Effects of metal ions on fibroblasts and spiral ganglion cells.

Degeneration of spiral ganglion cells (SGC) after deafness and fibrous tissue growth around the electrode carrier after cochlear implantation are two of the major challenges in current cochlear implant research. Metal ions are known to possess antimicrobial and antiproliferative potential. The use of metal ions could therefore provide a way to reduce tissue growth around the electrode array after cochlear implantation. Here, we report on in vitro experiments with different concentrations of metal salts with antiproliferative and toxic effects on fibroblasts, PC-12 cells, and freshly isolated spiral ganglion cells, the target cells for electrical stimulation by a cochlear implant. Standard cell lines (NIH/3T3 and L-929 fibroblasts and PC-12 cells) and freshly isolated SGC were incubated with concentrations of metal ions between 0.3 µmol/liter and 10 mmol/liter for 48 hr. Cell survival was investigated by neutral red uptake, CellQuantiBlue assay, or counting of stained surviving neurons. Silver ions exhibited distinct thresholds for proliferating and confluent cells. For zinc ions, the effective concentration was lower for fibroblasts than for PC-12 cells. SGC showed comparable thresholds for reduced cell survival not only for silver and zinc ions but also for copper(II) ions, indicating that these ions might be promising for reducing tissue growth on the surface of CI electrode arrays. These effects were also observed when combinations of two of these ions were investigated.

[Concept of a pressure-controlled microstent for glaucoma therapy]. / Konzept eines druckgesteuerten Mikrostents für die Glaukomtherapie.

A pressure-controlled microstent could permanently normalise the intraocular pressure (IOP) for open-angle glaucoma therapy by drainage into the suprachoroidal space. The complex requirements demand new technical solutions as well as an improved understanding of specific cell biological processes at the implant's surface to develop effective local drug delivery (LDD) concepts and surface modifications. Fluid mechanical requirements were derived from physiological data and the analysis of commercial glaucoma implants. The technological basics for the production of suitable structures are refined ultra-short pulse laser technology and 2-photon polymerisation (2PP). All known glaucoma implants induce unwanted cell proliferation resulting in a loss of function. It is assumed that the activity of fibroblasts is low in the suprachoroidal space. However, it was seen that LDD concepts are required to control cell proliferation. Fibroblasts from sclera and choroidea were isolated und cultured as the most relevant cell types for in vitro investigation. Potential materials and drugs were investigated by cell viability tests for biocompatibility or suppression of cell viability. The fluid mechanical analysis leads to smallest stent lumina (ID = 50 µm) at anatomically suitable implant lengths (7 - 10 mm). Only pressure control can manage the individual conditions with changing IOP. Finite element analysis of valves showed the need for highly flexible structures. This can be achieved by combining basic structures with micromechanically active valves added by 2PP. The potential materials show perfect in vitro and in vivo biocompatibility. Ormocers which are best suited for 2PP are also highly biocompatible. The selected drugs paclitaxel and triamcinolon acetonide open a wide therapeutic window to impair fibroblast growth. The surgical procedure was established by implantation of prototypes in rabbit eyes, connecting the anterior chamber with the suprachoroidal space. Highly flexible implants are required for correct placement within the eye. The new concept of the microstent combines biomechanical approaches, technologies for microfabrication and current LDD concepts and opens new perspectives for glaucoma therapy.

[Current requirements for polymeric biomaterials in ear, nose and throat medicine]. / Aktuelle Anforderungen an polymere Biomaterialien in der Hals-Nasen-Ohrenheilkunde.

