bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethical Decision Making in Family Therapy
Authors: ZYGMOND MARY JO , BOORHEM HARRIET
Published: August 2004

In family therapy, effective clinical decisions promote the welfare and interests of the family and its individual members. However, the needs of the family and its individual members are often in conflict. Resolving this conflict is an ethical as well as a therapeutic dilemma. Kitchener has developed a model of ethical decision making that we have found useful in teaching students and supervisees how to resolve conflicts between the family's needs and the needs of its members. The purpose of this article is to discuss this model and show how it can be applied to clinical decision making.
Definitional Deficit: A Model of Senile Dementia in Context
Authors: HANSON BARBARA GAIL
Published: August 2004

This article presents some general theoretical concepts that can be used to consider processes of reality construction in interpersonal contexts. I developed a model of family context that taps affective dimensions of reality construction and used this model to explore these processes as highlighted by the labeling of symptoms of senile dementia. Ethnographic observations of 45 families with aged members were used to sketch a dichotomous typology of family‐context patterns that promote symptom identification versus patterns that do not. The model suggests that the categorization of behavior as symptomatic or normal in context may be related to the extent to which reality construction processes are shared among members.
Transforming Helplessness: An Approach to the Therapy of “Stuck” Couples
Authors: FINEBERG DONALD E. , WALTER SYDNEY
Published: August 2004

Therapists working with couples often find themselves frustrated when they proceed to negotiate conflicts, even when the historical antecedents and psychological dynamics seem well understood. Despite the genuine willingness of each member to negotiate a solution, they remain stuck in demands that the other take the first steps toward change. This article proposes that a crucial step — transforming helplessness — must precede efforts at fostering communication/negotiation skills. A four‐square analysis of the situation helps to explain how this stalemate occurs. Also, it points the way to strategies that can transform the couple's attitudes from helpless complaining to empowered, creative action. Three case examples illustrate clinical applications of this approach.
Can Patients' Views of a Therapeutic System Predict Outcome? An Empirical Study with Depressive Patients
Authors: PRIEBE STEFAN
Published: August 2004

Using the principles of brief therapy as developed at the Mental Research Institute (MRI) in Palo Alto, this study examined how patients viewed psychiatrists' and significant others' attitudes toward the severity of their illness, as compared with their own attitude, and whether these views were related to outcome. Forty‐one depressive inpatients were asked a two‐part question — Who regards your illness as being more severe: (a) you or your significant others; (b) you or your psychiatrist? Two subsamples of patients were identified: those who viewed psychiatrists' and significant others' attitudes toward the illness as similar (equally structured systems) and those who viewed them as dissimilar (differently structured systems). Both groups showed equal and significant improvement during hospital treatment; but the group that viewed the attitudes held by psychiatrists and significant others as dissimilar reported improvement after discharge.
Observations about Family Interaction and the Effect of Therapy: Interviews with Families Eight Years after the Onset of Schizophrenia
Authors: VIRTANEN HILLKA , KEINÄANEN MATTI
Published: August 2004

This study focused on the development of and changes in the interaction within a family after the onset of schizophrenia in a family member. Special attention is given to the possible effects of various treatments on the interaction. Our method was a circular interview of all family members in a joint session 8 years after the onset of schizophrenia. We observed that changes in family interaction usually had taken place during the first year of the illness. Thereafter, family conditions and interactions seem to have remained relatively unchanged. On the other hand, in addition to actual family‐centered therapy, all other treatment modes — individual therapy, medication, hospitalization — seemed to have acted as systemic interventions on the family level. Our observation that family interactions and models of therapy often had a surprisingly strong resemblance led us to consider the idea of their coevolution over the years and the possible significance of this. This article aims at calling the reader's attention to the manifold influences that the onset of schizophrenia and its various treatments seem to have had on family systems.
Biology of Family Systems and Mood Disorders
Authors: SLOMAN LEON , GARDNER RUSSELL , PRICE JOHN
Published: August 2004

Ethology offers psychiatry and family therapy an alternative perspective for understanding hierarchical dysfunction and individual psychopathology and the relation between them. Dominance and submission behaviors — descriptions from ethology — represent communicational mechanisms that play pivotal roles in maintaining the stability of the family group. When conflict becomes acute, dominant and submissive states are experienced as euphoria and mild depression respectively. Smooth functioning of these communicational mechanisms at the individual level enhances cohesion at the group level. Feelings of inadequacy and inferiority may be manifestations of submissive patterns and may function to maintain negative or corrective feedback loops, which preserve group stability. However, these communicational mechanisms may exhibit positive feedback runaway effects such that family crises result. These and other clinical implications of the model are explored.
A Piagetian View of Family Therapy: Selvini‐Palazzoli and the Invariant Approach
Authors: GELCER ESTHER , SCHWARTZBEIN DAVID
Published: August 2004

