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Biomedical subjects

A Dumas

Publications and source records attributed to A Dumas.

At least 19 recordsLinked to original sources

Free and total insulin-like growth factor (IGF)-I, -II, and IGF binding protein-1, -2, and -3 serum levels in patients with active thyroid eye disease.

To determine whether serum levels of total (T) and free (F) IGF-I and -II and IGF binding protein (IGFBP),-1, -2, and -3 are normal in euthyroid patients with Graves' disease and active thyroid ophthalmopathy, we investigated the above-mentioned parameters in 21 patients (11 male, 10 female) aged 50.8 +/- 11.8 yr (range 35-70) and 19 healthy individuals matched for age, gender, and body mass index. All patients had active thyroid eye disease (TED) with clinical activity scores > or = 4 and positive orbital octreoscan in both eyes. Serum T and F IGF-I and IGF-II were determined using noncompetitive time-resolved monoclonal immunofluorometric assays, IGFBP-1 was determined by an in-house RIA, IGFBP-2 by a novel in-house time-resolved immunofluorometric assay, whereas IGFBP-3 by an immunoradiometric assay. All data are expressed as mean +/- SD. Our results show that T and F IGF-I, -II, and IGFBP-1, -2, and -3 levels in patients were similar to controls and did not show any significant difference. Specifically, mean T IGF-I for patients group was 131 (61), F IGF-I was 0.47 (0.16), T IGF-II was 1056 (300), F IGF-II was 1.45 (0.54), IGFBP-1 was 33 (14), IGFBP-2 was 848 (377), and finally IGFBP-3 was 3953 (1422). For controls, mean T IGF-I was 146 (51), F IGF-I was 0.85 (0.43), T IGF-II was 939 (197), F IGF-II was 1.53 (0.53), IGFBP-1 was 44 (24), IGFBP-2 was 764 (316) and finally IGFBP-3 was 3721 (1017). Furthermore, no statistically differences emerged in the ratio between molar weights of T IGF-I/IGFBP-3 and T IGF-II/IGFBP-3, as well as to the F/T IGF-I and F/T IGF-II. Finally, no relationship was found between the levels of the above-mentioned parameters and clinical activity scores, octreoscan scores, and thyroid hormones. Our data demonstrate for the first time that serum levels of IGFs (including free fractions) and IGFBPs are not increased in euthyroid Graves' patients with active TED. The increased IGF levels in retrobulbar tissues previously described, appear to be independent of serum IGFs concentration and probably represent autocrine and/or paracrine activity.

Adult↗

Mohs micrographic surgery of a plexiform fibrohistiocytic tumor.

BACKGROUND: Plexiform fibrohistiocytic tumor (PFT) is a rare mesenchymal neoplasm first described by Enzinger and Zhang in 1988. Clinically it is characterized by slow growth, frequent local recurrences, and rare systemic metastasis. These tumors occur chiefly in children and young adults and are most commonly located on the shoulders and forearms. OBJECTIVE: To present a case report of an incompletely excised PFT, its complete resection using simple excision and Mohs micrographic surgery, and review of the literature. METHODS: An 11-year-old Hispanic girl was evaluated for the treatment of an incompletely excised plexiform fibrohistiocytic neoplasm located in the right axilla. Mohs micrographic surgery (MMS) was chosen because of the ill-defined borders and the need for tissue conservation. The patient underwent a two-stage, six section, micrographically controlled excision. Upon completion of the MMS a 2 mm final stage, taken as a peripheral and deep section around and underneath the cleared area, was submitted for paraffin embedding. Residual plexiform histiocytic tumor was found at the margin of resection in one location. Reevaluation of the Mohs slides demonstrated the possible presence of tumor at one deep focus. The tumor was reexcised with a 5 mm margin and repeat hematoxylin and eosin staining showed no residual tumor. There has been no evidence of recurrence in 4 years. RESULTS: Complete resection of the PFT and absence of tumor recurrence 4 years later. CONCLUSION: Over the past few years the list of neoplasms for which MMS is the treatment of choice has steadily grown. PFT is a recently described locally aggressive mesenchymal neoplasm with potential for distant metastasis. To our knowledge this is the first time MMS has been used to resect this tumor. To ensure the chance of complete extirpation we recommend the harvest of an additional stage for hematoxylin and eosin staining, as is done in some aggressive squamous cell carcinomas.

Axilla↗

Early versus late extubation after coronary artery bypass grafting: effects on cognitive function.

