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Biomedical subjects

D Green

Publications and source records attributed to D Green.

At least 145 records · Page 8Linked to original sources
PubMed1996

Recombinant human erythropoietin: effect on the functional performance of anemic orthopedic patients.

OBJECTIVE: To determine whether rapid correction of anemia improves the functional and cognitive performance of postoperative orthopedic patients. DESIGN: A randomized, double-blind, placebo-controlled clinical trial. SETTING: A rehabilitation institute. PATIENTS: Persons having orthopedic surgery at least 2 weeks previously, and a hemoglobin concentration < 10g/dL. INTERVENTIONS: Recombinant human erythropoietin (rH-EPO) or the EPO vehicle for up to 8 weeks. All patients received ferrous sulfate. MEASUREMENTS: Blood counts were performed at weekly intervals, and functional and cognitive tests at baseline and weeks 4 and 8. RESULTS: In patients receiving vehicle only, hemoglobin levels increased from a mean of 9.0 at baseline to 11.0 at 4 weeks and 11.7 at 8 weeks; corresponding values for rH-EPO were 8.8 (p = NS), 12.6 (p = .02), and 13.5 (p = .01). However, functional improvement in dressing, toileting, and mobility was similar between groups, and the results of neuropsychological tests showed no trends favoring rH-EPO. CONCLUSIONS: Although hemoglobin increases more rapidly in anemic orthopedic patients treated with rH-EPO, equally rapid functional improvement occurs in those who receive only iron therapy.

Activities of Daily Living↗
PubMed1996

Longitudinal study of adrenal steroids in a cohort of HIV-infected patients with hemophilia.

The objective of the study was to relate plasma dehydroepiandrosterone sulfate (DHEA-S) concentrations to the progression of HIV infection in individual HIV-infected men with hemophilia and to obtain information on the cause of DH EA-S alterations. Blood samples were obtained from 16 men with hemophilia; in 9 men serial samples were available for up to 11 years after HIV-1 infection. Control samples were obtained from men of comparable ages without hemophilia or HIV infection. Measurements were made of CD4+ cell counts, plasma adrenocorticotropic hormone (ACTH), cortisol, DHEA, DHEA-S, and prolactin. Before HIV infection, men with hemophilia had significantly lower plasma levels of DHEA-S than control men. After infection, 3 of 9 subjects studied serially had little or no change in plasma DHEA-S levels or in CD4+ cell counts over 11 years. Four of the 9 i n whom AIDS developed had progressive decreases in plasma DHEA-S concentrations that, in some cases, preceded a precipitous fall in CD4+ cell counts. Major decreases in plasma DHEA-S levels before falls in CD4+ counts were observed in 2 ot her subjects who had other severe illnesses. None of the decreases in DHEA-S levels were associated with decreased concentrations of plasma cortisol, ACTH, or prolactin. We conclude that plasma DHEA-S is an indicator of general health rather than a specific indicator for progression of HIV. The decrease in plasma DHEA-S is not related to ACTH stimulation of the adrenal gland or to cortisol secretion, but it may be related to cytokines that can inhibit 17-hydroxylation of DH EA-S precursors.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Interaction of low molecular weight heparin with ketorolac.

Postoperative patients may receive ketorolac, a nonsteroidal antiinflammatory drug that inhibits platelet function, for analgesia and may receive low-molecular-weight heparin (LMWH) for thrombosis prevention. We investigated whether the combination of these two agents increases blood loss in a rabbit model of hemostasis. In a randomized, blinded study, animals received either intramuscular ketorolac (0.5 mg/kg or 1.0 mg/kg) and subcutaneous saline solution, subcutaneous LMWH (100 U/kg) and intramuscular saline solution, ketorolac (0.5 mg/kg or 1.0 mg/kg) and subcutaneous LMWH (100 U/kg), or intramuscular and subcutaneous saline solution given 30 minutes before ear incision and measurement of blood loss. Collagen-induced platelet aggregation was examined and anti-Xa levels were determined by using a chromogenic substrate method. As compared with results in saline-treated controls, blood loss was significantly increased in animals receiving ketorolac in a dose of 1.0 mg/kg but not in those treated with 0.5 mg/kg. The addition of LMWH did not further increase blood loss above that observed with either dose of ketorolac alone. Platelet aggregation was inhibited by both doses of ketorolac. The anti-Xa levels in the LMWH-treated animals were comparable to those measured in patients receiving these agents for prophylaxis (0.09 to 0.13 U/ml). We conclude that in the rabbit model, LMWH does not augment ketorolac-associated bleeding when both agents are used in doses comparable to those given to human patients.

