Amino-terminal proCNP: a putative marker of cartilage activity in postnatal growth

Recent evidence from rodents and humans shows that C-type natriuretic peptide (CNP) plays an essential role in endochondral bone growth. We recently identified a stable product of proCNP, amino-terminal proCNP (NT-proCNP), which unlike CNP is readily measurable in human and ovine plasma. Hypothesizing that plasma NT-proCNP concentrations reflect in part CNP synthesis within growth plates of rapidly growing cartilage, we studied levels of CNP forms in both children and lambs and related these to age, growth velocity, and biochemical markers of bone turnover. Plasma NT-proCNP levels were elevated at birth and fell progressively with age. Significant associations between plasma NT-proCNP and height velocity, alkaline phosphatase, and type 1 collagen C telopeptide were identified in children (aged 5-18 y). In longitudinal animal studies, elevated plasma concentration of NT-proCNP in 1-wk-old lambs fell progressively to mature adult levels at age 27 wk. Plasma NT-proCNP showed a highly significant association with alkaline phosphatase and metacarpal growth velocity. Glucocorticoids, a treatment known to inhibit cartilage proliferation, reduced metacarpal growth elongation in 4-wk-old lambs and markedly lowered circulating NT-proCNP levels during the treatment period. In summary, NT-proCNP levels in blood show a strong association with growth velocity and markers of bone formation and may well serve as a useful marker of growth plate activity in humans and other mammals.     

Granulocytic sarcoma presenting as pneumonia in a child with t(8;21) acute myelogenous leukemia: diagnosis by fluorescent in situ hybridization

Granulocytic sarcoma is a soft tissue collection of leukemic cells. The authors describe a 4-year-old boy with M2 acute myelogenous leukemia (AML) who presented with fever, mild nonproductive cough, and hematemesis. Although he was initially diagnosed with nodular pneumonia, rapid resolution of a pulmonary infiltrate following induction chemotherapy was suggestive of a pulmonary granulocytic sarcoma. Interphase fluorescent in situ hybridization (FISH) of the lung biopsy specimen for the t(8;21)(q22;q22) translocation confirmed the retrospective diagnosis of a well-differentiated pulmonary granulocytic sarcoma. Pulmonary granulocytic sarcomas may be underrecognized in children with AML; this may delay anti-leukemic therapy and may lead to ineffective therapy if misdiagnosed as pneumonia.     

A Prospective Evaluation of Positron Emission Tomography Scanning,Sentinel Lymph Node Biopsy,and Standard Axillary Dissection for Axillary Staging in Patients with Early Stage Breast Cancer

Background: Positron emission tomography (PET) is a noninvasive imaging modality that can detect malignant lymph nodes. This study determined the sensitivity, specificity, predictive values, and likelihood ratios of PET scanning compared with standard axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) in staging the axilla in women with early stage breast cancer.Methods: Women with clinical stage I or II breast cancer had whole body PET scanning before ALND and SLNB, in a prospective, blinded protocol. ALND were evaluated by standard hematoxylin and eosin (H&E) staining techniques, while sentinel nodes were also examined for micrometastatic disease.Results: A total of 98 patients were recruited. PET compared with ALND demonstrated sensitivity of 0.40 (95% CI, 0.16, 0.68), specificity 0.97 (CI, 0.90, 0.99), positive likelihood ratio 14.4 (CI, 3.21, 64.5), positive predictive value 0.75 (CI, 0.35, 0.97), and false–negative rate of 0.60 (CI, 0.32, 0.84). Test properties were similar for PET compared with sentinel nodes positive by H&E staining. A few false–positive scans (0.028, CI, 0.003, 0.097) were seen. Multiple logistic regression analysis found that PET accuracy was better in patients with high grade and larger tumors. Increased size and number of positive nodes were also associated with a positive PET scan.Conclusions: The sensitivity of PET compared with ALND and SLNB was low, whereas PET scanning had high specificity and positive predictive values. The study suggests that PET scanning cannot replace histologic staging in early stage breast cancer. The low rate of false–positive findings suggests that PET can identify women who can forego SLNB and require full axillary dissection.     

On the importance of using multiple methods of dietary assessment

BACKGROUND: Plasma carotenoid concentrations reflect intake of vegetables and fruits, the major food sources of these compounds. This study compared the ability of 2 measures of dietary intake (24-hour diet recalls and food frequency questionnaires [FFQs]) to corroborate plasma carotenoid concentrations in a subset of women participating in a diet intervention trial. METHODS: Plasma carotenoid concentrations and dietary intakes, estimated from 24-hour diet recalls and FFQs, were examined at baseline and 1 year later in a subset of 395 study participants (197 intervention and 198 comparison group). We used longitudinal models to examine associations between estimated intakes and plasma carotenoid concentrations. These analyses were stratified by study group and adjusted for body mass index (BMI), plasma cholesterol concentration, and total energy intake. We conducted simulations to compare mean-squared errors of prediction of each assessment method. RESULTS: In mixed-effects models, the estimated carotenoid intakes from both dietary assessment methods were strongly associated with plasma concentrations of alpha-carotene, beta-carotene, and lutein. Furthermore, modeling the 2 sources of intake information as joint predictors reduced the prediction error. CONCLUSION: These findings underscore the importance of using multiple measures of dietary assessment in studies examining diet-disease associations.     

