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Biomedical subjects

M Adler

Publications and source records attributed to M Adler.

At least 109 records · Page 6Linked to original sources
PubMed1996

Diagnostic efficacy of push-enteroscopy and long-term follow-up of patients with small bowel angiodysplasias.

Gastrointestinal angiodysplasias are the most common cause of obscure chronic digestive blood loss. Push-enteroscopy is likely to detect and to treat vascular lesions. Push-enteroscopy was performed in 83 patients (mean age 62 years) presenting with iron deficiency anemia of obscure origin. A nonrevealing preliminary evaluation included esophagogastroduodenoscopy, colonoscopy and, in 50% of the patients, small bowel barium studies. We employed a 240-cm Olympus push-enteroscope (XSIF-100), 11.3 mm in diameter. A potential bleeding lesion was observed in 49 patients (59%). Gastrointestinal angiodysplasias were the most common lesion (33 patients). Electrocoagulation (bicap) of angiodysplasias was performed when accessible and not diffuse (<20). If not contraindicated, hormonal treatment was proposed for patients who had at least five AD. Some patients had both treatments. Long-term follow-up (mean, 12.2 months) was obtained in 25 patients with small bowel angiodysplasias. A good outcome (neither recurrence of anemia nor blood transfusion requirements) was observed in 12 patients. The diagnostic efficacy of push-enteroscopy is high. Despite available and recommended therapeutic modalities, the long-term outcome was considered to be good in only 50% of the patients.

Adolescent↗
PubMed1996

Effect of 3,4-diaminopyridine on rat extensor digitorum longus muscle paralyzed by local injection of botulinum neurotoxin.

The actions of the K+ channel blocker, 3,4-diaminopyridine (3,4-DAP), were studied in the rat extensor digitorum longus (EDL) muscle following local inhibition of neuromuscular transmission by botulinum neurotoxin (BoNT). Local paralysis of the EDL muscle was induced by s.c. injections of BoNT serotypes A, B, E or F over the anterior tibialis muscle. One to 14 days later, the rats were anesthetized with urethane, and isometric twitch tensions following stimulation of the peroneal nerve were measured in situ. Muscles were paralyzed within 24 hr of administration of 5 mouse LD50 units (U) of BoNT/A and remained inhibited for the entire 14-day period of observation. Similar levels of inhibition, but of shorter duration, were observed after local injection of 20 U of BoNT/E, 10(4) U of BoNT/B or 20 U of BoNT/F. 3,4-DAP (4 mg/kg, i.v.) potentiated twitch tensions markedly in BoNT/A intoxicated muscle. The increase in tension developed rapidly (halftime = 5.81 +/- 0.6 min), persisted for approximately 1 hr, then decayed slowly with a halftime of 25.2 +/- 4.6 min. Subsequent administration of 3,4-DAP restored tensions to the original maxima, and this procedure could be repeated up to eight times with no decrement. The action of 3,4-DAP was comparable when given 1, 2, 3 or 7 days after BoNT/A and enhanced when administered 14 days after toxin injection. 3,4-DAP was less effective in reversing BoNT/E-induced muscle paralysis and nearly ineffective in antagonizing the paralytic actions of BoNT/B or BoNT/F. The results indicate that 3,4-DAP is of benefit in BoNT/A and BoNT/E intoxication, but is of marginal value after exposure to serotypes B and F.

4-Aminopyridine↗
PubMed1996

Relationship between hepatocyte proliferative activity and liver functional reserve in human cirrhosis.

