bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection
Authors: Cichewicz Robert H. , Kouzi Samir A.
Published: October 2003

3β‐Hydroxy‐lup‐20(29)‐en‐28‐oic acid (betulinic acid) is a pentacyclic lupane‐type triterpene that is widely distributed throughout the plant kingdom. A variety of biological activities have been ascribed to betulinic acid including anti‐inflammatory and in vitro antimalarial effects. However, betulinic acid is most highly regarded for its anti‐HIV‐1 activity and specific cytotoxicity against a variety of tumor cell lines. Interest in developing even more potent anti‐HIV agents based on betulinic acid has led to the discovery of a host of highly active derivatives exhibiting greater potencies and better therapeutic indices than some current clinical anti‐HIV agents. While its mechanism of action has not been fully determined, it has been shown that some betulinic acid analogs disrupt viral fusion to the cell in a post‐binding step through interaction with the viral glycoprotein gp41 whereas others disrupt assembly and budding of the HIV‐1 virus. With regard to its anticancer properties, betulinic acid was previously reported to exhibit selective cytotoxicity against several melanoma‐derived cell lines. However, more recent work has demonstrated that betulinic acid is cytotoxic against other non‐melanoma (neuroectodermal and malignant brain tumor) human tumor varieties. Betulinic acid appears to function by means of inducing apoptosis in cells irrespective of their p53 status. Because of its selective cytotoxicity against tumor cells and favorable therapeutic index, even at doses up to 500 mg/kg body weight, betulinic acid is a very promising new chemotherapeutic agent for the treatment of HIV infection and cancer. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 1, 90–114, 2004
Clinical significance of urokinase‐type plasminogen activator receptor (uPAR) expression in cancer
Authors: de Bock Charles Edo , Wang Yao
Published: October 2003

The involvement of the urokinase‐type plasminogen activator (uPA) system in particular has been extensively studied in the pathogenesis of cancer. The molecular role of the uPA receptor (uPAR) is well characterized with its participation in cell migration and extracellular matrix (ECM) degradation. Over‐expression of uPAR in cancer has been demonstrated in many studies and is considered an attractive target for anticancer agents. We and others have down‐regulated uPAR expression in an attempt to inhibit cancer metastasis based on its molecular role. Uniquely, uPAR which is a glycosyl phosphatidylinositol anchored protein is not only bound to the cell surface but also has a soluble form, suPAR. There is now accumulated clinical and experimental evidence supporting the significant role of uPAR and its soluble counterpart in a number of solid cancers. The expression of uPAR can be associated with tumor cells or stromal cells or both. Differences observed in the expression of uPAR using immunohistochemistry (IHC) are likely explained by the use of different antibodies and techniques rather than true cellular differences and are reviewed here. This review summarizes the clinical relevance of uPAR and its soluble form in the prognosis and diagnosis of different cancers. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 1, 13–39, 2004
Intracellular cargo delivery using tat peptide and derivatives
Authors: Zhao Ming , Weissleder Ralph
Published: October 2003

Efficient delivery of therapeutic and diagnostic agents across the plasma membrane is crucial in developing novel therapies. Membrane permeating peptides, in particular HIV‐1 tat peptide and its derivatives, have enabled the intracellular delivery of cargos of various sizes and physicochemical properties. This review summarizes the current knowledge of tat‐derived cell permeating peptides in the transduction of exogenous molecules/complexes. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 1, 1–12, 2004
Update on HIV resistance and resistance testing
Authors: Sebastian Joseph , Faruki Hawazin
Published: October 2003

The introduction of highly active antiretroviral therapy, including a combination of antivirals directed at various steps in the viral life cycle, has led to significant decreases in morbidity and mortality associated with human immunodeficiency virus (HIV‐1) infections. Despite the availability of numerous antivirals, many extensively treated patients gradually loose the ability to control viral replication because of development of antiviral resistance. Laboratory tests have been developed and validated to assist in recognizing such resistance and to help predict which antivirals may be more likely to control viral replication in a given patient. Both genotypic and phenotypic assays have been developed to assess HIV‐1 antiviral resistance. The assay methodologies, including the advantages and disadvantages of each method, as well as the limitations of each method are reviewed. The ability to predict likely drug response from a genotype or a phenotype is continually evolving, and the more recently discovered mutation/drug resistance associations are discussed in terms of their implications for HIV resistance assays. To provide additional options for those who have developed resistance to all currently available drugs, new antivirals, such as the fusion inhibitors, are being developed. These new classes of antivirals block the HIV viral life cycle at sites other than reverse transcriptase and protease. Unique and novel resistance assays are being developed to measure HIV resistance to these new drugs. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 1, 115–125, 2004
On the competitive growth of two sand heaps
Authors: Kuttler Christina
Published: October 2003

A simple quasistationary model for the growth of 1D sand heaps in form of a non‐linear system of ordinary differential equations is presented. The basic assumption for the model is the instantaneous deposition of the matter which is poured by punctiform sources. Existence and uniqueness of the solution is shown, and the qualitative evolution, especially the overrun phenomenon, is described. Copyright © 2003 John Wiley & Sons, Ltd.
Pseudo‐reflection phenomena for singularities in thin elastic shells
Authors: Karamian‐Surville P. , Sanchez‐Hubert J. , Sanchez Palencia E.
Published: October 2003

