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2.  The Evaluation and Followup of Children Referred to Pediatric Endocrinologists for Short Stature 
Objective. To characterize the pediatric endocrinologists' evaluation and followup of short-statured patients. Study Design. Observational study of 21,548 short-statured children (April 1996 to December 1999). Baseline demographics, laboratory testing, height standard deviation score (SDS), target height, and height relative to target height were analyzed at initial and return visits with the specialist. Patients were scheduled for at least one return visit and no recombinant human growth hormone therapy was administered. Results. Mean patient age was 8.6 years with a mean height SDS of −2.1. Patients were predominantly male (69%), prepubertal (73%), and white (76%). Few screening tests were obtained during initial evaluation. Nearly 40% of children did not return for their second scheduled visit. The follow-up rate was unrelated to demographics or degree of short stature. Conclusions. Low return rates limit specialists' ability to monitor growth or obtain laboratory testing over time. Further studies are needed to determine which tests should be obtained at the initial clinic visit as well as the basis for the low return rate in this group of children.
doi:10.1155/2010/652013
PMCID: PMC2905720  PMID: 20652081
3.  Documenting the NICU design dilemma: parent and staff perceptions of open ward versus single family room units 
Journal of Perinatology  2010;30(5):343-351.
Objective:
With neonatal intensive care units (NICUs) evolving from multipatient wards toward family-friendly, single-family room units, the study objective was to compare satisfaction levels of families and health-care staff across these differing NICU facility designs.
Study Design:
This prospective study documented, by means of institutional review board-approved questionnaire survey protocols, the perceptions of parents and staff from two contrasting NICU environments.
Result:
Findings showed that demographic subgroups of parents and staff perceived the advantages and disadvantages of the two facility designs differently. Staff perceptions varied with previous experience, acclimation time and employment position, whereas parental perceptions revealed a naiveté bias through surveys of transitional parents with experience in both NICU facilities.
Conclusion:
Use of transitional parent surveys showed a subject naiveté bias inherent in perceptions of inexperienced parents. Grouping all survey participants demographically provided more informative interpretations of data, and revealed staff perceptions to vary with position, previous training and hospital experience.
doi:10.1038/jp.2009.195
PMCID: PMC2864417  PMID: 20072132
NICU design; NICU survey; NICU parent satisfaction; NICU staff satisfaction
4.  AUTHOR RESPONSE 
PMCID: PMC2755108  PMID: 20046615
5.  Reduced Activities of Cytochrome P450 1A2 and Xanthine Oxidase in Children with Growth Hormone Deficiency 
doi:10.1038/clpt.2008.185
PMCID: PMC2650481  PMID: 18843262
growth hormone deficiency; drug metabolism; pediatric; cytochrome P450
9.  Phase II trial of imatinib mesylate in patients with metastatic melanoma 
British Journal of Cancer  2008;99(5):734-740.
Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.
doi:10.1038/sj.bjc.6604482
PMCID: PMC2528157  PMID: 18728664
phase II; imatinib; metastatic melanoma; protein tyrosine kinases; antiangiogenesis
10.  Extracellular purines are biomarkers of neutrophilic airway inflammation 
Purinergic signalling regulates airway defence mechanisms, suggesting that extracellular purines could serve as airway inflammation biomarkers in cystic fibrosis (CF).
The purines adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine were measured in sputum from 21 adults (spontaneously expectorated from seven CF patients, induced from 14 healthy controls) to assess normal values and CF-associated changes. Subsequently, purine levels were measured in bronchoalveolar lavage fluid (BALF) from 37 children (25 CF patients, 12 disease controls) and compared with neutrophil counts, presence of airway infection and lung function. To noninvasively assess airway purines, ATP levels were measured using luminometry in exhaled breath condensate (EBC) from 14 children with CF and 14 healthy controls, then 14 CF children during a pulmonary exacerbation.
Both ATP and AMP were elevated in sputum and BALF from CF subjects compared with controls. In BALF, ATP and AMP levels were inversely related to lung function and strongly correlated with neutrophil counts. In EBC, ATP levels were increased in CF relative to controls and decreased after treatment of CF pulmonary exacerbation.
