Rapid improvement in symptoms and physical function following ibrutinib initiation in chronic lymphocytic leukemia and the associated changes in plasma cytokines.

A prospective pilot study was carried out on 34 CLL patients treated with ibrutinib, evaluating the effects on symptoms and physical function with changes in plasma exosomes (EXs), ß2-microglobulin (ß2M) and 26 plasma cytokines. The revised Edmonton Symptom Assessment Scale (ESAS-R) demonstrated moderate fatigue, shortness of breath and a sense of unwellness before treatment, which significantly improved within 2 weeks of starting ibrutinib. These changes were associated with a rapid improvement in sit-to-stand and 4 m walking speeds. The plasma levels of CCL11, IL-7, -8 and -10 dropped initially while the levels of TNF-α/-ß, CCL3, CCL4, CCL17, and IL-16 continued to decline for 12 months. Despite the initial lymphocytosis, plasma ß2M levels fell but no consistent change in plasma EXs occurred. Thus, ibrutinib can produce a rapid and sustained improvement in symptoms and physical function in CLL, associated with a decline in multiple plasma cytokines.

Development and validation of a GEANT4 radiation transport code for CT dosimetry.

The authors have created a radiation transport code using the GEANT4 Monte Carlo toolkit to simulate pediatric patients undergoing CT examinations. The focus of this paper is to validate their simulation with real-world physical dosimetry measurements using two independent techniques. Exposure measurements were made with a standard 100-mm CT pencil ionization chamber, and absorbed doses were also measured using optically stimulated luminescent (OSL) dosimeters. Measurements were made in air with a standard 16-cm acrylic head phantom and with a standard 32-cm acrylic body phantom. Physical dose measurements determined from the ionization chamber in air for 100 and 120 kVp beam energies were used to derive photon-fluence calibration factors. Both ion chamber and OSL measurement results provide useful comparisons in the validation of the Monte Carlo simulations. It was found that simulated and measured CTDI values were within an overall average of 6% of each other.

Tumour-infiltrating FOXP3(+) lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer.

BACKGROUND: Regulatory T cells (Tregs) are commonly identified by expression of the transcription factor FOXP3 and are conventionally thought to promote cancer progression by suppressing anti-tumour immune responses. We examined the relationship between FOXP3(+) tumour-infiltrating lymphocytes (TIL) and prognosis in oestrogen receptor (ER)-negative breast cancer, a tumour subtype with poor clinical outcome in which TIL are abundant. METHODS: FOXP3(+) and CD8(+) TIL were assessed by immunohistochemistry in a cohort of 175 ER- breast tumours. Results were confirmed in an independent data set of 78 ER- breast tumours with publically available gene expression data. RESULTS: High FOXP3(+) TIL levels were strongly associated with prolonged recurrence-free survival (HR=0.461, P=0.0002), particularly among basal-like tumours (HR=0.280, P=0.0001), for which FOXP3 status was independent of standard prognostic factors. Over 75% of FOXP3(+) TIL in triple negative breast tumours displayed a conventional CD4(+)CD25(+) Treg phenotype. Importantly, FOXP3(+) TIL were positively correlated with CD8(+) (cytotoxic) T cells (r(s)=0.76, P<0.0001), and were prognostically insignificant in tumours with low levels of CD8(+) TIL. These observations were confirmed in an independent cohort. CONCLUSION: In contrast with current dogma, we show for the first time that FOXP3(+) TIL are associated with robust anti-tumour immunity and favourable prognosis in ER- breast cancer.

Medical, psychological and intellectual development of 5-year-old children born after intracytoplasmic sperm injection.