We consider problems of statics of thin elastic shells with hyperbolic middle surface subjected to boundary conditions ensuring the geometric rigidity of the surface. The asymptotic behaviour of the solutions when the relative thickness tends to zero is then given by the membrane approximation. It is a hyperbolic problem propagating singularities along the characteristics. We address here the reflection phenomena when the propagated singularities arrive to a boundary. As the boundary conditions are not the classical ones for a hyperbolic system, there are various cases of reflection. Roughly speaking, singularities provoked elsewhere are not reflected at all at a free boundary, whereas at a fixed (or clamped) boundary the reflected singularity is less singular than the incident one. Reflection of singularities provoked along a non‐characteristic curve C are also considered. Copyright © 2003 John Wiley & Sons, Ltd.
Conservation laws for Lotka–Volterra models
Authors: Schimming Rainer
Published: October 2003

We derive necessary and sufficient conditions on a Lotka–Volterra model to admit a conservation law of Volterra's type. The result and the proof for the corresponding linear algebra problem are given in graph‐theoretical terms; they refer to the directed graph which is defined by the coefficients of the differential equation system. Copyright © 2003 John Wiley & Sons, Ltd.
Modelling and optimal control of coupled structural acoustic systems with piezoelectric elements
Authors: Litvinov W. G. , Kröplin B.
Published: October 2003

We construct a model of a shell with piezoelectric elements (patches) that take into account the mutual influence of deformations and electric fields. Coupled problems for the shell with piezoelectric patches and an acoustic field, are studied and results on the existence and the uniqueness are obtained. For this system we consider an optimal control problem on noise attenuation and obtain results on the existence, the uniqueness, necessary and sufficient conditions of optimality. Copyright © 2003 John Wiley & Sons, Ltd.
Neuroblastoma in adolescents and adults: The Memorial Sloan‐Kettering experience
Authors: Kushner Brian H. , Kramer Kim , LaQuaglia Michael P. , Modak Shakeel , Cheung Nai‐Kong V.
Published: October 2003

Background

We reviewed the utility of different treatment modalities in a large series of adolescents/adults with neuroblastoma (NB).

Procedure

The 30 adolescents/adults (median age, 19 years) had stage 2B (n = 1), 3 (n = 2), or 4 (n = 27) NB. Treatments included conventional and myeloablative therapy; local radiotherapy (RT); immunotherapy with anti‐GD2 3F8 monoclonal antibody ± granulocyte–macrophage colony‐stimulating factor (GM‐CSF); and 3F8 alternating with low‐dose oral etoposide.

Results

Seven patients are in first (n = 4) or second (n = 3) complete/very good partial remission (CR/VGPR) at 9+ to 181+ (median, 45+) months. Among 13 newly diagnosed or minimally prior‐treated patients, no major responses were seen in 4/4 treated with N4/N5 chemotherapy, but 6/9 treated with the higher dose N6/N7 regimens and surgery had major responses, and immunotherapy produced CR in BM in three patients. Among 17 patients referred because of resistant NB, favorable responses occurred in 6/12 treated with high‐dose cyclophosphamide‐based salvage therapy, including one patient who is in CR 170+ months after myeloablative consolidation and five patients who achieved CR/VGPR after 3F8/GM‐CSF (n = 4) or 3F8/oral etoposide (n = 1). With a median follow‐up of 32+ months post‐RT, no local relapses occurred in 10/10 patients who received hyperfractionated 21 Gy RT to prevent regrowth of soft tissue masses that had been resected.

Conclusions

High‐dose chemotherapy and surgery can achieve a minimal disease state in >50% of newly diagnosed older NB patients. In that setting, local RT, and the use of agents with recently confirmed anti‐NB activity, including anti‐GD2 antibodies, and cis‐retinoic acid, may improve the poor prognosis of these patients reported to date. Med Pediatr Oncol 2003;41:508–515. © 2003 Wiley‐Liss, Inc.
Malawi pilot study of Burkitt lymphoma treatment
Authors: Hesseling Peter B. , Broadhead Robin , Molyneux Elizabeth , Borgstein Eric , Schneider Johann W. , Louw Mercia , Mansvelt Erna P.G. , Wessels Glynn
Published: October 2003

Background

Burkitt lymphoma (BL) accounts for 50% of childhood cancer in Malawi. Lack of resources precludes the use of new successful treatment approaches such as the LMB 89 group B protocol, which cures >80% of children with stage III BL with high dose chemotherapy and matching supportive care. Our objective was to achieve a good cure rate in Murphy stage I–III BL with manageable toxicity in Malawi at a drug cost of <1,000 US dollars per patient.

Procedure

The intensity and toxicity of the LMB 89 group B protocol was reduced and adapted to Malawi realities. All stages received the same treatment. Children with suspected BL in the period July 1997–November 1999 were subjected to abdominal ultrasound, a tumor biopsy and/or fine needle aspirate (FNA) and bone marrow (BM), cerebrospinal fluid (CSF), and peripheral blood examination. HIV seropositive children were excluded. Endpoints are projected event free survival (EFS) at minimum 1 year, blood and gastro‐intestinal tract toxicity, and risk for and severity of infections.

