Acute airway obstruction from insertion of a cuffed esophageal stent for malignant tracheoesophageal fistula.
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Biomedical subjects
Publications and source records attributed to K Atkinson.
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PURPOSE: Cougar attacks on humans appear to be on the rise. A review of all attacks on children was performed to determine the method of attack and injury patterns so that a treatment regimen as well as possible preventative measures could be determined. METHODS: A review of all attacks, including attacks on children, was performed, including three recent attacks treated at our institution. Situation, adult supervision, patient age, injuries recorded, survival, and mode of attack, if known, were reviewed. RESULTS: There were 50 documented attacks on children with a 25% fatality rate. Most children were not alone at the time of the attack (92%), and in many instances adult supervision was present or nearby. Severe head and neck lacerations along with puncture wounds were the most common injury. Examples of typical cervical injuries include a nonfatal vertebral artery injury, phrenic nerve injury, a fatal internal carotid artery injury, and a fatal cervical spine injury. The cougar was rabid in two cases. Pasteurella resulted in late infections in two patients. CONCLUSIONS: Based on the pattern of injuries, the authors recommend aggressive evaluation for occult cervical injuries as well as surgical debridement. Antibiotics should cover oropharyngeal flora including Pasteurella multocida. Rabies prophylaxis is indicated. Adult supervision in wilderness areas is not necessarily protective.
Populations of the biological control agent Candida oleophila on fruit in an orange grove were monitored by plating fruit washes and peel homogenates on a selective medium, followed by PCR analysis of DNA from yeast colonies resembling C. oleophila. The C. oleophila transformant ADGus-10 formed colonies on a selective medium that suppressed the development of 99% of the filamentous fungi and the indigenous yeasts, Aureobasium (a yeast-like fungus) and Rhodotorula. Only 6-8 indigenous yeasts/cm2 fruit surface gave rise to colonies that resembled C. oleophila on the selective medium. The identity of the C. oleophila transformant colonies was verified by PCR analysis of yeast DNA. The presence of a 599-bp band in the PCR product primed by beta-glucuronidase gene primers, confirmed the identity of C. oleophila transformant ADGus-10. Colony-forming units of C. oleophila were recovered efficiently from fortified washes of the fruit surface and from homogenates of wounds excised from fruit sprayed in the grove with C. oleophila.
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A comparison was made of the pattern of interstitial pneumonitis (IP) following allogeneic bone marrow transplantation before and after the introduction of ganciclovir prophylaxis to minimize the risk of cytomegalovirus (CMV) disease in the St Vincent's Hospital bone marrow transplant program in 1989. A total of 456 recipients of allogeneic transplants were included. 280 received no prophylactic ganciclovir while 176 received prophylactic ganciclovir. The overall incidence of interstitial pneumonitis dropped from 19.6 to 12.5% (P = 0.03) and this was primarily due to a reduction in the incidence of CMV-IP which fell from 12.9 to 1.7% (P < 0.0005). The incidence of idiopathic IP was not different between the two groups (6.3 vs 3.2%), nor was the incidence of Pneumocystis carinii pneumonia (2.9 and 0.6%). Prophylactic ganciclovir has thus had a significant impact in reducing both the overall incidence of IP and specifically cytomegalovirus IP in allogeneic marrow transplant recipients. The most common form of IP in patients given prophylactic ganciclovir is now idiopathic interstitial pneumonitis.
