High fat diet induced obesity is mitigated in Cyp3a-null female mice.

Recent studies indicate a role for the constitutive androstane receptor (CAR), pregnane X-receptor (PXR), and hepatic xenobiotic detoxifying CYPs in fatty liver disease or obesity. Therefore, we examined whether Cyp3a-null mice show increased obesity and fatty liver disease following 8-weeks of exposure to a 60% high-fat diet (HFD). Surprisingly, HFD-fed Cyp3a-null females fed a HFD gained 50% less weight than wild-type (WT; B6) females fed a HFD. In contrast, Cyp3a-null males gained more weight than WT males, primarily during the first few weeks of HFD-treatment. Cyp3a-null females also recovered faster than WT females from a glucose tolerance test; males showed no difference in glucose tolerance between the groups. Serum concentrations of the anti-obesity hormone, adiponectin are 60% higher and ß-hydroxybutyrate levels are nearly 50% lower in Cyp3a-null females than WT females, in agreement with reduced weight gain, faster glucose response, and reduced ketogenesis. In contrast, Cyp3a-null males have higher liver triglyceride concentrations and lipidomic analysis indicates an increase in phosphatidylinositol, phosphatidylserine and sphingomyelin. None of these changes were observed in females. Last, Pxr, Cyp2b, and IL-6 expression increased in Cyp3a-null females following HFD-treatment. Cyp2b and Fatp1 increased, while Pxr, Cpt1a, Srebp1 and Fasn decreased in Cyp3a-null males following a HFD, indicating compensatory biochemical responses in male (and to a lesser extent) female mice fed a HFD. In conclusion, lack of Cyp3a has a positive effect on acclimation to a HFD in females as it improves weight gain, glucose response and ketosis.

Annotation of the Nuclear Receptors in an Estuarine Fish species, Fundulus heteroclitus.

The nuclear receptors (NRs) are ligand-dependent transcription factors that respond to various internal as well as external cues such as nutrients, pheromones, and steroid hormones that play crucial roles in regulation and maintenance of homeostasis and orchestrating the physiological and stress responses of an organism. We annotated the Fundulus heteroclitus (mummichog; Atlantic killifish) nuclear receptors. Mummichog are a non-migratory, estuarine fish with a limited home range often used in environmental research as a field model for studying ecological and evolutionary responses to variable environmental conditions such as salinity, oxygen, temperature, pH, and toxic compounds because of their hardiness. F. heteroclitus have at least 74 NRs spanning all seven gene subfamilies. F. heteroclitus is unique in that no RXRα member was found within the genome. Interestingly, some of the NRs are highly conserved between species, while others show a higher degree of divergence such as PXR, SF1, and ARα. Fundulus like other fish species show expansion of the RAR (NR1B), Rev-erb (NR1D), ROR (NR1F), COUPTF (NR2F), ERR (NR3B), RXR (NR2B), and to a lesser extent the NGF (NR4A), and NR3C steroid receptors (GR/AR). Of particular interest is the co-expansion of opposing NRs, Reverb-ROR, and RAR/RXR-COUPTF.

Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9/10/13-null mice.

Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model. Compensatory changes in CYP expression that occur in these models may also occur in polymorphic humans, or may complicate interpretation of ADME studies performed using these models. The loss of CAR causes significant changes in several CYPs probably due to loss of CAR-mediated constitutive regulation of these CYPs. Expression and activity changes include significant repression of Cyp2a and Cyp2b members with corresponding drops in 6α- and 16ß-testosterone hydroxylase activity. Further, the ratio of 6α-/15α-hydroxylase activity, a biomarker of sexual dimorphism in the liver, indicates masculinization of female CAR-null mice, suggesting a role for CAR in the regulation of sexually dimorphic liver CYP profiles. The loss of Cyp3a causes fewer changes than CAR. Nevertheless, there are compensatory changes including gender-specific increases in Cyp2a and Cyp2b. Cyp2a and Cyp2b were down-regulated in CAR-null mice, suggesting activation of CAR and potentially PXR following loss of the Cyp3a members. However, the loss of Cyp2b causes few changes in hepatic CYP transcript levels and almost no significant compensatory changes in protein expression or activity with the possible exception of 6α-hydroxylase activity. This lack of a compensatory response in the Cyp2b9/10/13-null mice is probably due to low CYP2B hepatic expression, especially in male mice. Overall, compensatory and regulatory CYP changes followed the order CAR-null > Cyp3a-null > Cyp2b-null mice.