Results

Forty‐four children were eligible for treatment and analysis. Their median age was 7.2 years, M:F ratio 1.4:1 with 10 stage I, 5 stage II, and 29 stage III patients. Projected Kaplan–Meier EFS for all was 57% (CI 41–73) at 1 year with 90% EFS in stage I and 52% EFS in stage III. The survival curve remained stable at 500 days. Toxicity and delays in appropriate supportive care contributed to ten deaths during treatment. Local recurrent tumor caused five and CNS recurrence one death. Two children died from progressive disease. The incidence of severe (grade 3 and/or 4) hematologic toxicity varied from 13% to 36%, gastro‐intestinal toxicity (GIT) from 2% to 17%, and infections from 7% to 41% per chemotherapy module.

Conclusions

It is possible to administer less intense and less costly multiagent chemotherapy to children with BL in a developing society with acceptable EFS rates. Adequate supportive care of the at‐times associated severe toxicity must be made available to better the results. Med Pediatr Oncol 2003;41:532–540. © 2003 Wiley‐Liss, Inc.
Epigenetic changes in the DAP‐kinase CpG island in pediatric lymphoma
Authors: Shiramizu Bruce , Mick Paul
Published: October 2003

Background

Hypermethylation of CpG islands in the promoter region of death‐associated protein kinase (DAP‐kinase) coupled with the loss of γ‐interferon‐induced apoptosis have been reported in B‐cell malignancies suggesting a role in pathogenesis or prognosis. Along with B‐cell malignancies, pediatric lymphomas also include T‐cell non‐Hodgkin lymphoma (NHL), anaplastic large cell lymphoma, and Hodgkin disease, each with unique prognoses. The purpose of this study was to elucidate epigenetic changes in the DAP‐kinase promoter region of pediatric cases to determine associations with aberrant hypermethylation.

Procedures

Thirty‐nine cases of different lymphoid pathology [10 Burkitt lymphoma, 1 B‐cell NHL; 7 T‐cell lymphoblastic lymphoma; 4 anaplastic large cell lymphoma (LCL); 2 B‐cell LCL; 14 nodular sclerosing Hodgkin disease (NSHD); and 1 B‐cell acute lymphoblastic leukemia (ALL)] had methylation‐specific polymerase chain reaction performed on bisulfite‐treated DNA, which distinguishes the methylation status of the promoter region, and DAP‐kinase mRNA expression assays performed on available specimens.

Results

In normal lymphocytes, the CpG islands in the promoter region were unmethylated, as were the T‐cell lymphoblastic lymphoma and anaplastic LCL. In contrast, 100% of the Burkitt lymphoma (10/10) and B‐cell ALL (1/1) were hypermethylated. Of the specimens with mRNA available, 7/8 Burkitt lymphoma had no DAP‐kinase mRNA expression compared to normal expression in 3/3 and 4/4 T‐cell lymphoblastic lymphoma and NSHD, respectively.

Conclusions

In these pediatric lymphoid tumors, hypermethylation of the DAP‐kinase promoter region with associated loss of DAP‐kinase gene expression was associated with B‐cell malignancies and thus may be important in the development and/or provide a prognostic tool in B‐ cell lymphomas. Med Pediatr Oncol 2003;41:527–531. © 2003 Wiley‐Liss, Inc.
Langerhans cell histiocytosis patients have HLA Cw7 and DR4 types associated with specific clinical presentations and no increased frequency in polymorphisms of the tumor necrosis factor alpha promoter
Authors: McClain Kenneth L. , Laud Purnima , Wu Wen‐Shu , Pollack Marilyn S.
Published: October 2003

Background

Current theory on the etiology of Langerhans cell histiocytosis (LCH), formerly Histiocytosis‐X, is that abnormality(ies) of the immune system are responsible for dysregulation of Langerhans cells (LC) in patients' lesions. Among the known abnormalities in LCH patients are increased amounts of tumor necrosis factor alpha (TNF‐α) and other cytokines in the lesions.

Procedure

We investigated the human leukocyte antigen (HLA) phenotypes of 29 patients and 37 healthy family members to determine if any haplotypes segregate with the presence or locations of the disease. The lymphocyte subsets for 22 patients and 11 family members were also determined.

Results

Patients with single bone, multiple bone, or multi‐system LCH had different relative proportions of HLA types. Patients presenting with single bone disease had an especially high frequency of the DR4 type. In this patient group, every Caucasian patient had either Cw7 or DR4. Lymphopenia was documented in patients who had been off therapy as well as those who only had surgical curetage of their lesions. Family members also had low numbers of T lymphocytes. There were fewer mutations of the TNF‐α promoter in patients than in the general population.