Animals↗
PubMed1996

MDA435/LCC6 and MDA435/LCC6MDR1: ascites models of human breast cancer.

We have established a novel ascites tumour model (MDA435/LCC6) from the oestrogen receptor-negative, invasive and metastatic MDA-MB-435 human breast cancer cell line. MDA435/LCC6 cells grow as both malignant ascites and solid tumours in vivo in nude mice and nude rats, with a tumour incidence of approximately 100%. Untreated mice develop ascites following i.p. inoculation of 1 x 10(6) cells and have a reproducible life span of approximately 30 days, with all animals dying within a 48 h period. The in vivo response of MDA435/LCC6 ascites to several cytotoxic drugs, including doxorubicin, etoposide (VP-16), BCNU and mitomycin C, closely reflects the activity of these single agents in previously untreated breast cancer patients. MDA435/LCC6 cells also retain the anchorage-dependent and anchorage-independent in vitro growth properties of the parental MDA-MB-435 cells, and can be used in standard in vitro drug screening assays. The drug resistance pattern of the MDA435/LCC6 cells suggests that they may have few active endogenous drug resistance mechanisms. To generate a model for the screening of MDR1-reversing agents, MDA435/LCC6 were transduced with a retroviral vector directing the constitutive expression of the MDR1 cDNA, producing a cell line with a classical MDR1 resistance pattern (MDA435/LCC6MDR1). THese ascites models may be a viable alternative to the murine leukaemia ascites (L1210, P388) and, in conjunction with other breast cancer cell lines, facilitate the in vitro and in vivo screening of new cytotoxic drugs and drug combinations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

AIDS-associated non-Hodgkin's lymphomas as primary and secondary AIDS diagnoses in hemophiliacs. Hemophilia Malignancy Study Group.

We studied the characteristics and temporal trends of AIDS- associated non-Hodgkin's lymphoma (AIDS-NHL) in individuals with hemophilia. Prospective data were collected on 33 HIV-positive hemophiliacs with AIDS-NHL enrolled in the Hemophilia Malignancy Study (HMS), of whom 21 had primary and 12 had secondary or subsequent AIDS-defining illnesses, and analyzed for frequency and temporal trends. As compared with primary AIDS- NHL, secondary AIDS-NHL occurred at an older mean age, 37 versus 29 years (p = 0.12); at a lower mean CD4 count, 46 versus 154 (p = 0.07); after a longer period of immunosuppression (CD4 < 200/microl), 41 versus 16 months (p = 0.03); and with shorter median survival, 2 versus 7 months (p = 0.09). The presence of EBV in tumor tissue was associated with shorter survival, 1 versus 7 months (p = 0.17). Between 1981 and 1988 and 1989 and 1994, the proportion of primary AIDS diagnoses that were AIDS-NHL changed minimally, 4.6 versus 6.1%, whereas there were significant decreases in Pneumocystis carinii pneumonia (PCP, p = 0.02) and wasting (p = 0.07), and an increase in Candida (p = 0.004). These findings confirm that an increasing proportion of AIDS-NHL in hemophiliacs are occurring as secondary or later AIDS diagnoses, and they are associated with prolonged duration of immunosuppression.

AIDS-Related Opportunistic Infections↗
PubMed1996

Deep vein thrombosis in stroke. The use of plasma D-dimer level as a screening test in the rehabilitation setting.

