Pharmacokinetics of BAY 59-7939--an oral, direct Factor Xa inhibitor--in rats and dogs.

The pharmacokinetics of BAY 59-7939 - a novel, oral, direct Factor Xa inhibitor - were investigated in rats and dogs in support of preclinical safety studies and clinical development. BAY 59-7939 was rapidly absorbed after oral dosing, with an absolute bioavailability of 57-66% in rats, and 60-86% in dogs. Plasma pharmacokinetics of BAY 59-7939 were linear across the investigated dose range (1-10 mg kg(-1) in rats, 0.3-3 mg kg(-1) in dogs). Plasma clearance was low: 0.4 l kg(-1) h(-1) in rats and 0.3 l kg(-1) h(-1) in dogs; volume of distribution (V(ss)) was moderate: 0.3 l kg(-1) in rats, and 0.4 l kg(-1) in dogs. The elimination half-life after oral administration was short in both species (0.9-2.3 h). Whole-body autoradiography showed moderate tissue affinity. No retention or small volume enrichments of BAY 59-7939-related radioactivity were observed. The plasma-protein binding of BAY 59-7939 was high, species dependent and fully reversible. BAY 59-7939 was rapidly excreted in rats and dogs, and was not irreversibly retained. A dual mode of excretion (biliary/faecal and renal) was observed. In summary, BAY 59-7939 had a favourable, predictable pharmacokinetic profile, with high oral bioavailability and a dual route of excretion.

Stroke recurrences in patients with symptomatic vs asymptomatic middle cerebral artery disease.

BACKGROUND: Although the natural history of extracranial carotid artery disease has been investigated systematically, limited data are available on the course of middle cerebral artery (MCA) disease. METHODS: The authors observed 102 consecutive patients (67 men, 35 women; mean age 61.9 years) with significant MCA stenosis or occlusion as demonstrated by transcranial Doppler and transcranial color-coded duplex ultrasonography. Forty-six patients entered the study after TIA (n = 17) or stroke (n = 29); 56 patients were asymptomatic. Neurologic and ultrasound investigations were performed at regular intervals with a mean follow-up of 31 (range 6 to 117) months. Patients were continuously treated with either platelet inhibitors (n = 75) or anticoagulation (n = 27). RESULTS: Nineteen cerebral ischemic events (11 strokes, 8 TIAs) occurred during follow-up, resulting in an overall annual rate of 7.3%. Thirteen events (8 strokes, 5 TIAs) were attributable to the vascular territory ipsilateral to MCA disease. Patients with symptomatic MCA disease at study entry had an overall stroke risk of 12.5% per year (ipsilateral: 9.1%), whereas the annual incidence in primarily asymptomatic MCA disease was only 2.8% (ipsilateral: 1.4%; p < 0.01). Symptomatic MCA disease was an independent predictor for overall (hazard ratio [HR] 7.91, 95% CI 2.03 to 30.79; p < 0.01) and ipsilateral (HR 9.66, 95% CI 1.5 to 62.25; p = 0.02) cerebrovascular events. CONCLUSIONS: Compared with asymptomatic middle cerebral artery disease, there was a high and continuous recurrence rate of ischemic events in symptomatic patients, which was even higher than in patients with symptomatic extracranial carotid artery disease.

[Long-term hemodynamic compromise in internal carotid artery dissection: quantitative blood volume flow evaluation using 2D Cine phase-contrast MR imaging]. / Langzeit-Entwicklung von Dissektionen der A. carotis interna: Quantitative Blutvolumenfluss-Untersuchungen mit der 2D cine Phasen-Kontrast MR Technik.