OBJECTIVE: To compare the effects of a short period of mechanical ventilation and sedation and a longer one on cognitive functioning of patients exposed to cardiopulmonary bypass (CPB). DESIGN: A randomized, prospective study. SETTING: Tertiary-care university hospital. PARTICIPANTS: Forty-eight adult patients with surgical coronary artery disease. INTERVENTION: Elective coronary artery bypass surgery. MEASUREMENT AND MAIN RESULTS: Patients (n = 48; mean age, 60.12+/-9.30 years) were randomized to either group I (mean delay, 3.49+/-2.21 hours) or group II (mean delay, 10.32+/-1.75 hours). Cognitive functioning was evaluated before surgery, postoperatively, and at the 8-week follow-up. Tests included measures of central nervous system integrity, attention/concentration and psychomotor performance, verbal fluency, visual scanning speed, mental flexibility, auditory and visual attention, and verbal memory. Covariance analyses were used for group comparisons. Covariates were age, education, and baseline or postoperative performance. No differences in cognitive functioning were found between the two groups. Globally, performance deteriorated for 34.1% of the patients at the posttest evaluation, whereas 2.3% improved and 63.6% remained unchanged. At follow-up, nearly 40.5% of the patients showed an improvement from baseline, 2.4% still had deficits, and 57.1% had no change. None of the cognitive functions appeared to be more affected than others. CONCLUSION: Early extubation and a shortened period of anesthesia/analgesia do not appear to positively or negatively affect cognitive functioning at 3 to 5 days and 8 weeks postoperatively. Early extubation is suggested because it has no deleterious effect (besides the low risk for reintubation) and it may facilitate patients' care in the intensive care unit.

Adult↗

Immunohistochemical analysis of the interhemal membrane of the elephant shrew.

The placenta of the elephant shrew, an African insectivore, was examined histochemically to resolve the controversy surrounding the nature of its interhemal membrane. Immunohistochemistry suggests that trophoblast abuts the maternal blood spaces, and evidence of maternal capillary basement membrane is lacking. The mature placenta of these species is thus hemochorial. Earlier developmental stages would require examination to rule out the possibility of a preceding endotheliochorial condition.

Animals↗

Diffuse hyperplasia of the peribiliary glands.

Diffuse, severe, macroscopically recognizable dilatation and hyperplasia of the peribiliary glands of intrahepatic and extrahepatic bile ducts is an extremely rare condition. To our knowledge, this is the first such case reported in the literature. We encountered this condition in a patient with massive hepatic necrosis. The pathogenesis of the condition is discussed. Unfamiliarity with this pathology could lead to an erroneous diagnosis of a well-differentiated cholangiocarcinoma.

Adenocarcinoma↗

Retrograde replacement of the thoracic aorta under circulatory arrest and retrograde cerebral perfusion.

Single-stage replacement of the ascending, transverse and descending thoracic aorta remains a noteworthy surgical intervention associated with significant morbidity. Aside from the surgical aspects, brain preservation during the circulatory arrest period, which is generally needed to perform the procedure, is a constant preoccupation for the surgeon. A 43-year-old man had an extensive thoracic aneurysm 4 years after an initial type A aortic dissection involving the entire thoracic aorta. The Cooley technique of retrograde replacement of the thoracic aorta was performed along with retrograde cerebral perfusion. The combined sternal and thoracic approach suggested for this technique provided excellent exposure and, despite a circulatory arrest time of 88 minutes, the patient's cognitive abilities were found to be well preserved at follow-up 2 months after the surgery, indicating the efficacy of the cerebral retrograde perfusion. The authors conclude that retrograde replacement of the thoracic aorta combined with cerebral retrograde perfusion are convenient procedures that allow extensive aortic replacement without brain damage.

Adult↗

The synthetic pentasaccharide SR 90107A/Org 31540 does not release lipase activity into the plasma.

The present study was designed to find out whether the synthetic pentasaccharide SR 90107A/Org 31540, which is presently being evaluated in clinical trials as an antithrombotic agent, influences lipoprotein metabolism in rats as determined by plasma triglyceride (TG) lipase activity. A comparison with three clinically used sulphated polysaccharides-unfractionated heparin (UFH), low molecular weight heparin (LMWH) and pentosan polysulphate (PPS)- was performed. UFH evoked a dose-dependent increase in plasma TG lipase activity which plateaued at doses > or = 1 mg/kg i.v.. PPS and LMWH demonstrated a lower efficacy than heparin at 0.3 and 1 mg/kg i.v., but the maximum lipase releasing effect at 3 mg/kg i.v. was identical for UFH, PPS and LMWH. SR 90107A/Org 31540 did not release TG lipase activity at single i.v. doses up to 3 mg/kg. Repeated-dose experiments with SR 90107A/Org 31540 (1 mg/kg s.c. for 9 days) revealed no influence on the lipase releasing effect of UFH (1 mg/kg i.v. on day 10). These results demonstrate that SR 90107A/Org 31540 does not influence lipid metabolism in rats through lipase release, suggesting that SR 90107A/Org 31540 may offer an advantage over UFH and LMWH in clinical situations where an anticoagulant/antithrombotic effect is desired, but both an increase in plasma free fatty acids and atherogenic alterations of lipoprotein metabolism are considered harmful.

