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Biomedical subjects

D George

Publications and source records attributed to D George.

At least 91 records · Page 5Linked to original sources
PubMed1991

Thrombolytic therapy causes an increase in vascular permeability that is reversed by 1-deamino-8-D-vasopressin.

BACKGROUND: To examine the effect of plasminogen activator therapy on vascular permeability, we used a modified rabbit mesenteric model of extravascular tissue accumulation of radiolabeled albumin. METHODS AND RESULTS: Albumin deposition was measured after saline, tissue-type plasminogen activator (t-PA; 0.86 mg/kg for 1 hour followed by 0.29 mg/kg for 2 hours), or t-PA plus 1-deamino-8-D-arginine vasopressin (DDAVP; 0.6 mg/kg/hr for 30 minutes) infusion in animals with or without aspirin (ASA; 15-mg/kg bolus) pretreatment. In animals not given ASA, t-PA caused a 240% increase in tissue [125I]albumin accumulation over time (p less than 0.001). DDAVP prevented the rise in albumin accumulation normally seen with t-PA alone (p less than 0.05) in animals not given ASA. In animals pretreated with ASA, t-PA similarly caused an increase in tissue albumin accumulation, but this was significantly attenuated from that of animals not given ASA (p less than 0.03). Interestingly, DDAVP failed to block the response to t-PA in the animals given ASA. Because increases in vascular permeability correlated with increases in bleeding time (r = 0.37, p less than 0.03), these data suggest that the effect of plasmin generation on vascular permeability may contribute to the bleeding tendency seen with thrombolytic therapy. The ability of DDAVP to reverse the bleeding tendency and bleeding time may be due in part to its reversal of the increased vascular permeability induced by the administration of plasminogen activators. CONCLUSIONS: These data show that plasminogen activation causes an increase in vascular permeability that is inhibited by DDAVP; ASA blunts this action of t-PA and prevents the DDAVP blockade of the increase in permeability induced by t-PA in this rabbit model.

Albumins↗
PubMed1991

Idiopathic intracranial hypertension. A prospective study of 50 patients.

Management of patients with idiopathic intracranial hypertension (IIH) should be based on the presence and progression of visual loss. To characterize the clinical course of IIH more completely, we monitored the clinical status, especially visual function, in 50 consecutive newly-diagnosed patients over a period of 2 to 39 months (average follow-up 12.4 months). The mean age at onset of symptoms was 31 (range 11-58) yrs; 46 (92%) were women and 47 (94%) were obese (mean weight 90 kg). Common symptoms were headache (92%), transient visual obscurations (72%) and intracranial noises (60%); 13 of the patients (26%) initially had complaints of sustained visual loss. There was visual loss as determined by Goldmann perimetry in 96% and by automated perimetry in 92%. Contrast sensitivity testing was abnormal in 50% and Snellen acuity in 22%. Two patients (4%) became blind in both eyes. The Goldmann visual field grade improved in 60% of patients but visual function deteriorated in 5 (10%). Deterioration of visual field grade was significantly associated only with weight gain during the year before diagnosis. Visual loss in patients with IIH is common and is often reversible. Patients should be evaluated by perimetry using an appropriate strategy and contrast sensitivity testing, along with careful examination of the optic discs.

Adolescent↗
PubMed1990

Inhibition of fibrinogen binding to human platelets by S-nitroso-N-acetylcysteine.

