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Biomedical subjects

Brigitte Pittet

Publications and source records attributed to Brigitte Pittet.

8 recordsLinked to original sources
PubMed2007

Aging is associated with an increased susceptibility to ischaemic necrosis due to microvascular perfusion failure but not a reduction in ischaemic tolerance.

In the present study in a murine model of chronic ischaemia, we analysed: (i) whether aging was associated with an increased susceptibility to ischaemic necrosis, and (ii) whether this was based on microvascular dysfunction or reduced ischaemic tolerance. An ischaemic pedicled skin flap was created in the ear of homozygous hairless mice. The animals were assigned to three age groups, including adolescent (2+/-1 months), adult (10+/-2 months) and senescent (19+/-3 months). Microvascular perfusion of the ischaemic flap was assessed over 5 days by intravital microscopy, evaluating FCD (functional capillary density), capillary dilation response and the area of tissue necrosis. Expression of the stress-protein HO (haem oxygenase)-1 was determined by immunohistochemistry and Western blotting. Induction of chronic ischaemia stimulated a significant expression of HO-1 without a significant difference between the three age groups. This was associated with capillary dilation, which, however, was more pronounced in adolescent (10.5+/-2.8 microm compared with 3.95+/-0.79 microm at baseline) and adult (12.1+/-3.1 microm compared with 3.36+/-0.45 microm at baseline) animals compared with senescent animals (8.5+/-1.7 microm compared with 3.28+/-0.69 microm at baseline; P value not significant). In senescent animals, flap creation further resulted in complete cessation of capillary flow in the distal area of the flap (FCD, 0+/-0 cm/cm(2)), whereas adult (11.9+/-13.5 cm/cm(2)) and, in particular, adolescent animals (58.4+/-33.6 cm/cm(2); P<0.05) were capable of maintaining residual capillary perfusion. The age-associated microcirculatory dysfunction resulted in a significantly increased flap necrosis of 49+/-8% (P<0.05) and 42+/-8% (P<0.05) in senescent and adult animals respectively, compared with 31+/-6% in adolescent mice. Of interest, functional inhibition of HO-1 by SnPP-IX (tin protoporphyrin-IX) in adolescent mice abrogated capillary dilation, decreased functional capillary density and aggravated tissue necrosis comparably with that observed in senescent mice. Thus aging is associated with an increased susceptibility to tissue necrosis, which is due to a loss of vascular reactivity to endogenous HO-1 expression, rather than a reduction in ischaemic tolerance.

Aging↗
PubMed2006

Progressive tissue injury in burns is reduced by rNAPc2.

INTRODUCTION: Burn wounds are characterised by central necrosis surrounded by an area of stasis with compromised perfusion. Secondary aggravation of the burn wound due to ischaemia in the zone of stasis can also result in necrosis. This study aims to improve circulation in the zone of stasis by reducing microthrombus formation and thereby to reduce secondary aggravation. MATERIAL AND METHODS: Recombinant nematode anticoagulant protein (rNAPc2) was administered to Wistar rats at 3 or 30 microg/kg as a single or daily dose. A comb pattern burn was induced on the dorsum of these rats and its evolution monitored by serial photography, planimetry, laser doppler flowmetry and immunohistochemistry. RESULTS: In the 30 microg/kg daily group, extension of the burn wound was curbed, limiting the burn area to 1.99+/-0.67 cm(2) on day 28, compared to 3.51+/-0.37 cm(2) in the control group (p=0.015). Laser doppler evaluation showed a significant (p<0.001) increase in circulation in the first day post-burn. Significantly less (p<0.001) microvascular fibrin formation was observed by immunohistochemistry. CONCLUSION: Anticoagulation with rNAPc2 improved perfusion of the burn wound. The resultant reduction in the area of the burn led to earlier healing and less scar contracture.

Animals↗
PubMed2006

The free serratus anterior flap and its cutaneous component for reconstruction of the face: a series of 27 cases.

BACKGROUND: The serratus anterior flap is commonly used without its cutaneous component and is covered with a skin graft. The authors have successfully used the free serratus anterior flap along with its skin paddle and have found it to be valuable for reconstruction of the face. METHODS: Fresh cadaveric dissections and arteriography were performed to identify perforator vessels to the skin overlying the muscle. Clinically, free transfer of the musculocutaneous flap to the face was carried out in 27 patients, mostly for severe noma (infection) sequelae. RESULTS: Anatomical dissection and arteriography revealed no cutaneous perforator vessels directly communicating with the vascular pedicle of the muscle. However, large perforators from the intercostal vessels were found passing through the muscle to reach the skin. In the clinical cases, flap survival was 100 percent in 24 patients. CONCLUSIONS: The serratus anterior musculocutaneous flap is reliable and particularly well-suited for reconstruction of the face, and has many advantages. The authors speculate that the skin paddle may be vascularized by perforators from the intercostal vessels communicating with the thoracodorsal pedicle through intramuscular choke vessels.

Adolescent↗
PubMed2005

Infection in breast implants.

