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Biomedical subjects

A Adam

Publications and source records attributed to A Adam.

At least 127 records · Page 7Linked to original sources

Incidence and management of laser-associated oesophageal perforation.

The incidence of oesophageal perforation in 350 patients referred for laser treatment to palliate malignant dysphagia is reported. Perforation occurred in 6 per cent of patients or 2 per cent of treatment episodes. Perforation was usually due to oesophageal dilatation undertaken before laser treatment (23 of 25 perforations). Immediate recognition and the institution of an aggressive non-operative management protocol resulted in survival in 20 of 23 patients.

Deglutition Disorders↗

Self-expanding metal stents for the palliation of dysphagia due to inoperable oesophageal carcinoma.

Adequate palliation of dysphagia due to inoperable oesophageal carcinoma is difficult to achieve with low morbidity. Thirty-three patients (21 men and 12 women of mean(s.e.m.) age 69(2) years) with inoperable carcinoma of the oesophagus underwent insertion of self-expanding metal stents. In 22 patients the tumours were in the lower third of the oesophagus, in eight in the middle third and in three in the upper third. A stent was inserted as primary palliative therapy in 14 patients, after failed laser therapy in 13 and after oesophageal perforation following other treatments in six. Patients presented with dysphagia of grade 3 or 4. Three types of stent were used: Wallstent, Strecker and Gianturco; stents were inserted under fluoroscopic guidance after balloon dilatation of the stricture. All attempted insertions of metal stents were successful. Dysphagia reduced from grade 3 or 4 to 0 or 1. There were no perforations related to insertion. Patients who had stents inserted to seal previous perforations left hospital a median 7 days later. Dysphagia recurred in six patients, due to migration of the stent (three), blockage by food bolus (one) and tumour overgrowth (two). These problems were easily treated. Self-expanding metal stents seem to offer excellent palliation with minimal morbidity for patients with inoperable carcinoma of the oesophagus.

Adenocarcinoma↗

Expression of alkaline phosphatase by a B-cell hybridoma and its modulation during cell growth and apoptosis.

The 7TD1 B-cell hybridoma was found to spontaneously express alkaline phosphatase (ALP), an enzyme which is produced by splenic B lymphocytes once optimally activated. Determination of ALP levels during cell growth and departure to apoptosis showed fluctuations. Following a temporary increase within the first 24 h, enzyme expression was maintained at high levels during the early proliferation stage, and then declined from 3 to 4 days in mid-exponential phase to basal levels at day 6 when living cells were no longer detectable and the apoptotic process was completed. The protein synthesis inhibitor, cycloheximide (1 microg/ml), decreased ALP production while stimulating a strong apoptosis of 7TD1 cells, within 4 h. Aphidicolin (1 microg/ml) maintained ALP production and provoked a release of ALP activity into the surrounding medium; it also induced apoptosis, but with a 24 h delay. Quantification of apoptosis and ALP expression by flow cytometry, after simultaneous staining of DNA with Hoechst 33342 and ALP with naphthol AS-TR phosphate/Fast Red RC fluorescent reagent, revealed cell cycle modulation of ALP expression, its activity increasing as 7TD1 cells progressed from G1 phase into S and G2/M phases of the cell cycle in control as well as in drug-treated cells. Kinetics of drug-induced apoptosis and higher expression of ALP associated preferentially with active cell growth during the prevention stage of apoptosis suggested a possible link between cellular ALP expression and cell survival.

Alkaline Phosphatase↗

Radioimmunoassay for hexarelin, a peptidic growth hormone secretagogue, and its pharmacokinetic studies.

A radioimmunoassay (RIA) method for hexarelin, a peptidic growth hormone secretagogue, has been developed and applied to pharmacokinetic studies in dogs following an IV dose of 1 microgram/kg, and three SC doses of 1, 10, and 100 micrograms/kg. The sensitivity of the assay was determined to be 1.34 fmol/assay. Cross-reactivity of the antiserum with nine hexarelin analogues was less than 1% upon modification of positions 3, 4, or 5 of the peptide. No apparent cross-reaction with endogenous hexarelin metabolites were observed. Intra- and interassay coefficients of variation were less than 3% and 4%, respectively. Intravenous bolus pharmacokinetics of hexarelin displayed a high terminal half-life of 120 min, a fractional plasma clearance of 4.28 ml/min/kg, and a volume of distribution at steady state of 387.7 ml/kg. Following SC administration of hexarelin, despite the increase in dose administered, both clearance (3.93-5.17 ml/min/kg) and volume of distribution (316-544 ml/kg) parameters remained constant over the dose range studied.

Amino Acid Sequence↗

A chemiluminescence enzyme immunoassay (CLEIA) for the determination of medroxyprogesterone acetate in human serum.

