Safety and efficacy of lenalidomide (Revlimid) in recurrent ovarian and primary peritoneal carcinoma

OBJECTIVES: To conduct a phase I trial to determine the safety and toxicity profile of a novel immunomodulatory drug, lenalidomide, in recurrent ovarian and primary peritoneal cancer. The secondary objective is to evaluate the efficacy profile and quality of life (QOL) parameters in patients receiving this treatment. METHODS: Patients with recurrent ovarian or peritoneal cancer who received standard staging surgery and at least one prior platinum-based chemotherapy regimen were treated with single-agent oral lenalidomide 25 mg daily for 21 days of a 28-day cycle. Toxicities were monitored by patient report, physical exam, and laboratories. Response was assessed by imaging, physical exam, and CA-125. Therapy was discontinued with disease progression and/or unacceptable toxicity. RESULTS: 20 patients with recurrent ovarian or peritoneal cancer were enrolled and received 70 completed 28-day cycles and 10 partial cycles of lenalidomide therapy. The majority of adverse events were grades 1-2, including fatigue (25/80 cycles), nausea/vomiting (23/80), constipation (13/80), abdominal pain (17/80), rash (12/80), neutropenia (12/80), and anemia (12/80). Grade 3 toxicities occurred in 12 of 80 cycles (14%) and no grade IV toxicities were observed. Eleven patients completed > or = 2 cycles and were evaluable for response. Nine achieved stable disease (SD) of at least 3 months, with four patients maintaining SD for > 6 months. The mean time to progression was 5.8 months (range 2-12 months). CONCLUSION: Overall, oral lenalidomide was well tolerated and may have some activity as a single agent in this heavily pre-treated population. Further studies combining lenalidomide with cytotoxic treatments may be warranted in this disease setting.     

Collagen 1Alpha1 and transforming growth factor-beta polymorphisms in women with cervical insufficiency

OBJECTIVE: To estimate whether polymorphisms in the collagen 1Alpha1 gene (COL1Alpha1) and the transforming growth factor-beta gene (TGF-beta;1) are more common in women with cervical insufficiency than in those without the condition. METHODS: Medical, obstetric, and family histories and blood were obtained from women with (n=121) and those without (n=165) cervical insufficiency. DNA was extracted and purified by using commercial DNA isolation kits. Samples were analyzed for variants in two genes, the COL1A1 intron 1SP1 and TGF-beta Arg-25-Pro polymorphism, by using an allele-specific polymerase chain reaction assay. RESULTS: Thirty-four of 125 (27.2%) women with cervical insufficiency had at least one first-degree female relative affected. The frequency of the homozygous TT genotype in the COL1A1 gene was increased in women with a history of cervical insufficiency compared with controls (10.8% compared with 3.1%, P=.04). The TGF-beta polymorphisms (ArgPro and ProPro) also were increased in cases (38.3% compared with 14.6%, P<.001). CONCLUSION: Over one fourth of women with cervical insufficiency have a family history of cervical insufficiency, and the COL1A1 intron 1SP1 and TGF-beta Arg-25-Pro polymorphisms are associated with the condition. These observations suggest that, in part, cervical insufficiency is mediated by genetic factors. LEVEL OF EVIDENCE: II.     

Multi‐tissue cytogenetic analysis for the diagnosis of mosaic Down syndrome: A case report

Less than one percent of individuals with Down syndrome exhibit mosaicism, a biological phenomenon that describes an individual who has two or more genetically distinct cell lines. The percentage of mosaicism in different tissues can impact the presence of clinical findings and hinder cytogenetic diagnosis. We report a case of mosaicism for trisomy 21 diagnosed after multi‐tissue cytogenetic analysis of peripheral blood and buccal mucosa, associated with significant intellectual disability, dysmorphic facial features, congenital heart defects, macropenis, and imperforate anus.     

