Another indication for low-density lipoprotein apheresis.
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Biomedical subjects
Publications and source records attributed to D M Lane.
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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.
A 3-year-old boy with minor bleeding problems had no plasma fibrinogen measured by both clottable assay and immuno-precipitation. Low normal fibrinogen levels were present in the mother and father. Markedly decreased plasma cholesterol and apolipoprotein B levels were found in the father, proband's brother, and the paternal side of the kindred. The proband and his mother had normal plasma total cholesterol and apolipoprotein B levels. These findings are compatible with autosomal dominant transmission of hypobetalipoproteinemia and autosomal recessive transmission of afibrinogenemia. Two members of the father's family had plasma cholesterol levels below the fifth percentile but elevated levels of fibrinogen (6.0 and 4.4 g/L). Both have symptomatic coronary heart disease. Finding coronary heart disease with very low cholesterol but elevated fibrinogen levels is consistent with fibrinogen levels being an independent risk factor for coronary heart disease.
Ozer (1987) found that spatial visualization correlated with personality and verbal ability for girls but not for boys. To account for this finding, he hypothesized that "the causes of individual differences in spatial visualization [may be] different for the two sexes" (Ozer, 1987, p. 134). Although Ozer's conclusion is an intriguing one, it should be viewed with at least some skepticism until the discrepancies between his data and those of other researchers have been reconciled.
The pattern of attention movements underlying reorientation of visual selective attention independent of eye movements was studied developmentally in 2 experiments. In Experiment 1, 8-year-old, 11-year-old, and college-age subjects first oriented their attention to a central location and were then cued to direct their attention either to the left or the right peripheral field. Following variable intervals, the target appeared at the cued location and reaction times were recorded. The data were interpretable in terms of the attentional spotlight theory since there was an interaction between distance of the target from fixation and SOA. In terms of this theory, the data indicate that the velocity of attention movements increases throughout the age range studied. Experiment 2, in contradiction to attentional spotlight theory, failed to find evidence of an interaction between distance and SOA. This experiment suggested that young children can covertly orient their attention by including valid, neutral, and invalid cues, and that these cues can both facilitate and inhibit attentional orientation. This experiment also extended the findings to central as well as peripheral cues.
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Studies were carried out to investigate potential changes in apolipoprotein C-III (apoC-III) polymorphism from birth through the first month of life. Maternal serum at term and neonatal serum at birth, 3, 14, and 28 days were analyzed for the three principal polymorphic forms of apoC-III: apoC-III-0, apoC-III-1, and apoC-III-2. A two-dimensional electrophoretic procedure combining isoelectric focusing and electroimmunoassay was developed for this purpose. In maternal serum (n = 28), apoC-III-1 to apoC-III-2 ratios (1.45) were typical of normolipidemic adult serum, while the corresponding cord sera (n = 32) had a reversal of the apoC-III-1 to apoC-III-2 ratio (0.55). Basic polyacrylamide gel electrophoretic patterns of isolated cord sera lipoprotein density classes confirmed the reversal of the apoC-III-1 to apoC-III-2 ratio in each class. Following birth, the apoC-III-1 to apoC-III-2 ratio reached unity (1.04) at 3 days and did not change significantly thereafter. It can be concluded that the apoC-III-1 to apoC-III-2 ratio in the normal newborn increases shortly after birth primarily due to an increase in apoC-III-1, and this change appears to be associated with oral feeding, suggesting that intestinal factors may play a role in controlling the ratio of plasma apoC-III-1 to apoC-III-2.
Asymmetric enlargement of the right adnexa in a prepubertal, asymptomatic, 7-year-old girl with acute lymphocytic leukemia (ALL) was detected by pelvic sonography as part of examinations after the discontinuation of therapy. The case is the first where asymptomatic ovarian relapse has been detected prospectively by sonography. The technique should be considered for the follow-up female patients with ALL in remission, although more extensive studies are needed to establish its effectiveness.