Conclusions

Although there is an increased percentage of LCH patients with DR4 and/or Cw7 there was also an increased prevalence of this antigen as well as lymphopenia among unaffected family members. Additional genetic and/or environmental factors are necessary to explain this association. TNF‐α promoter mutations are not responsible for the increased production of this cytokine. Med Pediatr Oncol 2003;41:502–507. © 2003 Wiley‐Liss, Inc.
Prevalence and correlations of anal incontinence and constipation in Taiwanese women
Authors: Chen Gin‐Den , Hu Suh‐Woan , Chen Yi‐Ching , Lin Tzu‐Li , Lin Long‐Yau
Published: October 2003

Anal incontinence and constipation are not only physically and psychologically disabling symptoms but also a significant social and public health problem. The epidemiology of anal incontinence and constipation from community‐bases remains largely unknown, especially in Asian women. This study is a continuation of a previous survey taken on the epidemiology of urinary incontinence and overactive bladder in Taiwanese women by using a second questionnaire (correlation coefficient for symptoms, r=0.87; P<0.05). We evaluated the prevalence and potential risk factors associated with anal incontinence and constipation in the general population. Of the 1,584 (2.92%) women sampled, 1,253 (79.1%) were successfully interviewed at home. The prevalence of fecal incontinence and flatus incontinence was 35 (2.8%) and 107 (8.6%), respectively. There were 306 (24.5%) participants who reported constipation. However, according to the current medical criteria for constipation, the prevalence of constipation was only 2.7%. The prevalence of anal incontinence did not increase after the age of 65 years (9.7%, including 3.5% of elderly women with fecal incontinence and 6.2% of elderly women with flatus incontinence). The prevalence of constipation significantly increased in the women aged 65 years and over (self‐reported prevalence: 32.4%, fitted in medical criteria for constipation: 8.3%). Our results demonstrated that constipation shares some of the same risk factors, namely, symptoms of uterovaginal prolapse, prior gynecologic surgery, and overactive bladder that predispose women to the occurrence of anal incontinence. The questionnaire needs a higher discriminatory capacity, and a longitudinal study should be conducted to clarify this conflict further. Neurourol. Urodynam. 22:664–669, 2003. © 2003 Wiley‐Liss, Inc.
Bladder–anal reflex
Authors: Basinski Cindy , Fuller Elizabeth , Brizendine Edward J. , Benson J. Thomas
Published: October 2003

Aims

The purposes of this study were to evaluate the bladder–anal reflex (BAR) latency in asymptomatic women and determine the pathway of the reflex using selective anesthesia and neuromuscular block.

Methods

Urinary incontinence, voiding dysfunction, and pelvic organ prolapse are common problems in women. Evaluation of pelvic nerve function often augments the clinical assessment of these women. Urethral–anal and clitoral–anal reflex testing have been reported as methodologies to assess patients with neurogenic disorders. A bladder–anal reflex is also obtainable but has not been reported previously in the literature. Twenty‐two subjects and two patients were recruited for evaluation of the BAR.

Results

This study has allowed us to estimate reference ranges for BAR latency and threshold. We defined the upper limit of these reference ranges as two standard deviations above their respective means. For the BAR latency, the upper limit of the reference range is 91 msec. Any latency value above this limit should be considered abnormal. The upper limit for the BAR threshold reference range is 37.7 mA. Lower thresholds are not thought to be clinically meaningful due to the presence of several low sensory thresholds in this asymptomatic normal population.

Conclusions

The BAR was obtainable in asymptomatic women and compatible with known anatomy and innervation of the lower urinary tract. Neurourol. Urodynam. 22:683–686, 2003. © 2003 Wiley‐Liss, Inc.
Compliance with a pelvic muscle exercise program as a causal predictor of urinary stress incontinence amongst Chinese women
Authors: Siu L.S. , Chang A.M. , Yip S.K. , Chang A.M.Z.
Published: October 2003

Aim

To determine the importance and contribution of compliance in a pelvic muscle exercise program as a factor in reducing the severity of urinary stress incontinence amongst Chinese women.

Methods

Two hundred fourteen women presenting with urinary stress incontinence who agreed to undertake a program of pelvic muscle exercises were recruited into the study. Incontinence (wetting episodes), pelvic muscle strength, exercises compliance, correctness of pelvic muscle exercise technique, duration of stress incontinence, and previous history of pelvic surgery were recorded on four occasions: baseline (first clinic session) and second to fourth clinic sessions. Demographic data were also collected at baseline. Stepwise multiple regression analyses were used to determine the relative importance of compliance to exercise regime in predicting the severity of incontinence. Path analysis was used to provide a summary description of the influence of compliance on the outcomes over the four visits.

Results

The pelvic muscle training program appears to be able to reduce the overall urinary incontinence episodes by 85.2% and achieved a 73.1% increase in pelvic muscle strength. Although the number of wetting episodes in any visit are causally linked to that recorded in previous visit, those who were more compliant had a greater reduction. Age, mode of delivery, menopausal status, history of pelvic surgery, and duration of incontinence did not appear to contribute significantly to predicting incontinence.

Conclusion

Compliance with pelvic muscle exercises significantly contributed to a reduction in urinary stress incontinence. Neurourol. Urodynam. 22:659–663, 2003. © 2003 Wiley‐Liss, Inc.
Dissociation between electrical and mechanical bulbocavernosus reflexes
Authors: Amarenco Gerard , Ismael Samer Sheikh , Bayle Beatrice , Kerdraon Jacques
Published: October 2003

Aims

To record reflex motor responses, elicited by mechanical stimulation of the penis or clitoris, in each bulbocavernosus muscles and to compare left and right reflex pathways in normal subjects, then to compare electrical and mechanical responses in various neurological diseases.