The purines adenosine triphosphate and adenosine monophosphate are candidate biomarkers of neutrophilic airways inflammation. Measurement of purines in sputum or exhaled breath condensate may provide a relatively simple and noninvasive method to track this inflammation.
doi:10.1183/09031936.00089807
PMCID: PMC2723793  PMID: 18256064
Biomarker; bronchoalveolar lavage fluid; cystic fibrosis; exhaled breath condensate; inflammation; purinergic signalling
11.  Upper Limb Neural Tension and Seated Slump Tests: The False Positive Rate among Healthy Young Adults without Cervical or Lumbar Symptoms 
This study examined the false positive rate of the upper limb neural tension test (ULNTT) and seated slump test (SST) among healthy young adults with no history of cervical, lumbar, or peripheral symptoms. Eighty-four subjects (27 men and 57 women) with a mean age of 22.9 years participated in the investigation. All participants completed a screening questionnaire designed to exclude subjects with a history of cervical or lumbar spine pain or injury, or upper or lower extremity neurological symptoms. The ULNTT and the SST were performed on the left upper and lower extremity of each participant. Of the 84 participants tested, 73 (86.9%) were found to have a positive ULNTT at some point in the available range of elbow extension. Twenty-eight (33.3%) of the 84 subjects had a positive SST at some point in the available range of knee extension. The mean knee extension angle for those subjects with a positive SST was 15.1° with a 95% confidence interval (CI) of 12.3 and 19.7°. The mean elbow extension angle for those with a positive ULNTT was 49.4° with a 95% CI of 44.8 and 54.0°. The number of positive tests for both the ULNTT and the SST was found to be high in this sample of asymptomatic healthy young adults. Based on the results of this investigation, the authors suggest that the current criteria for determining a positive test for both the ULNTT and the SST should be examined using the proposed range of motion cut-off scores.
PMCID: PMC2582423  PMID: 19119402
Neural Tension Testing; Neurodynamics; Radiculopathy; Test Validity
12.  Parental preferences for neonatal resuscitation research consent: a pilot study 
Journal of Medical Ethics  2005;31(12):721-726.
Objective: Obtaining informed consent for resuscitation research, especially in the newborn, is problematic. This study aimed to evaluate parental preferences for hypothetical consent procedures in neonatal resuscitation research.
Design: Mail-out survey questionnaire.
Setting/participants: Randomly selected parents who had received obstetrical or neonatal care at a tertiary perinatal centre.
Main outcome measures: Parental levels of comfort (Likert-type scale 1–6) regarding different methods of obtaining consent in hypothetical resuscitation research scenarios.
Results: The response rate was 34%. The respondents were a group of highly educated women with a higher family income than would be expected in the general population. In terms of results, parents valued the impact the research would have on their baby and the importance of a positive interaction with the physicians conducting the research study. Parents felt most comfortable with prospective consent in the setting of prenatal classes or prenatal visits with a physician, but they were somewhat uncomfortable with prospective consent upon admission to hospital after labour had begun. Parents were uncomfortable with waived consent, deferred consent, and opting out, no matter when during the pregnancy consent was requested.
Conclusion: This pilot study reports parental preferences for prenatal information and consent for such research trials of neonatal resuscitation. A low response rate and potentially skewed demographics of the respondents prevent generalisability of this result. Interview studies should be performed to better determine parental preferences for informed consent in a more representative population.
doi:10.1136/jme.2004.011247
PMCID: PMC1734075  PMID: 16319238
13.  Surrogate markers in antiangiogenesis clinical trials 
British Journal of Cancer  2003;89(1):8-14.
doi:10.1038/sj.bjc.6601035
PMCID: PMC2394225  PMID: 12838293
laser scanning cytometry; biopsy; clinical trial; biomarkers; PET
14.  Does physical activity reduce the risk of developing peptic ulcers? 
Background—Although Helicobacter pylori has been identified as a major cause of chronic gastritis, not all infected patients develop ulcers, suggesting that other factors such as lifestyle may be critical to the development of ulcer disease.
Aim—To investigate the role physical activity may play in the incidence of peptic ulcer disease.
Methods—The subjects were men (8529) and women (2884) who attended the Cooper Clinic in Dallas between 1970 and 1990. The presence of gastric or duodenal ulcer disease diagnosed by a doctor was determined from a mail survey in 1990. Subjects were classified into three physical activity groups according to information provided at the baseline clinic visit (before 1990): active, those who walked or ran 10 miles or more a week; moderately active, those who walked or ran less than 10 miles a week or did another regular activity; the referent group consisting of those who reported no regular physical activity.