In recent years the ear, nose and throat medicine (ENT medicine) has been stimulated by numerous innovations in the field of implants which are based on new biomaterials and modern implant technologies. In this context, biomaterials integrated in living organisms have to allow for the technical requirements and the biological interactions between the implant and the tissue. With regard to their suitability, functional capability of the implant, which is complementary to the mechanical implant properties, sufficient stability against physiological media, as well as high biocompatibility are to be demanded. Another purpose of the use of biomaterials is the maintenance and the enhancement of biofunctionality over a long time period. These general requirements for biomaterials also have their validity in ENT medicine. Different materials are applied as biomaterials. Metals belong to the oldest biomaterials. In addition, alloys, ceramics, inorganic glasses and composites were tested. Furthermore, natural and synthetic polymers, which are primarily presented in this article regarding their properties and their applications as materials for cochlear implants, osteosynthesis implants, stents and novel scaffolds for tissue engineering, are increasingly applied. According to their use in permanent and temporary implants, polymers are to be differentiated between biostable and biodegradable polymers. The presented general and current requirements for biomaterials and biomaterial applications in ENT medicine demonstrate key aspects of the current biomaterial research in this field. They do as well document the high impact of the interdisciplinary collaboration of natural and medical scientists and engineers.

Association Between Vitamin D and Adrenal Parameters with Metabolic and Inflammatory Markers in Polycystic Ovary Syndrome.

Vitamin D deficiency has been related with metabolic alterations in polycystic ovary syndrome (PCOS). As well, hyperactivation of adrenal axis can be programmed early in life and could be related later with PCOS development. Our aim was to establish the relationship between vitamin D and adrenal parameters with metabolic alterations and inflammation markers in PCOS. In 73 patients and 33 controls, 25-hydroxyvitamin D (25-OH-D), total and bioavailable testosterone (TT and bioT), androstenedione (A4), SHBG, cortisol, insulin, and C-reactive protein (hs-CRP) were determined; HOMA and lipid accumulation product (LAP) index were calculated. All parameters were higher in patients than in controls, except for SHBG and 25-OH-D which were lower. Binary regression analysis showed that differences in TT, bioT, A4, insulin and HOMA were independent of body mass index and waist circumference but SHBG, hs-CRP, LAP and 25-OH-D were related to body weight and fat distribution. Binary logistic regression analysis showed that cortisol and 25-OH-D could be associated to PCOS development. Correlations found between LAP and insulin, HOMA and hs-CRP confirm it is a good indicator of metabolic complications. Vitamin D and cortisol association to PCOS development justifies future research to understand the role of vitamin D in PCOS and analyze patient's perinatal history and its possible relationship with hyperactivation of adrenal axis in adult life.

Anastomotic stenting in a porcine aortoiliac graft model.

The purpose of the study was to evaluate the feasibility of anastomotic stent application in a porcine aortoiliac graft model. In a total of 10 pigs, a polytetrafluoroethylene aortobi-iliac graft was implanted through a midline abdominal incision. The lower edge of the iliac vessel was graft-inverted about 1 mm to produce irregularities at the downstream anastomosis. After transverse graft incision, six stainless-steel stents, six poly-L-lactic acid (PLLA) stents and four PLLA stents with 10% polycaprolactone (PCL) were implanted at the iliac anastomotic site using a 6 mm balloon dilatation catheter. Four anastomotic sites were left untreated. After two weeks, the patency of graft limbs was evaluated by contrast-enhanced computed tomography (CT). Both metal and polymeric stent designs provided adequate flexibility to manoeuvre across the anastomotic site for expansion in the chosen position. After deployment, the stent-arterial wall contact was complete on a macroscopic view. On CT scan, all metal and PLLA-stented graft limbs were free of stenosis, whereas all PLLA/PCL stents were occluded. The non-stented graft limbs showed a stenosis of 50-70%. In summary, this model is feasible to assess preclinically the deployment and patency rate of an anastomotic stent and to test future stent developments.

Biodegradable polymeric stents for vascular application in a porcine carotid artery model: English version.

