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  • Springer  (1,942)
  • 1995-1999  (1,018)
  • 1990-1994  (816)
  • 1970-1974  (101)
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  • 1
    ISSN: 1573-2568
    Keywords: esophagus ; dysphagia ; esophageal motor disorders ; achalasia ; pneumatic dilatation ; Rider-Moeller technique ; esophageal perforation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fifty-three patients suffering from dysphagia because of suspected esophageal motor disorders were treated by pneumatic dilatation using the Rider-Moeller technique. Fifteen had achalasia demonstrated by manometric studies. Forty-nine of them had remarkable clinical improvement after the procedure. During the mean period of follow-up (average 5 years, range 1–11), 75% of the patients needed a new dilatation, with a delay of two years. The results of the dilatation were excellent or good in 80% of the cases. Early complications consisted in two esophageal perforations surgically treated. There was no mortality. We did not observe late complications of the procedure. We conclude that pneumatic dilatation should be the initial procedure in the treatment of dysphagia in suspected esophageal motor disorders.
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  • 2
    ISSN: 1432-2072
    Keywords: Milnacipran ; Fluoxetine ; Antidepressant ; Major depression ; Noradrenaline ; Serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients. The duration of the study was 6 weeks, with assessments every 2 weeks by means of the Montgomery and Asberg depression scale (MADRS), the Hamilton depression scale, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetine over milnacipran on most rating instruments: MADRS (P=0.01) including five individual items, Hamilton depression scale (P=0.002) including ten individual items, CGI of severity (P=0.01) and therapeutical index (P=0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran (P=0.0008). The tolerance of the two antidepressants was very similar, with the exception of symptoms of dizziness which were more frequently reported with milnacipran (P=0.01). These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes, whereas milnacipran possesses a plasma elimination half-life of only 7 h.
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  • 3
    ISSN: 1573-904X
    Keywords: immunoreactivity ; IgG and Fab fragments ; colchicine ; digoxin ; digitoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This study investigates immunoreactivity control procedures, i.e., specificity, affinity constant (K a ), and specific active binding sites (SABS), for polyclonal anticolchicine, monoclonal antidigitoxin IgG and Fab fragments, and antidigoxin Fab fragments (Digidot). Preliminary control procedures for IgG and Fab fragment purity indicated that all reagents were immunologically pure. All IgG and Fab fragments exhibited similar cross-reactivity and K a. No decrease in percentage of Fab fragment SABS was observed after papain cleavage of anticolchicine and antidigitoxin IgG. Nevertheless, only 4.3 ± 1.2% of nonimmunopurified anticolchicine polyclonal Fab fragments and 76.2 ± 2.3 to 88.7 ± 2.5% of different batches of immunopurified anti-digoxin Fab (Digidot) were active, the latter percentage being in the range of the 85% specified by the manufacturer. Only 58 ± 3% of digitoxin-specific monoclonal IgG was active and 67 ± 7% of its Fab fragments. Results show the importance of determining the ratio of SABS to presumed total specific binding sites for pharmaceutical monoclonal and polyclonal antibody preparations against haptens.
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  • 4
    ISSN: 1615-5947
    Keywords: Carotid artery lesions ; Doppler imaging ; carotid artery clamping ; intraluminal shunt ; hemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report 91 patients (mean age 70 years) operated upon, prospectively for a total of 100 carotid revascularizations (nine bilateral). Eighty-five of these patients had pre-, intra-, and postoperative transcranial Doppler investigations. Preoperatively, these 85 patients (92 procedures) were classified into two groups based on the results of their Doppler examinations: Group A (65 patients, 72 procedures), those who did not require an intraoperative indwelling shunt and Group B (20 patients, 20 procedures), those who did. The shunt was inserted only when the mean stump (back) pressure was less than 50 mmHg after cross-clamping. Group A all had satisfactory collaterality with a functional anterior and one or two posterior communicating arteries. Group B had no communicating arteries (anterior or posterior) identified by transcranial Doppler. In 17 of 20 patients in this group, the stump pressure was less than 50 mmHg and a shunt was placed. The overall prediction based on Doppler examination of whether or not patients would need a shunt during operation for the two groups A and B (i.e., 92 procedures) was correct in 95.6% (88/92) of cases. Moreover, six hemodynamically significant stenoses (four in the cavernous portion, two in the middle cerebral artery) were disclosed. Sensitivity and specificity of transcranial Doppler as correlated with arteriographic findings were 70 and 90%. Preoperative transcranial Doppler can measure the velocities of the principal cerebral arteries and the collateral capacity of the circle of Willis, and can forecast tolerance to carotid cross-clamping. Intraoperatively, the velocity of flow in the middle carotid artery was correlated with stump pressure, which allowed for surveillance of the shunt.