Methods

Two groups of patients were studied: 22 patients without neurological disease considered as normal subjects; and 25 patients with neurological disease (three multiple sclerosis, six spina bifida, nine conus medullaris syndrome, three peripheral neuropathies, two lumbosacral lesions, one multisystem atrophy, and one syringomyelia). Electrical bulbocavernosus reflex (EBCR) was evoked by orthodromic stimulation of the dorsal nerve of the penis at the penile base or the clitoris. Mechanical bulbocavernosus reflex (MBCR) was elicited with an electromechanical hammer, tapping directly on the clitoris zone or on the ventral part of glans penis. For EBCR and MBCR, bulbocavernosus muscle contractions were successively recorded in the left and in the right side with a needle inserted under visual guidance.

Results

Mean left mechanical latency was 31.7 msec (SD = 4.5) and right one 31.6 msec (SD = 3.8). The reproducibility of the responses was excellent (P < 0.0001). ). The mean difference between left and right latencies was 2 msec (SD = 1.2). In the neurological group, 22 EBCR (six right, nine left, seven bilateral) and 19 MBCR (eight right, nine left, two bilateral) were considered abnormal. The mean reflex latencies in patients with neurological lesions (lower motor neuron lesions) were statistically longer (P < 0.0001) than in normal subjects. Exact concordance (side of lesion) between MBCR and EBCR was observed in 15/25 cases (60%), poor concordance (presence of a sacral reflex alteration) in 3/25 (12%) cases, and in 7/25 (28%) cases there was a significant difference between the two techniques.

Conclusions

MBCR may provide a good alternative for electrical stimulation and can be used to evaluate urinary disorders when a neurological etiology is suspected. However, the presence of false negatives with MBCR suggest that it may be more useful as a screening test. Neurourol. Urodynam. 22:676–680, 2003. © 2003 Wiley‐Liss, Inc.
Urinary bladder hyperreflexia: A rat animal model
Authors: Shaker Hassan , Mourad Mohammed Sherif , Elbialy Mohammed Hatem , Elhilali Mostafa
Published: October 2003

In this work, we are presenting a rat animal model for bladder hyperreflexia after suprasacral spinal cord transection. Our aim was to standardize an animal model that can be useful in studying this condition. After standardizing the animal model in a pilot study, 26 female Sprague–Dawley rats were subjected to spinal cord transection at the level of T10 vertebra. Four animals were subjected to cystometrogram (CMG) 24 hr after spinalization and six rats 3 weeks post‐spinalization. These CMGs were compared to that of six normal controls. The detailed description of the model presented in this manuscript, is the final result after several modifications. All the animals consistently developed hyperreflexia after an initial period of spinal shock phase. Expressed volume of urine continued to decrease until it reached a plateau after peaking at 1‐week post‐spinalization. The attrition rate reached 27.3% after several improvements in the animal model and was mostly from self‐inflicted injuries. Post‐operative complications included hypothermia, decubitus ulcers, hematuria, urinary tract infection in addition to the unexplained death of two animals. In conclusion, we believe that this animal model closely resembles the clinical condition of hyperreflexia and follows similar course. The relative low cost of this animal model and the easy maintenance makes it a valuable tool to study such a condition. Neurourol. Urodynam. 22:693–698, 2003. © 2003 Wiley‐Liss, Inc.
Observations on the function of the female urethra: I: Relation between maximum urethral closure pressure at rest and urethral hypermobility
Authors: Schick Erik , Tessier Jocelyne , Bertrand Pierre E. , Dupont Charles , Jolivet‐Tremblay Martine
Published: October 2003

Aims

To study the relation between maximum urethral closure pressure at rest and urethral hypermobility in female patients.

Patients and Methods

We selected 255 patients aged 20 years and older, with a stable bladder on multichannel urodynamics, without known neurological pathology, and without a history of pelvic or anti‐incontinence surgery. A resting urethral pressure profile and the degree of urethral hypermobility were registered. Two‐tailed analyses of variance (ANOVA) with Fisher's post‐hoc tests were used to detect any statistically significant difference (P < 0.05) in urethral closure pressure between groups with varying degrees of urethral hypermobility.

Results

Mean age was 45.6 ± 12.7 (range 20–77) years. Mean maximum urethral closure pressure for the entire group was 62.7 ± 29 (range 10–150) cm of water. A statistically significant inverse relationship was found between age and maximum urethral closure pressure (r = 0.489, P < 0.0001) when both analyzed as continuous variables, and with age categorized in 10‐year increments (P < 0.0001). When comparing mean urethral closure pressure in each group examined for urethral hypermobility, a statistically significant difference was noted when grades I, II, and III were compared to grade 0 hypermobility. No significant difference was observed when grades I, II, and III were compared to each other. Even if statistically non‐significant, there exists an inverse relationship between the degree of urethral hypermobility and the maximum urethral closure pressure: a higher hypermobility is associated with a lesser urethral closure pressure.

Conclusions

Urethral closure pressure falls significantly when urethral hypermobility is present. This decrease is not related to patient's age or parity. Our observations demonstrate an inverse relation between urethral closure pressure and the degree of cysto‐urethrocele. As hypermobility increases, closure pressure decreases, even if this decrease does not reach the level of statistical significance. Neurourol. Urodynam. 22:643–647, 2003. © 2003 Wiley‐Liss, Inc.
Preconditioning protects the guinea‐pig urinary bladder against ischaemic conditions in vitro
Authors: Lorenzi Bruno , McMurray Gordon , Jarvis Gavin , Brading Alison F.
Published: October 2003

Aims

To investigate the ability of ischaemic preconditioning (IPC) to protect guinea‐pig detrusor from damage caused by a subsequent more prolonged exposure to ischaemic conditions.