Hepatocyte proliferative activity is elevated in cirrhotic patients who develop hepatocellular carcinoma (HCC) and decreased in alcohol-induced hepatitis patients with poor outcome. Hepatocyte proliferative activity has not been evaluated in an unselected population of cirrhotic patients regarding the severity of the disease. Forty-six cirrhotic patients (21 alcoholic, 20 viral, and 5 other) were prospectively analyzed by proliferating cell nuclear antigen (PCNA) immunostaining on methanol-fixed, paraffin-embedded liver biopsy specimens. In these conditions, the PCNA-labeling index (PCNA-LI) measures the number of cells in the S-phase and assesses tissue proliferation. The median value of the PCNA-LI for all samples was 4.3% (range, 0%-20.2%). It declined with worsening Child-Pugh score: 9.15% (range, 3.3%-20.2%), 5.3% (range, 1.2%-18%), and 2.4% (range, 0%-4.4%) in Child classes A, B, and C, respectively (P < .05). Using the best cutoff PCNA-LI value to divide cirrhosis into slowly and rapidly proliferating tissue subsets, the PCNA index was independently associated with serum albumin. The probability of survival in patients with a high PCNA-LI ( > 4.4%) was significantly higher than in those with a lower PCNA-LI (0.93 vs. 0.53, at a median follow-up of 153 days; P = .01). In all 6 patients undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS), the PCNA-LI decreased after the procedure. This early impairment of hepatocyte proliferative activity after TIPS placement might reflect the functional alterations induced by this treatment. In conclusion, hepatocyte proliferative activity assessed by PCNA-LI is increased in cirrhotic patients and decreases with worsening of the disease.

Adult↗
PubMed1996

[Contribution of enteroscopy in the diagnosis of digestive hemorrhages of unknown origin].

In this work we report our experience with enteroscopy and its contribution in the diagnosis of anaemia of unknown digestive origin. 90 enteroscopies had been performed in 83 anaemic patients with positive blood stool. 37 of the patients experienced episodes of melena. Preliminary minimal routine investigations including gastroscopy and coloscopy were not contributive. Potentially haemorrhagic lesions were diagnosed in 49 patients (59%), and 7 of these lesions were located in the small bowel. A small bowel lesion has been found in 17 patients with melena and in 19 patients without melena (p > 0.10). The most frequent lesions were angiodysplasias (AD). The mean age of patients with AD was 71.4 years old, vs. 57.2 years (p < 0.00001). Endoscopic bipolar electrocoagulation was performed in 22 patients. Enteroscopy is an efficient technique in the evaluation of patients suffering from obscure digestive bleeding, regardless the presence or absence of melena.

Adolescent↗
PubMed1996

[Pupillography for objective vigilance assessment. Methodological problems and possible solutions].

To measure vigilance disorders in healthy normals or in patients (narcolepsy, sleep apnea syndrome) is difficult, time-consuming and hardly objective with present methods. Recording and analysis of spontaneous pupillary behaviour in darkness by infrared video pupillography is an objective and time-saving method to measure daytime sleepiness. However, certain external conditions must be satisfied (avoid light, noise, stress) to get reliable results. Spontaneous pupillary oscillations are recorded in darkness over 10 min and data are analyzed by fast Fourier transformation, with additional calculation of the mean pupillary diameter for each time segment (approx. 1 min). While in the alert normal, pupil remains dilated during the measurement in darkness and oscillates with an amplitude below 0.3 mm and a frequency about 1 Hz, there are characteristic changes in fatigue: (1) low-frequency components dominate the spontaneous pupillary oscillations, with an amplitude reaching several millimeters, and (2) pupil diameter decreases with time. Infrared video pupillography could play a role as a screening method and therapy control for hypersonic patients (most frequent: sleep apnea syndrome) with excessive daytime sleepiness. An objective, time-saving method like infrared video pupillography would be useful in sleep medicine and psychiatry when testing the level of vigilance, and in psychology or industrial medicine as well, providing informations about acute vigilance problems in healthy normals.

Adult↗
PubMed1996

[Pupillography as an objective attention test].

