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Biomedical subjects

M C Robson

Publications and source records attributed to M C Robson.

At least 19 recordsLinked to original sources
PubMed2005

Nasal infection with Scedosporium apiospermum in a dog.

CASE HISTORY: A 2-year-old female Siberian Husky was presented with a 6-month history of sneezing and mucous discharge from the right nostril. CLINICAL FINDINGS: Reduced airflow through the right nostril was evident. Radiographs showed subtle loss of detail of turbinates within the right nasal chamber. Rhinoscopy revealed swollen and erythematous turbinates and a white mass within the caudal aspect of the right nasal cavity. Histopathologically, there was a heavy mixed inflammatory infiltrate in the submuscosa of the right turbinate, and the presence of fungal hyphae and spores in the white mass. A heavy growth of Scedosporium apiospermum was cultured from the mass. DIAGNOSIS: Chronic rhinitis of the right nasal cavity and infection with S. apiospermum. CLINICAL RELEVANCE: This is the first reported case of S. apiospermum isolated from the nasal cavity of a dog in New Zealand. Fungal culture is necessary to differentiate this fungus from Aspergillus spp.

Animals↗
PubMed2005

Pancreatic cyst in a cat.

CASE HISTORY: A 5-year-old neutered male Cornish Rex cat was presented for evaluation with a history of vomiting over the previous 5 days. CLINICAL FINDINGS: An abdominal mass was palpated, which was shown to be cystic by ultrasound examination. Exploratory surgery revealed this to be associated with the pancreas and it was duly resected. Histopathology was performed on the cystic mass. DIAGNOSIS: Pancreatic cyst with associated chronic active inflammation. CLINICAL RELEVANCE: This is the first report of a true pancreatic cyst in a cat.

Animals↗
PubMed2005

Current attitudes to, and use of, peri-operative analgesia in dogs and cats by veterinarians in New Zealand.

AIM: To investigate the attitudes of veterinary practitioners in New Zealand to pain and analgesia, and their use of analgesic drugs, in dogs and cats. METHODS: A questionnaire posted to 1,200 practising veterinarians was used to gather information about the use of analgesia in dogs and cats, assessment of pain, attitudes to pain relief, analgesic drugs and procedures used, factors affecting choice of analgesic agent, and veterinary demographics, continuing education and staffing. RESULTS: Three hundred and twenty questionnaires with useable data were returned, a response rate of 28%. Male and female veterinarians were evenly represented. The analgesic agents most commonly used were morphine (opioids) and carprofen (a non-steroidal anti-inflammatory drug; NSAID). Use of peri-operative pain relief ranged from 50% for castration of cats to 91% for fracture repair in dogs. For most procedures, female veterinarians scored pain at a significantly higher level than their male colleagues. Fifty-eight percent of respondents considered their knowledge in the area of assessment and treatment of pain was adequate. CONCLUSIONS: This survey was considered representative of veterinarians working in companion animal practice in New Zealand. Results indicated a relatively high use of peri-operative analgesia, including both pre-emptive and multi-modal analgesia, in cats and dogs, although there was still some disparity between the perception of how painful a procedure was and the consequent use of pain relief. CLINICAL RELEVANCE: The establishment of current attitudes and practices indicates to practising veterinarians how their own use of analgesics compares with that of their colleagues. It also provides information to educators on potential areas of focus, given that 42% of respondents felt their knowledge in the area of assessment and treatment of pain was inadequate.

Analgesia↗
PubMed2004

Initial healing rates of venous ulcers: are they useful as predictors of healing?

