To evaluate retrospectively the efficacy and durability of a novel approach using ureteroscopic laser papillotomy for the treatment of painful papillary calcifications. Chronic pain due to renal ...papillary calcifications has not been addressed by current techniques.
Ureteroscopic holmium laser lithotripsy and papillotomy were performed on patients with chronic pain and radiographically visible papillary calcifications without free collecting system calculi. The papillary urothelium overlying all cystic dilations and intraductal calcifications was vaporized. Treated patients answered a telephone survey to assess pain scores, duration of response, use of narcotics, and patient satisfaction. We reviewed the medical records to evaluate for procedure-related complications and serum creatinine measurements.
Of 20 patients who underwent laser papillotomy and responded to the telephone survey, 7 had bilateral procedures, yielding 27 renal units available for analysis. “Much less pain” was reported after 85% of the procedures, with a durable improvement reported after 59% of the procedures, at a median follow-up of 14.5 months. Significant improvements in the median pain scores were seen at 1 month (1.0,
P <0.001), 6 months (2.0,
P <0.001), and 1 year (1.5,
P <0.001) compared with a median preoperative pain score of 9.0. The mean serum creatinine was unchanged after the procedure.
Ureteroscopic laser papillotomy appears to be an effective treatment option for the chronic pain associated with papillary calcifications. Laser papillotomy offers hope to patients who would otherwise have been denied an attempt at treatment because of a lack of free calculi within the collecting system.
We have characterized the IL-8-induced signal transduction processes in T lymphocytes. A basal level of IL-8 receptor expression was shown on mixed PBL, as identified by using phycoerythrin ...(PE)-coupled IL-8, and this expression was increased following IL-2 stimulation. Scatchard analysis of T cells revealed competitive binding of IL-8 with a Kd of 0.55 nM, with approximately 1200 receptors per cell, on freshly isolated T cells. After 24 h in culture following purification, reverse transcriptase PCR (RT-PCR) analyses show the mRNA for only the type B IL-8R on these cultured T lymphocytes and the cell line MOLT-4. Stimulation of T lymphocytes or T cell clones with IL-8 led to generation of inositol trisphosphate and calcium flux. In addition, when T cells were prelabeled with 3Holeic acid, IL-8 caused a long lasting, time- and dose-related increase in 3Hphosphatidylethanol (PtE), indicating activation of phospholipase D (PLD). By contrast, this IL-8-dependent PLD activity was undetectable in IL-8-stimulated neutrophils. PLD activation appeared to be downstream of protein kinase C, because several inhibitors abrogated the increase in 3HPtE, whereas guanosine-5'-O-(3-thiotriphosphate (GTP(gamma)S) and inositol trisphosphorothioate (IP3S3) both increased the generation of 3HPtE. Together, these results demonstrate that the IL-8RB receptor is sufficient to mediate phospholipase C (PLC) and PLD activation in T lymphocytes, but not in neutrophils, and indicate an important difference in receptor usage and signal transduction pathways between IL-8-stimulated lymphocytes and neutrophils.
We characterized the differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into tenocyte-like cells in response to bone morphogenetic protein-12 (BMP-12). BM-MSCs were prepared ...from Sprague-Dawley rats and cultured as monolayers. Recombinant BMP-12 treatment (10 ng/ml) of BM-MSCs for 12 hours in vitro markedly increased expression of the tenocyte lineage markers scleraxis (Scx) and tenomodulin (Tnmd) over 14 days. Treatment with BMP-12 for a further 12-hour period had no additional effect. Colony formation assays revealed that ~80% of treated cells and their progeny were Scx- and Tnmd-positive. BM-MSCs seeded in collagen scaffolds and similarly treated with a single dose of BMP-12 also expressed high levels of Scx and Tnmd, as well as type I collagen and tenascin-c. Furthermore, when the treated BM-MSC-seeded scaffolds were implanted into surgically created tendon defects in vivo, robust formation of tendon-like tissue was observed after 21 days as evidenced by increased cell number, elongation and alignment along the tensile axis, greater matrix deposition and the elevated expression of tendon markers. These results indicate that brief stimulation with BMP-12 in vitro is sufficient to induce BM-MSC differentiation into tenocytes, and that this phenotype is sustained in vivo. This strategy of pretreating BM-MSCs with BMP-12 prior to in vivo transplantation may be useful in MSC-based tendon reconstruction or tissue engineering.
To date, there is no validated measure for pain catastrophizing at the daily level. The Pain Catastrophizing Scale (PCS) is widely used to measure trait pain catastrophizing. We sought to develop and ...validate a brief, daily version of the PCS for use in daily diary studies to facilitate research on mechanisms of catastrophizing treatment, individual differences in self-regulation, and to reveal the nuanced relationships between catastrophizing, correlates, and pain outcomes. After adapting the PCS for daily use, we evaluated the resulting 14 items using 3 rounds of cognitive interviews with 30 adults with chronic pain. We refined and tested the final daily PCS in 3 independent, prospective, cross-sectional, observational validation studies conducted in a combined total of 519 adults with chronic pain who completed online measures daily for 14 consecutive days. For study 1 (N = 131), exploratory factor analysis revealed adequate fit and-unexpectedly-unidimensionality for item responses to the daily PCS. Study 2 (N = 177) correlations indicated adequate association with related constructs (anger, anxiety, pain intensity, depression). Similarly, results for study 3 (N = 211) revealed expected correlations for daily PCS and measures of daily constructs including physical activity, sleep, energy level, and positive affect. Results from complex/multilevel confirmatory factor analysis confirmed good fit to a unidimensional model. Scores on the daily PCS were statistically comparable with and more parsimonious than the full 14-item version. Next steps include evaluation of score validity in populations with medical diagnoses, greater demographic diversity, and in patients with acute pain.
