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Biomedical subjects

A Adam

Publications and source records attributed to A Adam.

At least 19 recordsLinked to original sources

Kinin-dependent hypersensitivity reactions in hemodialysis: metabolic and genetic factors.

Although the association of angiotensin I-converting enzyme inhibitors (ACEis) with a negatively charged membrane is thought to be responsible for hypersensitivity reactions (HSRs) during hemodialysis, we hypothesize that these complications are due to changes in plasma aminopeptidase P (APP) activity and genotype. To test this hypothesis, we measured plasma APP activity in 14 patients who suffered HSR (HSR+) while dialyzed with an AN69 membrane and simultaneously treated with an ACEi. APP activity was also studied in a control group (n=39) dialyzed under the same conditions, but who did not suffer any side effect (HSR-). We found significantly decreased plasma APP activity (P=0.013) in HSR+ subjects as well as altered degradation of endogenous des-Arginine(9)-bradykinin, with a significantly lower beta value (P<0.001). The same analytical approach was taken in 171 relatives of HSR+ patients. Variance component analysis suggested that genetic differences may explain 61% of the phenotypic variability of plasma APP activity (P<0.001) and the kinetic parameters that characterized kinin degradation. We also showed that the C-2399A single-nucleotide polymorphism at the XPNPEP2 locus was a significant predictor of APP activity in the 39 HSR- controls (P=0.029). Furthermore, a recessive genetic model for the A allele disclosed a significant difference in mean APP activity by genotype (P<0.001). Finally, our study defined the nonspecific inhibition of recombinant APP by some ACEis. In conclusion, this paper highlights the complexity of HSR in hemodialysis, suggesting, as with angioedema, that these rare, but life-threatening adverse events are governed by several metabolic and genetic factors.

Adult↗

"Whatever happened to the class of 2000?" An outcome survey of potential interventional radiologists.

OBJECTIVES: To find out what final career choices were made by trainee doctors who had indicated a strong interest in pursuing a career in interventional radiology and to establish the reasons behind their final career choice. METHODS: Eighty-eight doctors who attended a meeting in 2000 designed to promote interventional radiology as a career were questioned as to whether the meeting influenced their potential career choices and then further surveyed via postal questionnaire 5 years later to find out their eventual career choices. Of the 88 doctors who attended, 56 were radiology trainees and 32 were training in either medical or surgical specialties. There were 25 women and 63 men. RESULTS: Five years after the meeting, six are now interventional radiologists (6.8%) though four of these are still in a 6th year interventional radiology fellowship. A further 12 (13.6%) are systems based, predominantly diagnostic radiologists with an interest in intervention. Thirty-two (43.2%) are diagnostic radiologists who undertake little or no therapeutic intervention. Of the 32 non-radiologists who attended the meeting only three entered radiology and are still in training. CONCLUSIONS: Interventional radiology is a popular initial career choice amongst trainee doctors. However, only a small number eventually pursue the specialty. If the manpower shortage of interventional radiologists is to be addressed, there needs to be improvements in training, accreditation, career opportunities and working conditions.

Career Choice↗

[Multifactorial aspect of acute side effects of angiotensin converting enzyme inhibitors].

Angiotensin converting enzyme inhibitors are a class of drugs successfully used in the treatment of cardiovascular diseases. Despite their effectiveness, treatment with these drugs is characterized by chronic and acute side effects with variable expression depending on the clinical context. Angioedema occurs in patients with hypertension or heart failure. Anaphylactoid reaction is also reported in hemodialysis patients and severe hypotensive reaction in patients receiving transfused blood products and plasmapheresis. In this paper, we describe the role of kinins and metallopeptidases in the pathophysiology of these acute side effects. We also propose different experimental and clinical evidences which plead for an ecogenetic nature of these rare but life-threatening events.

Acute Disease↗

Successful treatment of a chronic post-traumatic 5-year-old osteoporotic vertebral compression fracture by percutaneous vertebroplasty.