The Invariant Approach of Mara Selvini‐Palazzoli is a new development in the Milan approach to family therapy. In order to distinguish and explain it, an overview of the Invariant Approach is given. Jean Piaget's theory of cognitive development is used to provide a framework for explaining how Selvini‐Palazzo‐li's therapy alters the family's epistemology and facilitates change in the “family game.” It is suggested that family members in therapy tend to think about their problems in a style that resembles Piaget ‘s preoperational period. The process of therapy can be seen as geared to facilitate a shift from a preoperational to an operational style of cognitive functioning. This shift gives family members access to more adaptive ways of thinking about their problem‐solving strategies.
Cellular, Molecular and Clinical Characterization of Patients with Hermansky–Pudlak Syndrome Type 5
Authors: Huizing Marjan , Hess Richard , Dorward Heidi , Claassen David A. , Helip‐Wooley Amanda , Kleta Robert , Kaiser‐Kupfer Muriel I. , White James G. , Gahl William A.
Published: August 2004

Hermansky–Pudlak syndrome (HPS) is a disorder of lysosome‐related organelles such as melanosomes and platelet dense granules. Seven genes are now associated with HPS in humans. An accurate diagnosis of each HPS subtype has important prognostic and treatment implications. Here we describe the cellular, molecular, and clinical aspects of the recently identified HPS‐5 subtype. We first analyzed the genomic organization and the RNA expression pattern ofHPS5, located on chromosome 11p14, and demonstrated tissue‐specific expression of at least three alternatively splicedHPS5mRNA transcripts, coding for HPS5A and HPS5B proteins, that differ at their 5′‐ends. Genetic screening of 15 unassigned HPS patients yielded six newHPS5mutations in four patients. Clinically, our HPS‐5 patients exhibited iris transillumination, variable hair and skin pigmentation, and absent platelet dense bodies, but not pulmonary fibrosis or granulomatous colitis. In two patients with homozygous missense mutations, hemizygosity was ruled out by gene‐dosage multiplex polymerase chain reaction, and immunocytochemical analyses of their fibroblasts supported the HPS‐5 diagnosis. Specifically, LAMP‐3 distribution was restricted to the perinuclear region in HPS‐5 fibroblasts, in contrast to the normal LAMP‐3 distribution, which extended to the periphery. This specific intracellular vesicle distribution in fibroblasts, in combination with the clinical features, will improve the characterization of the HPS‐5 subtype.
Lysosome Associated Membrane Protein 1 (Lamp1) Traffics Directly from the TGN to Early Endosomes
Authors: Cook Neil R. , Row Paula E. , Davidson Howard W.
Published: August 2004

The precise trafficking routes followed by newly synthesized lysosomal membrane proteins after exit from the Golgi are unclear. To study these events we created a novel chimera (YAL) having a lumenal domain comprising two tyrosine sulfation motifs fused to avidin, and the transmembrane and cytoplasmic domains of lysosome associated membrane protein 1 (Lamp1). The newly synthesized protein rapidly transited from the trans‐ Golgi Network (TGN) to lysosomes (t1/2∼ 30 min after a lag of 15–20 min). However, labeled chimera was captured by biotinylated probes endocytosed for only 5 min, indicating that the initial site of entry into the endocytic pathway was early endosomes. Capture required export of YAL from the TGN, and endocytosis of the biotinylated reagent, and was essentially quantitative within 2 h of chase, suggesting that all molecules were following an identical route. There was no evidence of YAL trafficking via the cell surface. Fusion of TGN‐derived vesicles with 5 min endosomes could be recapitulated in vitro, but neither late endosomes nor lysosomes could serve as acceptor compartments. This suggests that contrary to previous conclusions, most if not all newly synthesized Lamp1 traffics from the TGN to early endosomes prior to delivery to late endosomes and lysosomes.
Bph1p, the Saccharomyces cerevisiae Homologue of CHS1/Beige, Functions in Cell Wall Formation and Protein Sorting
Authors: Shiflett Shelly L. , Vaughn Michael B , Huynh Dinh , Kaplan Jerry , Ward Diane McVey
Published: August 2004

Mutations in the Chediak–Higashi syndrome gene (CHS1) and its murine homologue Beige result in the formation of enlarged lysosomes. BPH1 (Beige Protein Homologue 1) encodes the Saccharomyces cerevisiae homologue of CHS1/Beige. BPH1 is not essential and the encoded protein was found to be both cytosolic and peripherally bound to a membrane. Neither disruption nor overexpression of BPH1 affected vacuole morphology as assessed by fluorescence microscopy. The δbph1 strain showed an impaired growth on defined synthetic media containing potassium acetate buffered below pH 4.25, increased sensitivity to calcofluor white, and increased agglutination in response to low pH. A library screen identified VPS9, FLO1, FLO9, BTS1 and OKP1 as high copy suppressors of the growth defect of δbph1 on both low pH potassium acetate and calcofluor white. The δbph1 strain demonstrated a mild defect in sorting vacuolar components, including increased secretion of carboxypeptidase Y and missorting of alkaline phosphatase. Overexpression of VPS9, BTS1 and OKP1 suppressed the carboxypeptidase Y secretion defect of δbph1. Overexpression of BPH1 was found to suppress the calcofluor white sensitivity of a class E VPS deletion strain, δvta1. Together, these data suggest that Bph1p associates with a membrane and is involved in protein sorting and cell wall formation.
Challenges and Artifacts in Quantitative Photobleaching Experiments
Authors: Weiss Matthias
Published: August 2004