BACKGROUND: The neurodevelopmental outcome of children born after intracytoplasmic sperm injection (ICSI) is controversial. PATIENTS AND METHODS: Thus, we compared the medical and developmental outcome at a mean age of 5 years and 6 months of 35 singletons born after an ICSI procedure performed at the Tübingen Medical Center with those of 37 naturally conceived (NC) matched control singletons born at the Tübingen Medical Center. Children with congenital anomalies which could interfere with mental development were excluded, these were reported earlier. Each child was assessed neurologically and physically. Cognitive function was assessed using the Kaufman assessment battery for children (K-ABC). Behaviour was tested using a German behavioural questionnaire for preschoolers (VBV). RESULTS: Medical and cognitive outcome, and behaviour pattern were similar in both groups. Nevertheless, there were sex-related differences in favour of ICSI children: ICSI boys had better social competence than the control boys, while ICSI girls had less emotional problems than the control girls. CONCLUSIONS: Once severe congenital anomalies were excluded, there were no differences in physical and neurodevelopmental outcome of 5-year-old ICSI children compared with controls.With regard to behaviour and emotional development, ICSI children seem to be similar or might be even more stable and socially competent than the control children. As our study is limited by the small sample size, further research is needed to confirm our results.

Characterization of Canadian cefoxitin-resistant non-typhoidal Salmonella isolates, 2005-06.

OBJECTIVES: Resistance to extended-spectrum cephalosporins has increased in Salmonella worldwide, and is a concern in both hospital and community settings. The aim of this report was to investigate cefoxitin-resistant Salmonella isolates identified from human clinical cases across Canada. METHODS: Cefoxitin-resistant isolates, defined as having an MIC > or = 32 mg/L, were screened for the ampC classes DHA, FOX, ENT and CIT in a multiplex PCR followed by sequence analysis. Plasmid analysis by restriction fragment length polymorphism (RFLP) and replicon typing was performed on a convenience sample of cefoxitin-resistant Salmonella. RESULTS: In 2005, 5.3% (181/3442) and in 2006, 3.1% (102/3250) of Salmonella isolates collected from all provinces across Canada displayed cefoxitin resistance. Seventy-one out of 283 (25.1%) were multidrug resistant (MDR), as defined by resistance to at least three different antibiotic classes. The bla(CMY-2) gene was harboured by 96.8% (274/283) of the cefoxitin-resistant isolates. Analysis of CMY-2 plasmids revealed that 19.7% contained genes conferring resistance to multiple antimicrobials. Replicon typing of transformant CMY-2 plasmid DNA revealed the predominance of I1-Igamma and A/C. Of the MDR CMY-2 plasmids, 75% contained replicon type A/C. RFLP patterns of CMY-2 plasmids revealed clusters corresponding to the I1-Igamma and A/C replicon types. CONCLUSIONS: Incompatibility group I1-Igamma is the most prevalent of the Salmonella CMY-2 plasmids, while A/C is associated with MDR CMY-2 plasmids.

Increased frequency of severe major anomalies in children conceived by intracytoplasmic sperm injection.

The neurodevelopmental outcome of children born after intracytoplasmic sperm injection (ICSI) is controversial. We compared the medical and developmental outcome of 34 singletons born after ICSI (20 males, 14 females; mean ages of 18 mo and 40 mo [SD 9 mo]; range 2 y 10 mo-4 y 8 mo) with 39 case control studies (21 males, 18 females; mean ages of 18 mo and 40 mo [SD 4 mo]; range 3 y-4 y 1 mo). Each child was assessed physically and tested in three development domains (fine motor, gross motor, and language). Five children born after ICSI versus two control children (p=0.2) had major congenital anomalies (MaCAs). Four children born after ICSI versus no control children had severe MaCAs (p=0.04). These were defined as having a significant impact on development or causing chronic disease: Angelman syndrome (n=1), lissencephaly (n=1), Hanhart syndrome (n=1), and persistent hyperinsulinemic hypoglycaemia of infancy (n=1). Karyotyping in 23 children born after ICSI revealed no abnormalities. An imprinting defect was found in the child with Angelman syndrome. Results of developmental assessment were in all cases normal at the age of 18 months except for the three children with Angelman and Hanhart syndromes, and lissencephaly. At the second assessment, five more children born after ICSI and four control children showed abnormalities in one or more developmental domains. We conclude that there seems to be a higher frequency of severe major anomalies in children born after ICSI. An increased risk for imprinting defects cannot be excluded. If we exclude children with severe MaCAs, the incidence of an abnormal somatic or neurodevelopmental outcome in the fourth year of life in children born after ICSI is similar to that of spontaneously conceived children.