Infrared video pupillography (IVP) allows continuous recording of spontaneous pupillary oscillations in darkness which change characteristically with fatigue. Pupil size in darkness is age-related, has its maximum in the second decade and subsequently decreases during life time. Normally, the pupil oscillates in darkness with a frequency of about 1 Hz and amplitudes of less than 0.3 mm. Excessive daytime sleepiness causes instability of this pupillary behaviour which is constant in alert normals, and so called fatigue waves appear with an amplitude reaching several millimeters. The frequency profile is dominated by slow frequencies below 0.5 Hz, while average pupil size decreases continuously with time. As IVP is an objective and time-saving method it could become an important supplement to test procedures used in sleep medicine and sleep research to measure daytime sleepiness.

Adult↗
PubMed1995

The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin.

The solution structure has been determined for a 19-residue peptide that is fully folded at room temperature. The sequence of this peptide is based on the C-loop, residues 371-389, of the fourth epidermal growth factor-like domain of thrombomodulin, a protein that acts as a cofactor for the thrombin activation of protein C. Despite its small size, the peptide forms a compact structure with almost no repeating secondary structure. The results indicate the structure is held together by hydrophobic interactions, which in turn stabilize the two beta-turns in the structure. The first beta-turn in the C-loop represents a conserved motif that is found in the published structures of five other epidermal growth factor-like proteins. The critical role of Phe376 in the stabilization of the first beta-turn is consistent with mutagenesis data with soluble thrombomodulin. The results also show that a small subdomain of a larger protein can fold independently, and therefore it could act as an initiation site for further folding.

Amino Acid Sequence↗
PubMed1995

Homology model of human interferon-alpha 8 and its receptor complex.

Human interferon-alpha 8 (HuIFN alpha 8), a type I interferon (IFN), is a cytokine belonging to the hematopoietic super-family that includes human growth hormone (HGH). Recent data identified two human type I IFN receptor components. One component (p40) was purified from human urine by its ability to bind to immobilized type I IFN. A second receptor component (IFNAR), consisting of two cytokine receptor-like domains (D200 and D200'), was identified by expression cloning. Murine cells transfected with a gene encoding this protein were able to produce an antiviral response to human IFN alpha 8. Both of these receptor proteins have been identified as members of the immunoglobulin superfamily of which HGH receptor is a member. The cytokine receptor-like structural motifs present in p40 and IFNAR were modeled based on the HGH receptor X-ray structure. Models of the complexes of HuIFN alpha 8 with the receptor subunits were built by superpositioning the conserved C alpha backbone of the HuIFN alpha 8 and receptor subunit models with HGH and its receptor complex. The HuIFN alpha 8 model was constructed from the C alpha coordinates of murine interferon-beta crystal structure. Electrostatic potentials and hydrophobic interactions appear to favor the model of HuIFN alpha 8 interacting with p40 at site 1 and the D200' domain of IFNAR at site 2 because there are regions of complementary electrostatic potential and hydrophobic interactions at both of the proposed binding interfaces. Some of the predicted receptor binding residues within HuIFN alpha 8 correspond to functionally important residues determined previously for human IFN alpha 1, IFN alpha 2, and IFN alpha 4 subtypes by site-directed mutagenesis studies. The models predict regions of interaction between HuIFN alpha 8 and each of the receptor proteins, and provide insights into interactions between other type I IFNs (IFN-alpha subtypes and IFN-beta) and their respective receptor components.

Amino Acid Sequence↗
PubMed1995

Antagonism of botulinum toxin-induced muscle weakness by 3,4-diaminopyridine in rat phrenic nerve-hemidiaphragm preparations.

