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Biomedical subjects

D Green

Publications and source records attributed to D Green.

At least 109 records · Page 6Linked to original sources
PubMed1998

Association of serum Rituximab (IDEC-C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin's lymphoma.

BACKGROUND: Monoclonal antibodies are being utilized for treatment of patients with low-grade non-Hodgkin's lymphoma as well as other cancers. Results from phase I and II clinical studies has shown that the chimeric monoclonal antibody Rituximab has minimal toxicity and significant therapeutic activity in low grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: We have recently reported on a multicentre pivotal phase III clinical trial involving 166 patients with recurrent low-grade lymphoma who were treated with four infusions of Rituximab. Eighty patients (48%) achieved objective responses including 10 patients (6%) with complete responses. Overall, 126 patients (76%) had a > or = 20% reduction in overall tumor size. The median response duration and time to progression are 11.6 and 13.2 months, respectively. The infusional and long term toxicities were limited. RESULTS: In this report we describe the pharmacokinetic data obtained on these patients. Measurable concentrations of Rituximab were detected in all patients after the first infusion and increased throughout the treatment course. The half-life of the monoclonal antibody increased from 76.3 hours after the first infusion to 205.8 hours after the fourth infusion and was concomitant with a four-fold decrease in the antibody clearance. At three months and six months post-treatment, the median Rituximab serum levels were 20.3 micrograms/ml (range 0.0 to 96.8 micrograms/ml in 104 patients) and 1.3 micrograms/ml (range 0.0-28.7 micrograms/ml in 13 patients), respectively. A statistically significant correlation was found between the median antibody concentration and response for multiple time points during the treatment and followup. The mean serum antibody concentration was also inversely correlated with measurements of tumor bulk and with the number of circulating B cells at baseline. CONCLUSIONS: We conclude that Rituximab is therapeutically effective against B-cell lymphoma. Pharmacokinetic data suggests that certain subsets of patients may possibly benefit from increased dosing and studies to address this are currently underway.

Antibodies, Monoclonal↗
PubMed1998

Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities. The Genital Ulcer Disease Surveillance Group.

To determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (HIV) infection in ulcer patients in 10 US cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city. Ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV); sera were tested for antibody to HIV. H. ducreyi was detected in ulcer specimens from patients in Memphis (20% of specimens) and Chicago (12%). T. pallidum was detected in ulcer specimens from every city except Los Angeles (median, 9% of specimens; range, 0%-46%). HSV was detected in >/=50% of specimens from all cities except Memphis (42%). HIV seroprevalence in ulcer patients was 6% (range by city, 0%-18%). These data suggest that chancroid is prevalent in some US cities and that persons with genital ulcers should be a focus of HIV prevention activities.

Female↗
PubMed1998

Reticular veins, incompetent reticular veins, and their relationship to telangiectases.

BACKGROUND: The pathological role that reticular veins, or their incompetent variants, play in the development and progression of telangiectases has been a subject of debate. The implications of their treatment on the disappearance of telangiectases has been a source of confusion. OBJECTIVE: This article explores the anatomical and functional relationship of reticular veins with telangiectases. The evidence for any pathological role that reticular veins, or their incompetent counterparts, play in the appearance of telangiectases is examined. METHODS: Medical literature on reticular veins of the lower extremity was reviewed. The consequences of their treatment on existing contiguous telangiectases and on the development of new telangiectases is discussed. RESULTS: Telangiectases occur both in the absence and presence of incompetent reticular veins. Incompetent reticular veins often exist without any associated telangiectases present. However, when telangiectases and reticular veins, or their incompetent counterparts, appear in close proximity, their intraluminal channels are, almost invariably, in direct communication. CONCLUSIONS: A causal role for reticular veins, or their incompetent counterparts, in the development or progression of telangiectases has not been established. Furthermore, the successful eradication of telangiectases does not depend on the prior or simultaneous eradication of any reticular veins with which they may communicate. Failure to eradicate telangiectases is not due to the persistence of the reticular veins but to inadequate treatment of the telangiectases.

Humans↗
PubMed1998

Association of dietary fish and n-3 fatty acid intake with hemostatic factors in the coronary artery risk development in young adults (CARDIA) study.