Clinical trials that follow venous ulcers to complete healing can be costly because of the prolonged healing time involved. Initial healing rates in venous ulcers are calculated by 2 methods, which are based on a metric using wound area and perimeter. It has been proposed that these rates allow the prediction of complete healing and that they may be useful as surrogate end points for clinical trials. The objective of this study was to compare the 2 proposed methods for calculating initial healing rates and determine their usefulness in predicting the healing of venous ulcers. Venous leg ulcers from patients enrolled in a randomized, double-blind, placebo-controlled study were measured weekly for up to 12 weeks. Their healing status was determined for up to 24 weeks. Initial healing rates were calculated using the 2 proposed methods. The ability of these rates to predict time to complete healing was assessed. Information from 17 patients was available. The initial healing rates, calculated by either method, were quite similar; both methods produced the same median value of 0.046 cm/week in our patients. Five of the patients had negative initial healing rates, which do not allow any prediction of a healing time. Three of 7 patients predicted to heal within 24 weeks failed to do so. One of the 5 patients was predicted to heal at some time after 24 weeks but actually healed within 24 weeks. None of the 5 patients with negative initial healing rates healed within 24 weeks. Initial healing rates, as calculated by either method, have limited utility in describing healing curves and predicting a healing time. This poor predictive ability argues against using these initial healing rates as surrogate end points for clinical trials. The great variability observed in venous ulcer healing curves may limit the development of useful predictive models in this patient population.

Aged↗
PubMed2004

Successful treatment of a pancreatic pseudocyst by omentalisation in a dog.

CASE HISTORY: A 3-year-old male Labrador retriever was presented with a history of dietary indiscretion followed by vomiting and abdominal pain. CLINICAL FINDINGS AND TREATMENT: Abdominal ultrasonography revealed the presence of a fluid-filled cystic structure in the region of the pancreas. Flocculent, dark fluid was drained from the cystic structure during exploratory celiotomy prior to resection of the lateral cystic wall. Omentum was sutured into the cystic cavity to provide drainage and enhance immune response. A jejunostomy feeding tube was placed. Post-surgical care consisted of antibiotic therapy. The dog was clinically normal at 1 and 7 months post-operatively and the pancreas appeared normal on final ultrasonographic examination. CLINICAL RELEVANCE: This case describes the use of omentum to provide physiological drainage of a pancreatic pseudocyst. This surgical technique may help clinicians manage patients with this condition in the future.

Journal Article↗
PubMed2001

Transforming growth factor beta(2) lowers the incidence of incisional hernias.

BACKGROUND: Approximately 200,000 incisional hernias are repaired annually in the United States. The high incidence (11-20%) and recurrence rate (24-54%) for incisional hernias have not changed appreciably in 75 years. Mechanical advances in suture material, incision orientation, and closure technique have failed to eliminate this common surgical complication. A biological approach to acute wound failure may offer a new strategy. METHODS: A rodent incisional hernia model was used. Seventy rats underwent 5-cm midline celiotomies and were closed with fine, fast-absorbing sutures to induce intentional acute wound failure. Group 1 received no other treatment. The midline fascia in groups 2 and 3 was injected immediately prior to incision with 100 microl of vehicle alone or vehicle containing 1 microg of transforming growth factor beta(2) (TGF-beta(2)). Necropsy was performed on Postoperative Day 28 and the wounds were examined for herniation. RESULTS: Incisional hernias developed in 88% (35/40) and 79% (11/14) of untreated incisions and those treated with vehicle alone. No hernias formed in the TGF-beta(2)-treated incisions (0/16, P < 0.05). Standard histology and immunohistochemistry demonstrated enhanced macrophage, lymphocyte, and fibroblast chemotaxis and increased collagen I and III production in TGF-beta(2) treated incisions. CONCLUSIONS: Treatment of abdominal wall fascial incisions with TGF-beta(2) prevented the development of incisional hernias in this rat model. TGF-beta(2) stimulated fascial macrophage and fibroblast chemotaxis as well as acute wound collagen production. A biological approach such as this may reduce the incidence of incisional hernia formation in humans.

Abdominal Muscles↗
PubMed2001

Abdominal wall repair is delayed during hepatic regeneration.