We have evaluated the antitumor activity of a murine antibody (IgG2a) against the leukocyte antigen CD48. CD48 is expressed on T and B lymphocytes, monocytes, and a wide range of lymphoid malignancies. To assess the therapeutic potential of an anti-CD48 antibody, we established a reproducible model of human B-cell (Raji) leukemia/lymphoma in C.B17/scid mice, where untreated mice develop hind leg paralysis due to tumor engraftment. Using this model, the murine anti-CD48 antibody HuLy-m3 was shown to mediate a strong in vivo antitumor effect. Long-term survival (>1 year) of scid mice was obtained after treatment with three 200-microg i.v. doses of anti-CD48 antibody on days 0, 2, and 4 after i.v. injection of tumor cells. In contrast, mice treated with an isotype control antibody developed hind leg paralysis after 34 +/- 3 days. A strong antitumor response was still observed when a dose of 20 microg of HuLy-m3 antibody was used. During preclinical investigations, we also examined a number of properties of the CD48 antigen. CD48 is present at high levels on the surface of T and B cells, but most (>95%) CD34-positive cells do not express CD48. Anti-CD48 antibodies are maintained on the surface of antigen-positive cells for extended periods (>24 h). These properties suggest that anti-CD48 antibodies may be useful in the treatment of a number of diseases including lymphoid leukemias and lymphomas.
BACKGROUND: Graft-versus-host disease (GVHD) remains the most significant obstacle to the use of allogeneic bone marrow transplantation as a treatment for leukemia and other hematological malignancies. Because current GVHD treatment regimens such as cyclosporine and methotrexate are only partially effective, there is a need for new immunosuppressive drugs for the treatment of this condition. METHODS: A recently developed immunosuppressive drug, mycophenolate mofetil (MM), was tested in a fully mismatched (C57BL/6 donors to BALB/c recipients) murine model of acute GVHD after bone marrow transplantation. RESULTS: A dose regimen of 30 mg/kg/day given by oral gavage and begun at 1 day before transplant had no positive effect on survival and was found to retard the rate of marrow engraftment as measured by absolute blood neutrophil counts. In all subsequent experiments, treatment was begun on day 5 after transplant. Three different doses (30, 60, and 90 mg/kg/day) were tested, but no significant improvement in mean survival time (MST) was observed for the first two doses (P=0.412 and 0.100, respectively). The highest dose (90 mg/kg/day) reduced MST (P=0.059), and no further dose increases were attempted. MM in combination with cyclosporine also failed to improve MST compared with animals treated with cyclosporine alone or controls. CONCLUSIONS: These results suggest that MM given orally is not effective in this murine model of GVHD and may not have a role in the treatment and prevention of acute GVHD arising from bone marrow transplantation in the clinical setting.
The majority of women with high-grade intraepithelial neoplasia (VAIN 3) are over 60 years of age and have a history of premalignant or malignant disease of the cervix. Although the natural history of VAIN is not well defined, high-grade lesions are premalignant. Ablative treatment with laser or 5-fluorouracil cream is commonly unsatisfactory. Several series have reported a low rate of recurrence and complications if VAIN 3 is treated with low-dose-rate brachytherapy. This retrospective review reports the outcome of 14 patients treated with high-dose-rate brachytherapy, with a dose of 34 to 45 Gy in 4.5- to 8.5-Gy fractions. Treatment was well tolerated with no severe early or late toxicity observed. At a median follow-up of 46 months 1 patient progressed to invasive carcinoma of the vagina; in another patient VAIN 3 persisted.
Cell function-based tests measure responses of cells at sublytic concentrations of test agents. The fluorescein leakage assay measures effects of substances on the barrier function of epithelial monolayers or multilayers (MDCK or NHEK cells) as in vitro models of corneal epithelial function. Two IRAG data submissions suggest that the fluorescein leakage assay shows promise as a screening test for surfactants and alcohols. The test method requires further optimization, standardization and evaluation to fully determine its utility as an in vitro ocular irritancy test. The silicon microphysiometer test measures effects of test substances on the metabolic rate of cells; although a large number of cell types have been evaluated, L929 cells have been used for irritancy screening. Three IRAG data submissions on the silicon microphysiometer test showed strong in vivo/in vitro correlations for surfactants and surfactant-based personal care and household cleaning products in a range of mild to moderate ocular irritancy. This and published information support the reproducibility of the method and its use as an ocular irritancy screening test for aqueous-soluble liquid, surfactant-based formulations.
