Provoked Vestibulodynia—Medical Factors and Comorbidity Associated with Treatment Outcome

IntroductionProvoked vestibulodynia (PVD) is the most common cause of dyspareunia in young women. The etiology is unclear, and there is little knowledge of how to predict treatment outcome.AimThe aim of this study was to identify medical factors associated with treatment outcome and coital pain in women with PVD.MethodsSeventy women previously treated for PVD at a vulvar open care unit completed questionnaires and a quantitative sensory testing session.Main Outcome MeasuresConcomitant bodily pain and treatment outcome were surveyed using a study specific questionnaire. Coital pain was rated on a visual analog scale (VAS), range 0–100. Psychometric screening was carried out using the Hospital Anxiety and Depression Scale. Pressure pain thresholds on the arm, leg, and in the vestibulum were measured using pressure algometers.ResultsMajor improvement/complete recovery was more likely in PVD patients with a maximum of one other concomitant pain disorder compared with patients with four or more (odds ratio = 7.8, confidence interval: 1.2–49.4, P = 0.03). In a multiple linear regression model, the number of other pain disorders (P < 0.01) and a diagnosis of primary PVD (P = 0.04) were positively associated with the coital VAS pain score. Women with secondary PVD reported major improvement/complete recovery to a higher extent than women with primary PVD (z = 2.11, P = 0.04).ConclusionA successful treatment outcome was more likely in PVD patients with fewer other concomitant pain conditions. The number of other bodily pain conditions was also associated to the intensity of the coital pain. Additionally, the results indicate higher incomplete response rates to treatment in women with primary PVD compared with secondary PVD. Heddini U, Bohm‐Starke N, Nilsson KW, and Johannesson U. Provoked vestibulodynia—Medical factors and comorbidity associated with treatment outcome. J Sex Med 2012;9:1400–1406.     

Treatment of HER2-positive breast cancer: current status and future perspectives

The advent of HER2-directed therapies has significantly improved the outlook for patients with HER2-positive early stage breast cancer. However, a significant proportion of these patients still relapse and die of breast cancer. Trials to define, refine and optimize the use of the two approved HER2-targeted agents (trastuzumab and lapatinib) in patients with HER2-positive early stage breast cancer are ongoing. In addition, promising new approaches are being developed including monoclonal antibodies and small-molecule tyrosine kinase inhibitors targeting HER2 or other HER family members, antibodies linked to cytotoxic moieties or modified to improve their immunological function, immunostimulatory peptides, and targeting the PI3K and IGF-1R pathways. Improved understanding of the HER2 signaling pathway, its relationship with other signaling pathways and mechanisms of resistance has also led to the development of rational combination therapies and to a greater insight into treatment response in patients with HER2-positive breast cancer. Based on promising results with new agents in HER2-positive advanced-stage disease, a series of large trials in the adjuvant and neoadjuvant settings are planned or ongoing. This Review focuses on current treatment for patients with HER2-positive breast cancer and aims to update practicing clinicians on likely future developments in the treatment for this disease according to ongoing clinical trials and translational research.     

Über das Sauerstottdefizit und die Kohlensäurespannung in der Alveolarluft

Ohne ZusammenfassungAbgekürzt als Vortrag in der Biologischen Gesellschaft, Kopenhagen, 10. X. 1929 gehalten.     

Merkel cell carcinoma: Long term survival in a patient with proven brain metastasis and presumed choroid metastasis

Merkel cell carcinoma (Trabecular carcinoma) is a rare malignant tumor of the skin. Because these tumors tend to spread locally via the lymphatic system, very few papers have dealt with the treatment of distant metastasis. Systemic disease is uncommon and usually fatal.

In this paper, we report a case of Merkel cell carcinoma with proven brain metastasis and a solid choroidal tumor. The patient responded well to radiation and chemotherapy and is alive and neurologically intact three years after diagnosis. All previous patients with metastatic Merkel cell carcinoma to the brain died within two months of the diagnosis. We use this case to discuss possible routes of metastatic dissemination and to review the treatment options in patients with distant metastatic disease. To our knowledge, this is the first reported case of presumed choroidal metastasis of Merkel cell carcinoma and the longest documented survival in a patient with brain involvement.     