PURPOSE: To use the magnetic resonance (MR) phase-contrast technique as a non-invasive method to determine blood volume flow in internal carotid artery (ICA) dissection, which has variable initial volume flow reduction and long term hemodynamic compromise. ICA dissection can lead to partial or complete recanalization or persistent occlusion, and strong clinical motivation exists for reliable assessment of the blood flow, in particular blood volume flow, in the carotid artery circulation after ICA dissection. MATERIALS AND METHODS: Blood volume flow in the carotid artery circulation was quantified in 28 patients with unilateral ICA dissection and 20 age-matched normal controls. Blood volume flow was measured in the ICAs and the common carotid arteries (CCAs) using 2D cine phase-contrast MR imaging. Final measurements were performed until after at least 6 months the hemodynamic compromise showed no changes by ultrasound and MRA. RESULTS: In long term follow up, 11/28 patients demonstrated remaining vessel occlusion, 10/28 partial and 7/28 complete recanalizations. Patients with ICA occlusion showed a significant contralateral volume flow increase (mean 56 %, p < 0.001) in comparison to normal controls. Patients with partial recanalization demonstrated volume flow rates between 24 ml/min and 188 ml/min in the dissected ICA and a less but significant (p < 0.001) increase in the contralateral volume flow. In patients with complete recanalization, normal volume flow conditions were found for both ICAs and CCAs. CONCLUSION: In ICA dissection, quantitative volume flow determination using 2D cine phase-contrast MR imaging is helpful in the initial assessment and long term follow-up of hemodynamic compromise. ICA dissection demonstrated a partial or complete recanalization in nearly (2/3) of the investigated patients and a persisting vessel occlusion in little more than (1/3). Compensatory contralateral increase in volume flow was found.

[Gastrointestinal extramucous running suture anastomosis]. / Die gastrointestinale extramuköse Fortlauf-Anastomose.

There is an ongoing discussion in surgery about what is the best or "correct" technique for gastrointestinal anastomosis. An ideal anastomosis should fulfill the following criteria: it must be well vascularised, safe ("waterproof"), easily feasible, tension-free, spillage should be avoided and it should be inexpensive. We give an illustrated report of the surgical technique of the continuous single-layer anastomosis in the gastrointestinal tract. On the basis of a pilot study, a randomised comparative study, a Swiss multicenter trial and, finally, a prospective 5-year-follow-up quality control study we demonstrate that this "Schweizer (Swiss)"-technique fulfills the criteria of an "ideal" anastomosis and can be used in almost all intestinal localisations.

[Fecal incontinence: evaluation, treatment concept and new therapeutic approaches]. / Stuhlinkontinenz: Abklärung, Behandlungskonzept und neue Therapieansätze.

Faecal incontinence is more frequent than generally assumed. The pathophysiological ground for faecal incontinence are injuries as well as infraclinic post childbirth injuries. However, faecal incontinence is frequently ideopathic by women probably due to weakness of the pelvic floor muscles. Interdisciplinary diagnosis include endoluminal-sonography, sphincter-manometry and in selected cases MR video-defaecography. Results of surgical sphincter repair combined with anterior anal repair may be excellent in up to 70% of the cases, however long-term results may become disappointing. Dynamic gracilis plastic is today a recognized therapy as sphincter replacement. However, provided that the sphincter-muscles remain intact, permanent sacral nerve-stimulation is a very promising emerging therapy. The initial results are very encouraging with recovery from faecal incontinence in up to 70-80% of the treated cases.

[Taste disorder caused by carotid artery dissection]. / Geschmacksstörung durch Karotisdissektion.

There exist only a few reports on loss of taste sensation caused by dissection of the internal carotid artery. We describe a patient with carotid dissection and ipsilateral ageusia in the anterior two thirds of the tongue, presumably from a lesion of the chorda tympani. Ageusia in carotid dissection is explained by the close anatomic relation of the internal carotid artery and the chorda tympani in the short petrous bone. However, since extension of the space-occupying, dissecting intramural hematoma into the carotid channel as in our patient occurs infrequently--a probable precondition for the chorda tympani lesion--loss of taste is accordingly very rare. Reduced perfusion of the vasa nervorum can be excluded as another cause, because the chorda tympani is supplied only from branches of the external carotid artery.

NO-independent regulatory site on soluble guanylate cyclase.

Nitric oxide (NO) is a widespread, potent, biological mediator that has many physiological and pathophysiological roles. Research in the field of NO appears to have followed a straightforward path, and the findings have been progressive: NO and cyclic GMP are involved in vasodilatation; glycerol trinitrate relaxes vascular smooth muscles by bioconversion to NO; mammalian cells synthesize NO; and last, NO mediates vasodilatation by stimulating the soluble guanylate cyclase (sGC), a heterodimeric (alpha/beta) haem protein that converts GTP to cGMP2-4. Here we report the discovery of a regulatory site on sGC. Using photoaffinity labelling, we have identified the cysteine 238 and cysteine 243 region in the alpha1-subunit of sGC as the target for a new type of sGC stimulator. Moreover, we present a pyrazolopyridine, BAY 41-2272, that potently stimulates sGC through this site by a mechanism that is independent of NO. This results in antiplatelet activity, a strong decrease in blood pressure and an increase in survival in a low-NO rat model of hypertension, and as such may offer an approach for treating cardiovascular diseases.

