmax (4.5 mL/s) and decrease in PVR (33.5 mL) in favour of β‐sitosterol when adjusted for the changes after placebo.

Conclusion

 These results show that β‐sitosterol is an effective option in the treatment of BPH.
Morphogenesis of the human lacrimal gland
Authors: De La Cuadra‐Blanco C. , Peces‐Peña M. D. , Mérida‐Velasco J. R.
Published: November 2003

The aim of this study was to determine the main stages of the lacrimal gland's developmental process in humans and to establish its precise morphogenetic timetable. Its onset is generally assumed to take place at O’Rahilly's stage 21, arising from an epithelial thickening of the superior extreme of the temporary conjunctival fornix. However, the present study points to a prior stage in the process: the presence of epithelial–mesenchymal changes in embryos at O’Rahilly's stage 19. The study was performed using light microscopy on serial sections of 37 human specimens: 23 embryos and 14 fetuses ranging from 15 to 137 mm crown–rump length (7–116 weeks of development). Three stages in lacrimal gland morphogenesis were identified: (1) the presumptive glandular stage, O’Rahilly's stages 19–20, characterized by a thickening of the superior fornix epithelium together with surrounding mesenchymal condensation; (2) the bud stage, generally assumed to be the first manifestation of glandular origin, characterized initially by the appearance of nodular formations in the region of the superior conjunctival fornix and concluding with the appearance of lumina within the epithelial buds; and (3) the glandular maturity stage, weeks 9–16, the period in which the gland begins to take on the morphology of adulthood.
Expression of fibroblast growth factor‐2 (FGF‐2) in early stages (days 3–11) of the development of the avian lung, Gallus gallus variant domesticus: an immunocytochemical study
Authors: Maina J. N. , Madan A. K. , Alison B.
Published: November 2003

In the avian lung, the bronchial system forms from epithelial (endodermal) cells. The intrapulmonary primary bronchus is the focal point of airway development. It originates secondary bronchi (SB) along its proximal–distal extent and parabronchi (tertiary bronchi) arise from and connect the SB. From as early as day 3.5, fibroblast growth factor‐2 (FGF‐2) is diffusely expressed in the epithelial and mesenchymal cells. Up‐regulation of FGF‐2 in discrete areas of the developing lung seem to set the growth rate, trajectories followed, areas appropriated, three‐dimensional symmetry and coupling of the airways. Expressed early in development and persisting into the incubation period, FGF‐2 may be involved in the formation of the avian lung. Morphogenetic differences between the avian and the mammalian lungs may explain the existing structural contrarieties.
Microscopic analysis of the cellular events during scatter factor/hepatocyte growth factor‐induced epithelial tubulogenesis
Authors: Williams M. J. , Clark P.
Published: November 2003

Scatter factor/hepatocyte growth factor (SF/HGF), a large multifunctional polypeptide growth and motility factor, is known to play important roles during embryonic development, adult tissue growth and repair. In an established three‐dimensional type I collagen model, SF/HGF induces Madin–Darby canine kidney (MDCK) epithelial cysts to form long, branching tubules (tubulogenesis). In addition, the composition of the surrounding extracellular matrix (ECM) has been shown to modulate SF/HGF‐induced morphogenesis, where tubulogenesis was completely abrogated in Matrigel basement membrane. Many cellular events that occur during SF/HGF‐mediated remodelling, and its modulation by the ECM, remain unclear. We have investigated these mechanisms through microscopic examination of the time‐course of SF/HGF‐induced responses in MDCK cysts cultured in type I collagen or Matrigel. We found that early responses to SF/HGF were matrix‐independent. Changes included increased paracellular spacing between normally closely apposed lateral membranes, and the formation of filopodial processes, indicating a partial motile response. Cell–cell contact was maintained, with the persistence of cell junctions. Therefore, while one or a number of ECM components are preventing SF/HGF‐primed cells from undergoing an invasive and/or migratory programme, non‐permissive matrices are not preventing SF/HGF signalling to the cell. Later matrix‐dependent responses, which occurred in type I collagen but not Matrigel, included the formation of basal protrusions that comprise two or more neighbouring cells, which extend to form nascent tubules. Modified polarity of cells comprising the basal protrusions was evident, with a marker for the apical membrane being found in the same region as adherens junctions and desmosomes, typically localized at lateral membranes. We propose a model for SF/HGF‐induced tubulogenesis in which tubules form from basal protrusions of adjacent cells. This mechanism of in vitro tubule formation has many similarities to reported in vivo epithelial tubulogenesis.
Effects of injury and progesterone treatment on progesterone receptor and progesterone binding protein 25‐Dx expression in the rat spinal cord
Authors: Labombarda F. , Gonzalez S. L. , Deniselle M. C. Gonzalez , Vinson G. P. , Schumacher M. , De Nicola A. F. , Guennoun R.
Published: November 2003

