Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency.

It is commonly accepted that the presence of high amounts of maternal T cells excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We report a SCID patient with a novel mutation in the recombination activating gene (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS. Several assays, including representatives of specific T cell receptors (TCR), Vß families and TCR-γ rearrangements, were performed in order to understand more clearly the nature and origin of the patient's T cells. The patient had oligoclonal T cells which, based on the patient-mother human leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal origin. These cell populations were different in their numbers of regulatory T cells (T(reg)) and the diversity of TCR repertoires. This is the first description of the co-existence of large amounts of clonal expanded autologous and transplacental-acquired maternal T cells in RAG1-deficient SCID.

Contactless respiratory and heart rate monitoring: validation of an innovative tool.

PRIMARY OBJECTIVE: To assess the accuracy of the EverOn™ piezoelectric sensor based contactless heart rate and respiration rate monitoring system. METHODS: Measurements of the EverOn™ and reference devices were performed in a sleep lab and an intensive care unit (ICU) setting. One minute measurements by both the reference device and the EverOn™ were averaged and compared. Accuracy was defined in accordance with industry criteria. RESULTS: Respiration rate (RR) accuracy in the 41 children and 16 adults evaluated in the sleep lab was 93.1% and 90.6% respectively, and heart rate (HR) accuracy was 94.4% and 91.5% respectively. For the 42 ICU patients RR accuracy was 82.0% and 75% (versus end-tidal CO(2) and manual respectively), while accuracy of HR was 94.0%. The EverOn™ was found to be superior to the impedance technique in measuring RR. CONCLUSIONS: The system described was found to be accurate in accordance with regulatory and industry criteria.

Postoperative brain stem tension pneumocephalus causing transient locked-in syndrome.

The incidence of pneumocephalus after supratentorial craniotomy has been reported to be as high as 100%. However, transformation of postoperative pneumocephalus into tension pneumocephalus (symptomatic intracranial air) is a rather rare phenomenon. Tension pneumocephalus after posterior fossa surgery is reported mainly when the surgery is performed in a sitting position. We hereby report on a patient who developed brain-stem tension pneumocephalus in the early postoperative period after posterior fossa craniotomy for an exophytic brainstem astrocytoma, operated in the prone position. A complete locked-in syndrome resolved following surgical relief of the trapped air.

Anion-binding properties of the tripyrrolemethane group: a combined experimental and theoretical study.

Tripyrrolemethane- and bistripyrrolemethane-containing systems were recently reported to be efficient and selective hosts for anions. Nevertheless, the basic intrinsic properties of tripyrrolemethane as a ligand for anions have not yet been explored. Here we report the study of the anion-binding properties of the tripyrrolemethane group. We applied a combined experimental and theoretical approach to determine the affinity of the tripyrrolemethane system for different anions in the gas phase, in solution and in the crystalline state. In the crystal, the tripyrrolemethane group forms a number of different complexes with the bromide ion, some involving the participation of more than one ligand species. Despite the very similar basicity of fluoride and dihydrogen phosphate, the tripyrrolemethane ligand exhibits a clear preference for the fluoride anion in solution, which indicates an anion-binding system and not merely deprotonation. Although the affinity of the tripyrrolemethane ligand for other ions was negligible in solution, gas-phase studies show that complexation with larger halide ions is favoured over complexation with fluoride.

Mediastinal tumors in children: a single institution experience.

