Biodegradable and photocrosslinkable polyphosphoester hydrogel

A new biodegradable, photocrosslinkable and multifunctional macromer, poly(6-aminohexyl propylene phosphate) (PPE-HA)-ACRL, was synthesized by conjugation of acrylate groups to the side chains of PPE-HA. By controlling the synthetic conditions, different weight fractions of acrylate in the macromers were achieved as confirmed by 1H NMR. The hydrogels obtained from PPE-HA-ACRL through photocrosslinking were dominantly elastic. With increasing acrylate contents in the macromers, the hydrogels exhibited a lower swelling ratio and higher mechanical strength. The hydrogels with different crosslinking densities lost between 4.3% and 37.4% of their mass in 84 days when incubated in phosphate-buffered saline at 37 degrees C. No significant cytotoxicity of the macromers against bone marrow-derived mesenchymal stem cells from goat (GMSC) was observed at a concentration up to 10mg/ml. Finally, GMSCs encapsulated in the photopolymerized gel maintained their viability when cultured in osteogenic medium for three weeks. Clear mineralization in the hydrogel scaffold was revealed by Von Kossa staining. This study suggests the potential of these biodegradable and photocrosslinkable as injectable tissue engineering scaffolds.     

Mechanism of acidic pH‐induced contraction in spontaneously hypertensive rat aorta: role of Ca2+ release from the sarcoplasmic reticulum

Aim: This study was conducted to investigate the mechanism of acidic pH‐induced contraction (APIC) with regard to Ca²⁺ handling using isometric tension recording experiments. Results: Decreasing extracellular pH from 7.4 to 6.5 produced a marked and sustained contraction of spontaneously hypertensive rat (SHR) aorta, that was 128.7 ± 2.0% of the 64.8 mm KCl‐induced contraction. Verapamil, an inhibitor of voltage‐dependent Ca²⁺ channels (VDCC) significantly inhibited the APIC. In Ca²⁺‐deficient solution, sustained contraction induced by acidic pH was abolished completely, while a transient contraction was still observed suggesting the release of Ca²⁺ from intracellular site. Ryanodine (1 μm ), a ryanodine receptor blocker, and 10 μm cyclopiazonic acid (CPA; a sarco/endoplasmic reticulum Ca²⁺ ATPase inhibitor) abolished the transient contraction induced by acidosis. In normal Ca²⁺‐containing solution, ryanodine significantly decreased the rate of rise as well as maximum level of APIC. Interestingly, ryanodine and CPA showed an additive inhibitory effect with verapamil and the combined treatment of ryanodine or CPA with verapamil nearly abolished the APIC. Conclusions: It is concluded that acidic pH induces Ca²⁺ release from ryanodine/CPA‐sensitive store of sarcoplasmic reticulum in SHR aorta. This Ca²⁺ plays an important role in the facilitation of the rate of rise of APIC, as well as contributing to the sustained contraction via a mechanism which is independent of Ca²⁺ influx through VDCC.     

Predicting recurrence after radical prostatectomy for patients with high risk prostate cancer

PURPOSE: Previous studies have shown that patients with clinical stage T2c-T3 prostate cancer, serum prostate specific antigen (PSA) at diagnosis greater than 20 ng./ml. or a biopsy Gleason score of 8 to 10 are at high risk for disease recurrence after radical prostatectomy. We determined the most important pretreatment predictors of disease recurrence in this high risk population. MATERIALS AND METHODS: We identified 547 patients with high risk prostate cancer who underwent radical prostatectomy at University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor data base, a longitudinal disease registry of patients with prostate cancer. High risk disease was defined as 1992 American Joint Committee on Cancer clinical stage T2c-T3 disease in 411 patients, serum PSA at diagnosis greater than 20 ng./ml. in 124 and/or biopsy Gleason score 8 to 10 in 114. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment more than 6 months after surgery. The Cox proportional hazards analysis was performed to determine significant independent predictors of disease recurrence. The likelihood of disease recurrence for clinically relevant patient groups was determined using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median followup after surgery was 3.1 years. Disease recurred in 177 patients (32%). Multivariate analysis demonstrated that serum PSA at diagnosis, biopsy Gleason score, ethnicity and the percent of positive prostate biopsies were significant independent predictors of disease recurrence, while patient age and clinical tumor stage were not. Patients with a Gleason score 8 to 10 tumor and a serum PSA of 10 ng./ml. or less had a significantly higher likelihood of remaining disease-free 5 years after surgery than those with PSA greater than 10 ng./ml. (47% versus 19%, p <0.05). Patients with a serum PSA at diagnosis of greater than 20 ng./ml. and a Gleason score of less than 8 had a significantly higher likelihood of remaining disease-free 5 years after surgery than similar patients with a Gleason score of 8 or greater (45% versus 0%, p <0.05). CONCLUSIONS: PSA, Gleason score, ethnicity and the percent of positive prostate biopsies appear to be the most important pretreatment predictors of disease recurrence in men with high risk prostate cancer. Patients with high grade disease may continue to be appropriate candidates for local therapy if PSA is less than 10 ng./ml. at diagnosis or there are fewer than 66% positive prostate biopsies.     

Association between presence of pneumonia and pressure ulcer formation following traumatic spinal cord injury

Objective: To determine if the presence of pneumonia and pressure ulcers are associated in individuals with an acute spinal cord injury during acute care and rehabilitation hospitalizations.