Musculoskeletal manifestations of sickle cell anaemia: a pictorial review.

Sickle cell anaemia is an autosomal recessive genetic condition producing abnormal haemoglobin HbS molecules that result in stiff and sticky red blood cells leading to unpredictable episodes of microvascular occlusions. The clinical and radiological manifestations of sickle cell anaemia result from small vessel occlusion, leading to tissue ischemia/infarction and progressive end-organ damage. In this paper we discuss and illustrate the various musculoskeletal manifestations of sickle cell disease focusing primarily on marrow hyperplasia, osteomyelitis and septic arthritis, medullary and epiphyseal bone infarcts, growth defects, and soft tissue changes.

Unsuspected pulmonary emboli adversely impact survival in patients with cancer undergoing routine staging multi-row detector computed tomography scanning.

BACKGROUND: While symptomatic venous thromboembolism adversely impacts survival among cancer patients, the outcome of cancer patients with unsuspected pulmonary embolism (UPE) found on routine cancer staging multi-row detector computed tomography (MDCT) scans is unknown. OBJECTIVE: To determine whether UPE detected on routine staging MDCT scans impacts overall survival among cancer patients. PATIENTS AND METHODS: We performed a matched cohort study of cancer patients diagnosed with UPE on routine staging scans between May 2003 and August 2006. Two controls (n = 137) were individually matched by age (± 5 years), cancer type and stage for each UPE patient (n = 70). We used Cox's proportional hazard models to compare the mortality between UPE patients and their matched controls. RESULTS: The hazard ratio (HR) for death among UPE patients was 1.51 (95% CI 1.01-2.27, P = 0.048). Compared with their matched controls, patients with UPE more proximal than the subsegmental arterial branches had a HR for death at 6 months of 2.28 (95% CI 1.20-4.33, P = 0.011) and an overall HR of 1.70 (95% CI 1.06-2.74, P = 0.027). Survival among UPE patients with isolated subsegmental PE (ISSPE) was not significantly different than that of matched controls (HR 1.04 95% CI 0.44-2.39, P = 0.92). CONCLUSIONS: UPE identified more proximal than the subsegmental arterial branches has a significant negative impact on survival among cancer patients.

Percutaneous endoscopic gastrostomy with T-bar fixation in children and infants.

BACKGROUND: The standard for placement of pediatric gastrostomy tubes has been percutaneous endoscopic gastrostomy (PEG) using the Ponsky "pull" technique. This study evaluated the safety and efficacy of PEG placement using the "push" technique with T-bar fixation in pediatric patients. This technique generally is limited to the adult population. With this technique, endoscopy is performed. The stomach is insufflated, and the anterior abdominal wall is transilluminated. T-bar fasteners are sequentially deployed to secure the stomach to the anterior abdominal wall. Using a modified Seldinger technique, a gastrostomy tube is placed through the center of the T-bars. METHODS: A retrospective review of all PEG tubes placed in pediatric patients from 1997 to 2003 using the T-bar gastroscopy "push" technique was conducted. Patients 18 years of age or younger were included in the study. Data collected included patient age, operative time, procedure location, and complications. RESULTS: The procedure was performed for 47 children (mean age, 6.4 years), including 15 infants younger than 1 year. The indications for long-term enteral access included failure to thrive (n = 11), feeding disorder secondary to neurologic dysfunction (n = 31), gastroparesis (n = 1), and dysphagia (n = 4). The operative time averaged 23 min (range, 12-45 min). One major complication occurred (gastrocolonic fistula). The one minor complication was early dislodgement of the gastrostomy tube, which required replacement. CONCLUSION: This study found the described technique to be safe and effective for the placement of gastrostomy tubes in infants and children.

