Cardiac troponin T in neonates.
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Biomarkers↗
Biomedical subjects
S J Clark
Publications and source records attributed to S J Clark.
Cardiac troponin T in cord blood.
BACKGROUND: Perinatal asphyxia is associated with cardiac dysfunction. This may be secondary to myocardial ischaemia. Cardiac troponin T is the ideal marker for myocardial necrosis. Elevated levels in cord blood may be associated with intrauterine hypoxia and increased perinatal morbidity. AIMS: To establish an upper limit of normal for cardiac troponin T concentration in the cord blood of infants. Relations between cardiac troponin T levels and other variables were investigated. METHODS: Cord blood samples were collected from 242 infants and analysed. Data on gestation, birth weight, sex, Apgar scores, respiratory status, and mode of delivery were recorded. RESULTS: A total of 242 samples were collected, and 215 samples from infants without respiratory distress were used to establish the 95th percentile of 0.050 ng/ml. The gestation of these infants ranged from 31 to 42 weeks and birth weight ranged from 1.4 to 5 kg. There were no relations between cardiac troponin T levels and the other variables in these healthy infants. Twenty seven infants developed respiratory symptoms requiring oxygen and/or ventilation. These infants had significantly higher cord cardiac troponin T levels than their healthy counterparts (median (interquartile range) 0.031 (0.010-0.084) v 0.010 (0.010-0.014) ng/ml respectively; p < 0.001). CONCLUSIONS: Cardiac troponin T levels in the cord blood are unaffected by gestation, birth weight, sex, or mode of delivery. Infants with respiratory distress had significantly higher cord cardiac troponin T levels, suggesting that cardiac troponin T may be a useful marker for myocardial damage in neonates.
Biomarkers↗
Accounting for a not-for-profit organization's fund-raising costs.
The AICPA's Statement of Position (SOP) 98-2 provides guidance on how a not-for-profit entity should account for costs associated with activities that involve a fund-raising component in combination with one or more mission-related components. Costs may be allocated among the various components of such an activity as long as the activity meets certain criteria specified by SOP 98-2. These criteria are related to the activity's purpose, audience, and content. If the activity does not meet the criteria, then all costs of the activity must be shown as fund-raising costs.
Accounting↗
Constructive use of race and ethnicity variables.
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Ethnicity↗
Disinfection/sterilization of extracted teeth for dental student use.
Extracted human teeth are used in many preclinical courses. While there has been no report of disease transmission with extracted teeth, sterilization of teeth used in the teaching laboratory should be a concern. The purpose of this study was to determine the effectiveness of different sterilization/disinfection methods of extracted human teeth using Bacillus stearothermophilus, a bacteria resistant to heat and frequently used to test sterilizers. In this study, 110 extracted molars with no carious lesions were collected and stored in buffered saline. An endodontic occlusal access preparation was cut into the pulp chamber of each tooth. Pulp tissue in the chamber was removed with a broach. Approximately 1 x 10(5) B. stearothermophilus endospores in culture medium were injected into the pulp chamber, sealed with Cavit G, and then placed in sterile saline for twelve hours. Ten teeth were placed into each of eleven groups. Seven groups were immersed for one week in one of the following solutions: a) sterile saline (control group), b) 5.25% NaOCl, c) 2.6% NaOCl, d) 1% NaOCl, e) 10% buffered formalin, f) 2% gluteraldehyde, g) 0.28% quaternary ammonium. Four additional groups were treated by h) 10% formalin for two days, i) 10% formalin for four days, j) autoclaving at 240 degrees F and 20 psi for twenty minutes, and k) autoclaving at 240 degrees F and twenty psi for forty minutes. Each tooth was then aseptically split and placed in an individual test tube with growth medium. Samples were examined for evidence of growth (turbidity) at forty-eight hours. Only autoclaving for forty minutes at 240 degrees F and 20 psi or soaking in 10 percent formalin for one week were 100 percent effective in preventing growth. A chi-square analysis of the data indicates these two methods were significantly better than all other methods (p<0.001).
Chi-Square Distribution↗
A distinct sequence (ATAAA)n separates methylated and unmethylated domains at the 5'-end of the GSTP1 CpG island.
