123rc/medical_text huggingface dataset:
Selective inhibition by a synthetic hirudin peptide of fibrin-dependent thrombosis in baboons. To determine the importance of the thrombin substrate recognition exosite for fibrinogen binding in the formation of both arterial and venous thrombi, we evaluated the antithrombotic effects of the tyrosine-sulfated dodecapeptide from residues 53-64 of hirudin (H peptide) in a nonhuman primate model. This peptide was studied because it inhibits thrombin cleavages of fibrinogen by simple competition without blocking enzyme catalytic-site function. When an exteriorized arteriovenous access shunt model was used in baboons (Papio anubis), thrombus formation was induced by placing a thrombogenic device made of (i) a segment of tubing coated covalently with type I collagen, which generated platelet-rich thrombi under arterial flow conditions, and (ii) two subsequent annular regions of flow expansion that produced fibrin-rich thrombi typically associated with venous valves and veins. Thrombus formation was quantified by measurements of 111In-labeled platelet and 125I-labeled fibrinogen deposition in both arterial-flow and venous-flow portions of the device. Continuous infusion of H peptide (0.5, 15, and 75 mg/kg) proximal to the device for 40 min interrupted, in a dose-response fashion, formation of fibrin-rich thrombus in the regions of disturbed flow and generation of fibrinopeptide A. In contrast, H peptide did not inhibit the capacity of platelets to deposit on the collagen surface (P greater than 0.2 at all doses) or to form hemostatic plugs (as assessed by measurements of bleeding time; P greater than 0.1 at all doses). These findings suggest that, by competitive inhibition of fibrinogen binding to thrombin, fibrin-rich venous-type thrombus formation may be selectively prevented. This strategy may be therapeutically attractive for preserving normal platelet function when conventional anticoagulant therapy is contraindicated.
A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. The French Epirubicin Study Group The French Epirubicin Study Group carried out a randomized trial comparing epirubicin alone 75 mg/m2 with fluorouracil (5FU) 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 50 mg/m2 (FEC 50) and 5FU 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 75 mg/m2 (FEC 75) as first treatment for advanced breast cancer patients. Patients were stratified according to whether or not there were bone metastases only. Four hundred twelve patients entered this trial; 378 were assessable for tolerability and 365 for efficacy. The overall response rates were comparable between FEC 50 (44.6%) and FEC 75 (44.7%), but both were better than the epirubicin alone (30.6%) (P = .04 and P = .0006, respectively). The complete response rate was better in FEC 75 (15.5%) than in FEC 50 (7%) (P = .025) or epirubicin (4%) (P = .002). Similar results were obtained in the group of patients without bone-only metastases. No difference in the three treatments was observed in the patients with bone metastases only. Mean durations of response were similar in the three groups, being 412 days, 440 days, and 350 days for FEC 50, FEC 75, and epirubicin, respectively. Patients without previous adjuvant chemotherapy fared better than those with previous treatment (without anthracyclines). Tolerability was fair in the three groups. Overall, the epirubicin-alone group showed better tolerance than the two other groups, which did not differ significantly. Time to progression and survival were not different among the three groups, but more early relapses occurred in the epirubicin and FEC 50 groups; survival seemed to be better during the first 8 months in the FEC 75 group, and the survival difference between the epirubicin group and the FEC 75 group was of borderline significance. No difference in survival was observed between epirubicin- and FEC 50-group patients, even though the response rate was significantly worse in the monochemotherapy group.
Radical vulvectomy with partial rectal resection and temporary colostomy as primary therapy for selected patients with vulvar carcinoma. The patient with carcinoma of the vulva may present with tumor involvement of the perirectal area. Traditional treatment has often involved ultraradical therapy including a radical vulvectomy with posterior or total pelvic exenteration in an effort to obtain adequate surgical margins. Five-year survival rates for these patients range from 20-50%, and major operative morbidity as well as psychological problems are associated with this extensive surgery. Five patients treated for a locally advanced vulvar carcinoma involving the perirectal area were thought to be candidates for a rectum-sparing procedure. They underwent a radical vulvectomy, bilateral inguinal lymphadenectomy, partial rectal resection, and a diverting colostomy. Four of the five patients agreed to a colostomy closure 6 months after their primary therapy; these four patients have resumed normal bowel function. All patients remain clinically free of tumor.