Over the past years the development of biodegradable polymeric stents has made great progress; nevertheless, essential problems must still be solved. Modifications in design and chemical composition should optimize the quality of biodegradable stents and remove the weaknesses. New biodegradable poly-L-lactide/poly-4-hydroxybutyrate (PLLA/P4HB) stents and permanent 316L stents were implantedendovascularly into both common carotid arteries of 10 domestic pigs. At 4 weeks following implantation, computed tomography (CT) angiography was carried out to identify the distal degree of stenosis. The PLLA/P4HB group showed a considerably lower distal degree of stenosis by additional oral application of atorvastatin (mean 39.81 ± 8.57 %) compared to the untreated PLLA/P4HB group without atorvastatin (mean 52.05 ± 5.80 %). The 316L stents showed no differences in the degree of distal stenosis between the group treated with atorvastatin (mean 44.21 ± 2.34 %) and the untreated group (mean 35.65 ± 3.72 %). Biodegradable PLLA/P4HB stents generally represent a promising approach to resolving the existing problems in the use of permanent stents. Restitutio ad integrum is only achievable if a stent is completely degraded.

Motivation for change and psychological distress in homeless substance abusers.

This study explores the treatment needs of homeless individuals participating in a large urban day shelter program. Alcohol and drug use, psychological distress, and stage of change were assessed in 100 participants presenting for services. The associations among substance use, risk perception, and readiness to change were examined for alcohol and drugs separately. Participants had high levels of psychological distress compared to "non-patient" samples. Eighty percent had used alcohol in the past 6 months, with 65% of those drinking at higher-risk levels; 60% had used drugs, with 82% in the higher-risk levels. While the majority felt that they drank and/or used drugs "too much", most were in precontemplation or contemplation stages of change. Intervention efforts for this population should focus on motivation, facilitation through the stages, and the associations between psychiatric symptoms and substance use.

Assessment of explanted PTCA balloons.

The data presented here are part of a on-going study to define the surface characteristics and properties of explanted PTCA catheters in a further effort to address some of the ramifications of the re-use issue. PTCA balloon catheter were examined after angioplasty in one hundred and sixty-eight patients (n = 168). This series included six balloon types from three manufacturers. The fresh fixed and dehydrated balloons were examined at first with light microscopy and then in a scanning electron microscope. X-ray semiquantitative microanalysis and FT-IR-ATR analysis were also performed on the balloons. Because most blood proteins are water soluble, we examined unfixed balloons with a protein silver staining kit for detection of adhered proteins described by Heukeshoven. A further method for protein detection is the Lowry-analysis. With this method water insoluble proteins can be observed. Our study has shown convincingly that all deployed angioplasty catheters were coated with adherent protein layers. Plaque particles were found embedded in the surfaces of most of the balloons examined. Fissuring and micro tearing of balloon surfaces was noted. FT-IR-ATR analyses of the blood contacted balloon surfaces did not show any peaks indicative of proteins on the balloon surface. The silver staining method also did not show any evidence of protein adsorption on the balloons. On the other hand, the Lowry-analysis yielded clear evidence that water insoluble proteins were adherent to the balloon surfaces. The average measured protein concentration was 17 microg/ml.

Use of a structured investigative protocol enhances young children's responses to free-recall prompts in the course of forensic interviews.

One hundred alleged victims of child sexual abuse (ages 4-12 years; M = 8.1 years) were interviewed by police investigators about their alleged experiences. Half of the children were interviewed using the National Institute of Child Health and Human Development's structured interview protocol, whereas the other children--matched with respect to their age, relationship with the alleged perpetrator, and seriousness of the alleged offenses--were interviewed using standard interview practices. Protocol-guided interviews elicited more information using open-ended prompts and less information using option-posing and suggestive questions than did standard interviews; there were no age differences in the amount of information provided in response to open-ended invitations. In 89% of the protocol interviews, children made their preliminary allegations in response to open-ended prompts, compared with 36% in the standard interviews.

Conducting investigative interviews of alleged sexual abuse victims.

