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Biomedical subjects

R A Fleming

Publications and source records attributed to R A Fleming.

At least 19 recordsLinked to original sources
PubMed2000

Effect of childhood and adolescent ultraviolet exposures on cumulative exposure in South East Queensland schools.

Quantitative estimates of the childhood and adolescent erythemal ultraviolet (UV) exposure received in South East Queensland schools are provided in this paper for age groups 0 to 6, 7 to 12 and 13 to 19 years. For the neck, hand and lower arm, sites of high UV exposure that are generally not covered by clothing, 13 to 19 year olds received the highest exposure of the three age groups, followed by 7 to 12 year olds. Exposure for 13 to 19 year olds contributed up to 44% of cumulative exposure to 20 years of age, and exposures for the 7 to 12 year olds contributed up to 31%. If the annual UV exposure for these two age groups were reduced to the average of all the age groups, cumulative erythemal UV exposure from 0 to 20 years would be reduced by up to 16%. On the other hand, if mothers can protect their babies by reducing the level of annual exposure to 30% of the annual UV exposure of the 7 to 12 year olds for the first four years then cumulative exposure to UV to age 20 would be reduced by up to 19%. These data confirm the importance of targeting young age groups in public campaigns for sun protection.

Adolescent↗
PubMed2000

Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for disseminated peritoneal cancer of gastrointestinal origin.

No standard effective treatment exists for peritoneal carcinomatosis of gastrointestinal origin. The pharmacokinetic advantage of intraperitoneal chemotherapy and the synergy of heat and certain anticancer agents have prompted researchers to investigate intraperitoneal hyperthermic chemotherapy in treating disseminated peritoneal cancers. We have conducted a large Phase II trial to determine the safety and efficacy of aggressive cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC) in treating peritoneal carcinomatosis of gastrointestinal origin. Patients with disseminated peritoneal carcinomatosis of gastrointestinal origin with or without malignant ascites were eligible. After aggressive surgical debulking, patients were administered a 2-hour heated (40.5 degrees C) intraperitoneal perfusion with mitomycin C. The major response variable monitored was overall survival. Patients were assessed for toxicity after IPHC administration using the National Cancer Institute Common Toxicity Criteria. Eighty-four patients with peritoneal carcinomatosis of gastrointestinal origin were evaluated for survival and toxicity (colon, n = 38; appendix, n = 22; stomach, n = 19; other gastrointestinal, n = 5). Thirty-nine (46%) patients had malignant ascites at the time of therapy. The operative mortality (30-day) was 6 per cent. Hematologic toxicity was the most common toxicity but was of mild to moderate severity (7 and 4% of patients had grade 3/4 white blood cell or platelet toxicity, respectively). The overall median survival was 14.3 months. The median survival of patients with peritoneal carcinomatosis of appendiceal, colorectal, and gastric origins were 31.1+, 14.6, and 10.1 months, respectively. Significant differences in median survival were seen in patients without and with malignant ascites (27.7 vs 7.6 months; P = 0.0004) and R0/R1 (complete gross tumor resection) versus R2 (gross residual tumor) surgical resection status (28.5+ vs 10.8 months, P = 0.0002). These data suggest that aggressive cytoreductive surgery with IPHC using mitomycin C is safe and effective in treating peritoneal carcinomatosis of gastrointestinal origin. Additional studies and broader applications of this treatment are encouraged.

Adolescent↗
PubMed1999

Administration and pharmacokinetics of high-dose cyclophosphamide with hemodialysis support for allogeneic bone marrow transplantation in acute leukemia and end-stage renal disease.

We report a patient with pre-existing end-stage renal disease (ESRD) who underwent successful matched related donor allogeneic bone marrow transplantation for AML in second complete remission (CR2) using conditioning with high-dose cyclophosphamide (CY, 60 mg/kg/day x 2) and TBI (165 cGy twice daily x 4 days). The timing of hemodialysis after high-dose CY was extrapolated from available data on the pharmacokinetics of high-dose CY and hemodialysis clearance of conventional dose CY and its metabolites. Pharmacokinetic analyses indicated that the elimination of high-dose CY and its alkylating metabolites is impaired in ESRD but is cleared with hemodialysis. The patient's early post-transplant course was uncomplicated, and WBC and platelet engraftment occurred by day +22. Bone marrow examination on day +25 showed trilineage engraftment with no AML; cytogenetics showed 100% donor karyotype. The patient remains in remission with 100% donor karyotype at 3 years post transplant. Clinical results indicate that the administration of high-dose CY is feasible with hemodialysis support for patients with ESRD.

Adult↗
PubMed1999

Lifetime ultraviolet exposure estimates for selected population groups in south-east Queensland.