Effectiveness of screening for craniosynostosis with ultrasound: a retrospective review

Background

Minimizing the ionizing radiation dose to children is fundamental to pediatric radiology. The most widely accepted imaging examination for evaluating craniosynostosis is computed tomography (CT) of the head, an examination that involves ionizing radiation.

Objective

To determine if sonography of the cranial sutures is an adequate screening examination for the diagnosis of craniosynostosis in patients with abnormal skull shape.

Materials and methods

A retrospective review of all cranial suture ultrasound (US) examinations performed during the course of a 3-year period (July 2012 – September 2015) was undertaken. Results were compared with clinical follow-up and/or head CT to evaluate the accuracy of this modality as a screening tool to determine the presence or absence of craniosynostosis. Fifty-two sonographic exams were adequate for inclusion.

Results

Forty-five of the examinations did not reveal synostosis. In each of these instances, follow-up physical exam findings and/or CT imaging confirmed that no abnormal premature suture closure was present. US findings demonstrated synostosis in seven cases. CT exam or operative reports of these cases confirmed all seven findings of premature suture closure. Statistical analysis demonstrated a sensitivity of 100% (95% confidence interval [CI]: 56.1–100.0%), a specificity of 100% (95% CI: 90.2–100.0%), and a negative predictive value of 100% (95% CI: 90.2–100.0%).

Conclusion

Cranial US is a reliable screening tool to rule out craniosynostosis in patients with abnormal head shape.

     

The Private Practice of Prosthodontists: Current and Future Conditions of Practice in the United States (Part 2)

PURPOSE: Data are used to examine current and future conditions important to the private practice of prosthodontics. A concern is raised as to whether the future supply of prosthodontists is in sync with the dynamics of the US population and patient population. MATERIALS AND METHODS: Four trends are examined using data from various sources. The trends include: (1) growth in the number of private practicing prosthodontists, (2) projections of the future number of private practicing prosthodontists, (3) first year enrollment in dental schools, and (4) enrollments and graduates in residency programs. RESULTS: The number of private practicing prosthodontists has increased modestly over the past 21 years, growing 1.33% per year. The number of private practitioners is projected to reach 4,125 in 2025. A key variable in this projection is the growing number of elderly adults. While dental school enrollments have been increasing, concern is raised about the amount of exposure by students to an undergraduate curriculum in prosthodontics. There has been a general decline in enrollment in the nation's prosthodontics residency programs at the rate of -2.9% per year. An average of 181 program graduates are needed to achieve the 4125 projected number of private practitioners. CONCLUSION: Increasing demand for services from prosthodontists is supported by an increasing US population size and a growing population of elderly. Efforts to grow the number of private practicing prosthodontists will have to consider several concerns including residency program enrollments, undergraduate exposure to prosthodontics, and the overall economic returns expected from engaging in the private practice of prosthodontics. Choosing a career as a private practicing prosthodontist is a timely consideration and complimented by expected increases in demand for care and favorable financial returns to practice.     

Amine Prodrugs Which Utilize Hydroxy Amide Lactonization. I. A Potential Redox-Sensitive Amide Prodrug

Several amides of 3-(3,6-dioxo-2,4-dimethylcyclohexa-l,4-diene)-3,3-diniethylpropionic acid (2) have been synthesized and tested as model redox-sensitive pro-prodrugs of amines. The reduction of these model pro-prodrugs generated hydroxy amide intermediates 4a-4h, the lactonization of which resulted in amine release. The rates of lactonization of 4a-4h were investigated at pH 7.4 and 37°C. The half-lives for appearance of the product lactone la from these intermediates were found to range from 1.4 to 3.4 min. With such rapid lactonization rates, it is believed that reduction will be the rate-limiting step in the two-step conversion of the pro-prodrug to the amine.