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Biomedical subjects

D Green

Publications and source records attributed to D Green.

At least 235 records · Page 13Linked to original sources

Prevention of thromboembolism after spinal cord injury using low-molecular-weight heparin.

OBJECTIVE: To examine the safety and effectiveness of a low-molecular-weight heparin in the prevention of thromboembolism in patients with recent spinal cord injury and complete motor paralysis. DESIGN: Randomized evaluation of two heparin regimens in 41 consecutive patients meeting eligibility requirements for anticoagulant prophylaxis. Daily bedside examinations were supplemented by serial venous flow studies; suspicious or positive tests were confirmed by venography. INTERVENTION: Standard heparin, 5000 units subcutaneously three times a day; low-molecular-weight heparin 3500 anti-Xa units subcutaneously once daily. MEASUREMENTS AND MAIN RESULTS: Five patients in the standard heparin group had thrombotic events, including two patients with fatal pulmonary embolism; two other patients had bleeding severe enough to necessitate withdrawing the heparin. The cumulative event rate was 34.7% (95% CI, 13.7% to 55.2%). None of the patients treated with low-molecular-weight heparin had thrombosis or bleeding (CI, 0% to 14%). The difference between the two groups was significant (P = 0.006, log-rank test). CONCLUSIONS: Low-molecular-weight heparin is safe and effective in the prevention of thromboembolism in selected patients with spinal cord injury and complete motor paralysis, and is superior to standard heparin in fixed doses of 5000 units three times a day.

Administration, Cutaneous↗

Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis.

It is common practice to begin anticoagulant treatment of deep-vein thrombosis with a 10-day course of intravenous heparin, with warfarin added on day 5 to 10 and continued for several months. We performed a randomized, double-blind trial comparing a shorter course of continuous intravenous heparin (5 days, with warfarin sodium begun on the first day) with the conventional 10-day course of heparin (with warfarin sodium begun on the fifth day) in the initial treatment of 199 patients with acute proximal venous thrombosis documented by venography. The frequency of objectively documented recurrent venous thromboembolism was low and essentially the same in the two groups (7.1 percent in the short-course group vs. 7.0 percent in the long-course group). Because the observed difference between the groups was 0.1 percent in favor of the long-course group, it is unlikely (P less than 0.05) that a true difference in favor of this group would be greater than 7.5 percent; the difference could be as much as 7.3 percent in favor of the short-course group. Major bleeding episodes were infrequent, and the rate was similar in both groups. We conclude that a five-day course of heparin is as effective as a 10-day course in treating deep venous thrombosis. Furthermore, using the shorter course would permit earlier discharge from the hospital and thus offer substantial cost savings.

Acute Disease↗

Thrombogenicity of intravenous 5-fluorouracil alone or in combination with cisplatin.

Acute myocardial infarction was observed in two patients receiving standard intravenous doses of 5-fluorouracil (5-FU)-based chemotherapy. Therefore, the authors prospectively assessed the thrombogenicity of this agent by studying ten patients, six with head and neck cancer and four with gastrointestinal malignancies, receiving 5-FU (1 g/m2/day) as a constant intravenous infusion over a 4-day or 5-day period. The six patients with head and neck cancer also received a single dose of 100 mg/m2 of cisplatin on day 1. Blood samples were obtained preinfusion, 24 hours into the infusion, and postinfusion. Samples were assayed for fibrinopeptide A (FpA) by enzyme-linked immunoassay, for protein C activity (PCa) using a chromogenic substrate (Spectrozyme PCa), and protein C (PCag) and free protein S antigen (PSag) by electroimmunoassay. No patient experienced a thrombotic event. A significant increase was observed in FpA levels during the infusion which returned toward baseline at the conclusion of the infusion. After infusion of 5-FU, the PCa value was significantly lower than the PCag (37 +/- 17 versus 69 +/- 24%; P less than 0.002). No effect on protein S was observed. The changes in the patients receiving 5-FU alone were comparable to those who also received CDDP. The authors conclude that during the infusion of 5-FU, the rise in FpA activation and reduction in PCa as compared to PCag are compatible with activation of coagulation.

Adult↗

Acute myocardial infarction, non-bacterial thrombotic endocarditis, and disseminated intravascular coagulation in a severe hemophiliac.