Hemostatic factors play an important role in the complications of ischemic heart and vessel disease. Dietary fats such as n-3 fatty acids have been shown to possibly influence hemostatic factors. However, most studies reporting an inverse association between cardiovascular disease and fish and n-3 fatty acid consumption used supplemental doses of fish oil or intakes exceeding the typical amount consumed by the US population. This report examined the associations of usual intakes of fish, linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid with fibrinogen, factor VII, factor VIII, and von Willebrand factor in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The analyses reported here included 1672 black and white men and women aged 24 to 42 years in 1992 to 1993. After adjustment for age, body mass index, diabetes, number of cigarettes smoked per day, race, and energy and alcohol consumption, no significant associations were observed between those who consumed no fish versus those who consumed the highest level of dietary fish with respect to fibrinogen, factor VIII, or von Willebrand factor for any race-sex group. Comparisons of tertile 1 versus tertile 3 for dietary linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid were also not significantly associated with fibrinogen, factor VII, factor VIII, or von Willebrand factor for any race-sex group. These data suggest that customary intakes of fish and n-3 fatty acids in populations that generally do not consume large amounts of these food items are not associated with these hemostatic factors.

Adult↗
PubMed1998

Constitutional WT1 mutations in Wilms' tumor patients.

PURPOSE: Patients with Wilms' tumors (WT) who carry constitutional mutations in the WT1 gene have been described in case reports and small case series. We sought to determine the frequency of constitutional WT1 mutations in a larger cohort, and to identify clinical manifestations associated with the risk for carrying a WT1 mutation. METHODS: We collected clinical data and blood samples from 201 patients with a history of WT. Southern blot analysis, single-strand conformation polymorphism (SSCP) analysis, and direct DNA sequencing were performed on DNA isolated from peripheral-blood lymphocytes from each patient. Odds ratios (ORs) for the carriage of a germline mutation of the WT1 gene were calculated for patients who had specific clinical risk factors compared with those who did not. RESULTS: Of 201 patients with WT in the cohort, eight patients were carriers of mutations in the WT1 gene. Six of the eight mutations were protein-truncating nonsense mutations. None of 56 patients with isolated unilateral WT was a carrier. The OR of carrying a WT1 mutation was elevated for patients with genitourinary anomalies (OR19.3; P < .002). Seven of 28 boys with WT with cryptorchidism carried WT1 mutations. No increased risk was observed for patients with nephrogenic rests, bilateral tumors, history of secondary cancers, or family history of WT. CONCLUSION: Germline WT1 mutations in patients with WT are associated with genitourinary anomalies, especially cryptorchidism and/or hypospadias. Patients with WT and no genitourinary anomalies are at low risk for carrying a WT1 mutation. Constitutional WT1 mutations that encode truncated WT1 proteins may predispose to the development of cryptorchidism, hypospadias, and WTs.

Adolescent↗
PubMed1998

Avoidable late diagnosis of significant sensorineural hearing loss: implications for practice.

The records for all children from a five-year birth cohort in the geographically defined area of Lothian who were referred by their health visitor to a centralized second tier audiology service after they failed their 7-9 month infant distraction hearing screen were reviewed. The sensitivities, specificities, positive predictive values and yield of this screen for the detection of significant sensorineural hearing loss > or =40 dBA requiring aiding and for a conductive loss persisting beyond one month over 30 dBA were determined. In addition, the records were studied for the same five-year birth cohort for children presenting to the centralized multidisciplinary third tier clinic with a significant sensorineural hearing loss requiring aiding, and the reasons for late diagnosis were determined. If high risk neonatal screening had been available for this population then potentially 67.5% (27 out of 40) of cases could have been identified by an appropriate age. Elimination of health visitor distraction screen false negatives for cases with loses over 60 dBA would potentially increase the case identification by the appropriate age to 45% (1 8 out of 40). Thus, there is greater scope for improving our present results with the introduction of high risk neonatal screening than by improvements in the health visitor screen.

Age Factors↗
PubMed1998

Evolution of a form of pure alexia without agraphia in a child sustaining occipital lobe infarction at 2 1/2 years.

The progress of cognitive visual dysfunction over an 8-year period of a child who sustained bilateral occipital-lobe infarctions at the age of 2 1/2 years is described. She survived with normal intelligence and went on to attend mainstream school. She manifested many features of cognitive visual impairment and, in particular, developed a form of pure alexia without agraphia. She achieved some letter-by-letter reading but no sight vocabulary development, including to her own name. She learned to write imaginatively employing phonetically true spelling but cannot read what she has written. Her progress and the difficulties encountered during the management of her condition are discussed in this first case report of the evolution of pure alexia without agraphia in childhood. The features of this syndrome in the developing child who has never developed the capacity to read are contrasted with that seen in affected adults.