Results—With the use of gender specific proportional hazards regression models that could be adjusted for age, smoking, alcohol use, body mass index, and self reported tension, active men were found to have a significant reduction in risk for duodenal ulcers (relative hazard (95% confidence interval) for the active group was 0.38 (0.15 to 0.94) and 0.54 (0.30 to 0.96) for the moderately active group). No association was found between physical activity and gastric ulcers for men or for either type of ulcer for women.
Conclusions—Physical activity may provide a non-pharmacological method of reducing the incidence of duodenal ulcers among men.
Key Words: alcohol; duodenal; exercise; gastric; ulcer; risk factors
doi:10.1136/bjsm.34.2.116
PMCID: PMC1724173  PMID: 10786867
15.  Herpes simplex encephalitis after brain surgery: case report and review of the literature 
Intracranial infection after neurosurgical intervention most often is caused by bacteria. A rare case of fatal herpes simplex encephalitis after removal of a meningioma is described and similar cases reported in the literature are reviewed. Recent diagnostic tools, including detection of herpes viral DNA sequences by polymerase chain reaction, complement clinical suspicion and facilitate mandatory early diagnosis, because herpes encephalitis, without rapid initiation of treatment, may lead to severe disability or death.


PMCID: PMC1736493  PMID: 10407001
16.  Endoplasmic Reticulum Dynamics, Inheritance, and Cytoskeletal Interactions in Budding YeastV⃞ 
Molecular Biology of the Cell  2002;13(3):854-865.
The endoplasmic reticulum (ER) in Saccharomyces cerevisiae consists of a reticulum underlying the plasma membrane (cortical ER) and ER associated with the nuclear envelope (nuclear ER). We used a Sec63p-green fluorescent protein fusion protein to study motility events associated with inheritance of cortical ER and nuclear ER in living yeast cells. During M phase before nuclear migration, we observed thick, apparently rigid tubular extensions emanating from the nuclear ER that elongate, undergo sweeping motions along the cell cortex, and shorten. Two findings support a role for microtubules in this process. First, extension of tubular structures from the nuclear ER is inhibited by destabilization of microtubules. Second, astral microtubules, structures that undergo similar patterns of extension, cortical surveillance and retraction, colocalize with nuclear ER extensions. During S and G2 phases of the cell cycle, we observed anchorage of the cortical ER at the site of bud emergence and apical bud growth. Thin tubules of the ER that extend from the anchored cortical ER display undulating, apparently random movement and move into the bud as it grows. Finally, we found that cortical ER morphology is sensitive to a filamentous actin–destabilizing drug, latrunculin-A, and to mutations in the actin-encoding ACT1 gene. Our observations support 1) different mechanisms and cytoskeletal mediators for the inheritance of nuclear and cortical ER elements and 2) a mechanism for cortical ER inheritance that is cytoskeleton dependent but relies on anchorage, not directed movement.
doi:10.1091/mbc.01-04-0184
PMCID: PMC99604  PMID: 11907267
17.  Reassessment of the lethal London fog of 1952: novel indicators of acute and chronic consequences of acute exposure to air pollution. 
Environmental Health Perspectives  2001;109(Suppl 3):389-394.
This article develops and assesses novel indicators of respiratory and other morbidity and mortality following London's lethal smog in the winter of 1952. Public health insurance claims, hospital admission rates for cardiac and respiratory disease, pneumonia cases, mortality records, influenza reports, temperature, and air pollutant concentrations are analyzed for December-February 1952-1953 and compared with those for the previous year or years. Mortality rates for the smog episode from December 1952 to February 1953 were 50-300% higher than the previous year. Claims that the smog only elevated health risks during and immediately following the peak fog 5-9 December 1952 and that an influenza epidemic accounted fully for persisting mortality increases in the first 2 months of 1953 are rejected. We estimate about 12,000 excess deaths occurred from December 1952 through February 1953 because of acute and persisting effects of the 1952 London smog. Pollution levels during the London smog were 5-19 times above current regulatory standards and guidelines and approximate current levels in some rapidly developing regions. Ambient pollution in many regions poses serious risks to public health.
PMCID: PMC1240556  PMID: 11427388
19.  Assessing the health benefits of urban air pollution reductions associated with climate change mitigation (2000-2020): Santiago, São Paulo, México City, and New York City. 