Design: Retrospective, secondary analyses of data obtained from the Spinal Cord Injury Model Systems enrolled from 1993 until 2006

Setting: Acute care hospitalization and inpatient rehabilitation facilities

Participants: A cohort of individuals hospitalized in acute care (n?=?3,098) and inpatient rehabilitation (n?=?1,768) was included in the analysis. Frequencies of pressure ulcer formation and episodes of pneumonia were noted in both settings.

Interventions: Not applicable.

Outcome Measures: Pressure ulcer formation and diagnosis of pneumonia

Results: The development of pressure ulcers, including stage I, was 20.3% acute care and 21.1% during in inpatient rehabilitation. Multivariate logistic regression analyses revealed a significant association of pneumonia with occurrence of pressure ulcers (P?≤?0.001, OR?=?2.3 and 2.2 respectively), the American Spinal Injury Association Impairment Scale grades (P?Conclusion: A higher presence of pressure ulcers was found in individuals with pneumonia, after adjusting for injury severity, age, sex, and utilization of mechanical ventilation. Impaired inflammatory response and decreased mobility in individuals with pneumonia may predispose these individuals to develop pressure ulcers. Surveillance and preventive measures for pressure ulcers should be rigorous in individuals with SCI and pneumonia.     

Vaginal vault prolapse in a patient with Mayer–Rokitansky–Küster–Hauser syndrome: a video case presentation

Introduction and hypothesis

Several reports have described vaginal prolapse in Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome patients after creation of a neovagina. To our knowledge, no reports of primary vaginal prolapse of a blind pouch without previous intervention, or surgery for this condition, have been described.

Methods

In this case report, we describe a 19-year-old woman with MRKH and complete prolapse of her shortened vaginal pouch. Surgical correction utilizing permanent suture-based sacrospinous ligament fixation was performed.

Results

The patient had a successful outcome.

Conclusions

Sacrospinous ligament fixation provided a safe and effective method for the management of vaginal pouch prolapse. Long-term follow-up is planned. To our knowledge, this is the first report describing surgical repair of primary prolapse of a blind vaginal pouch in the setting of MRKH.

     

Screening Mammography Following Autologous Breast Reconstruction: An Unnecessary Effort

Background

Currently, no standard guidelines exist regarding routine screening imaging in breast cancer patients following autologous reconstruction. Concern over nonpalpable chest wall recurrence has prompted many to pursue screening imaging. We analyzed the pattern of locoregional recurrence (LRR) and yield of screening imaging and exam in these patients.

Methods

We performed a retrospective chart review of all patients who had mastectomy with autologous reconstruction between 2000 and 2009. Presentation of LRR and utility of imaging and breast exam were analyzed. Screening mammography was performed at the discretion of the treating physicians.

Results

A total of 615 patients were identified and follow-up data were available for 541. Median follow-up from time of reconstruction was 7 years. Twenty-seven patients developed a LRR (5.0 %). Among patients screened with mammography (n = 397), an abnormality led to 25 biopsies in 25 patients, and 2 were malignant (8 %). Among patients receiving routine clinical exam (n = 537), an abnormality led to 77 biopsies in 66 patients, and 30 were malignant (39 %). The median time from cancer surgery to LRR was 2.6 years. LRR was detected on clinical exam in 24 of 27 patients (88.9 %). Screening mammography detected two recurrences that were palpable on follow-up exam. One patient had an incidental chest wall recurrence found on PET/CT. In summary, 26 of 27 (96.3 %) patients had a clinically detectable LRR.

Conclusions

Diligent surveillance with clinical breast exam is a reliable method of detecting LRR after autologous reconstruction, identifying 96.3 % of recurrences in our study. Our results do not support routine mammographic screening in this population.     

Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder.

BACKGROUND: Altered serotonergic function is thought to play a role in the pathophysiology of major depressive episodes based upon evidence from neuroimaging, pharmacological, postmortem and genetic studies. It remains unclear, however, whether depressed samples that differ with respect to having shown a unipolar versus a bipolar illness course also would show distinct patterns of abnormalities within the serotonergic system. The current study compared serotonin transporter (5-HTT) binding between unipolar-depressives (MDD), bipolar-depressives (BD) and healthy-controls (HC) to assess whether the abnormalities in 5-HTT binding recently found in depressed subjects with BD extend to depressed subjects with MDD. METHODS: The 5-HTT binding-potential (BP) measured using positron emission tomography (PET) and [(11)C]DASB was compared between unmedicated, depressed subjects with MDD (n = 18) or BD (n = 18) and HC (n = 34). RESULTS: Relative to the healthy group both MDD and BD groups showed significantly increased 5-HTT BP in the thalamus (24%, 14%, respectively), insula (15%) and striatum (12%). The unipolar-depressives had elevated 5-HTT BP relative to both BD and HC groups in the vicinity of the periaqueductal gray (PAG, 20%, 22%, respectively). The bipolar-depressives had reduced 5-HTT BP relative to both HC and MDD groups in the vicinity of the pontine raphe nuclei. Depression-severity correlated negatively with 5-HTT BP in the thalamus in MDD-subjects. CONCLUSIONS: The depressed phases of MDD and BD both were associated with elevated 5-HTT binding in the insula, thalamus and striatum, but showed distinct abnormalities in the brainstem. The latter findings conceivably could underlie differences in the patterns of illness symptoms and pharmacological sensitivity observed between MDD and BD.