Stability and peptide binding specificity of Btk SH2 domain: molecular basis for X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is caused by mutations in the Bruton's tyrosine kinase (Btk). The absence of functional Btk leads to failure of B-cell development that incapacitates antibody production in XLA patients leading to recurrent bacterial infections. Btk SH2 domain is essential for phospholipase C-gamma phosphorylation, and mutations in this domain were shown to cause XLA. Recently, the B-cell linker protein (BLNK) was found to interact with the SH2 domain of Btk, and this association is required for the activation of phospholipase C-gamma. However, the molecular basis for the interaction between the Btk SH2 domain and BLNK and the cause of XLA remain unclear. To understand the role of Btk in B-cell development, we have determined the stability and peptide binding affinity of the Btk SH2 domain. Our results indicate that both the structure and stability of Btk SH2 domain closely resemble with other SH2 domains, and it binds with phosphopeptides in the order pYEEI > pYDEP > pYMEM > pYLDL > pYIIP. We expressed the R288Q, R288W, L295P, R307G, R307T, Y334S, Y361C, L369F, and 1370M mutants of the Btk SH2 domain identified from XLA patients and measured their binding affinity with the phosphopeptides. Our studies revealed that mutation of R288 and R307 located in the phosphotyrosine binding site resulted in a more than 200-fold decrease in the peptide binding compared to L295, Y334, Y361, L369, and 1370 mutations in the pY + 3 hydrophobic binding pocket (approximately 3- to 17-folds). Furthermore, mutation of the Tyr residue at the betaD5 position reverses the binding order of Btk SH2 domain to pYIIP > pYLDL > pYDEP > pYMEM > pYEEI. This altered binding behavior of mutant Btk SH2 domain likely leads to XLA.

The evaluation of percutaneous central venous catheters--a convenient technique in pediatric patients.

OBJECTIVE: To evaluate the feasibility and effectiveness of 3 different types of silastic catheters that were used for percutaneous central venous catheterization (PCVC) through peripheral veins. DESIGN AND SETTING: The study was prospective and consecutive for 6 years at a pediatric/neonatal intensive care unit and pediatric ward in Veterans General Hospital-Taipei, a university-affiliated medical center, in Taiwan, ROC. PARTICIPANTS AND INTERVENTIONS: The patients who had PCVC were consecutively enrolled from January 1988 to December 1993. Three types of silastic catheters were used. The classification was according to the caliber as small catheter (SC, 0.30 mm ID), mid-size catheter (MC, 0.51 mm ID) and large catheter (LC, 0.64 mm ID). The same insertion technique, catheter-through-needle, was used for all PCVC placements through the peripheral vein. After insertion, each catheter was connected to a conventional short cannula (24-, 22-, or 20-gauge) of compatible caliber, and then linked to the infusion system. RESULTS: 1318 PCVCs were used in 1126 consecutive patients, that included 754 SCs in 649 infants (among them 60.9% were less than 1500 g), 383 MCs in 319 toddlers, and 181 LCs in 158 children. Mean (SD) body weight at the time of catheter insertion was SC 1.7(0.9)kg, MC 12.1(6.5)kg and LC 19.3(7.6)kg. Overall, mean (SD) duration of these PCVC was 16.4(8.4) days. A significantly longer duration was noted in: (a) SC group with 19.7(10.4) days than the other two groups [MC 12.4(6.5) days, LC 11.2(5.0) days]; (b) patients with body weight equal to or less than 3.0 kg [18.7(8.6) versus 14.1(6.1); and (c) insertion sites other than external jugular vein (EJV) [18.8(9.7) versus 11.7(6.0)]. These PCVCs provided reliable venous access for multiple purposes such as hyperalimentation, venous access or sampling of blood, antibiotic therapy and chemotherapy. MC and LC were also used for monitoring the central venous pressure. Most of the time, SC and MC were inserted through the superficial peripheral vein of the scalp, neck and extremities, while LC was almost approached via the EJV. The overall success rate of insertion was 92.4% (1318/1427). No significant difference was observed among the different catheter groups [93.4% (754/807) in SC, 90.5% (383/423) in MC and 91.9% (181/197) in LC] and the different insertion sites. Within each group of PCVC, more than eighty percent of catheters were removed electively: 83.3% in SC, 89.6% in MC and 84.5% in LC. Probable catheter-related sepsis accounted for 2.7% (36/1, 318) of all PCVCs. With this study, the cost of each PCVC set is 3.0 US dollar. CONCLUSION: This study indicates that the use of three different calibers of silastic catheter is feasible and effective for PCVC in pediatric practice.