What defines the boundaries between methylated and unmethylated domains in the genome is unclear. In this study we used bisulfite genomic sequencing to map the boundaries of methylation that flank the 5'- and 3'-ends of the CpG island spanning the promoter region of the glutathione S-transferase (GSTP1) gene. We show that GSTP1 is expressed in a wide range of tissues including brain, lung, skeletal muscle, spleen, pancreas, bone marrow, prostate, heart, and blood and that this expression is associated with the CpG island being unmethylated. In these normal tissues a marked boundary was found to separate the methylated and unmethylated regions of the gene at the 5'-flank of the CpG island, and this boundary correlated with an (ATAAA)(19-24) repeated sequence. In contrast, the 3'-end of the CpG island was not marked by a sharp transition in methylation but by a gradual change in methylation density over about 500 base pairs. In normal tissue the sequences on either side of the 5'-boundary appear to lie in separate domains in which CpG methylation is independently controlled. These separate methylation domains are lost in all prostate cancer where GSTP1 expression is silenced and methylation extends throughout the island and spans across both the 5'- and 3'-boundary regions.
5' Untranslated Regions↗
Hypermethylation of E-cadherin in leukemia.
E-cadherin gene is often termed a "metastasis suppressor" gene because the E-cadherin protein can suppress tumor cell invasion and metastasis. Inactivation of the E-cadherin gene occurs in undifferentiated solid tumors by both genetic and epigenetic mechanisms; however, the role of E-cadherin in hematologic malignancies is only now being recognized. E-cadherin expression is essential for erythroblast and normoblast maturation, yet expression is reduced or absent in leukemic blast cells. This study examined the messenger RNA (mRNA) and protein expression of the E-cadherin gene in bone marrow and blood samples from normal donors and patients with leukemia. We found that all normal donor samples expressed E-cadherin mRNA, whereas both samples of acute myelogenous leukemia and chronic lymphocytic leukemia had a significant reduction or absence of expression. However, normal blast counterparts expressed only a low level of E-cadherin surface protein. Sodium bisulphite genomic sequencing was used to fully characterize the methylation patterns of the CpG island associated with the E-cadherin gene promoter in those samples with matched DNA. All of the normal control samples were essentially unmethylated; however, 14 of 18 (78%) of the leukemia samples had abnormal hypermethylation of the E-cadherin CpG island. In fact both alleles of the E-cadherin gene were often hypermethylated. We conclude the E-cadherin gene is a common target for hypermethylation in hematologic malignancies.
Base Sequence↗
State-level perspectives on immunization policies, practices, and program financing in the 1990s.
This article reports on a series of structured interviews with immunization program officials in all 50 states regarding the effects of changes in federal policies and funding in the 1990s on the goals, priorities, and activities of state immunization programs. The purchase of vaccines is a major component of all state immunization programs. The Vaccines for Children (VFC) program, implemented in 1994, has become the primary source of vaccine purchase support in almost all states. A concern of many state immunization programs is their ability to ensure that vaccines are available to children who are not VFC eligible.State immunization programs also are involved in a myriad of activities necessary to ensure that children are adequately and appropriately immunized (e.g. , vaccine administration, outreach to parents). Federal funding to support these activities increased significantly during the mid-1990s, but was substantially reduced beginning in 1997. Because of these funding decreases, most states had to reduce the scale and scope of their immunization activities.State-level funding support for immunization programs varies, with state governments more likely to support vaccine purchase than immunization activities. Immunization will never be completed. Along with each new birth cohort, changes to the primary immunization schedule (i.e., addition of new vaccines and expansion of existing recommendations to encompass broader target groups) create ongoing needs for vaccine purchase and other immunization activities. Long-term immunization planning must reflect these continually expanding needs.
Centers for Disease Control and Prevention, U.S.↗
Randomized placebo-controlled trial of the activity of the morphine glucuronides.
BACKGROUND: Morphine-6-glucuronide (M6G) is an active metabolite of morphine with potent analgesic activity. Morphine-3-glucuronide (M3G), the most prevalent metabolite, has minimal affinity for opioid receptors. It has been suggested from animal model data and by examination of metabolite ratios in humans that M3G may functionally antagonize the respiratory depressant and analgesic actions of morphine and M6G. METHODS: We performed a double-blind placebo-controlled trial with 10 healthy volunteers. The trial had 6 arms: (1) placebo, (2) 10 mg/70 kg of morphine, (3) 3.3 mg/70 kg of M6G, (4) 30.6 mg/70 kg of M3G, (5) 30.6 mg/70 kg of M3G with 10 mg/70 kg of morphine, and (6) 30.6 mg/70 kg of M3G with 3.3 mg/70 kg of M6G; all were give by slow intravenous bolus. Analgesia was assessed with the use of the submaximal ischemic pain model. The effects were quantified on numerical and visual analogue scales. Respiratory parameters and response to steady state 5% carbon dioxide challenge were assessed with spirometry, mass spectroscopy, and earlobe blood gas analysis. RESULTS: Morphine and M6G produced significant pain relief compared with placebo (morphine, P < .0001; M6G, P = .033). Pain relief after M6G was less than after morphine (P = .009) and M3G was no better than placebo (P = .26). Pain relief with morphine and M6G were not significantly altered by M3G (P = .59 and P = .28, respectively). Significant and similar dysphoria and sedation occurred with both morphine (P < .002) and M6G (P < .016) but were absent with both M3G and placebo. Respiratory parameters suggested that M6G produced less respiratory depression than morphine. Both morphine and M6G caused a significant reduction in respiratory drive compared with placebo (morphine, P = .002; M6G, P = .013); this effect was not reversed by M3G (P = .35 and P = .83, respectively). CONCLUSIONS: M3G appears to be devoid of significant activity; in these circumstances and at these doses, it does not antagonize either the analgesic or respiratory depressant effects of M6G or morphine.
