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Biomedical subjects

M McCormack

Publications and source records attributed to M McCormack.

At least 19 recordsLinked to original sources
PubMed2002

Radiotherapy for perianal Paget's disease.

The role of radiotherapy in the management of perianal Paget's disease (PPD) is not well defined in clinical practice or within the medical literature. We present 6 cases, document the radiotherapy details and review our results. A comprehensive literature search has been undertaken attempting to identify all published cases of PPD and survey the number receiving radiotherapy. To further define the role for radiotherapy in PPD these cases have been reviewed. Published results are sporadic and often poorly documented with respect to technical radiotherapy details. Two main roles for radiotherapy in PPD were found. One is as primary treatment for in situ or invasive disease and the other is following surgical relapse of in-situ or invasive disease. Other possible uses of radiotherapy in PPD such as neoadjuvant or adjuvant treatment or chemo-radiotherapy are discussed. Results of radiotherapy treatment for case of in situ and invasive disease are presented. We disagree with the view in some areas of the surgical literature that radiotherapy has no place in the management of the disease. Despite a thorough surveying of the literature however, precise recommendations on several areas of the technical radiotherapy treatment such as dose-fractionation schedules and field margins are difficult because of the small number of cases and poor general documentation. Our practice recommendations are presented. Radiotherapists should be encouraged to publish their experience in this disease to help define further a role for this treatment.

Aged↗
PubMed2001

Current trends in colorectal cancer: site, incidence, mortality and survival in England and Wales.

The objective was to examine trends in colorectal cancer (CRC) incidence and mortality in England and Wales over the last 30 years. Age-standardized incidence, mortality and survival rates for CRC, based on data from the National Cancer Intelligence Centre at the Office for National Statistics, were calculated and trends assessed. Between 1971 and 1997 the total number of cases of CRC increased by 42%, from 20,400 to 28,900. The site distribution of CRC between 1971 and 1994 was: rectum 38%, sigmoid 29%, caecum 15%, transverse colon and flexures 10%, ascending colon 5%, and descending colon 3%. Between 1971 and 1997 the direct age-standardized incidence increased by 20% in males and by 5% in females. The direct age-standardized mortality fell by 24% in males and by 37% in females. Age-standardized relative 5-year survival in adults improved from 22%-27% for patients diagnosed during 1971-1975 to over 40% for those diagnosed during the period 1991-1993. In conclusion, the incidence of CRC in England and Wales has been steadily rising. It is more common in males and has increased more rapidly in males than in females. The reasons for these trends remain unclear. Five-year survival has improved substantially, but rates are still below those in comparable countries elsewhere in Europe and in the USA.

Adolescent↗
PubMed2000

The effect of superpulsed carbon dioxide laser energy on keloid and normal dermal fibroblast secretion of growth factors: a serum-free study.