BACKGROUND: Abdominal wall wound failure remains a common surgical problem. The signals that activate normal fibroplastic repair versus regeneration pathways are unknown. Transforming growth factor beta levels rise during incisional healing but fall during hepatic regeneration. Changes in the injured host cytokine milieu may therefore differentially effect abdominal wall repair versus hepatic regeneration. MATERIALS AND METHODS: Forty-eight rats were divided into four groups (n = 12). Groups 1-3 underwent sham celiotomy, 70% hepatectomy, or 80% enterectomy with anastamosis. Incisions from Group 4 were treated with either 1 microg of transforming growth factor beta(2) (TGF-beta(2)) or vehicle following hepatectomy. Isolated fascial and dermal incisions were harvested and tested for breaking strength on POD 7. Serum (TGF-beta(2)) and hepatocyte growth factor (HGF) levels were measured by ELISA. RESULTS: Recovery of incisional wound breaking strength was delayed following hepatectomy but not enterectomy (P<0.002). The inhibitory effect was observed in both the fascia and the dermis of the abdominal wall. TGF-beta(2) levels were depressed in hepatectomy animals on POD 7, while at the same time HGF levels were elevated. Exogenous TGF-beta(2) shifted the healing trajectory of deficient wounds back toward a control pattern. CONCLUSION: Abdominal wall fascial and dermal healing is delayed during hepatic regeneration. Elevated HGF and depressed TGF-beta(2) suggest a host mechanism that prioritizes hepatic parenchymal regeneration over fibroplastic repair (scar). Observations such as these are needed as therapeutic wound healing enters the clinical realm.

Abdominal Muscles↗
PubMed2001

Long-term outcome study of growth factor-treated pressure ulcers.

BACKGROUND: Exogenous application of growth factors have been reported in an attempt to accelerate healing of chronic wounds. Most of the trials were of brief duration with short to no follow-up periods. Long-term outcome studies are sparse for pressure ulcer therapies with success rates around 30% for both operative and nonoperative treatments. METHODS: Follow-up evaluations were performed serially up to 12 months for patients completing a 35 day blinded, placebo-controlled cytokine clinical trial of pressure ulcers. RESULTS: Fifty-four of 61 patients completed the follow-up period with 68.5% of the patients (37 of 54) being healed after 1 year. Of patients healing > or =85% during the active treatment phase, 84.6% were healed after 1 year compared with 61% of those that healed <85% during treatment (P <0.05). CONCLUSION: Long-term outcome was better in this growth factor trial than with surgical or standard nonoperative treatment of pressure ulcers. Since only patients receiving exogenously applied cytokines achieved >85% closure during the treatment phase of the trial, the excellent long-term outcome appears attributable to the cytokine therapy.

Administration, Topical↗
PubMed2001

Fascial incisions heal faster than skin: a new model of abdominal wall repair.

BACKGROUND: Optimal healing of the fascial layer is a necessary component of complete abdominal wall repair. The majority of acute wound healing studies have focused on the dermis. We designed a model of abdominal wall repair that, to our knowledge, for the first time simultaneously characterizes differences in the wound healing trajectories of the fascia and skin. METHODS: Full-thickness dermal flaps were raised on the ventral abdominal walls of rats, and midline fascial celiotomies were completed. The dimensions of the flap were developed so as to have no detrimental effect on skin healing. The dermal flaps were replaced so that the fascial incisions would heal separately from the overlying skin incisions. Animals were killed 7, 14, and 21 days after operation and fascial and dermal wounds were harvested and tested for breaking strength. Fascial and dermal wounds were also compared histologically for inflammatory response, fibroplasia, and collagen staining. RESULTS: Fascial wound breaking strength exceeded dermal wound breaking strength at all time points (9.16 +/- 2.17 vs 3.51 +/- 0.49 N at 7 days, P <.05). Fascial wounds also developed greater fibroblast cellularity and greater collagen staining 7 days after the incision. There was no difference in wound inflammatory response. CONCLUSIONS: Fascial incisions regain breaking strength faster than simultaneous dermal incisions. The mechanism for this appears to involve increased fascial fibroplasia and collagen production after acute injury.

Abdominal Muscles↗
PubMed2001

Cytokine manipulation of explanted Dupuytren's affected human palmar fascia.