The effects of the potassium channel inhibitor and putative botulinum toxin antagonist 3,4-diaminopyridine (3,4-DAP) were investigated in vitro on the contractile properties of rat diaphragm muscle. In the presence of 100 pM botulinum neurotoxin A (BoNT/A), twitches elicited by supramaximal nerve stimulation (0.1 Hz) were reduced to approximately 10% of control in 3 hr at 37 degrees C. Addition of 3,4-DAP led to a rapid reversal of the BoNT/A-induced depression of twitch tension. In the presence of 100 microM 3,4-DAP, antagonism of the BoNT/A-induced blockade began within 30-40 sec and reached 82% of control with a half-time of 6.7 min. The beneficial effect of 3,4-DAP was well maintained and underwent little or no decrement relative to control for at least 8 hr after addition. Application of 1 microM neostigmine 1 hr after 3,4-DAP led to a further potentiation of twitch tension, but this action lasted for < 20 min. Moreover, neostigmine caused tetanic fade during repetitive stimulation. In contrast to the efficacy of the parent compound, the quaternary derivative of 3,4-DAP, 3,4-diamino-1-methyl pyridinium produced little or no twitch potentiation up to a concentration of 1 mM. The potassium channel blocker, tetraethylammonium, generated a transient potentiation followed by a sustained depression of twitch tensions. It is concluded that 3,4-DAP is of benefit in antagonizing the muscle paralysis following exposure to BoNT/A. Co-application of neostigmine or tetraethylammonium with 3,4-DAP, however, appears to confer no additional benefit.

Aminopyridines↗
PubMed1995

A study of zinc-dependent metalloendopeptidase inhibitors as pharmacological antagonists in botulinum neurotoxin poisoning.

Zinc-dependent metalloprotease inhibitors phosphoramidon, captopril and a peptide hydroxamate were studied as potential pretreatment compounds by examining their ability to delay the onset or to prolong the time to 50% block of nerve-elicited muscle twitch tension in the mouse phrenic-nerve diaphragm (in vitro at 36 degrees C) after botulinum neurotoxin serotypes A and B (BoNT-A, BoNT-B). Addition of BoNT-A or BoNT-B (1 x 10(-10) M) produced 50% block of the twitch response at 56 +/- 9 min and 76 +/- 4 min, respectively. Preincubation (45 min) of muscles with phosphoramidon (0.2 mM) prolonged the time to 50% block by 15 min in BoNT-B-poisoned muscles with no effect on the time-course of paralysis in BoNT-A exposed muscles. When the same quantities of BoNT-A or BoNT-B (equivalent to 1 x 10(-10) M bath concentration) were preincubated for 2 hr with phosphoramidon (equivalent to 0.2 mM final bath concentration), and the incubation mixture was added to the muscle chamber, the times to 50% block were prolonged by 38 min and 18 min for BoNT-B and BoNT-A, respectively. Preincubation of diaphragms with captopril (up to 10 mM) or peptide hydroxamate (75 microM) failed to antagonize BoNT-A or BoNT-B-induced neuromuscular block. Among the three metalloprotease inhibitors examined here, only phosphoramidon showed a significant protection against both serotypes of BoNT. A search for better inhibitor compounds specifically tailored to match the active site on BoNT molecule deserves attention.

Amino Acid Sequence↗
PubMed1995

Diagnostic and therapeutic endoscopic retrograde cholangiography after liver transplantation.

BACKGROUND: We report our current experience using endoscopic retrograde cholangiography in the management of post-transplantation biliary tract complications. METHODS: Twenty-three patients among 109 adult liver transplant recipients underwent retrograde cholangiography because of cholestasis (18 patients) or bile leaks (5 patients). RESULTS: Eleven of 18 patients developed anastomotic strictures, all successfully dilated by plastic stents; one patient required Roux-en-Y revision due to recurrent cholangitis while stented. Three had biliary calculi extracted following sphincterotomy. Two developed intrahepatic ductal strictures secondary to severe rejection. One patient had hepatic artery thrombosis with a hilar stricture. One cholangiogram was normal. Three patients developed bile peritonitis following T-tube removal, all treated by sphincterotomy and nasobiliary drainage. Choledochal perforation resulting from an impacted T-tube limb was detected in two patients, both treated with sphincterotomy and nasobiliary drainage. CONCLUSIONS: Strictures within 3 months of surgery required 3 months of stenting; those occurring later required longer periods of time to respond. Bile leaks responded uniformly and rapidly to drainage. Endoscopic retrograde cholangiography is a useful diagnostic and therapeutic intervention for post-transplantation biliary tract complications.