An in vitro model was used to determine the effect of superpulsed CO2 laser energy on normal dermal and keloid-producing fibroblast proliferation and release of growth factors. Growth factors assayed included basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1). bFGF is mitogenic, inhibits collagen production, and stabilizes cellular phenotype. TGF-beta1 stimulates growth and collagen secretion and is thought to be integral to keloid formation. Growth in a serum-free medium allowed measurement of these growth factors without confounding variables. Keloid and normal dermal fibroblasts cell lines were established from facial skin samples using standard explant techniques. Samples consisted of three separate keloid and three separate normal dermal fibroblast cell lines. Cells were used at passage 4 to seed 24-well trays at a concentration of 6 x 10(4) cells per milliliter in serum-free medium. At 48 hours, 18.8 percent of each cell well was exposed to a fluence of 2.4, 4.7, and 7.3 J/cm2 using the superpulsed CO2 laser. Cell viability and counts were established at four time points: 0 (time of superpulsed CO2 laser treatment), 24, 72, and 120 hours. Supernatants were collected and assessed for bFGF and TGF-beta1 using a sandwich enzyme immunoassay. All cell lines demonstrated logarithmic growth through 120 hours (conclusion of experiment), with a statistically significant shorter population doubling time for keloid fibroblasts (p < 0.05). Use of the superpulsed CO2 laser shortened population doubling times relative to that of controls; the differences were statistically significant in keloid dermal fibroblasts when fluences of 2.4 and 4.7 J/cm2 were used (p < 0.05 and 0.01, respectively). bFGF was present in greater levels in normal dermal fibroblasts than in keloid dermal fibroblasts. Application of superpulsed CO2 demonstrated a trend toward increased bFGF secretion in both fibroblast types; the increase was significant in the keloid group at 4.7J/cm2. A consistent trend in suppression of TGF-beta1 was seen in both groups exposed to superpulsed CO2, with the maximal effect occurring at 4.7 J/cm2. Serum-free culture sustains logarithmic cell growth and allows growth factor measurement without confounding variables from serum-containing media. Superpulsed CO2 enhances fibroblast replication and seems to stimulate bFGF secretion and to inhibit TGF-beta1 secretion. Given the function of these growth factors, the application of superpulsed CO2 may support normalized wound healing. These findings may explain the beneficial effects of laser resurfacing on a cellular level and support the use of superpulsed CO2 in the management of keloid scar tissue.

Cell Division↗
PubMed1998

Dysregulated hematopoiesis and a progressive neurological disorder induced by expression of an activated form of the human common beta chain in transgenic mice.

Previously we described activating mutations of hbetac, the common signaling subunit of the receptors for the hematopoietic and inflammatory cytokines, GM-CSF, IL-3, and IL-5. The activated mutant, hbetacFIDelta, is able to confer growth factor-independent proliferation on the murine myeloid cell line FDC-P1, and on primary committed myeloid progenitors. We have used this activating mutation to study the effects of chronic cytokine receptor stimulation. Transgenic mice were produced carrying the hbetacFIDelta cDNA linked to the constitutive promoter derived from the phosphoglycerate kinase gene, PGK-1. Transgene expression was demonstrated in several tissues and functional activity of the mutant receptor was confirmed in hematopoietic tissues by the presence of granulocyte macrophage and macrophage colony-forming cells (CFU-GM and CFU-M) in the absence of added cytokines. All transgenic mice display a myeloproliferative disorder characterized by splenomegaly, erythrocytosis, and granulocytic and megakaryocytic hyperplasia. This disorder resembles the human disease polycythemia vera, suggesting that activating mutations in hbetac may play a role in the pathogenesis of this myeloproliferative disorder. In addition, these transgenic mice develop a sporadic, progressive neurological disease and display bilateral, symmetrical foci of necrosis in the white matter of brain stem associated with an accumulation of macrophages. Thus, chronic hbetac activation has the potential to contribute to pathological events in the central nervous system.

Animals↗
PubMed1997

Cancer-related thromboembolic disease in patients with solid tumours: a retrospective analysis.

BACKGROUND: Cancer patients frequently suffer thromboembolic events. This study assessed the incidence and resource implications of cancer-related thromboembolic disease (CTD) in a single, large cancer centre. PATIENTS AND METHODS: A retrospective analysis of patients admitted with CTD and/or the complications of treatment of CTD over a two-year period has been conducted. Forty-eight patients (23 male, 25 female, median age 60 years) with a variety of solid tumours were identified. RESULTS: The initial presentations were venous thromboses (28 patients) and pulmonary embolism (20 patients). The median interval from cancer diagnosis to the initial episode of CTD was eight (range 0-112) months. Twenty-two patients suffered additional thromboses, despite maintenance warfarin anticoagulation in 18 patients. Six patients experienced anticoagulation-induced haemorrhage. Forty-one (85.4%) patients have died. The median survival from the first thromboembolic event was 8.5 months. The median inpatient stay for management of the first event was 10 (range 4-75) days, accounting for 729 inpatient days during the study period. Recurrent episodes of CTD or complications of anticoagulation resulted in 28 readmissions, accounting for 295 inpatient days. During the two-year period 1024 inpatient days were directly caused by CTD and its complications, representing 6.1% bed occupancy on our unit. CONCLUSION: This study demonstrates that CTD represents a significant cause of morbidity in cancer patients with considerable resource implications for cancer centres. Improvements in prevention and management of CTD would reduce morbidity and lead to considerable cost savings.