Outcomes of Enhanced Recovery after Surgery (ERAS) in Gynecologic Oncology: A Review

Enhanced Recovery After Surgery (ERAS) is a global surgical quality improvement program that started in colorectal surgery and has now expanded to numerous specialties, including gynecologic oncology. ERAS guidelines comprise multidisciplinary, evidence-based recommendations in the preoperative, intraoperative, and postoperative period; these interventions broadly encompass patient education, anesthetic choice, multimodal pain control, avoidance of unnecessary drains, maintenance of nutrition, and prevention of emesis. Implementation of ERAS has been shown to be associated with improved clinical outcomes (length of hospital stay, complications, readmissions) and cost. Marx and colleagues first demonstrated the feasibility of ERAS in gynecologic oncology in 2003; since then, over 30 comparative studies and 4 guidelines have been published encompassing major gynecologic surgery, cytoreductive surgery, and vulvar/vaginal surgery. Implementation of ERAS in gynecologic oncology has been demonstrated to provide improvements in length of stay, complications, cost, opioid use, and patient satisfaction. Increased compliance with ERAS guidelines has been associated with greater improvement in outcomes.     

Exploring schizophrenic thinking in older adolescents with the WAIS,Rorschach and WIST

Literature that addresses the diagnosis of mental disorder in adolescents strongly suggests that it may not be possible to do so. Schizophrenic thinking, in particular, has been seen as generally characteristic of adolescents. Making judgments of specific responses from the Rorschach, the WAIS, and the WIST, 10 expert clinicians were able to make judgments with regard to 12 adolescents in the 16–19 age range that were suprisingly accurate in discriminating among schizophrenics, nonschizophrenic hospitalized adolescents, and a normal control group. Results indicate that schizophrenic thinking is not necessarily characteristic of adolescents and that information from the WIST may be helpful in identifying schizophrenic adolescents.     

Surface Characteristics and Microbiological Analysis of a Vat-Photopolymerization Additive-Manufacturing Dental Resin

The wide application of additive manufacturing in dentistry implies the further investigation into oral micro-organism adhesion and biofilm formation on vat-photopolymerization (VP) dental resins. The surface characteristics and microbiological analysis of a VP dental resin, printed at resolutions of 50 μm (EG-50) and 100 μm (EG-100), were evaluated against an auto-polymerizing acrylic resin (CG). Samples were evaluated using a scanning electron microscope, a scanning white-light interferometer, and analyzed for Candida albicans (CA) and Streptococcus mutans (SM) biofilm, as well as antifungal and antimicrobial activity. EG-50 and EG-100 exhibited more irregular surfaces and statistically higher mean (Ra) and root-mean-square (rms) roughness (EG-50-Ra: 2.96 ± 0.32 µm; rms: 4.05 ± 0.43 µm/EG-100-Ra: 3.76 ± 0.58 µm; rms: 4.79 ± 0.74 µm) compared to the CG (Ra: 0.52 ± 0.36 µm; rms: 0.84 ± 0.54 µm) (p < 0.05). The biomass and extracellular matrix production by CA and SM and the metabolic activity of SM were significantly decreased in EG-50 and EG-100 compared to CG (p < 0.05). CA and SM growth was inhibited by the pure unpolymerized VP resin (48 h). EG-50 and EG-100 recorded a greater irregularity, higher surface roughness, and decreased CA and SM biofilm formation over the CG.     

Effect of leak around the endotracheal tube on measurements of pulmonary compliance and resistance during mechanical ventilation: A lung model study

We studied the effect of leaks around the endotracheal tube (ETT) on the measurement of pulmonary mechanics during mechanical ventilation. We also evaluated the influence of different ventilator settings on the magnitude of leak. An adjustable leak was created at the end of the ETT in a lung model with constant compliance. Flow, tidal volume, and pressure changes were measured above and below the leak. Compliance (C_i) and resistance (R_i) during inspiration were determined by linear regression analysis (LRA) using the equation of motion and the Mead and Wittenberger method (MWM). The ventilatory change that influenced the degree of leak most was prolongation of inspiratory time (T_i). The presence of a leak around the ETT resulted in an overestimation of the C_i and R_i values, which was proportional to the size of the leak. This overestimation was also influenced by the method used to determine C_i and R_i. Because the contribution of the leak to the tidal volume progressively increased as inspiration continued, methods of analysis that depended mainly on measurement points at the end of inspiration showed a larger deviation from the true C_i and R_i values than methods mainly influenced by measurement points at the beginning of inspiration. Because of this, shortening of inspiration, or analysis of points at the beginning of inspiration reduces the error in the measurements of C_i and R_i when a leak is present. Breaths with a large leak should be excluded from any analysis of pulmonary mechanics. Pediatr Pulmonol. 1996; 22:35–43. © 1996 Wiley-Liss, Inc.