Mediastinal masses in children are a heterogeneous group of asymptomatic or potentially life-threatening congenital, infectious, or neoplastic lesions that present complex diagnostic and therapeutic dilemmas. Some patients are asymptomatic; in others, the mass may compress mediastinal structures and cause sudden asphyxia. In these cases, close cooperation is needed among pediatric surgeons, anesthesiologists, intensivists, oncologists, and radiologists. The files of 45 children with mediastinal masses admitted between 1986 and 1999 to the Pediatric Intensive Care Unit (PICU) of Schneider Children's Medical Center of Israel were reviewed. Twenty-one were admitted for perioperative care, and 21 for emergency care, including 19 with respiratory distress. Five of the emergency care group had asphyxia and 10 needed assisted ventilation. Two children were admitted for evaluation and 1 for leukopheresis. The children admitted on an emergency basis had more clinical findings than the postoperative group: almost 80% had dyspnea and more than 45% had oxygen desaturation; 33% had cough and noisy breathing, and 25%, superior vena cava syndrome or hepatosplenomegaly. Eight patients (17.8%) had benign disease and 37 (82.2%) malignant disease. The patients with a benign mass were significantly younger than the patients with a malignant mass (p<0.005); in 5 cases (12.5%), a congenital anomaly presented as a mediastinal mass. Most of the malignant masses were of hematologic origin (40.5%), followed by neurogenic tumors (27%). Twenty-seven patients underwent surgery, including 6 emergency procedures (3 partial resections, 2 biopsies, 1 lymph node biopsy). There were no intraoperative or postoperative deaths. The present series emphasizes the complex care children with a mediastinal mass require. They should be treated in a tertiary center with a multidisciplinary approach.

Blood transfusion practice indicated by paediatric intensive care specialists in response to four clinical scenarios.

OBJECTIVE: Several clinical guidelines exist for blood transfusion in adults but only one refers to children. There are no guidelines for blood transfusion in critically ill children and the paediatric intensive care specialist's approach is unknown. We wished to evaluate the approach toward blood transfusion among a group of paediatric intensive care specialists. METHODS: All certified paediatric intensive care specialists from the Israeli society of pediatric intensive care medicine were requested to complete a questionnaire, which described four hypothetical common scenarios in paediatric intensive care units. In each case, the physicians were asked to denote the haemoglobin threshold at which they would prescribe a blood transfusion and the transfusion volume they would use. The specialists were also asked for their reasons for increasing their haemoglobin threshold for blood transfusion. RESULTS: The questionnaire was posted to twenty six paediatric intensive care specialists, twenty one of whom responded (i.e. 80.8%). There was a wide variation for each scenario in both the suggested haemoglobin thresholds for transfusion (varying by 20-50 g/L) and the transfusion volume (varying by 10-20 mL/kg). The reasons given for increasing their blood transfusion threshold included, in order of importance, shock, haemodynamic instability and hypoxaemia. CONCLUSIONS: There is a marked variability among paediatric intensive care specialists regarding both the threshold haemoglobin level at which blood transfusion is prescribed as well as the volume used.

Benign occipital epilepsy mimicking a catastrophic intracranial event.

OBJECTIVE: To describe the rare, dramatic, presentation of benign occipital epilepsy. METHODS: We describe three children who presented to the pediatric emergency department from 1992 to 1996 with a clinical picture of catastrophic intracranial event. RESULTS: The main signs and symptoms were loss of consciousness in all patients, apnea in two, hemiclonus in two, general hypertonicity in two, eye deviation in two, fixed dilated pupils in one, and decorticate rigidity in two. All underwent emergency intubation, brain scan, and lumbar puncture, and all were treated with antibiotics, in addition to antiviral drugs in two. Two patients were also treated for suspected increased intracranial pressure. Two patients recovered within a few hours and one within 24 hours of admission without any residual neurologic deficit. Electroencephalograms, done within 48 hours after the event, revealed the classic pattern of occipital epilepsy in two patients and bilateral occipital slow wave in one. A 3- to 5-year clinical and electroencephalographic follow-up supported the diagnosis. CONCLUSION: Benign occipital epilepsy in children can mimic a catastrophic intracranial event. Electroencephalography, performed early in the Pediatric Intensive Care Unit, may avoid or shorten unnecessary and aggressive treatments such as hyperventilation, diuretic agents, and prolonged antiviral therapy.

Acute diaphragmatic paralysis caused by chest-tube trauma to phrenic nerve.

A 3 1/2-year-old child developed unilateral diaphragmatic paralysis after chest drain insertion. Plain chest X-ray demonstrated paravertebral positioning of the chest-tube tip, and magnetic resonance imaging revealed hematomas in the region of the chest-tube tip and the phrenic nerve fibers. The trauma to the phrenic nerve was apparently secondary to malposition of the chest tube. This is a rare complication and has been reported mainly in neonates. Radiologists should notify the treating physicians that the correct position of a chest drain tip is at least 2 cm distant from the vertebrae.