Because of the central role of fibrinogen binding in platelet aggregation and recent evidence implicating S-nitrosothiol compounds in the platelet inhibitory effects of endogenous and exogenous organic nitrate compounds, we examined the effect of the S-nitrosothiol S-nitroso-N-acetylcysteine (SNOAC) on fibrinogen binding to gel-filtered human platelets. We found that SNOAC markedly inhibited the binding of fibrinogen to normal human platelets in a dose-dependent fashion and that this inhibitory effect was the result of both an increase in the apparent Kd of the platelet receptor for the fibrinogen molecule (from 6.8 x 10(-7) to 1.8 x 10(-6) M, a 2.7-fold increase) and a decrease in the total number of fibrinogen molecules bound to the platelet (from 76,200 to 38,250, a 50% decrease). In addition, we noted a rapid, dose-dependent rise in platelet cyclic GMP levels following exposure of platelets to SNOAC which was significantly inversely correlated with fibrinogen binding and was accompanied by inhibition of intracellular calcium flux in response to a variety of platelet agonists. Similar dose-dependent inhibition of fibrinogen binding was found in the presence of cyclic GMP analogues and was significantly enhanced by inhibition of platelet cyclic GMP phosphodiesterase. These results describe the inhibition of platelet fibrinogen binding by an S-nitrosothiol compound, help define the biochemical mechanism by which S-nitrosothiols inhibit platelet aggregation, and lend support to the view that cyclic GMP is an important inhibitory intracellular mediator in human platelets.

Acetylcysteine↗
PubMed1990

Bleeding time prolongation with streptokinase and its reduction with 1-desamino-8-D-arginine vasopressin.

The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 microgram/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean +/- SEM value of 119 +/- 15 to 191 +/- 34 seconds in the control group and from 114 +/- 6 to 188 +/- 18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592 +/- 119 seconds in the control group and 810 +/- 114 seconds in the experimental group (p = NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302 +/- 29 seconds (p less than 0.01 versus streptokinase) compared with 572 +/- 79 seconds (p = NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n = 16), von Willebrand factor antigen concentration (n = 17), and von Willebrand factor multimer distribution (n = 14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio.

Animals↗
PubMed1990

Temporal effects of thrombolytic agents on platelet function in vivo and their modulation by prostaglandins.

To examine the temporal effects of plasmin generated in vivo on platelet function, we infused tissue-type plasminogen activator (t-PA) in rabbits over 3 hours and measured ex vivo platelet aggregation. We noted an initial increase in the aggregation response to ADP occurring 30 minutes after the start of infusion. This enhanced response was short-lived and by 180 minutes was reduced, compared with pretreatment levels. Baseline aggregation response was restored by 240 minutes. This pattern of aggregation response to t-PA infusion was also seen with thrombin as the agonist. Coinfusion of either prostaglandin I2 or prostaglandin E1 abolished the initial hyperaggregable phase induced by t-PA; the hypoaggregable phase occurred earlier (after 60 minutes) and persisted throughout the 1-hour recovery period. Similarly, streptokinase infused for 1 hour also increased platelet aggregation at early times and then reduced aggregation responses after the first hour. Plasma plasmin activity increased as expected with t-PA infusion alone, peaking at 30 minutes and returning to baseline by the first hour. Interestingly, prostaglandin E1 blunted the rise in plasma plasmin activity. This same dose of prostaglandin E1 or prostaglandin I2 used alone did not appreciably alter platelet function at any time during the experiment. Our data show that therapeutic doses of t-PA or streptokinase produce a biphasic effect on platelet aggregation response in the rabbit. Coinfusion of either of the antiplatelet agents, prostaglandin E1 or prostaglandin I2, abolishes the hyperaggregable phase and prolongs the inhibitory effects on platelet aggregation produced by t-PA. These data suggest that the effects of thrombolytic agents on platelet function are complex and can be modulated by antiplatelet prostaglandins.

Alprostadil↗
PubMed1989

Multicenter, randomized trial of ciprofloxacin plus azlocillin versus ceftazidime plus amikacin for empiric treatment of febrile neutropenic patients.

