Case Report of a Diagnosed Septic Hip Joint Treated with a 2-Stage Hip Arthroplasty.

Introduction: Identifying and determining appropriate treatment of adult hip septic arthritis (SA) can be quite challenging. Although rare, the annual incidence of this diagnosis is approximately 8 cases per 100,000 patients. The timing of patient symptoms is wide spread. The presentation may be acute, subacute, or even chronic, and moreover, the disease process may be masked by an underlying etiology. Once diagnosed, SA requires rapid and aggressive treatment. Case Report: A 67-year-old patient presented with left hip pain. Physical examination shifted the differential diagnosis from osteoarthritis to a possible septic joint. Elevated inflammatory markers were revealed. Joint aspiration was obtained, which demonstrated rare Group G streptococcus. Two-stage hip arthroplasty was performed. Intra-operative cultures still reveal no growth of bacteria, and the patient is progressing well. Conclusion: Adult septic hip arthritis is a rare diagnosis. Hence, a proper history, physical examination, infectious laboratory workup is important. The treatment of the condition is based on the duration of symptoms and the physician's clinical gestalt.

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative. PATIENTS AND METHODS: Hybrid capture-based genomic profiling was carried out on ctDNA from 254 female patients with estrogen receptor-positive breast cancer. Peripheral blood samples were submitted by clinicians in the course of routine clinical care between May 2016 and March 2017. Sequencing of 62 genes was carried out to a median unique coverage depth of 7503×. Genomic alterations (GAs) in ctDNA were evaluated and compared with matched tissue samples and genomic datasets of tissue from breast cancer. RESULTS: At least 1 GA was reported in 78% of samples. Frequently altered genes were TP53 (38%), ESR1 (31%) and PIK3CA (31%). Temporally matched ctDNA and tissue samples were available for 14 patients; 89% of mutations detected in tissue were also detected in ctDNA. Diverse ESR1 GAs including mutation, rearrangement and amplification, were observed. Multiple concurrent ESR1 GAs were observed in 40% of ESR1-altered cases, suggesting polyclonal origin; ESR1 compound mutations were also observed in two cases. ESR1-altered cases harbored co-occurring GAs in PIK3CA (35%), FGFR1 (16%), ERBB2 (8%), BRCA1/2 (5%), and AKT1 (4%). CONCLUSIONS: GAs relevant to relapsed/metastatic breast cancer management were identified, including diverse ESR1 GAs. Genomic profiling of ctDNA demonstrated sensitive detection of mutations found in tissue. Detection of amplifications was associated with ctDNA fraction. Genomic profiling of ctDNA may provide a complementary and possibly alternative approach to tissue-based genomic testing for patients with estrogen receptor-positive metastatic breast cancer.

Characterization of the novel HLA-B*18:79 allele.

Characterization of the novel HLA B*18:79 allele is described.

Characterization of three novel HLA alleles with silent nucleotide substitutions.

Characterization of the novel HLA alleles B*35:11:03, B*42:01:03, and B*51:01:35 is described.

Characterization of a novel allele, HLA-A*03:132.

A*03:132 differs from A*03:01:01:01 at nucleotide 853 (codon 261) in exon 4.

Characterization of four novel HLA alleles, including two in the same haplotype.

Characterization of the novel HLA alleles A*02:330, A*11:108, B*40:175, and B*40:176 is described.

Characterization of a novel allele, HLA-B*15:228.

B*15:228 differs from B*15:01:01:01 at three nucleotides in exon 4.

Comparative evaluation of culture- and BAX polymerase chain reaction-based detection methods for Listeria spp. and Listeria monocytogenes in environmental and raw fish samples.

Two commercial polymerase chain reaction (PCR)-based Listeria detection systems, the BAX for Screening/Listeria monocytogenes and the BAX for Screening/Genus Listeria, and a culture-based detection system, the Biosynth L. monocytogenes Detection System (LMDS), were evaluated for their ability to detect L. monocytogenes and Listeria spp. in raw ingredients and the processing environment. For detection of L. monocytogenes from raw fish, enrichment was performed in Listeria enrichment broth (LEB), followed by plating on both Oxford agar and LMDS L. monocytogenes plating medium (LMPM). Detection of Listeria and L. monocytogenes from environmental samples was performed using LMDS enrichment medium, followed by plating on both Oxford agar and LMPM. A total of 512 environmental samples and 315 raw fish were taken from two smoked fish processing facilities and screened using these molecular and cultural Listeria detection methods. The BAX for Screening/L monocytogenes was used to screen raw fish and was 84.8% sensitive and 100% specific. The BAX for Screening/Genus Listeria was evaluated on environmental samples and had 94.7% sensitivity and 97.4% specificity. In conjunction with enrichment in LEB, LMPM had a sensitivity and specificity for detection of L. monocytogenes from raw fish of 97.8 and 100%, respectively. Use of LMDS enrichment medium followed by plating on LMPM allowed for sensitivity and specificity rates of 94.8 and 100%, respectively, for detection of L. monocytogenes from environmental samples. We conclude that both the BAX systems and the use of LMPM allow for reliable and rapid detection of Listeria spp. and L. monocytogenes. While the BAX systems provide screening results in about 3 days, the use of LMPM allows for L. monocytogenes isolation in 4 to 5 days.