High-dose cytosine-arabinoside and cisplatin regimens as salvage therapy for refractory or relapsed AIDS-related non-Hodgkin's lymphoma.

No effective salvage regimen has been defined for patients with AIDS-related non-Hodgkin's lymphoma (AIDS-NHL) who do not respond to first-line chemotherapy that contains anthracycline. Combined dexamethasone, cytosine arabinoside, and cisplatin (DHAP) and etoposide, methylprednisolone, cytosine arabinoside, and cisplatin (ESHAP) have shown good response rates in HIV-negative patients with relapsed lymphomas. We retrospectively analyzed patients with refractory or relapsed AIDS-NHL who had been treated with either DHAP or ESHAP to evaluate the feasibility and efficacy of these regimens. Twenty-six patients with refractory or relapsed AIDS-NHL were treated between 1990 and 1999 either with DHAP ( n = 13) or with ESHAP ( n = 13). Only 1 patient from each group (8%) had achieved complete remission with any previous therapy, and most had progressive disease after the regimen immediately preceding DHAP or ESHAP. In the ESHAP group, 4 patients (31%) achieved complete remission (CR) and 3 patients (23%) attained partial remission (PR) for an overall response rate of 54%. The median survival was 7.1 months (range, 1-58.9+ months) from the time ESHAP was begun. Among the 3 patients with primary refractory lymphoma, there was 1 CR, 1 PR, and one patient with stable disease. In contrast, only 1 PR (7%) was observed with DHAP; the median survival was 3 months. Myelosuppression was the most significant toxicity with grade 4 neutropenia occurring in all who received ESHAP and in 54% of patients treated with DHAP. Neutropenic fever occurred in 8 (62%) ESHAP-treated and 6 (46%) DHAP-treated patients. Although hematologic toxicity is profound, ESHAP appears to be an active salvage regimen for patients with relapsed or refractory AIDS-NHL.

Liposomal daunorubicin in the treatment of relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: To assess the efficacy and toxicity of liposomal daunorubicin administered as a two-hour intravenous infusion to patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Eligible patients had relapsed or refractory NHL with measurable or evaluable disease, and low grade, select intermediate grade, or mantle cell pathologic types. Prior exposure to an anthracycline or anthracenedione was allowed. Liposomal daunorubicin at a dose of 100 mg/m2 was given intravenously over a minimum of 120 minutes every 3 weeks. as a single agent. RESULTS: Thirty-three patients were accrued: twenty-three (70%) had low-grade histologies; six (18%) had intermediate-grade histologies (follicular large-cell and diffuse small cleaved); and four (12%) patients had mantle-cell lymphoma. Eighteen (55%) had received two or more prior regimens; fourteen (42%) received a prior anthracycline. A median of six cycles of liposomal daunorubicin were administered (range 1-15). Of 31 patients evaluable for response, 2 complete and 10 partial remissions were documented for a major response rate of 39% (95% confidence interval (CI): 22%-58%). The median duration of response was 19.5 months (range 4.3-41.1+). Six responders (50%) had received a prior anthracycline; one responder had mantle-cell histology. The major toxicities were grade 3 or 4 neutropenia in 26 patients (79%), mild to moderate nausea in 22 (67%), and fatigue in 16 (48%). CONCLUSIONS: Liposomal daunorubicin at 100 mg/m2 every three weeks has activity in patients with relapsed or refractory NHL, including patients with prior exposure to an anthracycline. Further studies of liposomal daunorubicin in combination with other agents are warranted.

Vagus nerve stimulation in pediatric patients with intractable epilepsy: case series and operative technique.