Adult↗
Management of a horizontal root fracture after previous root canal therapy.
This case report concerns a 9-year-old girl who had a horizontal root fracture of her maxillary left central incisor and had root canal therapy performed by her family dentist immediately after the injury. Because of the incomplete canal obturation, the root canal filling material was removed, and calcium hydroxide therapy was initiated. Healing at the fracture site occurred, with hard tissue forming between the root segments. The coronal segment of the root was then obturated with gutta-percha. The patient later had orthodontic treatment with some movement of the coronal segment. Six-year post-treatment follow-up shows apparent clinical and radiographic success. This case illustrates the potential for repair of a horizontal root fracture after endodontic retreatment of the coronal segment and long-term splinting.
Child↗
Respiratory syncytial virus infection in high risk infants and the potential impact of prophylaxis in a United Kingdom cohort.
BACKGROUND: Bronchiolitis caused by respiratory syncytial virus (RSV) is an important cause of morbidity in ex-premature infants. In a randomised placebo controlled trial monoclonal antibody prophylaxis showed a 55% reduction in relative risk of hospital admission for these high risk infants, against a background incidence of 10.6 admissions per 100 high risk infants. AIMS: To follow a cohort of high risk infants in order to assess hospitalisation rate from RSV and the potential impact of prophylaxis for these patients in a UK local health authority. METHODS: A cohort of high risk infants from a local health authority were followed over the 1998/99 and 1999/2000 RSV seasons. The high risk population was defined as infants who, at the beginning of the seasons studied, were: (1) under 6 months old and born prior to 36 weeks gestation with no domiciliary oxygen requirement; or (2) under 24 months of age and discharged home in supplemental oxygen. All admissions with bronchiolitis during the season were identified. RESULTS: A total of 370 high risk infants were identified for the 1998/99 season and 286 for the following year. Over the two years there were 68 admissions. Significantly more admissions occurred from group 2 infants. RSV was identified in 27 cases (four admissions per hundred high risk infants). Prophylaxis may have saved up to pound 195,134 in hospital costs over the two years, but would have cost pound 1.1 million in drug acquisition costs. CONCLUSIONS: Careful consideration of risk factors is needed when selecting infants for RSV prophylaxis.
Antibodies, Monoclonal↗
Pediatrician and family physician prescription of selective serotonin reuptake inhibitors.