Progesterone provides neuroprotection after spinal cord injury, but the molecular mechanisms involved in this effect are not completely understood. In this work, expression of two binding proteins for progesterone was studied in intact and injured rat spinal cord: the classical intracellular progesterone receptor (PR) and 25‐Dx, a recently discovered progesterone membrane binding site. RT‐PCR was employed to determine their relative mRNA levels, whereas cellular localization and relative protein levels were investigated by immunocytochemistry. We observed that spinal cord PR mRNA was not up‐regulated by estrogen in contrast to what is observed in many brain areas and in the uterus, but was abundant as it amounted to a third of that measured in the estradiol‐stimulated uterus. In male rats with complete spinal cord transection, levels of PR mRNA were significantly decreased, while those of 25‐Dx mRNA remained unchanged with respect to control animals. When spinal cord‐injured animals received progesterone treatment during 72 h, PR mRNA levels were not affected and remained low, whereas 25‐Dx mRNA levels were significantly increased. Immunostaining of PR showed its intracellular localization in both neurons and glial cells, whereas 25‐Dx immunoreactivity was localized to cell membranes of dorsal horn and central canal neurons. As the two binding proteins for progesterone differ with respect to their response to lesion, their regulation by progesterone, their cellular and subcellular localizations, their functions may differ under normal and pathological conditions. These observations point to a novel and potentially important role of the progesterone binding protein 25‐Dx after injury of the nervous system and suggest that the neuroprotective effects of progesterone may not necessarily be mediated by the classical progesterone receptor but may involve distinct membrane binding sites.
NGF activates the phosphorylation of MAP1B by GSK3β through the TrkA receptor and not the p75NTRreceptor
Authors: Goold Robert G. , Gordon‐Weeks Phillip R.
Published: November 2003

We have recently shown that nerve growth factor (NGF) induces the phosphorylation of the microtubule‐associated protein 1B (MAP1B) by activating the serine/threonine kinase glycogen synthase kinase 3β (GSK3β) in a spatio‐temporal pattern in PC12 cells that correlates tightly with neurite growth. PC12 cells express two types of membrane receptor for NGF: TrkA receptors and p75NTRreceptors, and it was not clear from our studies which receptor was responsible. We show here that brain‐derived neurotrophic factor, which activates p75NTRbut not TrkA receptors, does not stimulate GSK3β phosphorylation of MAP1B in PC12 cells. Similarly, NGF fails to activate GSK3β phosphorylation of MAP1B in PC12 cells that lack TrkA receptors but express p75NTRreceptors (PC12 nnr). Chick ciliary ganglion neurons in culture lack TrkA receptors but express p75NTRand also fail to show NGF‐dependent GSK3β phosphorylation of MAP1B, whereas in rat superior cervical ganglion neurons in culture, NGF activation of TrkA receptors elicits GSK3β phosphorylation of MAP1B. Finally, inhibition of TrkA receptor tyrosine kinase activity in PC12 cells and superior cervical ganglion neurons with K252a potently and dose‐dependently inhibits neurite elongation while concomitantly blocking GSK3β phosphorylation of MAP1B. These results suggest that the activation of GSK3β by NGF is mediated through the TrkA tyrosine kinase receptor and not through p75NTRreceptors.
P‐glycoprotein in blood–brain barrier endothelial cells: interaction and oligomerization with caveolins
Authors: Jodoin Julie , Demeule Michel , Fenart Laurence , Cecchelli Roméo , Farmer Sarah , Linton Kenneth J. , Higgins Christopher F. , Béliveau Richard
Published: November 2003