Effects of carotenoids in cellular and animal systems. It has been suggested that carotenoid pigments may function as chemopreventive agents for reducing the risk of cancer in humans. Part of this suggestion rests on epidemiological evidence, and part rests on work done in cellular and animal systems. In this article, the experimental evidence for carotenoid inhibition of mutagenicity, malignant transformation, tumor formation, and immunoenhancement is reviewed. Although a mechanism for these effects cannot yet be identified, it is clear that the overwhelming evidence in these systems would indicate that carotenoids exert an important influence in modulating the actions of carcinogens.
The child with recurrent syncope: autonomic function testing and beta-adrenergic hypersensitivity. Recurrent syncope in the child with a normal heart poses both diagnostic and therapeutic problems. To assess autonomic contributions to syncope, formal autonomic function testing was performed in 22 children (aged 7 to 18 years) with recurrent syncope and a normal heart. Autonomic testing consisted of eight to nine separate tests; 14 of the 22 patients had reproduction of syncope or symptoms during testing. Patients with a positive test had a lower norepinephrine level while supine (334 +/- 86 versus 547 +/- 169 pg/ml, p less than 0.01) and lower norepinephrine level in the upright position (628 +/- 219 versus 891 +/- 270 pg/ml, p less than 0.05) than did patients with a negative test. The slope of heart rate response versus log isoproterenol dose was greater in patients with a positive test than in those with a negative test (1.70 +/- 0.70 versus 0.89 +/- 0.19, p less than 0.01). All five patients with a positive test who were given intravenous propranolol had elimination of syncope with repeat testing. Eight of 10 patients with a positive test were successfully treated with atenolol, including 2 patients without prior resolution of symptoms after pacemaker implantation for symptoms attributed to bradycardia. Beta-adrenergic hypersensitivity may cause recurrent syncope in young patients. Inappropriate heart rate response to standing may elicit the Bezold-Jarisch reflex, resulting in bradycardia or hypotension, or both, in some patients. Beta-adrenergic blockade is of benefit in many of these patients.
Intrathoracic current flow during transthoracic defibrillation in dogs. Transcardiac current fraction. To achieve transcardiac threshold current during transthoracic defibrillation, a considerably larger current must be delivered to the thorax to compensate for the shunting effect of the lungs, the thoracic cage, and other elements of the torso. This shunting effect is thus an important determinant of transthoracic defibrillation threshold and can be quantified by the transcardiac current fraction (FC, the ratio of transcardiac to transthoracic threshold currents). Previous estimates of FC have ranged from as low as 3% to as high as 45%. The purpose of of this study was to quantify both FC and the major intrathoracic current pathways. Transthoracic and intrathoracic voltages and currents were simultaneously measured during high-voltage transthoracic shocks in 20 dogs. With correction factors determined from another set of 12 dogs, these raw data were corrected to compensate for field distortion caused by the presence of the intrathoracic electrodes, and the adjusted data were fit to a resistive network model. The results showed that 82% of the transthoracic current was shunted by the thoracic cage, while 14% was shunted by the lungs. The remaining 4% (FC) is the portion that passed through the heart. There was good agreement between the two independent methods used to calculate FC. Analysis based on the model indicated that FC was 3.7%, whereas FC determined by direct measurement with calibrated electrodes was 4.2%. Therefore, the results of this study, in contrast to earlier estimates of FC, show that defibrillation in dogs is achieved by only 4% of the total transthoracic current.