Cancer statistics: everything you wanted to know about the cancer registry data but were too afraid to ask

Australia and New Zealand (ANZ) have had complete population cancer incidence registration for decades and are beginning to develop clinical data systems to collect details of staging and treatment. Sadly, this bounty of statistical data is often under utilized and occasionally abused. Many are unaware of the data and statistical services available from their local cancer registry. To promote the use of ANZ population cancer data, the following paper describes the principal statistics that are available and identifies common problems with their use.     

Ser392 phosphorylation regulates the oncogenic function of mutant p53

Despite the wealth of information on the regulation of wild-type p53 function by phosphorylation, nothing is known about the biological effect of phosphorylation on mutant p53. Here we show that p53H175 is phosphorylated like wild-type p53 in cells of the same background. Ser(392) nonphosphorylatable p53 mutants p53H175A392 and p53W248A392 more potently transformed rat embryo fibroblasts in cooperation with the ras oncogene than p53H175S392 and p53W248S392. p53H175A392 also had an enhanced ability to confer cellular resistance to the cytotoxic effect of cisplatin and UV radiation. This correlated with p53H175A392 being a more potent dominant negative mutant than p53H175 in inhibiting the apoptotic functions of wild-type p53. Moreover, p53H175E392, which mimics the phosphorylated form of p53H175, was less able to confer cellular resistance to DNA-damaging agents. p53H175 and p53W248 are phosphorylated like wild-type p53 in cells of the same background. Ser(392) nonphosphorylated p53 was present in human breast tumors expressing mutant p53 including p53H175. Together, these results demonstrated a novel function of Ser(392) phosphorylation in regulating the oncogenic function of mutant p53.     

Development and preliminary validation of the Meta-cognitions Questionnaire-Adolescent Version

This study describes the development of the Meta-cognitions Questionnaire for Adolescents (MCQ-A). The adult version of this questionnaire has been widely used, and the meta-cognitive theory of emotional disorders has become influential in the adult literature. This study sought to examine the prevalence and emotional correlates of meta-cognition in adolescents. The MCQ-A was administered to 177 schoolchildren aged 13 through 17 years, together with measures of emotional well-being. Factor analysis suggested a five-factor solution similar to that reported for the adult version. Internal consistency of the scale was high. Scores ranged from low to high across the age range, suggesting that meta-cognitive beliefs are well-established by adolescence. Scores on the MCQ-A were highly correlated with a number of measures of emotional symptoms. The MCQ-A is a reliable and valid instrument for measuring meta-cognitive beliefs in adolescents. Young people aged between 13 and 17 years report a range of types and levels of meta-cognitive beliefs and these are positively associated with emotional symptoms.     

N-acetylcysteine for the treatment of clove oil-induced fulminant hepatic failure

We present a 3-month-old female who developed fulminant hepatic failure after ingesting less than 8 mL of clove oil. Initial treatment involved gastrointestinal decontamination, supportive measures, and admission to hospital. She subsequently developed fulminant hepatic failure and was treated with intravenous N-acetylcysteine (N-AC) according to a protocol used for acetaminophen poisoning. Over the next 72 h her liver synthetic function and clinical status improved, and she made a complete recovery. Previous reported cases of clove oil toxicity and the potential role of N-AC therapy are reviewed.     

Trends in the etiology of infectious corneal ulcers at the F. I. Proctor Foundation

OBJECTIVE: We analyzed laboratory results from corneal ulcers seen from 1976 to 1999 at the Francis I. Proctor Foundation, a referral center in San Francisco, to determine the relative frequencies of pathogens and to analyze for trends in frequencies of the most common pathogens. The results were compared with a previous study of corneal ulcers seen from 1948 to 1976 at the same institution. METHODS: Ulcers presenting to the Proctor Foundation were Gram stained and cultured using standard techniques. Herpetic corneal ulcers were excluded from the study. RESULTS: Organisms were isolated from 427 ulcers, 38% of all cases. Two hundred seventy-eight (59%) isolates were gram-positive bacteria, 145 (31%) gram-negative bacteria, 16 (3%) Acanthamoeba spp., and 36 (8%) fungi. Staphylococcus aureus was the most common organism, composing 20% of all isolates, followed by viridans group streptococci (12%), Streptococcus pneumoniae (11%), Pseudomonas aeruginosa (6%), Moraxella spp. (5%), and Serratia marcescens (4%). Over the 24-year study period the proportion of positive cultures decreased and the incidence of S. marcescens increased significantly. Comparing the period of 1948-1976 to 1976-1999, the frequency of S. pneumoniae and P. aeruginosa decreased, and that of S. marcescens increased significantly. CONCLUSION: The common pathogens associated with corneal ulcers have changed over the past 50 years in Northern California, with S. pneumoniae and P. aeruginosa being isolated relatively less often and S. marcescens being isolated with increasing frequency. The decrease in isolation of organisms over the 1976-1999 period may have resulted from increasing empiric antibiotic treatment by referring ophthalmologists.