Solution to pet overpopulation may involve change in perspective.
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Biomedical subjects
Publications and source records attributed to D M Lane.
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Melanin synthesised in melanoma cells presents a unique target to which the treatment can be selectively addressed, provided the pigment is recognised by a suitable drug. Methylene blue (MTB) possesses a high affinity for melanin and, therefore, accumulates preferentially in melanoma cells. Since not directly toxic to the tumour, MTB serves as a carrier for radioisotopes and, once taken up by melanoma cells, acts as a selectively localised source of radiation. Hence, radioderivatives of the compound can be used for both diagnosis and therapy of disseminated melanoma. Eleven patients with confirmed metastatic melanoma and one with a recent local recurrence were studied using radioiodinated (iodine-123 or iodine-131) MTB and a gamma camera. Biopsies of cutaneous lesions were taken to determine directly the compound uptake in tumours. This first clinical investigation concerning the diagnostic potential of radioiodinated MTB in patients with disseminated melanoma confirmed the existence of approximately 80% of internal lesions previously identified by routine methods and, additionally, enabled detection of unknown secondaries in 6 of 12 patients studied. There were no false-positive gamma camera images regardless of whether 123I or 131I was used. 131I proved to be more suitable than 123I for detecting melanoma metastases with radioiodinated MTB. Hazy images of the lesions treated with external beam radiation and/or some drugs suggest that initial radio- and chemotherapy might affect MTB uptake in melanoma metastases and reduce the clarity of the scintigrams obtained from a gamma camera. However, small, untreated internal lesions that cannot be visualised easily with the standard diagnostic methods are revealed with 131I-MTB regardless of their localisation. It is concluded that use of radioiodinated MTB in conjunction with gamma camera or positron emission tomographic imaging might prove to be a useful and accessible tool for the detection of early melanoma dissemination.
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Heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) treatments selectively remove LDL with minimal effects on high-density lipoproteins (HDL), but limited data are available on effects between treatments. The levels of factors associated with increased coronary artery disease risk (atherogenic) among treatments may have therapeutic significance, especially for combined HELP and lipid-lowering drug therapy. Hypercholesterolemic and combined hyperlipidemic patients resistant to diet/drug therapy were treated with biweekly HELP therapy. Hypercholesterolemic patients received either lovastatin or no drug, whereas combined hyperlipidemic patients received gemfibrozil. Plasma lipid (total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol) and apolipoprotein A-I, A-II, B, C-III, and E levels were measured before treatment, then immediately, and 2, 4, 7, and 14 days after treatments (n = 28). Atherogenic factor (LDL cholesterol, total cholesterol, apolipoprotein B) levels decreased > 50% with treatment, gradually increasing over 14 days to pretreatment levels. Factors associated with reduced coronary artery disease risk (HDL cholesterol and apolipoproteins A-I and A-II) decreased 8% to 16% but recovered by 2 days. Components of triglyceride-rich lipoproteins (triglycerides and apolipoproteins C-III and E) decreased 38% to 55% with variable post-treatment recoveries. Lovastatin reduced pretreatment levels of atherogenic and triglyceride-rich lipoprotein components and slowed post-treatment increases compared with no drug therapy. Gemfibrozil produced changes similar to lovastatin. Drug therapy had little effect on factors associated with reduced coronary artery disease risk. HELP apheresis produced large reductions in plasma atherogenic factor levels with gradual return to pretreatment levels over 14 days, whereas antiatherogenic factors were minimally reduced and recovered rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PURPOSE: Biweekly (once every 2 weeks) heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) therapy was evaluated for safety and efficacy in selectively reducing LDL cholesterol levels compared with weekly HELP therapy. PATIENTS AND METHODS: Biweekly treatments were given to high-risk, diet/drug resistant hypercholesterolemic patients (n = 23) after 6 months of weekly HELP therapy. Lipids, lipoprotein cholesterol, apolipoproteins A-I and B, and fibrinogen were measured on plasma samples before and after treatment. RESULTS: Mean plasma volume treated was 2.8 l and mean treatment duration 1.7 h. Therapy complications were minimal. In 98% of 268 biweekly HELP treatments, LDL cholesterol levels were reduced by > 30%. For patients completing 6 months of biweekly therapy following 6 months' weekly therapy (n = 23), mean LDL cholesterol levels were reduced 138.5 mg/dl (111.2 mg/dl weekly) with a time-averaged decrease from mean pre-apheresis levels of 33% for biweekly therapy (39% weekly). Mean total cholesterol (161.2 mg/dl biweekly versus 132.9 weekly) and apolipoprotein B (104.6 mg/dl versus 92.6) levels were also reduced with each treatment. Mean HDL cholesterol was reduced only 6.1 mg/dl (6.3 mg/dl weekly). CONCLUSIONS: Biweekly HELP treatments can safely reduce LDL cholesterol levels as consistently as weekly HELP treatments. However, the higher pre-treatment LDL cholesterol levels with biweekly treatments may produce less therapeutic benefit than with weekly therapy.