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  • 5
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Mutations in the promoter region of the factor IX gene result in hemophilia B Leyden, which is characterized by considerable improvement in the disease after puberty. We have found that distinct nucleotide substitutions at the -6 position in the Leyden-specific (LS) region are associated with a different severity of hemophilia B. The proband (aged 2) from one family is a severe hemophiliac with factor IX activity (F.IXC) and antigen (F.IXAg) levels less than 1.0U/dl. F.IXC and F.IXAg levels in two affected uncles are approximately 30% of normal levels. The LS region was targeted for analysis because the phenotypes suggested the inheritance of a factor IX Leyden gene. An abnormal TaqI digestion pattern was found in amplified DNA from the proband, and sequencing showed a G (-6) to C transversion that was linked to the disease in the family. In another family, two brothers (aged 8 and 9) suffer from mild hemophilia with F.IXC ranging from 7 to 10 U/dl and F.IXAg from 3 to 4 U/dl. They are the only documented members of the family with a bleeding tendency. Denaturing gradient gel electrophoresis on amplified fragments from one of the patient's genomic DNA corresponding to the 8 exons and flanking sequences of the factor IX gene suggested a defect only in a segment from the 5′ region. This segment showed an altered TaqI digestion pattern, and sequencing demonstrated a G(-6) to A transition that was traced to the patients's mother and a grandmother. The different phenotypes associated with the G (-6) to A purine nucleotide transition compared with a G(-6) to C transversion provide evidence that this area is directly involved in the regulation of the human factor IX gene expression in vivo by binding of regulatory factors. The ability to predict that the conditions of a hemophilia B patient will improve with age has important implications for genetic counseling of the family. Therefore, the LS region should always be included when scanning the factor IX gene for mutations.
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  • 6
    ISSN: 1432-198X
    Keywords: Key words: Renal transplantation ; Acute rejection ; Chronic rejection ; Cyclosporine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. To determine the risk factors predictive of graft loss from chronic rejection in pediatric renal allograft recipients, we reviewed the collaborative study database of the Société de Néphrologie Pédiatrique which registered 314 grafts from January 1987 to December 1991. Of the 289 grafts analyzed, 71 failed during follow-up, chronic rejection being the most common cause of graft loss (35%). The clinical features of the chronic rejection group (n = 25) were compared with those of the group without failure (n = 218). The variables tested by monovariate analysis were cyclosporine dose at 1 year, donor type, donor and recipient age, and acute rejection episodes. The incidence of graft loss due to chronic rejection was 4% (4/109) in patients who had no acute rejection and 16% (21/134) in those with at least one acute rejection episode (P = 0.002). Donor age (≤5 years) was a risk factor for chronic rejection (P = 0.024). Recipient age and donor type were not significantly different between the chronic rejection group and the control group. Using time-dependent covariates, the risk factors were an acute rejection episode (P = 0.003) and low cyclosporine doses at 1 year (P = 0.02). We conclude that acute rejection and low cyclosporine doses in these pediatric patients were risk factors for graft loss due to chronic rejection.
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  • 7
    ISSN: 1573-904X
    Keywords: Fab fragment ; radioimmunoassay ; pharmacokinetics ; urinary metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Anti-sheep Fab fragment antisera were produced in rabbits using sheep digoxin-specific Fab fragments (Digidot) as immunogen. These antisera were used for the development of a radioimmunoassay (RIA) of sheep Fab fragments in human plasma and urine using 125I-labeled Fab fragments. Interference in the assays by digoxin, human proteins, and antibodies from different species was insignificant, but cross-reactivity between anti-sheep Fab antisera and goat IgG or Fab fragments was 22 to 67%. The limit of detection was 0.1 µg/mL and the assay was linear over a 0.6–28 µg/mL range of Fab fragments. Intra- and interassay coefficients of variation were less than 6.9 and 10.5%, respectively. Accuracy of plasma and urine assays at various Fab fragment levels ranged from 96 to 106%. RIA was applied to the pharmacokinetic study of sheep digoxin-specific Fab fragments in one patient acutely intoxicated by digitoxin and treated with Digidot. The Fab elimination half-life was 12.1 hr. Steady-state volume of distribution and total-body clearance were 10.8 L and 23.4 mL/min, respectively. Unchanged Fab fragments (50 kD) and degradation products (25 kD) isolated by gel filtration chromatography of a urine sample cross-reacted with the anti-Fab antiserum.
