Inhibition of p38 mitogen activate kinase attenuates the severity of pancreatitis-induced adult respiratory distress syndrome

OBJECTIVE: Adult respiratory distress syndrome (ARDS) is responsible for a significant portion of the morbidity and mortality during severe acute pancreatitis. Because inflammatory mediators such as tumor necrosis factor (TNF)-alpha and nitric oxide (NO) produced within the lungs have been implicated in sepsis-induced ARDS, we aimed to determine the role of these mediators in pancreatitis-induced ARDS using a model whereby ascites from animals with pancreatitis is transferred to otherwise healthy animals resulting in pulmonary injury. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory at a university medical school. SUBJECTS: Pathogen-free Sprague-Dawley rats weighing 225-250 g. INTERVENTIONS: Sterile, endotoxin- and cytokine-free pancreatic ascites tested for interleukin (IL)-1beta , TNF-alpha, interferon-gamma, and IL-6 was obtained from rats 18 hrs after the induction of severe, acute pancreatitis. Ascites was subsequently administered intravenously (20 mL/kg) to healthy rats. Sham animals were administered intravenous saline. Healthy animals administered intravenous ascites were randomized to receive a single intraperitoneal injection of the p38 mitogen activated kinase inhibitor CNI-1493 (1 mg/kg) or vehicle. MEASUREMENTS: Pulmonary injury was assessed at 24 hrs by histology and leukocyte and protein concentrations via bronchoalveolar lavage. Pulmonary TNF-alpha protein was detected by immunohistochemistry. Serum nitrite, as a measure of NO production, was measured utilizing the Griess reaction. MAIN RESULTS: After the intravenous administration of pancreatic ascites, the number of leukocytes and the protein concentration within the bronchoalveolar fluid were increased and pulmonary histology was worsened consistent with acute lung injury (all p < .001 vs. sham). Each of these variables of pulmonary injury was lessened in animals receiving CNI-1493 and intravenous ascites (p < .05 vs. vehicle). Pulmonary TNF-alpha protein and serum nitrites were decreased with the administration of CNI-1493 (p < .005 vs. vehicle). CONCLUSIONS: A component of pancreatic ascites other than endotoxin, bacteria, or cytokines (IL-1beta, TNF, interferon-gamma, or IL-6) is capable of inducing ARDS in healthy animals. Inhibition of p38 mitogen activated kinase decreases the pulmonary injury through attenuated production of TNF-alpha and NO suggesting a primary role for these mediators in pancreatitis-induced ARDS.     

Risk Factors for Early Dislocation Following Primary Elective Total Hip Arthroplasty

Background

Dislocation following total hip arthroplasty (THA) continues to be one of the most common reasons for revision THA. The purpose of this study is to measure the current rate of dislocation following THA in the United States. A secondary goal is to identify patients at highest risk of instability after THA.

Qualitative venous Doppler waveform analysis improves prediction of critical perinatal outcomes in premature growth-restricted fetuses.

BACKGROUND: Our aim was to test the hypothesis that qualitative ductus venosus and umbilical venous Doppler analysis improves prediction of critical perinatal outcomes in preterm growth-restricted fetuses with abnormal placental function. METHODS: Patients with suspected intrauterine growth restriction (IUGR) underwent uniform fetal assessment including umbilical artery (UA), ductus venosus (DV) and umbilical vein (UV) Doppler. Absent or reversed UA end-diastolic velocity (UA-AREDV), absence or reversal of atrial systolic blood flow velocity in the DV (DV-RAV) and pulsatile flow in the umbilical vein (P-UV) were examined for their efficacy to predict critical outcomes (stillbirth, neonatal death, perinatal death, acidemia and birth asphyxia) before 37 weeks' gestation. RESULTS: Seventeen (7.6%) stillbirths and 16 (7.1%) neonatal deaths were observed among 224 IUGR fetuses. Forty-one neonates were acidemic (19.8%) and seven (3.1%) had birth asphyxia. Logistic regression showed that UA-AREDV had the strongest association with perinatal mortality (R(2) = 0.49, P < 0.001), stillbirth (R(2) = 0.48, P < 0.001) and acidemia (R(2) = 0.22, P = 0.002) while neonatal death was most strongly related to DV-RAV and P-UV (R(2) = 0.33, P = 0.007). UA waveform analysis offered the highest sensitivity and negative predictive value and DV-RAV and P-UV had the best specificity and positive predictive values for outcome prediction. Overall, DV-RAV or P-UV offered the best prediction of acidemia and neonatal and perinatal death irrespective of the UA waveform. In fetuses with UA-AREDV, prediction of asphyxia and stillbirth was significantly enhanced by venous Doppler. CONCLUSION: Prediction of critical perinatal outcomes is improved when venous and umbilical artery qualitative waveform analysis is combined. The incorporation of venous Doppler into fetal surveillance is therefore strongly suggested for all preterm IUGR fetuses.     