Environmental Health Perspectives  2001;109(Suppl 3):419-425.
To investigate the potential local health benefits of adopting greenhouse gas (GHG) mitigation policies, we develop scenarios of GHG mitigation for México City, México; Santiago, Chile; São Paulo, Brazil; and New York, New York, USA using air pollution health impact factors appropriate to each city. We estimate that the adoption of readily available technologies to lessen fossil fuel emissions over the next two decades in these four cities alone will reduce particulate matter and ozone and avoid approximately 64,000 (95% confidence interval [CI] 18,000-116,000) premature deaths (including infant deaths), 65,000 (95% CI 22,000-108,000) chronic bronchitis cases, and 46 million (95% CI 35-58 million) person-days of work loss or other restricted activity. These findings illustrate that GHG mitigation can provide considerable local air pollution-related public health benefits to countries that choose to abate GHG emissions by reducing fossil fuel combustion.
PMCID: PMC1240560  PMID: 11427391
20.  Evaluating the effectiveness of 2 educational interventions in family practice 
BACKGROUND: Structured feedback of information can produce change in physician behaviour. The objective of this study was to assess the effectiveness of 2 educational interventions for improving the quality of care provided by family physicians in Ontario: the Practice Assessment Report (PAR) and the Continuing Medical Education Plan (CMEP) with a follow-up visit by a mentor. METHODS: The study was a randomized controlled trial. Physicians in the control group received only the PAR, whereas those in the experimental group received the PAR, CMEP and mentor interventions. The participants were 56 family physicians and general practitioners (27 in the PAR group and 29 in the CMEP group) in southern Ontario who agreed to participate in the interventions and provide data. A total of 2395 patients randomly sampled from the practices returned questionnaires and consented to have their medical records abstracted. The outcome measures were global scores in 4 areas--quality of care, charting, prevention and overall use of medications--and patient ratings of satisfaction with care and preventive practices. The measures were applied at the beginning (phase 1) and end (phase 2) of the study. RESULTS: The mean global scores at the end of the study for the PAR group were 70.1% for quality of care, 84.7% for prevention, 77.7% for charting and 82.2% for overall use of medications. The corresponding scores for the CMEP group were 68.3%, 82.1%, 76.4% and 83.2%. In the patient satisfaction component, the personal care scores at phase 2 were 93.6% for the PAR group and 94.6% for the CMEP group. Examples of the scores for prevention for the PAR group were 98.3% for children's current immunization, 96.6% for blood pressure measured within the previous 5 years, 79.4% for referral of women of the appropriate age for mammography within the previous 2 years, and 58.4% for discussion about alcohol use. The corresponding scores for the CMEP group were 95.8%, 97.6%, 77.6% and 64.6%. The changes in mean scores between phase 1 and phase 2 ranged from -1.9 to 2.3 points. There were no significant differences between the 2 groups in phase 1 or phase 2 scores or in change in scores. A total of 64.3% of the physicians rated the PAR as useful, 26.5% found the CMEP to be useful, and 41.0% considered the mentor strategy to be a useful form of continuing medical education. Although changes in practice related to the PAR, CMEP or mentor were reported by some physicians, they were not related to chart audit or patient scores. INTERPRETATION: Educational interventions based on quality-of-care assessments and directed to global improvements in quality of care did not result in improvements in the outcome measures. Educational interventions may have to be targeted to specific areas of the practice, with physicians being monitored and receiving ongoing feedback on their performance.
PMCID: PMC1230705  PMID: 10551192
21.  Genetic evidence of Dobrava virus in Apodemus agrarius in Hungary. 
Emerging Infectious Diseases  1999;5(3):468-470.
Using nested polymerase chain reaction, we sequenced Dobrava virus (DOB) from the rodent Apodemus agrarius in Hungary. The samples we isolated group with DOB samples previously isolated from A. flavicollis. This grouping may indicate host switching.
PMCID: PMC2640777  PMID: 10341190
22.  Water pollution and human health in China. 
Environmental Health Perspectives  1999;107(4):251-256.