BACKGROUND AND PURPOSE: Venous thromboembolism is a leading cause of morbidity and mortality during the acute recovery period after stroke. This study investigated the utility of plasma D-dimer level as a diagnostic test for deep vein thrombosis (DVT) in patients hospitalized for stroke rehabilitation. METHOD: Plasma samples were drawn from 105 nonambulatory rehabilitation patients with recent ischemic or hemorrhagic stroke and assayed for D-dimer with an enzyme-linked immunosorbent method. Samples were drawn within 24 hours of venous duplex ultrasound (VDU) screening for DVT. Optimal discriminant analysis was used to determine whether plasma D-dimer level, age, sex, days after stroke onset, stroke etiology. National Institutes of Health Stroke Scale score, and ambulatory status could correctly classify patients' DVT status. RESULTS: Fourteen of 105 patients had DVT identified by VDU scan. Of all attributes, only D-dimer level had significant ability to discriminate between patients with or without DVT (P < .0001). The optimal cut point for predicting DVT was D-dimer = 1591 ng/mL, resulting in 79% sensitivity, 78% specificity, 35% positive predictive value, and 96% negative predictive value. Reducing the D-dimer cut point to 1092 ng/mL improved both sensitivity and negative predictive value to 100% but reduced specificity to 66% and positive predictive value to 31%. CONCLUSIONS: A D-dimer level < or = 1092 ng/mL can exclude the presence of DVT in stroke rehabilitation patients. When a D-dimer level > 1092 ng/mL occurs, further diagnostic testing is necessary to confirm DVT. Plasma D-dimer level is a simple and inexpensive screening test for DVT during stroke rehabilitation.

Cerebrovascular Disorders↗
PubMed1996

Mass human exposure to rabies in New Hampshire: exposures, treatment, and cost.

OBJECTIVES: This study assessed the rabies exposure and treatment that at least 665 persons in Concord, NH, received as a result of one proven rabid pet-store kitten in October 1994. METHODS: All treatment recipients were interviewed by person or phone. RESULTS: The median age of the treatment recipients was 14 years; 58% were female. The most common exposures were low risk (e.g., picking up, petting, nuzzling, or being scratched by a potentially rabid kitten). Local reactions to vaccine or immune globulin were reported by 76.5% of recipients, while 48.8% reported at least one systemic reaction. Cost for the biologicals was estimated at more than $1.1 million. CONCLUSIONS: Because of the inadequacy of pet store records, the inconsistent application of treatment guidelines, and other factors, many people received postexposure treatment as a result of contacts that were unlikely to transmit rabies. The rates of local and systemic adverse reactions experienced were consistent with previous reports.

Adolescent↗
PubMed1996

High-volume intraocular lens surgery in a rural eye camp in India.

BACKGROUND AND OBJECTIVE: The appropriate surgical treatment for the enormous number of patients in developing nations who are blind due to cataract is a hotly debated issue. The authors objective is to demonstrate that modern surgical techniques (extracapsular cataract extraction and intraocular lens implantation, phacoemulsification and intraocular lens implantation) can be performed in a high-volume, cost effective manner, even in temporary settings. The authors believe that the approach to cataract blindness is not simple intracapsular cataract extraction, but rather the challenge of (1) training all ophthalmic personnel in modern techniques (microsurgery, biometry), (2) training managers in higher levels of organizational skill, and (3) doing these things in the face of limited resources. PATIENTS AND METHODS: A total of 1298 surgeries were performed in a public eye camp in Ganeshpuri, India (50 miles north of Bombay). Of these, 1214 (93.5%) of the patients received intraocular lens (IOL) implants. Ninety-three percent (1032/1108) of the patients who underwent extracapsular cataract extraction (ECCE) and IOL implantation and 89% (83/93) of the patients who underwent phacoemulsification and IOL implantation returned for follow-up. RESULTS: Postoperatively, 48% (498/1032) of the patients who underwent ECCE and IOL implantation achieved corrected vision of 6/12 or better and 65% (671/1032) attained corrected vision of 6/18 or better. Of the patients who underwent phacoemulsification and IOL implantation, 59 of 83 (71%) attained vision of 6/12 or better with correction and 68 of 83 (79%) achieved vision of 6/18 or better with correction. These results are almost identical to those obtained by the authors in their Ganeshpuri 1991 camp. Surgical complication rates were comparable to those reported in hospital-based studies. CONCLUSION: For this type of camp to operate efficiently, there must be standardization of skills among ophthalmic personnel, costs must be contained, and the organizational skills necessary to ensure smooth functioning of the camp must exist. However, on the basis of their data, these authors believe that with suitable organizational and surgical facilities, IOL implantation can be successfully performed in high-volume surgical eye camps.