OBJECTIVES: There were two aims: First, to describe the factors that influence children's competence and second, to discuss ways in which investigative interviewers can maximize the quality and quantity of information they obtain from alleged witnesses and victims. METHOD: No new research is described in this paper. Rather, the authors provide a focused review of the relevant literature designed to be maximally useful for practitioners. CONCLUSIONS: Children are often the only available sources of information about possible abusive experiences Research has shown that children can, in fact, be remarkably competent informants, although the quality and quantity of the information they provide is greatly influenced by the ways in which they are interviewed. This article describes ways in which investigative interviewers can maximize the amount and quality of information they elicit from alleged victims.

Investigative interviews of child witnesses in Sweden.

OBJECTIVE: To evaluate the structure and informativeness of interviews with 4- to 13-year-old alleged victims of sexual abuse in Sweden. METHOD: Seventy-two alleged victims of sexual abuse were interviewed by six experienced officers from one police district in Sweden. Our evaluation focused on the structure of the interviews, the distribution and timing of the investigators' utterance types, and the quantity and quality of the information provided by the children. RESULTS: Content analysis revealed that the interviewers relied primarily on option-posing and suggestive questions--together, these comprised 53% of their utterances--when interviewing the alleged victims. As a result, most of the details (57%) obtained from the children were elicited by option-posing and suggestive utterances. Only 6% of the interviewers' utterances were open-ended invitations, and these elicited only 8% of the information obtained. CONCLUSION: The reliance on option-posing and suggestive prompts may have reduced the accuracy of the information obtained, thereby interfering with the investigations, and reducing the forensic admissibility of the children's statements. This suggests a continuing need in Sweden, as in other countries, for interview practices that enhance the quality of information provided by young victims.

Criterion-based content analysis: a field validation study.

Transcripts of forensic interviews with 98 alleged victims of child sexual abuse were scored for the presence or absence of certain criteria believed to be more characteristic of accounts concerning experienced than nonexperienced events. Other information regarding the events was independently evaluated by individuals unfamiliar with the children's accounts. As predicted, more of the CBCA criteria were present in accounts independently rated as Likely or Very Likely to have occurred (M = 6.74) than in accounts of events deemed Unlikely or Very Unlikely to have occurred (M = 4.85). In addition, several of the criteria were helpful in distinguishing between plausible and implausible accounts. The group differences were not as dramatic as those reported in earlier studies, however, and the results suggest caution regarding forensic application of the CBCA system.

The effect of being a victim or witness of family violence on the retrieval of autobiographical memories.

OBJECTIVE: This study was designed to determine whether greater reliance on general memory retrieval in children was related to depression, and whether family violence affected the specificity of children's memory retrieval. METHOD: We compared children who had experienced some form of family violence with children who had never experienced any form of family violence, based on their responses to questions concerning child-parent and interparental disagreements. RESULTS: As expected, there was a positive correlation between the extent of "generic-categoric" memory retrieval and depression level. There was no evidence, however, that autobiographical memory was affected by family violence. CONCLUSIONS: This study is the first to report significant associations between depression and autobiographical memory style in children. The results suggest that the effect of family violence on children's memory retrieval may be mediated by depression.

The Memorandum of Good Practice: theory versus application.

OBJECTIVE: The goal of this study was to evaluate the quality of investigative interviews in England and Wales since implementation of the Memorandum of Good Practice (MOGP), which specified how forensic interviews of alleged child abuse victims should be conducted. METHOD: Transcripts of 119 videotaped interviews of alleged victims between the ages of 4 and 13 years were obtained from 13 collaborating police forces. Trained raters then classified the types of prompts used by the investigators to elicit substantive information from the children, and tabulated the number of forensically relevant details provided by the children in each response. RESULTS: Like their counterparts in the United States, Israel, and Sweden, forensic interviewers in England and Wales relied heavily on option-posing prompts, seldom using open-ended utterances to elicit information from the children. Nearly 40% of the information obtained was elicited using option-posing and suggestive prompts, which are known to elicit less reliable information than open-ended prompts do. CONCLUSION: Despite the clarity and specificity of the MOGP, its implementation appears to have had less effect on the practices of forensic interviewers in the field than was hoped. Further work should focus on ways of training interviewers to implement the superior practices endorsed by the MOGP and similar professional guidelines.