P‐glycoprotein (P‐gp), an adenosine triphosphate (ATP)‐binding cassette transporter which acts as a drug efflux pump, is highly expressed at the blood–brain barrier (BBB) where it plays an important role in brain protection. Recently, P‐gp has been reported to be located in the caveolae of multidrug‐resistant cells. In this study, we investigated the localization and the activity of P‐gp in the caveolae of endothelial cells of the BBB. We used an in vitro model of the BBB which is formed by co‐culture of bovine brain capillary endothelial cells (BBCEC) with astrocytes. Caveolar microdomains isolated from BBCEC are enriched in P‐gp, cholesterol, caveolin‐1, and caveolin‐2. Moreover, P‐gp interacts with caveolin‐1 and caveolin‐2; together, they form a high molecular mass complex. P‐gp in isolated caveolae is able to bind its substrates, and the caveolae‐disrupting agents filipin III and nystatin decrease P‐gp transport activity. In addition, mutations in the caveolin‐binding motif present in P‐gp reduced the interaction of P‐gp with caveolin‐1 and increased the transport activity of P‐gp. Thus, P‐gp expressed at the BBB is mainly localized in caveolae and its activity may be modulated by interaction with caveolin‐1.
Nuclear factor κB nuclear translocation as a crucial marker of brain response to interleukin‐1. A study in rat and interleukin‐1 type I deficient mouse
Authors: Nadjar Agnès , Combe Chantal , Layé Sophie , Tridon Viviane , Dantzer Robert , Amédée Thierry , Parnet Patricia
Published: November 2003

The signalling pathways that mediate early central effects of interleukin‐1 (IL‐1) during the acute phase reaction have been poorly elucidated. Interaction of IL‐1β to its specific receptor interleukin‐1 receptor type I (IL‐1RI) leads to nuclear factor kappa B (ΝFκB) nuclear translocation and a robust transcriptional activation of inhibitor of kappa B alpha (IκBα) within the rat brain. Indeed, we demonstrated that IL‐1RI expressed in blood brain barrier (BBB) cells and in circumventricular organs (CVOs) is crucial for p65‐NFκB translocation induced by peripheral injection of IL‐1β. Moreover, it has been previously shown that monitoring IκBα mRNA synthesis is an effective tool to investigate the activity of the transcription factor NFκB into the CNS. However in the present study we observed time‐related and cell‐type differences between IκBα mRNA synthesis and p65‐NFκB translocation. This indicates that the expression of IκBα mRNA does not strictly parallel p65‐NFκB nuclear translocation, suggesting that these markers are not interchangeable to investigate NFκB activity but must be studied together. Thus, we hypothesize that IL‐1β reached the brain across the CVOs that lack a BBB and endothelial cells all over the brain and interacted with its receptors to induce NFκB translocation. The study of the consequences of the impairment of NFκB pathway activation in in vivo experimentation should bring important clues about the precise role of this transcription factor.
Effects of tasting technique – sequential tasting vs. mixed tasting – on perception of dry white wine and blue mould cheese
Authors: Nygren Ingemar T. , Gustafsson Inga‐Britt , Johansson Lisbeth
Published: November 2003

The object of this study was to evaluate by means of descriptive sensory analysis the effect of mixed tasting on the perception of dry white wine and blue mould cheese, and to establish whether the tasting technique (sequential vs. mixed tasting) significantly affects this perception. A Swedish blue mould cheese, Bredsjö Blå, and a French blue mould cheese, Roquefort Société, and five commercial types of dry white wine were used. The same panel, selected and trained according to ISO standards, as in Nygren et al. (2002, 2003) carried out the descriptive analyses by means of a mixed tasting technique. The panel scored the same attributes for both cheese and wine as in Nygren et al. (2002, 2003). In general, the original wine attribute scores decreased more by means of mixed tasting technique than by means of sequential, while few changes of the original cheese attribute scores were observed. Overall, mixed tasting gave greater decreasing changes than sequential tasting.
Valproate Suppresses Status Epilepticus Induced by 4‐Aminopyridine in CA1 Hippocampus Region
Authors: Martín Eduardo D. , Pozo Miguel A.
Published: November 2003

Summary:  Purpose: We investigated the effects of valproate (VPA) on an in vivo model of status epilepticus (SE) induced by intrahippocampal application of 4‐aminopyridine (4‐AP).

Methods: To induce continuous epileptiform activity without a clinical component, 4‐AP (100 mM) was slowly injected in the hippocampus of adult rats. Extracellular field potential from the CA1 region of the rat hippocampus was recorded to assess abnormal epileptiform activity. Once the SE seizures were induced by 4‐AP, the test drug was injected. In some experiments to test the ability of a drug to prevent the induction of SE, the drug was administered before 4‐AP injection.