Thrombosis in hemophilia is very rare and is usually associated with the administration of prothrombin complex concentrates. We describe a severe hemophiliac with P. carinii pneumonia who had clinical and laboratory evidence of acute myocardial infarction and disseminated intravascular coagulation, and at autopsy, nonbacterial thrombotic endocarditis as well. We suggest that prothrombin complex concentrates should be used cautiously in the setting of acute infection, and perhaps be given with appropriate doses of anticoagulants such as heparin.

Adult↗

New sugar mitomycin C analogues: preparation, murine P388 antitumor activity, and leukopenia induction.

Four new sugar:mitomycin C derivatives were synthesized by coupling of N-1 of mitomycin C with tetra-O-acetylglucopyranosyl isothiocyanate and 3,4,6-tri-O-acetyl-2-(N-acetylamino)-2-deoxyglucopyranosyl isothiocyanate. Conversion of each derivative to its water-soluble analogue was achieved by deacetylation, using saturated NH3:CH3OH. Antitumor activity, assessed using the in vivo murine P388 ascitic leukemia system, demonstrated efficacy comparable with the parent mitomycin C. However, unlike the highly myelosuppressive parent drug, optimal antitumor activity is achieved at doses which produce only limited leukopenia.

Animals↗

Randomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis.

PURPOSE: To compare the efficacy and safety of recombinant human tissue-type plasminogen activator (rt-PA, supplied as Activase) with heparin alone or rt-PA plus heparin in the treatment of venographically documented proximal deep venous thrombosis (DVT) of the leg. PATIENTS AND METHODS: Sixty-four patients underwent 65 randomizations to rt-PA alone (n = 36), rt-PA plus heparin (n = 17), or heparin alone (n = 12) in a prospective, multicenter, randomized, open-label trial, with efficacy assessed by a radiology panel unaware of treatment assignment. Patients randomly assigned to rt-PA received 0.05 mg/kg/hour for 24 hours via a peripheral vein, with a maximum dose of 150 mg. All patients then received heparin and warfarin for the remainder of the hospitalization. Follow-up venography was performed 24 to 36 hours after initiation of therapy. RESULTS: Complete or more than 50% lysis occurred in 10 (28%) patients treated with rt-PA, five (29%) patients with rt-PA plus heparin, and no patient treated with heparin. No lysis occurred in 16 (44%) patients treated with rt-PA plus heparin, and 10 (83%) patients who received heparin alone (p = 0.04). There was one major complication, a nonfatal intracranial hemorrhage in a patient who received rt-PA alone. At 7 to 10 days after initiation of treatment, the level of serum glutamic oxaloacetic transaminase nearly doubled among all patients, including those assigned to receive heparin alone. CONCLUSION: (1) rt-PA and rt-PA plus heparin cause more clot lysis than heparin alone; (2) the addition of heparin to rt-PA does not improve the lysis rate; (3) DVT treated with heparin is commonly associated with a rise in the transaminase level; (4) heparin does not increase the risk of bleeding from rt-PA therapy; and (5) alternative dosing regimens and modes of administration of rt-PA should be investigated to improve further its efficacy and safety in the treatment of acute DVT.

Adolescent↗

Thermal self-regulation for pain control in reflex sympathetic dystrophy syndrome.

Reflex sympathetic dystrophy syndrome is comprised of a variety of changes in vasomotor and trophic responsivity, as well as, stiffness, edema and severe pain. This study examined 20 patients with reflex sympathetic dystrophy syndrome who had failed to respond to a variety of techniques commonly used to treat this disorder. These patients had documented histories of reflex sympathetic dystrophy syndrome ranging from 18 to 60 months. All had been referred for psychological evaluation and provision of pain management. A combination of thermal biofeedback, relaxation training, and supportive psychotherapy were used to reduce subjective pain. The results indicate that patients were able to significantly increase their initial (p less than 0.0001) and postrelaxation (p less than 0.0001) hand temperatures, as well as to significantly reduce their subjective pain ratings (p less than 0.0001). This reduction in pain was maintained at 1-year telephone follow-up, with 14 of the 20 patients returning to work by that time. This intervention was effective as a pain reduction strategy for our patients with reflex sympathetic dystrophy syndrome who had failed to benefit from other treatments.