Agraphia↗
PubMed1998

Beneficial effect of vitamin E administration on nitric oxide function in subjects with hypercholesterolaemia.

1. Vitamin E administration improves endothelial function in hypercholesterolaemic animals but, generally, has not been found to do so in man. The aim of this study was to determine whether vitamin E administration improves basal or stimulated function of the nitric oxide (NO) dilator system in patients with hypercholesterolaemia. 2. Seven subjects aged 47+/-3 (+/-S.E.M.) years with moderately elevated serum cholesterol concentrations (6.0+/-0.1 mmol/l) were given 4 weeks of placebo therapy followed by 500 i.u. of vitamin E twice daily for 4 weeks. Endothelium-dependent and -independent vasodilatation were assessed by intrabrachial infusion of acetylcholine and sodium nitroprusside, and forearm blood flow was measured by strain-gauge plethysmography. Basal NO function was assessed by infusion of NG-monomethyl-L-arginine. 3. Plasma alpha-tocopherol concentration was enhanced after administration of vitamin E (34.6+/-1.8 to 86.9+/-9.6 micromol/l; P<0.001). In addition, vitamin E administration significantly increased acetylcholine-mediated vasodilatation whether the results were expressed in terms of changes in absolute forearm blood flow (P<0. 01), forearm vascular resistance (P<0.05) or forearm blood flow ratios (P<0.001). Similarly, absolute forearm blood flow (P<0.05), forearm vascular resistance (P<0.01) and forearm blood flow ratio (P<0.01) responses to NG-monomethyl-L-arginine were augmented by vitamin E therapy. Sodium nitroprusside responses were unaltered. 4. These results indicate that 4 weeks therapy with 1000 i.u. of vitamin E daily improves basal and stimulated NO-related endothelial function in subjects with hypercholesterolaemia.

Acetylcholine↗
PubMed1998

College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: the clinical use and laboratory monitoring of low-molecular-weight heparin, danaparoid, hirudin and related compounds, and argatroban.

OBJECTIVE: To review the role of the laboratory in monitoring therapy with low-molecular-weight heparin, danaparoid, hirudin, and argatroban, as reflected in the medical literature and the consensus opinion of recognized experts in the field. DATA SOURCES: Review of the medical literature and current clinical practice by a panel of 6 international experts in the field of anticoagulant therapy. DATA EXTRACTION AND SYNTHESIS: The experts made an extensive review of the published literature and prepared a draft manuscript, which included preliminary recommendations. The draft manuscript was circulated to participants in the College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy prior to the conference. The manuscript and recommendations were then presented at the Conference for discussion. Recommendations were accepted if a consensus of the 26 experts attending the Conference was reached. The results of the discussion were used to revise the manuscript into its final form. CONCLUSIONS: This report reviews the mechanism of action and potential uses of these newer anticoagulant agents. General guidelines for monitoring these agents and 9 specific recommendations for laboratory monitoring of low-molecular-weight heparin and danaparoid are provided, along with citation of the appropriate supporting literature. Issues for which a consensus was not reached at the Conference are also discussed.

Anticoagulants↗
PubMed1998

Bilateral peroneal nerve palsy secondary to a knee board: report of two cases.

We report on two patients who developed bilateral peroneal nerve palsy after using a knee board behind a water ski boat. This device causes the rider's knees to be in a hyperflexed position secured with a strap across the thighs. Treatment for this compressive neuropathy is conservative. Recreational users may wish to limit the duration and frequency of participation in this sport, thus decreasing the predisposition to prolonged nerve compression. In addition, manufacturers may consider making fundamental design changes such as padding the nylon straps or outrigger devices that contact the proximal lateral tibia.

Adolescent↗
PubMed1997

Anionic- and lipophilic-mediated surface binding inhibitors of human leukocyte elastase.

We report the synthesis of a series of diphenylmethane-based oligomers containing anionic and lipophilic functionalities that are potent inhibitors of human leukocyte elastase (HLE). The enzyme inhibition is regulated by the size of the oligomer, as well as, the number of charges. Lipophilicity is an important element in determining potency and specificity against other basic enzymes. Compounds whose scaffolds contain three phenoxyacetic acid groups and three alkyl ethers are competitive and specific inhibitors of HLE with Ki = 20 nM. The mechanism of action of this class of compounds is believed to involve multidendate interactions with the surface of HLE near the active site which prevents substrate access to the catalytic site.