Patients with epilepsy refractory to medical therapy or who experience intolerable side effects from the medication may benefit from placement and activation of a vagus nerve stimulator (VNS) (Cyberonics, Houston, TX). We present our experience with the VNS implanted by a pediatric surgeon and its activation managed by a pediatric neurologist. Six patients (one male and five females) with average age 11 years, 10 months (range 7 years, 4 months to 18 years, 1 month) received VNS implants at a community-based teaching hospital. One patient developed a self-inflicted wound complication secondary to persistent trauma at the implant site that led to removal of the implant. Before VNS implantation the frequency of seizures among the remaining five patients averaged 73 per patient per month (range 20-165). Length of follow-up averaged 6.5 months (range 1.5-11 months). At most recent follow-up seizure frequency averaged 14 per month (range 1-42); this represents an average reduction of 78 per cent (range 30-99%). We conclude that a pediatric surgeon with pediatric neurologic support can safely and effectively perform the VNS implantation at a hospital equipped to administer anesthesia to pediatric patients.

Spontaneous perforation of the bile duct.

We present a classic but rare case of spontaneous perforation of the bile duct in infancy and a previously undescribed treatment technique. The patient, a male age 5 weeks, was admitted with abdominal distention, ascites, and conjugated hyperbilirubinemia. Ultrasound revealed ascites but did not provide visualization of the gallbladder. Although hepatobiliary scintigraphy with technetium [dimethyl iminodiacetic acid (HIDA scan)] showed normal uptake peritoneal excretion suggested perforation of the common bile duct (CBD). Exploratory laparotomy revealed 200 cm3 dark amber ascitic fluid in the peritoneal cavity and cholestasis of the liver. Intraoperative cholangiogram performed via the gallbladder showed a large perforation at the cystic duct/CBD junction. The perforation was large and leakage of contrast prevented demonstration of the distal CBD despite our attempt to primarily repair the perforation. The CBD was explored; a T-tube was placed. T-tube cholangiogram demonstrated flow of contrast into the duodenum. A large leak remained at the cystic CBD junction. A cholecystectomy was performed and a vascularized flap of the gallbladder wall was used to repair the CBD over the T-tube. The T-tube was clamped intermittently beginning 3 weeks postoperatively. T-tube cholangiogram performed 6 weeks postoperatively revealed no extravasation and normal intra- and extrahepatic biliary tree. The T-tube was subsequently discontinued and liver function tests remained normal at 6 months follow-up.

An empirical examination of self-reported work stress among U.S. managers.

This study proposes that self-reported work stress among U.S. managers is differentially related (positively and negatively) to work outcomes depending on the stressors that are being evaluated. Specific hypotheses were derived from this general proposition and tested using a sample of 1,886 U.S. managers and longitudinal data. Regression results indicate that challenge-related self-reported stress is positively related to job satisfaction and negatively related to job search. In contrast, hindrance-related self-reported stress is negatively related to job satisfaction and positively related to job search and turnover. Future research directions are discussed.

Cladribine in the treatment of advanced relapsed or refractory low and intermediate grade non-Hodgkin's lymphoma.