Continuous positive airway pressure by nasal prongs in bronchiolitis.

Ten infants with evidence of impending respiratory failure from severe bronchiolitis were successfully treated with continuous positive airway pressure (NCPAP) with double nasal prongs. Their mean (SD) age was 6.7 (3.8) months and mean (SD) body weight was 7.1 (2.1) kg. Respiratory assessments were made immediately before and 2 hours after application of NCPAP. Clinical symptoms, signs, and arterial blood gases improved in all patients, with a significant fall in mean (SD) respiratory rate [71 (6) vs. 54 (9) per minute], mean (SD) heart rate (178(9) vs. 154(15) per minute], and mean (SD) partial pressure of arterial carbon dioxide [Paco2; 48.0 (13.9) vs. 42.4 (12.9) mmHg]. There was a significant rise in mean (SD) arterial blood pH [7.33 (0.05) vs. 7.37 (0.05)] and mean (SD) oxygenation ratio [Fio2/Pao2, 155 (25) vs. 175 (22)]. We believe NCPAP is an effective method, with numerous advantages in the treatment of severe bronchiolitis. Early application of NCPAP is suggested to avoid the need for mechanical ventilation.

Stomach rupture associated with physical struggle in a child.

A 5-year-old girl with spontaneous rupture of the stomach was treated successfully with excision of the ischemic edges of the perforation with primary repair. In this case, vigorous resistance against medical measurement resulted in rupture of the stomach, which was already distended with a large amount of fluid and air. The child survived following immediate surgical intervention and intensive postoperative care.

Local interstitial emphysema caused by meconium aspiration: report of one case.

A neonate of meconium aspiration syndrome presented with respiratory distress and bilateral pneumothorax. The image studies, including chest X-ray, chest computed tomography and operation finding all showed cystic changes in the right lung. Therefore congenital cystic lesions of lung was the first impression. However, the pathologic report disclosed meconium aspiration with interstitial emphysema.

Intratracheal oxygen administration during bronchoscopy in newborns: comparison between two different weight groups of infants.

BACKGROUND: The development of ultrathin fiberoptic bronchoscopy (FB) has made the examination of neonatal airways a practical possibility. The aim of this study was to assess the effects of intratracheal oxygen (ITO) administration on blood oxygenation and carbon dioxide (CO2) changes during FB in different body-weight infants. METHODS: Newborns suspected of having airway problems, but in a stable cardiopulmonary condition were studied. An ultrathin (outside diameter, 2.2 mm) fiberoptic bronchoscope that was modified by adding an external tube (internal diameter, 0.3 mm; outside diameter, 0.64 mm) to deliver oxygen was used. For ITO administration, a low oxygen flow rate of 0.1 l/kg/min was delivered directly into the trachea. Oxygenation and CO2 measurements were obtained at five different stages: 1) just before FB (baseline); 2) with the tip of the bronchoscope at the supralarynx; 3) with the tip at the carina without ITO; 4) with the tip at the carina with ITO; and 5) 15 minutes after FB. Forty infants were studied completely and divided into two groups according to their body weight: 1) the light-weight group (< 2,500 g), 21 infants; and 2) the heavy-weight group (> or = 2,500 g), 19 infants. RESULTS: In both groups, arterial blood oxyhemoglobin saturation and oxygen tension decreased significantly (p < 0.05) when the tip of the bronchoscope advanced from the nostril to the supralarynx, and further decreased (p < 0.01) when at the carina level. Small infants had greater decrements of both oxygenation measurements (p < 0.05) than the large infants. After ITO administration, both oxygenation measurements increased significantly (p < 0.001) and returned to baseline following FB. Both end tidal pressure of CO2 (P(ET)CO2) and arterial CO2 tension (PaCO2) significantly increased from the baseline when the FB tip was advanced from the supralarynx to the carina (p < 0.05). During ITO administration, the PaCO2 increased (p < 0.01) but the P(ET)CO2 decreased (p < 0.001). After FB, both CO2 measurements returned to baseline. The pH only decreased during ITO administration. CONCLUSIONS: We conclude that FB causes significant hypoxemia and hypercapnia in newborns, especially in underweight infants. Appropriate ITO can be considered a safe and beneficial technique for maintaining oxygenation during FB. P(ET)CO2 monitoring may mask true blood CO2 retention during ITO administration.

