A Randomized Pilot Study of Behavioral Treatment to Increase Calorie Intake in Toddlers With Cystic Fibrosis

This pilot study examined a behavioral treatment to increase calorie intake in toddlers with cystic fibrosis. Eight toddlers were randomly assigned to behavioral plus nutrition (BEH) or nutrition intervention (NTR) conditions. Calorie intake and weight were measured at pre- and posttreatment. The BEH group showed a trend for changes in calorie intake pre- to posttreatment (p = .07; 40% increase). Results for the BEH and NTR groups did not differ significantly. Most participants achieved weight gains consistent with normal growth. Seventy-five percent had not shown this pattern during the year prior to intervention. These results support the feasibility and potential for behavioral interventions in this age group.     

The Relationship Between Daily Life Stress and Gastrointestinal Symptoms in Women with Irritable Bowel Syndrome

Research on irritable bowel syndrome (IBS), a functional disorder of the gastrointestinal (GI) system, has linked GI symptoms to stress. This study examined the relationship between daily stress and GI symptoms across women and within woman in IBS patients (n = 26), IBS nonpatients (IBS-NP; n = 23), and controls (n = 26), controlling for menstrual cycle phase. Women (ages 20–45) completed daily health diaries for two cycles in which they monitored daily GI symptoms and stress levels. The Life Event Survey (LES) was used as a retrospective measure of self-reported stress. The across-women analyses showed higher mean GI symptoms and stress in the IBS and IBS-NP groups relative to controls but no group differences in LES scores. The within-woman analyses found a significant and positive relationship between daily stress and daily symptoms in both the IBS-NP and the IBS groups. Controlling for menstrual cycle had no substantial impact on the results.     

Idarubicin metabolism and pharmacokinetics after intravenous and oral administration in cancer patients: a crossover study

The pharmacokinetics and metabolism of 4-demethoxydaunorubicin (idarubicin, IDA) were studied in 21 patients with advanced cancer after i.v. (12 mg/m2) and oral (30-35 mg/m2) treatment according to a balanced crossover design. Patients were divided into four groups: subjects who showed normal liver and kidney function (group N), those who presented with normal kidney function and liver metastases (group L), those with kidney dysfunction (creatinine clearance, less than or equal to 60 l/h; group R), and those with both liver and kidney dysfunction (group LR). Five patients showed variations in liver or kidney function after the first treatment and were considered to be nonevaluable for the crossover study but evaluable for the liver/kidney function study; some of them appeared in different groups for the i.v. as opposed to p.o. treatments. After i.v. administration, IDA plasma levels followed a triphasic decay pattern. The main metabolite observed in all patients was the 13C-reduced compound (IDAol), which attained plasma levels 2-12 times higher than those of the parent compound. IDA pharmacokinetics was not dependent on the presence of liver metastases but was related to the integrity of kidney function. Analysis of variance indicated a significant correlation between IDA plasma clearance and creatinine clearance; it was also found that IDA plasma clearance was lower in patients whose creatinine clearance was less than 60 ml/min [group N, 122.8 +/- 44.0 l/h; group L, 104.4 +/- 27.7 l/h (P = 0.58) vs group R, 83.4 +/- 18.3 l/h (P = 0.037)]. The IDAol terminal half-life and mean residence time (MRT) were significantly increased in patients with impaired kidney function [MRT: group N, 63.6 +/- 10.8 h; group L, 69.9 +/- 10.2 h (P = 0.27) vs group R, 83.2 +/- 10.9 h (P = 0.025) and t1/2 gamma: group N, 41.3 +/- 10.1 h; group L, 47.0 +/- 7.4 h (P = 0.31) vs group R, 55.8 +/- 8.2 h (P = 0.025)]. After oral treatment, drug absorption occurred during in the first 2-4 h after IDA administration; a biphasic decay pattern was observed thereafter. The main metabolite observed in all patients was again IDAol. The AUC of IDAol was greater after oral administration than after i.v. treatment in proportion to the AUC of IDA (i.v.: AUC-IDAol/AUC-IDA, 2.4-18.9; p.o.: AUC-IDAol/AUC-IDA, 4.1-21.4). Following oral dosing, a substantial amount of 4-demethoxydaunomycinone (AG1) was found in 11/21 patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Dopa-responsive parkinsonism secondary to right temporal lobe haemorrahage.

A 46-year-old man developed a symmetrical parkinsonian syndrome 7 weeks after large right temporal intracerebral haemorrhage resulting from a ruptured arteriovenous malformation. His signs included bradykinesia, rigidity, start hesitation, and poor postural reflexes, without a resting tremor. He also had signs of a Parinaud's syndrome. Computed tomography and magnetic resonance imaging of the brain demonstrated changes in the right temporal lobe associated with the haemorrhage but no abnormality of the basal ganglia or midbrain. Levodopa therapy produced a dramatic improvement within a few days of commencement. We postulate that the parkinsonism resulted from midbrain compression secondary to transtentorial herniation. Although parkinsonism is a rare complication of lobar intracerebral haemorrhage, it is important to recognise as it may be potentially treatable.     