In an attempt to accelerate marrow recovery after HLA-identical sibling bone marrow transplantation, the donors of 12 patients with haematological malignancy were given recombinant human granulocyte colony-stimulating factor (rHuG-CSF; lenograstim; Granocyte) 5 micrograms/kg/day for seven doses prior to marrow harvest. All 12 recipients also received lenograstim 5 micrograms/kg/day from the day of transplant until their neutrophil count was 1.0 x 10(9)/1. In addition to lenograstim post-transplant and lenograstim-stimulated donor bone marrow the first six recipients also received donor peripheral blood stem cells that had been enriched for CD34+ stem/progenitor cells and T cell depleted on an immune absorption column (cohort 1). The second six patients (cohort 2) received lenograstim post-transplant and lenograstim-stimulated donor marrow only. All 12 patients showed a marked elevation of their circulating white blood cell count (predominantly neutrophils) on day 1 post-transplant. Compared to carefully matched historical control patients the rate of neutrophil engraftment was significantly accelerated in both patient cohorts and platelet engraftment was accelerated in cohort 2.
We report a patient who underwent allogeneic bone marrow transplantation from a sibling with longstanding untreated severe active rheumatoid arthritis. After 4 years of follow-up there is no evidence of adoptive transfer of rheumatoid arthritis to the recipient. This case, along with another recently reported case, provides reassurance that haemopoietic stem cell transplantation from a donor with systemic autoimmune disease may not necessarily result in adoptive transfer of the disease. All previous reports of transfer of autoimmunity in humans have been of organ-specific autoimmune diseases and we speculate that pathophysiological differences might account for why systemic autoimmune disease is not transferred.
Treatment with busulphan and/or hydroxyurea rarely produces remission in patients with chronic myelogenous leukaemia (CML) in chronic phase. HLA-identical sibling transplants almost always produce remission, and only about 20% of patients relapse post-transplant. The increased anti-leukaemic efficacy of transplants results from intensive pretransplant treatment and immune-mediated anti-leukaemia effects. We studied 433 patients surviving > or = 2 years after diagnosis of CML to determine if patients who have relapsed after a transplant in chronic phase have longer survival from diagnosis than comparable subjects receiving chemotherapy. The chemotherapy cohort included 344 adults < 50 years of age treated on consecutive trials of the Italian Cooperative Study Group on CML between 1973 and 1986. The transplant cohort included 89 patients reported to the International Bone Marrow Transplant Registry who relapsed after an HLA-identical sibling bone marrow transplant carried out between 1978 and 1992. Survivals in the two groups were compared using Cox proportional hazards regression to adjust for prognostic variables. Median survival was 65 months in the chemotherapy cohort and 86 months in the transplant cohort. The 7-year probability (95% confidence interval) of survival was 34% (28-39%) in the chemotherapy cohort and 57% (43-70%) in the transplant cohort (P=0003). There was no difference in survival of patients relapsing after T-cell depleted and non-T-cell-depleted transplants. We conclude that patients who relapse after an HLA-identical sibling bone marrow transplant for CML in chronic phase have longer survival from diagnosis than comparable patients receiving chemotherapy. This effect is most likely to be the result of intensive chemotherapy and/or radiation given for pretransplant conditioning.
Mobilization of Philadelphia chromosome (Ph) negative blood progenitors was attempted in 23 newly diagnosed chronic myeloid leukaemia (CML) patients using a regimen of cyclophosphamide (CY) 5 g/m2 and rHUG-CSF 150 microg/m2 daily. This regimen was well tolerated with no major adverse events reported. More than 2 x 10(6)/kg CD34+ cells were collected in 21 patients (91%). Predominantly Ph-negative mobilization (0-25% Ph-positive) was seen in 30% of cases overall and was confined to patients with a Sokal prognostic score < 1 (7/11 with Sokal score <1; 0/12 with Sokal score > or = 1). Within the low Sokal index group, a low WBC count pre-mobilization and a low WBC nadir both correlated strongly with Ph-negative mobilization (P = 0.006 and 0.02 respectively). Five of 19 patients receiving at least 6 months of Roferon A therapy post mobilization achieved a major cytogenetic response; all five patients were Ph-negative mobilizers. Therefore CML patients can be divided into a good-prognosis group in whom predominantly Ph-negative progenitors can be mobilized using a regimen of moderate intensity if haematological control is achieved pre-mobilization, and a poor-prognosis group for whom predominantly Ph-positive cells are mobilized with this regimen regardless of haematological control.
