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Biomedical subjects

M Adler

Publications and source records attributed to M Adler.

At least 127 records · Page 7Linked to original sources

[Cholestatic hepatitis and amoxicillin-clavulanic acid combination. Personnel case report and literature review].

The association amoxicillin-clavulanic acid is a widely used medication. Only about 15 cases of cholestatic hepatitis were reported in Belgium between 1990 and 1993; about 100 cases have been reported to the pharmaceutical company. This effect is severe but reversible. The injury is probably idiosyncratic or immunologically based. Age, sex and treatment duration are as many agents of risk. The diagnosis is undertaken on basis of clinical examination, chronological study, biological evolution and histology.

Age Factors↗

[Tetanus--the forgotten disease].

Tetanus is preventable by proper immunization, which has almost eradicated the disease in countries with a high standard of living. However, the disease is still prevalent even in the most advanced countries and it often appears in the elderly. We emphasize this fact and alert primary care physicians, and duty physicians in emergency rooms, to the possibility of tetanus developing in older patients. Because of their age, they often do not remember when they last had tetanus immunization, nor are records always adequate. We point out the necessity and feasibility of incorporating a special immunization review program for the elderly, including a cost-benefit analysis.

Aged↗

Contribution of direct actions of the oxime HI-6 in reversing soman-induced muscle weakness in the rat diaphragm.

The actions of the bispyridinium oxime HI-6 ([[[(4-aminocarbonyl)pyridino]-methoxy]methyl]-2- [(hydroxyimino)methyl]-pyridinium dichloride) were investigated in vitro on rat phrenic nerve-hemidiaphragm preparations. Isometric twitch and tetanic tensions were elicited at 37 degrees C with supramaximal nerve stimulation at frequencies of 20 and 50 Hz. To approximate normal respiration patterns, trials consisting of 30 successive 0.55 s trains were alternated with 1.25 s rest periods. Under control conditions, the above stimulation pattern generated tensions that were well maintained at both frequencies. In contrast, a marked depression of muscle tension was observed in diaphragms removed from rats administered 339 micrograms/kg soman (3 LD50) and tested in vitro. Addition of HI-6, 4 h after soman exposure, led to a nearly complete recovery of muscle tension at 20 Hz. At 50 Hz, muscle tensions still declined especially when trains were elicited at 1.25 and 3 s intervals. The recovery by HI-6 observed in this study appears to be mediated by mechanisms unrelated to acetylcholinesterase reactivation since no increase of enzymatic activity was detected and the effect was reversed by a brief washout in oxime-free physiological solution. The results suggest that the direct action of HI-6 may play a role in restoring soman-induced diaphragmatic failure but this effect would be significant primarily under low use conditions.

Acetylcholinesterase↗

Hepatitis C virus and its genotypes in patients suffering from chronic hepatitis C with or without a cryoglobulinemia-related syndrome.

Recently, evidence has been presented for a possible association between hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia (EMC). Eleven consecutive patients with EMC and two with cryoglobulinemia type I were examined for the presence of markers of HCV infection. Eleven of 13 patients (10 with EMC and 1 with type I cryoglobulinemia) had anti-HCV antibodies (as determined by a second generation anti-HCV assay) and HCV-RNA in plasma or serum. HCV-RNA was also detected in liver biopsies of five patients. Genotyping showed that HCV genotype 1 was found in 10 of 11 patients with HCV-RNA (9 genotype 1b and 1 genotype 1a) and only one patient had HCV genotype 2. However, a similar high prevalence of genotype 1b (100%) was found in a group of 14 consecutive patients with chronic hepatitis C, who had no clinical evidence of cryoglobulinemia. Concomitant infection was present in three patients with genotypes 2, 3 and 4, respectively. These findings stress the high prevalence of HCV infection in patients with EMC and further study shows that a difference in genotype prevalence was not found between HCV-related EMC and chronic hepatitis C without clinical manifestations of EMC.

Adult↗

Tuberculosis presenting as acute hepatitis in a renal transplant recipient.

We observed a kidney transplant recipient in whom acute hepatitis was the initial manifestation of tuberculosis, preceding radiological lung involvement by several weeks. The diagnosis was suspected and treatment initiated based on the finding of a granulomatous hepatitis on liver biopsy. Mycobacterial tuberculosis was grown and identified first in liver samples and only later in sputum and bone marrow. This case illustrates the protean manifestations of tuberculosis in immunosuppressed patients.