BACKGROUND: Human mammary tissue metabolizes lipids from plasma, a process affected by female gonadal hormones. Both benign and malignant proliferation of breast tissue in women have been associated with changes in plasma lipid and lipoprotein levels. METHODS: One hundred consecutive women with breast masses (50 malignant, 50 benign) had diagnostic biopsies followed by axillary node dissection in those with cancer. Fasting serum samples were taken just prior to biopsy and analyzed for lipid fatty acid and lipoprotein levels. Malignant breast tissue was analyzed for hormone receptor binding. RESULTS: Low-density lipoprotein (LDL) components (total cholesterol, LDL-cholesterol, apolipoprotein B) were increased, but not significantly, in cancer patients compared to those with benign masses. Decreased levels of LDL-associated components were found in women with cancer recurrence by 3 years. Three apolipoproteins of high-density lipoprotein (apolipoprotein A-I, apolipoprotein A-II, apolipoprotein D) were more affected by the presence of breast masses than the lipids were. Fibrocystic disease, type of hormone binding, and recurrence within 3 years were significantly related to apolipoprotein changes, especially apolipoprotein D levels with hormone receptor binding and the apolipoprotein A-I/apolipoprotein B ratio with breast cancer recurrence. CONCLUSIONS: Prior to diagnostic biopsy, serum lipid and apolipoprotein components of low-density lipoproteins were increased in women with fibrocystic disease and early stage cancer but decreased in women with early recurrence. However, apolipoprotein A-I, apolipoprotein A-II, and apolipoprotein D, of the high-density lipoproteins, were more affected than serum lipids. The ratio of apolipoprotein A-I to apolipoprotein B serum levels at time of biopsy was the best predictor of cancer recurrence.
Coronary heart disease is the leading cause of mortality and morbidity in the United States at an estimated cost of $56 billion per year. Current approaches to treatment of coronary artery disease are not likely to reduce mortality and morbidity despite pressure to reduce costs in the changing health care environment. Evidence is now available that comprehensive noninvasive medical management, which includes aggressive lipid-lowering therapy, can produce results equivalent to current approaches at a lower cost. The author supports this approach, which can prevent progression and possibly produce regression of coronary artery disease. A new approach to management is proposed that integrates comprehensive noninvasive management as initial therapy for coronary heart disease.
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Studies in animal tumour models of colorectal cancer suggest that F(ab')2 antibody fragments to carcinoembryonic antigen (CEA) labelled with iodine-131 give superior therapy compared with intact anti-CEA antibody. The purpose of this study was to investigate this hypothesis in patients. Ten patients received intact A5B7 IgG1 mouse monoclonal antibody (MAb) to CEA and nine patients received the F(ab')2 fragment of the same antibody. The biodistribution for each molecule was compared using quantitative single-photon emission computerised tomographic (SPECT) gamma-camera imaging. Tumour responses were seen in both groups and myelosuppression was the limiting toxicity. F(ab')2 localised more rapidly than intact antibody in tumour, giving a mean percentage injected activity per kg at 4.25 h after injection of 8.2% for F(ab')2 compared with 4.4% for intact antibody (P < 0.05). No significant difference in antibody clearance from, or cumulative dose per unit administered activity (cGy MBq-1) to, tumour was seen. Distribution in blood was similar for both the intact and fragment antibody. These findings are consistent with more rapid penetration of the smaller F(ab')2 into tumour masses. More efficient early uptake will give higher maximum dose rates to the tumour which is valuable for radioimmunotherapy (RIT) when low dose rates may limit effectiveness of treatment. F(ab')2 fragments may provide a substantially enhanced method of delivering RIT.
