Laurie Montgomery Irvine

Topical negative pressure stimulates endothelial migration and proliferation: a suggested mechanism for improved integration of Integra.

Topical negative pressure is an effective technique to promote wound healing and the integration of skin graft and synthetic dermal equivalents. We describe an in vitro model to investigate the effect of negative pressure on angiogenesis, a pivotal step. Dermal fibroblasts or human microvascular endothelial cells were cultured on Integra and subjected to intermittent or continuous negative pressure. At fixed intervals of over 120 hours, the Integra was fixed and assessed for cell migration (microscopy), cell viability (MTS assay), and cell proliferation (Ki67 immunostaining).Under control conditions, endothelial cells formed a monolayer and failed to ingress, whereas fibroblasts migrated throughout the Integra within 24 hours. Negative pressure switches endothelial cell to a migratory and proliferative phenotype. Ingress is greatest with intermittent rather than continuous negative pressure. It has no effect on dermal fibroblast function. This study identifies an important, potential pro-angiogenic mechanism by which topical negative pressure promotes wound healing.

Differential gene expression in response to transforming growth factor-β1 by fetal and postnatal dermal fibroblasts

The multipotent growth factor transforming growth factor (TGF)‐β1 is consistently linked with fibrosis and scarring. The perfect (scarless) healing of cutaneous wounds in early gestational age fetuses is proposed to be due to this tissues predominance of the TGF‐β3 isoform over the profibrotic TGF‐β1 and 2. Nevertheless, TGF‐β1 is present during wound healing in the early fetus and recently we demonstrated that relevant intracellular signaling pathways are activated (albeit transiently) on TGF‐β1stimulation. This study aimed to determine whether TGF‐β1 has different effects on gene transcription in human fetal (<14 weeks) vs. human postnatal dermal fibroblasts, using real‐time polymerase chain reaction. The regulation pattern of a number of TGF‐β response genes differed dramatically between the two cell sources. The typical autocrine loop of TGF‐β1 autoinduction did not occur in fetal fibroblasts and genes that are normally up‐regulated, connective tissue growth factor and collagen type I were actually down‐regulated. Furthermore, other response genes responded in a delayed fashion (TGF‐β3) compared with that seen in the more developmentally mature postnatal fibroblasts. Finally, genes unaltered by TGF‐β stimulation in postnatal cells, TGF‐β2 and collagen III, were up‐regulated in fetal cells. These developmentally related differences in fibroblast response to TGF‐β1 may influence wound‐healing outcome, i.e., perfect regeneration or fibrosis.

Dermal fibroblasts derived from fetal and postnatal humans exhibit distinct responses to insulin like growth factors

BackgroundIt has been well established that human fetuses will heal cutaneous wounds with perfect regeneration. Insulin-like growth factors are pro-fibrotic fibroblast mitogens that have important roles in both adult wound healing and during development, although their relative contribution towards fetal wound healing is currently unknown. We have compared responses to IGF-I and -II in human dermal fibroblast strains derived from early gestational age fetal (<14 weeks) and developmentally mature postnatal skin to identify any differences that might relate to their respective wound healing responses of regeneration or fibrosis.ResultsWe have established that the mitogenic response of fetal cells to both IGF-I and -II is much lower than that seen in postnatal dermal fibroblasts. Further, unlike postnatal cells, fetal cells fail to synthesise collagen in response to IGF-I, whereas they do increase synthesis in response to IGF-II. This apparent developmentally regulated difference in response to these related growth factors is also reflected in changes in the tyrosine phosphorylation pattern of a number of proteins. Postnatal cells exhibit a significant increase in phosphorylation of ERK 1 (p44) in response to IGF-I and conversely the p46 isoform of Shc on IGF-II stimulation. Fetal cells however only show a significant increase in an unidentified 100 kDa tyrosine-phosphorylated protein on stimulation with IGF-II.ConclusionDermal fibroblasts exhibit different responses to the two forms of IGF depending on their developmental maturity. This may relate to the developmental transition in cutaneous wound healing from regeneration to fibrosis.

In vitro optimisation of topical negative pressure regimens for angiogenesis into synthetic dermal replacements

BACKGROUND The use of synthetic dermal replacements (SDRs) in the treatment of large wounds, which have associated morbidity and mortality, has attracted great interest. However, because of poor outcome, SDRs have limited use. The addition of topical negative pressure (TNP) has increased their success, but little research has focused on the underlying mechanisms. This paper studies the in vitro effects of TNP on commonly used SDRs to identify the most effective TNP regimen and optimum SDR for encouraging endothelial cell ingress. METHODS Endothelial cells were co-cultured in vitro on four SDRs with or without TNP. Negative pressure (125mmHg) was applied intermittently, continuously, for 4h per day, or not at all. Endothelial ingress was measured for each condition. RESULTS In the collagen controls, cell migration was minimal. Integratrade mark gave the greatest endothelial cell migration (p<0.05, n=3). TNP increased endothelial cell migration, intermittent application being the optimum regimen. CONCLUSIONS Integratrade mark has an open sponge structure which may account for greater angiogenicity than Allodermtrade mark, Permacoltrade mark and Xenodermtrade mark. In vitro intermittent TNP stimulates the greatest angiogenic response. The majority of clinical studies investigating SDR success with TNP have used continuous regimens; this study suggests a change in clinical practice to intermittent application.