Adult↗
PubMed1994

IAIMS and sharing.

The Integrated Academic Information Management System (IAIMS) concept is about sharing resources and information, and about improving the decision-making ability of health care professionals by integrating information. At Columbia-Presbyterian Medical Center, the IAIMS project has established an information architecture based on common, shared computing and networking resources. The institutional computing culture has been changed with increased sharing of information and, consequently, improved quality of information. Several classes of information in the areas of clinical, scholarly, administrative, basic research, and core resources have been identified for better understanding of information responsibility. Technical problems such as heterogeneity on workstation platforms and lack of universal syntactic and semantic standards for health care information exchange still impede inter-institutional sharing of information.

Artificial Intelligence↗
PubMed1993

Pregnancy outcome following first-trimester exposure to fluoxetine (Prozac)

OBJECTIVE: To compare pregnancy outcome following first-trimester fluoxetine (Prozac) exposure with pregnancy outcome in two matched control groups. Fluoxetine is a new antidepressant used by many young women. Currently, no published data exist on its safety in pregnancy. DESIGN: We prospectively collected and followed up 128 pregnant women exposed to a mean daily dose of 25.8 mg (+/- 13 mg) of fluoxetine during the first trimester and compared pregnancy outcome with two matched groups of women exposed during the first trimester of pregnancy to either nonteratogens or tricyclic antidepressants. RESULTS: Rates of major malformations were comparable within the three groups and did not exceed those expected in the general population. Women treated with fluoxetine had a tendency for increased risk for miscarriage when compared with women exposed to nonteratogens (relative risk, 1.9; 95% confidence interval, 0.92 to 3.92). The rate of miscarriages in the fluoxetine group was comparable with the tricyclic group (13.5% and 12.2% vs 6.8% in the nonteratogens). CONCLUSIONS: Our study suggests that the use of fluoxetine during embryogenesis is not associated with an increased risk of major malformations. Women exposed to both fluoxetine and tricyclic antidepressants tended to report higher rates of miscarriage; further studies will be needed to confirm this observation and to separate the effects of the psychiatric condition from the associated drugs. Long-term studies will be warranted to rule out potential developmental teratology of fluoxetine, which affects a central nervous system neurotransmitter.

Antidepressive Agents, Tricyclic↗
PubMed1993

Importance of tonicity of carbicarb on the functional and metabolic responses of the acidotic isolated heart.

In this study, the physiological and metabolic effects of Carbicarb administered as an isotonic (150 mmol/L Na[n[]I+) or hypertonic (1 mol/L Na[n[]I+) solution over 2 minutes in the acidotic isolated heart were compared. Physiological monitoring as well as 31P and 23Na nuclear magnetic resonance spectroscopy were performed. Both isotonic and hypertonic Carbicarb induced comparable dose-dependent increases in intracellular pH as well as decreases in inorganic phosphate and increases in creatine phosphate concentrations, which were sustained for 20 minutes. However, immediate functional improvement was greater in hearts receiving isotonic Carbicarb. Metabolic acidosis conditions resulted in a 27% increase in cytosolic sodium by 30 minutes (P < .05). In this setting, hypertonic Carbicarb induced a large transient increase in cytosolic sodium, whereas isotonic Carbicarb caused immediate and sustained decreases in cytosolic sodium. These data suggest that isotonic Carbicarb may have more beneficial effects on cardiac function than hypertonic Carbicarb. These effects may be related to associated changes in cytosolic sodium.

Acidosis↗