Branchial elimination of superhydrophobic organic compounds by rainbow trout (Oncorhynchus mykiss).

The branchial elimination of pentachloroethane and four congeneric polychlorinated biphenyls by rainbow trout was measured using a fish respirometer-metabolism chamber and an adsorption resin column. Branchial elimination was characterized by calculating a set of apparent in vivo blood:water partition coefficients (P(BW)). Linear regression was performed on the logarithms of P(BW) estimates and the log K(OW) value for each compound to give the fitted equation: log P(BW)=0.76 x log K(OW)-1.0 (r(2)=0.98). The linear nature of this relationship provides support for existing models of chemical flux at fish gills and suggests that a near equilibrium condition was established between chemical in venous blood entering the gills, including dissolved and bound forms, and dissolved chemical in expired branchial water. In vivo P(BW) estimates were combined with P(BW) values determined in vitro for a set of lower log K(OW) compounds (Bertelson et al., Environ. Toxicol. Chem. 17 (1998) 1447-1455) to give the fitted relationship: log P(BW)=0.73 x log K(OW)-0.88 (r(2)=0.98). The slope of this equation is consistent with the suggestion that chemical binding to non-lipid organic material contributes substantially to blood:water chemical partitioning. An equation based on the composition of trout blood (water content and the total amount of organic material) was then derived to predict blood:water partitioning for compounds with log K(OW) values ranging from 0 to 8: log P(BW)=log[(10(0.73 log K(ow)) x 0.16)+0.84].

A physiologically based toxicokinetic model for lake trout (Salvelinus namaycush).

A physiologically based toxicokinetic (PB-TK) model for fish, incorporating chemical exchange at the gill and accumulation in five tissue compartments, was parameterized and evaluated for lake trout (Salvelinus namaycush). Individual-based model parameterization was used to examine the effect of natural variability in physiological, morphological, and physico-chemical parameters on model predictions. The PB-TK model was used to predict uptake of organic chemicals across the gill and accumulation in blood and tissues in lake trout. To evaluate the accuracy of the model, a total of 13 adult lake trout were exposed to waterborne 1,1,2,2-tetrachloroethane (TCE), pentachloroethane (PCE), and hexachloroethane (HCE), concurrently, for periods of 6, 12, 24 or 48 h. The measured and predicted concentrations of TCE, PCE and HCE in expired water, dorsal aortic blood and tissues were generally within a factor of two, and in most instances much closer. Variability noted in model predictions, based on the individual-based model parameterization used in this study, reproduced variability observed in measured concentrations. The inference is made that parameters influencing variability in measured blood and tissue concentrations of xenobiotics are included and accurately represented in the model. This model contributes to a better understanding of the fundamental processes that regulate the uptake and disposition of xenobiotic chemicals in the lake trout. This information is crucial to developing a better understanding of the dynamic relationships between contaminant exposure and hazard to the lake trout.

Dermal absorption of three waterborne chloroethanes in rainbow trout (Oncorhynchus mykiss) and channel catfish (Ictalurus punctatus).