De novostructural chromosomal imbalances: molecular cytogenetic characterization of partial trisomies.

De novo structural chromosomal imbalances represent a major challenge in modern cytogenetic diagnostics. Based solely on conventional cytogenetic techniques it may be impossible to identify the chromosomal origin of additional chromosomal material. In these cases molecular cytogenetic investigations including multicolor-FISH (M-FISH), spectral karyotyping (SKY), multicolor banding (MCB) and cenM-FISH combined with appropriate single-locus FISH probes are highly suitable for the determination of the chromosomal origin and fine characterization of derivative chromosomes. Here we report on four patients with de novo chromosomal imbalances and distinct chromosomal phenotypes, three of them harboring pure partial trisomies: a mildly affected boy with pure partial trisomy 10q22.2-->q22.3 approximately 23.1 due to an interstitial duplication, a girl with pure trisomy 12p11.21-->pter and atypically moderate phenotype as the consequence of an X;autosome translocation, and a girl with multiple congenital abnormalities and severe developmental delay and a 46,XX,15p+ karyotype hiding a trisomy 17pter-->17q11.1. The fourth patient is a girl with minor phenotypic features and mental retardation with an inverted duplication 18q10-->p11.31 combined with a terminal deletion of 18p32. The clinical pictures are compared with previously described patients with focus on long term outcome.

Effect of dose and dose-distribution in damage to the kidney following abdominal radiotherapy.

PURPOSE: To define the effects of abdominal radiotherapy on the kidney with regard to dose-distribution parameters. MATERIALS AND METHODS: Ninety-one patients with abdominal radiotherapy were included in the study, and the minimum follow-up was 1 year. Conventional fractionation, 5 x 1.8-2.0 Gy week(-1) to total doses of 30.6-62.5 Gy, was employed. Assessment of organ function was performed before, immediately after, and at 6 months and 1 year after radiotherapy. In cases with a significant radiation response at 1 year, subsequent follow-ups were done at 6-month intervals. Documented parameters included clinical examination, static and sequential scintigraphy of the kidneys, abdominal computed tomography, and sonography. RESULTS: Twenty-one patients (23%) developed a reduction in kidney function detected by static scintigraphy. Only in 15 of these patients was impairment of renal function observed by sequential scintigraphy. The contribution of the irradiated kidney to overall renal function decreased progressively to 34-40% by the third year after treatment. Hypertension was seen in two patients. No changes were found in laboratory parameters. ED(50) for scintigraphic changes decreased from 27 Gy for 10% of the volume to 7.6 Gy for 100%. ED(5) were in the range of 3-6 Gy, and this was independent of volume. CONCLUSIONS: Sophisticated imaging techniques allow the identification of radiation effects in partial volumes of the kidneys. A dose-response relationship in relation to the volume of kidney irradiated can thus be established for scintigraphic changes. As in a number of other organs, such changes do not relate directly to loss of renal function due to the reserve capacity of unirradiated kidney tissue.

Pediatric emergency assessment tool (PEAT): a risk-adjustment measure for pediatric emergency patients.

OBJECTIVE: To develop a multivariable model predicting the level of care required by pediatric patients for use as a risk-adjustment tool in the evaluation of emergency medical services for children. METHODS: A random 10% sample of records of all visits over a 12-month period to a suburban, university-affiliated pediatric emergency department (PED) was selected and abstracted. The outcome variable, level of care received, was categorized in three levels: routine care only (R); diagnostic or therapeutic procedures performed in the ED but patient not admitted (EDT); and admission to hospital (ADM). Predictor variables included information routinely elicited and recorded at the time of triage. Using multinomial logistic regression, a predictive model was derived from a subset of 70% of the selected visits, and was validated in the remaining 30%. RESULTS: The total sample included 2,287 visits. The overall rate of each outcome was R-37%, EDT-53%, and ADM-10%. The final regression model included the following predictors significantly associated with the outcome: age, past medical history, temperature, abnormal respiratory rate or pulse oximetry in triage, chief complaint, and triage level (model likelihood ratio chi-square, 14 df = 332, p < 0.00001, R(2) = 0.14). The number of outcomes was well predicted by the model in both subsamples. Analysis of variance showed a significant association between Pediatric Emergency Assessment Tool (PEAT) score (weighted sum of the predicted probabilities of EDT and ADM) and both ED charges and time spent in the ED (p < 0.001). CONCLUSIONS: A model based on easily and routinely measured variables can accurately predict the level of care rendered in the PED. The predicted probabilities from such a model correlate well with other outcomes of care and may be useful in adjusting for differences in risk when evaluating quality of care.

