Contextualizing medications for opioid use disorder and peer support service provision in the probation system with implementation science.

BACKGROUND: Medications for opioid use disorder (MOUD) is an evidence-based approach that reduces opioid-related mortality, particularly among criminal legal-involved persons who are at increased risk of adverse outcomes related to OUD. Implementing evidence-based approaches in the context of probation settings requires an in-depth understanding of specific contexts to improve intervention efficacy and effectiveness. Here, we use the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework to understand implementation contexts for MOUD provision in the probation setting. METHODS: In-depth individual interviews were conducted with key programmatic stakeholders (treatment providers and probation staff involved in service provision for people on probation). The study examined stakeholder perspectives regarding MOUD and Peer Support Service (PSS) implementation among people who are involved in community supervision. Deductive and inductive thematic analysis was conducted, and subsequently the codes, subcodes, and themes were mapped onto the EPIS framework to better understand implementation contexts. RESULTS: We deduced key inner, outer, and bridging contexts that shape treatment service provision for individuals with OUD who are on probation. Inner contexts include a strong organizational climate that supports MOUD implementation and enthusiasm for peer support services. Outer contexts include difficulty navigating insurance among providers, treatment costs, and systemic stigma towards MOUD. Bridging contexts include a lack of collaboration/communication between relevant agencies (e.g., probation and courts). CONCLUSIONS: Findings indicate the implementation is complex and requires a coordinated effort between correctional systems, probation agencies, and community-based treatment providers.

Gender identity, stimulant drug use, and criminal justice history on internalized stigma among a nationally representative sample of adults who misuse opioids.

PURPOSE: The rise of fatal stimulant use among adults who use opioids is a public health problem. Internalized stigma is a barrier to substance use treatment, which is greater for women and populations with criminal justice involvement. METHODS: Using a nationally representative sample of adults in the United States from a probability-based survey on household opinions in 2021, we examined characteristics of women (n = 289) and men (n = 416) who misuse opioids. In gender-stratified multivariable linear regression, we investigated factors associated with internalized stigma, and tested for the interaction of stimulant use and criminal justice involvement. RESULTS: Compared to men, women reported greater mental health symptom severity (3.2 vs. 2.7 on a 1 to 6 scale, p < 0.001). Internalized stigma was similar between women (2.3 ± 1.1) and men (2.2 ± 0.1). Among women and not men, however, stimulant use was positively associated with internalized stigma (0.36, 95% CI [0.07, 0.65]; p = 0.02). Interaction between stimulant use and criminal justice involvement was negatively associated with internalized stigma among women (- 0.60, 95% CI [- 1.16, -0.04]; p = 0.04); among men, the interaction was not significant. Predictive margins illustrate among women, stimulant use eliminated the gap in internalized stigma such that women with no criminal justice involvement had a similar level of internalized stigma as women with criminal justice involvement. CONCLUSION: Internalized stigma between women and men who misuse opioids differed based on stimulant use and criminal justice involvement. Future research should assess whether internalized stigma influences treatment utilization among women with criminal justice involvement.

Lessons Learned from Implementation of a Post-opioid Overdose Outreach Program in a Rural Massachusetts Community.

Post-overdose outreach programs can play a key role in reducing opioid overdose deaths and increasing access to healthcare services. The design and implementation of these programs, especially in rural communities, remains a gap in knowledge. We aimed to understand the lessons learned from the implementation experiences of the Community, Opportunity, Network, Navigation, Exploration, and Connection Team (CONNECT), a post-overdose outreach program based in a rural community in Massachusetts. We conducted semi-structured focus groups and interviews with 21 community partners after the first year of implementation in 2022. Participants included behavioral health, medical, public health, and public safety personnel involved in the design and implementation of CONNECT. Using a combination of thematic and rapid qualitative analysis methods, we inductively coded transcripts for salient themes. Themes were mapped onto the Health Equity Implementation Framework to better understand implementation and health-equity factors. Facilitators to implementation of this innovation included efficient inter-partner data sharing and coordination, and ability to offer numerous health services to clients to meet their needs. Key partners identified that CONNECT serves clients who use opioids, have previous involvement with the legal system, and reside in low-income areas within this rural region. Unhoused individuals and individuals who do not call 9-11 after an overdose were identified as populations of need that CONNECT was missing due to structural barriers. Partners shared how the context of this rural community came with challenges related to limited access to health services and pervasive stigma towards substance use, while it was also perceived to foster a culture of collaboration and unity among multidisciplinary key partners. Post overdose outreach programs serve clients with complex health needs. The ability to access services for these health needs is shaped by the post overdose outreach program and its key partners, and by the broader community context. As post-overdose outreach programs continue to expand as a promising strategy to address the opioid overdose crisis, there exists a need to contextualize implementation strategies to inform adaptations and develop best-practices.