NO-independent regulatory site of direct sGC stimulators like YC-1 and BAY 41-2272.

BACKGROUND: The most important receptor for nitric oxide is the soluble guanylate cyclase (sGC), a heme containing heterodimer. Recently, a pyrazolopyridine derivative BAY 41-2272, structurally related to YC-1, was identified stimulating soluble guanylate cyclase in an NO-independent manner, which results in vasodilatation and antiplatelet activity. The study described here addresses the identification of the NO-independent site on soluble guanylate cyclase. RESULTS: We developed a photoaffinity label (3H-meta-PAL) for the direct and NO-independent soluble guanylate cyclase (sGC) stimulator BAY 41-2272 by introducing an azido-group into the tritium labeled compound. The synthesized photoaffinitylabel directly stimulates the purified sGC and shows in combination with NO a synergistic effect on sGC activity. Irradiation with UV light of 3H-meta-PAL together with the highly purified sGC leads to a covalent binding to the alpha1-subunit of the enzyme. This binding is blocked by unlabeled meta-PAL, YC-1 and BAY 41-2272. For further identification of the NO-independent regulatory site the 3H-meta-PAL labeled sGC was fragmented by CNBr digest. The 3H-meta-PAL binds to a CNBr fragment, consisting of the amino acids 236-290 of the alpha1-subunit. Determination of radioactivity of the single PTH-cycles from the sequencing of this CNBr fragment detected the cysteines 238 and 243 as binding residues of the 3H-meta-PAL. CONCLUSIONS: Our data demonstrate that the region surrounding the cysteines 238 and 243 in the alpha1-subunit of the sGC could play an important role in regulation of sGC activity and could be the target of this new type of sGC stimulators.

Dissociations among functional subsystems governing melody recognition after right-hemisphere damage.

This study describes an amateur musician, KB, who became amusic following a right-hemisphere stroke. A series of assessments conducted post-stroke revealed that KB functioned in the normal range for most verbal skills. However, compared with controls matched in age and music training, KB showed severe loss of pitch and rhythmic processing abilities. His ability to recognise and identify familiar instrumental melodies was also lost. Despite these deficits, KB performed remarkably well when asked to recognise and identify familiar song melodies presented without accompanying lyrics. This dissociation between the ability to recognise/identify song vs. instrumental melodies was replicated across different sets of musical materials, including newly learned melodies. Analyses of the acoustical and musical features of song and instrumental melodies discounted an explanation of the dissociation based on these features alone. Rather, the results suggest a functional dissociation resulting from a focal brain lesion. We propose that, in the case of song melodies, there remains sufficient activation in KB's melody analysis system to coactivate an intact representation of both associative information and the lyrics in the speech lexicon, making recognition and identification possible. In the case of instrumental melodies, no such associative processes exist; thus recognition and identification do not occur.

Richter's hernia and Sir Frederick Treves: an original clinical experience, review, and historical overview.

OBJECTIVE: To describe the clinical recognition, pathology, and management of Richter's hernia and to review the relevant literature of the past 400 years. SUMMARY BACKGROUND DATA: The earliest known reported case of Richter's hernia occurred in 1598 and was described by Fabricius Hildanus. The first scientific description of this particular hernia was given by August Gottlob Richter in 1778, who presented it as "the small rupture." In 1887, Sir Frederick Treves gave an excellent overview on the topic and proposed the title "Richter's hernia." To his work-a cornerstone to modern understanding-hardly any new aspects can be added today. Since then, only occasional case reports or small series of retrospectively collected Richter's hernias have been published. METHODS: The authors draw on their experience with 18 prospectively collected cases treated in the ICRC Lopiding Hospital for War Surgery in northern Kenya between February and December 1998 and review the relevant literature of the past 400 years. RESULTS: The classic features of Richter's hernia were confirmed in all case studies of patients: only part of the circumference of the bowel is entrapped and strangulated in the hernial orifice. The involved segment may rapidly pass into gangrene, yet signs of intestinal obstruction are often absent. The death rate in the authors' collective was 17%. CONCLUSION: Richter's hernia is a deceptive entity whose high death rate can be reduced by accurate diagnosis and early surgery. Considering the increasing incidence at laparoscope insertion sites, awareness of this special type of hernia with its misleading clinical appearance is important and of general interest.