Osteoporotic vertebral compression fracture (VCF) is a frequently encountered clinical problem associated with chronic pain and disability. Conservative treatment in the form of bed rest, pain control and bracing may create a vicious circle, in which reduced activity leads to further reduction in bone density and fracture risk. Percutaneous vertebroplasty (PVP) is an accepted treatment modality for osteoporotic vertebral body collapse present for less than 1 year, vertebral myeloma, haemangioma, metastasis and recent traumatic fractures (between 3 and 12 months). We describe an osteoporotic patient in whom successful PVP was performed, under general anaesthesia using CT and fluoroscopic guidance, in a post-traumatic 5-year-old VCF with complete alleviation of debilitating pain. In the light of our experience, we suggest that PVP should be carried out in a series of similar patients to asses its value as a treatment option in patients with chronic osteoporotic vertebral fractures for pain relief and improvement in mobility, independent of fracture age.

Back Pain↗

The use of SMARTeR stents in patients with biliary obstruction.

AIM: The purpose of the study was to evaluate the percutaneous use of the new nitinol SMARTeR stents in patients with biliary obstruction. MATERIALS AND METHODS: Four stents were placed in three patients percutaneously under ultrasound and fluoroscopic guidance. RESULTS: The deployment of the stents was successful in all three patients. All stents maintained their patency and position after short-term follow-up. CONCLUSION: The nitinol SMARTeR stent is useful in the management of patients with biliary obstruction although accurate placement across the ampulla was found to be technically more difficult than with the Wallstent. Larger, long-term follow-up studies are required to evaluate the long-term patency of these new devices.

Cholangiopancreatography, Endoscopic Retrograde↗

Registration of freehand 3D ultrasound and magnetic resonance liver images.

We present a method to register a preoperative MR volume to a sparse set of intraoperative ultrasound slices. Our aim is to allow the transfer of information from preoperative modalities to intraoperative ultrasound images to aid needle placement during thermal ablation of liver metastases. The spatial relationship between ultrasound slices is obtained by tracking the probe using a Polaris optical tracking system. Images are acquired at maximum exhalation and we assume the validity of the rigid body transformation. An initial registration is carried out by picking a single corresponding point in both modalities. Our strategy is to interpret both sets of images in an automated pre-processing step to produce evidence or probabilities of corresponding structure as a pixel or voxel map. The registration algorithm converts the intensity values of the MR and ultrasound images into vessel probability values. The registration is then carried out between the vessel probability images. Results are compared to a "bronze standard" registration which is calculated using a manual point/line picking algorithm and verified using visual inspection. Results show that our starting estimate is within a root mean square target registration error (calculated over the whole liver) of 15.4 mm to the "bronze standard" and this is improved to 3.6 mm after running the intensity-based algorithm.

Algorithms↗

[Ecogenetic aspects of acute side effects caused by angiotensin converting enzyme inhibitors].

Angiotensin converting enzyme inhibitors are currently used in the treatment of different cardiovascular diseases. Acute side effects of acei have been attributed to bradykinin. We have evidenced a decrease catabolism of des-arg9-bradykinin in the plasma of patients who presented such side effects. This anomaly is associated with a decreased activity of plasma aminopeptidase p which is, at least partially, of genetic origin.

Angiotensin-Converting Enzyme Inhibitors↗

Small epithelial cells in human liver cirrhosis exhibit features of hepatic stem-like cells: immunohistochemical, electron microscopic and immunoelectron microscopic findings.

AIMS: To investigate whether cells with features similar to those of the oval cells of rodents and the small epithelial cells (SEC) recently described in certain human liver diseases, i.e. hepatic progenitor cells, also occur in human liver cirrhosis. METHODS AND RESULTS: Surgical specimens from 35 cases of hepatitis B virus-positive cirrhosis (30 cases containing hepatocellular carcinoma) were investigated by immunohistochemical staining for cytokeratin 7 and albumin. Electron microscopic investigations, and immunoelectron microscopic investigations using the same antibodies and a double-labelling technique were performed in 15 and seven cases, respectively. SEC were observed in proliferated bile ductules, at the margins of regenerating nodules and in the fibrous septa in all cases of cirrhosis. The SEC were morphologically similar to the SEC described previously, and to the oval cells seen in experimental hepatocarcinogenesis. They were characterized by their small size, oval shape, scanty electron-dense or electron-lucent cytoplasm, a high nucleo-cytoplasmic ratio, tonofilaments and intercellular junctions. Immunoelectron microscopy revealed that the SEC co-expressed cytokeratin 7 and albumin. Both relatively undifferentiated SEC and SEC with morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes were found. CONCLUSIONS: SEC that exhibit morphological and immunophenotypical features of the SEC seen in certain other liver diseases are found in cirrhosis. These findings further support the hypothesis that a bipotent hepatic stem cell that may give rise to biliary epithelial cells and hepatocytes exists in the human liver.