Results: Intrahippocampal injection of 4‐AP induced continuous epileptic activity without a clinical component that lasted >60 min. The intravenous injection of 400–600 mg/kg VPA rapidly (∼100 s) abolished the SE, and this effect persisted for ≥4 h in our experimental model. The intravenous injection of 100–300 mg/kg VPA did not abolish previously induced SE, but prevented the appearance of SE when applied before the induction of SE. The intravenous injection of 80 mg/kg phenytoin or carbamazepine did not abolish or prevent SE.

Conclusions: We conclude that 4‐AP–induced SE was suppressed by VPA at 400–600 mg/kg, whereas minor doses (100–300 mg/kg) only prevent the 4‐AP–induced SE. Present results suggest the revisiting of VPA as a useful drug for the treatment of SE.
Seizure Outcome after Temporal Lobectomy in Temporal Lobe Cortical Dysplasia
Authors: Srikijvilaikul Teeradej , Najm Imad M. , Hovinga Collin A. , Prayson Richard A. , Gonzalez‐Martinez Jorge , Bingaman William E.
Published: November 2003

Summary:  Purpose: To identify the temporal lobe cortical dysplasia (CD) histopathology classification subtype and determine the seizure outcome of patients who underwent temporal lobectomy with coincident CD.

Methods: We reviewed the data of 28 patients with temporal lobe epilepsy who underwent surgery with pathologically verified CD at our institution from 1990 to 2000. The seizure outcome was assessed at a minimum of 1 year after surgery according to Engel's classification.

Results: Of 28 patients who underwent surgery, nine (32.1%) had isolated CD, and 19 (67.9%) had CD and hippocampal sclerosis (CD&HS). Twenty‐six (92.9%) patients had histopathology subtype Ia (architectural abnormalities). Twenty (71.4%) patients were seizure free (Engel class I). Favorable seizure outcome (Engel class I, II) was achieved in 26 (92.9%) patients. No difference in seizure outcome was noted between patients with CD and CD&HS.

Conclusions: The most common histopathologic subtype in patients with temporal lobe CD is type Ia (architectural abnormalities). Temporal lobectomy in temporal lobe epilepsy patients with CD can achieve favorable seizure outcome.
Knowledge of Epilepsy and Familiarity with This Disorder in the U.S. Population: Results from the 2002 HealthStyles Survey
Authors: Kobau Rosemarie , Price Patricia
Published: November 2003

Summary:  Purpose: To assess perceptions of knowledge and experience with epilepsy and seizures in the U.S. population to develop communication campaigns to improve the public's understanding of epilepsy. In a national survey, focal points included the public's knowledge of the disorder, whether people know someone who has it, exposure to epilepsy‐related information, and knowledge about how to respond to a person having a seizure.

Methods: The Epilepsy Program of the Centers for Disease Control and Prevention included nine items on an annual mail survey that targeted a representative sample of the U.S. population. Data were weighted to be representative of the U.S. population. χ2 analyses were performed, and standardized residuals were used to examine the associations between responses and demographic variables.

Results: Responses were obtained from 4,397 persons. Despite the low prevalence of epilepsy, results indicate that about half of all persons have witnessed an epileptic seizure either in person or on television; about one third of all persons know someone with epilepsy, but relatively few are familiar with epilepsy, how to respond to a seizure, or with the Epilepsy Foundation.

Conclusions: In general, the public has relatively little knowledge about epilepsy. Educational campaigns that inform the public about this disorder and about seizures should work through community settings to improve the general public's understanding of epilepsy.
Analysis of Cerebrospinal Fluid Glial Fibrillary Acidic Protein after Seizures in Children
Authors: Gurnett Christina A. , Landt Michael , Wong Michael
Published: November 2003

Summary:  Purpose: To evaluate pediatric seizure patients for astrocytic injury by measuring cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP), determine risk factors for GFAP elevation after seizures, and compare seizure‐induced astrocyte injury with neuronal injury by concurrent measurement of CSF neuron‐specific enolase (NSE).

Methods: CSF obtained from pediatric patients (n = 52) within 24 h of seizure was assayed for GFAP and NSE. Retrospective chart review was performed for seizure type, duration, and etiology.

Results: Overall, children with seizures had elevated CSF GFAP compared with controls (p = 0.0075), but no elevation of NSE (p = 0.1437). No effect of seizure type or etiology was found, but a significant positive effect of seizure duration (p = 0.0010) and status epilepticus (p = 0.0296) was seen on CSF GFAP. Individually, seven children (13%) had elevated GFAP (>440 pg/ml); in five children, the increased GFAP was not accompanied by elevations in NSE (<12 ng/ml). Five children with elevated GFAP had symptomatic etiologies for their seizures, but the etiology of one child with elevated GFAP was cryptogenic, and one had febrile seizures.

