Extracorporeal photochemotherapy for paediatric patients with graft-versus-host disease after haematopoietic stem cell transplantation

This study aimed to ascertain whether extracorporeal photochemotherapy (ECP) is an effective treatment for paediatric patients with refractory graft-versus-host disease (GVHD). From January 1992 to December 2000, 77 children (median age 8.6 years) with either acute (n = 33) or chronic (n = 44) GVHD, resistant to conventional immunosuppressive therapy, were treated with ECP in four Italian paediatric hospitals. After ECP, acute GVHD involving skin, liver and gut responded completely in 76%, 60% and 75% of patients respectively. The 5-year overall survival was 69% for responding patients vs 12% for non-responders (P = 0.001). Among the 44 children with chronic GVHD, 15 (44%) showed a complete response and 10 (29%) a significant improvement after ECP. The 5-year overall survival was 96% for responders vs 58% for non-responders (P = 0.04). Our results suggest that ECP is an effective treatment that may be useful in paediatric patients with either acute or chronic GVHD who have failed to respond to standard immunosuppressive therapy.     

In vitro adherence of lymphocytes to dermal endothelium under shear stress: implications in pathobiology and steroid therapy of acute cutaneous GVHD

The extravasation of leukocytes at sites of inflammation critically depends on initial shear-resistant adhesive interactions between leukocytes in blood flow and target tissue endothelium. Dermal lymphocytic infiltrates are a hallmark feature of acute cutaneous graft-versus-host disease (acGVHD) following allogeneic hematopoietic stem cell (allo-HSC) transplantation. These infiltrates occur commonly during periods of profound lymphopenia, suggesting that the dermal endothelial adhesive mechanism(s) promoting lymphocyte emigration in acGVHD are highly efficient. To examine this issue, we performed Stamper-Woodruff assays on frozen sections of biopsy specimens of cutaneous lesions occurring within 100 days of HSC transplantation in 22 autologous hematopoietic stem cell transplant (auto-HSCT) and 25 allo-HSCT recipients. By using this shear-based assay, we observed lymphocyte adherence to papillary dermal vascular structures in all punch biopsy specimens of allo-HSCT recipients who had clinicohistologic evidence of acGVHD and who were not receiving steroids, whereas no lymphocyte adherence was observed within skin specimens from allo-HSCT recipients who did not develop acGVHD. Within the group of auto-HSCT recipients, 2 of 22 skin biopsies demonstrated lymphocyte binding to dermal vessels. Among allo-HSCT patients receiving steroid therapy for acGVHD, lymphocyte binding to dermal endothelium was abrogated prior to resolution of rash in those who responded, yet binding was persistent in skin from one patient whose rash did not respond to steroid therapy. Collectively, these data indicate that the papillary endothelium of skin in acGVHD displays heightened capacity to support lymphocyte adhesion under shear stress conditions and suggest that down-modulation of this endothelial adhesive capability may be one mechanism by which steroids abrogate acGVHD reactions.     

Evaluation of postoperative mucosa and skin temperature after surgery for impacted third molar

Surgery for impacted third molar is often characterized, in the postoperative period, by pain, trismus and swelling. The study evaluates temperature variations of mucosa and skin after application of ice packs, in three different modalities, to the region overlying the surgical site. The goal was to identify any correlation between variations of temperature and postoperative clinical symptoms. For this purpose we selected 54 patients programmed for impacted third molar surgery. The patients were divided into three groups of 18. Time and frequency of application of the ice pack varied in the three groups; 5'/30' (group 1); 10'/60' (group 2); 20'/60' (group 3). During the four hours following surgery, temperatures of mucosa and of skin at the surgical site were measured with high-precision thermocouples, maximum response 5". The results indicate that application of an ice pack for 5'/30' or for 10'/60' controls the temperature of the mucosa post-surgery more effectively, and that the duration of surgery appears not to influence temperature variations. In the postoperative phase we recommend a rational application of ice packs appropriate to the constitution of each patient.     

Laparoscopic diagnostic exploration of the vaginal processus in the pediatric age. Preliminary experiences

BACKGROUND: Laparoscopic surgical procedures, employed even in the paediatric age, bearing both diagnostic and therapeutic value, are currently used in the evaluation of peritoneal-vaginal duct patency during surgery for controlateral inguinal hernia or other diseases requiring opening of abdominal wall. METHODS: From January 1996 to December 2000, at the Department of Pediatric Surgery of the University of Siena a prospective study protocol has been performed to evaluate the effectiveness of laparoscopy versus traditional surgery in showing patency of peritoneal-vaginal duct. RESULTS: From our study we have been able to see how this laparoscopic procedure is well tolerated by children and parents, and is lacking in clinical complications. Patency of peritoneal-vaginal duct has been pointed out in 21.73% of cases. This result is in line with the international literature; in fact, the majority of authors have found a negative controlateral exploration in 50-80% of patients examined, thus confirming the uselessness of routine surgical controlateral inguinal exploration in hernia cases. CONCLUSIONS: The use of diagnostic laparoscopy in the study of peritoneal duct patency is a rapid and relatively easy technique, practically without intra- and peri operative risks. It allows an easy solution of the diagnostic doubt, without the need to necessarily perform a traditional explorative surgical procedure.     