Asphyxiated bladder syndrome in a pediatric intensive care unit.

Sixteen neonates and infants with asphyxiated bladder syndrome (ABS) were prospectively studied over a two-year period. Their transient urinary bladder distention had developed as a sequel of asphyxial events, and presented as delayed micturition in the absence of obstructive lesion. The incidence was 1.9 percent in this Pediatric Intensive Care Unit. Five cases occurred in the neonatal period. All patients were younger than three years of age (mean: 9.1 months), and the incidence of ABS was 2.8 percent within this age group. For intermittent decompression of the bladder, all responded successfully to the suprapubic bladder expression method (Crede's maneuver). Most (81.3%, 13/16) ABS cases coexisted with intestinal dysfunction as either paralytic ileus (62.5%, 10/16) or as gas-less abdomen (18.8%, 3/16). There was no evidence of association with either systemic or urinary bacterial infection. Normal spontaneous voiding and bowel function were regained in all cases except one, who died early. Mean (SD) duration of bladder dysfunction was 66.9 (40.3) hours. Sonography showed normal kidneys and collecting system in all patients both during and after ABS episodes. Half of the patients (8/16) died ultimately. No urinary tract abnormality was found in post-mortem examinations in five cases.

Percutaneous central venous catheterization: five year experiment in a neonatal intensive care unit.

We evaluated the clinical application of percutaneous central venous catheter (PCVC) in our neonatal intensive care unit (NICU). During a five-year study, 610 PCVCs were placed in 496 infants for a total of 10,243 days. The success catheterization rate was 92%. Among them, 82.7% needed only one PCVC. The body weight of babies ranged from 460 g to 5,340 g. Of 610 PCVCs, 337 (45.2%) were placed in infants weighing 1,500 g or less. About half (50.7%) of the PCVCs were placed within the first 24 hours of life. Common sites for insertion were the dorsal aspect of hands (48.8%) and the antecubital region (25.1%). Mean PCVC stay was 17.6 days (range, less than 1 to 74 days). The duration was longer (18.5 days) in infants weighing 1,500 g or less. Almost four fifth (79.2%) of 586 PCVCs were removed electively and one tenth was due to either mechanical problems (10.7%) or suspected catheter-related infection (10.1%). Of 586 PCVCs, catheter-related sepsis was confirmed in 3.4% (20/586), or 2.1 per 1,000 catheter-days. No immediate complication was attributed to the insertion procedure. We conclude that PCVC is a safe and effective technique for prolonged intravenous therapy in NICU.

Selective placement of bronchial suction catheters in intubated full term and premature neonates.

Flexible straight suction catheters were passed through nasal endotracheal tubes in 30 newborn infants (gestation age 26-42 weeks; birth weight 800-4,100 g) undergoing mechanical ventilation just before chest radiographic examination for clinical purpose. With the head in midline position, 63% (19/30) and 37% (11/30) of the catheters, entered the right and left main bronchus, respectively. With the head turning to either the left or right side, 87% (26/30) and 73% (22/30) of the catheters, entered the contralateral bronchus, respectively. Both success rates increased significantly (p less than 0.05 and p less than 0.01). Thus, turning the head facilitates passage of the cather into the contralateral mainstem bronchus in full term and premature neonates.

The application of a modified mini-flexible-fiberoptic endoscopy in pediatric practice.

