A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes

Objective　To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods　Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results　DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions　DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up.     

Angiographic embolization for arrest of bleeding after penetrating trauma to the abdomen

BACKGROUND: Angiographic embolization is an effective technique to control bleeding after blunt trauma to the liver or pelvis. Its role in penetrating trauma to the abdomen has not been studied. METHODS: From January 1992 to May 1998, 40 patients underwent angiography for bleeding resulting from intra-abdominal penetrating injuries (33 gunshot wounds, 7 stab wounds). Angiographic embolization of intraperitoneal or retroperitoneal vessels was performed by standard angiographic techniques with gelatin sponge and/or coils. Data were extracted from medical records, radiology data bank, trauma registry, and morbidity/mortality records, and compared by Student's t test and chi-square test. The main outcome measures were failure of angiographic embolization to control bleeding and complications of angiographic embolization. RESULTS: Angiography was performed during a course of nonoperative management in 6 patients (group A), because of failure to control bleeding surgically in 23 (group B), and because of late vascular complications after an initially successful operation in 11 more (group C). In 32 patients, angiography revealed active bleeding; 29 (91 %) underwent successful angiographic embolization. Of the remaining 3 patients, 2 were successfully managed surgically (1 each from groups A and B) and 1 died despite multiple surgical maneuvers (group B). One patient who developed postoperatively a large, bleeding superior mesenteric artery pseudoaneurysm, suffered extensive bowel necrosis after angiographic embolization. No other significant complication was related to angiographic embolization. CONCLUSIONS: Angiographic embolization after penetrating injuries to the abdomen is safe and effective for a small number of selected patients. It is a valuable tool for bleeding control when surgery has failed. It may be ideal for control of late vascular complications when reoperation is not desirable. It may prove to be a useful adjunct in the nonoperative treatment of selected injuries.     

Physiologic Monitoring of Circulatory Dysfunction in Patients with Severe Head Injuries

RID=" ID=" <E5>Correspondence to:</E5> G.C. Velmahos, M.D., Ph.D.     

Efficacy of "high-intensity" blue-light and "standard" daylight phototherapy for non-haemolytic hyperbilirubinaemia

We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy.     

Angiographic Embolization for Intraperitoneal and Retroperitoneal Injuries

Angiographic embolization (AE) has been used extensively for bleeding control after injuries to the face and neck. Its role in abdominal trauma requires further exploration. We reviewed the medical records of 137 consecutive patients who underwent angiography with the intent to embolize bleeding sites within the abdomen. Of them, 97 (71%) had blunt and 40 (29%) had penetrating trauma. AE was performed for hemorrhage associated with pelvic fractures (97 patients), liver lacerations (n= 26), renal lacerations (n= 12), splenic lacerations (n= 5), other injuries (n= 9), and multiple injuries (n= 12). On angiography, 102 patients were found to have bleeding sites and underwent AE, with angiographic and clinical bleeding control in 93 (91%). The rate of successful hemostasis by AE was identical in blunt and penetrating trauma patients. There was no major morbidity after AE. No factors predicted patients with a high likelihood to have a positive angiogram. Patients who had AE before or after a period of attempted hemodynamic stabilization in the intensive care unit were no different with respect to hemodynamic parameters immediately before AE or effectiveness of AE for bleeding control. AE is a safe and effective method for controlling bleeding after blunt and penetrating intra- and retroperitoneal injuries. Early AE may be used in selected patients as a front-line therapeutic intervention that offers expeditious hemostasis and prevents delays in definitive bleeding control.     

Bedside Percutaneous Tracheostomy: Prospective Evaluation of a Modification of the Current Technique in 100 Patients

Percutaneous dilatational tracheostomy (PDT) is being increasingly used. Concerns have been raised as to its safety, especially when it is done at the bedside. A prospective evaluation was conducted of 100 consecutive, unselected critically ill patients with PDT. The mean intensive care unit (ICU) stay before PDT was 12 days. One surgeon performed PDT alone (5 cases) or assisted residents (95 cases) in all operations; 84 were performed at the ICU bedside. Only the first six patients were taken to the operating room solely for tracheostomy. A modified technique was used: (1) the endotracheal tube was left in place during sequential dilations; (2) dilators were inserted in a 60-degree cephalad orientation to the skin and directed caudally after penetration of the anterior tracheal wall; (3) a digit was inserted through the tracheal opening to guide withdrawal of the endotracheal tube to the level of the vocal cords; and (4) size 8 tracheostomy cannulas were inserted over 28F dilators. The average time from skin incision to insertion of the tracheostomy tube was 12 minutes (< 10 minutes, 41 patients; 10 to 15 minutes, 37 patients; > 15 minutes, 22 patients). Sixty-five percent had unfavorable anatomic conditions due to spinal precautions or diffuse neck edema. Postoperative complications occurred in four patients; surgical emphysema after tracheal lacerations in three, cannula dislodgment in one. All complications were successfully managed without an operation by tube exchange (n= 3) or observation (n= 1); there was no procedure-related mortality. Forty patients were available for long-term follow-up (6–18 months after tracheostomy) by telephone; one had persistent hoarseness without respiratory difficulty. We concluded that bedside PDT is safe and easy to teach when performed with a technique that ensures correct instrumentation.     

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.     

Intraabdominal abscess rate after laparoscopic appendectomy

BACKGROUND: Studies suggest increased intraabdominal abscess (IA) rates following laparoscopic appendectomy (LA), especially for perforated appendicitis. Consequently, an open approach has been advocated. The aim of our study is to compare IA rates following LA performed by a laparoscopic surgery and a general surgical service within the same institution. METHODS: Data of LA patients treated at Los Angeles County-University of Southern California (LAC-USC) Medical Center between March 1992 and June 1997 were reviewed. The main outcome measure was postoperative IA. RESULTS: In all, 645 LA were reviewed. A total of 413 LA (285 acute, 61 gangrenous, 67 perforated appendicitis) were performed by three general surgical services (10 attendings). Ten abscesses occurred postoperatively (2.4%), 6 with perforated appendicitis. After the laparoscopic service was introduced, 232 standardized LA (126 acute, 46 gangrenous, 60 perforated) were performed by two attendings. One IA occurred (gangrenous appendicitis). The IA rate for perforated appendicitis was significantly lower on the laparoscopic service (P = 0.025). There was no difference in IA rates for acute and gangrenous appendicitis. There was no mortality in either group. CONCLUSION: IA rate following LA for perforated appendicitis was significantly reduced on the laparoscopic service. Mastery of the learning curve and addition of specific surgical techniques explained this improved result. Therefore, laparoscopic appendectomy for complicated appendicitis may not be contraindicated, even for perforated appendicitis.