INTRODUCTION: Dupuytren's disease plagues human hands and digits producing fibrotic nodules and fascial cords with resultant debilitating flexion contracture deformities. Interest in this condition is great but because the disease is specific to humans and study has been hampered by the lack of an in vivo model. By utilizing an in vivo "nude" rat model it is possible to maintain and study explanted Dupuytren's contracted palmar fascia for prolonged periods of time. MATERIALS AND METHODS: Human specimens were divided into four, one for in vitro analysis, and three for model explantation. The explanted tissue was perfused with either transforming growth factor beta-2 (TGFbeta2), its antibody, or a control vehicle. Explant biopsies were obtained at 30 and 60 days and compared to tissue prior to explantation. Immunohistochemistry of collagen I and III, DNA synthesis, protein production, and fibroblast kinetics were serially determined. RESULTS: Perfusion of explanted Dupuytren's tissue by TGFbeta2 upregulated collagen I and III from biopsies obtained from the explants at 30 days when compared to vehicle control (P < 0.001). Perfusion with antibody prevented this upregulation when compared to vehicle control (P < 0.001). Cell cultures derived from fibroblasts obtained from biopsies of the explants perfused with TGFbeta2 increased DNA synthesis, protein production and fibroblast kinetics. CONCLUSION: These findings paralleled those from other fibroproliferative disorders suggesting a role for TGFbeta2 in the pathogenesis of Dupuytren's contracture as well as possible novel treatment approaches.

Analysis of Variance↗
PubMed2001

Silicone sheeting decreases fibroblast activity and downregulates TGFbeta2 in hypertrophic scar model.

BACKGROUND: Fibroproliferative disorders, which include hypertrophic scars and keloids, represent deviations from the normal process of wound healing. The fibrogenic cytokines have been associated with excessive scarring. It has been proposed that placing silicone in contact with hypertrophic scars may prove to be an effective form of treatment. This may be a result of downregulating fibroblasts and/or decreasing the fibrogenic cytokines. An in vitro model to study wound contraction is a fibroblast populated collagen lattice (FPCL). This study used FPCL as a method to study the effect of silicone sheeting on hypertrophic scar fibroblasts. METHODS: Fibroblast cultures were obtained and collagen lattices were prepared. Silicone sheeting was placed over the collagen matrix versus Saran wrap used as a treatment control. The amount of gel contraction was measured every 24 hours for five days. The supernatant obtained from the culture medium following completion of the FPCL portion of the experiment was then used in an immunoassay for TGFbeta2. RESULTS: A statistically significant decrease in amount of FPCL contraction occurred between three of the four brands of silicone sheets used compared to untreated control or Saran wrap treated FPCL. The immunoassay for TGFbeta2 showed a statistically significant decrease with all four types of silicone sheeting. CONCLUSION: FPCLs populated with burn hypertrophic scar fibroblasts exposed to silicone sheeting have decreased contraction compared to an unexposed control and Saran wrap treated control. In addition, TGFbeta2 is downregulated in the silicone exposed group. It appears that silicone sheeting may act by downregulating fibroblasts and decreasing fibrogenic cytokines.

Cells, Cultured↗
PubMed2000

Wound healing trajectories as predictors of effectiveness of therapeutic agents.

BACKGROUND: One goal of wound healing research is to discover agents to accelerate healing. Regulatory agencies have suggested stringent criteria to determine efficacy, that of 100% wound closure. Data analysis at a single point such as 100% closure does not provide detailed information about agent effectiveness over the entire span of healing. HYPOTHESIS: Wound healing trajectories can provide such information and can be used to demonstrate utility as alternative end points for wound healing trials. DESIGN: Data from 160 patients in 11 clinical trials of diabetic foot ulcers conducted at 2 centers were evaluated. Wound healing trajectories were constructed for patients whose wounds healed (100% closure) and those whose did not (<100% closure) over a 20-week period. The percentage of patients achieving total healing vs time of treatment was plotted and divided into patients receiving a test agent or placebo. RESULTS: The healing trajectories were almost identical for patients achieving complete healing at the 2 centers, as were the trajectories for patients with less than 100% closure. However, the trajectories of patients achieving total healing were significantly different from those not achieving 100% closure. Fifty-two percent of all patients achieved 100% healing by 20 weeks; 61% of patients receiving an experimental agent had total healing compared with 39% of placebo-treated patients. Linear regression suggested that all patients would achieve total healing by 37 weeks. CONCLUSIONS: Since wound healing trajectories for diabetic foot ulcers treated at 2 centers so closely mimic one another, trajectories might be useful efficacy end points, and used to compare significant points along a continuum rather than a single static end point. Shifting of the wound healing trajectory from an impaired to a more ideal course may be considered when determining efficacy of new wound treatments.