BACKGROUND: The application of bronchoscopy in infants and small children is still restricted in most institutions because of their limited airways. The purpose of this study was to evaluate the usefulness of a modified mini (2.1 mm OD) flexible fiberoptic endoscope (FFE) in diagnosis and therapy of suspected pediatric airway problems. METHODS: A prospective two-year study was carried out in a tertiary care neonatal/pediatric intensive care unit and general ward in a children medical center of a university-affiliated hospital. The employed mini-FFE (Machida ENT-30 F III, Tokyo, Japan) was modified with the addition of an external silastic catheter (0.5 mm inward diameter, 0.9 mm outward diameter) for suctioning, oxygen delivery, and medications during study. RESULTS: Totally, 247 laryngoscopies and 212 bronchoscopies were performed in 207 patients without significant morbidity or any associated mortality. The age of patients ranged from 1 day to 10 years. About one-fifth of the procedures (larngoscopy 21.5%, 53/247; bronchoscopy 19.8%, 42/212) were performed in patients under the age of one month. Patient's body weight ranged from 650 g to 40 kg. About fifty-five percent of the procedures (laryngoscopy 55.1% 136/247; bronchoscopy 55.2%, 117/212) were performed in patients weighing less than 5 kg. The most common path of either laryngoscopy (94.3%, 233/247) or bronchoscopy (94.8%, 201/212) was through the nasal route. In 102 patients who had been demonstrated to have upper airway problems, 16 patients (15.7%) also proved to ahve significant lesion(s) below the glottis. CONCLUSIONS: This modified FFE is a safe and a valuable instrument that can serve as an important aid in the diagnosis and therapy as well as a guide for surgical intervention of respiratory tract disorders in small infants and children.

Non-traumatic injuries in childhood: an epidemiological survey.

BACKGROUND: Accident is the major cause of morbidity and mortality in childhood. The incidence of various non-traumatic injuries has increased due to proliferation of many chemical products and curiosity of little children, which needs our special attention for prevention. METHODS: Two hundred and sixty-six children were sent to the pediatric emergency room of Veterans General Hospital-Taipei from January 1990 to December 1993 with a diagnosis of non-traumatic injuries. Retrospective analysis of their medical records was performed. RESULTS: Household materials were the most common ingested material causing non-traumatic injuries, followed by drugs, foreign bodies and gases. The male to female ratio was 1.3:1. The children were most commonly 1 to 3 years of age (66.2%), especially between 13 to 24 months. Benzodiazepines, pesticides and coins were the most common causes in drug, household material and foreign body groups, respectively. Sixty-two percent of cases had symptoms, and the major presentations occurred in central nervous system. Ninety-two percent of non-traumatic injuries happened at home, and ninety-two percent of the events were accidental. Approximately thirty percent of patients needed hospitalization. Ultimately, two cases died and another three had severe sequelae. CONCLUSIONS: Boys at 1-3 years of age had the highest proportion among young victims of non-traumatic injuries especially via accidental ingestion or poisoning, and home was the most common site of event. Proper prevention with education to the parents and children is of the most importance to eliminate such injuries.

Hemolytic impact of central venous catheters on fresh whole blood.

An in vitro study was conducted to determine the degree of hemolysis of fresh whole blood, transfused at rates of 10, 20, and 40 ml per hour through three different sizes of central venous catheters by using the same piston-type syringe pump. The catheter lengths were 20 cm, 30 cm and 30 cm; the intraluminal calibers were 0.18 mm, 0.30 mm and 0.51 mm, respectively. A total of 20 healthy volunteers were enrolled as blood donors. Nine 20-ml aliquots of fresh whole blood were obtained from each donor. These samples were assigned to infuse through nine infusion combinations of three different-gauge catheters with each of three different speeds. Three hemolysis parameters which included red blood cell counts, hematocrit and plasma potassium of the effluent were measured and compared with those of the controls (preinfusion). The results showed no significant hemolysis during passage through any infusion system. It was concluded that fresh whole blood may be transfused at regular rates through these three fine-bore central venous catheters without fear of hemolysis.

[Effect of light on total micro-bilirubin values in vitro].

In order to elucidate the effect of light on total bilirubin values in vitro, 616 capillary blood samples were collected from jaundiced newborn infants at the nursery of Veterans General Hospital-Taipei. Samples were divided into 3 groups: 1. Phototherapy light group-133 samples were irradiated with blue fluorescent light (spectral irradiance 425-475 nm = 4 mu watt/cm2/nm); 2. Room light group-202 samples were irradiated with white fluorescent light (spectral irradiance 425-475 nm = 0.2 mu watt/cm2/nm); 3. Dark group-the last 215 samples were placed in the dark. Total bilirubin values were checked with spectrophotometry, at 0, 2, 4, 6, 24 and 48 hours after being placed in different environments. Total bilirubin values varied significantly in different light source and time groups (p less than 0.0001), plus both had statistical interactions (p less than 0.0001). There were significant decreases in the bilirubin values of the phototherapy group beginning at 2 hours (p less than 0.05), and in the room light group beginning at 6 hours (p less than 0.05), but there was no change in the dark group. We conclude that blood samples for total bilirubin values should not be placed under the light of phototherapy even 2 hours. If blood samples are exposed to room light inevitably, it is safe to be checked within 4 hours. If immediate measurements are unavailable, the samples can be placed in a dark environment allowing the values to remain unchanged for 48 hours.