In a multicenter, randomized clinical trial, the efficacy of ciprofloxacin plus azlocillin was compared with that of a standard regimen of ceftazidime plus amikacin for the initial empiric treatment of fever in neutropenic cancer patients. In addition, the efficacy of early conversion from intravenous therapy to orally administered ciprofloxacin was compared with that of continued ceftazidime plus amikacin. Seventy-one oncology patients with 79 episodes of fever and neutropenia were randomly assigned to receive initial empiric antibiotic therapy with either intravenously administered ciprofloxacin and azlocillin followed by orally administered ciprofloxacin (regimen 1, 25 episodes); ceftazidime and amikacin (regimen 2, 30 episodes); or ceftazidime and amikacin followed by oral ciprofloxacin (regimen 3, 24 episodes). Microbiologically documented infections were the cause of fever in 10 (40 percent), seven (23 percent), and nine (38 percent) episodes in regimens 1, 2, and 3, respectively, including six, five, and four episodes of bacteremia. Patient survival was 90 to 92 percent in each regimen; however, some modification of antimicrobial therapy occurred in 65, 44, and 41 percent of surviving patients in regimens 1, 2, and 3, respectively. The rate of clearance of initial bacteremia was 67 percent (four of six) in regimen 1, 100 percent (five of five) in regimen 2 and 50 percent (two of four) in regimen 3. Patients in regimens 1 and 3 were able to convert to orally administered ciprofloxacin in 32 (65 percent) of 49 episodes after a mean of six days of intravenous therapy. Superinfections occurred in 24, 10, and 12 percent of patients receiving regimens 1, 2, and 3, respectively, and occurred similarly for patients receiving orally administered ciprofloxacin, 12 percent (four of 32), and intravenous therapy, 17 percent (eight of 47). Parenteral ciprofloxacin was generally well tolerated. One (4 percent) of 25 patients receiving regimen 1 experienced oto- or nephrotoxicity, compared with eight (15 percent) of 54 patients receiving regimens 1, 2, and 3 (p = 0.15), including three patients who required premature termination of aminoglycoside therapy. Our data suggest that the combination of ciprofloxacin and azlocillin is an effective alternative to ceftazidime and amikacin for the initial empiric therapy of febrile neutropenic patients, is generally well tolerated, and avoids the oto- and nephrotoxicity associated with aminoglycoside use. In addition, a majority of patients could change to orally administered ciprofloxacin alone after six days of parenteral therapy.

Adult↗
PubMed1989

The cytostatic effects of alpha-interferon may be mediated by transforming growth factor-beta.

There is some evidence to suggest that transforming growth factor-beta (TGF-beta) mediates the cytostatic effects of the anti-oestrogen tamoxifen. In this study we have demonstrated that alpha-interferon has a significant anti-proliferative effect on the oestrogen receptor-positive human breast cancer cell line ZR-75. There is decreased phenotypic expression of the oestrogen receptors (to about 30% of control values) and increased TGF-beta mRNA. Under the growth conditions used here, ZR-75 cells had approximately 5800 TGF-beta binding sites per cell, with an apparent dissociation constant of 70 pm, and we have shown that the anti-proliferative effects of alpha-interferon can be reduced by 60% by co-treating the cells with a TGF-beta polyclonal antibody. The cytostatic effects of alpha-interferon may therefore be mediated by TGF-beta in this human breast cancer cell line.

Antibodies↗
PubMed1988

Diagnostic value of the history and examination in giant cell arteritis: a clinical pathological study of 81 temporal artery biopsies.

To determine the value of the history and examination in predicting a temporal artery biopsy result, 81 temporal artery biopsies between 1974-1980 were studied. Each biopsy was scored blindly and independently by 2 pathologists and correlated with clinical data and the indications for biopsy at the time of the biopsy. Thirteen biopsies had giant cells and were considered positive, 8 had mononuclear inflammatory cells in the wall (7 cases) or healed arteritis (1 case) and were considered probable, and 60 were negative. In patients with an elevated sedimentation rate, the presence of a sign (tenderness or abnormal temporal artery), or a symptom (visual change or headache) predicted 18 of 21 (86%) positive-probable biopsies, but misclassified 32 of 60 negative biopsies. Attempts to derive a clinical decision rule with improved specificity resulted in unacceptably low sensitivity (missing 5 of 21 positive-probable biopsies). A minimum 5-year followup showed that those patients treated with steroids had a 6-fold increase in fractures and a 4-fold increase in cataracts.

Aged↗
PubMed1988

Cerebral malignant tumors with ependymal and choroidal differentiation in two siblings.

Two siblings in a family without a history of phacomatosis or cerebral tumors developed malignant tumors in the posterior fossa at age 28 months and in the left cerebral hemisphere at age 15 months, respectively. Dual ependymal and choroid plexus epithelium differentiation was established by histological, ultrastructural, and immunocytochemical studies. The development of this rare tumor in siblings suggests an inherited predisposition, a common environmental insult, or both.

