Cross-sectional follow-up of voice outcomes in children who have a history of airway reconstruction surgery.

OBJECTIVES: This study reports vocal function in a cross-section of children with subglottic stenosis. Each child had a history of laryngotracheal reconstruction and/or cricotracheal resection surgery. Vocal function was measured using laryngoscopy, acoustic analysis, perceptual evaluation and impact of voice on quality of life. DESIGN: All patients aged >5 years with history of laryngotracheal reconstruction and/or cricotracheal resection surgery at the Scottish National Complex Airways service were invited to participate. SETTING: Data were gathered in the Royal Hospital for Children in Glasgow in a single outpatient appointment. PARTICIPANTS: Twelve of 56 former patients (aged 5-27) provided a voice sample and eleven consented to awake laryngoscopy. All consented for detailed evaluation of their medical records. MAIN OUTCOME MEASURES: Acoustic analysis of fundamental frequency and pitch perturbation was conducted on sustained vowel [a]. Perceptual evaluation was conducted by 4 trained listeners on a series of spoken sentences. Impact on quality of life was measured using the paediatric voice-related quality of life questionnaire. Laryngeal function was descriptively evaluated. RESULTS: Four children had normal voice acoustically, perceptually and in relation to voice-related quality of life. One of these had vocal fold nodules unrelated to surgical history. Two other children had "near normal" vocal function, defined where most voice measurements fell within the normal range. CONCLUSIONS: Normal or "near normal" voice is a possible outcome for children who have had this surgery. Where there is an ongoing complex medical condition, voice outcome may be poorer.

Medial Occipital Lobe Hyperperfusion Identified by Arterial Spin-Labeling: A Poor Prognostic Sign in Patients with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy carries an uncertain prognosis. We sought to retrospectively assess the prognostic value of arterial spin-labeling MR imaging in 22 adult patients diagnosed with hypoxic-ischemic encephalopathy. Quantitative CBF maps were generated from the M0 map, and arterial spin-labeling data on a per-voxel basis were regionally interrogated via visual inspection and ROI placement. Hyperperfusion was defined as regional increases in CBF of >20% (relative to global CBF) and/or >100 mL/100 g/min. Eleven of 22 patients had prominent bilateral medial occipital lobe hyperperfusion, all of whom died before hospital discharge. One patient who had nondistinct arterial spin-labeling hyperperfusion and restricted diffusion survived. Medial occipital lobe hyperperfusion is a distinctive pattern that merits prospective investigation in a cohort of patients with moderate hypoxic-ischemic encephalopathy to determine its predictive ability in patients with a higher likelihood of survival.

Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model.

BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an individual from a family with inherited thrombophilia is of major importance, it is often not feasible. OBJECTIVES: To develop a simple risk assessment model that improves prediction of the risk of VT for individuals of families with inherited thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited thrombophilia (deficiencies of antithrombin, protein C or protein S, and the factor V Leiden and F2 20210A mutations) were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and twenty-two individuals had a personal history of VT. Sixteen preselected clinical and laboratory variables were used to derive the VT risk score. RESULTS: The scores based on the 16 variables and on the five most strongly associated variables performed similarly (areas under receiver operating characteristic curves of 0.85 and 0.83, respectively). For the five-variable score, named the MARNI score, derived from family history score of VT, von Willebrand factor antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for individuals with a score of ≥ 7 (n = 27). The model was validated with an internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system, assessment of the risk of VT in subjects from families with inherited thrombophilia can be greatly improved. External validation is now needed to replicate these findings.

Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model.

BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an individual from a family with inherited thrombophilia is of major importance, it is often not feasible. OBJECTIVES: To develop a simple risk assessment model that improves prediction of the risk of VT for individuals of families with inherited thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited thrombophilia (deficiencies of antithrombin, protein C or protein S, and the factor V Leiden and F2 20210A mutations) were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and twenty-two individuals had a personal history of VT. Sixteen preselected clinical and laboratory variables were used to derive the VT risk score. RESULTS: The scores based on the 16 variables and on the five most strongly associated variables performed similarly (areas under receiver operating characteristic curves of 0.85 and 0.83, respectively). For the five-variable score, named the MARNI score, derived from family history score of VT, von Willebrand factor antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for individuals with a score of ≥ 7 (n = 27). The model was validated with an internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system, assessment of the risk of VT in subjects from families with inherited thrombophilia can be greatly improved. External validation is now needed to replicate these findings.

Maternal separation produces, and a second separation enhances, core temperature and passive behavioral responses in guinea pig pups.