The lifetime erythemal UV exposures received by selected population groups in southeast Queensland from birth up to an age of 55 years have been quantitatively estimated. A representative sample of teachers and other school workers received (64 +/- 22) x 10(5) J m(-2) to the neck compared with (4.1 +/- 1.4) x 10(5) J m(-2) to the upper leg. A sample of indoor workers (bank officers, solicitors and psychologists) received approximately 2% less and a sample of outdoor workers (carpenters, tilers, electricians and labourers) received approximately 10% more to the neck than the school workers. These differences in erythemal UV exposures may influence the risk of non-melanoma skin cancer.

Adolescent↗
PubMed1997

Direct comparison of arbutamine and dobutamine stress testing with myocardial perfusion imaging and echocardiography in patients with coronary artery disease.

Arbutamine, a new sympathomimetic compound, appears to elicit a more balanced inotropic and chronotropic response than dobutamine, currently used as a pharmacologic stress agent. The present study was performed to compare standard dobutamine stress testing with arbutamine for the detection of myocardial ischemia with technetium (Tc)-99m sestamibi tomographic imaging and 2-dimensional echocardiography in patients with coronary artery disease. Twenty-six patients with evidence of coronary artery disease underwent dobutamine infusion of 5 to 40 microg/kg/min in 3-minute stages. On a separate day, arbutamine was administered by an automated, computerized, closed-loop device monitoring both heart rate and blood pressure. Both infusions were terminated upon achievement of target heart rate, completion of maximal infusion dose (dobutamine), heart rate saturation (arbutamine), or standard clinical end points. Tc-99m sestamibi was injected before termination of both infusions followed by tomographic myocardial perfusion imaging, whereas echocardiography was performed at baseline and throughout the infusions. There were no significant differences in maximal heart rate, blood pressure, and rate-pressure product as well as in the development of anginal symptoms or electrocardiographic changes during both infusions. The location and severity of myocardial perfusion defects and echocardiographic wall motion abnormalities were similar between both agents. It is concluded that arbutamine produces similar imaging results compared with standard dobutamine stress with both Tc-99m sestamibi single-photon emission computed tomographic myocardial perfusion imaging and 2-dimensional echocardiography.

Adult↗
PubMed1997

Thoracic complications in patients undergoing intraperitoneal heated chemotherapy with mitomycin following cytoreductive surgery.

BACKGROUND: The purpose of this study was to determine the incidence and severity of thoracic reactions in patients undergoing intraperitoneal heated chemotherapy (IPHC). METHODS: Forty-two patients who had intraperitoneal disseminated malignancies were treated with cytoreductive surgery (CS) and IPHC. The primary malignancies included carcinoma of the colon (n = 17), stomach (n = 6), appendix (n = 6), pseudomyxoma peritonei (n = 3), mesothelium (n = 2), ovaries (n = 2), jejunum (n = 2), gallbladder (n = 1), urachus (n = 1), and peritoneal carcinomatosis (n = 2). After CS, IPHC with mitomycin (MMC) was administered by perfusion at 40.5 degrees C. After IPHC, multiple radiographs of the chest were reviewed in comparison to the control group. RESULTS: Thoracic complications occurred in 36 patients (86%), including atelectasis in 32 patients (76%), pleural effusions in 27 (64%), pulmonary edema in 10 (24%), pneumonia in 2 (5%), and pneumothorax in 2 (5%). The incidence of thoracic complications in the IPHC group was significantly higher than that of patients in the control group (P < .05). Correlations between the prevalence of pleural effusion and the dose of MMC, duration of procedure, and presence of thrombocytopenia were not significant (P > .05). CONCLUSIONS: Bibasilar atelectasis and pleural effusions are common findings after IPHC with MMC, but most of them do not necessarily warrant intervention.

Adolescent↗
PubMed1997

Peritoneal carcinomatosis with urachal signet-cell adenocarcinoma.

Urachal adenocarcinoma is an uncommon clinicopathologic entity associated with a dismal prognosis. We report a case of peritoneal carcinomatosis from urachal adenocarcinoma (signet cell type) treated with cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC). Prior to treatment, disease had progressed with systemic chemotherapy. The patient remained free of symptomatic peritoneal disease or local recurrence but eventually died 23 months after IPHC and 31 months after diagnosis due to widespread bone metastases.

Adult↗
PubMed1997

Fast measurements of transmission of erythema effective irradiance through clothing fabrics.