Benzhydryl Compounds↗
PubMed1997

Low-molecular-weight heparin in the management of Trousseau's syndrome.

BACKGROUND: Thrombophlebitis migrans is a major cause of morbidity in approximately 11% of patients with cancer. Thrombosis may predate the appearance of malignancy, and patients with thrombosis often respond poorly to warfarin. METHODS: Four patients with extensive thrombosis and cancer are described in this article. Enoxaparin, a low-molecular-weight heparin, was administered subcutaneously to these patients for 5, 6, 26, and 27 months, respectively. The literature on the management of Trousseau's syndrome was reviewed and analyzed. RESULTS: All four patients remained free of venous thromboembolism while being treated with low-molecular-weight heparin, acutely and during follow-up. Previously published studies suggest that therapy with low-molecular-weight heparin results in lower mortality than standard heparin therapy. CONCLUSIONS: Further study to evaluate the safety and efficacy of low-molecular-weight heparin for both prophylaxis and treatment of thromboembolism in association with malignancy may lead to decreased morbidity and better quality of life for patients with this disorder.

Adult↗
PubMed1997

Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin-dependent diabetes mellitus.

We postulated that nitric oxide (NO)-mediated endothelial function would be improved by acute and short-term treatment with an angiotensin converting enzyme (ACE) inhibitor in patients with type I diabetes mellitus, in whom endothelial function is depressed. Nine type I diabetic patients and eight healthy subjects underwent forearm blood flow measurement using strain gauge plethysmography during intraarterial infusion of incremental doses of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasodilators. Pretreatment ACh responses were depressed in diabetic patients relative to the normal subjects (P < 0.05). No difference between the groups was evident in response to SNP. Acute ACE inhibition (with intrabrachial enalaprilat) enhanced ACh responses in the diabetic patients (P < 0.005), with a further improvement evident after 1 mo of oral therapy with enalapril (P < 0.001) when ACh responses were normalized. ACE inhibition did not affect SNP responses. We conclude that acute administration of the ACE inhibitor, enalaprilat, enhances NO-mediated endothelial function in type I diabetic patients, with further improvement evident after 4 wk of enalapril therapy.

Administration, Oral↗
PubMed1997

Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas/FasL-mediated apoptosis.

T helper cell (Th) 1, but not Th2, effectors undergo rapid Fas/Fas ligand (FasL)-mediated, activation-induced cell death upon restimulation with antigen. Unequal apoptosis is also observed without restimulation, after a longer lag period. Both effectors undergo delayed apoptosis induced by a non-Fas-mediated pathway. When Th1 and Th2 effectors are co-cultured, Th2 effectors survive preferentially, suggesting the responsible factor(s) is intrinsic to each population. Both Th1 and Th2 effectors express Fas and FasL, but only Th2 effectors express high levels of FAP-1, a Fas-associated phosphatase that may act to inhibit Fas signaling. The rapid death of Th1 effectors leading to selective Th2 survival provides a novel mechanism for differential regulation of the two subsets.

Animals↗
PubMed1997

Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month.

BACKGROUND: Cholesterol-lowering therapy can improve cardiovascular morbidity and mortality in patients with atherosclerosis. Although the mechanisms responsible are unclear, these benefits precede macroscopic changes in the vasculature. Emerging evidence that improvement in endothelial function may occur requires substantiation; in particular, it is unclear how early any such improvement would be detectable after initiation of therapy. METHODS AND RESULTS: This randomized, double-blind, placebo-controlled crossover study evaluated the effect of simvastatin (20 mg daily for 4 weeks) on endothelium-dependent and endothelium-independent vasodilation and on the response to the inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (L-NMMA), in the forearm vasculature of subjects with moderate elevation of total serum cholesterol (6.0 to 10.0 mmol/L) by use of strain-gauge plethysmography. Studies were repeated after 3 more months of open therapy. When the results are expressed as percentage changes in flow in the infused arm relative to the noninfused arm, the vasodilator response to acetylcholine was significantly increased after 4 weeks of treatment with simvastatin (P < .0005), and this improvement was further enhanced after 3 months (P < .005). Concurrently, simvastatin augmented the vasoconstrictor response to L-NMMA, an effect that was maintained at 3 months (P < .0005). The response to the endothelium-independent vasodilator sodium nitroprusside was unaltered. CONCLUSIONS: These observations indicate that within 1 month of treatment with simvastatin, both the stimulated and basal nitric oxide dilator functions of the endothelium are augmented, and the benefits of this HMG-coenzyme A reductase inhibitor persist with continued therapy.

