Biomedical subjects
Publications and source records attributed to B Pittet.
Humanitarian plastic surgery has become very fashionable and more and more surgeons are attracted by this type of commitment. The authors remind here of the necessary conditions and limitations of these actions. The communicative action according to J. Habermas, which means a true partnership with the local health care specialists should be the only valid engagement.
Noma is a devastating gangrenous disease that leads to severe tissue destructions in the face. It is seen almost exclusively in children living in less developed countries. The exact prevalence of the disease is unknown and the cause remains unknown too. Risk factors are: malnutrition, a compromised immune system, poor oral hygiene and a lesion of the gingival mucosal barrier, as well as an unidentified bacterial factor. Herpes viruses might also contribute. Studies of the buccal flora in acute phases of noma and comparison with control children do not exist. Our study takes place in Niger. For each child (cases and controls) we take samples of gingival fluid, saliva, blood and mouth mucosal swabs. The samples are analysed in Geneva in different laboratories. We control the serologies for Herpes viruses and measles. We also perform a nutritional assessment and the mucosal swabs are cultivated for the presence of viruses. The gingival flora is investigated by microarrays. These microarrays are instrumental to test for the presence of thousands of different bacteria in each clinical sample. This method allows a qualitative and quantitative description of the oral flora in noma-children and control cases. This is the first large scale study on the etiology of noma which uses new technical approaches for humanitarian purposes.
Lip expansion is an old procedure used by some ethnic groups to follow traditions of their ancestry. Medically speaking since the beginning of the XIXth century, various devices have been designed for distending the angles of the mouth in order to recreate the normal width of the mouth aperture. In the recent years, thanks to the development and refinements of new flaps, expanding the lips is rarely necessary. In proper indications however, specially in the vermillon border, lip expansion remains a good indication.
Noma is a grangenous stomatitis which might extend to other facial structures leading to extensive soft tissue and bony defects. Reconstruction of noma sequellae should take into account a few principles in relation to the particular aspect of this disease: (1) correction of the mandibular constriction; (2) removal of scar tissue in order to recreate the initial defect; (3) reconstruction of the missing bony framework; (4) reconstruction of the maxilla and upper lip before building the nose in case it is destroyed; (5) anticipation of the facial growth. Reconstruction of the lips, in case of extensive defects often necessitates a distant skin flap. As free flaps, the forearm fascio-cutaneous flap or the serratus musculo-cutaneous flap were used according to the size of the defect. The mucosal part of the lip is usually reconstructed with a local flap from the adjacent lip or an heterolabial flap (Estlander flap).
The study of microcirculation using angiography is essential to the advancement of flap and angiogenesis research in plastic surgery. Until the mid-1980s, barium sulphate was the most commonly used contrast material, although it did not provide optimal visualisation of the vascular tree. In 1986, a new technique using lead oxide was proposed, which permitted very high-quality imaging and rapidly became the technique of choice, despite its high toxicity. We reconsider the former technique of barium-sulphate injection and combine it with soft-tissue radiology using mammographic film to achieve a radiological definition similar to that obtained with lead oxide, and discuss the advantages and disadvantages of the two methods. We conclude that barium sulphate and the use of mammographic film is an accurate, simple and non-toxic method of analysing the cutaneous circulation in small animals.
BACKGROUND: Increasing incidence of ductal carcinoma in situ (DCIS) confronts patients and clinicians with optimal treatment decisions. This multidisciplinary study investigates therapeutic modalities of DCIS in daily practice and provides recommendations on how to increase quality of care. PATIENTS AND METHODS: All women (n = 116) with unilateral DCIS recorded in the Geneva Cancer Registry from 1995 to 1999 were considered. Information concerned patient and tumor characteristics, treatment and outcome. Factors linked to therapy were determined using a case-control approach. Cases were women with treatment of interest and controls other women on the study. RESULTS: Most DCIS cases (62%) were discovered by mammography screening. Ninety (78%) women had breast-conserving surgery (BCS), 18 (16%) mastectomy and seven (6%) bilateral mastectomy. Eight (7%) patients had tumor-positive margins, 18 (16%) lymph node dissection and two (1.7%) chemotherapy. Twenty-five per cent of women with BCS had no radiotherapy, three had radiotherapy after mastectomy. Less than 50% underwent breast reconstruction after mastectomy. Method of discovery, multifocality, tumor localization, size and differentiation were linked to the use of BCS or lymph node dissection. CONCLUSIONS: Because of important disparities in DCIS management, recommendations are made to increase quality of care, in particular to prevent axillary dissection or bilateral mastectomy and to increase the use of radiotherapy after BCS.
In selected cases of cervical retractions after burns, the authors show that pedicled latissimus dorsi musculocutaneous flaps may be of great help if properly performed. The main advantages of this method are its simplicity and the lack of need for a postoperative cervical splint.