For efficiently measuring ultraviolet transmission through clothing materials for a large number of samples, an automated measuring system with a broad-band method has been built and calibrated against a spectroradiometer based instrument. The apparatus can be used to test 60 samples in 25 min. A selection of clothing materials of known composition, weave, color and state have been tested, using the broad band method and the automated measuring system together with a solar ultraviolet simulator. Variations of about eleven times for different weave structure, about two times in the ultraviolet transmittance for different colors, and about 20 times for some stretched samples were observed. For wet conditions, an increment in ultraviolet transmittance for cotton and lycra materials and a decrement for polyester and polyester(65%)/cotton(35%) were also observed.

Clothing↗
PubMed1997

An estimate of the total UV-B exposure for outdoor workers during a south-east Queensland summer.

A numerical model was used to calculate the facial UV-B exposure received during summer (December-February) by typical outdoor farm workers in south-east Queensland (27.5 degrees S), a population among the groups at highest risk of skin cancer. The exposure was calculated using new, more detailed measurements of the probability of outdoor activity of farmers (FO-measured by the Fraction of time spent Outside), the distribution of incident solar radiation on the human face (ER-the Exposure Ratio, measured by the fraction of the ambient radiation which falls on each site) and the ambient UV-B levels (AE-the Ambient Exposure) for the region. Only the exposure of unprotected faces was considered. An analysis of the distribution of exposure over a typical working day and of the likely spread of exposures is also presented. The group average of exposures at three facial sites (the forehead, nose and cheek) were 8.7 J cm(-2), 14.0 J cm(-2), and 9.5 J cm(-2), respectively, which is substantially higher than estimates for summer made for populations in more temperate latitudes.

Face↗
PubMed1997

Treatment and prevention of malignant ascites associated with disseminated intraperitoneal malignancies by aggressive combined-modality therapy.

No satisfactory treatment exists to treat or prevent malignant ascites secondary to nonovarian intraperitoneal (IP) disseminated malignancies. A Phase I/II clinical trial combining radical cytoreductive surgery (CS) and IP hyperthermic chemotherapy (IPHC) with mitomycin C is presented. Between December 9, 1992 and July 31, 1995, 39 patients (pts) were explored for IP cancer. Five pts with known liver metastases were excluded, leaving 34 pts (15 female, 19 male) of median age 53 (range, 17-76). The majority of pts had disseminated IP cancers of gastrointestinal origin (80%). Prior therapy included the following: chemotherapy, 20 pts (59%); surgery, 29 pts (85%); and radiation, 2 pts (6%). Following CS, IPHC with mitomycin C was done. At surgery, 12 pts (35.3%) had frank ascites, and 12 pts (35.3%) had positive IP cytology without ascites. The median hospital stay was 9 days (range, 5-65) with no 30-day mortality. Complications for 36 treatments included: thrombocytopenia Eastern Cooperative Oncology Group grade 3 or 4, two cases (5.6%); neutropenia requiring granulocyte colony-stimulating factor, seven cases (19.4%); sepsis, four cases (11.1%); bowel leak, two cases (5.6%); and serous wound leak, two cases (5.6%). Ascites correlated with worse resection status (P = 0.025). Ascites was controlled in 9 of 12 (75.0%) pts, with failures at 1, 4, and 14 months (median follow-up, 7.5 months). No cytology-positive ascites-negative pts developed clinical ascites (median follow-up, 9.4 months). The median survival time in pts with ascites was 10.1 months versus 32.7 for patients without ascites (P = 0.013). For the entire study population, the 1- and 2-year survival rates were 74.6 and 48.5 per cent, respectively (median follow-up, 18.2 months). In this study, malignant ascites was controlled in 75 per cent of cases and prevented in all pts with positive IP cytology. CS plus IPHC appears to be relatively well tolerated and may be effective for the treatment and prevention of malignant ascites.

Antibiotics, Antineoplastic↗
PubMed1996

Complications of heated intraperitioneal chemotherapy and strategies for prevention.

Heated intraperitoneal chemotherapy is a potentially useful strategy for therapy of peritoneal carcinomatosis in adult patients, and we have found it to be associated with an acceptable complication rate. Careful perioperative management is critical, and we have presented our current experience guidelines for management and overview of complications.

Adult↗
PubMed1996

The effects of body size and orientation on ultraviolet radiation exposure.

A method has been developed for determining the UV and erythemal exposures to the entire body. The difference between the ambient erythemal exposure and that to the body compared to the ambient exposure may be as high as 76%. The height, orientation, and overall height had a minimal effect on the exposure to the body with size, time of day and time of year having a significant effect. The diffuse component of UV to a side of the body ranged from 20% to 41% between different times of the year with different levels of cloud cover. The ratio of the body to the ambient erythemal exposures varied from 0.24 to 0.61, with the time of day and time of year with the smaller value for periods of high solar altitude.