During separation in a novel cage, guinea pig pups exhibit passive behavior that appears due to increased proinflammatory activity. To determine if separation also produces a febrile response, the present study used telemetry to provide continuous core temperature measurement of pups exposed to a novel cage for 3h while either alone or with their mother on two consecutive days. Separation from the mother increased core temperature, with the clearest effects occurring early during separation the second day. The increased temperature was not associated with an increase in locomotor activity. Further, passive behavior during isolation exhibited pronounced sensitization from the first to second day of separation. These results show that separation produces an increase in core temperature in our testing situation, and suggest that this increase represents true fever. The findings also provide further support for the hypothesis that maternal separation induces aspects of an acute phase response in guinea pig pups. The potential role of proinflammatory activity in promoting change across days in temperature and behavior is discussed.

The end of a myth: cloning and characterization of the ovine melatonin MT(2) receptor.

BACKGROUND AND PURPOSE: For many years, it was suspected that sheep expressed only one melatonin receptor (closely resembling MT(1) from other mammal species). Here we report the cloning of another melatonin receptor, MT(2), from sheep. EXPERIMENTAL APPROACH: Using a thermo-resistant reverse transcriptase and polymerase chain reaction primer set homologous to the bovine MT(2) mRNA sequence, we have cloned and characterized MT(2) receptors from sheep retina. KEY RESULTS: The ovine MT(2) receptor presents 96%, 72% and 67% identity with cattle, human and rat respectively. This MT(2) receptor stably expressed in CHO-K1 cells showed high-affinity 2[(125)I]-iodomelatonin binding (K(D)= 0.04 nM). The rank order of inhibition of 2[(125)I]-iodomelatonin binding by melatonin, 4-phenyl-2-propionamidotetralin and luzindole was similar to that exhibited by MT(2) receptors of other species (melatonin > 4-phenyl-2-propionamidotetralin > luzindole). However, its pharmacological profile was closer to that of rat, rather than human MT(2) receptors. Functionally, the ovine MT(2) receptors were coupled to G(i) proteins leading to inhibition of adenylyl cyclase, as the other melatonin receptors. In sheep brain, MT(2) mRNA was expressed in pars tuberalis, choroid plexus and retina, and moderately in mammillary bodies. Real-time polymerase chain reaction showed that in sheep pars tuberalis, premammillary hypothalamus and mammillary bodies, the temporal pattern of expression of MT(1) and MT(2) mRNA was not parallel in the three tissues. CONCLUSION AND IMPLICATIONS: Co-expression of MT(1) and MT(2) receptors in all analysed sheep brain tissues suggests that MT(2) receptors may participate in melatonin regulation of seasonal anovulatory activity in ewes by modulating MT(1) receptor action.

Labour characteristics and neonatal Erb's palsy.

OBJECTIVE: To determine risk factors for Erb's palsy, with a focus on graphic labour patterns. DESIGN: A case-control study. SETTING: New York City. SAMPLE: A total of 45 consecutive cases of Erb's palsy and 90 controls. METHODS: Pregnancies and labours of neonatal Erb's palsy cases were compared with 90 controls using univariate and multiple logistic regression analysis. MAIN OUTCOME MEASURES: Erb's palsy and shoulder dystocia. RESULTS: Mothers of children with Erb's palsy had a higher term body mass index and more gestational diabetes than those of controls. Even cases without diabetes had higher blood glucose values after a 50-g glucose challenge than did controls. Cases had a higher birthweight and a lower ratio of head-to-thoracic circumference than controls. Shoulder dystocia occurred in 67% of cases and in 2% of controls (P = 0.001). Only 46% of labours had a completely normal dilatation pattern. In a multiple logistic regression model, variables independently associated with brachial plexus injury were long deceleration phase of labour, long second stage, high birthweight, black race, and high neonatal or maternal body mass. CONCLUSIONS: Erb's palsy was frequently preceded by abnormal labour and shoulder dystocia; however, a substantial proportion of cases occurred after normal labour and delivery. Predictive models will be necessary to determine to what extent careful monitoring of the terminal portion of dilatation and of fetal descent and incorporation of maternal body mass and race (all independent risk factors in this study) will help identify fetuses at risk for brachial plexus palsy.

Correlation of MR imaging findings with intraoperative findings after cervical spine trauma.