Animals↗

Lanreotide in the treatment of patients with thyroid eye disease.

Octreotide, a potent synthetic somatostatin (SM) analogue, was recently evaluated and found to have a beneficial effect in thyroid eye disease (TED), mostly in those patients with a positive Octreoscan-111. Lanreotide (LRT; Somatuline-Ipsen), a new SM long-acting analogue, is more active than natural SM and shows a much longer duration of action. The aim of the present preliminary study was to evaluate the therapeutic effect of LRT in the treatment of TED. Five patients, three males and two females, mean age 50.6 +/- 7.6 S.D. (45-64) years, all with severe symptoms of TED were studied. A similar number of patients, matched for age, sex and severity of ophthalmopathy served as controls. All the patients and controls were investigated with orbital scintigraphy using 111 In DTPA-D-Phe1-octreotide (Octreoscan-111) and selected on the basis of positive octreoscan. The NOSPECS system, as adapted by Donaldson et al. (Journal of Clinical Endocrinology and Metabolism 1973 37 276-285) and a disease activity score, as proposed recently by an International Workshop, have been followed in this study in order to evaluate the response to treatment. The five patients who comprised the treatment group received 0.04 g LRT i.m. once every 2 weeks over a period of 3 months, after which the Octreoscan-111 was repeated. The control patients were given an injection of water i.m., also once every 2 weeks for 3 months, after which they were evaluated clinically. No Octreoscan-111 was performed in the controls. All patients and controls were evaluated by the same physician, who was unaware of the type of treatment used. A decrease in the NOSPECS score and the clinical activity score was regarded as a positive response, while no change or an increase in the NOSPECS score along with no clinical improvement was regarded as a negative response. After 3 months of treatment with LRT, four patients showed a statistically significant improvement in ophthalmopathy in both eyes and one in one eye. Three of the control patients with TED did not show any change, one showed a minor improvement in one eye and no change in the other and one showed deterioration in both eyes. An interesting finding was that orbital Octreoscan-111 activity was absent in all the patients after LRT treatment. In conclusion, these preliminary results show that LRT has a beneficial effect on patients with TED, and that since it has to be given only once every 2 weeks, it is probably superior to any other form of SM treatment. However, as the number of patients was small, further studies are needed to confirm our results.

Adult↗

V2 receptor antagonism of DDAVP-induced release of hemostasis factors in conscious dogs.

The synthetic arginine vasopressin (AVP) analog 1-desamino-8-D-arginine vasopressin (DDAVP) is used in a variety of hemorrhagic disorders. The present experiments were designed to further characterize the mechanism of DDAVP-induced release of hemostasis factors. The [3H]AVP-labeled AVP receptor in canine renomedullary membranes exhibited an AVP V2 profile because the V2 receptor agonist DDAVP displayed similar subnanomolar affinities as the natural hormone AVP, whereas the two selective V1a compounds SR 49059 and d(CH2)5Tyr(Me)AVP as well as the selective V1b agonist D-Pal and oxytocin were much less potent. The rank order of the binding affinities of three V2 receptor antagonists was SR 121463 (a newly described selective V2 receptor antagonist) > OPC 31260 >> d(CH2)5D-Ile2,Ile4AVP. In conscious dogs, DDAVP (0.1-1 microg/kg I.V.) caused a dose-related increase (maximum, 43-52% at 30 min) in plasma levels of factor VIII (FVIII), von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA), but not in levels of plasminogen activator inhibitor-1. A DDAVP-induced hemostasis factor release was also observed in bilaterally nephrectomized dogs. Pretreatment with SR 121463 inhibited DDAVP-induced (1 microg/kg I.V.) increases in FVIII, vWF and t-PA plasma levels in a dose-dependent manner (ID50 = 14.0 +/- 4.0, 12.4 +/- 3.0 and 16.7 +/- 1.0 microg/kg I.V., respectively). OPC 31260 (300 microg/kg I.V.) revealed a lower activity than SR 121463, and d(CH2)5[D-Ile2,Ile4]AVP (30 microg/kg I.V.) was without effect on the DDAVP response. Pretreatment with SR 49059 (1 mg/kg I.V.) and SR 27417 (a platelet-activating factor receptor antagonist) (1 mg/kg I.V.) had no effect on the DDAVP-induced (1 microg/kg I.V.) increases in FVIII, vWF and t-PA plasma levels. The present results, therefore, strongly suggest that the effect of DDAVP on hemostasis factors occurs via a specific interaction with extrarenal V2 receptors.