Confocal fluorescence recovery after photobleaching (FRAP) is today the prevalent tool when studying the diffusional and kinetic properties of proteins in living cells. Obtaining quantitative data for diffusion coefficients via FRAP, however, is challenged by the fact that both bleaching and scanning take a finite time. Starting from an experimental case, it is shown by means of computer simulations that this intrinsic temporal limitation can lead to a gross underestimation of diffusion coefficients. Determining the binding kinetics of proteins to membranes with FRAP is further shown to be severely hampered by additional diffusional contributions, e.g. diffusion‐limited binding. In some cases, the binding kinetics may even be masked entirely by diffusion. As current efforts to approach biological problems with biophysical models have to rely on experimentally determined model parameters, e.g. binding rates and diffusion constants, it is proposed that the accuracy in evaluating FRAP measurements can be improved by means of accompanying computer simulations.
Comparison Between Malignant and Nonmalignant Splenic Masses in Dogs using Contrast‐Enhanced Computed Tomography
Authors: Fife Wendy D. , Samii Valerie F. , Drost Wm Tod , Mattoon John S. , Hoshaw‐Woodard Stacy
Published: August 2004

The ability of computed tomography (CT) to distinguish malignant from nonmalignant splenic masses was evaluated in 21 dogs with 24 masses. CT scans of the abdomen were performed pre‐ and postintravenous contrast medium administration before splenectomy or euthanasia. Splenic masses were evaluated objectively based on Hounsfield units (HU) and volume. Subjective criteria included location within the spleen (head, body, or tail), margination, homogeneity, and attenuation compared to the remaining splenic parenchyma. Characteristics of malignant and nonmalignant masses were compared. The nonmalignant masses were divided into splenic hematomas and nodular hyperplasia for further analysis. Fourteen (58.3%) of the masses were nonmalignant; 10 (41.7%) were malignant. Malignant splenic masses had significantly lower attenuation values, measured in HU, than nonmalignant splenic masses, on both pre‐ and postcontrast images (P<0.05). On postcontrast images, there was a significant difference in attenuation characteristics among all three subsets of splenic masses (malignant, hematoma, hyperplasia), with nodular hyperplasia having the highest HU values (90.3), hematomas having intermediate HU values (62.5), and malignant splenic masses having the lowest HU values (40.1). A receiver operator characteristic curve of postcontrast medium HU values revealed 55 as the best threshold value to distinguish malignant from nonmalignant masses, with those less than the threshold value being malignant. Abdominal CT is a useful diagnostic imaging modality for evaluation of focal canine splenic masses, with a significant difference in imaging characteristics between malignant and nonmalignant masses.
Comparison of Seven Digital Cameras for Digitizing Radiographs
Authors: Brault Benjamin , Hoskinson James , Armbrust Laura , Milliken George
Published: August 2004

The purpose of this study was to evaluate seven digital cameras for their ability to adequately capture quality radiographic images and their relative cost effectiveness. Radiographs of line pair (LP) phantoms (ranging from 0.6 to 16.6 LP/mm) and a 20‐step contrast phantom were photographed at a near distance of 30.0 cm and a far distance (determined for each camera) at which a full 14 × 17 in film filled the viewfinder. Of the seven cameras tested, the Canon EOS‐D30 consistently performed the best in LP/mm resolved (7.7 at close distance, 1.4 at far distance) and in contrast latitude (all 20 steps at both close and far distances). The Canon EOS‐D30, determined to be the best camera used in this study for photographing radiographic images, is also the most expensive camera that was used. Two cameras, the Nikon Coolpix 995 and the Sony DSC‐F707, were very close to the Canon in performance at considerably less cost. Certain inexpensive cameras may not be acceptable choices for teleradiology.
Intramedullary Intervertebral Disk Extrusion in a Cat
Authors: Fraser McConnell J. , Garosi Laurent S.
Published: August 2004

Intervertebral disk extrusion is rarely reported in the cat. In this case, the clinical, radiologic, and magnetic resonance imaging findings of an acute intramedullary intervertebral disk extrusion in a 5‐year‐old domestic shorthaired cat are described. Radiographically, there was mineralized disk material within the vertebral canal. On magnetic resonance images, the disk material was found to be within the spinal cord. A linear disk trail extending from the disk space into the spinal cord may be specific for intramedullary disk extrusion.
Ultrasound‐Guided Atlanto‐Occipital Puncture for Myelography in the Horse
Authors: Audigié Fabrice , Tapprest Jackie , Didierlaurent D. , Denoix J.‐M.
Published: August 2004