Materials and Methods

Smooth muscle strips were mounted for tension recording in small organ baths continuously superfused with Krebs' solution at 37°C. Ischaemia was mimicked by removing oxygen and glucose from the superfusing solution. Contractile responses to electrical field stimulation (EFS) and carbachol were monitored. Three regimes of preconditioning were examined: 15, 10, and 5 min of ischaemic conditions followed by 15, 10, and 5 min of normal conditions, respectively.

Results

Without preconditioning, nerve‐mediated responses were significantly and proportionally reduced by periods of ischaemic conditions lasting for 45, 60, and 90 min, but recovered fully after exposure to ischaemic conditions for 30 min. The recovery of the responses to EFS was significantly improved in preconditioned strips when the period of ischaemic conditions was 45 or 60 min. However, no significant differences were seen with preconditioning when the period of ischaemic conditions was 90 min. The recovery of responses to carbachol was much greater than for the responses to EFS, and no significant differences were found between control and preconditioned strips.

Conclusions

It is suggested that in vivo short periods of transient ischaemia may be able to protect the guinea‐pig bladder from the impairment associated with longer periods of ischaemia and reperfusion, which might happen in obstructed micturition. Our results also indicate that the phenomenon affects mainly the intrinsic nerves, which are more susceptible to ischaemic damage than the smooth muscle. Neurourol. Urodynam. 22:687–692, 2003. © 2003 Wiley‐Liss, Inc.
Development of a dynamometer for measuring the isometric force of the pelvic floor musculature
Authors: Dumoulin Chantale , Bourbonnais D. , Lemieux M.‐C.
Published: October 2003

Aims

The aim of this study was to design and develop a dynamometer providing a direct measurement of pelvic floor muscle (PFM) strength.

Materials and Methods

Two pairs of strain gauges were mounted on the moveable branch of a dynamometric speculum allowing measurements at different vaginal apertures. Linearity, repeatability, independence of the site of application of the resultant force to the lower branch of the speculum and hysteresis were tested by means of in vitro calibration studies.

Results

The linearity proved excellent over a range of 0–15 N with regression coefficients close to unity between imposed loads and voltage outputs. The slopes and intercepts of the regression lines were not significantly different between repeated sessions, indicating the high reliability of these in vitro measurements. The slopes and intercepts of the calibrations, using the same repertoire of loads imposed at three locations on the moving branch of the dynamometer, were not significantly different, confirming that the force measurement is independent of the site of the force application. Hysteresis was considered to be minimal.

Conclusions

This study demonstrates that the dynamometer provides reliable measurements. The new device thus appears to have conceptual and measuring advantages over conventional methods and seems to be a very promising instrument for measuring pelvic floor strength. Neurourol. Urodynam. 22:648–653, 2003. © 2003 Wiley‐Liss, Inc.
Frequency‐volume charts: A tool to evaluate bladder sensation
Authors: Wachter Stefan De , Wyndaele Jean‐Jacques
Published: October 2003

Aims

Bladder sensation is routinely evaluated by cystometric bladder filling and electrical stimulation. These methods require catheterization and stimulate the bladder artificially. In this study, we evaluated whether frequency‐volume charts can be used as a non‐invasive tool to study bladder sensation during normal daily life. Furthermore the agreement between sensory data obtained from frequency‐volume charts and conventional cystometric bladder filling is studied.

Materials and Methods

Fifteen healthy female students filled out frequency‐volume charts at home and scored the grade of perception of bladder fullness at each micturition. They also measured the volume of three voidings after postponing micturition as long as possible. Sensation of bladder filling was finally evaluated during cystometry.

Results

On frequency‐volume charts, 65% of all voidings was made without desire to void, only 9.5% was with strong desire. Urgent desire to void was not reported except after voluntarily postponing micturition. Higher grades of perception of fullness were associated with significantly higher voided volumes. Mean volumes for the different sensations of fullness on the charts were not significantly different from volumes at different sensations reported during cystometry.

Conclusions

In conclusion, bladder sensation during daily life can be evaluated by scoring the grade of perception of fullness on frequency‐volume charts. During life voiding usually occurs without desire to void. The voided volumes at different sensations of fullness are comparable to the volumes at different sensations of filling during cystometry. Therefore, frequency‐volume charts with evaluation of perception of fullness may provide an initial non‐invasive tool to study bladder sensation. Neurourol. Urodynam. 22:638–642, 2003. © 2003 Wiley‐Liss, Inc.
Functions of intermediate filaments in neuronal development and disease
Authors: Lariviere Roxanne C. , Julien Jean‐Pierre
Published: October 2003

