Urine vascular endothelial growth factor-A is not a useful marker for endometriosis

OBJECTIVE: To determine whether urine VEGF is elevated in women with endometriosis. DESIGN: Prospective observational study. SETTING: Tertiary care government and private hospitals. PATIENT(S): During laparoscopy for pelvic pain or infertility, urine was collected and possible endometriosis lesions were excised. Of 62 women, 40 had histology-proven endometriosis and 22 had no histological proof of the disease. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Urine VEGF-A(121, 165) was measured and compared in women with and without biopsy-proven endometriosis. RESULT(S): Urine VEGF levels corrected for creatinine excretion were similar in women with (83.6 +/- 11.3 pg/mg Cr) and without (88.5 +/- 10.4 pg/mg Cr) endometriosis (P =.77). The frequency distribution of urine VEGF measurements for women with and without endometriosis was similar. No significant difference was noted in urine VEGF levels when comparing endometriosis stages or in those with endometriomas compared to controls. Urine VEGF did not vary significantly over the menstrual cycle or between groups by cycle phase. No cutoff point discriminated individuals with and without the condition. CONCLUSION(S): It is unlikely that urine VEGF-A(121, 165), as measured in this study, will be a useful non-invasive marker for endometriosis.     

Sacral insufficiency fracture

Insufficiency fractures of the sacrum are not uncommon and usually occur in osteoporotic bone with minimal or unremembered trauma. However, they appear to be relatively under-diagnosed and this pictorial review aims to highlight the condition, discuss the expected imaging features and some of the potential imaging pitfalls. Owing to its relationship with osteoporosis, the majority occur in elderly females and are frequently bilateral, often presenting as low back pain. Plain radiographs are generally normal and both clinician and radiologist need to consider the possibility of sacral insufficiency fracture to allow prompt accurate diagnosis and correct treatment. Lumbar spine MRI is among the first investigations performed and can enable the correct diagnosis to be made. Occasionally the MR appearances can mimic tumour or osteomyelitis. The "H" sign on an isotope bone scan is considered diagnostic in the right clinical setting, but this sign is often not present. CT is useful to confirm the diagnosis and exclude tumour or infection.     

Inhibition of mixed lineage kinase 3 attenuates MPP+-induced neurotoxicity in SH-SY5Y cells

5-HT(1B) autoreceptors regulate serotonin release from terminals of dorsal raphe nucleus (DRN) projections. Due to postsynaptic 5-HT(1B) receptors in DRN terminal fields, it has not previously been possible to manipulate 5-HT(1B) autoreceptor activity without also changing 5-HT(1B) heteroreceptor activity. We have developed a viral gene transfer strategy to express epitope-tagged 5-HT(1B) and green fluorescent protein in vivo, allowing us to increase 5-HT(1B) expression in DRN neurons. We have shown that increased 5-HT(1B) autoreceptor expression reduced anxiety in unstressed animals but increased anxiety following inescapable stress. These findings suggest that effects of increased 5-HT(1B) autoreceptor expression are dependent on stress context. To better understand the mechanisms underlying these observations, we have used fear-potentiated startle (FPS). FPS is especially sensitive to the activity of the amygdala, which shares reciprocal connections with DRN. In the absence of an inescapable stressor, increased 5-HT(1B) autoreceptor expression attenuated FPS response compared with animals injected with a virus expressing only green fluorescent protein. Administration of the 5-HT(1B) antagonist SB224289 (5 mg/kg i.p.) before startle testing blocked the effects of increased 5-HT(1B) autoreceptor expression. Since SB224289 had no effect on FPS in the absence of viral gene transfer, these results suggest that the antagonist reversed the behavioral effects of increased 5-HT(1B) autoreceptor expression through blockade of transgenic receptors. When tested 24 h following water-restraint stress, animals with increased 5-HT(1B) autoreceptors demonstrated restoration of robust FPS response. These results extend our previous studies and suggest explanations for the complex relationship between 5-HT(1B) autoreceptor expression, stress, and anxiety behavior.     