Acetylcholine↗
PubMed1997

Treatment of proximal vein thrombosis with subcutaneous low-molecular-weight heparin vs intravenous heparin. An economic perspective.

BACKGROUND: Subcutaneous low-molecular-weight heparin is at least as effective and safe as classic intravenous heparin therapy for the treatment of proximal vein thrombosis. Anticoagulant monitoring is not required with low-molecular-weight heparin. OBJECTIVE: To perform an economic evaluation of these therapeutic approaches by comparing cost and effectiveness. PATIENTS AND METHODS: A randomized trial in 432 patients with proximal vein thrombosis that compared intravenous heparin and low-molecular-weight heparin with objective documentation of clinical outcomes provided the opportunity to perform an analysis of cost-effectiveness to rank these alternative therapies in terms of both their cost and effectiveness. The economic viewpoint of this analysis was that of a third-party payer (ie, a ministry of health in Canada or an insurance company in the United States). RESULTS: In the intravenous heparin-treated group, the cost incurred for 100 patients was $414,655 (Canadian dollars) or $375,836 (US dollars), with a frequency of objectively documented venous thromboembolism of 6.9%. In the low-molecular-weight heparin-treated group, the cost incurred for 100 patients was $399,403 (Canadian dollars) or $335,687 (US dollars), with a frequency of objectively documented venous thromboembolism of 2.8%, thus providing a cost saving of $15,252 (Canadian dollars) or $40,149 (US dollars). Multiple sensitivity analyses were performed, and these procedures did not alter the findings of the study. CONCLUSIONS: The findings indicate that low-molecular-weight heparin therapy is at least as effective and safe but less costly than intravenous heparin treatment. The potential for outpatient therapy in up to 37% of patients who are receiving low-molecular-weight heparin would substantially augment the cost saving.

Anticoagulants↗
PubMed1997

Subcutaneous low-molecular-weight heparin vs warfarin for prophylaxis of deep vein thrombosis after hip or knee implantation. An economic perspective.

BACKGROUND: Postoperative venous thrombosis and pulmonary embolism present a major clinical threat to patients undergoing total hip or knee arthroplasty. We performed an economic evaluation of warfarin sodium and subcutaneous low-molecular-weight heparin sodium prophylaxis comparing cost and effectiveness. METHODS: A consecutive series of 1436 patients who underwent hip or knee arthroplasty comparing these 2 regimens in a randomized trial with objective documentation of outcomes provided the opportunity to perform economic evaluations for Canada and the United States. RESULTS: Deep vein thrombosis was documented in 231 (37.4%) of 617 patients given warfarin and in 185 (31.4%) of 590 patients given low-molecular-weight heparin (P = .03). In Canada, warfarin and low-molecular-weight heparin (tinzaparin sodium) incurred costs per 100 patients of $11,598 and $9,197, respectively, providing a cost savings of $2,401 for the low-molecular-weight heparin group. The drug cost of low-molecular-weight heparin (tinzaparin) was $6 per day and for warfarin was $0.32 per day. Sensitivity analysis showed that low-molecular-weight heparin is more costly if drug costs are increased by 1.5-fold (ie, the cost of tinzaparin is increased from $6 per day to $8.82 per day or more). In the United States, the analysis was also not definitive; low-molecular-weight heparin was more costly than warfarin at drug costs of $15 and $2.01 per day, respectively. CONCLUSIONS: Our findings indicate that the decision to use low-molecular-weight heparin or warfarin prophylaxis in patients undergoing major joint replacement surgery is a finely tuned trade-off. Prophylaxis with low-molecular-weight heparin is equally or more effective than the more complex prophylaxis with warfarin. Major bleeding is uncommon but less frequent with warfarin use. The most significant parameters that influence the comparative cost-effectiveness are the cost of the drug, the cost of international normalized ratio monitoring, and the costs associated with major bleeding. The analysis also demonstrates that the results are health care system dependent (Canada vs US). In Canada, low-molecular-weight heparin (tinzaparin) is less costly because it avoids the need for international normalized ratio monitoring. In the United States, the drug cost for low-molecular-weight heparin will likely be the principal determinant of relative cost-effectiveness.

Adult↗