Complications of cervical myelography arising from the puncture of the subarachnoid space to collect the cerebrospinal fluid and to inject the contrast medium have been described in humans and animals. In this study, 2 ultrasound‐guided procedures were developed for puncture of the atlanto‐occipital subarachnoid space, collection of cerebrospinal fluid, and injection of contrast medium. Myelography was performed on 6 ataxic horses using these procedures. The first attempt to puncture the subarachnoid space was successful in 5 horses and in one horse, a second attempt was necessary. Collection of cerebrospinal fluid and injection of contrast medium were achieved without difficulty. Ultrasound‐guided myelography allowed reduction of potential complications associated with blind percutaneous puncture of the subarachnoid space. Methods described in this study should be tried—at least initially in an experimental setting—to collect cerebrospinal fluid from the atlanto‐occipital site in standing horses where it may represent an alternative method when lumbosacral cerebrospinal fluid collection has been unsuccessful or contaminated with blood.
LABOR AND CORPORATE GOVERNANCE: INITIAL LESSONS FROM SHAREHOLDER ACTIVISM
Authors: Chakrabarti Monami
Published: August 2004

The recent crisis in the financial markets has revealed serious, systematic flaws in corporate governance and has cost union pension funds billions of dollars. However, the labor movement has begun to take charge of governance reform by mobilizing its pension assets, organizing other investors, and launching company‐specific shareholder campaigns. Drawing on the academic literature on social embeddedness, I argue that unions will be more likely to succeed through investor activism if they form coalitions with key non‐union actors. Through a detailed comparative case study of the American Federation of Labor‐Congress of Industrial Organizations’ efforts to stop the reincorporation of Nabors Industries and Stanley Works, Inc. and a larger empirical study of labor's 2002 shareholder campaigns, this article examines and outlines the factors that influence the success of these efforts. This research also elucidates how unions can continue to take the lead in corporate governance reform and build the necessary financial and political leverage to win shareholder campaigns.
EMPLOYER OPINIONS ON LIVING WAGE INITIATIVES*
Authors: Grant Don , Trautner Mary Nell
Published: August 2004

Why do some contractors oppose living wage ordinances (LWOs) while others do not? Can local government programs that take a more voluntary approach to creating living wages succeed? This article begins to address these questions through surveys of two sets of employers in the same community: a group of contractors subject to an LWO and the other a group of businesses that voluntarily pledged to pay their workers a living wage. Results suggest that contractors oppose such ordinances either because they are incapable of realizing efficiency gains or for purely ideological reasons. Findings also suggest that the only companies to participate in more voluntary programs are those that were already paying their workers a living wage. Implications of these results for the living wage movement are discussed.
Summary of the Recommendations on Sexual Dysfunctions in Men
Authors: Lue Tom F. , Giuliano François , Montorsi Francesco , Rosen Raymond C. , Andersson Karl-Erik , Althof Stanley , Christ George , Hatzichristou Dimitrios , Hirsch Mark , Kimoto Yasasuke , Lewis Ronald , McKenna Kevin , MacMahon Chris , Morales Alvaro , Mulcahy John , Padma-Nathan Harin , Pryor John , De Tejada Inigo Saenz , Shabsigh Ridwan , Wagner Gorm
Published: August 2004

Introduction

There are few published guidelines for the management of sexual dysfunctions in men and women, despite the prevalence and lack of attention to these problems. Disorders of sexual function in men include erectile dysfunction, orgasm/ejaculation disorders, priapism, and Peyronie's disease.

Aim

To provide evidence-based and expert-opinion consensus guidelines for the clinical management of men's sexual dysfunctions.

Methods

An International Consultation in collaboration with major urological and sexual medicine societies assembled over 200 multidisciplinary experts from 60 countries into 17 consultation committees. Committee members established the scope and objectives for each chapter. Following intensive review of available data and publications, committees developed evidence-based guidelines in each area.

Main Outcome Measure

New algorithms and guidelines for assessment and treatment of men's sexual dysfunction were developed. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of the medical literature, in addition to cultural and ethical considerations.

Results

Recommendations and guidelines for men's sexual dysfunction are presented. These guidelines were developed as evidence-based, patient-centered, and multidisciplinary in focus. For the clinical assessment and diagnosis of ED, a basic evaluation was recommended for all patients, with optional and specialized testing reserved for special cases. A new treatment algorithm is proposed. This algorithm provides a clinically relevant guideline for managing ED in the large majority of men. New treatment guidelines and algorithms are provided for men's orgasm and ejaculation disorders, including premature ejaculation, retrograde and delayed ejaculation. Finally, expert opinion-based guidelines for the clinical management of priapism and Peyronie's disease are provided.

Conclusions

Additional research is needed to validate and extend these guidelines. Nonetheless, this summary encompasses the recommendations concerning men's sexual dysfunctions presented at the 2nd International Consultation on Sexual Medicine in Paris, France, June 28–July 1, 2003.
Clinical Evaluation and Management Strategy for Sexual Dysfunction in Men and Women
Authors: Hatzichristou Dimitrios , Rosen Raymond C. , Broderick Gregory , Clayton Anita , Cuzin Beatrice , Derogatis Leonard , Litwin Mark , Meuleman Eric , O'Leary Michael , Quirk Frances , Sadovsky Richard , Seftel Allen
Published: August 2004

Introduction

The optimal approach for identification and evaluation of the sexual problems in men and women in primary care or general medicine practice has not been consensed.