Ambulance use by high-acuity patients in a pediatric ED.

The objective of this study was to analyze ambulance usage by highest acuity patients as compared with all patients in a suburban pediatric hospital ED. A 1-year retrospective records analysis was conducted of all highest acuity patients (those patients triaged as emergent or critical or admitted to the intensive care unit). A total of 245 patients made 270 high-acuity visits to the ED in 1995. Thirty-one (13%) of the high-acuity patients arrived via ambulance; the rest arrived via private vehicle. The 31 high-acuity patients constituted 8% of the total number of patients arriving by ambulance. There was no significant difference in ambulance usage between insurance groups in the high-acuity patients. Only high-acuity patients with neurologic symptoms (primarily seizures) had a greater relative use of EMS transportation, with 39% of these patients arriving via ambulance (odds ratio 6.6, 95% confidence interval 2.6,16.6). High-acuity patients account for the minority of total ambulance usage in our ED.

[Prevention of radiation-induced diarrhea by smectite. Results of a double-blind randomized, placebo-controlled multicenter study]. / Prophylaxe der strahleninduzierten Diarrhö durch Smektit. Ergebnisse einer doppelblind randomisierten, plazebokontrollierten Multicenterstudie.

PURPOSE: Diarrhea and abdominal pain are well-known side effects abdominal or pelvic of radiation therapy that may lead to interruption of treatment in serious cases. In recent trials the silicate smectite has proven a promising drug in the prophylaxis of these adverse events. The presented trial aimed at the verification of earlier studies and the evaluation of a dose-effect relationship. PATIENTS AND METHODS: Between April 1994 and May 1995, a total of 176 patients obtaining radiotherapy of the pelvis or the abdomen were evaluated in a double-blind, randomized placebo-controlled investigation regarding the prophylactic effect of smectite (= Colina) against radiotherapy-induced diarrhea. During the whole period of radiotherapy 85 patients obtained 2 x 6 g smectite daily and 91 patients received 2 x 6 g placebo. The primary end point of the analysis was the time to the first appearance of diarrhea (> or = 3 pappy stools). RESULTS: All 176 patients were evaluated according to an intent-to-treat analysis. There was no significant difference between the prophylactic effects of smectite and placebo. For an explorative post-hoc analysis the total study group was split up into 2 subgroups, one with an irradiated small bowel volume < or = 837.5 ml, the other with a small bowel volume > 837.5 ml (median); the analysis indicated that the first subgroup showed a benefit for the smectite-treated patients in contrast to the placebo treatment (32 vs. 18 calendar days to the first appearance of diarrhea). This benefit was statistically not significant. CONCLUSION: Prophylactic application of smectite during irradiation of the pelvis and the abdomen can delay the development of radiotherapy-induced diarrhea, a statistical significance could not be verified neither in the total study group nor in the post-hoc subgroup analysis.

Appropriateness of ambulance transportation to a suburban pediatric emergency department.

OBJECTIVE: To assess the appropriateness of ambulance use in patients presenting to a pediatric emergency department (ED), with regard to both medical necessity and insurance status. METHODS: The authors conducted a one-year retrospective chart analysis of all patients (age range 2 weeks to 19 years) who were transported via ambulance in 1994 to a suburban children's hospital ED. ED records of all patients who arrived by ambulance were abstracted for demographic data, type of insurance, chief complaint, medical interventions, discharge diagnosis, and disposition. Ambulance transportation was deemed unnecessary unless the medical record revealed any of the following criteria: 1) requiring cardiopulmonary resuscitation, 2) respiratory distress, 3) altered mental status or seizure, 4) immobilization, 5) inability to walk, 6) admission to intensive care, 7) ambulance recommended by medical personnel, 8) motor vehicle collision, or 9) parents not on scene. RESULTS: 43% of the ambulance patients were insured by Medicaid, compared with 29% of the overall ED population. Thus, Medicaid patients were significantly more likely to use ambulance transportation than were patients with commercial insurance (p<0.001). 28% of patients who arrived by ambulance were judged to have used the ambulance transportation unnecessarily. Of the unnecessary transports, 60% were insured by Medicaid. Thus, Medicaid patients were significantly more likely to have used ambulance transportation unnecessarily (p<0.001). The most common reason for appropriate ambulance use was seizure activity; the most common reason for inappropriate use was fever. CONCLUSION: Inappropriate use of ambulance transportation is common in this pediatric population, with Medicaid patients accounting for a significant majority of the misuse.