Acute Disease↗

Transjugular intrahepatic portosystemic stent shunt as a rescue treatment after sclerotherapy failure in variceal bleeding.

BACKGROUND: Variceal bleeding carries high early mortality, especially after failure of conventional treatments such as endoscopic injection therapy. The present study analyses the efficacy of transjugular intrahepatic portosystemic stent shunt (TIPS) in cirrhotic patients after failure of sclerotherapy for variceal bleeding. METHODS: Twenty-four consecutive patients underwent TIPS in this indication. RESULTS: The procedure was successful in all patients, with reduction of size or disappearance of varices in 96% of them. Four patients (17%) developed encephalopathy and six (25%) rebled during the follow-up period (median 5 months; range 1-19). Thirty-day mortality was only 17% and 29% during the follow-up period. Deaths were mainly due to liver failure, especially after procedures performed in emergency. Significant decrease in liver function was observed in the days following the procedure. To maintain long-term patency of the shunt, revision was required in nine patients (38%). CONCLUSIONS: TIPS seems to be a promising salvage therapeutic procedure after failed sclerotherapy, but this needs to be addressed in controlled trials.

Esophageal and Gastric Varices↗

[Pyridoxine for severe metabolic acidosis and seizures due to isoniazid overdose].

A 15-year-old girl took 3 g of isoniazid (15 tablets) in a suicide attempt and was brought unconscious to the emergency room. She was in respiratory failure, with seizures that could not be stopped with diazepam. Severe metabolic acidosis with normal serum lactate developed (pH 6.85), but did not improve after infusion of bicarbonate. Intravenous administration of pyridoxine led to prompt cessation of the seizures and to gradual improvement of acid-base status. She recovered consciousness after several hours and was discharged a week later.

Acidosis↗

Cysteine pairing in the glycoprotein IIbIIIa antagonist kistrin using NMR, chemical analysis, and structure calculations.

The pairing of the cysteines in disulfide bonds was investigated for the 68-residue RGD-containing protein kistrin, a potent antagonist of the integrin GP IIbIIIa and an inhibitor of platelet aggregation. Kistrin belongs to a family of homologous proteins found in snake venoms termed disintegrins, all of which have a cysteine content. The disulfide pairing of the 12 cysteines was investigated by chemical analysis, NMR spectroscopy, and distance geometry calculations. The data show that the disulfide pairs are 4-19, 6-14, 13-36, 27-33, 32-57, and 45-64. The various means for assigning the disulfide bonds are described, and the results are compared with the cysteine pairings reported for other disintegrin proteins.

Amino Acid Sequence↗

Anorectal stenosis in patients with prolonged use of suppositories containing paracetamol and acetylsalicylic acid.

We report five cases in which anorectal stenosis was associated with chronic administration of suppositories containing paracetamol and acetylsalicylic acid. All patients were females taking suppositories for chronic migraine. Patients experienced anal pain, tenesmus, fecal incontinence, and, in two cases, intestinal obstruction. Lesions were characterized by a severe circular narrowing of the distal rectum with superficial ulcerations. Radiographs demonstrated the presence of sinus-tract-like formations in the diseased segment and thickening of the rectal wall. Histologic examination showed signs of chronic inflammation with deep ulcerations associated with obliteration of the lamina propria by a fibromuscular proliferation, as was described in the solitary ulcer syndrome of the rectum. Rectal administration of suppositories was discontinued in all the patients. Two patients were improved by anorectal dilatation, but the remaining three required a left proctocolectomy with subsequent coloanal anastomosis. The use of such suppositories must be restricted.

Acetaminophen↗

Differential actions of brevetoxin on phrenic nerve and diaphragm muscle in the rat.

The mechanism of inhibition of skeletal muscle function by brevetoxin (PbTX-3) was examined in vitro in the rat phrenic nerve-diaphragm preparation. PbTX-3 in low concentrations (< 0.06 microM) preferentially blocked conduction in the phrenic nerve without altering the resting membrane potential of the muscle fibers. Endplate potential failure occurred in an all-or-none fashion in the presence of PbTX-3 (> 0.06 microM). An increase in the frequency of miniature endplate potentials resulting from nerve terminal depolarization was observed only after endplate potential failure. Higher concentrations of toxin (> 0.3 microM) depressed directly-elicited muscle twitches and produced significant muscle membrane depolarization. Tetrodotoxin was effective in reversing membrane depolarization and alterations in MEPP frequency caused by PbTX-3. These findings suggest that diaphragmatic failure in PbTX-3 is primarily caused by a block of impulse conduction in the phrenic nerve due to a higher sensitivity of nerve than muscle membrane to the toxin.

