Can classic metaphyseal lesions follow uncomplicated caesarean section?

BACKGROUND: Classic metaphyseal lesion (CML) is the term given to a fracture that most often occurs in the posteromedial aspect of the distal femur, proximal tibia, distal tibia, and proximal humerus in infants; this finding is strongly associated with non-accidental injury. OBJECTIVE: To demonstrate that the CML may occur following simple lower segment caesarean section (LSCS). MATERIALS AND METHODS: A review of 22 years of an obstetric practice that delivers 8,500 babies per year. RESULTS: We identified three neonates born by elective LSCS, each with distal femoral metaphyseal fractures on postpartum radiographs. All caesarean sections were elective and uncomplicated. External cephalic version was not employed preoperatively. Postpartum radiographs demonstrated a fracture of the distal femoral metaphysis in each neonate, typical of a CML. CONCLUSION: We propose that a CML can occur in the setting of a simple, elective and uncomplicated LSCS where no external cephalic version is employed.     

Auditory interhemispheric transfer deficits, hearing difficulties, and brain magnetic resonance imaging abnormalities in children with congenital aniridia due to PAX6 mutations

OBJECTIVE: To assess auditory processing, hearing difficulties, and brain magnetic resonance (MR) imaging abnormalities in children with panocular developmental aniridia due to PAX6 mutations. DESIGN: Case-control study. SETTING: Great Ormond Street Hospital and Institute of Child Health. PARTICIPANTS: Eleven case subjects with PAX6 mutations and 11 age-matched and sex-matched healthy control subjects. INTERVENTIONS: All subjects completed a structured hearing questionnaire, baseline audiometry, and central auditory tests (dichotic speech tests, frequency and duration pattern tests, and gaps-in-noise test). Case subjects underwent brain MR imaging with volumetry, and the results were compared with those of age-matched and sex-matched healthy control subjects randomly selected from the Radiology and Physics Unit database. MAIN OUTCOME MEASURES: Brain MR imaging, central auditory test results, and questionnaire scores. RESULTS: The corpus callosum area was significantly smaller on brain volumetry in the cases compared with the controls. The anterior commissure was small in 7 cases and was normal in 3 cases on visual inspection of brain MR images (conducted in 10 of 11 cases). Audiograms showed no abnormalities in any of the children. Central auditory test results were normal in all the controls and were abnormal in all the cases except for 1 case with a pattern of abnormalities consistent with reduced auditory interhemispheric transfer. The cases had greater difficulty localizing sound and understanding speech in noise than the controls. CONCLUSIONS: Despite normal audiograms, children with PAX6 mutations may experience auditory interhemispheric transfer deficits and have difficulty localizing sound and understanding speech in noise. In view of their additional visual difficulties, thorough audiological evaluation of these children is indicated to initiate appropriate management.     

Injury and nucleotides induce phosphorylation of epidermal growth factor receptor: MMP and HB-EGF dependent pathway

The early events that occur rapidly after injury trigger signal cascades that are essential for proper wound closure of corneal epithelial cells. We hypothesize that injury releases ATP, which stimulates purinergic receptors and elicits the phosphorylation of epidermal growth factor receptor (EGFR) tyrosine residues and subsequent cell migration by a MMP and HB-EGF dependent pathway. We demonstrated that the inhibition of purinergic receptors with the antagonist, Reactive Blue 2, abrogated the phosphorylation of EGFR and ERK. Pre-incubation of cells with the EGFR kinase inhibitor, AG1478, and subsequent stimulation by injury or ATP resulted in a decrease in phosphorylation of EGFR and migration. Furthermore, downregulation of EGFR by siRNA, inhibited the EGF-induced intracellular Ca(2+) wave. However, the response to injury and ATP was retained indicating the presence of two signaling pathways. Inhibition with either CRM197 or TIMP-3 decreased injury and nucleotide-induced phosphorylation of both EGFR and ERK. Incubation in the presence of a functional blocking antibody to HB-EGF also resulted in a decrease in the phosphorylation of EGFR. In addition, cell migration was inhibited by CRM197 and rescued when cells were incubated with HB-EGF. We showed that injury-induced phosphorylation of specific tyrosine residues and found that a similar pattern of phosphorylation was induced by trinucleotides. These studies indicate that injury-induced purinergic receptor activation leads to phosphorylation of EGFR, ERK and migration.     