Animals↗

Somatostatin receptor scintigraphy and octreotide treatment in patients with thyroid eye disease.

OBJECTIVE: Octreotide, a potent long-acting synthetic somatostatin analogue, has been reported to have a beneficial effect in thyroid eye disease (TED), but the precise mechanism of action remains unexplained. 111In-DTPA-D-Phe1-octreotide (Octreoscan-111) has been used to localize a number of endocrine tumours and visualize somatostatin receptors in the retrobulbar tissue of patients with TED. Furthermore, this technique can predict the inhibitory effect of octreotide on hormone secretion by endocrine tumours, as there is a close relation between the clinically observed inhibition and visualization of the tumour using Octreoscan-111. The aims of the present study were to confirm the beneficial effect of octreotide in patients with TED, to investigate the presence of somatostatin receptors in the orbital area and also, if possible, to ascertain whether this technique could select those patients with TED who might benefit from treatment with octreotide. DESIGN: A prospective study. SETTING: An endocrine clinic of a national hospital. PATIENTS: Twenty treated thyrotoxic patients with TED, 5 treated thyrotoxic patients without TED and 5 normal individuals were studied. In 12 patients with TED, 5 without TED and 5 normal individuals, Octreoscan-111 scintigraphy of the orbits was performed. The remaining 8 patients with ophthalmopathy served as controls. In patients with TED who were investigated with Octreoscan-111, 300 micrograms octreotide daily was given for 12 weeks. RESULTS: Six patients in both eyes and one patient in one eye showed an improvement in ocular manifestations as assessed by clinical criteria and changes in the NOSPECS score, while the rest showed no improvement. The patients who showed an improvement had a high number of somatostatin receptors and positive orbital scans, while with one exception the patients who did not respond had a low number of receptors and negative orbital scans (P < 0.02). None of the 5 patients without TED nor the normal individuals had a positive orbital scan. Seven out of 8 control patients with TED showed no change in the disease during the trial, while 1 deteriorated. CONCLUSIONS: We conclude that octreotide has a beneficial effect in thyroid eye disease and that Octreoscan-111 could predict those patients with thyroid eye disease who might benefit from this treatment.

Adult↗

Effect of aspirin and clopidogrel on platelet-dependent tissue factor expression in endothelial cells.

Tissue factor is an ubiquitous membrane-anchored glycoprotein that initiates blood coagulation by forming a complex with circulating factors VII and VIIa. Under normal circumstances, endothelial cells do not express tissue factor but, in some pathological situations, when the endothelium or the monocytes are exposed to inflammatory mediators, they can acquire procoagulant properties. When rat platelets were incubated with cultured bovine aortic endothelial cells, a significant increase in tissue factor expression was obtained. When added simultaneously, thrombin or 2-methylthio-ADP, a stable analogue of ADP, potentiated in a time and dose-dependent manner the effect obtained with platelets alone. In order to determine if antiplatelet agents can modulate these effects, the activity of two compounds was evaluated. When administered orally at the dose of 25 mg/kg, clopidogrel, a potent and selective analogue of ticlopidine, was able to inhibit platelet-induced tissue factor expression whereas aspirin (100 mg/kg, p.o.) was ineffective. These effects were closely correlated to their respective anti-aggregatory and antithrombotic activities showing that platelet activation which has already been shown to be mainly involved in arterial-type thrombosis could also play an important role in the initiation of venous thrombosis where tissue factor expression is thought to play a major role.

Adenosine Diphosphate↗

Effects of memory load on interhemispheric relay.

Experimentation with unilateral and bilateral tachistoscopic stimulation (the Dimond paradigm) increasingly suggests that interhemispheric cooperation (bilateral advantage) occurs or increases as a function of task complexity in general and memory load in particular. However, tachistoscopic experimentation with ipsilateral and contralateral field/hand relation conditions (the Poffenberger paradigm) has failed to provide any conclusive supporting evidence. The present investigation comprised a Sternberg "high speed memory scanning" task, modified as a go/no-go task, and formatted into the Poffenberger paradigm. Sets of items to be scanned (memory load) varied in size from one to four. A highly significant effect of load and a significant field/hand interaction were found, but the field/hand/load interaction did not reach significance. We concluded that the interhemispheric transfer time (ITT) metric drawn from this paradigm is not reliably sensitive to increasing memory load. However, our finding of significantly longer ITT in women than in men suggests that commissural anatomy and physiology may be sexually dimorphic.