Action Potentials↗

Brevetoxin depresses synaptic transmission in guinea pig hippocampal slices.

Extracellular recordings were obtained from area CA1 of guinea pig hippocampal slices. PbTx-3, a brevetoxin fraction isolated from the red tide dinoflagellate Ptychodiscus brevis, was applied by bath perfusion. The toxin produced a concentration-dependent depression of the orthodromically evoked population spike with an EC50 of 37.5 nM. Brevetoxin concentrations below 10 nM were without effect, and concentrations above 100 nM led to total inhibition of evoked responses. PbTx-3 did not produce spontaneous synchronous discharges but did induce afterdischarges following evoked responses in about 50% of the slices tested, particularly at concentrations between 10 nM and 100 nM. Orthodromically evoked responses were more sensitive to PbTx-3 than were those elicited by antidromic stimulation. High-Ca2+ solution, 4-aminopyridine, and tetraethylammonium failed to antagonize either orthodromic or antidromic effects of the toxin. Although the precise mechanism by which PbTx-3 depresses evoked responses is not certain, depolarization of the presynaptic nerve terminals leading to failure of transmitter release could explain the toxin's actions. This is the first report of the effects of brevetoxin applied directly to central nervous system tissue.

Animals↗

Listeria monocytogenes hepatitis in a liver transplant recipient: a case report and review of the literature.

Listeria is an uncommon cause of hepatitis in adults. We report the case of a liver transplant recipient who presented with a clinical picture of acute hepatitis, 8 months after grafting. Blood cultures yielded Listeria monocytogenes. The patient made a full clinical recovery after adequate antimicrobial therapy (ampicillin and gentamicin intravenously for 4 weeks). Hepatitis was attributed to the Listeria infection. We believe this is the first reported case of Listeria hepatitis in an organ transplant recipient.

Hepatitis↗

Sequential 1H NMR assignments of kistrin, a potent platelet aggregation inhibitor and glycoprotein IIb-IIIa antagonist.

Sequence-specific nuclear magnetic resonances assignments have been obtained for the protons of kistrin. Kistrin is a small naturally occurring snake venom protein that inhibits platelet aggregation by blocking the interaction of fibrinogen with the membrane-bound glycoprotein IIb-IIIa (GP IIb-IIIa), a receptor from the integrin family. Kistrin has an Arg-Gly-Asp sequence which is believed to form an adhesion recognition sequence that is essential for activity. Therefore, the interaction between kistrin and GP IIb-IIIa may provide important information on the motif used by integrins to recognize their target proteins which bear RGD sequences. Kistrin consists of 68 residues and contains six intramolecular disulfide bonds. Although one-third of the amide protons are protected from exchange with the solvent, there appears to be little or no regular secondary structure. The large number of NOE's between residues separated by two and three positions in the sequence indicates that the protein contains a large number of tightly packed loops. Along with the sequential assignments, this paper also discusses the construction and use of computerized data bases for manipulating NMR results. A strategy for computer-assisted sequential resonance using these data bases is also presented.

Amino Acid Sequence↗

NMR studies of structure and dynamics of isotope enriched proteins.

Structural studies of globular proteins by nmr can be enhanced by the use of isotope enrichment. We have been working with proteins enriched with 15N, and with both 15N and 13C. Due to the isotope enrichment we could assign several large proteins with up to 186 residues and could address structural questions. Furthermore, we can accurately measure heteronuclear and homonuclear vicinal coupling constants. This involves in part multidimensional multiple resonance experiments. This is important for characterization of minor conformational changes caused by mutations. We have also made use of isotope enrichment to study the internal mobility of proteins. We also have developed novel methods for measuring accurately 15N relaxation parameters, in particular transverse relaxation rates. This has led us toward a method for directly mapping spectral density functions of the rotational motions of N-H bond vectors in proteins. The protein systems that are discussed include the unlabeled proteins kistrin and cytochrome c551, and the labeled proteins eglin c, a flavodoxin, and human dihydrofolate reductase.

Bacterial Proteins↗