Brain Neoplasms↗
PubMed1987

Visual loss in pseudotumor cerebri. Incidence and defects related to visual field strategy.

Visual field examinations were performed serially on 20 patients with pseudotumor cerebri using a modified Armaly-Drance visual field strategy with a Goldmann perimeter as well as an automated perimeter (Octopus). Visual loss was found in 75% of eyes using the manual strategy and in 77.5% of eyes with automated threshold perimetry. This incidence of visual loss is 50% greater than any previously reported series. All major defects detected were present with both types of perimetry. Both strategies were more sensitive for documenting visual loss than previously described strategies. Since therapy for pseudotumor cerebri is determined by the degree and progression of visual loss, a specific sensitive strategy, rather than routine screening perimetry, should be used for determination of visual loss.

Adult↗
PubMed1987

Ultrastructural morphology and cellular differentiation in acinic cell carcinoma.

Acinic cell carcinomas, in some instances, contain a component of intercalated duct cells. However, the manner in which this element is integrated within the more obvious acinar cells, as well as the role neoplastic intercalated duct cells play in determining morphologic patterns in acinic cell tumors, has not been fully investigated. Ultrastructural study and immunostaining with antibodies to cytokeratins and to S-100 protein carried out in nine cases of parotid acinic cell carcinoma suggest two basic differentiation patterns. In three cases, the lesions were essentially composed of acinar cells (with variation in the number and form of secretory granules), and one of these tumors was unique in having ultrastructural evidence of differentiated myoepithelial cells. In the second group of six cases, there was light microscopic, ultrastructural, and immunohistochemical evidence of a significant component of intercalated duct cells. By means of both immunostaining (intercalated ducts were positive for keratin and S-100 protein; acinar cells were negative for both antigens) and electron microscopy, flattened-to-cuboidal intercalated duct cells were noted to enclose and, presumably, to be involved in the formation of microcystic spaces. Acinic cell carcinomas with a more solid growth pattern contained groups of intercalated duct cells positive for keratin and S-100 protein. Ultrastructurally, these cells were organized into well-formed ducts related to nests of acinar cells. Acinic cell carcinoma is another class of salivary gland tumor in which there can be an integrated proliferation of intercalated duct and acinar cells and, infrequently, of myoepithelial cells, all organized in a simulation of the intercalated duct-acinar unit of the normal salivary gland.

Carcinoma↗
PubMed1987

Retropharyngeal hematoma as a new cause of acute upper airway obstruction in rheumatoid arthritis.

A patient with severe rheumatoid arthritis (RA) receiving chronic anticoagulation therapy developed acute life threatening airway obstruction. The source of obstruction was a retropharyngeal hematoma compressing the upper airway rather than acute laryngeal dysfunction from the patient's RA. Our case illustrates a new cause of acute stridor and airway obstruction in RA. Publications on upper airway obstruction in RA and airway obstruction secondary to retropharyngeal hematoma are discussed.

Airway Obstruction↗
PubMed1985

Evolution of karyotypic abnormalities and C-MYC oncogene amplification in human colonic carcinoma cell lines.

Cell lines (COLO 320 DM and COLO 320 HSR), established from a human neuroendocrine tumor, contain an amplified cellular oncogene (c-myc). We have previously shown that the homogeneously staining regions (HSRs) of a marker chromosome in the COLO 320 HSR cells that evolved in culture from COLO 320 DM cells contain amplified c-myc. Molecular hybridization in situ has now been used to demonstrate that the HSRs are on both arms of what was once an X chromosome. We also show that amplified c-myc copies are present in the isolated double minute chromosomes (DMs) of the COLO 320 DM cells that were characteristic of the tumor cells initially established from the patient. The results suggest that the amplified c-myc appeared first as DMs and was subsequently transposed to engender HSRs on an X chromosome. The initial COLO 320 tumor cell may have acquired two "early replicating" (i.e., active) X chromosomes and lost the "late replicating" (i.e., inactive) X.

Cell Line↗