Developmental patterns of intermediate filament gene expression in the normal hamster brain

We have examined the patterns of expression of the major intermediate filament (IF) protein mRNAs during development of the hamster brain. Quantitative northern blotting was used to examine changes in the levels of mRNAs for the low, middle and high molecular weight neurofilament proteins (NF-L, NF-M, NF-H) as well as peripherin, vimentin and glial fibrillary acidic protein (GFAP). Total RNA was isolated from hamster brains at embryonic (E) days 12 and 14 and postnatal (P) days 1, 3, 5, 7, 9, 11, 13, 15, 20, 28 and 60-90 (adult), and probed with specific IF cDNAs. Northern blotting revealed that NF-L and NF-M mRNAs were present at very low levels in embryonic brain and that significant expression of these genes only occurred postnatally when the levels increased dramatically until P28 and then declined again in the adult. Increases in NF-H mRNA levels were somewhat delayed relative to those of NF-L and NF-M. NF-H mRNA was not seen at embryonic stages and was expressed at very low levels prior to P9; after that time the levels increased rapidly until P28 and then declined in the adult. Two of the type III IF genes, peripherin and vimentin, followed a pattern of expression opposite that of the NF genes. Both peripherin and vimentin mRNAs were present in embryonic brain and were expressed at higher levels during early postnatal stages than at later times. The magnitude and rate of reduction in vimentin gene expression in the postnatal interval was much greater than that of peripherin. GFAP mRNA levels were extremely low prior to P9 after which a robust increase occurred, followed by a decline in the adult. We discuss the implication of the dramatic changes in IF isotype expression in brain to the pathways of both neuronal and glial development in vivo.     

Infants with single umbilical artery studied in a national registry. General epidemiological characteristics

Summary. In this paper, registry data on infants born in Sweden between 1983 and 1986 are reviewed to describe the epidemiological characteristics of infants with single umbilical artery (SUA). During this period 372 066 births were registered with information on the number of umbilical vessels. Our data set contains 1782 SUA infants. The incidence at birth was: in multiple births 0.8%, in infants with chromosome anomalies 6.1% and in singletons without a known chromosome anomaly 0.46%. Incidence was higher in girls than in boys. There were no consistent seasonal variations in the date of presumed conception. Low birthweight (<2500 g) and preterm birth (<37 weeks) were seen more frequently in SUA singleton infants than in infants with three vessels. At any given gestation, SUA infants had a lower mean birthweight than infants with three vessels. The risk of having a SUA infant was increased in women over 40 years, and slightly increased at or above parity of three.     

Prognostic relevance of histological grade and its components in node-negative breast cancer patients.

Available results highlight the lack of good level of evidence studies on the pure prognostic value of histological grade. In the present study, the prognostic relevance of histological grade and of its three components, tubule formation, nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients with node-negative breast cancer treated with locoregional therapy alone until early relapse. Histological grade was determined blindly by two observers and discordance between evaluations was resolved after joint review using a multihead microscope. No relation was observed between histological grade and any of its three components and disease-free survival. Conversely, a significant relation was observed between histological grade and distant metastasis-free survival (at 6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P=0.013) as well as overall survival (98, 90 and 86%, P=0.001). A breakdown analysis as a function of the three components showed that neither tubule formation nor nuclear pleomorphism was associated with prognosis, and only mitotic count strongly influenced both distant metastasis-free survival (91, 82 and 74%, P=0.014) and overall survival (97, 87 and 85%, P=0.011). Histological grade suffers from a much higher subjectivity than any other microscopic evaluation of biomarkers as it is the sum of three different morphological features. Within the Italian Network for Quality Assessment of Tumor Biomarkers program we observed that histological grade is an independent prognostic variable, but also that this role is ascribable only to the number of mitotic figures. In conclusion, due to the ever smaller size of diagnosed breast cancers, resulting in less cancer tissue for biofunctional and molecular analysis, mitotic count evaluated under strict quality control conditions seems to be an accurate and feasible prognostic variable.     

Evaluation of clinical criteria for the acute respiratory distress syndrome in pediatric patients.

OBJECTIVE: The primary goal of this study was to evaluate the validity of the North American-European Consensus Committee (NAECC) definition for acute respiratory distress syndrome (ARDS) in pediatric patients. A secondary aim was to evaluate the threshold value for the PaO2/FiO2 ratio, used to determine which pediatric patients have ARDS. DESIGN: Retrospective cohort study. SETTING: Pediatric intensive care unit. PATIENTS: Pediatric intensive care unit patients who required mechanical ventilation, died, and underwent autopsy between January 1, 1996, and December 31, 2002 (n = 34). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and chest radiograph information was collected retrospectively through chart review using a standardized data collection tool. Data included the criteria specified in the NAECC definition of ARDS and demographic information. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of clinical diagnosis of ARDS compared with a pathologic diagnosis. The threshold value of PaO2/FiO2 was identified by plotting receiver operating characteristics curves and comparing the areas under the curves. The NAECC definition yielded a sensitivity of 80.7% (95% confidence interval 60-92%), specificity of 71.4% (95% confidence interval 30-95), positive predictive value of 91.3% (95% confidence interval 70-98), negative predictive value of 50.0% (95% confidence interval 20-78), and likelihood ratio of 2.82. A PaO2/FiO2 <150 had a slightly higher (but not significantly different) specificity for ARDS than a value >200 (71% vs. 86%, p = .15) without changing sensitivity. CONCLUSIONS: Our study suggests the need for further research with larger number of children to identify an optimal Pao2/Fio2 threshold for identifying ARDS in this population.