"And Then COVID Hits": A Qualitative Study of How Jails Adapted Services to Treat Opioid Use Disorder During COVID-19.

Background: Jails in Massachusetts are among the first nationwide to provide correctional populations with medications to treat opioid use disorder (MOUD). The COVID-19 pandemic caused jails to pivot and adapt MOUD programming. We aimed to identify adaptations and barriers to MOUD access that COVID-19 exacerbated or created, and document new elements that staff wish to sustain as COVID-19 recedes. Methods: We conducted semi-structured in-depth interviews and focus groups in 2020-2021 with 29 jail staff who implement MOUD programming in two Massachusetts jails. We conducted qualitative data analysis in Atlas.ti 8 using an inductive approach. Results: Participants shared that access to MOUD among correctional populations is understood by jail staff to be an essential health service. Thus, to facilitate continued access to MOUD, both during incarceration and also at community reentry, jail staff quickly implemented changes in MOUD regulations and dosing protocols and established telehealth capacity. Despite these program adaptations, participants identified how COVID-19 increased health and social needs among correctional populations, reduced availability of community-based healthcare and recovery-supportive services, and introduced new factors that could undermine recovery. Innovations that participants wished to sustain as COVID-19 receded included telehealth capacity, smaller-sized therapeutic groups, and application of a public health approach to treat opioid use disorder among correctional populations. Conclusions: During disruptive events, jails can adapt MOUD programming to ensure access for people living in jail and upon release. Findings identify factors for understanding the outcomes of jail-based MOUD programming during COVID-19 and highlight opportunities to improve service delivery after COVID-19.

Holyoke Early Access to Recovery and Treatment (HEART): A case study of a court-based intervention to reduce opioid overdose.

The District Court in Holyoke, Massachusetts, is among the first courts nationwide to provide access to medications for opioid use disorder (MOUD) and other treatment. The program uses an innovative multisectoral approach to serve a primarily Latinx population living in communities of concentrated poverty with high opioid overdose rates. We document the origins, adaptations, and current status of program operations, including the use of on-site peer recovery specialists and robust data collection efforts. From August 16, 2021, to February 28, 2022, of the 1040 individuals who entered the court for an arraignment, 47.9% (n = 498) were eligible for program participation. Of those 498 individuals, 54.2% (n = 270) spoke with a recovery specialist. Many self-identified as Latinx (53.0%) and male (69.3%). Over one-fourth (27.0%) were connected to a long-term peer recovery specialist and 11.5% were directly connected to a MOUD provider. Semi-structured interviews with key implementers and participants revealed a shared appreciation for the life-saving efforts of the program. We conclude with practical and theoretical considerations required to offer linkage to MOUD in court-based contexts. Future efforts will assess participant outcomes to determine whether the program is an effective and feasible intervention that can be adopted by other court-based settings.

Endometrioma, the follicular fluid inflammatory network and its association with oocyte and embryo characteristics.