Accidental busulfan overdose: enhanced drug clearance with hemodialysis in a child with Wiskott-Aldrich syndrome.

A 4.6 kg infant with Wiskott-Aldrich syndrome received an accidental overdose of busulfan during preparation for allogeneic stem cell transplantation. Pharmacokinetic analysis of plasma busulfan levels alerted staff to the dosing error. Hemodialysis was immediately performed and resulted in accelerated clearance of busulfan. There were no acute neurologic and hepatic side-effects of the busulfan overdose, and despite 2 months of cough accompanied by rales, the patient is now free of pulmonary symptoms. Stable partial donor chimerism occurred after transplantation. At present, the patient is thriving and infection-free 12 months after transplantation, although his platelet count remains at the lower limit of normal.

Yield of bronchoalveolar lavage in ventilated and non-ventilated children after bone marrow transplantation.

A study was undertaken to retrospectively evaluate the yield of bronchoalveolar lavage (BAL) in a single-institution series of children after bone marrow transplantation (BMT) and to compare the yield of BAL between the ventilated and nonventilated patients. We reviewed charts of 52 consecutive children after BMT who underwent BAL. Thirty patients (41 BALs) were nonventilated (group 1) and 33 patients (45 BALs) were ventilated for respiratory failure (group 2). Eleven patients were included in both groups. BAL was performed a median of 255 and 28.5 days after BMT in groups 1 and 2, respectively (P < 0.001). Group 1:17 pathogens were isolated from 13 BALs; a single pathogen from 10 BALs. Group 2:15 pathogens were isolated from 14 BALs (31.1% positive). Viruses were isolated from 13 BALs in group 2. A severe complication of BAL occurred in only one patient from group 1 (1.1%). Open lung biopsies were performed in one patient in group 1 and eight patients in group 2. The histological findings correlated with the BAL findings in 66.7%. In conclusion, there was no difference in the yield of BAL between the groups. Therapy was changed in one third of the patients dictated by the BAL findings. The risk of severe complications was relatively low. A good correlation between open lung biopsy (OLB) and BAL was found.

Cytokine response during hyperoxia: sequential production of pulmonary tumor necrosis factor and interleukin-6 in neonatal rats.

BACKGROUND: Exposure of newborn animals to high concentrations of oxygen leads to diffuse alveolar damage similar to that seen in bronchopulmonary dysplasia in human infants. Therefore, neonatal rats are a suitable practical model of hyperoxic lung damage in human infants. OBJECTIVE: To determine the involvement of tumor necrosis factor-alpha and interleukin-6 in lung injury in neonatal rats exposed to 100% O2 concentration. METHODS: A randomized controlled study was designed in which litters of term Sprague-Dawley rat pups were assigned to experimental or control groups. The pups in the experimental group were placed in 100% O2 from birth for 9 days, while the control pups were placed in room air. Twelve to 15 pups from each group were sacrificed on day 1, 3, 6, 9 and 13 after birth for bronchoalveolar lavage collection and lung histologic study. The bronchoalveolar lavage fluid was assayed for TNF alpha and IL-6. RESULTS: Newborn rats exposed to 100% O2 for the first 9 days of life showed severe pulmonary edema and hypercellularity on days 1 and 3, which then improved to nearly complete resolution on days 6 and 9. Pulmonary TNF alpha was produced early on O2 exposure (day 3) and pulmonary IL-6 later (days 6 and 9). CONCLUSIONS: Hyperoxia induces sequential production of pulmonary TNF alpha and IL-6, which corresponds to the severity of the pathological findings and the known inflammatory and anti-inflammatory role of these cytokines.

Superantigens and cystic fibrosis: resistance of presenting cells to dexamethasone.