Adult↗

Chelerythrine, a selective protein kinase C inhibitor, counteracts pyrogen-induced expression of tissue factor without effect on thrombomodulin down-regulation in endothelial cells.

Endotoxin, interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) dose-dependently increased the expression of tissue factor and at the same time induced thrombomodulin down-regulation on the surface of cultured bovine aortic endothelial cells. Chelerythrine, a selective protein kinase C inhibitor, strongly reduced endotoxin-, IL1 beta- and TNF alpha-induced tissue factor expression but remained without effect with regard to thrombomodulin down-regulation measured in parallel. On the contrary, staurosporine, a highly potent, non-selective PKC inhibitor, simultaneously abolished tissue factor expression and thrombomodulin down-regulation induced by endotoxin, IL1 beta and TNF alpha. These results show that protein kinase C is deeply involved in the process leading to pyrogen-induced tissue factor expression and suggest that thrombomodulin down-regulation is regulated by a different pathway.

Alkaloids↗

IL-4 and IL-13 exhibit comparable abilities to reduce pyrogen-induced expression of procoagulant activity in endothelial cells and monocytes.

Endotoxin (LPS), interleukin-1 beta (IL-1) and tumor necrosis factor-alpha (TNF) increased the expression of tissue factor, a membrane-anchored glycoprotein that initiates blood coagulation on the surface of cultured bovine aortic endothelial cells (ABAE) and human monocytes. These compounds simultaneously reduced the amount of thrombomodulin on the endothelial cell surface, further contributing to the procoagulant activity of the endothelium or monocytes. On endothelial cells and monocytes, interleukin-4 (IL-4) and interleukin-13 (IL-13), a newly described lymphokine, both strongly inhibited LPS-induced tissue factor expression, a similar activity also being obtained with regard to the pyrogenic effects of IL-1 or TNF. When measured in parallel, IL-4 and IL-13 counteracted thrombomodulin down-regulation induced by LPS, IL-1 or TNF in endothelial cells. These results therefore show that both IL-4 and IL-13 protect the endothelial and the monocyte surface against inflammatory mediator-induced procoagulant changes.

Animals↗

Furosemide-131I-hippuran renography after angiotensin-converting enzyme inhibition for the diagnosis of renovascular hypertension.

PURPOSE: We have previously demonstrated the greater sensitivity of 131I-hippuran renography than 99mTC-DTPA scintigraphy to diagnose renovascular hypertension (RVH). This study assesses the predictive diagnostic value of furosemide-131I-hippuran renography after angiotensin-converting enzyme (ACE) inhibition in patients with and without RVH. PATIENTS AND METHODS: All patients were investigated at the University of Miami/Jackson Memorial Medical Center. Twenty-eight patients had RVH and 22 did not. Twenty-eight patients had normal or minimally decreased renal function (serum creatinine level 1.5 mg/dL or less) and 22 had renal insufficiency (serum creatinine level 1.8 mg/dL or more). Renography was performed 60 minutes after oral administration of 50 mg captopril or 10 minutes after intravenous injection of 40 micrograms/kg enalaprilat. Forty milligrams of furosemide were administered intravenously 2 minutes after injection of 131I-hippuran. The residual cortical activity (RCA) of 131I-hippuran was measured at 20 minutes. RESULTS: RVH was unlikely when RCA after ACE inhibition was less than 30% of peak cortical activity. Conversely, RVH was present when 131I-hippuran cortical activity steadily increased throughout the test to reach 100% at 20 minutes. In azotemic patients with RCA between 31% and 100%, RVH was differentiated from intrinsic renal disease by obtaining a baseline renogram without ACE inhibition and comparing RCA in that study and RCA after ACE inhibition. If RCA increased (indicating worsening renal function) after ACE inhibition, RVH was likely; whereas, intrinsic renal disease was more likely if RCA remained unchanged or decreased (indicating improved renal function) with ACE inhibition. The test had a specificity of 95% and a sensitivity of 96% in this population. There was a direct correlation between the results of angioplasty or surgery on high blood pressure and the changes in RCA before and after intervention (n = 20). CONCLUSION: Furosemide-131I-hippuran renography with ACE inhibition is highly predictive in identifying patients with RVH.

Adult↗