An enzyme immunoassay with chemiluminescence detection (CLEIA) for measuring serum levels of medroxyprogesterone acetate (MPA), a synthetic progestational agent currently used in fertility control and hormonal cancer, is reported. The polyclonal antiserum was obtained by immunizing rabbits with the synthetized 17-hemisuccinate derivative of medroxyprogesterone (MPS) coupled to serum albumin. This antiserum does not display any cross reactivity with extracted metabolites or with corticosteroid analogs with modifications at positions 11 and 16. The same MPS coupled to alkaline phosphatase is used as tracer. For the chemiluminescent detection system, adamantyl-1,2-dioxetane phosphate is selected as substrate. The typical standard curve ranges from 18.5 to 1182 pg per well and displays a slope factor of 0.74, with an ED50 of 143.8 pg of MPA per well and a minimum detectable and maximal level of 0.83 and 12,400 pg per well respectively. The assay has been validated on spiked serum samples in terms of precision (intra- and interassay coefficient variations of less than 8% and 13%, respectively), and of accuracy (mean recovery 105%). The validation on clinical samples demonstrates a good correlation of MPA serum values obtained both by radioimmunoassay and CLEIA. This specific and sensitive CLEIA, which requires less than 100 microliters of serum sample, appears to be an interesting alternative for the monitoring of serum levels of MPA in humans.

Administration, Oral↗

Plastic-covered metallic endoprostheses in the management of oesophageal perforation in patients with oesophageal carcinoma.

OBJECTIVE: To evaluate the role of plastic-covered self-expanding metallic endoprostheses in patients with oesophageal perforation occurring during endoscopically guided dilatation prior to laser treatment for malignant obstruction. SUBJECTS AND METHODS: Six patients with oesophageal perforation following laser treatment for malignant obstruction were treated. Four patients received the polyurethane-covered Wallstent endoprosthesis (Schneider SA, Bulach, Switzerland) and two patients the barbed polyethylene-covered Gianturco stent (William Cook, Europe). RESULTS: All patients had successful stent placement under intravenous sedation and fluoroscopic guidance with immediate relief of dysphagia and sealing of the perforation. Following the procedure all patients could eat either a normal diet or soft food and five patients were discharged within 3-4 days. None of the serious sequelae usually associated with oesophageal perforation were observed. Two patients required second overlapping stents to be inserted within 1 week because of minor migration of the initial endoprostheses. In one patient two stents were necessary because the carcinoma extended over 17 cm. Five patients died after stent insertion (mean survival time = 49 days, range 16-80; median survival time = 37 days, range 16-80) due to a general deterioration in their condition, although all could swallow normally until death. The remaining patient was well and tolerating a light diet at 1 month. CONCLUSION: This technique is quick, safe and cost-effective and is now our preferred method of managing malignant oesophageal obstruction associated with perforation.

Aged↗

The use of the Wallstent endovascular prosthesis in the treatment of malignant inferior vena cava obstruction.

We report three cases of inferior vena cava (IVC) obstruction due to metastatic liver disease treated with a self-expanding Wallstent endoprosthesis (Schneider SA, Zurich, Switzerland). All three patients experienced symptomatic relief during their remaining few weeks of life. The Wallstent is effective and easy to deploy, and should be considered for use in the management of such patients. The literature to date on IVC stenting is also reviewed.

Aged↗

Inhibition of plasma kallikrein prevents peptidoglycan-induced arthritis in the Lewis rat.

We investigate whether the previously shown contact system activation plays a pathogenetic role in a rat model of acute inflammation induced by peptidoglycan-polysaccharide (PG-APS) using a new specific plasma kallikrein inhibitor, Bz-Pro-Phe-boroArg-OH (P8720). Group I (control) received neither PG-APS nor inhibitor. Group II (disease-treated) received PG-APS intraperitoneally (IP) and P8720 orally. Group III (disease-untreated) received PG-APS IP. Anemia was evident at 49 h in group III but was not present (P < 0.01) in groups I and II. Spleen weight was significantly decreased in group II compared to group III. Acute arthritis progressively developed in group III from 27 to 49 h, but P8720 decreased the joint swelling in group II by 61% (P < 0.0005). We observed a significant fall in prekallikrein and factor XI (P < 0.01) in groups II and III but not in group I. The decrease in the functional levels of high molecular weight kininogen (P < 0.05) observed in group III were prevented by P8720 in group II. The changes in T-kininogen and alpha 1-inhibitor 3 acute-phase proteins were partially prevented by P8720. We conclude that the inflammatory reactions leading to arthritis and anemia, as well as the acute-phase reaction, are due in part to contact activation, and that specific kallikrein inhibitors may have therapeutic potential.

Acute-Phase Proteins↗

Effect of enalaprilat on bradykinin and des-Arg9-bradykinin release following reperfusion of the ischaemic rat heart.