RESEARCH QUESTION: What is the association between endometrioma-affected ovaries, their follicular fluid inflammatory microenvironment, and ovary-specific oocyte and embryo yield and quality? DESIGN: Exposure-matched prospective cohort study conducted at a university-affiliated infertility clinic. Thirty-four women presenting for oocyte retrieval were enrolled between 2012 and 2013: women with unilateral endometrioma and no other observed peritoneal or deep lesions (n = 10) and women with no signs or symptoms of endometriosis (n = 24). Follicular fluid was aspirated at the time of oocyte retrieval. Samples from each ovary were analysed using a 27-plex immunoassay panel. The associations were evaluated by ovary-specific endometrioma exposure status (affected, unaffected, unexposed) with cytokine levels, oocyte yield and embryo quality. RESULTS: Levels of interleukin (IL)-8 and monocyte chemoattractant protein-1 were higher in fluid obtained from endometrioma-affected ovaries compared with the unexposed ovaries from women without endometriosis, with intermediate levels observed in the contralateral unaffected ovaries. More modest differences were observed for IL-1ß and IL-6. The affected ovaries of women with endometriosis yielded fewer oocytes (mean ± SD = 4.6 ± 2.3) compared with both the unaffected (6.0 ± 3.8) and unexposed (7.9 ± 5.6) ovaries. After adjusting for potential confounders and variables generated in a cytokine principal components analysis, oocyte yield remained slightly lower for the endometrioma-affected ovaries compared with unexposed ovaries. No informative differences among ovary groups for embryo quality parameters were observed. CONCLUSIONS: The results suggest that the inflammatory milieu of ovarian endometriosis is strongly localized and has a more modestly systemic effect. The effect of endometriomas on infertility, however, cannot be entirely explained by increased inflammation.

Effect of body mass index on in vitro fertilization outcomes in women with polycystic ovary syndrome.

OBJECTIVE: The objective of the investigation was to study the effect of body mass index (BMI) on in vitro fertilization (IVF) outcomes within a polycystic ovary syndrome (PCOS) population. STUDY DESIGN: This was a retrospective cohort study including 101 cycles from 79 women younger than 40 years old with a clinically documented diagnosis of PCOS by Rotterdam criteria undergoing IVF at a university-based infertility clinic from 2001 through 2010. All participants were stratified by BMI calculated from height and weight recorded within 3 months of cycle start: lean (18.7-24.9 kg/m(2), n = 51), overweight (25-29.9 kg/m(2), n = 19), and obese (≥30 kg/m(2), n = 31). Linear, logistic, and Poisson regressions were used as appropriate to estimate the effect of a range of BMIs on IVF outcomes while adjusting for potential confounders. RESULTS: Obese PCOS women had 69% lower odds of clinical pregnancy per cycle start (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11-0.86; P = .02) and 77% lower odds of clinical pregnancy per embryo transfer (OR, 0.23; 95% CI, -0.08 to 0.68; P = .008) compared with lean PCOS women. Among obese PCOS women, the odds of live birth were 71% lower per cycle start (OR, 0.29; 95% CI, 0.10-0.84; P = .02) and 77% lower per embryo transfer (OR, 0.23; 95% CI, 0.07-0.71; P = .01) compared with lean PCOS women. There was a trend toward decreased ovarian hyperstimulation syndrome incidence with increasing BMI among women with PCOS: 19.6% in lean, 10.5% in overweight, and 3.2% in obese. CONCLUSION: PCOS is a broad syndrome, with our results demonstrating 2 distinct populations, lean and obese, which have different IVF outcomes including ovarian hyperstimulation syndrome risk profiles. This information is important for clinicians because it informs treatment decisions.

Greater surgical precision of a flexible carbon dioxide laser fiber compared to monopolar electrosurgery in porcine myometrium.

The objective of this experimental animal study was to compare the surgical precision of a flexible CO2 laser fiber with that of monopolar electrosurgery in porcine myometrium. The subjects were 6 live adult non-pregnant female pigs. Linear injury to the uterine horns was created using a flexible CO2 laser fiber at 5W, 10W, and 15W and with monopolar electrosurgery at 10W, 20W, 30W, and 40W in both cut and coagulation modes. Hysterectomy was then performed in the live animals. Cross-sections of the tissue were processed and stained using Masson trichrome to differentiate damaged from undamaged myometrium. Measurement means were compared using analysis of variance with Tukey honest significant difference correction; p <.05 indicated significance. Incision width of the laser at 5W and 10W was significantly less than both monopolar coagulation at all power settings and monopolar cut at 30W and 40W (all p <.01), at 5W was also significantly less than monopolar cut at 10W (p = .03), and at 15W was significantly less than monopolar coagulation at 40W (p = .001). Incision depth of the laser at 5W was significantly less than monopolar coagulation at 40W and laser at 15W (both p = .01), at 15W was significantly greater than monopolar coagulation at 10W and monopolar cut at 10, 20, and 30W (p ≤.01), and increased proportional to power for all 3 energy types. Collateral thermal damage width at all laser power settings was significantly less than at all monopolar coagulation power settings (p ≤.04) with the exception of the laser at 15W compared with monopolar coagulation at 10W (p = .30), and at all laser power settings was significantly less than at all monopolar coagulation power settings (p <.001). Collateral thermal damage depth of the laser at 5W and 10W was significantly less than monopolar cut at 30W (p ≤.002) and increased proportional to power in monopolar coagulation mode but remained constant with the laser. Incising efficiency of the laser at 5W was significantly greater than monopolar coagulation at 10W (p = .04), at 10W was significantly greater than at all monopolar power settings (p ≤.007) except cut at 40W (p = .29), and at 15W was significantly greater than that of every other energy type and power setting tested (p ≤.04). These findings support the hypothesis that CO2 laser energy delivered via a flexible fiber system would exhibit greater surgical precision than monopolar electrosurgery, in both cut and coagulation modes, as defined by 3 parameters: incising efficiency, changes in incision depth compared with width as power increases, and variability in the resulting incision measurements. Because increased thermal damage has been associated with delayed tissue necrosis and adhesion formation, these findings prompt the design of a comparative survival animal study to assess additional clinically relevant parameters.