Glucose intolerance and hyperinsulinemia of cirrhosis are not results of spontaneous or surgical portosystemic shunting. To assess if spontaneous portosystemic shunting from collaterals contributes to the hyperinsulinemia of cirrhosis, 12 patients with alcoholic cirrhosis underwent a 5-hour oral glucose tolerance test 1 day before and 10 days after an elective side-to-side portacaval shunt. The glucose, insulin, and C peptide responses to oral glucose post-shunt were exaggerated but comparable to preoperative values. Compared with preoperative values, the fasting molar ratio of C peptide to insulin postoperatively had increased 40% (6.0 +/- 1.2 versus 8.4 +/- 0.7), indicating improved hepatic function. These results suggest that extrahepatic portosystemic shunting secondary to spontaneous splanchnic collaterals plays little or no role in the hyperinsulinemia of cirrhosis. It appears that decreased hepatic degradation of insulin in these patients is secondary to hepatocellular dysfunction rather than a result of shunting of portal blood around the liver.
Cerebral infarction: early detection by means of contrast-enhanced cerebral arteries at MR imaging. The authors describe a new magnetic resonance (MR) imaging sign of acute cerebral ischemia/infarction. Abnormally contrast material-enhanced curvilinear structures were demonstrated in eight patients in the evolving area of cerebral ischemia/infarction within 26 hours after the ictus on contrast-enhanced, high-field-strength (1.5-T), T1-weighted spin-echo images. The abnormal enhancement is considered to represent cortical arterial vessels of markedly slowed circulation in areas of underlying brain injury, which will eventually progress to frank brain infarction. This was demonstrated at computed tomographic (CT) and follow-up MR examinations. Characteristically, the degree of the contrast enhancement of vessels appeared most intense in the proximal portions, and the intensity of enhancement gradually diminished in the more distal portions of these vessels as they pass over the convexities and finally disappear.
Diagnosis of thymoma in myasthenics using anti-striated muscle antibodies: predictive value and gain in diagnostic certainty. Assay of anti-striated muscle antibodies (StrAb) is used as a diagnostic test for thymoma in individuals with myasthenia gravis. Unfortunately, false positive results are common, and their effect on test accuracy is magnified by the relatively low frequency of thymoma in myasthenics. We estimated the predictive values of positive and negative StrAb assays (PV+ and PV-) and gain in diagnostic certainty using values for sensitivity, specificity, and thymoma frequency previously reported in the literature. Sensitivity for indirect immunofluorescence assays ranged from 0.83 to 0.84 (pooled estimate = 0.84; n = 68). Specificity ranged from 0.73 to 0.88 (pooled estimate = 0.77; n = 898). Frequency of thymoma ranged from 0.07 to 0.17 (pooled estimate = 0.12; n = 4,515). The expected gain in diagnostic certainty from StrAb was minimal in those aged 0 to 20 and those aged 60+. In those aged 20 to 60, a negative test helped to exclude thymoma, and a positive test raised diagnostic suspicion but was not sufficient to establish a diagnosis of thymoma (PV+ = 0.46).
The vagus nerve, gastric secretions, and their relationship to peptic ulcer disease. Although peptic ulcer disease was known to the ancients, the process by which the disease was produced remained a mystery. As advances were made in medicine and science, so too were advances made in the understanding of digestion and gastrointestinal disease. The treatment of peptic ulcer disease improved as our understanding of the digestive process grew. The current surgical treatment for peptic ulcer disease follows the principals articulated by Lester R. Dragstedt, MD, PhD, which he based on his observations in the research laboratory. We present a historical perspective of the role of the vagus nerve in the control of gastric secretions and its relationship to peptic ulcer disease, placing particular emphasis on Dragstedt's contributions.
Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. The hypothesis that the high mortality from coronary heart disease (CHD) in South Asians settled overseas compared with other populations is due to metabolic disturbances related to insulin resistance was tested in a population survey of 3193 men and 561 women aged 40-69 years in London, UK. The sample was assembled from industrial workforces and general practitioners' lists. In comparison with the European group, the South Asian group had a higher prevalence of diabetes (19% vs 4%), higher blood pressures, higher fasting and post-glucose serum insulin concentrations, higher plasma triglyceride, and lower HDL cholesterol concentrations. Mean waist-hip girth ratios and trunk skinfolds were higher in the South Asian than in the European group. Within each ethnic group waist-hip ratio was correlated with glucose intolerance, insulin, blood pressure, and triglyceride. These results confirm the existence of an insulin resistance syndrome, prevalent in South Asian populations and associated with a pronounced tendency to central obesity in this group. Control of obesity and greater physical activity offer the best chances for prevention of diabetes and CHD in South Asian people.
