Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism

The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pH(o)) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pH(o) can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pH(o) from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)(i)) mobilization, whereas raising pH(o) to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)(o)). Similar pH(o) effects were observed for Ca(2+)(o)-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)(i) mobilization. Intracellular pH was unaffected by acute 0.4-unit pH(o) changes, and the presence of physiologic albumin concentrations failed to attenuate the pH(o)-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pH(o) sensitivity. Finally, pathophysiologic pH(o) elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pH(o) changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo

A nearly continuous measure of birth weight for gestational age using a United States national reference

BACKGROUND: Fully understanding the determinants and sequelae of fetal growth requires a continuous measure of birth weight adjusted for gestational age. Published United States reference data, however, provide estimates only of the median and lowest and highest 5(th )and 10(th )percentiles for birth weight at each gestational age. The purpose of our analysis was to create more continuous reference measures of birth weight for gestational age for use in epidemiologic analyses. METHODS: We used data from the most recent nationwide United States Natality datasets to generate multiple reference percentiles of birth weight at each completed week of gestation from 22 through 44 weeks. Gestational age was determined from last menstrual period. We analyzed data from 6,690,717 singleton infants with recorded birth weight and sex born to United States resident mothers in 1999 and 2000. RESULTS: Birth weight rose with greater gestational age, with increasing slopes during the third trimester and a leveling off beyond 40 weeks. Boys had higher birth weights than girls, later born children higher weights than firstborns, and infants born to non-Hispanic white mothers higher birth weights than those born to non-Hispanic black mothers. These results correspond well with previously published estimates reporting limited percentiles. CONCLUSIONS: Our method provides comprehensive reference values of birth weight at 22 through 44 completed weeks of gestation, derived from broadly based nationwide data. Other approaches require assumptions of normality or of a functional relationship between gestational age and birth weight, which may not be appropriate. These data should prove useful for researchers investigating the predictors and outcomes of altered fetal growth

Splenic artery embolization in a woman with bleeding gastric varices and splenic vein thrombosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Gastric variceal bleeding due to splenic vein thrombosis is a life-threatening situation and is often difficult to manage by endoscopy. In the worst cases, an emergency splenectomy may be required to stop variceal bleeding.</p> <p>Case presentation</p> <p>We report the case of a 60-year-old Caucasian woman with bleeding gastric varices secondary to splenic vein thrombosis treated by splenic artery embolization. Successful embolization was performed by depositing coils into the splenic artery resulting in cessation of variceal bleeding. After embolization there was no recurrence of bleeding.</p> <p>Conclusion</p> <p>Splenic artery embolization can be an effective and definite treatment for variceal bleeding secondary to splenic vein thrombosis.</p

International Paediatric Mitochondrial Disease Scale

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Lessons from SARS: A retrospective study of outpatient care during an infectious disease outbreak

<p>Abstract</p> <p>Background</p> <p>During severe acute respiratory syndrome (SARS) outbreak in Toronto, outpatient clinics at SickKids Hospital were closed to prevent further disease transmission. In response, a decision was made by the neonatal neuro-developmental follow up (NNFU) clinic staff to select patients with scheduled appointments to have a mail/telephone assessment using Ages and Stages Questionnaire (ASQ) or to postpone/skip their visit. The objective of this study was to compare the developmental assessment and its outcome in two groups of NNFU clinic patients, SARS versus non-SARS, over three standard clinic appointments.</p> <p>Methods</p> <p>We compared the diagnostic accuracy (identification of developmental delay), and patient management (referral for therapy or communication of a new diagnosis) of the strategies used during SARS, April/May 2003, to the standard assessment methods used for patients seen in April/May 2005 (non-SARS). In all cases data were obtained for 3 patient visits: before, during and after these 2 months and were compared using descriptive statistics.</p> <p>Results</p> <p>There were 95 patients in the SARS group and 99 non-SARS patients. The gestational age, sex, entry diagnosis and age at the clinic visit was not different between the groups. The NNFU clinic staff mailed ASQ to 27 families during SARS, 17 (63%) were returned, and 8 of the 17 were then contacted by telephone. Criteria used to identify infants at risk selected for either mailed ASQ or phone interviews were not clearly defined in the patients' charts. There was a significant under identification of developmental delay during SARS (18% versus 45%). Of those who responded to the mailed questionnaire, referrals for therapy rates were similar to non-SARS group. The lost to follow up rate was 24% for the SARS group compared with 7% for non-SARS. There was no difference in the overall rate of developmental delay in the two groups as identified at the 'after' visit.</p> <p>Conclusions</p> <p>Poor advanced planning led to a haphazard assessment of patients during this infectious disease outbreak. Future pandemic plans should consider planning for outpatient care as well as in hospital management of patients.</p

Ki-1 Large Cell Lymphoma with Regressing Lesions in a Child

An 8-year-old boy was seen with a cutaneous Ki-1 anaplastic, large cell lymphoma with multiple lesions. Some of the lesions showed spontaneous regression. During more than seven years of disease no systemic Involvement was observed, but recurrent, self-healing lesions did appear. Histopathologic examination of five lesions revealed a variety of findings, from an inflammatory infiltrate to a highly anaplastic pattern. The neoplastic cells expressed Ki-1 and leukocyte common antigens. Ultrastructurally, those cells showed ruffled indentations. The differential diagnosis includes microvillous malignant lymphoma. The patient has had a four-year follow-up without relapses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72895/1/j.1525-1470.1992.tb01226.x.pd