BACKGROUND: Bone marrow and blood stem cell transplantation is increasingly utilised in Australia. The Australian Bone Marrow Transplant Recipient Registry was founded in 1991 to record this activity. AIM: To describe allogeneic and autologous bone marrow and blood stem cell transplantation in Australia during 1992-95. METHODS: Each bone marrow transplant programme in each State of Australia has been invited to contribute information to the Registry and all do. A single information sheet is compiled by the data manager in each programme when a marrow transplant is performed and mailed to the Registry office. An annual follow-up sheet is then mailed from the Registry to the contributing centre at the anniversary of each individual transplant. RESULTS: Australia-wide, haemopoietic cell transplants have increased in number from 478 in 1992 to 681 in 1995. The number of hospitals contributing registrations to the Australian Bone Marrow Transplant Registry has increased from 20 in 1992 to 25 in 1995. The main reason for the increased number of transplants is an increase in the number of autologous blood stem cell transplants including an increase in the number of staged autologous blood stem cell transplants. The most common indication for a single autologous transplant in 1995 was non-Hodgkin's lymphoma and for a staged autologous transplant was breast cancer. The commonest indication for an allogeneic family member transplant in 1995 was acute myeloid leukaemia and for an allogeneic unrelated donor transplant, acute lymphoblastic leukaemia. The three year actuarial overall survival for patients receiving a haemopoietic stem cell transplant between 1992 and 1994 was 54% with a median follow-up time of 2.04 years. Recurrence of the underlying malignant disease was the main cause of death during both the first and second year post transplant after both allogeneic (13.3% and 8.3%) and autologous (22.1% and 11.8%) transplantation. Treatment-related mortality was 13.1% after allogeneic transplantation and 3.3% after autologous transplantation. CONCLUSIONS: Trends in bone marrow and blood stem cell transplantation practice in Australia during 1992-1995 have been outlined and both practice and outcome can be compared with that in other countries. The main cause of treatment failure, recurrence of the underlying malignant disease, indicates that this is where current and future research needs to be focused.
High-dose-rate brachytherapy was introduced at this hospital for the treatment of gynaecological malignancy in 1985. A retrospective analysis was performed of 103 patients with cervix cancer treated with this technique from 1985 to June, 1993. The patients were analyzed for treatment parameters, response, survival, relapse and toxicity. Five-year survival was 78% for Stage 1B, 72% for Stage 2A, 42% for Stage 2B and 29% for Stage 3B. The severe late toxicity rate was 4.9%. These results are similar to reported international series that have used either low-dose-rate or high-dose-rate brachytherapy.
Research contradicts the common assumption that older people are not sexually active. Questions about the patient's sexual health should be included in the assessment. Health professionals must recognise the need to offer support and advice to patients on this issue.
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Large perineal defects can occur after surgery for recurrent malignancy particularly after adjuvant radiotherapy or in complex chronic perineal inflammatory conditions. Quality of life can be severely impaired by perineal wounds or chronic sinuses. Muscle and myocutaneous flaps can be used to close large defects, increase vascular supply to poorly healing wounds, and provide bulk for sitting. We report 5 cases where the gracilis flap was used to repair large perineal defects. The defects were created after wide perineal excision for recurrent tumours associated with radiation damaged skin (2 cases) and after excision of chronic sinuses complicating the perineal wounds after abdominoperineal excision of the anus for inflammatory bowel disease (3 cases).