Stimulating angiogenesis by gene transfer approaches offers the hope of treating tissue ischemia which is untreatable by currently practiced techniques of vessel grafting and bypass surgery. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) are potent angiogenic molecules, making them ideal candidates for novel gene transfer protocols designed to promote new blood vessel growth. In this study, an ex vivo gene therapy approach utilizing cell encapsulation was employed to deliver VEGF and FGF-2 in a continuous and localized manner. C(2)C(12) myoblasts were genetically engineered to secrete VEGF(121), VEGF(165) and FGF-2. These cell lines were encapsulated in hollow microporous polymer membranes for transplantation in vivo. Therapeutic efficacy was evaluated in a model of acute skin flap ischemia. Capsules were positioned under the distal, ischemic region of the flap. Control flaps showed 50% necrosis at 1 week. Capsules releasing either form of VEGF had no effect on flap survival, but induced a modest increase in distal vascular supply. Delivery of FGF-2 significantly improved flap survival, reducing necrosis to 34.2% (P < 0.001). Flap vascularization was significantly increased by FGF-2 (P < 0.01), with numerous vessels, many of which had a large lumen diameter, growing in the proximity of the implanted capsules. These results demonstrate that FGF-2, delivered from encapsulated cells, is more efficacious than either VEGF(121) or VEGF(165) in treating acute skin ischemia and improving skin flap survival. Furthermore, these data attest to the applicability of cell encapsulation for the delivery of angiogenic factors for the treatment and prevention of tissue ischemia.
We report a cohort of 148 African children operated on between 1985 and 2000 for noma sequelae. A total of 440 operations were performed. Lesions included mouth constriction in 70 of 148 cases, and severe bone destruction in 69 of 148 cases. A large proportion of children was transferred to Switzerland for surgical treatment, whereas the others were operated on in local hospitals in Africa. Vascularized calvarium flap was mostly used for bone reconstruction (n = 36). Pedicled latissimus dorsi myocutaneous flap was the preferred strategy for cheek reconstruction (n = 40). Expanded frontal flap was used for nasal reconstruction (n = 18), and pedicled heterolabial flap for lip construction (n = 37). Given the elevated level of recurrence of mouth constriction (extraarticular ankylosis), a minimum of 2 years' follow-up after surgical treatment was considered mandatory. Follow-up was conducted by field nurses from the humanitarian organizations, and a third of the patients were seen directly by our surgical team during special missions to Africa.
Angiopoietins are ligands for the endothelial cell tyrosine kinase receptor Tie-2. Ang-1, the major physiological activator of Tie-2, promotes blood vessel maturation and stability. Ang-2 counteracts this effect by competitively inhibiting the binding of Ang-1 to Tie-2. Using a combined RNase protection/semiquantitative reverse transcriptase-polymerase chain reaction approach, we demonstrate that hypoxia up-regulates Ang-2 mRNA levels by up to 3.3-fold in two human endothelial cell lines. In bovine microvascular endothelial (BME) cells, the flavoprotein oxidoreductase inhibitor diphenylene iodonium (DPI) and the related compound iodonium diphenyl mimic induction of Ang-2 but not vascular endothelial growth factor (VEGF) by hypoxia; in combination with hypoxia, DPI further increases Ang-2 expression but has no effect on the induction of VEGF by hypoxia. Neither Ang-2 or VEGF was increased by cyanide or rotenone, suggesting that failure in mitochondrial electron transport is not involved in the oxygen-sensing system that controls their expression. In ischemic rat dorsal skin flaps or in the brain of rats maintained for 12 hours under conditions of hypoxia, Ang-2 mRNA was up-regulated 7.5- or 17.6- fold, respectively. VEGF was concomitantly increased, whereas expression of Ang-1, Tie-2, and the related receptor Tie-1 was unaltered. In situ hybridization localized Ang-2 mRNA to endothelial cells in hypoxic skin. These findings 1) show that up-regulation of Ang-2 by hypoxia occurs widely in endothelial cells in vitro and in vivo; 2) suggest that induction of Ang-2, but not VEGF, by hypoxia in BME cells is controlled by a flavoprotein oxidoreductase that is sensitive to iodonium compounds; and 3) point to Ang-2 and VEGF as independently regulated and selective effectors of hypoxia-induced vascular sprouting.
A 4-year-old girl underwent craniofacial reconstruction for giant cystlike encephalocele deriving from the temporo-maxillary region and giving impression of the duplicated head. The case of temporal encephalocele in this report is especially unusual in the extent of encephalocele, the degree to which it had expanded the zygomatic arch, mandible, cranial vault, and the radiologically undetectable bony defect. The use of craniofacial principles in the resection and reconstruction of the temporal encephalocecle are described.
After analysing their concept of humanitarian plastic surgery, the authors present their personal experience which started in the 1970s, concerning two aspects: in the field (Burkina-Faso, Mali, Niger) and in Geneva, Switzerland, where the more difficult cases are operated. They illustrate their approach by a clinical case of sequelae of noma. They analyse the problems and/or questions raised by humanitarian plastic surgery: sufficient training, choice of surgical techniques, postoperative follow-up, assessment of the results obtained, possible innovations.