Lipiodol, an iodinated derivative of poppyseed oil, is selectively retained in hepatocellular carcinoma and has been used as a vehicle to deliver localized doses of chemotherapeutic and radioactive agents to such tumours, thereby reducing the problems of external beam irradiation and the systemic toxicity of chemotherapy. We describe the first reported case where Lipiodol-targeted radiotherapy has been administered to a patient with secondary renal cell carcinoma in the liver. Localization was good and there were no complications. This case suggests that in future such patients may benefit from this therapy for unresectable lesions.
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Heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) weekly therapy was evaluated for safety and efficacy in selectively reducing LDL cholesterol levels. Weekly treatments (25) were given to high-risk hypercholesterolemic patients (n = 33) with screening LDL cholesterol levels > 160 mg/dl despite prior diet and drug therapy. Lipids, lipoprotein cholesterol, apolipoproteins A-l and B, and fibrinogen were measured on plasma samples before and after treatment. Mean plasma volume treated was 2.66 liters and mean treatment duration 1.7 hours. Therapy complications were infrequent and were primarily vascular access problems or hypotension. Treatment goals were > 30% LDL cholesterol reduction with each treatment. In 98% of 686 HELP treatments, LDL cholesterol levels were reduced > or = 30%. Mean LDL cholesterol levels were reduced 111.0 mg/dl (54%) with a time-averaged decrease of 39% over a 25-week course. Mean HDL cholesterol was reduced only 6.2 mg/dl (15%). Total cholesterol (134.4 mg/dl; 47% decrease) and apolipoprotein B (88.7 mg/dl; 53% decrease) levels were also reduced. Fibrinogen decreased 158.2 mg/dl (58%) without bleeding complications. HELP therapy can safely and selectively remove plasma LDL cholesterol, producing consistent reductions in LDL cholesterol, total cholesterol and apolipoprotein B levels.
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The ability to rapidly reorient attention in the auditory modality was studied in hyperactive children. Hyperactive and nonhyperactive subjects matched on age, sex, and IQ listened to dichotically presented lists for prespecified targets. Reorientation was studied by comparing performance on trials requiring subjects to reorient their attention during a list to performance on trials requiring no switching of attention. The results indicate that although nonhyperactive children were temporarily disrupted by the switch, they eventually reoriented to the cued ear. In contrast, once hyperactive children were disrupted by the switch, they did not reorient to the cued ear. As the pattern in performance comparing hyperactive and nonhyperactive subjects resembles the pattern previously found in comparing younger and older subjects, these results are consistent with the hypothesis that the auditory reorientation skills of hyperactive children are developmentally immature.
The developmental course of the ability to rapidly allocate attention was studied using a dichotic listening task with 8-year old, 11-year old and college age subjects. In this task, subjects were instructed to listen to one ear for predescribed targets and then were later signaled (on some trials) to switch their attention to the other ear. Reorientation was assessed by comparing the pattern of subjects' omission and intrusion errors on trials following a command to switch ears with the pattern of errors on no-switch trials. Older subjects were better able to reallocate their attention in accordance with task demands, with the greatest gains in performance occurring between ages 8 and 11. This developmental change appears to be generally continuous and quantitative in nature. Since successful performance of this task requires flexibility in subjects' ability to control their focus of attention, these results support the hypothesis that the basis of the developmental improvement in the ability to ignore irrelevant information is linked to the ability to use active attentional strategies.