Investigative interviews of alleged sexual abuse victims with and without anatomical dolls.

Verbal and nonverbal responses by alleged victims of child sexual abuse were coded for length, amount of information, and the manner in which they were elicited by the interviewer. In 16 of the interviews, anatomical dolls were employed for the purposes of demonstration, whereas they were not used in another eight cases matched with respect to other characteristics of the children and the alleged events. Children interviewed with dolls provided an equivalent number of details and spoke as many words in the substantive portion of the interview as did children interviewed without dolls, and interviewers in the two groups used similar probes to elicit information. However, the average responses by the children were significantly longer and more detailed when dolls were not used. Children gave longer and more detailed responses to open-ended invitations when dolls were not used. Caution is necessary when interpreting these findings.

Assessing the value of structured protocols for forensic interviews of alleged child abuse victims.

OBJECTIVE: To evaluate the effectiveness of a structured interview protocol (NICHD Investigative Interview Protocol) operationalizing universally recommended guidelines for forensic interviews. METHOD: The NICHD Investigative Protocol was designed to maximize the amount of information obtained using recall memory probes, which are likely to elicit more accurate information than recognition memory probes. Forensic investigators were trained to use the NICHD protocol while conducting feedback-monitored simulation interviews. The utility of the protocol was then evaluated by comparing 55 protocol interviews with 50 prior interviews by the same investigators, matched with respect to characteristics likely to affect the richness of the children's accounts. The comparison was based on an analysis of the investigators' utterance types, distribution, and timing, as well as quantitative and qualitative characteristics of the information produced. RESULTS: As predicted, protocol interviews contained more open-ended prompts overall as well as before the first option-posing utterance than non-protocol interviews did. More details were obtained using open-ended invitations and fewer were obtained using focused questions in protocol interviews than in non-protocol interviews, although the total number of details elicited did not differ significantly. In both conditions, older children provided more details than younger children did. CONCLUSION: The findings confirmed that implementation of professionally recommended practices affected the behavior of interviewers in both the pre-substantive and substantive phases of their interviews and enhanced the quality (i.e., likely accuracy) of information elicited from alleged victims.

Effects of introductory style on children's abilities to describe experiences of sexual abuse.

OBJECTIVE: The goal of this study was to evaluate the relative effectiveness of two rapport-building techniques for eliciting information from children who made allegations of sexual abuse. METHOD: Fourteen interviewers conducted 51 investigations of child sexual abuse with children ranging from 4.5 to 12.9 years of age. In 25 of the investigations, interviewers used a script including many open-ended utterances to establish rapport, whereas in 26 of the investigations the same interviewers used a rapport-building script involving many direct questions. Both rapport-building scripts took about 7 minutes to complete. All children were asked the same open-ended question to initiate the substantive phase of the interview. RESULTS: Children who had been trained in the open-ended condition provided 2 1/2 times as many details and words in response to the first substantive utterance as did children in the direct introduction condition. Children in the open-ended condition continued to respond more informatively to open-ended utterances in the later (unscripted) portion of the interview. Two-thirds of the children mentioned the core details of the incident in their responses to the first substantive utterance and a further 20% mentioned core details more vaguely. CONCLUSIONS: These results demonstrate that children respond more informatively to an open-ended invitation when they have previously been trained to answer such questions rather than more focused questions. These results demonstrate the sensitivity of children to the goals and expectations of forensic interviewers. Structured interview protocols also increase the amount of information provided by young interviewees.

[Bioartificial materials in urology]. / Bioartifizielle Materialien in der Urologie.