Body Constitution↗
PubMed1996

Annual reduction of solar UV exposure to the facial area of outdoor workers in Southeast Queensland by wearing a hat.

The total annual exposure to erythemally effective UVR was estimated for average work situations in a high exposure environment, viz, farm workers in Southeast Queensland (27.5 degrees S), and the effect of hat usage was examined. If no sun protection is used, the annual erythema exposures for this group of workers at three facial sites forehead, nose and cheek are 40, 57 and 34 J.cm-2 respectively. If a hat is worn throughout the year, the exposures are reduced to 6, 19 and 20 J.cm-2, respectively. The mean ratio of exposure without the hat to that with the hat (mean protection factor, MPF) was found to be 6 for the forehead, 3 for the nose and 2 for the cheek. The risk of non-melanoma skin cancers without the protection of the hat is estimated to increase by up to 100 times for basal cell carcinomas and 13 times for squamous cell carcinomas for a whole year of exposure.

Face↗
PubMed1996

Urinary elimination of cyclophosphamide alkylating metabolites and free thiols following two administration schedules of high-dose cyclophosphamide and mesna.

Twenty patients with a variety of neoplastic diseases were treated with preparative regimens containing high-dose cyclophosphamide (CY) administered as a 2-h infusion (60 mg/kg) for 2 days or by continuous infusion (1500 mg/m2/day) for 4 days. In patients receiving CY by 2-h infusion, the uroprotectant 2-mercaptoethane sulfonate (MESNA) was administered as an intermittent, bolus intravenous infusion (20% of CY dose) every 6 h. In patients receiving continuous infusion CY, MESNA was administrated concomitantly at an equivalent dose to CY by continuous infusion. During the first 24 h of CY administration, urine was collected at 2-h intervals and analyzed for free thiols and CY-alkylating metabolites. In patients receiving CY by short infusion and MESNA by intermittent bolus infusion, urinary concentrations of alkylating metabolites peaked at 4-8 h. During each dose of MESNA, urinary free thiols peaked at 2 h following administration but fell to pre-treatment levels at subsequent intervals. In patients receiving CY by continuous infusion, CY alkylating metabolites increased gradually over the 24-h study period while free thiols remained at a constant level during this period. With bolus administration of CY and intermittent bolus administration of MESNA every 6 h, there are periods where urinary CY-alkylating metabolites are elevated and free thiol concentrations are diminished. During continuous infusion of CY and MESNA, urinary CY alkylating metabolites reached peak concentrations at 18-22 h while the exposure of the bladder to free thiols remained constant. Recommendations are provided to increase the exposure of free thiols in the bladder when MESNA is administered by bolus or continuous infusion.

Adult↗
PubMed1996

Phase I study of N-(phosphonacetyl)-L-aspartate with fluorouracil and with or without dipyridamole in patients with advanced cancer.

We conducted a combined biochemical modulation trial of N-(phosphonacetyl)-L-aspartate (PALA), dipyridamole (DP), and fluorouracil (5-FU) in patients with cancer. Eighty-eight patients with advanced cancer were entered into this Phase I trial. During the first part of the study, four doses of PALA (125, 250, 500, and 1000 mg/m2, administered on day 1) were evaluated to determine the PALA dose with maximal suppression of aspartate transcarbamylase (ATCase) activity that was clinically tolerable. Patients were randomized to receive DP (or no DP), 50 mg/m2, p.o. every 6 h on days 1-6, and all patients received 5-FU, 400 mg/m2, by bolus administration on days 2-5. Prior to and during therapy, WBCs were collected and assayed for ATCase activity. After the maximally tolerated PALA dose with 400 mg/m2 5-FU +/- 50 mg/m2 DP was defined, the 5-FU dose was escalated using the same administration schedule of 5-FU, PALA, and DP. The dose of 5-FU was escalated by 25% in each of the DP cohorts until dose-limiting toxicity was reached. ATCase activity was inhibited in a dose-dependent manner with PALA doses of 125, 250, 500, and 1000 mg/m2, resulting in 0, 13, 17, and 49% inhibition of ATCase activity. Only at the higher PALA doses (i.e., 500 and 1000 mg/m2) was ATCase activity suppressed during days 2-5, but the activity returned to pretreatment levels by day 15. Based on the clinical tolerance and significant suppression of ATCase activity, a PALA dose of 500 mg/m2 was selected for the 5-FU dose escalation phase. At a 5-FU dose of 625 mg/m2, dose-limiting toxicity (leukopenia, stomatitis, and diarrhea) occurred in both DP cohorts. We recommend that for this monthly treatment schedule, 500 mg/m2 PALA and 500 mg/m2 5-FU, with or without 50 mg/m2 DP, be used in subsequent Phase II trials.

Adult↗