In vivo estimates of xenobiotic chemical flux across the dermal surface of intact fish were obtained by measuring chemical loss from venous blood to expired water. An experimental system was developed to separate the dermal route of exposure from all other routes. The system was then used to measure dermal absorption of tetrachloroethane (TCE), pentachloroethane (PCE), and hexachloroethane (HCE) in channel catfish (Ictalurus punctatus) and rainbow trout (Oncorhynchus mykiss), two fish with very different skin anatomies. The kinetics of accumulation varied among chemicals, but for each compound were similar among species. TCE accumulated rapidly, reaching steady state in blood within 48 hr. Steady state was not reached in 48 hr with PCE or HCE, although blood levels of PCE were probably close to steady-state values. Dermal flux estimates (based on branchial efflux) for TCE, PCE, and HCE were two to four times greater in catfish than in trout. Arterial blood concentrations of each compound were three to six times greater in catfish. These observations are indicative of greater flux across catfish skin, augmented by higher blood:water chemical partitioning. Trout skin is covered with scales and has no taste buds, while catfish skin does not possess scales and has numerous taste bud papillae. Both scales and taste bud papillae originate in the dermis and extend to the skin surface through the epidermis. In catfish these taste buds may offer channels through which chemicals diffuse across the epidermis to the more vascularized dermis. A comparison of dermal and branchial uptake was made by estimating zero-time dermal and branchial fluxes for all three chloroethanes. The mean dermal fluxes for TCE, PCE, and HCE ranged from 1.4 to 2.8, 1.8 to 3.6, and 1.4 to 3.2% of the total flux (branchial plus dermal) in rainbow trout and channel catfish, respectively. This research demonstrates that dermal absorption of waterborne chemicals occurs in large adult fish and results in distribution kinetics similar to those observed in inhalation exposures. Compared to branchial uptake, the dermal route of exposure appears to be relatively unimportant in large fish. It may, however, be very important in smaller fish and for juveniles of larger species.

A physiologically based toxicokinetic model for dermal absorption of organic chemicals by fish.

A physiologically based toxicokinetic model was developed to describe dermal absorption of waterborne organic chemicals by fish. The skin was modeled as a discrete compartment into which compounds diffuse as a function of chemical permeability and the concentration gradient. The model includes a countercurrent description of chemical flux at fish gills and was used to simulate dermal-only exposures, during which the gills act as a route of elimination. The model was evaluated by exposing adult rainbow trout and channel catfish to hexachloroethane (HCE), pentachloroethane (PCE), and 1,1,2,2-tetrachloroethane (TCE). Skin permeability coefficients were obtained by fitting model simulations to measured arterial blood data. Permeability coefficients increased with the number of chlorine substituent groups, but not in the manner expected from a directly proportional relationship between dermal permeability and skin:water chemical partitioning. An evaluation of rate limitations on dermal flux in both trout and catfish suggested that chemical absorption was limited more by diffusion across the skin than by blood flow to the skin. Modeling results from a hypothetical combined dermal and branchial exposure indicate that dermal uptake could contribute from 1.6% (TCE) to 3.5% (HCE) of initial uptake in trout. Dermal uptake rates in catfish are even higher than those in trout and could contribute from 7.1% (TCE) to 8.3% (PCE) of initial uptake in a combined exposure.

Expression of retinoic acid receptor beta in human renal cell carcinomas correlates with sensitivity to the antiproliferative effects of 13-cis-retinoic acid.

The differentiation and growth suppressive effects of retinoic acid are mediated through retinoic acid nuclear receptors (RARs and RXRs), which are ligand-activated transcription factors. Recent data suggest that both altered and regulated expression of RARs are linked to retinoic acid response in a cell context-dependent manner. This study examined the antiproliferative effects of 13-cis-retinoic acid (cRA) on 12 renal cancer cell lines and correlated these findings with the basal and induced expression of RAR-alpha, -beta and -gamma. Eleven of 12 renal cancers that were either resistant to or only minimally inhibited by cRA did not basally express RAR-beta as determined by Northern blot analysis. In these cells, cRA treatment did not induce RAR-beta expression. In contrast, 1 of 12 cell lines (SK-RC-06) was >90% inhibited by cRA and basally expressed RARbeta. Furthermore, RAR-beta mRNA in SK-RC-06 cells was up-regulated by cRA treatment. Amplification of cDNA using PCR and RAR-beta isoform-specific primer pairs revealed that only SK-RC-06 cells expressed the RAR-beta1 isoform. Expression of RAR-alpha transcripts was abundant in all 12 cell lines examined, whereas low levels of RAR-gamma transcripts were detectable in 6 of 10 renal cancers. Expression of RAR-alpha and RAR-gamma was not affected by cRA. These data showing that the majority of renal cancer cell lines are resistant to cRA suggest that: (a) resistance to the antiproliferative action of cRA correlates with repressed RAR-beta mRNA expression; and (b) the antiproliferative effects of cRA in renal cancer cells are mediated through RAR-beta1.

A neuropsychiatric disorder associated with dense calcification of the external ears and distal muscle wasting: 'Primrose syndrome'.