Anionic complex-carbohydrate units of human thyroglobulin. Human thyroglobulin (hTG) contains sulfate in chondroitin 6-sulfate chains and in complex carbohydrates. In this study the sulfate-containing complex carbohydrates were characterized by the number of sulfate and sialic acid residues that they contain. Samples of normal and nodular thyroid tissue were incubated for 16 h in [35S]sulfate-containing medium, and hTG was purified from the tissues and the media. Complex carbohydrates were enzymatically removed from hTG. Subsequent analysis on an HPLC anion exchange column at pH 2.2 separated the carbohydrate units according to their number of negative charges. Sulfate-containing peaks were monitored by radioactivity, and sialic acid-containing peaks were identified by their shift to lower charge after treatment with neuraminidase. Peaks corresponding to sialic acid-free carbohydrate units with one to four sulfates were identified. Also, carbohydrate units with two and three negative charges containing both sulfate and sialic acid were present. In the nodular tissue of one patient there were more sulfated units with higher charge, especially units containing sialic acid. In this patient the proportion of sulfated polyvalent units with sialic acid was 22.4% for normal and 64.6% for nodular tissue. No difference in the composition of the charged units between the tissues and their corresponding media was seen, making it unlikely that the sulfate-containing carbohydrates play a role in hTG release. It is concluded that hTG contains complex carbohydrate units with up to four sulfate groups and units with both sulfate and sialic acid. In some patients, the sulfate-containing anionic carbohydrate units of hTG from normal and nodular thyroid tissue are different.
Estrogen receptors in the external anal sphincter. Inasmuch as anal competence in women is reduced after the age of 50 years, it may be dependent on effects of estrogens. In this study, samples of the external anal sphincter were analyzed for the presence of estrogen receptors and were found to be present at a median concentration of 5.0 fmol per milligram of protein (range, 1.9 to 13) in women (n = 7), and 1.1 fmol per milligram of protein (range, 0 to 3.2) in men (n = 7). These findings are of interest with regard to the treatment of idiopathic anal incontinence.
Zollinger-Ellison syndrome: prospective assessment of abdominal US in the localization of gastrinomas. The ability of abdominal ultrasound (US) to help localize gastrinomas was prospectively studied in 79 patients with Zollinger-Ellison syndrome. The results were assessed by means of laparotomy, autopsy, or percutaneous liver biopsy. For hepatic gastrinoma, US had a sensitivity of 63% and a specificity of 100%, with a positive predictive value of 100% and a negative predictive value of 89%. US was slightly less sensitive for detecting gastrinoma in the liver than were computed tomography (CT) (66%) and selective angiography (78%). For detection of extrahepatic gastrinoma, US had a sensitivity of 30%, a specificity of 94%, a positive predictive value of 100%, and a negative predictive value of 25%. US enabled detection of tumor in eight cases not detected with CT and in four not detected with angiography. Specificity for extrahepatic gastrinoma was similar for all three modalities (89%-95%). CT and US were equally effective for the detection of extrahepatic gastrinoma, and angiography was significantly more effective than both US and CT (P less than .01). The authors conclude that US, although of low sensitivity, remains useful as the initial imaging modality in patients with Zollinger-Ellison syndrome.