Infection is the leading cause of morbidity that occurs after breast implantation and complicates 2.0-2.5% of interventions in most case series. Two-thirds of infections develop within the acute post-operative period, whereas some infections may develop years or even decades after surgery. Infection rates are higher after breast reconstruction and subsequent implantation than after breast augmentation. Risk factors for infection associated with breast implantation have not been carefully assessed in prospective studies with long-term follow-up. Surgical technique and the patient's underlying condition are the most important determinants. In particular, breast reconstruction after mastectomy and radiotherapy for cancer is associated with a higher risk for infection. The origin of infection in women with implants remains difficult to determine, but potential sources include a contaminated implant, contaminated saline, the surgery itself or the surgical environment, the patient's skin or mammary ducts, or, as suggested by many reports, seeding of the implant from remote infection sites. Late infection usually results from secondary bacteraemia or an invasive procedure at a location other than breasts. Diagnostic and management strategies are proposed and the value of peri-operative surgical prophylaxis is revisited. The current hypothesis of the possible role of low-grade or subclinical infection in the origin of capsular contracture is also reviewed.

Bacterial Infections↗
PubMed2004

Active-site inactivated FVIIa decreases thrombosis and necrosis in a random skin flap model of acute ischemia.

BACKGROUND: Previous studies have emphasized the role of ischemia in inducing vascular thrombosis. MATERIALS AND METHODS: Using a skin flap model of acute ischemia in the rat, we studied the effect of active-site inactivated factor VIIa (FVIIai), an inhibitor of tissue factor (TF), on tissue survival during acute ischemia. RESULTS: Ribonuclease protection analysis revealed an increase in TF in ischemic parts of the flap, and in situ hybridization localized this increase mainly to perivascular cells. A decrease in vascular thrombosis, as determined by fibrin immunostaining, was observed in FVIIai-treated animals. Intravenous administration of FVIIai had a positive impact on survival of the flap. Laser Doppler flowmetry revealed an increase in blood flow in the FVIIai-treated group. In treated animals, prothrombin time (PT) was increased (P < 0.01), whereas partial thromboplastin time (APTT) was unaltered; no significant impairment in systemic hemostasis (peri- and postoperative bleeding) was observed. CONCLUSIONS: These findings demonstrate that TF expression is increased in perivascular cells in ischemic skin flaps and that FVIIai, by inhibiting TF, increases flap survival.

Acute Disease↗
PubMed2003

Noma: an "infectious" disease of unknown aetiology.

Noma (cancrum oris) is a devastating gangrenous disease that leads to severe tissue destruction in the face and is associated with high morbidity and mortality. It is seen almost exclusively in young children living in remote areas of less developed countries, particularly in Africa. The exact prevalence of the disease is unknown, but a conservative estimate is that 770000 people are currently affected by noma sequelae. The cause remains unknown, but a combination of several elements of a plausible aetiology has been identified: malnutrition, a compromised immune system, poor oral hygiene and a lesion of the gingival mucosal barrier, and an unidentified bacterial factor acting as a trigger for the disease. This review discusses the epidemiology, clinical features, current understanding of the pathophysiology, and treatment of the acute phase and sequelae requiring reconstructive surgery. Noma may be preventable if recognised at an early stage. Further research is needed to identify more exactly the causative agents.

Africa↗
PubMed2002

Skin flap-induced regression of granulation tissue correlates with reduced growth factor and increased metalloproteinase expression.

Previous studies have shown that covering granulation tissue of a full-thickness skin wound by a vascularized skin flap induces tissue remodeling, with a rapid loss of granulation tissue cells by apoptosis. In the present study, in situ hybridization has been used to examine mRNA expression for several factors that may be implicated in the apoptosis seen in this tissue. Skin wounds were made on the dorsal skin of 8-week-old rats. Ten days after wounding, skin flaps were created surgically and sutured over the granulation tissue. Tissue sections of granulation tissue from various times after addition of the skin flap were hybridized with 33P-labelled cRNA probes for transforming growth factor-beta1 (TGF-beta1), beta-inducible gene H3 (beta-ig-h3), alpha1 (1) procollagen, alpha-smooth muscle actin, matrix metalloproteinase-13 (MMP-13) and -2 (MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), and inducible nitric oxide synthase (iNOS). Control granulation tissue prior to addition of the skin flap showed high levels of TGF-beta1, beta-ig-h3, alpha1 (1) procollagen, alpha-smooth muscle actin, and TIMP-1 expression. MMP-13, MMP-2, and iNOS mRNA were low in 10-day granulation tissue. Addition of a skin flap resulted in a decrease in the expression of TGF-beta1, beta-ig-h3, alpha1 (I) procollagen, alpha-smooth muscle actin, and TIMP-1, but increased expression of MMP-13 and MMP-2. Similarly, an increase in iNOS mRNA expression was observed in the granulation tissue after addition of the skin flap. Addition of a vascularized skin flap may result in rapid remodelling of granulation tissue due to a decrease in expression of the trophic growth factor TGF-beta1 and increased degradation of extracellular matrix due to an alteration in the balance between MMPs and their inhibitor, TIMP-1. Additionally, increased iNOS expression may also favour apoptosis through the generation of free radicals. The additive effect of reduced growth factor expression, increased extracellular matrix turnover, and nitric oxide generation may result in the fibroblast and vascular cell apoptosis seen during the rapid remodelling of this tissue.

Animals↗