Essential infantile esotropia in neurologically impaired pediatric patients: is botulinum toxin better primary treatment than surgery?

A prospective study was performed over a 10 year period on 25 children with infantile esotropia and neurological problems to answer this question. From November 1996 to March 2006 they were treated with injections of botulinum toxin (Botox) of both medial rectus extraocular muscles. Mean age was 26.4 months, (range 9-76 months) and mean initial angle was 35 prism diopters (PD)(range 20-60 PD). RESULTS: 18 patients (72%) remained orthotropic+/-10 PD at 29 months (range 6-59 months). Average number of injection treatments was 1.5 per patient. We compared our success rate data with those obtained with primary conventional strabismus surgical procedures in 2 previously published series. Treatment with botulinum toxin seemed to produce better results than one surgical series and at least equally similar results to the other one. Because there are, as well, so many other advantages to the injection procedure including superior safety and economy, we now use botulinum injections as our primary treatment in these patients.     

Alcohol consumption and endometrial cancer risk: the multiethnic cohort

The role of alcohol intake in the etiology of endometrial cancer is unclear. We examined the impact of alcohol intake on endometrial cancer risk among 41,574 postmenopausal African-American, Japanese-American, Latina, Native-Hawaiian and White women recruited to the prospective Multiethnic Cohort Study in 1993-1996. During an average of 8.3 years of follow-up, 324 incident invasive endometrial cancer cases were identified among these women. Data on alcohol intake and endometrial cancer risk factors were obtained from the baseline questionnaire. Relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with alcohol intake were estimated using log-linear (Cox) proportional hazard models stratified by age, year of recruitment, ethnicity and study center, and adjusted for several confounding factors. Increased alcohol consumption was associated with increased risk (p trend = 0.013). Compared to nondrinkers, women consuming >or=2 drinks/day had a multivariate RR of 2.01 (95% CI: 1.30, 3.11). There was no increase in risk associated with <1 drink/day (RR = 1.01; 95% CI: 0.77, 1.33) and 1 to <2 drinks/day (RR = 1.09; 95% CI: 0.62, 1.93). There was no clear effect modification by body mass index, postmenopausal hormone use, parity, oral contraceptive use or smoking status, though our power to detect such interactions was limited. Our results suggest that only alcohol consumption equivalent to 2 or more drinks per day increases risk of endometrial cancer in postmenopausal women.     

Pharmacokinetics of the adrenocorticolytic compounds 3-methylsulphonyl-DDE and o,p′-DDD (mitotane) in Minipigs

The pharmacokinetics of the adrenocorticolytic drug candidate 3-Methylsulphonyl-DDE (3-MeSO2-DDE) and the anticancer drug o,p'-DDD (mitotane) were studied in G?ttingen minipigs. The animals were given 3-MeSO2-DDE or o,p'-DDD as single oral doses (30 mg/kg). Concentrations in plasma and subcutaneous fat were measured by gas chromatography at different time points during 180 days. Maximal plasma concentrations appeared within 24 h for both compounds, but were about 2 times higher for 3-MeSO2DDE. o,p'-DDD plasma concentrations declined rapidly to low levels during 4 days. 3-MeSO2-DDE also decreased rapidly, but remained at high concentrations throughout the study. In fat, 3-MeSO2-DDE reached about 25-fold higher levels than o,p'-DDD at 30 days, and both substances were eliminated slowly from this tissue. 3-MeSO2-DDE liver concentrations were about 18-fold higher than those in plasma at 180 days. In contrast, o,p'-DDD liver and plasma levels were about equal at 180 days. o,p'-DDD had roughly 45 times larger CL/F than 3-MeSO2-DDE, confirming that the elimination of this compound was more rapid. Both compounds were characterised by their localisation and retention in fat tissue, and the individual size of the fat stores clearly determined the plasma concentrations. It is concluded that although 3-MeSO2-DDE is an interesting candidate for therapeutic use due to its potential characteristics to specifically target adrenocortical tumour cells the slow elimination of the compound might make it challenging to design appropriate dosage regimes.     