Blindness↗
PubMed1995

The squalestatins: synthesis and biological activity of some C3-modified analogues; replacement of a carboxylic acid or methyl ester with an isoelectronic heterocyclic functionality.

A series of squalestatins modified at the C3-position with a heterocyclic functionality was prepared and evaluated in vitro as inhibitors of squalene synthase (SQS). Structure-activity relationships for compounds with the 4,6-dimethyloctenoate at C6(S1 analogues) were different from those for analogues lacking the C6 ester (H1 analogues), with a greater dependence on the nature of the C3-substituent for the H1 series. Potent SQS inhibitory activity equivalent to that of H1 is retained by a C3-(tetrazol-5-yl) analogue, i.e., a carboxylic acid mimetic. The C3-methyl ester derivative is 10-fold less active than H1, and SQS inhibitory activity similar to that of the methyl ester was retained only in those C3-heterocycle-substituted H1 analogues for which electrostatic potential maps of the C3-substituent were closely similar to that of a methyl ester.

Animals↗
PubMed1995

A prospective study of treatment of acquired (autoimmune) factor VIII inhibitors with high-dose intravenous gammaglobulin.

A decrease in inhibitor titer has been reported in some patients with acquired factor VIII inhibitors treated with intravenous gammaglobulin (IGIV). We have conducted a prospective, multicenter study of high-dose IGIV in treatment of this disorder to determine efficacy. Nineteen patients received induction therapy with IGIV, 1,000 mg/kg x 2 consecutive days or 400 mg/kg x 5 consecutive days, followed by maintenance doses at intervals as clinically indicated. A > or = 25% reduction in inhibitor titer was observed in 8 of 16 assessable patients, six of whom met the criteria for response. A rapid decline in inhibitor titer over 3 to 4 days was observed in two patients, but in four additional responding patients--two of whom received repetitive maintenance doses of IGIV--the decline was more gradual, with final nadirs being reached several weeks to many months after treatment. The inhibitor disappeared in three patients with low-level inhibitors, less than 1 Bethesda unit (BU). Concomitant therapy with prednisone may have contributed to the response in two of the patients but was not a factor in four patients; the response rate is, therefore, estimated to be between 25% and 37.5%. These results confirm the beneficial effect of IGIV in treatment of some patients with acquired autoimmune factor VIII inhibitors.

Adult↗
PubMed1995

Characterization of a class of peptide boronates with neutral P1 side chains as highly selective inhibitors of thrombin.

Z-D-Phe-Pro-boroMpg-OPin (9a)1,2 has been shown previously to be a highly specific inhibitor of thrombin in spite of lacking an arginine-like guanidino group at the P1 site. A range of compounds have been synthesized based upon this lead compound, varying the neutral side chain at the P1 site. Of the 20 examples based upon the structures at P2 and P3 of Z-D-X-Pro (X being Phe or beta,beta-diphenylalanine), all were found to be effective inhibitors of thrombin (Ki's between 10 and 100 nM). Furthermore all exhibited a high specificity toward thrombin having values for a Ki(trypsin)/Ki(thrombin) ratio of between 10- and 100-fold. High ratio values were found for a number of the compounds tested against a range of serine proteinases (plasmin, factor Xa, kallikrein, urokinase, protein Ca, chymotrypsin, elastase, and cathepsin G). As far as potency toward thrombin, compounds containing the methoxypropyl group at P1 were favored over those with a methoxy grouping on a shorter alkyl chain (8) or without the methoxy group (1-5). The compounds display potent anticoagulant activity with values for 18 in thrombin time of 0.63 microM and in activated partial thromboplastin time of 2.0 microM. 11B NMR has been used to confirm interaction of the boron atom with the active site. From the high specificity shown with all the compounds we propose that the compounds, constitute a new class of thrombin inhibitors.