Physician gender and psychosocial care for children: attitudes, practice characteristics, identification, and treatment

OBJECTIVE: To examine differences by physician gender in the identification and treatment of childhood psychosocial problems. DESIGN: Survey of patients (n = 19,963) and physicians (n = 366) in primary care offices in 2 large, practice-based research networks. Multivariate regressions were used to control for patient, physician, and visit characteristics, with a correction for the clustered sample. SUBJECTS: Children ages 4 to 15 years seen consecutively for nonemergent care. MEASURES: Physician report of attitudes, training, practice factors, and identification and treatment of psychosocial problems. Parental report of demographics and behavioral symptoms. RESULTS: Compared with male physicians, female physicians were less likely to view care for psychosocial problems as burdensome. They were more likely to see children who were female, younger, black or Hispanic, in single-parent households, enrolled in public or managed health plans, and with physical health limitations. Children seen by male physicians had higher symptom counts. Male physicians were more likely to report having primary care responsibility for their patient and that parents agree with their care plan. Female physicians spent more time with patients. After controlling for these differences, female physicians did not differ from male physicians in identification or treatment of childhood psychosocial problems. CONCLUSIONS: Male and female physicians see different kinds of children for different visit purposes and have different kinds of relationships with their patients. After controlling for these factors, management of childhood psychosocial problems does not differ by physician gender. Improving management of psychosocial conditions depends on identifying modifiable factors that affect diagnosis and treatment; our work suggests that characteristics of the practice environment, physician-patient relationship, and patient self-selection deserve more research.     

Desmoplastic medulloblastoma in a 48-year-old male

Medulloblastoma is a malignant invasive embryonal tumor of the cerebellum with preferential manifestation in children. The peak of occurrence is seven years of age. Seventy percent of medulloblastomas occur in individuals younger than 16. In adulthood, 80% of medulloblastomas arise in the 21-40 years age group. A 48-year-old male patient was admitted to the hospital with complains of headache, ataxia, morning vomiting and difficulty in speech was operated with the diagnosis of presence of mass of 4 x 7 cm size retaining a diffuse homogenous contrast in the posterior fossa. The diagnosis of desmoplastic medulloblastoma was given after histopathological examination. Immunohistochemical examination revealed that neoplastic cells showed staining with neuron-specific enolase and synaptophysin but not with glial fibrillary acidic protein. This lesion showed nodular, reticulin free-zones (pale islands) surrounded by densely packed, highly proliferative cells. The pale regions within the tumor did not contain reticulin fibers. Desmoplastic medulloblastoma is encountered especially in adulthood. This type of tumor rarely occurs beyond the fifth decade of life. We present a case of desmoplastic medulloblastoma in a 48-year-old male.     

Computerized fetal heart rate analysis, Doppler ultrasound and biophysical profile score in the prediction of acid-base status of growth-restricted fetuses.