Strong association between diabetes and displacement of mouse anti-rat insulinoma cell monoclonal antibody by human serum in vitro. In an attempt to identify novel pancreatic beta-cell surface antigens, mouse monoclonal antibodies (MoAbs) were raised against rat insulinoma (RIN5F) cells with standard techniques. Several clones were identified whose antibodies bound specifically to RIN5F cells but not to other rat, mouse, and human target cells. Each of these MoAbs was radiolabeled, and the specificity of binding of each MoAb was determined by the ability of excess cold homologous MoAb to displace the labeled MoAb. Six RIN5F cell-specific MoAbs of different epitopic specificities were identified. The relevance of these beta-cell epitopes to human insulin-dependent diabetes (IDDM) was demonstrated by the differential ability of human serums from control and diabetic children to displace the radiolabeled MoAbs from the RIN5F cells. Serums from 333 children without diabetes or a family history of diabetes and from 156 newly diagnosed IDDM patients were tested. Only one IgM MoAb was specifically displaced by the IDDM serums, i.e., 146 of 156, compared to serums from control children, i.e., 10 of 333. With immunofluorescence, the serum component responsible for the displacement of the mouse MoAb was identified as IgG. Most of the positive control serums were from children with active autoimmune thyroiditis. Serums from children with other forms of glucose intolerance did not displace MoAb 1A2. There was no correlation between age and the degree of displacement of 1A2. Thus, the displacement of 1A2 is a specific and sensitive marker of diabetes susceptibility easily applicable to mass screening.
Effects of epidermal growth factor and analogues of luteinizing hormone-releasing hormone and somatostatin on phosphorylation and dephosphorylation of tyrosine residues of specific protein substrates in various tumors. Analogues of somatostatin (SS) and luteinizing hormone-releasing hormone (LH-RH) activate tyrosine phosphatases in MIA PaCa-2 human pancreatic cancer cell line membranes and inhibit growth. We compared the substrates phosphorylated by epidermal growth factor (EGF) to those dephosphorylated by the SS analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) and [D-Trp6]LH-RH in cancer cell lines such as MIA PaCa-2 (human pancreatic cancer), HCPC (hamster cheek pouch carcinoma), A-549 (human lung cancer), HT-29 (human colon cancer), and R3230AC (breast cancer). EGF phosphorylated proteins of 170, 65, and 60 kDa and analogues of SS and LH-RH promoted the dephosphorylation of these proteins in MIA PaCa-2 and HCPC cell lines. The EGF receptor is 170 kDa. pp60src (60 kDa) is known to be a substrate for EGF receptor. The LH-RH receptor is also 60 kDa. The effects of RC-160 and [D-Trp6]LH-RH were quantitatively different. Examinations of HT-29, A-549, and R3230AC cancer cell lines revealed no phosphorylation by EGF or dephosphorylation by RC-160 and [D-Trp6]LH-RH. In addition to the 170-, 65-, and 60-kDa proteins, 35-kDa proteins were also phosphorylated in some cancer cell lines. This work demonstrates that analogues of SS and LH-RH can reverse the effects of EGF biochemically as well as functionally.
Human atherosclerotic coronary artery xenografts: a model for investigation of transluminal recanalization. A model for testing transluminal recanalization techniques was developed. Fragments of human atherosclerotic coronary arteries were transplanted into carotid arteries of dogs and evaluated by angiographic, angioscopic, and histologic study within a three-month period. An inflammatory response was most intense within the first week. By two weeks no inflammation was noted. Total occlusion (n = 13) and stenosis (n = 11) of the carotid arteries were achieved without complications. The model is easy to produce within a short period and the arterial occlusion resembles human vascular disease. This model has been used to evaluate laser recanalization of vascular obstructions.
Genitourinary cancer in the elderly. The subject of genitourinary cancer in the elderly becomes increasingly more important as our population of patients older than 50 years expands. Carcinoma of the kidney, bladder, and prostate all have an increasing incidence over the age of 50 and have a predilection for afflicting men more commonly than women. Etiologic factors, especially with bladder and kidney carcinomas, are well documented and in some cases preventable. Screening the urine for hematuria and careful digital rectal examinations may uncover a higher percentage of these malignancies in earlier, more curable stages. Recent advances in the treatment of all of these malignancies have improved survival and quality of life for these patients.