A Systematic Narrative Review of Recent Obesity Interventions with Black Women in the United States.

OBJECTIVES: This study is to comprehensively review recent obesity interventions for Black women in the United States. METHODS: We searched PubMed and EBSCOhost for articles published between 2013 and 2022 using a comprehensive search strategy. Two reviewers screened titles, abstracts, and full texts. Data from the included articles were extracted. Qualitative themes related to the intervention designs were identified across studies. RESULTS: Fifty-two studies were included in the review. Interventions typically aimed to reduce weight by targeting diet and/or physical activity. Intervention activities were delivered virtually and in-person via several formats including didactic content and interactive sessions. Outcomes were assessed through a variety of research designs. Across papers, we identified six key themes of intervention design: integration of technology, centering community and culture, personalization of content, use of social support, skill-building through intervention activities, and addressing comorbid health conditions. CONCLUSIONS: To address the obesity epidemic, future research can build upon key lessons learned from recent interventions tailored to Black women.

Provision of medications to treat opioid use disorder via a mobile health unit: A scoping review.

INTRODUCTION: Mobile health units (MHUs) provide a variety of low-barrier services to populations that face systemic barriers to healthcare access. However, MHUs are not a common delivery method for medications to treat opioid use disorder (MOUD), and, of these, there is no consensus regarding MHU targeted objectives and outcomes. This scoping review seeks to summarize the state of the literature examining the delivery of MOUD by MHUs in the United States. METHODS: A search of PubMed, PsycInfo, and CINAHL on February 21, 2023, found 223 articles. Two authors completed title and abstract and full text reviews and extracted data relevant to intervention and study design, program objectives, and study outcomes. Ten articles fit the study's inclusion criteria (nine total interventions). RESULTS: Of the 10 studies, six were cohort designs, three were cross-sectional (one with qualitative interviews), and one study conducted qualitative interviews only. Most studies were located in the Northeastern United States. MHU interventions primarily aimed to provide MOUD and to retain populations in treatment. Two interventions aimed to engage patients and then transfer them to fixed-site MOUD providers. Across four interventions that provided buprenorphine, 1- and 3-month retention rates varied from 31.6 % to 72.3 % and 26.2 % to 58.5 %, respectively. Qualitative interviews found that MOUD delivery from the MHU was characterized by less stigma/judgment and greater privacy compared to fixed-site, and it was flexible and low-barrier. MHUs were reportedly underutilized by the target populations, suggesting a lack of awareness from community members with opioid use disorder. CONCLUSIONS: MHUs that deliver MOUD are both under-provided and -utilized. Future research should continue to assess MOUD provision from MHUs with an emphasis on robust study design, application to other formulations of MOUD, and evaluation of outcomes such as participant satisfaction and key informant perceived challenges. REGISTRATION: Submitted to Open Science Framework (OSF) Repository on February 6, 2023.

A square peg in a round hole: treating hepatitis C.

Several barriers along the cascade of care reduce hepatitis C treatment access. We propose an investment in patient-centered care strategies to initiate and engage this vulnerable population with curative treatment, such as the implementation of community-based educational peer support groups. Barriers to implementing these patient-centered care strategies remain.