The role of C-reactive protein in modern obstetric and gynecological practice

C‐reactive protein is an acute phase protein widely used as an indicator of infectious or inflammatory conditions. Traditionally it has been used as an adjunctive test for inflammation and as a marker of disease activity. Though sensitive, its nonspecific nature imposes limitation on its clinical use. Currently C‐reactive protein is used in the management of chorioamnionitis, preterm premature rupture of membranes, pelvic inflammatory disease, and urinary tract infection. Interestingly, several obstetric conditions such as pre‐eclampsia and gestational diabetes are now known to have an underlying inflammatory basis and there is an emerging role of C‐reactive protein testing in managing these diseases. Additionally C‐reactive protein testing has an established place in management of several acute abdominal conditions. The aim of this paper is to review the place of C‐reactive protein in modern obstetric and gynecological practice.

The effects of patient obesity in gynaecological practice

Abstract Obesity is an increasing problem in the developed world, is more common in women than men and affects gynaecological practice in three ways. It has a direct effect in terms of increased risk of polycystic ovarian syndrome problems with ovulation induction, and endometrial carcinoma. It has an indirect effect in terms of difficulty in pelvic examination and imaging techniques. Obesity also leads to technical difficulties at surgery and an increase in morbidity and mortality post-operatively.

Risk Management and Litigation in Obstetrics and Gynaecology

Money paid out for clinical negligence now accounts for a sizeable part of National Health Service spending. The trend to litigation is increasing and the specialty of obstetrics and gynaecology suffers particularly because of high awards for brain damage in babies. Numerous books and courses offer advice on how to avoid such litigation, under the titles risk management and clinical governance. However, some clinicians feel that risk management is a drain on time and resources, without much benefit to the patient. This view, I believe, is partly due to a mistaken idea that risk management is synonymous with defensive medicine. Defensive medicine is a sloppy mode of practice whereby patients are overinvestigated so that the clinician escapes criticism if the outcome is unsatisfactory. (Most investigations yield some false-positives which then lead to further tests, which may be hazardous to the patient.) Risk management, by contrast, is about identifying the risks, deciding on practical strategies to minimize them and also deciding whether they are worth taking. Individuals and departments reach differing conclusions, hence the variations in management policies nationwide.

A rare sequel following cornual ectopic pregnancy: a case report.

One of the major concerns following cornual ectopic pregnancy, as shown in this case, is uterine rupture in future pregnancies. Uterine rupture has been described at 20 weeks gestation in a woman who had a cornual pregnancy treated by salpingectomy at 24 weeks, and as such it has been suggested by some experts that suturing the uterine wall to reinforce the defective area is advisable. Conversely, term deliveries have been described in patients with laparoscopic treatment of cornual pregnancies without reinforcing sutures. There is general agreement that suturing the uterine wall should be performed in cases where the cornual pregnancy sac extends into the endometrial cavity. Long-term follow-up of patients treated with cornual pregnancies with endometrial involvement may reveal the optimum treatment technique. In addition to surgical technique, patient counselling and appropriate debriefing regarding increasing interpregnancy interval is paramount in reducing maternal and fetal morbidity. Proper documentation in operative notes is vitally important for future reference.

Ectopic pregnancies in two consecutive menstrual cycles

were ten deaths from sepsis after vaginal delivery and five were due to group A streptococcal infection. One of these women had a hysterectomy, and the specimen showed extensive haemorrhagic infarction; another woman died before onset of labour9. The common feature of all these cases, including ours, was insidious onset with rapid progress to septicaemia. Our report emphasizes the recommendations of the Report on Confidential Enquiries that puerperal sepsis is not a disease of the past and all health care professionals must be aware of this aggressive illness.

The Labour Ward Handbook

Clinical decisions on the labour ward often have to be made quickly and the choice between management options is seldom guided by the results of randomized controlled trials. For this reason, many units develop their own set of labour ward protocols, based as much on the experience of the senior obstetricians and midwives as on published evidence. The Labour Ward Handbook is based on protocols from the Royal Oldham Hospital. The first two sections deal with the care of pregnant women and the management of normal and low-risk labour. The third and last covers abnormal and high-risk labour, in six parts including medical and haematological aspects. We begin with those with cornerstones of good labour ward practice communication, documentation and incident reporting, often poorly covered in textbooks but well handled here. Another highly informative section is that on management of latex allery, which seems to be getting more common. If recognized too late in a patient this can lead to cancellation of elective procedures; and in an emergency it can greatly complicate the preparation of operating theatres and equipment, including anaesthetic machines. The book provides a list of all those items of equipment containing latex—some of which, such as cardiotocographic monitors—are not obvious, together with six recent references on latex allergy. I was also impressed by some of the flow diagrams, such as the one on management of a woman with a history of genital herpes. With its numerous headings and bullet points The Labour Ward Handbook is not something one wants to read from cover to cover. Moreover, the style is dictatorial, with scant discussion of alternative options. It should be read in conjunction with the local labour ward protocol; any differences might generate useful debate on what is best practice. Though this handbook will interest obstetricians of all levels, I would recommend it especially to those sitting examinations, and those writing or updating local labour ward protocols. It is easy to use and encourages further reading with its large number of recent references.