BACKGROUND: Cladribine (2-chlorodeoxyadenosine) is a purine nucleoside analog with cytotoxic activity against both resting and proliferating cells. Clinical studies with cladribine have reported antitumor activity against various hematologic malignancies. METHODS: The authors studied responses to cladribine among patients with low and intermediate grade non-Hodgkin's lymphoma that had been refractory to or relapsed after prior chemotherapy. Cladribine was given intravenously over 2 hours at a dose of 0.14 mg/kg daily for 5 consecutive days, repeated every 4 weeks. RESULTS: Twenty-eight patients (16 males, 12 females) with a median age of 58 years (range, 41-75 years) were accrued. Twenty-three patients had low grade and 5 had intermediate grade lymphoma. Stage IV disease was present in 22 (79%), and 17 (61%) had systemic B-symptoms. The majority (57%) had received 2 or more prior chemotherapy regimens (median, 2; range, 1-5); 6 had had prior fludarabine therapy. Major responses were documented in 32% (9 of 28 patients), with 4 complete remissions (CR) and 5 partial remissions (PR) after a median of 4 cycles (range, 1-9). One CR occurred in one patient with intermediate grade diffuse large cell lymphoma, and three of six patients who had had prior fludarabine therapy experienced CR or PR with cladribine. Severe hematologic toxicities included reversible neutropenia, protracted thrombocytopenia, and lymphopenia. Other reported adverse effects included mild-to-moderate fatigue, nausea, and diarrhea. CONCLUSIONS: Cladribine is an active single agent in the treatment of patients with refractory or relapsed advanced stage indolent lymphoma, with major responses in one third of patients.

Phase II trial of liposomal daunorubicin in the treatment of AIDS-related pulmonary Kaposi's sarcoma.

PURPOSE: Kaposi's sarcoma (KS) is the most common tumor in patients with AIDS and can be fatal in patients with lung involvement. Systemic chemotherapy is the most effective treatment for pulmonary KS. We thus conducted this study to determine the efficacy of liposomal daunorubicin in the treatment of patients with pulmonary KS. METHODS: Patients with biopsy-proven, symptomatic pulmonary KS were accrued. Liposomal daunorubicin was given at a dose of 60 mg/m2 intravenously every 2 weeks. Response was monitored by chest radiographs, pulmonary function tests, arterial blood gases, and grading of pulmonary symptoms. RESULTS: Fifty-three male patients were accrued. The median CD4+ lymphocyte count was 13/microL (range, 0 to 200); 70% reported a prior AIDS-defining opportunistic infection. All patients were symptomatic, with cough reported in all patients, shortness of breath in 94%, and hemoptysis in 55%. The mean study entry diffusing capacity of carbon monoxide (DLCO) was 58.5% (percent of predicted). The median dose of liposomal daunorubicin delivered was 360 mg/m2 (range, 60 to 1,380). More than 75% of patients had complete or partial resolution of baseline pulmonary symptoms. Complete or partial improvement in DLCO was observed in 22%; complete or partial resolution of radiographic abnormalities was reported in 32%. The most common treatment-related toxicity was neutropenia, which occurred in 85%. There were no instances of cardiac toxicity observed, even at high cumulative doses. CONCLUSION: Liposomal daunorubicin at 60 mg/m2 is safe and active in patients with pulmonary KS. Trials combining liposomal daunorubicin with other active agents in KS should be considered.

Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin.

PURPOSE: Response rates to fluorouracil (5-FU)-based therapy remain low. As new, active agents are being tested, information regarding specific intratumoral genetic determinants of chemotherapy sensitivity or resistance can be used to plan therapy rationally. Intratumoral thymidylate synthase (TS) quantitation may be among the most important determinants of sensitivity or resistance to 5-FU. MATERIALS AND METHODS: Forty-six disseminated colorectal cancer patients had measurable tumor biopsies for polymerase chain reaction (PCR)-based determination of TS mRNA pretreatment. Protracted infusion of 5-FU 200 mg/m2/d for 21 days with weekly intravenous leucovorin 20 mg/m2 each cycle was given. After two cycles, responses were evaluated. Response data were correlated with independently determined intratumoral ratios of TS/beta-actin mRNA for each patient. RESULTS: TS/beta-actin ratios were successfully obtained for 42 patients (91%). TS/beta-actin ratios ranged from 0.3 x 10(-3) to 18.2 x 10(-3) (median, 3.5 x 10[-3]). Twelve patients (26%) responded to treatment (median TS/beta-actin ratio, 1.7 x 10[+3]). Thirty-four patients did not respond (median TS/beta-actin ratio, 5.6 x 10[-3]). No patient with a TS mRNA level greater than 4.1 x 10(-3) responded. The median TS/beta-actin ratio (3.5 x 10[-3]) significantly segregated responders from nonresponders (P = .001). Median survival for patients with TS/beta-actin ratios < or = 3.5 x 10(-3) was 13.6 months; for patients with TS/beta-actin ratios greater than 3.5 x 10(-3), it was 8.2 months (P = .02). CONCLUSION: For this cohort, the intratumoral TS/beta-actin ratio had a statistically significant association with response and survival. This relationship for other 5-FU schedules remains unknown. Confirmation of these data in a larger patient population could lead to determination of therapy for disseminated colorectal cancer based on a specific intratumoral molecular parameter.