A scoping review of community-based post-opioid overdose intervention programs: implications of program structure and outcomes.

BACKGROUND: An emergent intervention to address the opioid epidemic is the use of multidisciplinary outreach teams which connect an individual in the community to healthcare resources after the experience of an opioid overdose. While these interventions are receiving federal funding, less is known empirically to inform future interventions. Understanding the process and outcomes of these interventions is advisable due to the novel partnerships of public health and law enforcement agencies who sometimes hold divergent goals. The objective of the present review was to describe program structure and evaluated outcomes of community-based post-overdose interventions. RESULTS: A search of PubMed, PsycInfo, and Web of Science yielded 5 peer-reviewed articles that detail the implementation and outcomes of interventions delivered in the United States published from 2001 to July 2021. Most interventions used a multidisciplinary outreach team and referenced first responder data to contact individuals who recently experienced an overdose at their residence. Services offered often included referral to substance use treatment, recovery coaches, and social services. Method of outreach, evaluation measures, and outcomes varied. From the available literature, facilitators of program engagement included communication, information sharing, and leadership buy-in among multidisciplinary partners. CONCLUSIONS: Future studies could benefit from exploration of service provision in rural areas, for family affected by overdose, and for minoritized populations. Community-based post-overdose interventions utilizing a law enforcement partnership are emergent with promising yet limited examples in empirical literature.

Contextualizing Medications for Opioid Use Disorder and Peer Support Service Provision in the Probation System with Implementation Science.

Background: Medications for opioid use disorder (MOUD) is an evidence-based approach that reduces opioid-related mortality, particularly among criminal legal-involved persons who are at increased risk of adverse outcomes related to OUD. Implementing evidence-based approaches in the context of probation settings requires an in-depth understanding of specific contexts to improve intervention efficacy and effectiveness. Here, we use the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework to understand implementation contexts for MOUD provision to the probation setting. Methods: In-depth individual interviews were conducted with key programmatic stakeholders (treatment providers and probation staff involved in service provision for people on probation). The study examined stakeholder perspectives regarding MOUD and Peer Support Service (PSS) implementation among people who are involved in community supervision. Deductive and inductive thematic analysis was conducted, and subsequently the codes, subcodes, and themes were mapped onto the EPIS framework to better understand implementation contexts. Results: We deduced key inner, outer, and bridging contexts that shape treatment service provision for individuals with OUD who are on probation. Inner contexts include a strong organizational climate that supports MOUD implementation and enthusiasm for peer support services. Outer contexts include difficulty navigating insurance among providers, treatment costs, and systemic stigma towards MOUD. Bridging contexts include a lack of collaboration/communication between relevant agencies (e.g., probation and courts). Conclusions: Findings indicate the implementation is complex and requires a coordinated effort between correctional systems, probation agencies, and community-based treatment providers.

Correlates and Patterns in Use of Medications to Treat Opioid Use Disorder in Jail.

OBJECTIVES: Little is known about the correlates of use of medications to treat opioid use disorder (MOUD, ie, buprenorphine, methadone, naltrexone) offered in jails. We evaluated the implementation and outcomes of a MOUD program offered by 2 of the first jails nationwide to provide access to such care. METHODS: We examined use of MOUD among adults with opioid use disorder (n = 347) incarcerated by 2 rural jails in Massachusetts (2018-2021). We examined MOUD transitions from intake to during incarceration. Using logistic regression, we examined factors associated with in-jail use of MOUD. RESULTS: At jail entry, 48.7% of individuals with opioid use disorder were being treated with MOUD. During incarceration, 65.1% received MOUD, attributable to a 9.2% increase in use of methadone (from 15.9% to 25.1%) and a 10.1% increase in use of buprenorphine (from 28.5% to 38.6%). During incarceration, 32.3% of individuals were continued on the same MOUD from the community, 25.4% were started, 8.9% stopped, and 7.5% switched type. A total of 25.9% entered jail not on any MOUD and were not started on it. Use of MOUD during incarceration was positively associated with having received MOUD in the community (odds ratio, 12.2; 95% confidence interval, 5.8-25.5) and incarceration at site 1 compared with site 2 (OR, 24.6; 95% CI, 10.9-54.4). CONCLUSIONS: Expanded access to MOUD in jails can engage an at-risk population with treatment. Understanding factors related to this population's use of MOUD may aid efforts to optimize care during incarceration and after community re-entry.