OBJECTIVES: Selective serotonin reuptake inhibitor (SSRI) prescriptions for children and adolescents have increased greatly in recent years despite a paucity of demonstrated safety and efficacy data and a lack of clear guidelines for use. Our study sought to describe family physician and pediatrician SSRI prescribing patterns for children and adolescents, identify influences on SSRI prescription variations, and describe the use of SSRI within the overall management of depression and other mental disorders in primary care. DESIGN: A survey was mailed to all 596 active North Carolina general pediatricians and a random sample of 557 family physicians in primary care practice. Family physicians who did not see children in their practice were excluded. The survey instrument consisted of a 4-page questionnaire. Survey items included physician demographics, practice characteristics, general management, volume of pediatric patients with depressive symptoms, prescription of SSRIs for depression and other diagnoses, and potential influences on SSRI prescribing practices. The main outcomes were self-reported physician prescription of SSRIs for children and adolescents. Results were analyzed using chi(2) comparisons and logistic regression. RESULTS: The overall response rate was 66% (55% family physicians and 76% pediatricians). Of the physicians, 72% had prescribed an SSRI for a child or adolescent. Depression was the most common reason for prescribing an SSRI; over two thirds of respondents had prescribed an SSRI for depression in a child 18 years of age or younger. Over half of the physicians reported they had prescribed an SSRI for a diagnosis other than depression in a child 18 years of age or younger. Attention-deficit/hyperactivity disorder was the most frequent use cited other than depression, followed by obsessive-compulsive disorder, aggression, eating disorders, and enuresis. Primary care physicians prescribed SSRIs for adolescents more commonly than for younger children. Only 6% of the respondents had ever prescribed an SSRI for a child younger than 6 years of age. In terms of SSRI prescriptions written for depression in the last 6 months, 32% of the physicians had recently prescribed SSRIs for adolescent patients and 6% for patients younger than 12 years of age. Family physicians were more likely than pediatricians to have recently prescribed SSRIs for adolescent patients (41% vs 26%), but there was no difference in recent SSRI prescriptions for children <12 years of age by physician specialty (4% vs 6%). Prescription of SSRIs was not associated with decreased use of counseling for treatment of depression, but prescription of SSRIs was associated with decreased use of referrals (63% vs 74%). There was no difference in the use of counseling between family physicians and pediatricians (61% vs 59%). However, pediatricians were more likely to use referrals in their usual approach to depression (77% vs 48%) compared with family physicians. More family physicians had prescribed SSRIs for pediatric patients compared with pediatricians (91% vs 58%), and more family physicians had prescribed SSRIs in combination with other psychotropic medications (54% vs 31%). For the majority of respondents, SSRI prescriptions constituted most of the medications used to treat childhood depression (75% of family physicians vs 61% of pediatricians). Family physicians were more likely to report a belief in the safety (63% vs 48%) and effectiveness (40% vs 32%) of SSRIs. Only 8% of physicians reported adequate training in the treatment of childhood depression and just 16% were comfortable with the treatment of depression. There were no specialty differences in training for the treatment of childhood depression; however, more family physicians than pediatricians agreed that they were comfortable with the management of childhood depression (22% vs 11%). (ABSTRACT TRUNCATED)
Adolescent↗
Oral idarubicin in patients with late chronic phase chronic myelogenous leukemia or chronic myelomonocytic leukemia.
Patients with chronic myelogenous leukemia (CML) who have failed or cannot receive interferon alpha (IFN-alpha) based regimens or patients with advanced chronic myelomonocytic leukemia (CMML) have very limited current therapeutic options. Hence, there is a need to develop new strategies for these patients. This study was undertaken to determine the efficacy and toxicity of a chronic low-dose oral idarubicin regimen in these patients as positive data has been generated on this agent in shorter schedules given to patients with other hematological malignancies. Eighteen patients were treated on study. The starting dose of oral idarubicin was 2 to 5 mg/m2 daily depending in initial WBC count. This dose was escalated in the absence of Grade 4 myelosuppression or Grade 3 or 4 extramedullary toxicity. Oral idarubicin was given daily for 28 days followed by a 21 day break off treatment in repeated cycles until there was evidence of disease progression or intolerable toxicity. The dose of idarubicin was adjusted, at 2-week intervals, by 25% to maintain a white blood cell (WBC) count between 2 and 4x10(9)/L and a platelet count of >75x10(9)/L. The dose was reduced by 25% for grade 2 extramedullary toxicity and held until toxicity resolved to grade 2 or better for grade 3 toxicity. Oral idarubicin was then restarted at 75% of the initial dose. Five out of 14 CML patients achieved a complete hematologic remission. No CMML patient responded (median survival 3 months). The overall median survival was 24 months. CML patients had a median survival of 28 months. Major toxicities (myelosuppression, gastrointestinal, cardiac) were infrequent with a median cumulative dose of 1110 mg/m2 (range 54-9750). Five patients have received oral idarubicin for > 1 year with no overt cardiotoxicity, reaching median cumulative dose of 2756 mg/m2 (range 2550-9750) which is higher than those documented in prior studies. We conclude that oral idarubicin is sufficiently safe and active to warrant phase II studies investigating it as part of interferon-based regimens in patients with advanced CML.
Administration, Oral↗
Primary care role in the management of childhood depression: a comparison of pediatricians and family physicians.
OBJECTIVE: To provide a self-described assessment of pediatricians' and family physicians' management of childhood depression. DESIGN: Mail survey of 595 general pediatricians and 557 family physicians in North Carolina. RESULTS: The response rate was 66%. Most primary care physicians used referral (65%) and counseling (61%) for management of childhood depression. Family physicians used medications more commonly (18% vs 9%), and pediatricians referred patients more commonly (77% vs 48%). In logistic regression analysis, physicians comfortable with management of depression (odds ratio [OR], 4.8: 2.7-8.4), physicians who believed that antidepressants are more effective than counseling (OR, 2.6: 1.4-4.8), and family physicians (OR, 2.2: 1.9-4.1) were more likely to have used medications for childhood depression. CONCLUSIONS: Most primary care physicians refer pediatric patients with depression; however, practice patterns vary by specialty and other factors. Future studies must consider the role of primary care and evaluate how interspecialty variations affect costs and outcomes of childhood depression.