Acute abdomen. Outcomes.

The outcome for children with common surgical conditions that cause an acute abdomen is discussed. These conditions include appendicitis, intussusception, malrotation, inflammatory bowel disease, intestinal obstructions, and nonorganic pain. Emphasis is placed on surgical intervention and disease processes that significantly affect outcome. The outcome of many of the diseases discussed is strongly influenced by the timing of diagnosis and treatment. These children should have prompt care and intervention to prevent morbidity and mortality. In addition, many children who present with common pediatric surgical emergencies have other medical conditions and are best treated in an environment that has a multidisciplinary team to handle their care and decrease the long-term complications.

Saline MR peritoneography.

OBJECTIVE: Our objective was to describe a new method for the evaluation of peritoneal surfaces in patients with intraperitoneal carcinomatosis and sarcomatosis. CONCLUSION: Fast spin-echo T2-weighted imaging in conjuction with intraperitoneally instilled saline permits detailed evaluation of peritoneal surfaces, omentum, and mesenteries. The detection of tumor implants is facilitated by their visualization against the saline background. Additionally, normal and abnormal saline distribution patterns can be identified. This technique may also be useful in predicting response to intraperitoneally instilled chemotherapy.

Percutaneous endoscopic gastrostomy with T-bar fixation in children.

Percutaneous endoscopic gastrostomy (PEG) with the Ponsky "pull" technique has been the standard technique for pediatric gastrostomy tube placement since 1979. We evaluated safety and efficacy of PEG with the "push" technique and T-bar fixation. We reviewed PEGs performed in pediatric patients (< or = 17 years) over a 31-month period, excluding patients with previous abdominal surgery. We evaluated age, indications, location, time, and complications. Endoscopy was performed, the stomach insufflated, and the anterior abdominal wall transilluminated. T-bar fasteners were inserted percutaneously under endoscopic control. Fasteners were ejected from the needle tip with a stylet and secured. A 14 or 18 French gastrostomy tube was placed through the center of previously placed T-bar fasteners by using a modified Seldinger technique. Fifteen children (mean age, 9 years) underwent the procedure for the need for long-term enteral alimentation (severe closed head injury) (n = 7), for progressive neurologic dysfunction with feeding disorder (n = 7), or for failure to thrive (cystic fibrosis) (n = 1). No significant major postoperative complications occurred. The technique proved safe and effective for gastrostomy in children.

Low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone with zalcitabine in patients with acquired immunodeficiency syndrome-related lymphoma. Effect on human immunodeficiency virus and serum interleukin-6 levels over time.