China's extraordinary economic growth, industrialization, and urbanization, coupled with inadequate investment in basic water supply and treatment infrastructure, have resulted in widespread water pollution. In China today approximately 700 million people--over half the population--consume drinking water contaminated with levels of animal and human excreta that exceed maximum permissible levels by as much as 86% in rural areas and 28% in urban areas. By the year 2000, the volume of wastewater produced could double from 1990 levels to almost 78 billion tons. These are alarming trends with potentially serious consequences for human health. This paper reviews and analyzes recent Chinese reports on public health and water resources to shed light on what recent trends imply for China's environmental risk transition. This paper has two major conclusions. First, the critical deficits in basic water supply and sewage treatment infrastructure have increased the risk of exposure to infectious and parasitic disease and to a growing volume of industrial chemicals, heavy metals, and algal toxins. Second, the lack of coordination between environmental and public health objectives, a complex and fragmented system to manage water resources, and the general treatment of water as a common property resource mean that the water quality and quantity problems observed as well as the health threats identified are likely to become more acute.
Images
PMCID: PMC1566519  PMID: 10090702
23.  Independent review of industry-generated data. 
Environmental Health Perspectives  1998;106(12):A583-A584.
PMCID: PMC1533253  PMID: 10048944
24.  Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease. 
Journal of Clinical Investigation  1998;102(9):1690-1703.
We describe a metabolic defect in bile acid synthesis involving a deficiency in 7alpha-hydroxylation due to a mutation in the gene for the microsomal oxysterol 7alpha-hydroxylase enzyme, active in the acidic pathway for bile acid synthesis. The defect, identified in a 10-wk-old boy presenting with severe cholestasis, cirrhosis, and liver synthetic failure, was established by fast atom bombardment ionization-mass spectrometry, which revealed elevated urinary bile acid excretion, a mass spectrum with intense ions at m/z 453 and m/z 510 corresponding to sulfate and glycosulfate conjugates of unsaturated monohydroxy-cholenoic acids, and an absence of primary bile acids. Gas chromatography-mass spectrometric analysis confirmed the major products of hepatic synthesis to be 3beta-hydroxy-5-cholenoic and 3beta-hydroxy-5-cholestenoic acids, which accounted for 96% of the total serum bile acids. Levels of 27-hydroxycholesterol were > 4,500 times normal. The biochemical findings were consistent with a deficiency in 7alpha-hydroxylation, leading to the accumulation of hepatotoxic unsaturated monohydroxy bile acids. Hepatic microsomal oxysterol 7alpha-hydroxylase activity was undetectable in the patient. Gene analysis revealed a cytosine to thymidine transition mutation in exon 5 that converts an arginine codon at position 388 to a stop codon. The truncated protein was inactive when expressed in 293 cells. These findings indicate the quantitative importance of the acidic pathway in early life in humans and define a further inborn error in bile acid synthesis as a metabolic cause of severe cholestatic liver disease.
PMCID: PMC509117  PMID: 9802883
25.  Rethinking breast cancer risk and the environment: the case for the precautionary principle. 
Environmental Health Perspectives  1998;106(9):523-529.
The World Health Organization recently reported that breast cancer has become the most common cancer in women throughout the world. Known risk factors account for less than half of all cases of breast cancer, and inherited germ line mutations occur in at most only 10% of all cases. Cumulative exposure to estradiol and other hormones links many of the established risk factors for breast cancer. This paper reviews epidemiologic and toxicologic evidence on breast cancer risks and presents a comprehensive construct of risk factors intended to focus on the identification of those factors that can be controlled or modified. We attempt to provide a framework for interpreting the etiologic interplay of endogenous metabolic changes and environmental changes in the etiology of breast cancer. The construct we develop distinguishes between those risk factors that are directly causal, such as ionizing radiation and inherited germ cell defects, those vulnerability factors that extend the time period during which the breast undergoes development, and those contributing factors that increase total hormonal stimulation of the breast. Some hormonally active compounds, such as those in soy and broccoli and other phytoestrogen-containing foods, can be protective against breast cancer, while others, such as some environmental contaminants, appear to increase the risk of the disease by increasing levels of harmful hormones. Efforts to explain patterns of breast cancer should distinguish between these different risk factors. Identification of vulnerability and contributing risk factors can foster the development of public policy to reduce the burden of this prevalent cancer. Prudent precautionary principles suggest that reducing exposure to avoidable or modifiable risk factors should receive high priority from the public and private sectors.
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PMCID: PMC1533169  PMID: 9721252

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