Comparison of cytokines in the peritoneal fluid and conditioned medium of adolescents and adults with and without endometriosis.

PROBLEM: To compare inflammatory- and immune-associated peritoneal cytokines of adolescents and adults with and without endometriosis. METHODS OF STUDY: In a nested case-control study in multiple university-affiliated scientific centers, ten adolescents and thirteen adults with visually and histologically confirmed endometriosis (cases), thirteen adolescents with visually suspected endometriosis but indeterminate (seven patients) or negative (six patients) histology, and fifteen adults undergoing surgery for non-malignant gynecologic disease without endometriosis (controls) underwent laparoscopic aspiration of peritoneal fluid (PF), from which PF and conditioned medium (CM) cytokine levels were assayed. RESULTS: Compared to adults with endometriosis, MCP-3, IL-12p40, MIP-1ß, and IL-15 were significantly higher among adolescents with endometriosis, while TNF-ß and CTACK were lower among adolescents. These differences were similar comparing adolescents with endometriosis to adult controls except for MIP-1ß, which was not statistically different. MIP-1ß was, however, the only cytokine observed to differ between adult cases and controls. There were no significant differences in CM cytokines among the three groups. Results were similar when analyses were restricted to samples collected (a) during menstrual cycle days 1-10, (b) from patients unexposed to exogenous hormones, or (c) from all adolescents despite presence or absence of histologic endometriosis. CONCLUSION: Biologically relevant and statistically significant differences in six PF cytokines were observed and suggest a more pro-invasion cytokine profile among adolescents with endometriosis. Adolescents with endometriosis have unique peritoneal cytokine profiles and molecular behavior when compared to adults with and without endometriosis.

Loop electrosurgical excision procedure with an intrauterine device in place.

Patients using an intrauterine device (IUD) who require a loop electrosurgical excision procedure (LEEP) for cervical dysplasia have traditionally had the IUD removed prior to the procedure. The only other options have been methods that lead to suboptimal sampling or risk cutting the strings. Our study suggests a procedure for performing the LEEP without removing the IUD, and review of the literature suggests that this method has not been reported before. The LEEP is performed using a conization electrode or a cone biopsy excisor. After noting that the IUD strings are of adequate length, a 0-polyglactin free tie is secured around the visible portion of the IUD strings without applying tension on the strings. A large, sterile absorbent-tipped applicator with a hollow handle becomes an 8 cm hollow plastic tube by removing the cotton tip with sterile scissors. The long end of the suture is threaded through the sterile tube. Without pulling on the IUD, the tube is then passed over the strings into the cervical canal approximately 2.5 cm to protect the strings from the excisor well into the cervical canal. Then, the LEEP is performed. After the specimen is removed, hemostasis can be obtained using a ball cautery electrode, keeping the protecting tube with the enclosed IUD strings out of the way. The tube is then carefully removed. The suture is now cut close to the polyglactin knot around the IUD strings, making certain not to shorten the IUD strings and making certain the visible length of the strings is the same as before the procedure. Ferric subsulfate is applied to the operative area to provide continued hemostasis. Follow-up for the LEEP is unchanged. This procedure may be performed on either levonorgestrel-releasing or copper IUDs.

Vascular endothelial growth factor receptor inhibitor enhances dietary salt-induced hypertension in Sprague-Dawley rats.

Clinical evidence links the inhibition of VEGF to hypertension. However, the mechanisms by which VEGF affects the pathogenesis of hypertension remain in question. We determined 1) whether administration of VEGF receptor inhibitor SU5416 enhances dietary salt-induced hypertension in Sprague-Dawley (SD) rats, and 2) whether VEGF or SU5416 directly affects proliferation of cultured human renal proximal tubular epithelial cells (HRPTEC) and endothelial nitric oxide synthase (eNOS) expression in cultured human glomerular microvessel endothelial cells (HGMEC). Ten 10-wk-old male SD rats received a high sodium diet (HS; 8%) and the other 10 SD rats received a normal sodium diet (NS; 0.5%) for 4 wks. After 2 wks of the dietary program, five rats were administered with SU5416 at 10 mg x kg(-1) x day(-1) ip or DMSO (vehicle) for 14 days in HS and NS groups. Mean arterial pressure was significantly higher in rats treated with SU5416, as opposed to those treated with DMSO and fed with HS for 4 wk (157.6 +/- 3.9 vs. 125.9 +/- 4.3 mmHg, P < 0.01). Increased proteinuria and albuminuria were associated with marked renal histological abnormalities in HS group with SU5416 administration, compared with those in the vehicle HS group. 3H-thymidine incorporation assay showed that SU5416 blocked the actions of both exogenous and endogenous VEGF on the proliferation of HRPTEC. VEGF (10 ng/ml) significantly increased eNOS protein levels by 29% in cultured HGMEC, but its action was completely abolished by SU5416. These results suggest that VEGF receptor inhibition enhances dietary salt-induced hypertension and kidney injury, possibly by direct damage on renal cells and decreasing NO production by eNOS.