BACKGROUND AND PURPOSE: There are limited data correlating MR imaging and anatomic findings of ligamentous injury in cervical spine trauma. This study compares acute MR imaging with surgical observations of disk/ligamentous injury after blunt cervical trauma. MATERIALS AND METHODS: Consecutive patients with acute cervical spine trauma who underwent preoperative MR imaging and surgery from 1998 to 2001 were identified. MR imaging was obtained within 48 hours of injury for most patients. All scans included sagittal T1, T2 fat-saturated, and short tau inversion recovery sequences. At surgery, extent of injury at the operated level was recorded on a standardized form for either anterior or posterior structures or both depending upon the operative approach. MR examinations were separately evaluated by 2 readers blinded to the intraoperative findings. Radiologic and surgical findings were then correlated. RESULTS: Of 31 patients, an anterior surgical approach was chosen in 17 patients and a posterior approach in 13 patients. In one patient anterior and posterior approaches were utilized. Seventy-one percent of patients had spinal cord injury on MR imaging. MR imaging was highly sensitive for injury to disk (93%), posterior longitudinal ligament (93%), and interspinous soft tissues (100%), but it was less sensitive for injury to the anterior longitudinal ligament (71%) and ligamentum flavum (67%). For most ligamentous structures, there was limited agreement between specific MR imaging findings and injury at surgery. CONCLUSION: In acute cervical spine trauma, MR imaging has moderate to high sensitivity for injury to specific ligamentous structures but limited agreement between specific MR imaging findings and injury at surgery. MR imaging may overestimate the extent of disruptive injury when compared with intraoperative findings, with potential clinical consequences.

Study of antigen-processing steps reveals preferences explaining differential biological outcomes of two HLA-A2-restricted immunodominant epitopes from human immunodeficiency virus type 1.

Cytotoxic T-lymphocyte (CTL) responses directed to different human immunodeficiency virus (HIV) epitopes vary in their protective efficacy. In particular, HIV-infected cells are much more sensitive to lysis by anti-Gag/p17(77-85)/HLA-A2 than to that by anti-polymerase/RT(476-484)/HLA-A2 CTL, because of a higher density of p17(77-85) complexes. This report describes multiple processing steps favoring the generation of p17(77-85) complexes: (i) the exact COOH-terminal cleavage of epitopes by cellular proteases occurred faster and more frequently for p17(77-85) than for RT(476-484), and (ii) the binding efficiency of the transporter associated with antigen processing was greater for p17(77-85) precursors than for the RT(476-484) epitope. Surprisingly, these peptides, which differed markedly in their antigenicity, displayed qualitatively and quantitatively similar immunogenicity, suggesting differences in the mechanisms governing these phenomena. Here, we discuss the mechanisms responsible for such differences.

In vitro morphogenesis of amphibian erythroblasts.

Non-mammalian vertebrate erythrocytes are flattened nucleated ellipsoids containing marginal bands (MBs) of microtubules that assemble during cellular morphogenesis. Earlier work suggested that pointed erythroid cells containing pointed MBs were intermediate stages in terminal differentiation, rather than aberrant forms, but direct evidence was lacking. Here we report on morphogenesis in individual post-cytokinetic amphibian erythroblasts in culture. Daughter cells remained adjacent in pairs, and developed pointed morphology over 1-2 h in the following sequence: (a) ends opposite the cytokinetic furrow became pointed, producing a spheroidal singly-pointed stage; (b) furrow ends usually became pointed, yielding doubly-pointed cells; (c) furrow-end points disappeared, producing a second singly-pointed stage that was flattening. Over a longer term, the single points sometimes disappeared, yielding a flattened discoid. These observations support the hypothesis that pointed cells are normal intermediates in a biogenetic program in which post-mitotic centrosomes organize MBs while occupying the singly-pointed ends of differentiating erythroblasts.

Intra-arterial urokinase for acute ischemic stroke: factors associated with complications.

The authors abstracted the records of 43 patients treated with intra-arterial urokinase for acute ischemic stroke to identify predictors of serious complications. Sixteen (37%) had such a complication. Higher urokinase dose (>1.5 x 10(6) U), higher mean arterial blood pressure before treatment (>130 mm Hg), basilar occlusive strokes, and severe strokes were most predictive of these complications. Although urokinase is no longer manufactured, these findings identify patients at risk for complications from other intra-arterial thrombolytics.

Growth hormone treatment after cesarean delivery in rats increases the strength of the uterine scar.

OBJECTIVE: We sought to determine whether postcesarean treatment of rats with growth hormone (GH) affected the strength of the uterine incision in the puerperium and in a subsequent pregnancy. STUDY DESIGN: Forty-eight near-term pregnant rats were delivered by cesarean section. Half received subcutaneous recombinant human GH (2.0 mg x kg(-1) x d(-1)) for 7 days; control animals received saline injections. Four weeks after delivery, the uterine bursting pressure was determined in 5 treated and 5 control animals. Eight rats in each group were used to study uterine hydroxyproline concentrations and the histologic characteristics of the scar. Twenty-two animals were rebred 30 to 40 days after their cesarean sections. After repeat cesarean delivery, on day 19, the bursting pressure and hydroxyproline concentrations of the previous hysterotomy scar were determined. RESULTS: The uterine horn bursting pressure in the GH-treated animals was significantly greater than that in the control animals both 28 days postpartum and near term in a subsequent pregnancy. The uterine hydroxyproline concentrations followed the same pattern. Histologic study of the scars showed they were thicker and had less cellularity in the treated animals than in the control animals. CONCLUSION: Postcesarean treatment with GH increased the bursting strength of rat uterine incisions. This effect was accompanied by a significant increase in collagen content and persisted through a subsequent pregnancy.