Aim

To provide recommendations/guidelines concerning state-of-the-art knowledge for clinical evaluation and management strategies in the evaluation and treatment of sexual dysfunction in men and women, emphasizing evidence-based medicine and a patient-centered framework.

Methods

An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a 2-year period. Concerning the Clinical Evaluation and Management Strategies Committee, there were 12 experts from five countries.

Main Outcome Measure

Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate.

Results

Three concepts underlie sexual medicine management: (i) adoption of a patient-centered framework for evaluation and treatment; (ii) application of the principles of evidence-based medicine in diagnostic and treatment planning; and (iii) use of a unified management approach in men and women. When taken together, these three principles provide a balanced and integrated approach to sexual dysfunction management. Common algorithms for diagnosis and management of men and women with sexual dysfunction, brief sexual symptom checklists, basics in history and physical examination, indications for specialized referral and development of a follow-up strategy are presented.

Conclusions

More research is needed in understanding the role of evidence-based and patient-centered medicine in the clinical evaluation and management strategies of men and women with sexual dysfunction.
Disorders of Orgasm and Ejaculation in Men
Authors: McMahon Chris G. , Abdo Carmita , Incrocci Luca , Perelman Michael , Rowland David , Waldinger Marcel , Xin Zhong Cheng
Published: August 2004

Introduction

Ejaculatory/orgasmic disorders, common male sexual dysfunctions, include premature ejaculation, inhibited ejaculation, anejaculation, retrograde ejaculation and anorgasmia.

Aim

To provide recommendations/guidelines concerning state-of-the-art knowledge for management of ejaculation/orgasmic disorders in men.

Methods

An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a 2-year period. Concerning the Disorders of Ejaculation/Orgasm in Men Committee, there were nine experts from six countries.

Main Outcome Measure

Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate.

Results

Premature ejaculation management is dependent upon etiology. When secondary to ED, etiology-specific treatment is employed. When lifelong, initial pharmacotherapy (SSRI, topical anesthesia, PDE5 inhibitors) is appropriate. When associated with psychogenic/relationship factors, behavioral therapy is indicated. When acquired, pharmacotherapy and/or behavioral therapies are preferred. Retrograde ejaculation, diagnosed with spermatozoa and fructose in centrifuged post-ejaculatory voided urine, is managed by education, patient reassurance, pharmacotherapy or bladder neck reconstruction. Men with anejaculation or anorgasmia have a biologic failure of emission and/or psychogenic inhibited ejaculation. Men with age-related penile hypoanesthesia should be educated, reassured and be instructed in revised sexual techniques which maximize arousal.

Conclusions

More research is needed in understanding management of men with ejaculation/orgasmic dysfunction.
Endocrine Aspects of Female Sexual Dysfunction
Authors: Davis Susan R. , Guay André T. , Shifren Jan L. , Mazer Norman A.
Published: August 2004

Introduction

Various endogenous hormones, including estrogen, testosterone, progesterone and prolactin, may influence female sexual function.

Aim

To provide recommendations for the diagnosis and treatment of women with endocrinologic sexual difficulties.

Methods

The Endocrine Aspects of Female Sexual Dysfunction Committee was part of a multidisciplinary International Consultation. It included four experts from two countries and several peer reviewers.

Main Outcome Measure

Expert opinion was based on committee discussion, a comprehensive literature review and evidence-based grading of available publications.

Results

The impact of hormones on female sexual function and their etiological roles in dysfunction is complex. Research data are limited as studies have been hampered by lack of precise hormonal assays and validated measures of sexual function in women. Sex steroid insufficiency is associated with urogenital atrophy and may also adversely affect central sexual thought processes. Systemic estrogen/estrogen progestin therapy alleviates climacteric symptoms but there is no evidence that this therapy specifically improves hypoactive sexual desire disorder (HSDD) in premenopausal or postmenopausal women. Exogenous testosterone has been shown in small randomized controlled trials (RCT) to improve sexual desire, arousal and sexual satisfaction in both premenopausal and postmenopausal women. However, as there is no biochemical measure that clearly identifies who to treat, use of exogenous testosterone should be considered only after other causes of HSDD have been excluded, such as depression, relationship problems and ill health. The clinical assessment of HSDD should include detailed medical, gynecologic, sexual and psychosocial history and physical examination including the external/internal genitalia. Hormonal therapy should be individualized and risks/benefits fully discussed, and all treated women should be carefully followed up and monitored for therapeutic side effects.

Conclusions

There is a need for prospective, multi-institutional clinical trials to define safe and effective endocrine treatments for female sexual dysfunction.
Standards for Clinical Trials in Male Sexual Dysfunction: Erectile Dysfunction and Rapid Ejaculation
Authors: Hirsch Mark , Donatucci Craig , Glina Sidney , Montague Drogo , Montorsi Francesco , Wyllie Michael
Published: August 2004

Introduction

The introduction of safe and effective therapies for sexual dysfunctions depend upon appropriate clinical protocol design, study procedures, data collection and analysis.