Boronic Acids↗
PubMed1995

Vertebral osteomyelitis after blunt traumatic esophageal rupture.

STUDY DESIGN: This is a report of a case. OBJECTIVE: To document the occurrence and characteristics of vertebral osteomyelitis after blunt traumatic esophageal perforation. SUMMARY OF BACKGROUND DATA: Vertebral osteomyelitis in association with esophageal rupture has been reported after penetrating, but not blunt traumatic injuries. METHODS: All of the listed authors were involved in the care of this patient. All medical records, laboratory and radiologic investigations, and related literature were reviewed. RESULTS: The mixture of oral aerobic and anaerobic organisms inoculated into vertebral bone after blunt traumatic esophageal perforation caused a rapidly destructive vertebral osteomyelitis reminiscent of bite-wound injuries of the hand. CONCLUSIONS: Awareness of the occurrence of blunt traumatic esophageal perforation and the associated risk of vertebral osteomyelitis may lead to earlier detection and treatment of these infections.

Esophagus↗
PubMed1995

Recombinant aprotinin in coronary artery bypass graft operations.

OBJECTIVE: To evaluate the role of recombinant bovine aprotinin in reducing blood loss in coronary artery bypass graft surgery. DESIGN: An open-label, randomized, controlled study evaluating two dosage levels of recombinant aprotinin. SETTING: Two acute care hospitals (Northwestern Memorial Hospital, Chicago, Ill., and the Scott & White Memorial Hospital, Temple, Texas). PATIENTS: Patients undergoing primary and reoperation coronary artery bypass grafting were assigned to groups by means of a computer-generated table of random numbers. Treated (n = 48) and control (n = 36) patients did not differ significantly in age, sex, weight, number of grafts, or preoperative hemoglobin level. INTERVENTIONS: Recombinant aprotinin was given at two dosages. Dosage level 1 consisted of a bolus of 2 mg/kg intravenously immediately after the induction of anesthesia, 1 mg/kg added to each liter of the oxygenator prime, and 0.5 mg.kg-1.hr-1 infused continuously during operation. At dosage level 2, doses were doubled. Intraoperative monitoring of anti-factor Xa activity was performed, and additional doses of heparin were given on the basis of anti-factor Xa results. MAIN OUTCOME MEASURES: Preoperative and postoperative hemoglobin levels, amounts of autotransfusion device and chest tube drainage blood, and transfusions of allogeneic red blood cells. Adverse clinical events (alterations in renal function, graft thrombosis, myocardial infarction, and death) were recorded. RESULTS: Additional heparin was given to 48% patients in the aprotinin group and to 44% of control patients. Overall red blood cell loss (in milliliters, mean +/- standard deviation [SD]) was decreased with aprotinin at dosage level 1 for reoperations (1040 +/- 162 vs 1544 +/- 198, p < 0.01), and at dosage level 2 for all operations (primary operations, 886 +/- 362 vs 1333 +/- 618, p = 0.02; reoperations, 1191 +/- 560 vs 1815 +/- 1116, p = 0.2). Fewer patients in the aprotinin than in the control group had transfusions of donated blood (6/48 vs 12/36, p = 0.02) or reinfusion of chest tube drainage blood (12/48 vs 20/36, p < 0.01). Among patients receiving dosage level 1, there were no myocardial infarctions or deaths. At dosage level 2, one patient had profound bradycardia and died on day 12 and two patients had late graft closures. Two control patients had hypotension after bypass necessitating intraaortic balloon pumps, and one of these patients died. Postoperative increases in blood urea nitrogen and creatinine levels were small in both aprotinin and control groups. No hypersensitivity or other allergic reactions occurred. CONCLUSION: We conclude that, at the dosages given, recombinant bovine aprotinin decreases surgical blood loss and transfusion requirements in patients undergoing coronary artery bypass grafting, but its use requires appropriate monitoring of heparin use during bypass. Whether higher dosages of aprotinin increase the risk of graft thrombosis must be further assessed with a larger patient sample.

