BCOR regulates myeloid cell proliferation and differentiation.

BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1). Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukemia (AML). However, the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with upregulated expression of Hox genes. Mutation of Bcor reduced protein levels of RING1B, an H2A ubiquitin ligase subunit of PRC1 family complexes and reduced H2AK119ub upstream of upregulated HoxA genes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with enhanced cell proliferation and myeloid differentiation. Our results strongly suggest that BCOR plays an indispensable role in hematopoiesis by inhibiting myeloid cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes.

Methicillin-resistant Staphylococcus aureus infection in liver transplantation: a matched controlled study.

UNLABELLED: The purpose of this study was to evaluate the clinical impact of methicillin-resistant Staphylococcus aureus (MRSA) infections on transplant recipients. METHODS: Liver and kidney recipients with MRSA infections were retrospectively identified and compared to an age, gender, UNOS status, organ transplanted, and transplant date matched (2:1) non-MRSA-infected recipient control group. All MRSA infections were initially treated with vancomycin, and four (33%) liver recipients were converted to linezolid therapy after failing to improve with vancomycin. RESULTS: The overall MRSA infection incidence was 1.4% (24/1770) with MRSA more common in liver (3.75%; 12/320) than kidney transplants (0.8%; 12/1450) (P < .001). The most common sites of MRSA infection were blood (42%), lung (38%), and abdomen (29%). The MRSA group had a greater percentage of prior antibiotic usage (79% vs 40%; P < .0015). The MRSA group experienced more posttransplant complications (52% vs 19%; P < .011)), and exhibited a trend toward greater length of stay in the intensive care unit (7.8 vs 4.6 days; P = .09), but not overall length of stay. Survival was similar in MRSA and non-MRSA groups (75% vs 88%; P = .17). No significant differences in mortality were noted between liver and kidney recipients infected with MRSA (P = .6). CONCLUSION: MRSA infection is associated with a higher incidence of posttransplant complications and antibiotic usage in both liver and kidney recipients compared to patients with MRSA infection.

The risk assessment profile score identifies trauma patients at risk for deep vein thrombosis.

BACKGROUND: The identification of trauma patients at risk for the development of deep venous thrombosis (DVT) at the time of admission remains difficult. The purpose of this study is to validate the risk assessment profile (RAP) score to stratify patients for DVT prophylaxis. METHODS: All patients admitted from November 1998 thru May 1999 were evaluated for enrollment. We prospectively assigned patients as low risk or high risk for DVT using the RAP score. High-risk patients received both pharmacologic and mechanical prophylaxis. Low-risk patients received none. Surveillance duplex Doppler scans were performed each week of hospitalization or if symptoms developed. Hospital charges for prophylaxis were used to determine the savings in the low-risk group. Statistical differences between the risk groups for each factor of the RAP and development of DVT were determined by the chi-squared test, with significance at a probability value of less than .05. RESULTS: There were 102 high-risk (64%) and 58 low-risk (36%) individuals studied. Eleven of the high-risk group (10.8%) experienced the development of DVT (asymptomatic, 64%). None of the low-risk group was diagnosed with DVT. Five of the 16 RAP factors were statistically significant for DVT. Eliminating prophylaxis and Doppler scans in low-risk patients resulted in a total savings of $18,908 in hospital charges. CONCLUSIONS: The RAP score correctly identified trauma patients at increased risk for the development of DVT. Despite prophylaxis, the high-risk group warrants surveillance scans. Withholding prophylaxis in low-risk patients can reduce hospital charges without risk.

Worsening of liver function with fluconazole and review of azole antifungal hepatotoxicity.

OBJECTIVE: To report a case of fluconazole worsening of liver dysfunction. CASE SUMMARY: A patient with hepatitis experienced worsening of her liver function when treated with fluconazole for a Candida infection in her urine. Elevations in aspartate aminotransferase, alanine aminotransferase, and total bilirubin concentrations along with increased prothrombin time and activated partial thromboplastin time were noted as early as the second day of therapy. After discontinuation of the fluconazole, the liver parameters returned to their normal baseline level. DISCUSSION: Hepatotoxicity associated with azole antifungal therapy is reviewed. This patient experienced elevations in liver function enzymes; the literature relating to this topic is evaluated. CONCLUSIONS: It is probable that fluconazole therapy was involved in the worsening of this patient's liver function. Liver function should be monitored during the course of fluconazole therapy in patients with underlying liver dysfunction. It appears from the published reports that HIV-positive patients may be at risk for hepatotoxicity with fluconazole.

Foscarnet-induced severe hypomagnesemia and other electrolyte disorders.