Staphylococcus aureus, a common pulmonary pathogen in cystic fibrosis (CF), produces exotoxins that are extremely potent superantigens. A number of animal studies have shown that superantigens cause pulmonary inflammation, but the possible role of superantigens in CF has not been investigated. The present study assessed possible differences between control and CF B cells in presenting superantigens to T cells. Immortalized B-cell lines were used as superantigen-presenting cells to avoid environmental influences (e.g., infection or antibiotics) common to freshly isolated cells. The results show that CF B-cell lines presented a staphylococcal superantigen to the immortalized T-cell line (Jurkat) as effectively as did control B-cell lines as measured by interleukin-2 production. However, in contrast to the case for control B-cell lines, dexamethasone did not inhibit CF B-cell lines from presenting superantigen. The resistance of superantigen-presenting CF B cells to corticosteroids suggests that the pulmonary response to superantigens may be poorly regulated in CF, leading to an exaggerated inflammatory response to S. aureus.

Hemophagocytic lymphohistiocytic syndrome: Unrecognized cause of multiple organ failure.

OBJECTIVE: To describe an often-unrecognized clinical picture of multiple organ failure in hemophagocytic lymphohistiocytic syndrome (HLS). DESIGN: Retrospective chart review. SETTING: A ten-bed pediatric intensive care unit (PICU) in a tertiary children's university hospital. PATIENTS: A total of 11 children (age, 5 months to 13 yrs) who fulfilled the criteria for the diagnosis of familial- or infectious-associated hemophagocytic lymphohistiocytosis and who required intensive care support for organ failure. INTERVENTION: None. MAIN RESULTS: During a 10-yr period, 5,439 children were hospitalized in our PICU. A total of 11 children were diagnosed as suffering with HLS. Of these 11 patients, three (27%) had the familial form and eight had the infectious-associated form. After admission to the PICU, seven patients (63%) were diagnosed as suffering with HLS and each had one or more organ failures (patients 3-7, 9, and 10). All presented with fever, hepatomegaly, and splenomegaly; in addition, all had at least two of the following: anemia, neutropenia, or thrombocytopenia. All 11 had lymphohistiocytic accumulation in bone marrow (n = 10), lymph node (n = 2), lung (n = 2), and/or liver (n = 1). Organ failure was noted most often in the respiratory system (n = 7) attributable to severe, acute respiratory distress syndrome and pleural effusion. Of the 11 patients, six had cardiovascular involvement that manifested as shock in three and as capillary leak syndrome in three. Renal failure occurred in four patients. Of these, two required hemodiafiltration and one required peritoneal dialysis. Liver failure occurred in three and central nervous system involvement and coma in three. Most of the patients required massive therapeutic intervention, including assisted ventilation (n = 6), inotropic support (n = 3), and hemofiltration (n = 3). A total of seven patients (63%) died. CONCLUSIONS: Hemophagocytic lymphohistiocytic syndrome in the pediatric population may have a dramatic clinical picture, with multiple organ failure as a presenting symptom or early in the disease course, mandating intensive support in the PICU.

Open lung biopsy--successful diagnostic tool with therapeutic implication in the critically ill paediatric population.

Open lung biopsy (OLB) is an important diagnostic tool in children with immune deficiency and/or chronic lung disease with diffuse pulmonary compromise. These patients require a tailored therapeutic approach owing to their fragile status and the side effects of unnecessary or inadequate treatment. Twenty-six patients of mean age 5.6 y underwent 41 open lung biopsies in our centre between 1991 and 1995. Seventeen (65%) were immunocompromised (including 13 with malignancy) and 9 had other lung diseases. The biopsies were diagnostic in 25 patients (96%), and complete clinical-pathological correlation was found in 11 (42%). A specific infectious aetiology was detected in nine patients (35%), all of them immunocompromised. Therapeutic changes were instituted on the basis of the biopsy findings in 18 patients (69%). Two patients had postoperative complications (prolonged pleural leak). We conclude that OLB is a safe diagnostic procedure even in the critically ill child and should be employed without hesitation when conventional methods fail to provide a definitive diagnosis to help redirect therapy.

Prolonged croup due to herpes simplex virus infection.