Adult↗
Clinical features, anthropometric characteristics, and racial influences on the 'white-coat effect' in a single-centre cohort of 1553 consecutive subjects undergoing routine ambulatory blood pressure monitoring.
BACKGROUND: Patients with high office blood pressures but relatively normal readings during daytime ambulatory monitoring have been the subject of much investigation and debate. This clinical finding in part depends on an alerting reaction to the circumstances of the clinical measurement, often described as the 'white-coat effect' (WCE). Little is known of the characteristics of patients that are associated with the white coat effect in a large population of routinely referred patients. OBJECTIVE: To relate the size of the WCE (defined as the difference between office and ambulatory daytime readings) to clinical features that may influence this phenomenon. METHODS: We categorized 1553 consecutive subjects (51.3% men, aged 17-88 years), who had been referred to a single centre for the assessment of suspected hypertension prospectively into three groups: those aged <40, 40-59, and >/=60 years. RESULTS: WCE on systolic blood pressure (SBP) increased significantly with advancing age and was correlated positively to body mass index (BMI), age and treatment. We found significant correlations to sex (higher in women) and race. WCE on diastolic blood pressure (DBP) decreased slightly with advancing age and was correlated positively to BMI and significantly to race and sex. We found no correlation to age or treatment. Caucasians had a greater WCE than did non-Caucasians (P<0. 001 for SBP and DBP) and hypertensives had greater WCE than did normotensives (P<0.0001 for SBP and DBP). Multiple linear regression analysis showed that age and BMI are the most important factors influencing WCE on SBP and DBP. CONCLUSIONS: Factors such as race, age and BMI may exert important influences on the size of WCE possibly via effects on sympathetic nervous system activity.
Adult↗
Concurrent DNA hypermethylation of multiple genes in acute myeloid leukemia.
Hypermethylation in cancer often occurs in CpG islands that span the promoter regions of tumor suppressor genes. However, it is not clear if hypermethylation is limited to single target genes or if multiple genes are simultaneously methylated. To understand the extent of aberrant de novo methylation, we have analyzed the methylation pattern of a number of tumor-related genes in leukemia from the same cohort of patients. We used bisulfite genomic sequencing to characterize the methylation pattern of the CpG islands associated with the calcitonin, estrogen receptor, E-cadherin, p15, p16, Rb, GST-Pi, and HIC1 genes in the bone marrow from 9 normal and 20 patients with acute myeloid leukaemia (AML). All of the normal control samples were essentially unmethylated for each of the eight tumor-related genes studied. In contrast, 19 of 20 (95%) of the AML patients had an abnormal methylation pattern in at least one gene, and 15 of 20 (75%) had abnormal methylation patterns in two or more of the target genes. We conclude that there is a general deregulation of CpG island methylation in leukemia and that hypermethylation is not limited to single genes, but a number of genes are methylated concurrently. Moreover, the subset of genes that are commonly methylated in leukemia appear to be cancer type specific.
Acute Disease↗
Detailed methylation analysis of the glutathione S-transferase pi (GSTP1) gene in prostate cancer.
Glutathione-S-Transferases (GSTs) comprise a family of isoenzymes that provide protection to mammalian cells against electrophilic metabolites of carcinogens and reactive oxygen species. Previous studies have shown that the CpG-rich promoter region of the pi-class gene GSTP1 is methylated at single restriction sites in the majority of prostate cancers. In order to understand the nature of abnormal methylation of the GSTP1 gene in prostate cancer we undertook a detailed analysis of methylation at 131 CpG sites spanning the promoter and body of the gene. Our results show that DNA methylation is not confined to specific CpG sites in the promoter region of the GSTP1 gene but is extensive throughout the CpG island in prostate cancer cells. Furthermore we found that both alleles are abnormally methylated in this region. In normal prostate tissue, the entire CpG island was unmethylated, but extensive methylation was found outside the island in the body of the gene. Loss of GSTP1 expression correlated with DNA methylation of the CpG island in both prostate cancer cell lines and cancer tissues whereas methylation outside the CpG island in normal prostate tissue appeared to have no effect on gene expression.
Alleles↗