1. The release of bradykinin (BK) and its metabolite, des-Arg9-bradykinin (des-Arg9-BK), was studied following reperfusion of a globally ischaemic rat heart. 2. BK-like immunoreactivity increased from 13 +/- 3 (preischaemic value) to 48 +/- 12 fmol min-1 g-1 (P < 0.05, n = 14) 30 s after reperfusion. No difference in BK release was found between control hearts and hearts pretreated with the angiotensin converting enzyme (ACE or kininase II) inhibitor, enalaprilat (50 ng ml-1). 3. No significant change in des-Arg9-BK-like immunoreactivity during reperfusion was observed in control hearts. In contrast, des-Arg9-BK-like immunoreactivity rose from 44 +/- 15 to 177 +/- 61 fmol min-1 g-1 (P < 0.05, n = 7) 30 s after reperfusion in enalaprilat-treated hearts. 4. In conclusion, BK is released upon reperfusion of the globally ischaemic rat heart. ACE inhibitors, through the inhibition of kininase II, increase the formation of the active metabolite, des-Arg9-BK.

Angiotensin-Converting Enzyme Inhibitors↗

Esophageal carcinoma: initial results of palliative treatment with covered self-expanding endoprostheses.

PURPOSE: To assess the effectiveness of a polyurethane-covered self-expanding metallic endoprosthesis in the relief of dysphagia due to irresectable esophageal carcinoma. MATERIALS AND METHODS: Thirty-two patients (20 men, 12 women) aged 41-89 years (median, 70 years) with inoperable esophageal carcinoma underwent stent placement (44 stents). All patients underwent both clinical and radiologic examination before and after treatment. Clinical follow-up was performed at 4-week intervals. RESULTS: Stent placement was successful in all patients, with good symptomatic relief and no serious complications. Eleven patients needed more than one stent because of early partial migration, late complete migration, tumor overgrowth, or long stricture. Seven patients had associated esophageal fistulization or perforation; leaks were successfully sealed after stent insertion. The mean dysphagia score was 3.38 +/- 0.49 (standard deviation) before treatment and 0.81 +/- 0.88 at 3-4 days after insertion. Nineteen patients died, with a median survival time of 78 days (range, 12-245 days), and 13 were alive 14-67 days (median, 30 days) after treatment and were swallowing a near normal diet. CONCLUSION: The insertion of plastic-covered endoprostheses provides rapid, safe, and effective palliation of malignant esophageal obstruction.

Adult↗

[Role of kinins in local and systemic inflammatory reactions].

The development of highly sensitive and specific immunoassays allowed the characterization of bradykinin and desArg9-BK metabolism in vitro. The same methods were used to study the time course evolution of the tissue content of both kinins in an carragenan inflammatory model. Quantification of T-kininogen in the same animal model allowed to show an influence of BK on the neosynthesis of this acute phase protein.

Animals↗

An ultrasensitive chemiluminoenzyme immunoassay for the quantification of human tissue kininogens: application to synovial membrane and cartilage.

A sandwich enzyme immunoassay using a chemiluminescent detection has been developed for the quantification of total human (high and low molecular weight) kininogens in tissue extracts. This assay uses monospecific polyclonal IgG labelled with alkaline phosphatase and the commercially available dioxetane derivatives as substrates, for the detection of immune complexes. This method exhibits a sensitivity level of 1 fmol/ml and allows a precise quantification of total kininogens in synovium and cartilage extracts. When characterized by Western blot, the immunoreactive material reveals the presence of both high and low molecular weight kininogens.

Aged↗

Expression and visualization during cell cycle progression of alkaline phosphatase in B lymphocytes from C3H/HeJ mice.

The expression of alkaline phosphatase (APase) activity by purified B cells from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice was determined. Optimal APase activity was expressed after costimulation with interleukin-5 and dextran sulfate (DXS), whereas LPS, which is highly effective on B lymphocytes from normal mice, was unable to induce enzyme expression, even in the presence of DXS. The simultaneous determination by flow cytometry of both cellular APase, by using a fluorescent azo dye technique, and DNA content showed that APase was highly expressed by about one-tenth of cells in G1 phase, whereas it was present in more than 50% of cells in S and G2/M phases. The enzyme, as visualized by confocal microscopy after cell sorting on the basis of DNA content, was found to be localized mainly in vesicular structures distributed throughout the cytoplasm in G1 cells. It was distributed in patches and essentially localized at the cell periphery in S cells, whereas clear capping of activity was observed in G2/M cells.

Alkaline Phosphatase↗

Regional changes in the extravasation of albumin in the canine kidney: comparison of bradykinin and water diuresis.