[Tracheal reconstruction with preserved tracheal homograft--new aspects]. / Trachealrekonstruktion mit konserviertem trachealen Homograft--Neue Aspekte.

BACKGROUND: The treatment of long-segment tracheal stenosis is a biological and surgical problem. The introduction of preserved allografts established new possibilities for functional tracheal reconstruction. PATIENTS AND METHODS: Since 1979 preserved allografts were used in 112 patients (including 20 children) with tracheal stenosis. Increasing knowledge in preservation, surgical treatment and pathohistology were put into practice. RESULTS: Implantation of the preserved allografts into the infrahyoid muscles proved to be advantageous. Preservation with the tutoplast method prevented the risk of viral infection, and led to faster and trouble-free post-operative healing. Pathohistological studies let to improve surgical techniques by increasing the knowledge of the nature of tracheal stenosis. CONCLUSION: Functional tracheal reconstruction for long-segment tracheal stenosis can be achieved by implantation of preserved allografts.

Peritoneal dialysis immediately post transplantation.

Many peritoneal dialysis (PD) patients undergo successful renal transplantation. The outcome is similar to that for transplanted hemodialysis (HD) patients. For delayed graft function, dialysis is necessary in the immediate post-transplant period. PD can be undertaken, with a small risk of peritonitis and other PD-related complications. Delayed graft function is less prevalent in patients who were on PD before transplantation than in those who were on HD. The dialysis modality may have an impact on graft survival. The graft thrombosis rate is unaffected by the prior mode of dialysis. Catheter-related problems are infrequent, but there must be a low threshold for catheter removal for any sign of non response to therapy for peritonitis or for exit-site and tunnel infections. PD can be undertaken successfully in the immediate post-transplant period.

[D-xylose test of resorption as a method to determine radiation side effects in the small intestine]. / D-Xylose-Resorptionstest als Methode zur Erfassung der Strahlenreaktion des Darms.

BACKGROUND: The D-xylose test is the most important method to determine a disorder of carbohydrates resorption in proximal small intestine. The application is based on an impaired resorption due to pathological change of small intestine surface, leading to a decreased blood level or decreased excretion in urine. PATIENTS AND METHOD: D-xylose test was applied in 91 patients before, shortly after, 1/2 and 1 year after radiotherapy. All patients received an abdominal radiotherapy. We determined the blood level of D-xylose by a capillary blood sample 1 hour after oral D-xylose administration. RESULTS: A significant decrease of the mean blood level of D-xylose to 1.88 mmol/l was determined after radiotherapy in comparison with 2.17 mmol/l before radiotherapy. Half a year after radiotherapy the mean blood level of D-xylose returned to normal. Regarding a threshold value of D-xylose blood level of 1.70 mmol/l 29 patients (32%) showed a pathologically decreased D-xylose resorption after radiotherapy. Twenty out of the 29 patients already showed a normal resorption half a year after the determination of the resorption disorder, 5 patients after 1 year and 4 patients after 1 1/2 years. There was no correlation between the detection of a disorder of D-xylose resorption and of a loss of body weight. The acute clinical side effects seemed to be more marked in connection with a disorder of D-xylose resorption, but this correlation is not significant. Eleven or 14 of the 29 patients, respectively, with pathologically decreased D-xylose resorption only had complaints of lower or upper gastrointestinal tract, respectively, and 10 patients did not have abdominal complaints at all. CONCLUSIONS: The D-xylose test is an important and simple method for determination of radiogen induced carbohydrate malabsorption in proximal small intestine. By means of it radiation side effects on small intestine can also be determined in patients who are otherwise free of complaints.

