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Biomedical subjects

I E Willetts

Publications and source records attributed to I E Willetts.

14 recordsLinked to original sources

Experience with cyclosporine in pediatric renal transplantation.

Three decades ago renal transplantation had become the accepted therapy for end-stage renal disease in children. Cyclosporine (CsA) was introduced into the majority of clinical immunosuppressive protocols in the 1980s and attained a vital place in the armamentarium of antirejection drugs for children. However, CsA therapy is not without adverse effects, notably posttransplant hypertension, hyperlipidemia, and nephrotoxicity. The cosmetic side effects of CsA, principally hirsutism and gum hyperplasia, are significant and very important to children particularly when drug compliance issues are vital to achieve success. The central role CsA has played to date in the development of successful treatment protocols for children undergoing renal transplantation is explored, including the importance of therapeutic drug level monitoring to optimize clinical outcomes.

Age Factors↗

Laparoscopic excision of a prostatic utricle in a child.

Prostatic utricle cysts result from incomplete regression of Mullerian duct structures and occur most frequently in males with perineal or peno-scrotal hypospadias. Utricular cysts may present with various signs and symptoms including urinary tract infection, pain and post-void incontinence, a palpable abdominal mass or recurrent epididymitis. Treatment is reserved for symptomatic cysts and various techniques have been described including transurethral deroofing, endoscopic incision or surgical excision by suprapubic, posterior and midline transvesical approaches. We present a successful minimally invasive approach for excision of a prostatic utricle cyst in a child. Laparoscopic excision is a safe and viable alternative to open procedures in the surgical treatment of symptomatic utricle cysts in childhood. The presence of a cystoscope within the utricle orifice aids identification and safe dissection of the utricular remnant.

Child, Preschool↗

Jessop and the Wilms' tumor.

The earliest specialists in the field of pediatric surgical oncology were the surgeons of 19th century Europe, particularly Billroth, Kocher, and Wilms. However, the first successful nephrectomy for a Wilms' tumor in a child was performed by a less famous name, Thomas Richard Jessop (1837-1903) at the Leeds General Infirmary on June 7, 1877. Jessop ultimately became Vice President of the Royal College of Surgeons of England and was a gifted teacher, being at the forefront in the development of medical education outside of London as first Professor of Surgery in Leeds. The clinical case history and operative procedure of this first successful nephrectomy for Wilms' tumor in a child is presented.

Child↗

Endotoxin, cytokines and lipid peroxides in children with intussusception.

BACKGROUND: Intussusception is a relatively common paediatric surgical emergency. The aim of this study was to investigate selected inflammatory mediators in children with acute intussusception and to identify potentially useful plasma markers of clinical outcome. METHODS: Clinical, radiographic, operative and pathological details were recorded prospectively of all children presenting to a single institution with a confirmed diagnosis of acute intussusception during 1 year. Paired acute and convalescent venous blood samples were collected in a standard manner for blinded analysis of the following: malondialdehyde, C-reactive protein (CRP), interleukin (IL) 6, neopterin, tumour necrosis factor alpha, endotoxin, and immunoglobulin (Ig) G and IgM antiendotoxin core antibody (EndoCAb). RESULTS: Thirty-two consecutive children (23 boys, nine girls) with a median age of 4 months were studied. Acute ileocolic intussusception was managed by air enema reduction (n = 19), operative reduction (n = 8) or surgical resection (n = 5). Peripheral blood cultures were sterile. Acute levels of plasma IL-6, neopterin and CRP were significantly raised in comparison to both normal laboratory ranges and convalescent samples (P < 0.001). Using stepwise discriminant analysis, CRP was identified as the best variable at distinguishing between the three treatment groups (P < 0.001). IgM EndoCAb concentrations were significantly greater in the convalescent sera of all the patients (P < 0.001). CONCLUSION: Acute ileocolic intussusception in childhood is associated with endotoxinaemia and significantly raised levels of circulating inflammatory cytokines. Plasma CRP at diagnosis showed a statistically significant positive correlation with disease severity.

Biomarkers↗

Venous patency after open central-venous cannulation.

To investigate the value of Doppler ultrasound scan (USS) assessment of internal jugular vein (IJV) patency after previous open central-venous cannulation (CVC), a prospective study of 66 consecutive children (median age 4.5 years; range 4 months-17 years) who had previously undergone open insertion of at least one indwelling IJV line and required further CVC for completion of therapy was undertaken. All underwent Doppler USS examination prior to surgery. Where patency of the previously cannulated vein was suggested ultrasonographically, the accuracy of this finding was confined at open surgical exploration. Initial CVCs were in situ for a median of 9 months (1 month-4 years) prior to removal. The median interval to repeated CVC was 11 months (3 weeks-45 months). In 79 Doppler USS, 70 (88.6%) veins appeared patent, 3 (4.2%) stenosed, and 6 (7.6%) obliterated. Of the 70 "USS patent" veins, 66 were explored. Patency was confirmed surgically in 59 (89.4%) and a new CVC successfully inserted. Seven (10.6%) apparently patent veins on USS were found to be obliterated at open exploration. Review of USS images in these cases suggested that enlarged collateral veins were usually responsible. Overall, successful recannulation was possible in 74.6% of all previously accessed veins. In children requiring repeated CVC, Doppler USS of neck veins is a valuable but not entirely reliable guide to the presence of underlying vessel patency and should be interpreted with caution. At least three-fourths of previously cannulated IJVs remain patent after catheter removal and can be reused for CVC.

Adolescent↗

John Hunter, Frederick Treves and intussusception.