This report describes the adaptation of the albumin bound Evans blue dye (EB) extraction technique and its use in identifying regional changes in albumin extravasation rates. We present data to justify our technical approach and highlight the use of this method by describing differences resulting from two different models of induced diuresis and natriuresis. Results observed under control conditions (Group 1) are compared to those obtained following the infusion of bradykinin (BK) into the left kidney (Group 2) or hypotonic saline-induced water diuresis (Group 3). EB and water content of tissue samples of cortex (CTX), outer medulla (OM), inner medulla (IM), and papilla (PAP) regions are reported. Under control conditions a significant heterogeneous distribution of EB and water content (wet/dry tissue weight) between zones was observed. Left kidney EB values for the CTX, OM, IM, and PAP in Group 1 were 125 +/- 11, 398 +/- 56, 763 +/- 51, and 741 +/- 52 micrograms EB/g dry tissue and respective wet/dry tissue ratios were 4.48 +/- 0.05, 5.10 +/- 0.19, 7.13 +/- 0.37, and 6.35 +/- 0.32. In Group 2, BK caused a selective increase in cortex EB content to 201 +/- 7 (P < 0.01) micrograms EB/g dry tissue, without altering water content values. Results of EB extraction in Group 3 revealed no change in the CTX but significant increases in the OM, IM, and PAP regions: 576 +/- 40 (P < 0.01), 910 +/- 60 (P < 0.01), and 850 +/- 69 (P < 0.05) micrograms EB/g dry tissue, respectively. Likewise, tissue water content values were unchanged in the CTX but significantly greater in the OM, IM, and PAP: 6.02 +/- 0.22, 8.90 +/- 0.25, and 8.40 +/- 0.17, respectively (P < 0.01, all three values). This technique clearly shows the regional heterogeneity of the renal microvascular network and allows the localization of intrarenal changes in albumin extravasation. This method provides evidence that BK increases albumin extravasation in the cortex only and that changes in the renal medulla are obtained in hypotonic saline-induced water diuresis.

Albumins↗

Development of digoxigenin-labeled peptide: application to chemiluminoenzyme immunoassay of bradykinin in inflamed tissues.

A new ultrasensitive chemiluminoenzyme immunoassay (CLEIA) using digoxigenin-labeled bradykinin (BK) as a tracer is proposed to quantify kinins in tissue samples. Rabbit polyclonal IgGs anti-BK directed against the C-terminal end were used for the immunoconcentration step along with dioxetane derivative for the revelation step. The sensitivity of the assay for BK was 0.1 fmol/ml with ED50 of 0.78 pmol/ml. This method was applied on extracts of normal and carrageenan-inflamed tissues. The edema produced by the injection of carrageenan in rat hindpaws was associated with a sevenfold increase of immunoreactive kinins in the inflamed paw extract (from 0.021 +/- 0.007 to 0.141 +/- 0.021 pmol/g tissue; p < 0.01), the immunoreactivity corresponded to BK, kallidin, and T-kinin after HPLC separation. When a mixture of inhibitors of kininase I (mergepta) and kininase II (captopril) was coinjected with carrageenan, the carrageenan-induced edema was unaffected but the kinin tissue content was significantly enhanced (0.207 +/- 0.003 pmol/g tissue; p < 0.01). However, the kinin tissue content and the edema response were unaltered by inhibitors given separately. Hence, this highly sensitive assay provides a biochemical evidence that kinins may act as proinflammatory mediators, and highlights a compensatory increase of kininase I and II activities in inflamed tissues.

3-Mercaptopropionic Acid↗

Combined immunoextraction approach coupled to a chemiluminescence enzyme immunoassay for the determination of trace levels of salbutamol and clenbuterol in tissue samples.

A monoclonal immunoglobulin G1 (IgG1) antisalbutamol, which exhibits a 75% cross-reactivity with clenbuterol, has been used in the setup of an immunoaffinity chromatography method and a chemiluminescence enzyme immunoassay for the extraction and the quantification of salbutamol and clenbuterol in tissue samples. After analytical validation, the proposed methodology was applied to liver, kidney and muscle samples obtained from calves and pigs treated with these beta 2-agonists (100 micrograms per kg of body weight) for 10 d. This methodology allowed the quantification of both drugs until 6 d after the final dose. At this time, however, salbutamol and clenbuterol were concentrated in the liver. Our results indicate that the liver is the preferred tissue to sample for the detection of illegal use of beta 2-agonists as growth promoters, in the absence of urine samples.

Albuterol↗

Detection of clenbuterol residues in hair.

Sixty rats were grown in the presence of 10 (n = 30) and 100 (n = 30) micrograms kg-1 body mass of clenbuterol for a period of 10 d. An immunoextraction step coupled with a competitive enzyme immunoassay allowed the quantification of clenbuterol in hair upon 20 (10 micrograms kg-1) and 30 d (10 micrograms kg-1) after the last dose. This accumulation in hair contrasts with the rapid clearance in tissues. The nature of the immunoreactive material was confirmed by mass spectrometry.

Animals↗