Plasmodium falciparum malaria, a parasitic disease, and sickle cell anemia, a hereditary disease, are two diseases affecting erythrocyte cycle, occurring with a high prevalence in tropical Africa. They may induce microthrombosis inducing vaso-occlusion, organ dysfunction and flap necrosis. During the acute phase of Plasmodium falciparum malaria, destruction of parasitized and healthy erythrocytes, release of parasite and erythrocyte material into the circulation, and secondary host reaction occur. Plasmodium falciparum infected erythrocytes also sequester in the microcirculation of vital organs and may interfere with microcirculatory flow in the flap during the postoperative period. The lower legs of homozygous sickle cell anemia patients are areas of marginal vascularity where minor abrasions become foci of inflammation. Inflammation results in decreased local oxygen tension, sickling of erythrocytes, increased blood viscosity and thrombosis with consequent ischemia, tissue breakdown and leg ulcer. Tissue transfer has become the procedure of choice for reconstruction of the lower third of the leg although flaps may become necrotic. The aim of this study is to analyse circumstances predisposing to surgical complications and to define preventive and therapeutic measures. A review of the literature will describe the current research and the new perspectives to treat sickle cell anemia, for example hydroxyurea and vasoactive substances (pentoxifylline, naftidrofuryl, buflomedil).
Acquired large nasal defects are much more common in adulthood than in childhood because of the frequency of skin tumors after a certain age. However, from their experience in treating a number of children with sequelae of noma and burns, the authors have collected a series of 17 total and 12 partial nasal reconstructions in children aged 1 to 15 years. After reviewing the various methods used for recreating the lining, the support, and the skin cover in the whole series, three cases are reported in detail. A 1-year-old patient received a tempororetroauricular flap after total amputation of the nose and was observed for 17 years. Another patient, who was burned as a baby, underwent reconstruction at age 10 with a deltopectoral flap and was observed for 7 years. The third patient underwent total nose reconstruction at age 12 with an Indian forehead flap. From their experience, the authors conclude that, for psychosocial reasons, nasal reconstruction should be started early, despite possible reoperation at a later age. The best results are certainly obtained at the end of growth or at least after the age of 12. Adjacent bone or soft tissue defects further enhance the difficult challenge of restoring a satisfactory aesthetic appearance in these children.
Two patients with recurrent parotid gland carcinoma required subtotal petrosectomy and infratemporal fossa type C approach. To achieve en bloc resection, the ascending mandibular ramus and the entire temporomandibular joint, including the adjacent temporal bone, were removed. An original technique for immediate reconstruction of the infratemporal region, including the glenoid fossa and the ramus of the mandible, is described. Rigid fixation, as well as good functional and aesthetic results, was achieved with autologous calvarial bone and full-thickness rib grafts, allowing the patients to mobilize their jaw very rapidly.
A case of gigantic orbital neurofibromatosis (2,500 gm) is presented. It is believed to be the largest such tumor reported since the famous elephantiasis neurofibromatosis pictured in von Bruns' Chirurgischer Atlas in 1857.
Sandwich epicranial flaps are prefabricated composite flaps that have multiple uses in reconstructing the middle and the lower facial region. Sandwich epicranial flaps always comprise the galea and a full-thickness skin graft; they may, in addition, include the temporal muscle and a fragment of parietal bone. According to their composition, four types of sandwich epicranial flaps are described. Experience with a use of 36 sandwich epicranial flaps (13 with vascularized bone) is reported. A few examples demonstrate the use of sandwich epicranial flaps in dramatic facial mutilation following noma in children. The sandwich epicranial flap can be performed at any age, does not require microsurgical anastomoses, and has a low complication rate. It is particularly useful for major reconstructive procedures in children.
This study compares survival of arterialized venous flaps placed on normal and impaired recipient beds in New Zealand White rabbit ear. Fasciocutanous flaps (4 x 5 cm) were perfused by an arteriovenous anastomosis; outflow was provided by one vein. In group 1, the arterialized venous flap was sutured into its bed on the ear; in group 2, a sheet of silicone was placed between the flap and the ear, providing an experimentally impaired recipient bed. Flap survival was expressed as a percentage of the total flap surface by means of a computerized image analysis system. Excellent survival (> or =95 percent) was noted in 16 of 21 arterialized venous flaps in group 1 versus 2 of 21 in group 2 (p < 0.01). Partial survival (50 to 94 percent) was observed in 2 of 21 arterialized venous flaps in group 1 and 15 of 21 in group 2. Poor survival (<50 percent) was noted in 3 of 21 in group 1 and in 4 of 21 in group 2. Microangiography was used to illustrate arteriovenous fistulas, the vascular network within the flaps, and neovessels in the periphery of the flaps. These data indicate that neovascularization is necessary for optimal survival of arterialized venous flaps in this experimental rabbit ear model.