[Radiation effects in the left kidney after irradiation of the spleen]. / Strahlenfolgen an der linken Niere nach Milzbestrahlung.

BACKGROUND: An important component of treatment of malignant lymphoma is the radiotherapy. If the spleen has to be included in the irradiation field, the left kidney has to be considered as a risk organ. PATIENTS AND METHOD: In 25 patients, splenic pedicle or spleen was included in the irradiation field. These patients were followed up at 6-monthly intervals clinically and by renal scintigram. For 21 out of 25 patients, a volume-dose-histogram of the kidneys was made. RESULTS: A decreased uptake of activity by the left kidney was found in the static renal scintigram of 13 out of the 25 patients and was seen 6 months to 1 year after radiotherapy for the first time at a moderate intensity. The decreased uptake improved in 1 patient, but was progressive in 8 patients until a storage defect or a shrinking of the whole left kidney appeared. The volume-dose-histogram showed that a decreased uptake was seen in the upper half or whole left kidney respectively if at least 40% of the volume or the whole organ was irradiated with at least 20 Gy. 40% of the volume of the left kidney were exposed to at least 20 Gy in only for 3 out of the 12 patients with no decreased uptake. By means of the renal sequence scintigram a reduced function of the left kidney was determined for 11 out of 13 patients. The functional contribution of the left kidney deteriorated to 16 to 37% of the total function of the 2 kidneys. One patient developed a hypertension 1 1/2 years after radiotherapy; all other patients showed no clinical symptoms. Retention of substances in blood was not observed. CONCLUSIONS: The static renal scintigram enables defined radiation-induced lesions of parenchyma of the left kidney to be determined after irradiation of the splenic pedicle or spleen. The changes are predominantly subclinical but possible long-term effects are unknown. In the treatment planning all possibilities should be used to minimize the irradiation volume of the left kidney. Furthermore, all patients should be followed up at regular intervals on a long-term basis.

Effect of number of blood cultures and volume of blood on detection of bacteremia in children.

OBJECTIVE: To determine whether bacteremia can be detected more rapidly and completely by (1) obtaining two blood cultures instead of one and/or (2) collecting a larger volume of blood. STUDY DESIGN: Prospective comparison of different strategies in 300 patients undergoing blood culture for suspected bacteremia. Each patient had two samples of blood, A (2 ml) and B (9.5 ml), obtained sequentially from separate sites. The B sample was divided into three aliquots: B1 (2 ml), B2 (6 ml), and ISO (1.5 ml, quantitative culture). RESULTS: A pathogen was isolated from one or more blood cultures in 30 patients (10% of cases). When measured at 24 hours, the pathogen recovery rate for the B2 sample (72%) was higher than that for the individual small-volume samples (A = 37%, B1 = 33%; p < 0.01 for each comparison) and for the combination of the two small-volume samples (A + B1 = 47%; p = 0.04). At final (7-day) reading the pathogen recovery rate for the B2 sample (83%) was higher than that for B1 (60%; p = 0.02) and similar to the recovery rate observed with the combination of the two small-volume cultures (A + B1 = 73%; p = 0.55). CONCLUSIONS: Increasing the volume of blood inoculated into blood culture bottles improves the timely detection of bacteremia in pediatric patients and spares the patients the cost and pain of an additional venipuncture.

Coordinate regulation of tubulin and microtubule associated protein genes during development of hamster brain.