Adult↗
PubMed1995

Cholangiographic findings in deteriorating primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: The evolution of primary sclerosing cholangitis (PSC) is difficult to predict, and ERCP may be helpful in diagnosing its complications and treating them. Few descriptions of cholangiographic findings during the course of the disease have yet appeared. We report here on our experience in the management and follow-up by ERCP of six patients with deteriorating PSC. PATIENTS AND METHODS: Between 1981 and 1992, PSC was diagnosed in 18 patients. Clinical, biochemical, and cholangiographic findings were recorded during the follow-up period. An initial group of 12 patients had a good clinical and biochemical course (mean 56 months) and did not require systematic control ERCPs. A second group of six patients, showing cholangiographic features similar to those of the first group at presentation, developed clinical and biochemical deterioration within a mean period of 43 months (range 6-96). RESULTS: These six patients had a significant elevation of serum bilirubin and at ERCP showed worsening bile duct lesions, with marked strictures and a subsequent increase in the maximum duct diameter in both the extrahepatic and intrahepatic ducts compared to the initial ERCPs. In two of these six patients, the strictures were due to a superimposed cholangiocarcinoma. Endoscopic drainage was unsuccessful, transplantation impracticable due to extrahepatic spread, and both patients died three and five months, respectively, after diagnosis of cholangiocarcinoma. By contrast, four patients with dominant extrahepatic duct involvement benefited from endoscopic procedures (mean follow-up 19 months) without any recurrence of cholangitis and without requiring long-term antimicrobial treatment. The follow-up checks included regular ERCPs performed every six months for duct and stent assessment, and cytology brushing. CONCLUSIONS: Since there are no effective means of early and accurate detection of cholangiocarcinoma, the use of ERCP to compare the course of cholangiographic lesions over time may be of interest. Patients with extrahepatic duct involvement may benefit from endoscopic therapy. By contrast, in patients with dominant intrahepatic duct disease and a deteriorating clinical status, attempts at endoscopic therapy are not helpful, and liver transplantation needs to be considered promptly.

Adult↗
PubMed1995

Design and implementation of the stavudine parallel-track program.

In a randomized, double-blind, large, simple trial, the safety and efficacy of two weight-adjusted dose levels of stavudine were evaluated in patients with advanced human immunodeficiency virus (HIV) infection. All patients were refractory to or intolerant of both zidovudine and didanosine. Patients weighing > or = 60 kg received 20 or 40 mg of stavudine twice daily. The dose was reduced to 15 or 30 mg for patients weighing 40-59 kg and to 10 or 20 mg for those weighing < 40 kg. The primary efficacy end points were survival and time to clinical progression of HIV disease. The primary safety end point was time to dose-limiting neuropathy. A total of 8127 patients were enrolled as of 31 July 1993. Although many patients who might have benefitted from stavudine were reached by the parallel-track program, a review of demographic data revealed disproportionate representation by white men from large metropolitan areas on both coasts.

Adult↗
PubMed1995

Mesalazine (Mesasal/Claversal) 1.5 g b.d. vs. placebo in the maintenance of remission of patients with Crohn's disease.