Direct tracheobronchial suction for massive post-extubation atelectasis in premature infants.

UNLABELLED: A prospective four-year study was done in a neonatal intensive care unit (NICU) to evaluate a technique, called direct tracheobronchial suction (DTBS), for rapidly removal of obstructive secretions from the tracheobronchial tree in newborn infants with massive post-extubation atelectasis (PEA). Selected cases who met the following criteria were enrolled: 1) developing new massive atelectasis within 48 hours after extubation; 2) no response to vigorous chest physiotherapy(CPT) and continuous deterioration; and 3) no air-bronchogram in the atelectatic lung field. DTBS was carried on at bedside by direct insertion a 6.5 Fr suction catheter into tracheobronchial tree and suctioning. Clinical and laboratory assessments were made in each case prior to and at two hours after DTBS for comparison. A total of 145 (19.7%, 145/736)) PEA occurred in a consecutive 736 postextubated newborn infants. Thirty-one atelectasis (4.2%, 31/736) that developed in 18 infants were managed with DTBS. There was a significant higher incidence of PEA developed, as well as a higher ratio of PEA been treated by DTBS, in the group of body weight < 1,500 g than the group of > or = 1,500 g. All except one infants weighed less than 1,500 g, with a mean of 1,043 +/- 269 g. Sixteen infants had been intubated for more than seven days with a mean of 14.1 +/- 5.0 days. Nine infants required more than one session of DTBS. DTBS was quite effective in immediate removal of retained secretions and improvement of pulmonary condition. By clinical assessment, respiratory distress improved with increased audible air entry on the affected lung, decreased chest retractions, and a significant fall in respiratory rate and heart rate. Arterial blood gases analysis showed significant improvement of pH, partial pressure of carbon dioxide and oxygenation ratio. By chest radiograph, DTBS resulted partial or nearly complete resolution of the atelectasis in all cases. DTBS procedures were well tolerated by all infants without significant sequelae. CONCLUSION: This study suggests that DTBS is a simple and effective therapeutic modality to rapidly correct the massive PEA which resist to vigorous CPT in small infants.

Indomethacin for the prevention of symptomatic patent ductus arteriosus in very low birth weight infants.

To assess the efficacy of prophylactic indomethacin in reducing the incidence of symptomatic patent ductus arteriosus, thirty two preterm infants weighing 750-1500 gm at birth were randomized to receive oral indomethacin or placebo. Fifteen infants received oral indomethacin with a dosage of 0.2 mg/kg at the 24th, 36th and 60th hour of age as the study group. The other 17 infants received 1 ml 0.33% saline in 5% G/W solution at the same schedule. Birth weight, gestational age, male/female ratio and severity of respiratory distress syndrome were similar for both groups. Nine of the 16 survivors of control group developed symptomatic patent ductus arteriosus. On the contrary, only two of the 14 survivors who received prophylactic indomethacin developed symptomatic PDA (P less than 0.05). There were no significant difference in the development of bronchopulmonary dysplasia, duration of oxygen therapy, duration of endotracheal intubation, days required to regain birth weight or complication between these two groups. The results indicated that the use of prophylactic oral indomethacin is beneficial in the prevention of symptomatic PDA in very low birth weight infant.

[Asphyxiating thoracic dystrophy: a case report].

Asphyxiating thoracic dystrophy (ATD) is a rare case of autosomal recessive disease. We report a case of full term female infant, who was noted to have small chest cage with severe respiratory distress soon after birth. On physical examination. The chest wall was fixed and small with the narrowest circumference about 29 cm in size, general cyanosis and distended abdomen were noted, there was a umbilical hernia around 1 cm in diameter. Otherwise, no other gross anomalies were found. Radiologic studies revealed short and horizontal ribs, small lung volume but depressed diaphragm, the clavicles and the spine were normal. The abdomen and long bone series all showed negative findings. The patient died of respiratory failure at 18 hours after birth. Autopsy was documented as a case of ATD. According to family history, there was one sibling die in the similar condition, although no autopsy available. Because the disease is transmitted as autosomal recessive trait, so 25% of next sibling will get the same condition. Therefore genetic consulting is necessary.