Debridement↗
PubMed2000

Initiating the inflammatory phase of incisional healing prior to tissue injury.

BACKGROUND: The time required for incisional healing accounts for the majority of postoperative pain and convalescence. Impaired healing prolongs the process further. If a method for accelerating acute incisional wound healing could be developed, patients would benefit from decreased wound failure and an earlier return to their premorbid condition. MATERIALS AND METHODS: In a rat dermal model, cytokine or vehicle infiltration prior to incision was performed using a single dose or four daily doses preincision. Planned incision sites were primed with the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) or platelet-derived growth factor BB (PDGF-BB) in an effort to activate the inflammatory phase of healing prior to wounding. At the time of incision closure, one half of the incisions were treated with transforming growth factor beta(2) (TGF-beta(2)). Incisional sites were biopsied and stained with hematoxylin and eosin and immunohistochemistry for inflammatory cells and fibroblast populations and breaking strength was measured. RESULTS: Priming skin with GM-CSF or PDGF-BB mimicked the early inflammatory phase of wound healing. Macrophage staining (EB1) and fibroblast staining (vimentin) were significantly increased prior to incision. Inflammatory priming as well as priming coupled with TGF-beta(2) at the time of the incision closure synergistically improved breaking strength. CONCLUSION: This study demonstrates that sequential therapy consisting of priming of tissue with an inflammatory cytokine followed by application of a proliferative cytokine at the time of incision closure nearly doubles the breaking strength of an acute wound. By manipulating the inflammatory and early proliferative phases of wound healing with tissue growth factors, it may be possible to accelerate acute wound repair and shift the wound healing trajectory to the left.

Animals↗
PubMed2000

Periprosthetic breast capsules contain the fibrogenic cytokines TGF-beta1 and TGF-beta2, suggesting possible new treatment approaches.

Periprosthetic breast capsules composed of fibrotic collagenous material with increased collagen production are not dissimilar to other fibrotic conditions occurring in other organs. Fibrosis in the lung, liver, kidney, and skin has been associated with overproduction of the fibrogenic isoforms of transforming growth factor beta (TGF-beta1 and TGF-beta2). If periprosthetic breast capsules contained high levels of these cytokines, possibly new treatment approaches for capsular contraction could be proposed. Breast implant capsules of 35 patients harvested at the time of explantation were examined using indirect immunohistochemistry. Staining intensity for TGF-beta1 and TGF-beta2 was measured in all specimens. Immunohistochemical staining for TGF-beta1 and TGF-beta2 revealed that these two cytokines were present in all capsules analyzed. Minimal TGF-beta1 and TGF-beta2 were found in normal breast tissue. Levels of control vs. TGF-beta1 and control vs. TGF-beta2 were significant (p = 0.004 and p < 0.001 respectively). The presence of TGF-beta isoforms that are known to be fibrogenic may suggest new therapeutic approaches, which are being investigated for other fibrotic conditions.

Breast↗
PubMed2000

Overexpression of transforming growth factor beta-2 and its receptor in rhinophyma: an alternative mechanism of pathobiology.

Proliferative scarring is one of the clinical features of rhinophyma. The following study was undertaken to test the authors' hypothesis that fibrosis might also play an important role in the pathobiology of rhinophyma. The rhinophyma specimens were obtained from 5 white men (mean age, 67.8 years). Normal skin biopsies near benign facial lesions from 5 additional white men of similar age were obtained to serve as controls. Peroxidase-labeled immunohistochemical staining was performed in the rhinophyma and normal skin specimens for the presence of transforming growth factor (TGF) beta-2 and/or TGF-beta II receptor. Histological slides were then measured for the intensity of staining for TGF-beta2 and TGF-beta II receptor using a computer-aided imaging system. The dermis of the rhinophyma tissue displayed stronger immunoreactivity of TGF-beta2 (p = 0.014) and TGF-beta II receptor (p = 0.006) compared with the normal skin. The results of this study demonstrate the overexpression of the fibrogenic protein TGF-beta 2 and TGF-beta II receptor in rhinophyma tissues. These findings support the authors' hypothesis that fibrosis may also play an important role in the pathobiology of rhinophyma.