We report a 43-year-old man with a slowly progressive neurological disorder associated with impaired intellect, general stiffening of the spine and joints, craniofacial dysmorphism, hearing loss, and massive calcification of the external ears. Extensive laboratory investigations were nondiagnostic. This patient appears to have the same disorder reported previously in two individual case reports, supporting the idea that this phenotype may represent a recognizable new clinical entity. A review of literature pertaining to calcification of the external ears is presented.

Interferon alfa-2a and 13-cis-retinoic acid in renal cell carcinoma: antitumor activity in a phase II trial and interactions in vitro.

PURPOSE: A phase II trial of interferon alfa-2a (IFN) and 13-cis-retinoic acid (CRA) was conducted in patients with renal cell carcinoma (RCC). In vitro studies were performed to investigate potential mechanisms of interaction. PATIENTS AND METHODS: Forty-four patients were treated. IFN was given daily at 3 MU and escalated to 6 and 9 MU if tolerated. The dose of CRA was 1 mg/kg/d. The effects of combining CRA and IFN on the proliferation of five RCC cell lines were examined, and retinoid sensitivity was correlated to the expression of retinoic acid receptors. RESULTS: Thirteen (30%) of 43 assessable patients achieved a major response (three complete and 10 partial). Responding sites included bone metastases and renal primary tumors. Seven responding patients remain progression-free at 10+ to 19+ months. The response proportion was higher than in our prior experience with IFN, which was 10% in 149 patients. Eleven of 12 renal cancer cell lines were resistant to CRA alone; one, SK-RC-06, showed 90% inhibition of cell growth. CRA augmented the antiproliferative effect of IFN in several IFN-sensitive cell lines, but not in IFN-resistant lines. Northern blot analysis showed that expression of retinoic acid receptor-beta (RAR-beta) was repressed and not induced by retinoic acid in retinoic acid-insensitive RCC lines. However, RAR-beta expression was induced by retinoic acid in SK-RC-06 cells. CONCLUSION: IFN and CRA showed antitumor activity in patients with advanced RCC, and the proportion and nature of response suggested CRA added therapeutic benefit to IFN. A phase III randomized trial of IFN plus CRA versus IFN alone and a phase II trial of single-agent CRA have been initiated.

Imaging diagnosis and follow-up of infantile hepatic haemangioendothelioma: a case report.

A 4-week-old male infant was admitted to the hospital with acute gastrointestinal bleeding and marked coagulopathy secondary to vitamin K malabsorption in the presence of cholestasis. Physical examination revealed hepatomegaly and cutaneous haemangiomas. Ultrasonography, CT, and MRI demonstrated a multifocal vascular process and allowed the diagnosis of infantile hepatic haemangioendothelioma to be made without the use of more invasive diagnostic procedures. To avoid high-output congestive heart failure, the patient was treated with oral corticosteroids. After 5 months, rapid involution of the vascular malformations ensued. At age 2 years, a magnetic resonance scan confirmed complete resolution of the hepatic haemangioendothelioma.

In vivo microdialysis sampling of phenol and phenyl glucuronide in the blood of unanesthetized rainbow trout: implications for toxicokinetic studies.

Microdialysis (MD) is a sampling method that allows continuous in vivo collection of free, unbound chemicals in blood and interstitial fluids. In the present study we describe a surgical method for placement of a MD probe in the dorsal aorta of 600- to 900-g rainbow trout (Onchorhynchus mykiss). A specially designed probe guide was inserted into the dorsal aorta via the mouth. A PE-50 polyethylene cannula was then inserted into the probe guide and used to further position and maintain the probe guide in the dorsal aorta. Once proper placement of the probe guide was ascertained, the cannula was removed and a CMA-10 MD probe (4-mm tip) was inserted. The animal was then placed into a respirometer-metabolism chamber and allowed to recover from anesthesia. The placement and functionality of the probe were evaluated by examining the in vivo toxicokinetics of phenol (PH) and phenyl glucuronide (PG) in the blood of an unanesthetized rainbow trout exposed to water-borne PH (7.0 mg/liter). Prior to and following the introduction of PH into the metabolism chamber, MD samples (150 microliters) were collected at 30-min intervals and analyzed for free plasma PH and PG by HPLC. Total PH in exposure water and blood was also monitored every 30 min. Free PH and total PH in plasma accumulated rapidly and reached apparent steady-state levels of 54 and 142 pmol/microliters, respectively, in about 60 min. A blood:water partition coefficient of 2.0-2.6 was determined from these data, while bound and free plasma PH were 60 and 40%, respectively. PG was not detected until approximately 90 min of PH exposure.(ABSTRACT TRUNCATED AT 250 WORDS)