The present study documents the patterns of mRNA expression for 5 different tubulin genes and 4 of the structural microtubule-associated protein (MAP) genes during normal development of hamster forebrain. Northern blotting in conjunction with densitometric analysis was used to study changes in the levels of the mRNAs for alpha 1-tubulin, classes beta I-, beta II-, beta III- and beta IV-tubulin, as well as the mRNAs for tau, MAP1A, MAP1B and MAP2, using total RNA isolated from hamster forebrain at various embryonic (E) and postnatal (P) stages. Densitometric analyses of the autoradiograms from the Northern blots revealed that each of the tubulin genes exhibited distinct developmental patterns of expression, several of which appeared to be temporally correlated with the expression of specific MAP mRNAs. The beta I-, beta II- and beta III-tubulin mRNAs increased rapidly between late embryonic stages to birth, reached peak levels early in the first postnatal week, and declined thereafter. alpha 1-Tubulin mRNA was easily detected during embryonic stages, rose to peak levels at P7-P9 and then gradually declined. A similar pattern was seen for tau mRNA. After the first postnatal week, the size of the tau mRNA also shifted to a slightly larger size, presumably due to differential splicing. beta IV-Tubulin mRNA levels did not become significant until very late in postnatal development (3-4 weeks). MAP2 mRNA expression was unusual in that peak levels were reached at two different stages of development--an initial peak occurred in the first postnatal week, followed by a decline, and then a second rise occurred during the third and fourth postnatal weeks. The expression of the beta IV-tubulin mRNA coincided temporally with the second peak in MAP2 mRNA expression. MAP1B mRNA abruptly reached high levels at birth, remained abundant during the first two postnatal weeks, and then decreased. In contrast, MAP1A mRNA levels were low in the initial postnatal interval and increased only at very late developmental stages. The findings of a temporal correspondence in expression of high levels of tau and MAP1B with beta I-, beta II-, beta III- and alpha 1-tubulin mRNAs suggest that this profile of gene expression is one that endows greater plasticity to the neuronal cytoskeleton. Conversely, the transition to increased expression of beta IV-tubulin, MAP1A, and a larger tau mRNA species defines a portion of the molecular pattern that underpins the increased stability of neuronal form during maturation.

Utility of routine laboratory testing for detecting intra-abdominal injury in the pediatric trauma patient.

OBJECTIVE: To assess the prevalence of laboratory abnormalities (complete blood cell count, electrolytes, blood urea nitrogen, creatinine, glucose, aspartate aminotransferase, alanine aminotransferase, amylase, lipase, urinalysis [U/A]) and the sensitivity and specificity of the physical examination (PE) and screening laboratory tests for identifying intra-abdominal injury (IAI) in moderately injured pediatric patients. DESIGN, PARTICIPANTS, AND SETTING: Phase I: Retrospective chart review of 285 consecutive level II (moderately injured) trauma patients seen at a children's hospital emergency department/pediatric trauma center. All patients were received directly from the scene and had the following data recorded: mechanism of injury, Glasgow coma score, trauma score, pediatric trauma score, systematically recorded PE findings, laboratory results, and injuries detected during hospitalization. Phase II: To confirm the sensitivity of the PE and U/A found in phase I, the model was applied to 91 additional trauma patients identified by International Classification of Diseases, 9th revision (ICD-9) codes as having IAI. INTERVENTION: None. RESULTS: Phase I: A total of 3939 tests were ordered for the 285 patients entered in phase I. Aspartate aminotransferase and alanine aminotransferase values were obtained in 59% of patients; glucose level was obtained in 78% of patients; complete blood cell count, U/A, and levels of electrolytes, blood urea nitrogen, creatinine, amylase, and lipase were obtained in more than 85% of patients. The overall prevalence of laboratory abnormalities was 5.7%. Fourteen patients (4.8%) were identified who had a total of 23 significant IAIs (9 pancreatic, 6 splenic, 5 renal, 3 hepatic). The PE combined with U/A showing more than five red blood cells per high-power field had a sensitivity of 100%, specificity of 64%, positive predictive value of 13%, and negative predictive value of 100% for the detection of IAI. The presence of laboratory abnormalities suggesting injury did not increase the sensitivity of the model and significantly decreased both specificity and positive predictive value. Phase II: The PE combined with U/A identified an abnormality in 89 (97.8%) of 91 cases (95% confidence interval = 94.8% to 100%). CONCLUSIONS: In the moderately injured pediatric trauma patient, (1) there is a low prevalence of laboratory abnormalities; (2) the PE combined with U/A is a highly sensitive screen for IAI; and (3) in patients with a normal PE of the abdomen and a normal U/A, laboratory testing seldom identifies unsuspected IAI.