BACKGROUND: Use of multiagent chemotherapy has been associated with complete remission (CR) in approximately 50% of patients with newly diagnosed acquired immunodeficiency syndrome (AIDS)-lymphoma, although additional AIDS-related complications may occur. Both chemotherapy and antiretroviral therapy were employed in an attempt to ascertain if the combination was safe, and associated with changes in human immunodeficiency virus (HIV) p24 antigen levels during the course of treatment. METHODS: Low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone(M-BACOD) chemotherapy and zalcitabine (ddC) were employed in 28 patients. Since both vincristine and zalcitabine may cause peripheral neuropathy, a Phase I/II study design was employed. Serum was analyzed for immune complex dissociated (ICD) HIV p24 antigen and interleukin (IL)-6 levels during therapy. RESULTS: CR was achieved in 14 of 25 patients (56%), with partial response (PR) in 5 (20%). CRs were equivalent in patients with good or poor prognostic indicators, including a history of AIDS prior to lymphoma (CR = 60%); and/or CD4 lymphocytes < 200/mm3 (CR = 53%). Five patients with a CR subsequently relapsed (36%); median survival of CR patients was 29.2 months (4.1-61+), whereas that of all of the treated patients was 8.1 months. No significant peripheral neuropathy or other toxicity was observed. Serum ICD p24 antigen levels either fell (7/14) or remained consistently negative (2/14) in 9 of 14 patients (64%), whereas 36% experienced an increase. Elevated serum IL-6 levels at diagnosis were associated with systemic "B" symptoms (P = 0.023), whereas changes in IL-6 correlated with response to therapy over time (P = 0.006). CONCLUSIONS: Combination antineoplastic and zalcitabine antiretroviral therapy may be safely administered to patients with AIDS-related lymphoma, resulting in CR in 56%, lack of significant neurotoxicity, and favorable effect on HIV p24 antigen in 50%. Elevation of serum IL-6 is associated with systemic "B" symptoms, whereas changes in serum IL-6 may correlate with response.

Sigmoid volvulus in pregnancy.

During pregnancy, intestinal obstruction due to sigmoid volvulus is extremely rare. Only 73 cases have been reported. A 24-year-old black woman, gravida 2, para 1, presented during Week 36 of an otherwise uneventful pregnancy, with intermittent abdominal pain and constipation, and no history of nausea, vomiting, fever, chills, previous medical problems, or prior abdominal surgery. Her previous pregnancy was a spontaneous vaginal delivery of a normal full-term neonate. On examination, she was afebrile, with abdominal tenderness. Laboratory studies revealed elevated WBC count of 13,500. She was admitted and given a Fleet enema, with no result or change in abdominal pain. Pain worsened; reexamination of her cervix revealed 3 cm dilation. After Pitocin augmentation, a viable male infant with Apgars of 7 and 9 was delivered. Postpartum, abdominal pain continued, with worsening abdominal distention. Radiograph revealed a massively distended colon. Physical examination 12 hours postdelivery indicated peritonitis. Exploratory laparotomy revealed volvulated, gangernous, massively distended sigmoid colon. The sigmoid colon was resected and Hartmann's colostomy performed. She was discharged on postoperative Day 4. Sigmoid volvulus complicating pregnancy is an uncommon and potentially devastating development that should be suspected with worsening abdominal pain and evidence of bowel obstruction. Prompt intervention is necessary to minimize maternal and fetal morbidity.

Prevention of pediatric mortality from trauma: are current measures adequate?

Trauma accounts for nearly half of pediatric deaths in the United States. We reviewed all pediatric trauma-related deaths that occurred over a 5-year period at two Georgia trauma centers to determine the number of trauma deaths in children, mechanism of injury, cause of death, and compliance with safety standards. Of the 69 fatalities, 31 were caused by motor vehicle accidents. Twenty-five of these victims (81%) were unrestrained; 17 were 4 years old or less, and only 1 of them was restrained in a car seat. Pedestrian versus vehicle accidents resulted in 19 deaths, 10 of the victims being 4 years old or less. Bicycle versus vehicle accidents resulted in 4 deaths, 2 of them due to closed head injury; none of the victims wore headgear. All-terrain vehicle accidents resulted in 2 deaths from massive head injury; neither victim wore a helmet. One death occurred from bicycle handlebar injury; 12 deaths resulted from causes other than vehicle accidents. Major causes of pediatric fatalities were motor vehicle accidents (45%), pedestrian-vehicle accidents (28%), and bicycle accidents (6%). This study indicates that when safety measures such as restraint systems, helmets, or proper supervision are ignored, children may die as a result of trauma.