Quantitative whole-body autoradiography: recommendations for the standardization of the method.

The objective of this article is to identify the best conditions for preparing, handling, and exposing radioactive sections by using the Fujix BAS 2000 system for quantitative radioluminography. Regarding the influence of thickness of sections, thicker sections may allow shorter exposure times due to the increased radioactivity, but on the other hand they take more time for the freeze-drying process, resolution will be reduced, and the recovery of radioactivity will be lower due to increased self-absorption particularly in organs like bones or teeth. The pretreatment of the sections should depend on the method of exposure. Powdering with talcum is the most recommendable method when vacuum packaging the imaging plates and sections. Spraying with Nobecutan is recommended when using the cartridge method. Particularly for low concentrations, the vacuum-contact method should be the method of choice. To avoid a flare effect, the geometrical arrangement of the sections on the imaging plate (IP) should always be vertical to the scanning direction of the laser. An exposure time longer than 10 days is not recommended and the time between the end of exposure and start of scanning should be as short as possible. In order to reduce the background signal, it is necessary to expose the IPs in a shielding box in a cold environment. No positive chemographic effects of sections were found.

Quantification of tissue self-absorption of weak beta-radiation in lyophilized whole-body sections of rats.

Whole-body autoradiography has been widely used in the investigation of the distribution of radiolabeled compounds in animals. The newly introduced radioluminography offers a reliable way of quantifying the radioactivity distribution within whole-body sections. Since the radioactivity is distributed over the entire depth of the section, self-absorption of beta-radiation in tissues is supposed to relevantly affect the detection of radioactivity at the section surface. The self-absorption of radiation energy ((14)C) was investigated in 28 organs/tissues of routinely produced lyophilized rat sections. Nonradioactive whole-body sections with different thickness between 20 and 120 microm were placed between a homogeneous (14)C source and the imaging plates to detect the transmitted radioactivity. The self-absorption was expressed in terms of percentage of transmission of the radioactivity through the sections. Transmission decreased with increasing section thickness, e.g., from 44% (20 microm) to 28% (120 microm) for blood. Comparison of three complete sets of data disclosed intertissue variations of up to about 30% (i.e., +/-15%) disregarding bone. A defined bandwidth of +/-15% around the blood transmission would cover the transmission of almost all tissues. Thus, for most organs radioactivity can be quantified by direct comparison with radioactive blood calibration samples.

Quantitative distribution studies in animals: cross-validation of radioluminography versus liquid-scintillation measurement.

The results of a cross-validation of the radioluminography (RLG) and liquid scintillation counting (LSC) methods are presented. The methods for the determination of radioactivity concentrations were compared in 16 organs, after administration of (14)C-labeled substances to rats. LSC measurements of two kinds were used as reference methods for RLG: (1) quantitative determination of radioactivity after conventional dissection (interindividual comparison) and (2) quantitative determination of radioactivity in tissue punches taken from the whole-body sections after they had undergone RLG measurement (intraindividual comparison). Blood standards containing known concentrations were used for calibration. For statistical evaluation log-linear regression analysis of paired concentration values and organ-specific 95% confidence intervals of the log-transformed RLG/LSC concentration quotients were compared. For most organs, the slopes of the regression lines and the means of the concentration quotients were within the defined equivalence range of 0.80-1.25. Deviations were distinctly smaller in the intraindividual comparison. For some organs, however, it became clear that found concentrations were affected by self-absorption (RLG) and by differences in sample preparation (LSC). In conclusion, quantification with RLG is a reliable and reproducible method with comparable measurement precision and greater accuracy in respect of tissue localization, compared to LSC (dissection).

Posterior cerebral artery territory infarcts: clinical features, infarct topography, causes and outcome. Multicenter results and a review of the literature.