UNLABELLED: INVESTIGATORS: This multicentre study was conducted by 29 principal investigators in 11 countries. AIMS: To compare the safety and efficacy of oral mesalazine (Mesasal/Claversal, 5-ASA) 1.5 g b.d. in comparison with placebo in the maintenance of remission in 286 patients with Crohn's disease. MATERIALS AND METHODS: Patients had to score less than 150 in their Crohn's Disease Activity Index (CDAI), and had to have had one period of clinical activity (CDAI > 150) within 18 months of the study start. Patients were randomized to receive 5-ASA 1.5 g b.d. daily or matching placebo for 12 months. Study visits were scheduled for months 1, 3, 6, 9 and 12, or when symptoms suggested a relapse of the disease. Relapse was defined as a CDAI score greater than 150, with at least a 60-point increase from the baseline index score. None of the patients used glucocorticoids or immunosuppressants during the trial. RESULTS: In the first group, 207 patients with Crohn's colitis or ileocolitis were randomized: there were 101 females and 106 males, in age range 18-71 years. A total of 106 patients (51 in the 5-ASA group and 55 in the placebo group) were withdrawn from the study due to adverse events, insufficient therapeutic effect, or for other reasons. This left 101 patients (51 in the 5-ASA group and 50 in the placebo group) who completed the 12-month trial. In the second group, 79 patients with Crohn's ileitis were randomized to treatment. There were 53 females and 26 males, age range 18-66 years. A total of 41 patients (19 in the 5-ASA group and 22 in the placebo group) were withdrawn from the study. This left 38 patients (17 in the 5-ASA group and 21 in the placebo group) who completed the 12-month trial. The primary efficacy variable was the CDAI. A protocol-eligible analysis and an intent-to-treat analysis were performed. No statistical differences were noted between the two analyses. In patients with Crohn's colitis or ileocolitis, or in those with ileitis, no statistically significant differences were noted with respect to the relapse rates between the 5-ASA and the placebo treatment groups. Adverse events in the gastrointestinal system were the most frequently reported in both treatment groups. Many of the events such as diarrhoea or abdominal pain are symptoms of Crohn's disease. The majority of the events reported were mild or moderate in severity. In neither study was the prevalence of adverse events or the proportion of drop-outs different between patients in the treatment or in the placebo groups. The site of the Crohn's disease had no effect on the frequency of adverse events. CONCLUSION: The relapse rates of Crohn's disease were similar for up to 12 months in both the 5-ASA 1.5 g b.d. and the placebo treatment groups.

Adult↗
PubMed1995

Severe hepatotoxicity related to benzarone: a report of three cases with two fatalities.

We report three cases of severe hepatotoxicity related to benzarone, a benzofuran derivative. Our cases include a 35-year-old woman with (sub)fulminant hepatitis, a 67-year-old woman with macronodular cirrhosis, and a 68-year-old man with severe chronic active hepatitis and cirrhosis, with positivity of anti-smooth muscle antibodies. Two patients died. We stress the potential of benzarone to cause hepatotoxicity, which usually resembles severe chronic active hepatitis. Our cases constitute the most severe cases of benzarone hepatotoxicity reported so far, and comprise the first cases of (sub)fulminant hepatitis and cirrhosis related to benzarone.

Adult↗
PubMed1995

Diagnosis of partial tears of the anterior cruciate ligament of the knee: value of MR imaging.

OBJECTIVE: The purpose of our study was to assess the ability of MR imaging to detect partial tears of the anterior cruciate ligament (ACL) as these injuries, if extensive enough, may result in ligamentous insufficiency or predispose to subsequent acquired knee instability. MATERIALS AND METHODS: A review of all arthroscopic reports from two institutions during the periods 1990-1992 and 1992-1993, respectively, revealed 13 patients with partial tears of the ACL. Thirteen cases each of intact and completely ruptured anterior cruciate ligaments on arthroscopy were randomly selected as controls from the same report review. Preoperative MR images for all cases selected were obtained. Criteria for diagnosis included the absence of findings of complete ACL tear in conjunction with abnormal intrasubstance signal, bowing of the ACL, or nonvisualization of the ACL on one MR imaging sequence with visualization of intact fibers on other sequences. Inter- and intraobserver agreement was assessed using the kappa statistic. RESULTS: The sensitivity of MR imaging for detecting partial ACL tears ranged from 0.40 to 0.75, and the specificity ranged from 0.62 to 0.89. Variability of both inter- and intraobserver interpretations was greater than 0.7 kappa in all but one combination, comparing the diagnostic consistency of each of three readers both with himself, using two readings on separate days, and with each separate interpretation by the other two radiologists. CONCLUSION: Our results show that MR evaluation of partial ACL tears is not sufficiently sensitive to establish the diagnosis without arthroscopy. This study was limited, however, by its small size and by the heterogeneity of the MR imaging technique.

Adolescent↗