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  • 8
    ISSN: 1573-7217
    Keywords: breast cancer ; immunohistochemistry ; Ki‐S4 ; prognosis ; proliferation ; topoisomerase IIα
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the prognostic relevance of Ki‐67 and topoisomerase IIα expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki‐S11 (Ki‐67) and Ki‐S4 (topoisomerase IIα). pS2, c‐erbB2, and p53 were additionally considered as prognostic variables. The median follow‐up time was 149 months. Eight‐hundred‐and‐sixty‐three tumors reacted with Ki‐S11 and Ki‐S the labeling indices of the two antigens were closely associated (r=0.93). Both correlated positively with the tumor size, c‐erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki‐S11 and Ki‐S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis‐free survival (p 〈0.00001). Estrogen receptor status, p53, and c‐erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki‐S4 score 〉25% (p 〈 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki‐S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki‐S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIα expression as assessed by monoclonal antibody Ki‐S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.
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  • 9
    ISSN: 1573-6822
    Keywords: Hepatocyte ; Ha-ras EJ ; cell transformation ; liver cell line ; liposome encapsulated plasmid ; carcinogen metabolic activation ; 2-AFAF ; bile acids ; albumin ; transferrin ; hGH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Collagenase isolated rat hepatocytes were transfected with liposome encapsulated pEJ (LE-pEJ), a plasmid carrying the human cellular activated Ha-rasEJ oncogene. A proliferative cell line was cloned from these cells transfected in vitro. It secreted per day 0.87 µg albumin and 0.32 µg transferrin per 106 cells, and 11.06 nmol free and conjugated bile acids (BA) per mg protein. Also, it metabolized 2-acetylaminoflourene (2-AFAF) into N- and ring-hydroxylated metabolites and 2-aminofluorene at rates of 1.50, 9.73, and 1.98 nmol/mg cell protein/24 hr, respectively. Rats were i.v. injected with both LE-pEJ and LE-p17hGHnneo carrying the hGH cDNA gene, and secreted hGH in the plasma which induced the synthesis of anti-hGH antibodies. A cell line was cloned from cultures of primary hepatocytes isolated from the liver of transfected rats. After 2 to 3 months in culture, this cell line secreted per day 18.9 µg albumin and 11.0 µg transferrin per 106 cells, 38.75 nmol total BA per mg cell protein, and up to 31 ng hGHper 106 cells without cloning hGH recombinant cells. A 24 hr control culture of primary hepatocytes isolated from non transfected rats secreted 25.5 µg albumin and 11.7 µg transferrin per 106 cells, and produced 21.64 nmol total BA and 2.13 nmol N-OH-2-AFAF per mg cell protien. Hence, Ha-ras EJ transfection of either hepatocytes in vitro or liver cells in vivo, initiated cell cycles leading to presumptive proliferating hepatocytes which express liver function.
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  • 10
    ISSN: 1573-904X
    Keywords: horse F(ab′)2 ; antivenoms ; immunoradiometric assay ; rabbit pharmacokinetics ; absolute bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The pharmacokinetics of a currently available horse F(ab′)2 antivenoms to Vipera aspis, V. ammodytes, and V. berus (Ipser Europe) and a new more purified and pasteurized preparation (SAV) was investigated in the rabbit. Methods. An immunoradiometric assay using an affinity-purified goat IgG horse F(ab′)2 specific and the same IgG labelled with iodine 125 as a tracer was developed. The limit of quantification in plasma was 0.032 µg/ml. Specificity study showed that mouse F(ab′)2 and Fab did not cross-react. Results. Pharmacokinetic analysis showed that the plasma F(ab′)2 concentration followed a biexponential decline after intravenous bolus administration with distribution and elimination half-lives of 2.66 ± 0.18 hrs and 49.69 ± 4.13 hrs, respectively. The total volume of distribution (Vdss or Vdβ) was between 209 and 265 ml.kg−1 and was similar to the volume of the extracellular fluid in the rabbit (300 ml.kg−1). Total body clearance ranged from 3.33 to 3.96 ml. h−1 · kg−1. After intramuscular administration which was only investigated with SAV, Tmax was 48 hrs and the absolute bioavailability was 42%. Conclusions. No difference in pharmacokinetics was observed between the two antivenom preparations following the intravenous administration. In contrast, a reduced rate and extent of absorption was shown following intramuscular administration.
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