Only a few large series of posterior cerebral artery (PCA) stroke exist, and clinical features and causes have not been studied as extensively as in other vascular territories. The PCA syndrome includes more clinical signs than the well-known visual field deficits. Concomitant findings are frequently sensory, slight motor and neuropsychological deficits. Unilateral headaches are the common presenting symptom making complicated migraine an important differential diagnosis. Combined deep and superficial PCA territory infarcts involving the lateral thalamus are more frequent than commonly assumed and are mostly associated with sensory and reversible slight motor deficits. Occlusion of the precommunal PCA segment with associated paramedian midbrain infarction causes severe motor deficits, oculomotor signs, and decreased consciousness and has a poorer outcome than other PCA territory infarcts. Embolism from a cardiac or undetermined source is the leading mechanism accounting for up to half of the cases, whereas arterial embolism from significant proximal vertebrobasilar disease is less frequent. Local atherothrombotic stenosis or occlusion of the PCA is uncommon. In spite of thorough diagnostic evaluation, the etiology of PCA territory infarction cannot be determined in at least one quarter of patients. Among the rare causes of PCA territory infarction carotid artery disease is important while the significance of migraine remains controversial.

Vasoneuronal coupling in migraineurs after subcutaneous sumatriptan: a TCD study.

According to the trigeminovascular model of pain in migraine, sterile neurogenic inflammation of dural vessels stimulates nociceptive fibres of the trigeminal nerve. Sumatriptan, a 5-HT1 receptor agonist, blocks this reaction and mediates vasoconstriction of meningeal arteries. However, it is uncertain, whether sumatriptan also has a vasoconstrictive effect on cerebral arteries, which may influence vasoneuronal coupling and induce secondary cerebral blood flow changes. We studied changes of cerebral blood flow velocity (CBFV) and the pulsatility index (PI) in the posterior cerebral artery (PCA) after stimulus activation before, 10 min and 30 min after subcutaneous application of 6 mg sumatriptan, in order to assess potential vasoactive effects on cerebral circulation. CBFV was recorded from both PCAs simultaneously in 27 migraineurs (twenty women, seven men, mean age 29 years), and arterial blood pressure (BP), heart rate (HR) and respiration rate (RR) were monitored. Although the mean diastolic blood pressure rose significantly from 75 mm Hg to 81 mm Hg (P<0.05) and systolic blood pressure and respiration rates remained constant, average CBFV values remained constant. Similarly, the relative increase of CBFV by visual stimulation, which is clearly higher compared to controls in other studies (55.0% before, 52.6% after 10 min, and 52.4% after 30 min), and absolute mean values for CBFV and PI did not change after visual stimulation. These results provide evidence against the hypothesis that sumatriptan produces vasoconstriction in the intracranial human arterial circulation as a potential risk of cerebral ischemia.

Pharmacokinetics of the 8-methoxyquinolone, moxifloxacin: tissue distribution in male rats.

BAY 12-8039 (moxifloxacin-HCl) and 14C-labelled BAY 12-8039 were administered to male rats as single i.v. and oral doses of 4.6 and 5.0 mg/kg bodyweight respectively. The distribution of substance-associated radioactivity in the body was investigated by whole-body autoradiography. The concentrations of the unchanged compound in plasma, skin suction blister fluid and lung tissue were determined by HPLC. Whole-body autoradiography revealed distinctly higher concentrations of radioactivity in the gastrointestinal tract, urinary bladder and in most organs and tissues (e.g. kidneys, liver, spleen, lungs, various glands, cartilaginous tissues and in melanin-containing structures located in the eye, meninges and hair follicles of pigmented skin) than in blood. Radioactivity crossed the blood-brain barrier only to a small extent. The results show a high tissue affinity and a rapid and homogeneous distribution of radioactivity from blood to organs or tissues. No relevant difference in the distribution of radioactivity was found following i.v. and oral administration. After i.v. and oral dosing similar concentrations of the unchanged compound were determined in skin suction blister fluid and plasma. The concentrations of the unchanged compound in lung tissue were about three times higher than those in plasma following both i.v. and oral administration. The concentration-time courses for moxifloxacin in plasma and lung tissue were parallel.

Preclinical review of cerivastatin sodium--a step forward in HMG-CoA reductase inhibition.