UNLABELLED: Herpes simplex virus (HSV) is an uncommon cause of acute laryngitis in immunocompetent patients since it mostly occurs in immunocompromised subjects. We present two previously healthy children with prolonged gingivostomatitis and stridor (lasting 3 and 4 weeks) in whom HSV-1 was isolated from subglottal ulcers. CONCLUSION: HSV should be considered a possible pathogen in cases of prolonged or atypical croup not only in immunocompromised or elderly patients but also in otherwise healthy children.

Interleukin-6 levels in serum and lung lavage fluid of children undergoing open heart surgery correlate with postoperative morbidity.

OBJECTIVE: To evaluate the relationship of perioperative levels of interleukin 6 (IL-6) in serum and bronchoalveolar fluid with morbidity and mortality in children undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective, noninterventional study. SETTING: Operating room and pediatric intensive care unit (PICU) of a university hospital. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: IL-6 levels were measured in serum and lung lavage fluid obtained before, during, and after CPB using the B9.9 bioassay. Alveolar epithelial lining fluid (AELF) volume was calculated using the urea correction method. Mean intraoperative AELF IL-6 levels increased fourfold compared to preoperative levels, and mean serum IL-6 levels increased fivefold after CPB. Mean intraoperative AELF IL-6 levels correlated with intraoperative blood transfusion (r2 = 0.18; p = 0.049) and duration of inotropic support (r2 = 0.29; p = 0.009), mechanical ventilation (r2 = 0.24; p = 0.019), and PICU stay (r2 = 0.29; p = 0.008). Mean serum IL-6 levels 2 h after CPB correlated with intraoperative blood transfusion (r2 = 0.3;p = 0.007), and with Pediatric Risk of Mortality score on postoperative day 3 (r2 = 0.24; p = 0.022), and were higher in patients with massive fluid retention (p = 0.014) and in nonsurvivors (p = 0.003). CONCLUSIONS: Serum and alveolar IL-6 levels increase after CPB, and correlate with postoperative morbidity. Serum IL-6 levels also correlate with mortality. They may be useful in assessing the severity of the systemic inflammatory response after CPB.

Experimental use of raffinose as an osmotic agent for peritoneal dialysis.

Conventional glucose-based solutions for peritoneal dialysis fluids have been shown to raise problems of biocompatibility. We therefore evaluated the ultrafiltration capabilities of raffinose as an alternative osmotic agent in a non-uremic rat model. Animals were divided into four groups and injected intraperitoneally with solutions containing raffinose (4.5%, 345 mOsm/kg; 16.7%, 518 mOsm/kg) or glucose (1.5%, 346 mOsm/kg; 4.25%, 489 mOsm/kg). Data obtained from animals exposed to 16.7% raffinose were excluded because of precipitation of the osmotic agent. Low-osmolality raffinose solution induced higher ultrafiltered volume than the low-osmolality glucose-enriched fluid at 120 minutes of dwelling time. No significant differences were observed in effluent sodium and potassium concentration and protein dialysate-to-plasma (D/P) ratio. The D/P ratio of phosphate was higher in the low-osmolality raffinose-based fluid than in the low-osmolality glucose solution. The osmolality of the solutions was significantly decreased after a dwelling time of 120 minutes. We conclude that 4.5% raffinose is an effective osmotic agent. Total or partial replacement of glucose by raffinose for clinical peritoneal dialysis could be eventually considered after appropriate evaluation of its biocompatibility and general side effects.

Sclerosing encapsulating peritonitis.

Sclerosing encapsulating peritonitis (SEP), idiopathic or secondary, is a form of intraperitoneal fibrosclerosis that causes intestinal obstruction. In the case of a 41-year-old man with dialysis-induced SEP presented here, we show that intraperitoneal hemorrhage may play an important pathogenetic role and that the process may develop in < or = 12 weeks. Regardless of cause, the treatment of obstruction is operative, with dissection of the encasing membrane from the intestine and separation of adherent loops of small bowel until they are laid free and returned to their normal configuration. The prognosis after appropriate operative therapy is good but depends on coexisting diseases.