Integrated fellowship in vascular surgery and intervention radiology: a new paradigm in vascular training

OBJECTIVE: To evaluate an integrated fellowship in vascular surgery and interventional radiology initiated to train vascular surgeons in endovascular techniques and to train radiology fellows in clinical aspects of vascular diseases. SUMMARY BACKGROUND DATA: The rapid evolution of endovascular techniques for the treatment of vascular diseases requires that vascular surgeons develop proficiency in these techniques and that interventional radiologists develop proficiency in the clinical evaluation and management of patients who are best treated with endovascular techniques. In response to this need the authors initiated an integrated fellowship in vascular surgery and interventional radiology and now report their interim results. METHODS: Since 1999 vascular fellows and radiology fellows performed an identical year-long fellowship in interventional radiology. During the fellowship, vascular surgery and radiology fellows perform both vascular and nonvascular interventional procedures. Both vascular surgery and radiology-based fellows spend one quarter of the year on the vascular service performing endovascular aortic aneurysm repairs and acquiring clinical experience in the vascular surgery inpatient and outpatient services. Vascular surgery fellows then complete an additional year-long fellowship in vascular surgery. To evaluate the type and number of interventional radiology procedures, the authors analyzed records of cases performed by all interventional radiology and vascular surgery fellows from a prospectively maintained database. The attitudes of vascular surgery and interventional radiology faculty and fellows toward the integrated fellowship were surveyed using a formal questionnaire. RESULTS: During the fellowship each fellow performed an average of 1,201 procedures, including 808 vascular procedures (236 diagnostic angiograms, 70 arterial interventions, 59 diagnostic venograms, 475 venous interventions, and 43 hemodialysis graft interventions) and 393 nonvascular procedures. On average fellows performed 20 endovascular aortic aneurysm repairs per year. There was no significant difference between the vascular surgery and radiology fellows in either the spectrum or number of cases performed. Eighty-eight percent (23/26) of the questionnaires were completed and returned. Both interventional radiologists and vascular surgeons strongly supported the integrated fellowship model and favored continuation of the integrated program. Vascular surgery and interventional radiology faculty members wanted additional training in clinical vascular surgery for the radiology-based fellows. With the exception of the radiology fellows there was uniform agreement that vascular surgery fellows benefit from training in nonvascular aspects of interventional radiology. CONCLUSIONS: Integration of vascular surgery and interventional radiology fellowships is feasible and is mutually beneficial to both disciplines. Furthermore, the integrated fellowship provides exceptional training for vascular surgery and interventional radiology fellows in all catheter-based techniques that far exceeds the minimum requirements for credentialing suggested by various professional societies. There is a clear need for cooperation and active involvement on the parts of the American Board of Radiology and the American Board of Surgery and its Vascular Board to create hybrid training programs that meet mutually agreed-on criteria that document sufficient acquisition of both the cognitive and technical skills required to manage patients undergoing endovascular procedures safely and effectively.     

Women with pregnancy-related polymyositis and high serum CK levels in the newborn

Two previously healthy women developed an inflammatory myopathy before the term of their first pregnancy. Skeletal muscle biopsy led to a diagnosis of T cell-mediated polymyositis. Both babies were healthy, but their serum creatine kinase levels remained elevated for a few months after birth. Their mothers did well after corticosteroid treatment.     

Lack of apoptosis in mitochondrial encephalomyopathies

BACKGROUND/OBJECTIVE: Apoptosis, or programmed cell death, is an evolutionary conserved mechanism essential for morphogenesis and tissue homeostasis, but it plays an important role also in pathologic conditions, including neurologic disorders. Its execution pathway is critically regulated at the mitochondrial level. Evidence of apoptosis in muscle specimens was investigated in patients with genetically defined mitochondrial encephalomyopathies. METHODS: Thirty-three muscle biopsies from patients with genotypically different mitochondrial diseases (single and multiple deletions, A3243G/A8344G point mutations of the mitochondrial DNA) were studied. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) reaction was used as a marker of nuclear DNA fragmentation, as well as antibodies against pro- (Fas) or anti- (Bcl-2) apoptotic factors. Also, because one hallmark of apoptosis is morphologic, ultrastructural studies were performed on skeletal muscle from 18 of 33 patients, examining both phenotypically normal and ragged red fibers. RESULTS: In all muscle biopsies, no significant expression of either pro (Fas) and inhibiting (Bcl-2) apoptosis-related proteins was found, nor TUNEL positivity. This latter finding is confirmed by lack of morphologic evidence of apoptosis in all the fibers examined at the ultrastructural level. CONCLUSION: The authors' findings suggest that genetically determined defects of oxidative phosphorylation do not induce the apoptotic process and that apoptosis is not involved in the pathogenesis of mitochondrial disorders.