Aged↗
PubMed1995

Lack of effect of vitamin E administration on basal nitric oxide function in male smokers and non-smokers.

1. The antioxidant properties of vitamin E (alpha-tocopherol) have been proposed to account for a possible protective effect in coronary artery disease. Coronary risk factors are associated with depressed endothelium-derived nitric oxide responses, and some evidence suggests increased quenching of the vasodilator effect of nitric oxide by oxygen free radicals. This study examined the possibility that vitamin E supplementation would improve basal function of the nitric oxide dilator system in long-term smokers and non-smokers. 2. Nine healthy male life-long non-smoking subjects and eight smokers (36 +/- 6 cigarettes per day, > 7 years) were given 1000 i.u. of vitamin E per day for a 4-week period, while five additional non-smokers received placebo. Forearm blood flow responses to intra-arterial infusion of noradrenaline (60, 120 and 240 rho mol/min) and the competitive inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (1, 2 and 4 mumol/min) were measured before and after therapy. 3. No changes were evident in the constrictor responses to noradrenaline or NG-monomethyl-L-arginine in any group. These results indicate that vitamin E supplementation does not influence basal activity of the nitric oxide-dilator system in vivo.

Adult↗
PubMed1995

Analysis of the proenkephalin second messenger-inducible enhancer in rat striatal cultures.

We have previously shown that in cell extracts from rat striatum, cyclic AMP response element (CRE) binding protein (CREB), rather than AP-1 proteins, preferentially interacts with the CRE-2 element of the proenkephalin second messenger-inducible enhancer, even under conditions in which AP-1 proteins are highly induced. Here we use primary striatal cultures to permit a more detailed analysis of CRE-2 function and protein binding in relevant neural cell types. By transfection we find that in primary striatal cultures, as in transformed cell lines, the CRE-1 and CRE-2 elements are required for significant induction by cyclic AMP. We report that cyclic AMP induction of the proenkephalin gene in striatal cultures is protein synthesis independent, excluding a role for newly synthesized proteins like c-Fos. We also show that cyclic AMP induces CREB phosphorylation and that phosphorylated CREB interacts strongly with CRE-2 and weakly with CRE-1. The predominant protein bound to CRE-1 is not CREB, however, and remains to be identified. Despite some prior predictions, we do not find a role for c-Fos in cyclic AMP regulation of proenkephalin gene expression in neurons.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1995

Hepatic ultrasonic changes in workers exposed to perchloroethylene.

OBJECTIVE: To determine if subclinical hepatotoxicity is associated with exposure to perchloroethylene at concentrations commonly experienced in the workplace, and whether surveillance with serum hepatic transaminase activity underestimates such effects. METHODS: Hepatic parenchymal echogenicity on ultrasonography and serum hepatic transaminase activity were compared in 29 community based dry cleaning operators exposed to perchloroethylene, and a control group of 29 non-exposed laundry workers. Perchloroethylene exposure was assessed by work history and air monitoring. RESULTS: Mean hepatic transaminase activities were minimally increased in dry cleaners compared with laundry workers. Increased alanine aminotransferase activities, between 1.0 and 1.5 times the normal limits, were found in five of 27 (19%) dry cleaners compared with one of 26 (4%) laundry workers. In contrast, diffuse parenchymal changes in echogenicity, as determined by hepatic ultrasonography, were increased nearly twofold in dry cleaners, occurring in 18 of 27 (67%) dry cleaners compared with 10 of 26 (39%) laundry workers (P < 0.05), and were most strongly associated with increased perchloroethylene exposure in older dry to dry or wet transfer operations (odds ratio 4.2, 95% confidence interval 1.1-15.3). Mean eight hour time weighted average perchloroethylene exposure for dry cleaners was 16 ppm, which is less than the permissible exposure limit of 100 ppm in the United States. CONCLUSIONS: It was concluded that mild to moderate hepatic parenchymal changes occur more frequently in workers exposed to perchloroethylene than in populations not exposed to chemical solvents, and that these effects are underestimated by serum hepatic transaminase activity.

Adult↗