Behaviourally Mediated Phenotypic Selection in a Disturbed Coral Reef Environment

Natural and anthropogenic disturbances are leading to changes in the nature of many habitats globally, and the magnitude and frequency of these perturbations are predicted to increase under climate change. Globally coral reefs are one of the most vulnerable ecosystems to climate change. Fishes often show relatively rapid declines in abundance when corals become stressed and die, but the processes responsible are largely unknown. This study explored the mechanism by which coral bleaching may influence the levels and selective nature of mortality on a juvenile damselfish, Pomacentrus amboinensis, which associates with hard coral. Recently settled fish had a low propensity to migrate small distances (40 cm) between habitat patches, even when densities were elevated to their natural maximum. Intraspecific interactions and space use differ among three habitats: live hard coral, bleached coral and dead algal-covered coral. Large fish pushed smaller fish further from the shelter of bleached and dead coral thereby exposing smaller fish to higher mortality than experienced on healthy coral. Small recruits suffered higher mortality than large recruits on bleached and dead coral. Mortality was not size selective on live coral. Survival was 3 times as high on live coral as on either bleached or dead coral. Subtle behavioural interactions between fish and their habitats influence the fundamental link between life history stages, the distribution of phenotypic traits in the local population and potentially the evolution of life history strategies

Characteristics, Access, Utilization, Satisfaction, and Outcomes of Healthy Start Participants in Eight Sites

To describe the characteristics, access, utilization, satisfaction, and outcomes of Healthy Start participants in eight selected sites, a survey of Healthy Start participants with infants ages 6–12-months-old at time of interview was conducted between October 2006 and January 2007. The response rate was 66% (n = 646), ranging from 37% in one site to >70% in seven sites. Healthy Start participants’ outcomes were compared to two national benchmarks. Healthy Start participants reported that they were satisfied with the program (>90% on five measures). Level of unmet need was 6% or less for most services, except for dental appointments (11%), housing (13%), and child care (11%). Infants had significantly better access to medical care than did their mothers, with higher rates of insurance coverage, medical homes, and checkups, and fewer unmet needs for health care. Healthy Start participants’ rates of ever breastfeeding (72%) and putting infants to sleep on their backs (70%) were at or near the Healthy People 2010 objectives, and considerably higher than rates among low-income mothers in the ECLS. The high rate of health education (>90%) may have contributed to these outcomes. Elimination of smoking among Healthy Start participants (46%) fell short of the Healthy People 2010 objective (99%). The low-birth weight (LBW) rate among Black Healthy Start participants (14%) was three times higher than the rate for Whites and Hispanics (5% each). Overall, the LBW rate in the eight sites (7.5%) was similar to the rate for low-income mothers in the ECLS, but both rates were above the Healthy People 2010 objective (5%). Challenges remain in reducing disparities in maternal and child health outcomes. Further attention to risk factors associated with LBW (especially smoking) may help close the gaps. The life course theory suggests that improved outcomes may require longer-term investments. Healthy Start’s emerging focus on interconception care has the potential to address longer-term needs of participants

The impact on neonatal mortality of shifting childbirth services among levels of hospitals: Taiwan's experience

<p>Abstract</p> <p>Background</p> <p>There is considerable discussion surrounding whether advanced hospitals provide better childbirth care than local community hospitals. This study examines the effect of shifting childbirth services from advanced hospitals (i.e., medical centers and regional hospitals) to local community hospitals (i.e., clinics and district hospitals). The sample population was tracked over a seven-year period, which includes the four months of the 2003 severe acute respiratory syndrome (SARS) epidemic in Taiwan. During the SARS epidemic, pregnant women avoided using maternity services in advanced hospitals. Concerns have been raised about maintaining the quality of maternity care with increased demands on childbirth services in local community hospitals. In this study, we analyzed the impact of shifting maternity services among hospitals of different levels on neonatal mortality and maternal deaths.</p> <p>Methods</p> <p>A population-based study was conducted using data from Taiwan's National Health Insurance annual statistics of monthly county neonatal morality rates. Based on a pre-SARS sample from January 1998 to December 2002, we estimated a linear regression model which included "trend," a continuous variable representing the effect of yearly changes, and two binary variables, "month" and "county," controlling for seasonal and county-specific effects. With the estimated coefficients, we obtained predicted neonatal mortality rates for each county-month. We compared the differences between observed mortality rates of the SARS period and predicted rates to examine whether the shifting in maternity services during the SARS epidemic significantly affected neonatal mortality rates.</p> <p>Results</p> <p>With an analysis of a total of 1,848 observations between 1998 and 2004, an insignificantly negative mean of standardized predicted errors during the SARS period was found. The result of a sub-sample containing areas with advanced hospitals showed a significant negative mean of standardized predicted errors during the SARS period. These findings indicate that despite increased use of local community hospitals, neonatal mortality during the SARS epidemic did not increase, and even decreased in areas with advanced hospitals.</p> <p>Conclusion</p> <p>An increased use of maternity services in local community hospitals occurred during the SARS epidemic in Taiwan. However, we observed no increase in neonatal and maternity mortality associated with these increased demands on local community hospitals.</p