Five major types of intermediate filament (IF) proteins are expressed in mature neurons: the three neurofilament proteins (NF‐L, NF‐M, and NF‐H), α‐internexin, and peripherin. While the differential expression of IF genes during embryonic development suggests potential functions of these proteins in axogenesis, none of the IF gene knockout experiments in mice caused gross developmental defects of the nervous system. Yet, deficiencies in neuronal IF proteins are not completely innocuous. Substantial developmental loss of motor axons was detected in mice lacking NF‐L and in double knockout NF‐M;NF‐H mice, supporting the view of a role for IFs in axon stabilization. Moreover, the absence of peripherin resulted in ≈30% loss of small sensory axons. Mice lacking NF‐L had a scarcity of IF structures and exhibited a severe axonal hypotrophy, causing up to 50% reduction in conduction velocity, a feature that would be very detrimental for large animal species. Unexpectedly, the NF‐M rather than NF‐H protein turned out to be required for proper radial growth of large myelinated axons. Studies with transgenic mice suggest that some types of IF accumulations, reminiscent of those found in amyotrophic lateral sclerosis (ALS), can have deleterious effects and even cause neurodegeneration. Additional evidence for the involvement of IFs in pathogenesis came from the recent discovery of neurofilament gene mutations linked to ALS and Charcot‐Marie‐Tooth disease (CMT2E). Conversely, we discuss how certain types of perikaryal neurofilament aggregates might confer protection in motor neuron disease. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 131–148, 2004
How actin filaments and microtubules steer growth cones to their targets
Authors: Zhou Feng‐Quan , Cohan Christopher S.
Published: October 2003

Guidance molecules steer growth cones to their targets by attracting or repelling them. Turning in a new direction requires remodeling of the growth cone and bending of the axon. This depends upon reorganization of actin filaments and microtubules, which are the primary cytoskeletal components of growth cones. This article discusses how these cytoskeletal components induce turning. The importance of each component as well as how interactions between them result in axon guidance is discussed. Current evidence shows that microtubules are influenced by both the organization and dynamics of actin filaments in the peripheral domain of growth cones. Cytoskeletal models for repulsive and attractive turning are presented. Molecular candidates that may link actin filaments with microtubules are suggested and potential signal transduction pathways that allow these cytoskeletal components to affect each other are discussed. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 84–91, 2004
Cytoskeletal‐associated proteins in the migration of cortical neurons
Authors: Bielas Stephanie L. , Gleeson Joseph G.
Published: October 2003

Neuronal migration is a hallmark of cerebral cortical development as neurons born deep within the brain migrate to the surface in a highly choreographed process. The cytoskeleton extends throughout the cell, mediating the dramatic morphological changes that accompany migration. On a cellular level, proper migration is accompanied by polarization of the cytoskeleton and cellular contents and by dynamic reorganization that generates the force for cell locomotion. Genetic analyses of human brain malformations, as well as genetically engineered mouse mutants, have highlighted a number of cytoskeletal‐associated proteins underlying these functions, which are necessary for proper cortical development. While these proteins are involved in diverse molecular mechanisms, disruption during development results in the ectopic placement of neurons in the cortex. We review key cytoskeletal events and the critical cytoskeletal‐associated proteins involved in cortical neuronal migration. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 149–159, 2004
Regulation of growth cone actin filaments by guidance cues
Authors: Gallo Gianluca , Letourneau Paul C.
Published: October 2003

The motile behaviors of growth cones at the ends of elongating axons determine pathways of axonal connections in developing nervous systems. Growth cones express receptors for molecular guidance cues in the local environment, and receptor‐guidance cue binding initiates cytoplasmic signaling that regulates the cytoskeleton to control growth cone advance, turning, and branching behaviors. The dynamic actin filaments of growth cones are frequently targets of this regulatory signaling. Rho GTPases are key mediators of signaling by guidance cues, although much remains to be learned about how growth cone responses are orchestrated by Rho GTPase signaling to change the dynamics of polymerization, transport, and disassembly of actin filaments. Binding of neurotrophins to Trk and p75 receptors on growth cones triggers changes in actin filament dynamics to regulate several aspects of growth cone behaviors. Activation of Trk receptors mediates local accumulation of actin filaments, while neurotrophin binding to p75 triggers local decrease in RhoA signaling that promotes lengthening of filopodia. Semaphorin IIIA and ephrin‐A2 are guidance cues that trigger avoidance or repulsion of certain growth cones, and in vitro responses to these proteins include growth cone collapse. Dynamic changes in the activities of Rho GTPases appear to mediate responses to these cues, although it remains unclear what the changes are in actin filament distribution and dynamic reorganization that result in growth cone collapse. Growth cones in vivo simultaneously encounter positive and negative guidance cues, and thus, growth cone behaviors during axonal pathfinding reflect the complex integration of multiple signaling activities. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 92–102, 2004
Actin and microtubules in neurite initiation: Are MAPs the missing link?
Authors: Dehmelt Leif , Halpain Shelley
Published: October 2003