Albumins↗

The interventional radiological management of cholangiocarcinoma.

The successful management of cholangiocarcinoma requires the collaboration of several clinical disciplines. Modern imaging can demonstrate the liver and the surrounding structures in exquisite detail. Complete surgical resection offers the only potential for cure. The judgement of whether resection is feasible requires precise staging of the tumour. Unfortunately, in most cases, imaging delineates an advanced and inoperable tumour, requiring non-surgical palliative treatment, usually by means of endoscopic or percutaneous radiological techniques. The management of hilar lesions can be problematic requiring substantial experience and skill.

Bile Duct Neoplasms↗

A randomised prospective comparison of the Flamingo Wallstent and Ultraflex stent for palliation of dysphagia associated with lower third oesophageal carcinoma.

BACKGROUND: Covered metallic oesophageal stents offer effective palliation of malignant oesophageal strictures. However, first generation devices were associated with a high rate of migration, particularly when used in the lower oesophagus. AIM: To compare the rate of complications and palliative effect of two newer covered metallic oesophageal stents. PATIENTS AND METHODS: We performed a prospective randomised study using two of these newer stent designs in the treatment of malignant lower third oesophageal tumours. Fifty three patients with dysphagia due to inoperable oesophageal carcinoma involving the lower third of the oesophagus were randomly selected to receive either a Flamingo covered Wallstent (Boston Scientific Inc., Watertown, Massachusetts, USA) or an Ultraflex covered stent (Boston Scientific Inc.). Dysphagia was scored on a five point scale, recorded before stent insertion, the day after, and at least one month later at follow up. Technical success, early and late complications (perforation, migration, severe gastro-oesophageal reflux, haematemesis, and reobstruction due to tumour overgrowth) were also recorded. RESULTS: In both stent groups, a significant improvement in dysphagia score was seen both the next day post stenting and at late follow up (p<0.05). No significant difference was seen in the improvement in dysphagia between the two groups (p>0.1). The frequency of complications encountered in the two groups was similar. Three patients in the Ultraflex group required two stents at primary stenting. CONCLUSION: The two types of stent are equally effective in the palliation of dysphagia associated with lower third oesophageal malignancy and the complication rates associated with their use are comparable.

Aged↗

Bronchogastric fistula successfully treated with the insertion of a covered bronchial stent.

We present what we believe to be the first case of a bronchogastric fistula successfully treated with a plastic-covered metallic bronchial stent. This developed 5 years after a transhiatal oesophagectomy with gastric pull-up for carcinoma of the oesophagus. The successful outcome in this case suggests that this method of treatment should be considered in patients in whom this post-operative complication cannot be managed easily by other means.

Bronchial Fistula↗

Risk factors for the HIV-associated lipodystrophy syndrome in a closed cohort of patients after 3 years of antiretroviral treatment.