Aim

To provide recommendations/guidelines concerning state-of-the-art knowledge for standards for clinical trials in sexual dysfunction in men, particularly in the areas of erectile dysfunction and rapid ejaculation.

Methods

An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a 2-year period. Concerning the Standards for Clinical Trials in Male Sexual Dysfunction Committee, there were six experts from four countries.

Main Outcome Measure

Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate.

Results

Drug development requires a multiphased approach. Phase 1 studies investigate multiple-dose safety, tolerability and pharmacokinetic issues. Phase 2 programs explore dose ranging (lowest effective, maximally tolerated and toxic doses). Phase 3 trials provide the substantial evidence including drug–drug interaction data and studies in special populations. Clinical studies require validated outcome assessment instruments conducted in defined but representative patient populations. Daily diaries or per-event questionnaires are patient-reported outcomes that assist in retrospective questionnaire interpretation. A qualified biostatistician should calculate the sample power for the trial, type of statistical model and design employed, use of covariate or subgroup analyses, and calculation of effect sizes.

Conclusions

More research is needed in developing standards for use in the development of clinical trials and outcomes assessment researching either erectile dysfunction or rapid ejaculation.
Standards for Clinical Trials in Sexual Dysfunctions of Women: Research Designs and Outcomes Assessment
Authors: Heiman Julia R. , Guess Marsha K. , Connell Kathleen , Melman Arnold , Hyde Janet Shibley , Segraves R. Taylor , Wyllie Michael G.
Published: August 2004

Introduction

Clinical trials on sexual dysfunctions in women are limited in spite of the fact that sexual dysfunctions are likely more common in women than in men. Currently there are no medications approved for treatment in women, and limited data on drug efficacy or psychological efficacy in well-controlled studies.

Aim

To provide recommendations/guidelines concerning state-of-the-art knowledge for the research design and outcome assessment standards for clinical trials in women's sexual dysfunctions.

Methods

An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a 2-year period. Concerning the Standards for Clinical Trials in Women's Sexual Dysfunctions Committee, there were seven experts from two countries.

Main Outcome Measure

Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate.

Results

A comprehensive update was created which included references and recommended guidelines for rationale and design of clinical trials, study populations, outcome assessments, protocol design and implementation, data analysis and reporting, as well as ethical and clinical issues related to sexual dysfunction research.

Conclusions

There is a need for more research in developing standards to be used when performing clinical trials and outcomes assessment research in sexual dysfunctions of women.
Salt-Inducible Multidrug Efflux Pump Protein in the Moderately Halophilic Bacterium
Chromohalobacter
sp
Authors: Tokunaga Hiroko , Mitsuo Kenjiro , Ichinose Sachiyo , Omori Akira , Ventosa Antonio , Nakae Taiji , Tokunaga Masao
Published: August 2004

It has been known that halophilic bacteria often show natural resistance to antibiotics, dyes, and toxic metal ions, but the mechanism and regulation of this resistance have remained unexplained. We have addressed this question by identifying the gene responsible for multidrug resistance. A spontaneous ofloxacin-resistant mutant derived from the moderately halophilic bacterium
Chromohalobacter
sp. strain 160 showed a two- to fourfold increased resistance to structurally diverse compounds, such as tetracycline, cefsulodin, chloramphenicol, and ethidium bromide (EtBr), and tolerance to organic solvents, e.g., hexane and heptane. The mutant produced an elevated level of the 58-kDa outer membrane protein. This mutant (160R) accumulated about one-third the level of EtBr that the parent cells did. An uncoupler, carbonyl cyanide
m
-chlorophenylhydrazone, caused a severalfold increase in the intracellular accumulation of EtBr, with the wild-type and mutant cells accumulating nearly equal amounts. The
hrdC
gene encoding the 58-kDa outer membrane protein has been cloned. Disruption of this gene rendered the cells hypersusceptible to antibiotics and EtBr and led to a high level of accumulation of intracellular EtBr. The primary structure of HrdC has a weak similarity to that of
Escherichia coli
TolC. Interestingly, both drug resistance and the expression of HrdC were markedly increased in the presence of a high salt concentration in the growth medium, but this was not observed in
hrdC
-disrupted cells. These results indicate that HrdC is the outer membrane component of the putative efflux pump assembly and that it plays a major role in the observed induction of drug resistance by salt in this bacterium.
Culture-Independent Analysis of Fecal Enterobacteria in Environmental Samples by Single-Cell mRNA Profiling
Authors: Chen Han , Ponniah Gomathinayagam , Salonen Nancy , Blum Paul
Published: August 2004