Aged↗
PubMed2000

Sequential cytokine therapy for pressure ulcers: clinical and mechanistic response.

OBJECTIVE: To compare the healing response of sequential topically applied cytokines to that of each cytokine alone and to a placebo in pressure ulcers, and to evaluate the molecular and cellular responses. SUMMARY BACKGROUND DATA: Because of a deficiency of cytokine growth factors in chronic wounds and the reversal of impaired healing in animal models, pressure ulcer trials have been performed with several exogenously applied growth factors. Because single-factor therapy has not been uniformly successful, combination or sequential cytokine therapy has been proposed. Laboratory data have suggested that sequential treatment with granulocyte-macrophage/colony-stimulating factor (GM-CSF)/basic fibroblast growth factor (bFGF) might augment the previously reported effect of bFGF alone. METHODS: A masked, randomized pressure ulcer trial was performed comparing sequential GM-CSF/bFGF therapy with that of each cytokine alone and with placebo during a 35-day period. The primary measure was wound volume decrease over time. Cytokine wound levels and mRNA levels were serially determined. Fibroblast-populated collagen lattices (FPCLs) were constructed from serial fibroblast biopsies. Cellular ultrastructure was evaluated by electron microscopy. Changes in ease of surgical closure and its relative cost were determined. RESULTS: Ulcers treated with cytokines had greater closure than those in placebo-treated patients. Patients treated with bFGF alone did the best, followed by the GM-CSF/bFGF group. Patients treated with GM-CSF or bFGF had higher levels of their respective cytokine after treatment. Patients with the greatest amount of healing showed higher levels of platelet-derived growth factor (PDGF) on day 10 and transforming growth factor beta (TGFbeta1) on day 36. Message for the bFGF gene was upregulated after treatment with exogenous bFGF, suggesting autoinduction of the cytokine. FPCLs did not mimic the wound responses. Ultrastructure of wound biopsies showed response to bFGF. Treatment with any of the cytokines improved the wound by allowing easier wound closure. This was most marked for the bFGF-alone treatment, with a cost savings of $9,000 to $9,200. CONCLUSIONS: Treatment with bFGF resulted in significantly greater healing than the other treatments in this trial. The clinical response appeared to be related to upregulation of the bFGF message and to increased levels of PDGF-AB, bFGF, and TGFbeta1 in the wounds and changes in ultrastructure. The resultant improvements could be correlated with cost savings.

Double-Blind Method↗
PubMed2000

The effect of TGF-beta2 in various vehicles on incisional wound healing.

BACKGROUND: The isoforms of transforming growth factor beta (TGF-beta) have been shown to be deficient in models of impaired wound healing. Exogenous application of the growth factor to enhance healing as been investigated. TGF-beta1 has been shown to enhance incisional wound strength, but to be dependent on the vehicle used to carry the cytokine. Because TGF-beta2 has shown safety in human trials of chronic wound healing, this study evaluates TGF-beta2 in acute incisional healing using a variety of vehicles. METHODS: Using an acute incisional wound model in healthy rats, rhTGF-beta2 was suspended in various vehicles including fibrin sealant (normal commercial concentration), fibrin sealant (dilute concentration), phosphate buffered saline/serum albumin, and a carboxymethycellulose gel. A single dose of the agent was instilled into the incisions at the time of wound closure and breaking strength analyses and histology performed periodically from days 3-14. RESULTS: TGF-beta2 enhanced the gain of incisional strength in all vehicles during the first two weeks of healing. This was most noticeable by day three with the carboxymethycellulose gel, but by day 7 with the other vehicles. Like reports with TGF-beta1, TGF-beta2 accelerated the gain of wound strength by about three days by day 11. Normal density fibrin sealant delayed incisional healing; whereas, the other vehicles without TGF-beta2 had no significant effect. CONCLUSIONS: The use of TGF-beta2 appears to be of value in increasing incisional wound strength in the first 14 days post-wounding in healthy rats and this effect is demonstrated in a variety of vehicles. These data support the hypothesis that the "normal" incisional wound healing curve can he shifted to the left. Shortening the time for gain of incisional wound strength may have potential clinical use.

Animals↗