Characteristics of HIV-1 Nef regions containing multiple CD8+ T cell epitopes: wealth of HLA-binding motifs and sensitivity to proteasome degradation.

First and foremost among the many factors that influence epitope presentation are the degradation of Ag, which results in peptide liberation, and the presence of HLA class I molecules able to present the peptides to T lymphocytes. To define the regions of HIV-1 Nef that can provide multiple T cell epitopes, we analyzed the Nef sequence and determined that there are 73 peptides containing 81 HLA-binding motifs. We tested the binding of these peptides to six common HLA molecules (HLA-A2, -A3, -A24, -B7, -B8, and -B35), and we showed that most of them were efficient binders (54% of motifs), especially peptides associating with HLA-A3, -B7/35, and -B8 molecules. Nef peptides most frequently recognized by T cells of HIV-1-infected individuals were 90-97, 135-143, 71-81, 77-85, 90-100, 73-82, and 128-137. The frequency of T cell recognition was not directly related to the strength of peptide-HLA binding. The generation of Nef epitopes is crucial; therefore, we investigated the digestion by the 20S proteasome of a large peptide, Nef(66-100). This fragment was efficiently cleaved, and NH(2)-terminally extended precursors of epitope 71-81 were recognized by T cells of an HIV-1-infected individual. These results suggest that a high frequency of T cell recognition may depend on proteasome cleavage.

Caring for children with Down syndrome and their families.

The overall purpose of this article is to provide pediatric nurses with the knowledge and motivation necessary to implement best clinical practice with children who have Down syndrome and their families. First, changes that have occurred in the care of children with Down syndrome are briefly reviewed. Next, recommendations concerning best clinical practice for children with Down syndrome are presented. Finally, implications for pediatric nurses practicing in an expanded role are discussed.

Arteriovenous fistula construction in the thigh with transposed superficial femoral vein: our initial experience.

PURPOSE: The National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines favor autogenous vein for arteriovenous fistulas (AVFs). This report describes our experience constructing AVFs in the lower extremities of selected patients with the superficial femoral vein (SFV). PATIENTS AND METHODS: This is a retrospective analysis of 25 patients who had AVF construction with SFV from March 1998 to July 2000. In all patients upper extremity access had been exhausted. Eighteen (72%) patients were female, 15 (60%) had diabetes, and 14 (56%) were obese (body mass index > 30 kg/m(2)). The SFV was freed from the supragenicular popliteal level to the profunda femoris vein and divided distally. Eighteen (72%) patients had SFV transposition and distal superficial femoral artery reimplantation; 10 veins were banded to reduce the incidence of postoperative steal syndrome. In seven patients (28%) a composite loop fistula was constructed with a deeply buried 4- to 7-mm polytetrafluoroethylene (PTFE) graft proximally and with superficially transposed SFV distally. One of these seven patients had a PTFE above-knee femoral-popliteal bypass graft with banding of the vein at its takeoff from the distal PTFE graft. RESULTS: Mean follow-up was 9.1 months. One patient died before the fistula could be used. Seven patients (28%) experienced major wound complications. Mean ankle/brachial index before operation was 1.03, and after operation it was 0.81 (paired difference [n = 16] = -0.26.) Mean ankle circumference before operation was 19.5 cm, and after operation it was 20.7 cm (paired difference [n = 17] = +0.87.) Cumulative primary fistula patency at 6 and 12 months was 78% and 73%, respectively. Cumulative secondary fistula patency at 6 and 12 months was 91% and 86%, respectively. There were no fistula infections. One patient eventually had an above-knee amputation after experiencing an acute compartment syndrome. Eight patients required a second operation to alleviate a symptomatic steal syndrome. CONCLUSIONS: The SFV is an excellent conduit for vascular access, whether it is transposed or is part of a composite PTFE-SFV fistula. In this series, fistula infection was nonexistent, thrombosis rates were low, and clinical evidence of venous hypertension was minimal. The major impediment to unrestricted use of SFV in constructing AVFs is a high incidence of clinically significant postoperative ischemia requiring reoperation.