OBJECTIVE: To report a case of possible foscarnet-induced severe hypomagnesemia and other electrolyte disorders. CASE SUMMARY: An AIDS patient experienced an exacerbation of cytomegalovirus retinitis and was treated with foscarnet. The patient experienced muscle twitches, tremulousness, and anxiety on day 17 of foscarnet therapy. Laboratory results indicated hypomagnesemia, hypocalcemia, hypokalemia, and hypophosphatemia. After electrolyte supplementation and discontinuation of foscarnet, the symptoms resolved and laboratory indices returned to normal. DISCUSSION: Electrolyte disorders associated with foscarnet are reviewed. Severe hypomagnesemia occurred in this patient and published literature is highlighted. In addition, known and/or possible mechanisms of the disorders are discussed. CONCLUSIONS: It is probable that foscarnet contributed to the electrolyte disorders and symptomatology in this patient. Electrolytes must be monitored frequently during foscarnet therapy. Also, concomitant therapy with antianxiety medications that may mask the symptoms of electrolyte disorders should be undertaken with caution.

Intravenous pentamidine-induced bronchospasm.

A 41-year-old man with AIDS developed a recurrence of Pneumocystis carinii pneumonia and was treated with intravenous pentamidine. This was associated with a significant bronchospastic reaction requiring treatment with an antihistamine and an aerosolized beta-agonist therapy. To our knowledge, this is the first report of bronchospasm induced by intravenous pentamidine.

Relationship of changes in condition score to cow health in Holsteins.

The relationship of body condition score with disease occurrence was examined in 561 cows in nine herds. Cows were body condition scored on a five-point scale (1 = thin, 5 = obese) every 2 wk from drying off until 150 d in milk. Cows scored between 3- and 3+ were considered to be in average or good condition. Cows scored less than or equal to 2+ were considered to be underconditioned, whereas those scored greater than or equal to 4- were considered to be overconditioned. Relationships of health and condition score were examined using multiple logistic regression for dichotomous outcomes (e.g., diseased or healthy). Cows that developed dystocia or were culled lost more condition during the dry period than those that did not develop dystocia or were not culled. Cows overconditioned at drying off were more likely to develop cystic ovarian disease and reproductive problems. Cows underconditioned or overconditioned at drying off were more prone to foot problems after calving. Cows overconditioned at 30 d postpartum were more likely to have metritis.

Real-time ultrasonography for determining pregnancy status and viable fetal numbers in ewes.

The reproductive tracts of 26 estrus synchronized, bred ewes were scanned with a portable 5.0 MHz real-time ultrasound unit within 1 to 6 d postbreeding. Intrarectal scanning was performed on alternate days until Days 28 to 30 and twice weekly until Days 50 of gestation. Transabdominal uterine scans were conducted twice weekly from Days 25 to 65 and continued weekly until parturition. A total of 24 ewes (92%) became pregnant. A nonpregnant ewe was recognized 100% of the time by both methods of ultrasonic screening. Correct identification of a gravid ewe as pregnant was 100% from Days 51 to 150 of gestation using transabdominal real-time ultrasonography. There was a significant association (P < 0.005) between the number of lambs born and the number of fetuses observed using transabdominal real-time ultrasonography after Day 25 of gestation. Accurate differentiation of fetal numbers by transabdominal scanning was 100.0% for ewes carrying one lamb and 97.3% for ewes carrying two lambs at Days 51 to 75 of gestation. Fetal attrition was documented in one ewe at Day 49 of gestation. Hydrops allantois was diagnosed in another ewe at 110 d of gestation. A total of 37 lambs were born to 23 ewes in the project flock. No congenital abnormalities were noted in any of the lambs. Transabdominal real-time ultrasonography is a safe, rapid, accurate and practical method for assessing pregnancy status, fetal number and fetal viability in sheep.

Serum neutralizing antibody titers in dairy cattle administered an inactivated vesicular stomatitis virus vaccine.

Two doses of a formalin-killed, cell culture-derived vesicular stomatitis virus (vsv)-New Jersey serotype vaccine were administered intramuscularly, 30 days apart, to all lactating and nonlactating cows in a 350-cow dairy herd. Serum specimens were obtained serially from 96 cows before vaccination and at 30, 52 and 80 days after vaccination and from 24 of these cows 175 days after vaccination. Serum neutralizing antibody titers to vsv-New Jersey serotype were determined from serum-dilution, plaque-reduction tests. Serum neutralizing antibody titers also were determined during the same period for 67 nonvaccinated heifers in the herd. Peak group geometric mean serum neutralizing antibody titers of 1:530.46 +/- 1.14 (group geometric mean titer log10, 2.725 +/- 0.055) developed 21 days after the second vaccination, but decreased to a low value of 1:65.36 +/- 1.38 (group geometric mean titer log10, 1.815 +/- 0.142) by 175 days after vaccination. The nonvaccinated group had no detectable antibody titer to vsv-New Jersey serotype throughout the study. All serum specimens from the vaccinates and controls were negative for heterologous reactivity to vsv-Indiana serotype.

Bilateral lower palpebral demodicosis in a dairy cow.

A registered 3 year old Guernsey heifer, recently fresh, was examined for sudden appearance of diffuse, firm swelling beneath both eyes. Vital signs and physical examination were within normal limits; no lymphadenopathy was present. Biopsy revealed a chronic eosinophilic granulomatous cellulitis and degenerate Demodex bovis. the lesions selfresolved within three months.