OBJECTIVE: To investigate the performance of non-stress test (NST), computerized fetal heart rate analysis (cCTG), biophysical profile scoring (BPS) and arterial and venous Doppler ultrasound investigation in the prediction of acid-base status in fetal growth restriction. METHODS: Growth-restricted fetuses, defined by abdominal circumference < 5(th) percentile and umbilical artery (UA) pulsatility index > 95(th) percentile, were tested by NST, cCTG, BPS, and UA, middle cerebral artery (MCA), ductus venosus (DV) and umbilical vein (UV) Doppler investigation. The short-term variation (STV) of the fetal heart rate was calculated using the Oxford Sonicaid 8002 cCTG system. Relationships between antenatal test results and cord artery pH < 7.20 were investigated, using correlation, parametric and non-parametric tests. RESULTS: Fifty-six of 58 patients (96.6%) received complete assessment of all variables. All were delivered by pre-labor Cesarean section at a median gestational age of 30 + 6 weeks. The UA pulsatility index (PI) was negatively correlated with the cCTG STV (Pearson correlation - 0.29, P < 0.05). The DV PI was negatively correlated with the pH (Pearson correlation - 0.30, P < 0.02). The cCTG mean minute variation and pH were not significantly correlated (Pearson correlation 0.13, P = 0.34). UV pulsations identified the highest proportion of neonates with a low birth pH (9/17, 53%), the highest number of false positives among patients with an abnormal BPS, abnormal DV Doppler and a STV < 3.5 ms, and also stratified false negatives among patients with an equivocal or normal BPS. Abnormal DV Doppler correctly identified false positives among patients with an abnormal BPS. cCTG reduced the rate of an equivocal BPS from 16% to 7.1% when substituted for the traditional NST. Elevated DV Doppler index and umbilical venous pulsations predicted a low pH with 73% sensitivity and 90% specificity (P = 0.008). CONCLUSION: In fetal growth restriction with placental insufficiency, venous Doppler investigation provides the best prediction of acid-base status. The cCTG performs best when combined with venous Doppler or as a substitute for the traditional NST in the BPS.     

The management of lichen planus with low-molecular-weight heparin (enoxaparin)

The aim of this study is to evaluate the efficiency of low-dose, low-molecular-weight heparin (enoxaparin) in the treatment of lichen planus (LP). Twenty-four patients clinically and histopathologically diagnosed as LP with intense pruritus were treated with 3 mg of enoxaparin (Clexane), subcutaneously once a week for 4-14 weeks. Complete remission was observed in 20 of 24 patients (83%) who had widespread cutaneous involvement, but no or minimal effect was observed in four of 24 patients, three of whom had chronic hypertrophic LP. Low-dose enoxaparin was observed to be effective in the treatment of LP without any side-effects. Enoxaparin may be an effective and simple alternative therapy for LP.     

Abnormal first-trimester ductus venosus blood flow: a risk factor for adverse outcome in fetuses with normal nuchal translucency.

OBJECTIVES: First-trimester nuchal translucency thickness (NT) is a potent tool for assessment of fetal risks of aneuploidy and other adverse outcomes. When NT is increased, Doppler assessment of the ductus venosus (DV) enhances the prediction specificity for Down syndrome. This study assessed abnormal Doppler DV waveform as a predictor of adverse outcome when the NT is normal. METHODS: This was a case-control study of 2,505 consecutive patients undergoing NT screening in our certified first-trimester screening program. First-trimester Doppler assessment of DV was performed and atrial systolic velocity was rated as antegrade (normal) or absent/reversed (DV-RAV; abnormal). Each case with normal NT (< 95(th) percentile) and DV-RAV was matched with two controls with respect to maternal age within 1 year, NT within 0.2 mm, crown-rump length within 3 mm, and closest calculated aneuploidy risk. Outcomes for paired variables were compared using t-test and Chi-square test. RESULTS: Forty-seven (1.9%) patients had normal NT and DV-RAV. After exclusion of three cases with obvious first-trimester anomalies and two with incomplete outcome data, 42 remained for analysis. Adverse outcome included cardiovascular defects (n = 6), fetal growth restriction (n = 3), renal anomaly (n = 2), aneuploidy (n = 3) and multiple defects (n = 3), in a total of 11/42 cases (26.2%). Cardiac abnormalities, renal abnormalities and perinatal death were all significantly more common in the study group (all P < 0.05). CONCLUSIONS: Abnormal first-trimester DV Doppler findings appear to predict adverse outcome independently of a normal NT. These patients need detailed mid-trimester assessment of fetal anatomy with formal echocardiography, and subsequent follow-up.