OBJECTIVE: To identify prevalence and risk factors associated with the HIV-associated lipodystrophy syndrome (HIVLD) after 3 years of antiretroviral therapy, to investigate the diagnostic value of anthropometric measures and to assess the impact of HIVLD on quality of life. DESIGN AND METHODS: A prospective, cross-sectional, multicentre, observational, cohort study was performed in 27 German teaching hospitals, nonacademic hospitals and private practices. A total of 221 HIV-positive patients commencing antiretroviral therapy between July and September 1996 were studied. The main outcome measure was lipodystrophy, defined as otherwise unexplained truncal fat accumulation and/or fat loss in face or extremities. The analysis consisted of multiple logistic regression models, receiver operating characteristics (ROC) curves for anthropometric measures and visual analogue scales for quality of life. RESULTS: The prevalence of HIVLD after 3 years was 34%. The following variables were independently associated with HIV-LS: stavudine use > 12 months [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-3.9], CD4 count nadir < 200 cells/microL (OR 2.2, CI 1.1-4.6), hypertriglyceridaemia (OR 2.3, CI 1.3-4.2) and nonnucleoside reverse transcriptase inhibitor (NNRTI) intake > 12 months (OR 0.2, CI 0.04-0.87). No cut-off point was found for anthropometric indices with a sensitivity and specificity of > or = 0.8. The mean visual analogue ratings for impaired quality of life, on a scale of 0-10, were: 5.2 (self-esteem), 2.9 (social contacts), 4.2 (sexuality) and 3.5 (daily activities). CONCLUSIONS: These findings suggest a multifactorial aetiology for HIVLD. Stavudine use and a CD4 count below 200 cells/microL may be associated with an increased risk for the development of HIVLD. In contrast, NNRTI treatment may be associated with a reduced risk. Anthropometric indices were found to be insufficient as a diagnostic tool. Quality of life was severely affected by HIVLD.

Adult↗

First-line ritonavir/indinavir 100/800 mg twice daily plus nucleoside reverse transcriptase inhibitors in a German multicentre study: 48-week results.

OBJECTIVES: To evaluate safety and efficacy of the protease inhibitor combination ritonavir/indinavir 100/800 mg twice daily plus 2-3 nucleoside reverse transcriptase inhibitors (NRTI) in antiretroviral-naive patients. METHODS: Within this open-label, uncontrolled multicentre trial, antiretroviral-naive patients (n = 57) with median baseline HIV-RNA of 308,000 copies/mL (range 170-3.01 million copies/mL) and median CD4 cell count of 50 cells/microL (range 0-853 cells/microL) were started on 2-3 NRTIs plus ritonavir/indinavir 100/800 mg twice daily. CD4 cell counts and HIV-RNA were determined at weeks 0, 4, 8, 12, 16, 20, 24 and 48. Statistical analysis was performed on treatment as well as intent-to-treat. RESULTS: Viral load decreased by a median of 3.79 log10 copies/mL (range 2.0-4.60 log10 copies/mL) until week 48. At week 48, 23/57 (40%, intent-to-treat) patients showed a viral load </= 80 copies/mL. In parallel, median CD4 cell counts increased by a median of 149 cells/microL (range -60-420 cells/microL). Median triglycerides and cholesterol increased from baseline 160 mg/dL (range 33-364 mg/dL) to 218 mg/dL (range 110-527 mg/dL) at week 48 and from 166 mg/dL (range 63-262 mg/dL) to 233 mg/dL (range 95-359 mg/dL), respectively. Twenty-seven of fifty-seven patients (47%) discontinued study medication, 19 (33%) due to nephrolithiasis. Two patients changed their antiretroviral regimen after failing virologically. CONCLUSION: Ritonavir/indinavir 100/800 mg twice daily appears to be effective up to 48 weeks despite high baseline viraemia and low CD4 cell count in antiretroviral-naive patients. However, discontinuation due to adverse events, especially nephrotoxicity, is frequent and limits treatment duration. Therefore, extra hydration appears inevitable with this combination.

Adult↗

Interventional radiology in the treatment of hepatic metastases.

Recent technical developments have enabled the development of a range of non-surgical interventions for liver metastases. These include cryotherapy, chemoembolisation, and radiofrequency, laser or microwave ablation. These techniques are reviewed and their role in the management of liver metastases discussed. Chemoembolization does not reliably achieve destruction of hepatic metastases. Cryotherapy and radiofrequency treatment can ablate metastases in 50-90% of cases and are relatively safe compared to hepatic resection. There has been no randomised comparison to show that either cryotherapy or radiofrequency treatment alter long-term survival compared with chemotherapy alone. However, this may be related to the fact that most patients being referred for ablative treatment are considered unsuitable for hepatic resection. Randomised trials to accurately define the place of these innovative techniques are needed.

Catheter Ablation↗

Treatment of superior vena cava obstruction secondary to pacemaker wires with balloon venoplasty and insertion of metallic stents.