The scope of our research is the development of polymer-based bioabsorbable stents for urologic applications and in vitro testing of tissue reactions of cultured ureteral and urethral segments induced by implanted polymer stent prototypes. For these purposes a tissue cultivation model was developed using selected techniques of tissue engineering. Essential advantages of degradable over nondegradable urethral stents are elimination of the adverse extraction of epithelialized stents and the potential for recovery of organ-specific functionality. Moreover, the biocompatibility of a degradable urethral stent could potentially reduce the risk of restenosis due to hyperplasia and could be used, even repeatedly, for the treatment of a number of subvesical obstructions. For the treatment of tumor-induced strictures, application of degradable polymer stents coated with cytostatic drugs may be possible. The mechanical effect of the drug-loaded stent as a "place holder" could be complemented by adjuvant or palliative approaches such as local chemotherapy. We have developed and tested in vitro a degradable urethral stent incorporated with the model drug methotrexate for local drug delivery (LDD) by diffusion and during stent degradation.

Construct validity of the short inventory of problems among Spanish speaking Hispanics.

OBJECTIVE: Research on ethnic health disparities requires the use of psychometrically sound instruments that are appropriate when applied to ethnically diverse populations. The Short Inventory of Problems (SIP) assesses alcohol-related consequences and is often used as a measure to evaluate intervention effectiveness in alcohol research; however, whether the psychometric properties of this instrument are comparable across language and ethnicity remains unclear. METHOD: Multi-group confirmatory factor analysis (MGCFA) was used to test for the invariance of the measurement structure of the SIP across White Non-Hispanic English speaking (N=642), Hispanic English speaking (N=275), and Hispanic Spanish speaking (N=220) groups. RESULTS: The MGCFA model in which factor loadings, measurement intercepts, and item residuals were constrained to be equal between English speakers and Spanish speakers exhibited a reasonable fit to the data, χ(2)(221)=1089.612 p<.001, TLI=.926; CFI=.922, RMSEA=.059 (90% CI=.055-.062). The ΔCFI supported strict factorial invariance, ΔCFI=.01, across groups; no significant group differences were found between factor loadings, measurement intercepts, or item residuals between English speakers and Spanish speakers. CONCLUSIONS: This study extends the existing confirmatory factor analysis results of the SIP by providing additional data to inform the utility of the SIP among Hispanics. Strict factorial invariance between Spanish and English speakers is necessary to: conclude that the underlying constructs have the same meaning across groups; test for group differences in the latent variables across groups; and presume that group differences are attributable only to true differences between groups. Thus, the SIP is strongly supported for evaluating the effectiveness of alcohol treatment among Hispanics.

Biodegradable polymeric coatings on cochlear implant surfaces and their influence on spiral ganglion cell survival.

To improve the electrode-nerve interface of cochlear implants (CI), the role of poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P(4HB)) as potential coating matrices for CI was assessed both in vitro and in vivo in terms of degradation behavior and effects on spiral ganglion neurons, the main target of the electrical stimulation with a CI. Growth rates of fibroblasts on the polymers were investigated and a direct-contact test with freshly isolated spiral ganglion cells (SGC) was performed. In addition, the effects of the polymer degradation inside the inner ear were evaluated in vivo. The polymer degradation was assessed by use of scanning electron microscopy in combination with an energy-dispersive X-ray analysis. In vitro, no influence of the polymers was detected on fibroblasts' viability and on SGC survival rate. In vivo, SGC density was decreased only 6 months after implantation in the basal and middle turns of the cochlea in comparison to normal-hearing animals but not between implanted groups (coated or uncoated). The analysis of the electrode models showed that in vivo P(4HB) is characterized by a gradual degradation completed after 6 months; whereas, the PLLA coatings burst along their longitudinal axis but showed only little degradation within the same time frame. In conclusion, both polymers seem to justify further evaluation as possible coating for CI electrodes. Of the two options, due to its excellent coating adhesion/stability and optimal degradation behavior, P(4HB) may prove to be the more promising biodegradable polymer for designing a drug delivery system from the surface of CI electrodes.