Beneficial effects of Helicobacter pylori eradication on migraine: a 12-month follow-up study

Helicobacter pylori (H. pylori) has been recently associated with some organic and functional vascular disorders. In particular, our group found a high prevalence of H. pylori in patients affected by migraine and a significant improvement of migraine symptoms after eradication of the bacterium, during a follow-up period of 6 months. However, seasonal variations may affect clinical manifestations of migraine, thus influencing our previous results. The present study evaluated the effect of H. pylori eradication during a 1-year follow-up period in a population of 148 consecutively enrolled migraine patients. H. pylori infection was assessed by ¹³C-urea breath test. Infected subjects underwent specific antibiotic treatment in order to eradiate the bactrium. Frequency, intensity and duration of attacks of migraine were assessed during a 1-year follow-up period. 42% of the patients showed H. pylori infection. 82% resulted eradicated. Interestingly, 28% of the patietns reported a disappearance of migraine during the follow-up period. Moreover, a significant decrease of intensity, frequency and duration of the migraine attacks evaluated 2, 4, 6 and 12 months from H. pylori eradication was observed in the remaining patients. The beneficial effects of H. pylori eradication on migraine seem to be confirmed by this prolonged 1-year follow-up study. Received: 27 March 2000 / Accepted in revised form: 5 February 2001     

Developing a Virtual Equity Hub: Adapting the Tumor Board Model for Equity in Cancer Care

We define cancer equity as all people having as the same opportunity for cancer prevention, treatment, and survivorship care. However, marginalized populations continue to experience avoidable and unjust disparities in cancer care, access to clinical trials, and cancer survival. Racial and ethnic minorities, and individuals with low socioeconomic status, Medicaid insurance, limited health literacy, disabilities, and mental health disorders are more likely to experience delays to cancer diagnosis and less likely to receive guideline-concordant cancer care. These disparities are impacted by the social determinants of health including structural discrimination, racism, poverty, and inequities in access to healthcare and clinical trials. There is an urgent need to develop and adapt evidence-based interventions in collaboration with community partners that have potential to address the social determinants of health and build capacity for cancer care for underserved populations. We established the Virtual Equity Hub by developing a collaborative network connecting a comprehensive cancer center, academic safety net hospital, and community health centers and affiliates. The Virtual Equity Hub utilizes a virtual tumor board, an evidence-based approach that increases access to multi-specialty cancer care and oncology subspecialty expertise. We adapted the tumor board model by engaging person-centered teams of multi-disciplinary specialists across health systems, addressing the social determinants of health, and applying community-based research principles with a focus on populations with poor cancer survival. The virtual tumor board included monthly videoconferences, case discussion, sharing of expertise, and a focus on addressing barriers to care and trial participation. Specifically, we piloted virtual tumor boards for breast oncology, neuro-oncology, and individuals with cancer and serious mental illness. The Virtual Equity Hub demonstrated promise at building capacity for clinicians to care for patients with complex needs and addressing barriers to care. Research is needed to measure the impact, reach, and sustainability of virtual equity models for patients with cancer.

Despite rapid advances in cancer treatment, disparities in cancer care persist. This article describes a virtual tumor board developed to provide a collaborative network of multi-disciplinary specialists, which showed promise at building capacity for clinicians to care for patients with complex needs and addressing barriers to care.