Ventilatory response to consecutive short hypercapnic challenges in children with obstructive sleep apnea.

In healthy adults, a ventilatory pattern characterized by progressively increased tidal volume (VT), and decreased respiratory rate (RR) accompany repeated short hypercapnic ventilatory challenges, while minute ventilation (VE) remains constant. We hypothesized that the peculiar ventilatory pattern seen in adults would be blunted in children with obstructive sleep apnea syndrome (OSAS) who undergo comparable intermittent or chronic alveolar PCO2 elevation. We measured ventilatory responses to five challenges of 2-min duration (C1-C5) with 5% CO2 in O2, separated by 5-min room-air breathing intervals (R1-R4), in nine children with OSAS and in eight age-, sex-, and body mass index-matched controls. In all children, CO2 significantly increased VE when compared with baseline conditions (22.3 +/- 2.2 vs. 9.5 +/- 0.9 (SE) l/min; P < 0.001). In control subjects, progressive VT increases from 0.67 +/- 0.10 liter in C1 to 0.92 +/- 0.13 liter in C5 occurred (P < 0.01), whereas RR decreased from 33.9 +/- 5.1 breaths/min in C1 to 27.8 +/- 3.7 breaths/min in C5 (P < 0.02), resulting in VE increases across CO2 challenges (22.3 +/- 4.9 l/min in C1 vs. 25.1 +/- 5.0 l/min in C5; P < 0.005). The RR decrease was primarily related to progressive prolongation of expiratory time (TE) (1.1 +/- 0.1 s in C1 to 1.5 +/- 0.2 s in C5; P < 0.002). In contrast, VT, RR, and TE did not change in a consistent fashion in OSAS patients with repeated CO2 challenges (OSAS vs. control: P < 0.0001). Furthermore, in OSAS, VE was similar with repeated challenges (22.4 +/- 2.2 1/min in C1 vs. 23.9 +/- 1.9 l/min; P = not significant), such that changes in VE over time significantly differed in OSAS and controls (P < 0.001). We conclude that healthy children modify their ventilatory strategy to repeated hypercapnia. We speculate that in OSAS these mechanisms are already fully implemented because of recurrent alveolar hypoventilation accompanying increased upper airway resistance, leading to blunted temporal trends of ventilatory response.

Ventilatory responses to repeated short hypercapnic challenges.

In early phases of respiratory disease, patients are more likely to experience intermittent hypercapnia than a continuous increase in PCO2. The effect of intermittent arterial PCO2 elevation on subsequent breathing patterns is unclear. To examine this issue, a series of six ventilatory challenges (CH1-CH6), consisting of 2 min of breathing 5% CO2 in O2, followed by 5 min in room air (RA) were performed in 10 naive healthy subjects (age 12-39 yr). Minute ventilation (VE) increased from 11.9 +/- 1.0 (SE) l/min in RA to 27.6 +/- 3.0 l/min in 5% CO2 (P < 0.0005) in each of the six hypercapnic challenges. Respiratory rate increased from 21.3 +/- 2.6 breaths/min on RA to 29.6 +/- 3.9 breaths/min during CH1 (P < 0.05). However, respiratory rate consistently decreased with successive CO2 challenges (CH6: 21.5 +/- 2.6 breaths/min; P < 0.02). Thus, maintenance of VE was achieved by gradual increases in tidal volume with each of the first four consecutive CO2 challenges (CH1: 1.05 +/- 0.09 liters; CH4: 1.44 +/- 0.13 liters; P < 0.002). Similarly, the ratio of tidal volume to inspiratory time increased from CH1 (1.16 +/- 0.16 l/s) to CH6 (1.57 +/- 0.21 l/s; P < 0.001). These changes in ventilatory strategy were not observed when RA recovery periods were extended to 15 min in five subjects. We conclude that during repeated short hypercapnic challenges similar levels of VE are achieved. However, increased mean inspiratory flows are generated to maintain VE. We speculate that intermittent hypercapnia either modifies central controller gain or induces a long-term modulatory effect to account for the progressive changes in ventilatory components.