Adult↗

Plasminogen, alpha 2-antiplasmin, and protein C decline following infusions of recombinant tissue plasminogen activator.

We examined a variety of hemostatic functions in a subset of patients participating in a multicenter trial of rt-PA in the treatment of DVT. There were declines in systemic levels of plasminogen and alpha 2-antiplasmin at 24 hours following therapy. Additionally, levels of protein C antigen and protein C activity were also seen to decrease over the same time course. We propose that therapy with rt-PA has more systemic effects than previously thought and suggest that the effect on protein C may have some role in reocclusion following thrombolysis.

Drug Synergism↗

DNA restriction fragment length polymorphism of HLA-DR2 haplotypes in normal individuals and in patients with rheumatoid arthritis.

A strong association between HLA-DR4 and rheumatoid arthritis (RA) has been found in a number of populations. In contrast, the incidence of DR2 is decreased in patients with RA, suggesting that this specificity may confer some protection against the disease. A number of subtypes of DR2 have been defined by serology, by responses in mixed lymphocyte culture reaction, and, more recently, by restriction fragment length polymorphism. These subtypes of DR2 are in linkage disequilibrium with different subspecificities of DQw1. It is thus likely that the distribution of these subtypic DR,DQ haplotypes in DR2 positive patients with RA may be important in understanding the genetic basis of susceptibility/resistance to RA. In this paper a study of the subtypes of DR2,DQw1 haplotypes in 18 patients with RA, who required sodium aurothiomalate as a disease remitting drug, and unrelated healthy individuals is reported. Three subtypes of DR2 haplotypes, DRw15 (Dw2),DQw1.2(DQw6), DRw15(Dw12),DQw1.12(DQw6), and DRw16(Dw21),DQw1, AZH (DQw5), were analysed with a cDNA probe for the DQ beta gene. The data show that DR2 positive patients with RA carried either the DRw15(Dw2),DQw6 or DRw15(Dw12),DQw6 haplotype. No patient with RA was positive for the DRw16(Dw21),DQw5 subspecificity. In contrast, six of 29 (21%) normal healthy DR2,DQw1 positive individuals carried the DRw16(Dw21),DQw5 haplotype. These data together with earlier results on the distribution of the DR4,DQw7 haplotype in patients with RA support the hypothesis that DQB1 chain polymorphism may be important in determining susceptibility to severe RA.

Arthritis, Rheumatoid↗

Polymorphism of major histocompatibility complex extended haplotypes bearing HLA-DR3 in patients with rheumatoid arthritis with gold induced thrombocytopenia or proteinuria.

The distribution of DR3 and of extended haplotypes bearing DR3 was studied in three groups of subjects: 35 patients with rheumatoid arthritis (RA) with gold induced thrombocytopenia or proteinuria, 185 patients with RA without these side effects, and 300 normal healthy controls. The extended haplotypes bearing DR3 were analysed with cDNA probes for DR alpha, DR beta, DQ alpha, and DQ beta genes. The data showed that the prevalence of DR3 was significantly higher in patients who developed gold induced thrombocytopenia or proteinuria than in normal controls or patients with RA without these side effects. Distribution of three extended haplotypes bearing DR3 (B8, DR3; B18,DR3; non-B8,non-B18,DR3) in patients with RA with thrombocytopenia or proteinuria was significantly different from that in normal controls, but not from that in patients with RA without these toxic reactions. Southern blot analysis of DR, DQ genes with cDNA probes showed that the extended haplotype bearing B8,DR3, which carries DQA2.1 and DQB2.1 genes, was present in a significantly higher proportion of patients with RA with gold induced thrombocytopenia or proteinuria (22/24, 92%) than in patients with RA without these side effects (32/45, 71%) or normal subjects (40/61, 66%). The data suggest that the genomic region on chromosome 6 involved in susceptibility to gold induced thrombocytopenia or proteinuria should be extended to the DQA2, DQB2 gene loci.

Arthritis, Rheumatoid↗

Erythema multiforme and Stevens-Johnson syndrome. Descriptive and therapeutic controversy.