Long-term high salt diet causes hypertension and alters renal cytokine gene expression profiles in Sprague-Dawley rats.

OBJECTIVE: The present study examines whether a long-term high salt diet causes hypertension and renal injury in normal subjects [Sprague-Dawley (SD) rats] and alters renal cytokine-related gene expression profiles. METHODS: Four 10 week old male SD rats received a high salt diet (HS, 8%) and the other 4 SD rats received a normal salt diet (NS, 0.5%) for 8 weeks. Mean arterial pressure (MAP) and renal damages such as albuminuria and histological renal injury were determined. The relative mRNA levels of 514 cytokine-related genes (normalized by beta-actin) in rat kidneys following NS or HS were determined quantitatively through analysis of 4 sets of gene expression profiles using the mouse cDNA membrane microarrays. RESULTS: We demonstrated that 8 weeks of HS diet increased MAP [(140.0+/-5.3) vs (112.0+/-2.2) mmHg; 1 mmHg=0.133 kPa, P<0.01], albuminuria [(41.4+/-3.2) vs (20.1+/-4.5) mg/d; P<0.01], and caused histological renal injury in SD rats, compared to NS group. Of the 514 genes in the array, there were 27 (5.25%) genes with significantly different expression in the kidney of SD rats with HS compared to those of SD rats with NS. Functional clustering analysis indicated the following functional pathways related to high salt diet-induced hypertension: (1) pro-inflammatory response ( upward arrowIL-17, CCL28; downward arrow NFkappabib); (2) endothelial dysfunction ( downward arrowVEGF-A, VEGF-B, endoglin); (3) pro-matrix formation ( upward arrowosteopontin, IGFBP-5; downward arrow IFN-gamma); and (4) attenuated cell survival and differentiation ( downward arrowCNTF, IGF-II R, ephrin-B1). Northern blot confirmed that 8 weeks of HS diet significantly decreased renal expression of VEGF mRNA, compared to NS group (P<0.01). ELISA showed that HS diet significantly decreased renal protein levels of VEGF and CCL28. CONCLUSION: These findings support the hypothesis that hypertension can be induced in normal rats by a long-term high salt diet, which is associated with increased renal injury and marked changes in renal cytokine gene expression profiles that are closely related to the pro-inflammatory response, pro-matrix formation, endothelial dysfunction, and attenuated cell survival and differentiation.

Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006.

A review of pregnancy-associated thrombotic thrombocytopenic purpura (TTP) in 166 pregnancies was undertaken using 92 English-language publications from 1955 to 2006. Initial and recurrent TTP presents most often in the second trimester (55.5%) after 1-2 days of signs/symptoms; postpartum TTP usually occurs following term delivery. TTP with preeclampsia (n = 28) exhibits 2-4 times higher aspartate aminotransferase (AST) values and lower total lactate dehydrogenase (LDH) to AST ratios (LDH to AST ratio = 13:1), compared with TTP without preeclampsia (LDH to AST ratio = 29:1). Maternal mortality is higher with initial TTP (26% vs 10.7%), especially with concurrent preeclampsia (44.4% vs 21.8%, P < .02). Although maternal mortality with TTP has substantially declined when plasma therapy is utilized, delay of diagnosis and therapy for initial TTP confounded by preeclampsia/hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome remains a significant maternal-perinatal threat. Rapid and readily available laboratory testing to quickly diagnose TTP and HELLP syndrome/preeclampsia is desperately needed to improve care.