During neurite initiation microtubules align to form a tight bundle and actin filaments reorganize to produce a growth cone. The mechanisms that underlie these highly coordinated cytoskeletal rearrangements are not yet fully understood. Recently, various levels of coordination between the actin‐ and microtubule‐based cytoskeletons have been observed during cellular migration and morphogenesis, processes that share some similarities to neurite initiation. Direct, physical association between both cytoskeletons has been suggested, because microtubules often preferentially grow along actin bundles and transiently target actin‐rich adhesion complexes. We propose that such physical association might be involved in force‐based interactions and spatial organization of the two networks during neurite initiation as well. In addition, many signaling cascades that affect actin filaments are also involved in the regulation of microtubule dynamics, and vice versa. Although several candidates for mediating these effects have been identified in non‐neuronal cells, the general mechanism is still poorly understood. In neurons certain plakins and neuron‐specific microtubule associated proteins (MAPs), like MAP1B and MAP2, which can bind to both microtubules and F‐actin, are promising candidates to play key roles in the specific cytoskeletal rearrangements controlling the transition from an undifferentiated state to neurite‐bearing morphology. Here we review the effects of MAPs on microtubules and actin, as well as the coordination of both cytoskeletons during neurite initiation. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 18–33, 2004
Myosin function in nervous and sensory systems
Authors: Brown Michael E. , Bridgman Paul C.
Published: October 2003

Development of the nervous system requires remarkable changes in cell structure that are dependent upon the cytoskeleton. The importance of specific components of the neuronal cytoskeleton, such as microtubules and neurofilaments, to neuronal function and development has been well established. Recently, increasing focus has been put on understanding the functional role of the actin cytoskeleton in neurons. Important modulators of the actin cytoskeleton are the large family of myosins, many of which (classes I, II, III, V, VI, VII, IX, and XV; Fig. 1) are expressed in developing neurons or sensory cells. Myosins are force‐producing proteins that have been implicated in a wide variety of cellular functions in the developing nervous system, including neuronal migration, process outgrowth, and growth cone motility, as well as other aspects of morphogenesis, axonal transport, and synaptic and sensory functions. We review the roles that neuronal myosins play in these functions with particular focus on the first three events listed above, as well as sensory function. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 118–130, 2004
Efficient preconditioners for boundary element matrices based on grey‐box algebraic multigrid methods
Authors: Langer U. , Pusch D. , Reitzinger S.
Published: October 2003

This paper is concerned with the iterative solution of the boundary element equations arising from standard Galerkin boundary element discretizations of first‐kind boundary integral operators of positive and negative order. We construct efficient preconditioners on the basis of so‐called grey‐box algebraic multigrid methods that are well adapted to the treatment of boundary element matrices. In particular, the coarsening is based on an auxiliary matrix that represents the underlying topology in a certain sense. This auxiliary matrix is additionally used for the construction of the smoothers and the transfer operators. Finally, we present the results of some numerical studies that show the efficiency of the proposed algebraic multigrid preconditioners. Copyright © 2003 John Wiley & Sons, Ltd.
A polynomial collocation method for the numerical solution of weakly singular and singular integral equations on non‐smooth boundaries
Authors: Monegato G. , Scuderi L.
Published: October 2003

The aim of this paper is to show the efficiency of the use of smoothing changes of variable in the numerical treatment of 1D and 2D weakly singular and singular integral equations. The introduction of a smoothing transformation, besides smoothing the solution, allows also the use of a very simple and efficient collocation method based on Chebyshev polynomials of the first kind and their zeros. Further, we propose proper smoothing changes of variable also for the numerical approximation of those collocation matrix elements, which are given by weakly singular, singular or nearly singular integrals. Several numerical tests are given to point out the efficiency of the numerical approach we propose. Copyright © 2003 John Wiley & Sons, Ltd.
A solid‐like shell element allowing for arbitrary delaminations
Authors: Remmers Joris J. C. , Wells Garth N. , Borst René de
Published: October 2003

In this contribution a new finite element is presented for the simulation of delamination growth in thin‐layered composite structures. The element is based on a solid‐like shell element: a volume element that can be used for very thin applications due to a higher‐order displacement field in the thickness direction. The delamination crack can occur at arbitrary locations and is incorporated in the element as a jump in the displacement field by using the partition of unity property of finite element shape functions. The kinematics of the element as well as the finite element formulation are described. The performance of the element is demonstrated by means of two examples. Copyright © 2003 John Wiley & Sons, Ltd.
An enriched finite element method and level sets for axisymmetric two‐phase flow with surface tension
Authors: Chessa Jack , Belytschko Ted
Published: October 2003

A finite element method for axisymmetric two‐phase flow problems is presented. The method uses an enriched finite element formulation, in which the interface can move arbitrarily through the mesh without remeshing. The enrichment is implemented by the extended finite element method (X‐FEM) which models the discontinuity in the velocity gradient at the interface by a local partition of unity. It provides an accurate representation of the velocity field at interfaces on an Eulerian grid that is not conformal to the weak discontinuity. The interface is represented by a level set which is also used in the construction of the element enrichment. Surface tension effects are considered and the interface curvature is computed from the level set field. The method is demonstrated by several examples. Copyright © 2003 John Wiley & Sons, Ltd.
Analysis of a subdomain‐based error estimator for finite element approximations of elliptic problems
Authors: Prudhomme S. , Nobile F. , Chamoin L. , Oden J. T.
Published: October 2003

In this article we analyze a subdomain residual error estimator for finite element approximations of elliptic problems. It is obtained by solving local problems on patches of elements in weighted spaces and provides an upper bound on the energy norm of the error when the local problems are solved in sufficiently enriched discrete spaces. A guaranteed lower bound on the error is also derived by a simple postprocess of the solutions to the local problems. Numerical tests show very good effectivity indices for both the upper and lower bounds and a strong reliability of this estimator even for coarse meshes. © 2003 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 20: 165–192, 2004