Conclusions: Elevation of CSF GFAP after seizures suggests that astrocytic injury may occur in a subgroup of children, primarily in the context of prolonged seizures and symptomatic etiologies. Increased GFAP levels may occur in patients with normal NSE, suggesting that GFAP may be a more sensitive marker of brain injury in some cases.
Physiology of Human Cortical Neurons Adjacent to Cavernous Malformations and Tumors
Authors: Williamson Anne , Patrylo Peter R. , Lee Sunghoon , Spencer Dennis D.
Published: November 2003

Summary:  Purpose: Focal neocortical seizures can be associated with a number of specific pathologies including supratentorial tumors and cavernous malformations (CMs), both of which are highly epileptogenic.

Methods: To begin to address the question of whether these lesions have different mechanisms of epileptogenesis, we used intracellular recordings from neurons adjacent to intracerebral neoplasms and cerebral CMs. Developmental anomalies were not included in this study.

Results: Neurons adjacent to CMs had a greater propensity to show large (>5 mV), complex spontaneous synaptic events than did neurons neighboring neoplastic substrates (50 vs. 4.7% of cells and 75 and 8% of patients, respectively; p < 0.004; p < 0.05). Both spontaneous excitatory and inhibitory events were noted. In contrast, in tissue adjacent to tumors, low‐amplitude (<3 mV) spontaneous excitatory activity predominated. Neurons neighboring CMs also exhibited more excitable responses to synaptic stimulation, with multiple action potentials riding on prolonged excitatory postsynaptic potentials (EPSPs) being evoked in 71% of these cells, versus 32% of cells from the tumor group; p < 0.05. In studies using hippocampal tissue, we noted a similar pattern of spontaneous activity in tissue adjacent to CMs.

Conclusions: These data suggest that CMs may induce seizure activity via a different pathophysiologic mechanism(s) than glial tumors.
Recurrent Nonstatus Generalized Seizures Alter the Developing Chicken Brain
Authors: Gong Zhao , Obenaus André , Li Nan , Sarty Gordon E. , Kendall Edward J.
Published: November 2003

Summary:  Purpose: Noninvasive magnetic resonance imaging was used to assess the evolution of seizure‐induced pathology in epileptic, carrier, and normal chickens. Our objective was to determine whether repetitively evoked seizures in an epileptic fowl model of generalized seizures resulted in altered brain development.

Methods: Data were obtained from seizure and control groups at 45, 90, and 180 days after hatching.

Results: At 180 days, apparent diffusion coefficient (ADC) values in the optic tectum and archistriatum of the stimulated epileptic chicks were reduced, whereas ADC values in the nonstimulated group remained unchanged. The mean brain volume of epileptic chickens from the stimulated group was smaller than that from the nonstimulated group at 90 and 180 days.

Conclusions: These findings establish that recurrent seizures modify the brain matrix.
Thalamic Dysfunction in Juvenile Myoclonic Epilepsy: A Proton MRS Study
Authors: Mory Susana B. , Li Li M. , Guerreiro Carlos A. M. , Cendes Fernando
Published: November 2003

Summary:  Purpose: To investigate neuronal dysfunction in the thalami of patients with juvenile myoclonic epilepsy (JME) by using proton magnetic resonance spectroscopy (MRS).

Methods: We performed single‐voxel proton MRS over the right and the left thalami of 10 consecutive patients (five women) with JME (mean age, 31.6 years) and 10 age‐matched healthy volunteers (five men). All patients had seizure onset in late childhood–teenage, normal neurologic examination, typical EEG of JME, and normal high‐resolution MR imaging (MRI). We determined ratios of N‐acetylaspartate (NAA) over creatine‐phosphocreatine (Cr). Values <2 standard deviations from controls were considered abnormal. We performed analysis of variance to evaluate group differences.

Results: Group analysis showed that thalami NAA/Cr ratios were significantly decreased in JME patients (left side, 1.58 ± 0.26; right side, 1.5 ± 0.15) as compared with controls (left side, 1.98 ± 0.18; right side, 1.88 ± 0.15; p = 0.001 and p = 0.007, respectively). Individual analysis showed that nine of the 10 patients had abnormal NAA/Cr in at least one of the thalami.

Conclusions: This study shows evidence of neuronal dysfunction in the thalami of patients with JME, which may have relevance for the mechanisms of seizure generation in this form of generalized epilepsy.