A culture-independent method called mRNA profiling has been developed for the analysis of fecal enterobacteria and their physiological status in environmental samples. This taxon-specific approach determines the single-cell content of selected gene transcripts whose abundance is either directly or inversely proportional to growth state. Fluorescence in situ hybridization using fluorochrome-labeled oligonucleotide probes was used to measure the cellular concentration of
fis
and
dps
mRNA. Relative levels of these transcripts provided a measure of cell growth state and the ability to enumerate fecal enterobacterial cell number. Orthologs were cloned by inverse PCR from several major enterobacterial genera, and probes specific for fecal enterobacteria were designed using multiple DNA sequence alignments. Probe specificity was determined experimentally using pure and mixed cultures of the major enterobacterial genera as well as secondary treated wastewater samples seeded with pure culture inocula. Analysis of the fecal enterobacterial community resident in unseeded secondary treated wastewater detected fluctuations in transcript abundance that were commensurate with incubation time and nutrient availability and demonstrated the utility of the method using environmental samples. mRNA profiling provides a new strategy to improve wastewater disinfection efficiency by accelerating water quality analysis.
Benzoic Acid, a Weak Organic Acid Food Preservative, Exerts Specific Effects on Intracellular Membrane Trafficking Pathways in
Saccharomyces cerevisiae
Authors: Hazan Reut , Levine Alexandra , Abeliovich Hagai
Published: August 2004

Microbial spoilage of food causes losses of up to 40% of all food grown for human consumption worldwide. Yeast growth is a major factor in the spoilage of foods and beverages that are characterized by a high sugar content, low pH, and low water activity, and it is a significant economic problem. While growth of spoilage yeasts such as
Zygosaccharomyces bailii
and
Saccharomyces cerevisiae
can usually be retarded by weak organic acid preservatives, the inhibition often requires levels of preservative that are near or greater than the legal limits. We identified a novel synergistic effect of the chemical preservative benzoic acid and nitrogen starvation: while exposure of
S. cerevisiae
to either benzoic acid or nitrogen starvation is cytostatic under our conditions, the combination of the two treatments is cytocidal and can therefore be used beneficially in food preservation. In yeast, as in all eukaryotic organisms, survival under nitrogen starvation conditions requires a cellular response called macroautophagy. During macroautophagy, cytosolic material is sequestered by intracellular membranes. This material is then targeted for lysosomal degradation and recycled into molecular building blocks, such as amino acids and nucleotides. Macroautophagy is thought to allow cellular physiology to continue in the absence of external resources. Our analyses of the effects of benzoic acid on intracellular membrane trafficking revealed that there was specific inhibition of macroautophagy. The data suggest that the synergism between nitrogen starvation and benzoic acid is the result of inhibition of macroautophagy by benzoic acid and that a mechanistic understanding of this inhibition should be beneficial in the development of novel food preservation technologies.
Ecology and Transmission ofListeria monocytogenesInfecting Ruminants and in the Farm Environment
Authors: Nightingale K. K. , Schukken Y. H. , Nightingale C. R. , Fortes E. D. , Ho A. J. , Her Z. , Grohn Y. T. , McDonough P. L. , Wiedmann M.
Published: August 2004

A case-control study involving 24 case farms with at least one recent case of listeriosis and 28 matched control farms with no listeriosis cases was conducted to probe the transmission and ecology ofListeria monocytogeneson farms. A total of 528 fecal, 516 feed, and 1,012 environmental soil and water samples were cultured forL. monocytogenes. While the overall prevalence ofL. monocytogenesin cattle case farms (24.4%) was similar to that in control farms (20.2%), small-ruminant (goat and sheep) farms showed a significantly (P< 0.0001) higher prevalence in case farms (32.9%) than in control farms (5.9%). EcoRI ribotyping of clinical (n= 17) and farm (n= 414) isolates differentiated 51 ribotypes.L. monocytogenesribotypes isolated from clinical cases and fecal samples were more frequent in environmental than in feed samples, indicating that infected animals may contribute toL. monocytogenesdispersal into the farm environment. Ribotype DUP-1038B was significantly (P< 0.05) associated with fecal samples compared with farm environment and animal feedstuff samples. Ribotype DUP-1045A was significantly (P< 0.05) associated with soil compared to feces and with control farms compared to case farms. Our data indicate that (i) the epidemiology and transmission ofL. monocytogenesdiffer between small-ruminant and cattle farms; (ii) cattle contribute to amplification and dispersal ofL. monocytogenesinto the farm environment, (iii) the bovine farm ecosystem maintains a high prevalence ofL. monocytogenes, including subtypes linked to human listeriosis cases and outbreaks, and (iv)L. monocytogenessubtypes may differ in their abilities to infect animals and to survive in farm environments.
Identification ofCarnobacteriumSpecies by Restriction Fragment Length Polymorphism of the 16S-23S rRNA Gene Intergenic Spacer Region and Species-Specific PCR
Authors: Rachman Cinta , Kabadjova Petia , Valcheva Rosica , Prévost Hervé , Dousset Xavier
Published: August 2004