This article describes the development and validation of a daily PCS. This daily measure may facilitate research that aims to characterize pain mechanisms, individual differences in self-regulation, adaptation, and nuanced relationships between catastrophizing, correlates, and pain outcomes.
In the pediatric population, vaginoplasties can be performed in patients with either congenital malformations or acquired conditions. To our knowledge, there has been no study to date investigating ...the outcomes of vaginoplasty in the pediatric population using a nationwide database. Here, we present a national cohort study of perioperative characteristics and 30-day complications of vaginoplasty in pediatric patients.
A level II retrospective, prognosis cohort study was performed using the Pediatric National Surgical Quality Improvement Program (NSQIP-P) database from 2012 to 2020. Data from patients age 0 to 18 who underwent vaginoplasty was queried using CPT code 57,335. Descriptive analysis was performed to elucidate patterns in patient demographics, perioperative characteristics, and 30-day postoperative outcomes.
A total of 183 patients were identified. Median age was 2.41 years (IQR 0.9 to 12.1). In this population, 58.5% of patients had ASA class 2, and 33.3% ASA class 3. Congenital malformation was present in 75.9%. Average total length of stay was 2.7 days (SD = 3.8) and readmission rate was 7.86%. Complications included urinary tract infection (3.3%), bleeding/transfusions (2.2%), organ/space surgical site infection (1.1%), and superficial incisional surgical site infection (0.6%). The most common procedures performed simultaneously with vaginoplasty included cystourethroscopy (n = 66), clitoroplasty for intersex state (n = 58), and plastic repair of introitus (n = 22).
Vaginoplasties in the pediatric population were found to have low rates of 30-day readmission and low incidence of 30-day postoperative complications. Further studies focusing on prospective clinical data related to pediatric vaginoplasty can help identify factors to improve long-term outcomes in this population.
This white paper provides a critical analysis of methods for estimating transporter kinetics and recommendations on proper parameter calculation in various experimental systems. Rational ...interpretation of transporter‐knockout animal findings and application of static and dynamic physiologically based modeling approaches for prediction of human transporter‐mediated pharmacokinetics and drug–drug interactions (DDIs) are presented. The objective is to provide appropriate guidance for the use of in vitro, in vivo, and modeling tools in translational transporter science.
Clinical Pharmacology & Therapeutics (2013); 94 1, 64–79. doi:10.1038/clpt.2013.45
Based on epidemiologic and embryologic patterns, nonsyndromic orofacial clefts- the most common craniofacial birth defects in humans- are commonly categorized into cleft lip with or without cleft ...palate (CL/P) and cleft palate alone (CP), which are traditionally considered to be etiologically distinct. However, some evidence of shared genetic risk in IRF6, GRHL3 and ARHGAP29 regions exists; only FOXE1 has been recognized as significantly associated with both CL/P and CP in genome-wide association studies (GWAS). We used a new statistical approach, PLACO (pleiotropic analysis under composite null), on a combined multi-ethnic GWAS of 2,771 CL/P and 611 CP case-parent trios. At the genome-wide significance threshold of 5 x 10.sup.-8, PLACO identified 1 locus in 1q32.2 (IRF6) that appears to increase risk for one OFC subgroup but decrease risk for the other. At a suggestive significance threshold of 10.sup.-6, we found 5 more loci with compelling candidate genes having opposite effects on CL/P and CP: 1p36.13 (PAX7), 3q29 (DLG1), 4p13 (LIMCH1), 4q21.1 (SHROOM3) and 17q22 (NOG). Additionally, we replicated the recognized shared locus 9q22.33 (FOXE1), and identified 2 loci in 19p13.12 (RAB8A) and 20q12 (MAFB) that appear to influence risk of both CL/P and CP in the same direction. We found locus-specific effects may vary by racial/ethnic group at these regions of genetic overlap, and failed to find evidence of sex-specific differences. We confirmed shared etiology of the two OFC subtypes comprising CL/P, and additionally found suggestive evidence of differences in their pathogenesis at 2 loci of genetic overlap. Our novel findings include 6 new loci of genetic overlap between CL/P and CP; 3 new loci between pairwise OFC subtypes; and 4 loci not previously implicated in OFCs. Our in-silico validation showed PLACO is robust to subtype-specific effects, and can achieve massive power gains over existing approaches for identifying genetic overlap between disease subtypes. In summary, we found suggestive evidence for new genetic regions and confirmed some recognized OFC genes either exerting shared risk or with opposite effects on risk to OFC subtypes.
We randomly allocated 50 total knee replacements to scrub teams wearing body-exhaust suits (BES) or Rotecno occlusive clothing. The effectiveness of the clothing was assessed using air andwound ...bacterial counts. Bacteria were recovered from 62% of wounds (64% BES, 60% Rotecno). The mean air count was 0.5 CFU/ m3 with BES and 1.0 CFU/m3 with Rotecno (p = 0.014). The mean wound counts were 14 bacteria/wound with BES and eight bacteria/wound with Rotecno (p = 0.171). There was no correlation between the air and wound counts (r = -0.011, Spearman's). The higher air counts suggest that Rotecno occlusive clothing is less effective than BES, but wounds were equally contaminated with both types of clothing suggesting that at very low levels of air contamination the contribution of bacteria to the wound from the air is irrelevant. Even doubling the air counts from 0.5 to 1.0 CFU/m3 had no detectable effect on the wound. This allows a reassessment to be made of other sources of contamination the effect of which would previously have been overwhelmed by contamination from air.
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