Snowmobile injuries and fatalities in children

Background/Purpose: Snowmobiling is a popular form of wintertime recreation but can be associated with significant morbidity and mortality. To better understand snowmobile trauma in children, medical records were reviewed, evaluating the relationships between demographic data, mechanisms, and resultant injuries. In addition, because prior studies of childhood snowmobile fatalities have reviewed only national databases, state and national data were combined to evaluate possible underreporting. Methods: Medical records were reviewed of children [le ]17 years old admitted to one trauma center between 1991 and 2000 with snowmobile-related injuries. Demographics, helmet usage, driver versus passenger, mechanism, injuries, injury severity score (ISS), and outcome data were recorded. Statistical analyses were performed to identify relationships between potential causative factors and ISS. State mortality data were acquired from state agencies and 2 databases of the U.S. Consumer Product Safety Commission (CPSC). Data from the 3 sources were compared, and a single list of fatalities was compiled and evaluated. Results: Thirty-one children (65% boys; mean age, 12 years) were admitted with snowmobile-related injuries. Fifty-two percent were driving the snowmobile. Helmet usage was 68%. The most common mechanisms were collisions with a fixed object (42%) and with a motor vehicle (35%). The head was the most commonly injured site (71%) followed by the extremities (58%). ISS ranged from 1 to 38 (median, 10). Increased age and the child driving were the only factors associated with increased ISS (P [lt ] .05). One child died of a massive head injury. Twenty-two fatalities (70% boys; mean age, 14 years) statewide were identified from state and national databases, only 12 of which were identified by the CPSC Death Certificate file. Head injury was the most common cause of death. Conclusions: Reckless snowmobiling leads to significant morbidity and mortality among children. Prior reports based on CPSC data likely underestimated the number of snowmobile-related fatalities. Our findings support previous American Academy of Pediatrics recommendations, including the restriction of snowmobile driving by children under 16, graduated licensing for older children, and universal helmet usage. J Pediatr Surg 38:784-787. [copy ] 2003 Elsevier Inc. All rights reserved.     

Identification of 1-arylmethyl-3- (2-aminoethyl)-5-aryluracil as novel gonadotropin-releasing hormone receptor antagonists

Based on SAR from bicyclic GnRH antagonists such as 6-aminomethyl-7-arylpyrrolo[1,2-a]pyrimid-4-ones (1) and 2-aryl-3-aminomethylimidazolo[1,2-a]pyrimid-5-ones (2a,b), a series of novel uracil compounds (4) were derived as the GnRH antagonists. Their syntheses and initial SAR are discussed herein. This is the first time that monocycle-based GnRH receptor antagonists are reported.     

Baclofen overdose in two siblings

Baclofen is a muscle relaxant used in both adults and children with neuromuscular disorders to control spasticity. In children, relatively few cases of overdose have been previously reported. We report two cases of baclofen overdose occurring in two siblings. One sibling with cerebral palsy was being treated with baclofen at the time of overdose. Both cases presented with severe respiratory depression requiring mechanical ventilation. Serum baclofen concentrations from both children were significantly elevated. We also review the published literature on baclofen overdose in children and adolescents. These cases emphasize the importance of warning parents about the potential toxicity of baclofen when prescribing the drug to a family member.     

Delayed diagnosis in pediatric blunt trauma

OBJECTIVE: Identification of injuries of a traumatized patient is a mandate for the emergency department (ED) and the trauma team. Delayed diagnosis of injury in trauma patients leads to increased morbidity, mortality, dissatisfaction, and risk of litigation. Comparing children admitted for blunt trauma, with and without delay, this study examines risk factors for delayed diagnosis. METHODS: Delays in diagnosis from 1991 to 1996 were identified during prospective collection of trauma registry data. Controls were randomly selected from the trauma registry. Charts from both groups were retrospectively reviewed. RESULTS: Fifty-eight patients had 65 delays in diagnosis. Significant independent delay variables included: female, motor vehicle crash (MVC)-related mechanism, altered consciousness, higher injury severity score, and multiple injuries (P < 0.05). Trauma team activation, documentation of tertiary survey, and length of hospitalization were greater in patients with delay injuries (P < 0.05). Logistic regression identified MVC-related mechanism, female, facial, and extremity injuries as a combination of predictors. CONCLUSIONS: Delays occurred in 1% of patients. Trauma team care itself did not protect all patients from delay. Injury severity at presentation alone is not an adequate predictor of delayed diagnosis in the pediatric patient. A combination of variables was identified as negative predictors of delay. Further study is needed to validate these criteria, and determine if earlier diagnosis would effect quality.     

The incidence of lymphoid and myeloid malignancies among hospitalized Crohn's disease patients

An association may exist between Crohn's disease (CD) and lymphoid/myeloid malignancies. We aimed to evaluate the 2-year cumulative incidence rate of lymphoid/myeloid malignancy among hospitalized CD patients. This is a retrospective cohort study using hospital discharge data from California and Virginia. Cohorts were defined by the presence or absence of a CD diagnosis in all patients discharged during a single calendar year (Year-2). The presence or absence of lymphoid/myeloid malignancy was determined for all hospitalizations during a 4-year period (Year-1 to Year-4) for each member of both cohorts. To obtain a 2-year cumulative incidence rate, patients with lymphoid/myeloid malignancy prior to or at the time of their first admission in Year-2 were excluded. Patients were followed for 8 quarters after this admission for the incidence of lymphoid/myeloid malignancy. Cumulative incidence rates and odds ratios were calculated. The crude 2-year incidence rate of lymphoid/myeloid malignancy among hospitalized CD patients was 3.87/1.000 CD patients (21/5,426; 95% CI = 2.40-5.92). The odds ratio adjusted for age, gender, and race was 2.04 (95% CI = 1.33-3.14, p < 0.001). The 2-year cumulative incidence of lymphoid/myeloid malignancies among hospitalized CD patients is greater than that seen in hospitalized patients without CD. This finding supports the need for further prospective population-based studies.