Early this century, intussusception in childhood was usually fatal. John Hunter, one of the founding fathers of scientific surgery was amongst the first to accurately describe the clinico-pathological features of the condition and one of the great nineteenth century surgeons, Sir Frederick Treves, suggested a plan of management for intussusception which remains little changed up to the present day.

England↗

Cow's milk enteropathy: surgical pitfalls.

BACKGROUND: Cow's milk-induced intestinal bleeding is a well-recognized cause of rectal bleeding in infancy. The authors report on 5 older children who presented with either visible rectal bleeding or profound anemia associated with occult intestinal bleeding secondary to cow's milk enteropathy. METHODS: Five children (3 boys and 2 girls) aged between 20 months and 9 years were referred for further investigation of gastrointestinal bleeding. Two had been investigated previously on multiple occasions, and both had undergone laparotomies with negative results. Further investigations showed evidence of allergic colitis in 3 detected only on proximal colonic biopsy findings. RESULTS: In all cases, bleeding resolved completely after instituting a cow's milk-free diet. Two of the patients subsequently have undergone a cow's milk challenge leading to prompt recurrence of symptoms, which again resolved after simple dietary manipulation. CONCLUSIONS: Cow's milk enteropathy may cause overt rectal bleeding or profound anemia from occult intestinal bleeding even in older children. Histological abnormalities in such cases may be confined to the proximal colon. After appropriate investigation, a trial of cow's milk exclusion should always be considered before laparotomy for obscure, chronic gastrointestinal bleeding in children.

Child, Preschool↗

Endoscopic treatment of recurrent tracheo-oesophageal fistulae: long-term results.

Recurrent tracheo-oesophageal fistula (RTOF) occurs in 5%-15% of patients following oesophageal atresia repair. Re-thoracotomy is technically challenging and associated with significant morbidity, including a re-fistulation rate of 10%-22%. Endoscopic occlusion of the RTOF with tissue adhesives (fibrin glue, Histoacryl) is reported to be safe and highly effective. However, long-term results of such therapy are absent from the literature. A postal survey of 13 institutions reporting the use of such treatment regimes for RTOF in the literature between 1974 and 1995 was performed, and data collected concerning the long-term outcomes of their reported patients. Eleven institutions responded to the request for data, providing 22 patients (age range 1 month to 12 years) for review. All had undergone initially successful RTOF closure by endoscopic methods and had been followed up for a median of 107 months (range 3-264 months). There was no morbidity or mortality directly related to the procedure. Overall, only 55% of these endoscopically treated fistulas remained closed long-term. Fistula recurrence invariably occurred within 12 months of successful therapy (median 46 days, range 9-335). Most patients required multiple endoscopic procedures to achieve successful RTOF closure (median 2.0, range 1-4 attempts), although significantly fewer attempts were required with fibrin glue therapy. Surgical re-exploration remains the treatment of choice in the fit child. Endoscopic therapy offers a safe and elegant alternative to high-risk surgery in the sick child, although repeated treatments may be required for successful RTOF closure.

Child↗

Treatment with an HLA-peptide and cyclosporine A prolongs rat small bowel allograft survival.

BACKGROUND: The ultimate treatment for severe short bowel syndrome is small bowel transplantation (SBT). Current immunosuppression for SBT is relatively ineffective and toxic. Peptides derived from residues 75-84 of the HLA-B7 molecule are immunomodulatory in vitro, and in rodents, when combined with subtherapeutic doses of cyclosporine (CsA), prolong cardiac and skin allograft survival without altering the recipient's rejection kinetics to third party allografts. We investigated the effects of HLA-B7 peptide fragment in a rat model of SBT. METHODS: Heterotopic allogeneic SBT was performed in Dagouti (RT1a) to Lewis (RT1l) high-responder rat strain combination. B7.75-84 (40 mg/kg/d) and subtherapeutic CsA (10 mg/kg/d) were administered alone, or in combination, by gavage to allograft recipients on days 0 to 4 after SBT. Recipient pretreatment with B7.75-84 on days -14, -12, -10, and -7 followed by subtherapeutic CsA on days 0 to 4 after SBT was also carried out. Graft rejection was determined by the presence of a palpable abdominal mass on daily examination or by loss of more than 10% initial body weight. RESULTS: Without immunosuppression allografts rejected at a median time of 6 days (range, 5 to 7; n = 7). This was not significantly altered with either CsA therapy alone (median 6 days; range, 6 to 7; n = 6) or B7.75-84 alone (median, 5 days; range, 5 to 6; n = 6). Recipient combination therapy with B7.75-84 and CsA after allografting significantly prolonged allograft survival (median, 11 days; range, 9 to 13; n = 9), as did recipient B7.75-84 pretransplant therapy (median, 10 days; range, 9 to 12; n = 6), when administered over a 2-week period before allografting. CONCLUSION: Post-SBT recipient treatment with B7.75-84 produced statistically significant improvement in allograft survival only after combination with subtherapeutic CsA. Recipient pre-SBT treatment with B7.75-84 alone however, resulted in statistically significant improvement in allograft survival in combination with post-SBT subtherapeutic CsA. These synergistic effects may be valuable in achieving improved SBT survival clinically and warrant further exploration.

Animals↗

James H Nicoll: pioneer paediatric surgeon.

James H Nicoll is a little known figure in the history of surgery. Yet, this Glasgow surgeon was a pioneer, particularly in the care of the infant patient both in hospital and after discharge. A great teacher and innovator, he developed effective techniques for the surgical cure of pyloric stenosis of infancy and for the outpatient postoperative care of children with spina bifida.

Child↗