The genusCarnobacteriumis currently divided into the following eight species:Carnobacterium piscicola,C. divergens,C. gallinarum,C. mobile,C. funditum,C. alterfunditum,C. inhibens, andC. viridans. An identification tool for the rapid differentiation of these eightCarnobacteriumspecies was developed, based on the 16S-23S ribosomal DNA (rDNA) intergenic spacer region (ISR). PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of this 16S-23S rDNA ISR was performed in order to obtain restriction profiles for all of the species. Three PCR amplicons, which were designated small ISR (S-ISR), medium ISR (M-ISR), and large ISR (L-ISR), were obtained for allCarnobacteriumspecies. The L-ISR sequence revealed the presence of two tRNA genes, tRNAAlaand tRNAIle, which were separated by a spacer region that varied from 24 to 38 bp long. This region was variable among the species, allowing the design of species-specific primers. These primers were tested and proved to be species specific. The identification method based on the 16S-23S rDNA ISR, using PCR-RFLP and specific primers, is very suitable for the rapid low-cost identification and discrimination of all of theCarnobacteriumspecies from other phylogenetically related lactic acid bacteria.
Bactericidal Activity of Glycinecin A, a Bacteriocin Derived from
Xanthomonas campestris
pv. glycines, on Phytopathogenic
Xanthomonas campestris
pv. vesicatoria Cells
Authors: Pham Huy Thang , Riu Key Zoung , Jang Kong Man , Cho Somi K. , Cho Moonjae
Published: August 2004

The ability of glycinecin A, a bacteriocin derived from
Xanthomonas campestris
pv. glycines 8ra, to kill closely related bacteria has been demonstrated previously by our group (S. G. Heu et al., Appl. Environ. Microbiol.
67:
4105-4110, 2001). In the present study, we aimed at determining the glycinecin A-induced cause of death. Treatment with glycinecin A caused slow dissipation of membrane potential and rapid depletion of the pH gradient. Glycinecin A treatment also induced leakage of potassium ions from
X. campestris
pv. vesicatoria YK93-4 cells and killed sensitive bacterial cells in a dose-dependent manner. Sensitive cells were killed within 2 h of incubation, most likely due to the potassium ion efflux caused by glycinecin A. These results suggest that the bactericidal mechanism of action of glycinecin A is correlated with the permeability of membranes to hydroxyl and potassium ions, leading to the lethal activity of the bacteriocin on the target bacteria.
Expression of a Temperature-Sensitive Esterase in a Novel Chaperone-Based
Escherichia coli
Strain
Authors: Ferrer Manuel , Chernikova Tatyana N. , Timmis Kenneth N. , Golyshin Peter N.
Published: August 2004

A new principle for expression of heat-sensitive recombinant proteins in
Escherichia coli
at temperatures close to 4°C was experimentally evaluated. This principle was based on simultaneous expression of the target protein with chaperones (Cpn60 and Cpn10) from a psychrophilic bacterium,
Oleispira antarctica
RB8
T
, that allow
E. coli
to grow at high rates at 4°C (maximum growth rate, 0.28 h
−1
) (M. Ferrer, T. N. Chernikova, M. Yakimov, P. N. Golyshin, and K. N. Timmis, Nat. Biotechnol. 21:1266-1267, 2003). The expression of a temperature-sensitive esterase in this host at 4 to 10°C yielded enzyme specific activity that was 180-fold higher than the activity purified from the non-chaperonin-producing
E. coli
strain grown at 37°C (32,380 versus 190 μmol min
−1
g
−1
). We present evidence that the increased specific activity was not due to the low growth temperature per se but was due to the fact that low temperature was beneficial to folding, with or without chaperones. This is the first report of successful use of a chaperone-based
E. coli
strain to express heat-labile recombinant proteins at temperatures below the theoretical minimum growth temperature of a common
E. coli
strain (7.5°C).
Polydextrose, Lactitol, and Fructo-Oligosaccharide Fermentation by Colonic Bacteria in a Three-Stage Continuous Culture System
Authors: Probert Hollie M. , Apajalahti Juha H. A. , Rautonen Nina , Stowell Julian , Gibson Glenn R.
Published: August 2004

In vitro fermentations were carried out by using a model of the human colon to simulate microbial activities of lower gut bacteria. Bacterial populations (and their metabolic products) were evaluated under the effects of various fermentable substrates. Carbohydrates tested were polydextrose, lactitol, and fructo-oligosaccharide (FOS). Bacterial groups of interest were evaluated by fluorescence in situ hybridization as well as by species-specific PCR to determine bifidobacterial species and percent-G+C profiling of the bacterial communities present. Short-chain fatty acids (SCFA) produced during the fermentations were also evaluated. Polydextrose had a stimulatory effect upon colonic bifidobacteria at concentrations of 1 and 2% (using a single and pooled human fecal inoculum, respectively). The bifidogenic effect was sustained throughout all three vessels of the in vitro system (
P
= 0.01 seen in vessel 3), as corroborated by the bacterial community profile revealed by %G+C analysis. This substrate supported a wide variety of bifidobacteria and was the only substrate where
Bifidobacterium infantis
was detected. The fermentation of lactitol had a deleterious effect on both bifidobacterial and bacteroides populations (
P
= 0.01) and decreased total cell numbers. SCFA production was stimulated, however, particularly butyrate (beneficial for host colonocytes). FOS also had a stimulatory effect upon bifidobacterial and lactobacilli populations that used a single inoculum (
P
= 0.01 for all vessels) as well as a bifidogenic effect in vessels 2 and 3 (
P
= 0.01) when a pooled inoculum was used. A decrease in bifidobacteria throughout the model was reflected in the percent-G+C profiles.