AIMS: Pacemaker wires can result in stenosis of the superior vena cava and other central veins. The aim of this study is to demonstrate the safety and effectiveness of treating stenoses of the superior vena cava (SVC) and central veins with balloon venoplasty and metallic stent insertion in the presence of cardiac pacemaker wires. METHODS AND RESULTS: Three patients were referred to the department after developing symptomatic SVC obstruction following implantation of a cardiac pacemaker several years earlier. They were examined with duplex ultrasound and venography, which revealed significant stenoses of the central veins. These patients subsequently underwent endovascular treatment which involved balloon dilation and stent insertion. The treatment was successful in all three patients, without any complications. Long-term patency of up to 4 years is recorded. No pacemaker function dysfunction was encountered. CONCLUSION: SVC stenting is safe and effective in patients who develop the SVC obstruction after cardiac pacemaker insertion.

Adult↗

Separation and characterization of mares' milk alpha(s1)-, beta-, kappa-caseins, gamma-casein-like, and proteose peptone component 5-like peptides.

The equine alpha(s1)- and beta-caseins (CN) were purified by chromatography on DEAE-cellulose and by reversed-phase HPLC. The alpha(s1)-, beta-, and kappa-CN were characterized either by monodimensional urea-PAGE or sodium dodecylsulfate (SDS)-PAGE or by bidimensional electrophoresis. Kappa-casein was characterized after electrophoresis by glycoprotein-specific staining. To identify alpha(s1)-CN without ambiguity, internal sequences were determined after trypsin or chymosin digestion of purified alpha(s1)-CN. These sequences, that could be estimated to correspond to 62% of the full protein, presented strong identities with regions of alpha(s1)-CN primary structures of other species. In particular, 51, 48, 43, and 40% identities were obtained with corresponding regions of sow, dromedary, cow, and human alpha(s1)-CN, respectively. On the other hand, trace amounts of equine gamma-CN-like and proteose peptone component 5-like peptides were found in the whole CN. They were identified by microsequencing and corresponded to beta-CN peptides generated by plasmin action on the whole CN. The equine alpha(s1), beta-, and kappa-CN were separated by bidimensional electrophoresis in numerous isoelectric variants with apparent isoelectric points distributed between pH 4.4 to 6.3, 4.4 to 5.9, and 3.5 to 5.5, respectively. The beta- and kappa-CN displayed a more acidic character in the mare than in the cow.

Amino Acid Sequence↗

Cardioprotective effects of ramipril and losartan in right ventricular pressure overload in the rabbit: importance of kinins and influence on angiotensin II type 1 receptor signaling pathway.

BACKGROUND: The role of kinins in the cardioprotective effects of ACE inhibitors remains controversial. METHODS AND RESULTS: Right ventricular pressure overload in rabbits was produced by pulmonary artery banding for 21 days. Rabbits were untreated, or they received the ACE inhibitor ramipril with or without bradykinin B(1) and B(2) receptor blockers or the angiotensin (Ang) II type I (AT(1)) receptor blocker losartan. Pulmonary artery banding caused right ventricular hypertrophy, depressed papillary muscle contractility, and loss of Ang II contractile effects because of a signaling defect downstream of AT(1) receptors. Paradoxically, AT(1) receptor density and G protein alpha subunits alphaq and alphai1/2 increased. Inotropic responsiveness to the alpha-receptor agonist phenylephrine was normal. Ramipril preserved cardiac contractility, but this effect was attenuated by simultaneous use of kinin receptor blockers. Ramipril also maintained responsiveness to Ang II and prevented AT(1) receptor and G protein upregulation. The simultaneous use of a kinin receptor blocker attenuated but did not prevent upregulation in the AT(1) receptor and G protein. Losartan had no effect on baseline contractility, but it maintained cardiac inotropic responsiveness to Ang II, prevented upregulation of AT(1) receptors, but did not modify G protein upregulation. CONCLUSIONS: Pressure overload of the right ventricle decreases contractility, uncouples AT(1) receptors to downstream signaling pathways, and changes the expression of components of the AT(1) receptor signaling pathway. Ramipril attenuates these effects via kinins. Interventions that prevent local increases in Ang II or block AT(1) receptors also prevent decreased responsiveness of the AT(1) receptor in this model.

Angiotensin II↗