Diagnosis and particularly the management of erythema multiforme and Stevens-Johnson syndrome are controversial in medical textbooks and thus in individual cases. In these diseases, fatalities may result from various causes, including secondary infection or visceral organ damage to lung, liver, or kidneys. We present a series of 13 cases managed by one group of physicians which demonstrates the controversy in certain cases, and we review the controversy in the medical literature. Corticosteroid therapy used in this series was considered beneficial in every case by the managing physician and lifesaving in some cases. There were no fatalities in this series. Although the summation may be considered as our opinion only, the frequently suggested "controlled trial of corticosteroid therapy" can probably never be done for ethical reasons, and series such as this will have to establish the standard of therapy.

Erythema Multiforme↗

Instrument for the measurement of individual and societal attitudes toward drugs.

Due to the importance of the relation between attitudes and the experimentation with and use of drugs among adolescents, an instrument was developed composed of individual and societal attitudes toward drugs. A pilot study was carried out on the basis of which a questionnaire containing 63 items was constructed. This questionnaire was given to the research sample of 566 Israeli high school students aged 15-17. Three criteria were used to determine the final version of the instrument, which contains 55 items. Factor analysis revealed seven factors: curiosity and willingness to use drugs, social concern, individual freedom, attribution of positive characteristics to drugs, perceived harmfulness of drugs, perceived characteristics of drug users, and legalization of drugs. Reliability of the factors ranges from alpha = 0.64 to alpha = 0.88; reliability of the entire questionnaire is alpha = 0.89. A short version of the questionnaire consisting of 27 items (alpha = 0.80) was developed for special populations. These findings suggest that the Green Individual and Societal Attitudes Toward Drugs Questionnaire can be employed as a diagnostic tool to identify potential drug experimenters, and as a planning and evaluation measure to preventive drug educational programs.

Adolescent↗

Murine anti-tumor activity of new water soluble platinum(II) complexes with reduced toxicity.

A series of new water soluble sugar and non-sugar containing platinum(II) complexes was synthesized and evaluated for effects of the sugar moiety on water solubility, anti-tumor activity, and acute leukopenia. When tested in vivo against the murine P388 and L1210 leukemias at LD10/maximally effective doses, the compound cis-[(gluconylamino)malonato-O,O'](1R,2R-cyclohexanediami ne-N,N')platinum (II), R,RG-AMP produced comparable or superior anti-tumor activity to cisplatin, carboplatin, and tetraplatin. Efficacy was also demonstrated for the L1210/DDP (cisplatin-resistant) leukemia. Further, R,R-G-AMP is non-nephrotoxic and produces less leukopenia than cisplatin, carboplatin, and tetraplatin.

Animals↗

Dysvascular amputee rehabilitation. The role of continuous noninvasive cardiovascular monitoring during physical therapy.

Recognition of cardiac problems and their impact on the treatment of dysvascular amputees is important during rehabilitation because the energy demands and cardiac work loads of functional activities are substantially greater when performed by persons with amputation than when performed by control subjects. For this reason, monitoring the cardiovascular response to therapeutic exercise might be expected to enhance the medical and rehabilitative management of dysvascular amputees. In the present study, 31 amputees with peripheral vascular disease underwent continuous noninvasive dynamic cardiovascular monitoring during an initial physical therapy session. The sample had a mean age of 65 yr. There were 20 females. Twenty patients had unilateral below knee amputation. Fifty-two percent had a preamputation history of cardiac disease and six experienced major cardiovascular complications during rehabilitation. After a mean acute hospitalization of 20 days and a mean rehabilitation stay of 36 days, 11 patients were walking independently and 25 were discharged to home. During the monitored physical therapy session, patients achieved a mean maximum heart rate of 113 beats/min, mean maximum blood pressure of 159/81, mean maximum rate-pressure product of 14,546, and mean percent of age-predicted maximal heart rate of 73%. Seventeen (55%) patients demonstrated abnormalities during the monitored session, four of whom had no prior history of heart disease. These changes consisted predominantly of ST-T segment abnormalities, but also included exercise-induced arrhythmias and decreases in blood pressure. Patients with a history of heart disease demonstrated significantly more abnormalities during the monitored session than did those without a history of heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