Epidemiological studies have established that elevated concentrations of plasma cholesterol, particularly the low density lipoprotein (LDL) cholesterol, is one of the major risk factors for the development of arteriosclerosis and ischemic heart disease. Treatment with HMG-CoA reductase inhibitors (vastatins) has become the most successful drug treatment in lowering total plasma and LDL cholesterol concentrations in the last years. The vastatins already available for treatment are therapeutically used in a dose-range between 10 and 80 mg/day. The new enantiomerically pure pyridine derivative cerivastatin sodium has demonstrated its efficacy in significantly lower doses in the microgram-range, not only in preclinical but also in clinical studies with daily doses of only 0.1-0.3 mg. The differences in the therapeutic doses are reflected by the Ki- and IC50-values from enzyme inhibition tests in comparison with various HMG-CoA reductase inhibitors. Cerivastatin sodium exhibits much higher enzyme affinity with factors between 70 and almost 200. The Ki-value for cerivastatin sodium was 1.3 x 10(-9) M in comparison to 150 x 10(-9) M for lovastatin. The extremely high enzyme affinity of cerivastatin sodium was also reflected in its high activity in vivo. In acute in vivo studies cerivastatin sodium inhibited the hepatic [14C]cholesterol synthesis from [14C]acetate in both rats and dogs by 50% after oral administration at doses of 0.002 mg/kg body weight (ED50-values). This dose was comparable to 0.3 mg/kg of lovastatin. In subchronic dog studies a dose of 0.03 mg/kg lowered the serum LDL cholesterol concentration by 35% which is comparable with doses of 8-10 mg lovastatin/kg. Interesting results were observed in cholestyramine-primed dogs when 0.1 mg cerivastatin sodium/kg p.o. markedly decreased the serum triglycerides up to 70%. Cerivastatin shows a favourable pharmacokinetic profile with high liver selectivity. Rat studies have shown almost complete absorption and rapid hepatic clearance. Cerivastatin was highly bound to plasma proteins of rats, dogs and humans (>98%). Cerivastatin metabolites were excreted mainly via feces. The metabolism of cerivastatin sodium in man follows two metabolic pathways, demethylation to metabolite M1 and stereospecific hydroxylation to M23. The three major metabolites M1, M23 and the hydroxylated and demethylated metabolite M24 are highly active inhibitors not only in vitro but also in vivo. The human specific metabolites M23 and M24 inhibited the HMG-CoA reductase isolated from rat liver with the same potency as the parent compound cerivastatin sodium (IC50: 1.0-1.2 x 10(-9) M). M1 was slightly less active. Corresponding pharmacological activity was observed in vivo. M23 and M24 inhibited [14C]cholesterol synthesis from [14C]acetate in rat liver with ED50)-values between 0.001 and 0.002 mg/kg body weight which is similar to cerivastatin sodium and M1 exhibited an ED50-value of <0.006 mg/kg The strong inhibitory activity of these metabolites, in addition to cerivastatin's high enzyme affinity may explain the extraordinary pharmacological activity of cerivastatin and its ultra-low dose in man and demonstrates cerivastatin to be the most active HMG-CoA reductase inhibitor amongst all vastatins.

Alcohol-related acute axonal polyneuropathy: a differential diagnosis of Guillain-Barré syndrome.

BACKGROUND: Chronic axonal polyneuropathy is a well-known clinical sequela of excessive alcohol consumption; however, acute axonal polyneuropathy related to alcohol abuse is less well recognized. OBJECTIVE: To describe alcohol-related acute axonal polyneuropathy in 5 chronic alcoholics who developed ascending flaccid tetraparesis and areflexia within 14 days. METHODS: Case series with clinical, laboratory, electrophysiological, and, in 1 patient, biopsy data. RESULTS: All 5 patients consumed a daily average of 250 g of alcohol, and 4 had lost a substantial amount of weight recently. Additional clinical features included painful paresthesia, myalgia, and glove and stocking-type sensory loss. Repeated cerebrospinal fluid examinations failed to show the marked increase of protein concentration with normal cell count typical of Guillain-Barré syndrome, although the protein level was mildly elevated in 1 patient. Blood laboratory findings were consistent with longstanding alcohol abuse. Compound muscle and sensory nerve action potentials were absent or reduced, while conduction velocities were normal or mildly reduced. Three to 4 weeks after onset, needle electromyography displayed moderate to severe fibrillations and positive sharp waves in addition to normal motor unit potentials, indicating an acute axonal polyneuropathy; this was confirmed by sural nerve biopsy in 1 patient. CONCLUSIONS: Excluding other factors, we assume that in these patients the combination of alcohol abuse and malnutrition caused severe acute axonal polyneuropathy. Its distinction from Guillain-Barré syndrome is important because treatment requires balanced diet, vitamin supplementation, and abstinence from alcohol, while immunotherapy may not be indicated.