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Harmonic MR elastography (MRE) monitors the propagation of acoustic waves in tissues in the audio regime. Oscillatory motions with large amplitudes can induce nonlinear wave propagation effects resulting in harmonics that evolve over space. In order to understand these effects, knowledge of the motions of applied mechanical motion is needed to rule out the presence of harmonic motion arising from the mechanical source. We propose a simple technique to measure the spectral content of mechanical excitation based on the use of a set of detection coils mounted on the elastography excitation system. The motion of these coils causes a small signal to be induced from the applied static magnetic field of the MRI system. A detailed analysis shows that quantitative assessment of excitations is possible with correct geometrical arrangement of the detector coils. However, it shows that nonlinear effects can also occur depending on the alignment of the detection coils with respect to Bo. The system is easy to operate and allows for the time resolved observation of the actuator motion for each experimental setup. The system is intended to be used before and after MRE experiments to determine excitation spectral content and repeatability. We demonstrate its use in a one-dimensional elastography experiment and show that this information is an essential prerequisite for studying material nonlinear elastic properties using MRE. © 2004 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 21B: 32–39, 2004

Magnetic dipolar couplings between the ¹⁵N atom (labeled) and neighboring ¹³C atoms (natural abundance) in three solid modifications of N-octyl-d-gluconamide are measured with rotational echo double resonance (REDOR). A unique spectral assignment of ¹³C resonances is possible by means of their dipolar dephasing. While in the monolayer crystal and in the fiber modification the assignment is amenable to the solution spectra, in the bilayer crystallites a different assignment is found. The dipolar couplings in the range 45 to 1220 Hz are converted into CN distances. These distances are employed in conjunction with the ¹³C chemical shieldings of the CP-MAS spectra to determine sets of possible torsion angles, which define the molecular conformation in the neighborhood of the amide group. In contrast to the monolayer crystal, for the fiber and bilayer crystallite modifications a gauche bend at the C2–C3 bond is found, giving the molecules the shape of a ₂G sickle.

The application of short composite pulse schemes ([figure] and [figure]) to the rotational echo double-resonance (REDOR) spectroscopy ofX–2H (X: spin12, observed) systems with large deuterium quadrupolar interactions has been studied experimentally and theoretically and compared with simple 180° pulse schemes. The basic properties of the composite pulses on the deuterium nuclei have been elucidated, using average Hamiltonian theory, and exact simulations of the experiments have been achieved by stepwise integration of the equation of motion of the density matrix. REDOR experiments were performed on15N–2H in doubly labeled acetanilide and on13C–2H in singly2H-labeled acetanilide. The most efficient REDOR dephasing was observed when [figure] composite pulses were used. It is found that the dephasing due to simple 180° deuterium pulses is about a factor of 2 less efficient than the dephasing due to the composite pulse sequences and thus the range of couplings observable byX–2H REDOR is enlarged toward weaker couplings, i.e., larger distances. From these experiments the2H–15N dipolar coupling between the amino deuteron and the amino nitrogen and the2H–13C dipolar couplings between the amino deuteron and the α and β carbons have been elucidated and the corresponding distances have been determined. The distance data from REDOR are in good agreement with data from X-ray and neutron diffraction, showing the power of the method.

It was recently shown by others that the clearance of midazolam/kg body weight after iv administration correlates with hepatic cytochrome P450 (CYP or P450) 3A content in liver transplant patients. However, after po administration midazolam undergoes significant first-pass metabolism, with significant intestinal extraction. The relationship between hepatic CYP3A and midazolam disposition after po administration had not previously been investigated. The aim of this study was to compare intraindividually hepatic CYP3A content and activity with the in vivopharmacokinetics of midazolam (7.5 mg) administered po. For 15 patients scheduled for partial liver resection, the AUC values for the observed time period (AUC0–5hr) and to infinity (AUCinf) and the clearance were determined. In a macroscopically normal area of resected liver tissue, the microsomal CYP3A4 content (nanomoles per nanomole of total P450) was measured by immunoblot analysis and parameters (apparent Vmax, apparent KM, and intrinsic clearance) for the microsomal α-hydroxylation of midazolam were determined. Clearance/kg in vivocorrelated with the apparent Vmax(r2= 0.45, p< 0.01) and the CYP3A4 content (r2= 0.29, p< 0.05). We conclude that interindividual variability in the pharmacokinetics of po administered midazolam is in part determined by interindividual variability in the hepatic microsomal Vmaxfor the α-hydroxylation of midazolam. However, the relationship between the disposition of midazolam administered po and hepatic CYP3A content is weaker than that reported after iv administration, indicating the importance of the contribution of intestinal CYP3A to the in vivodisposition of midazolam administered po.

Allopurinol is converted almost completely into a single active metabolite, oxipurinol, which has the same therapeutic pattern but a much longer elimination half-life than the parent compound. Therefore both allopurinol and oxipurinol were evaluated in our bioequivalence study in healthy volunteers comparing two allopurinol brands. Bioequivalence determination was based on the 90% confidence intervals (CI) of the area under the plasma concentration time curve from time zero to infinity (AUC0-8), of the area from time zero to the last measurable plasma concentration (AUC0-t (last)), and Cmax. Because of the lack of compound-specific criteria we used conventional limits for the bioequivalence range. Under these conditions the brand chosen as test preparation was judged to be bioequivalent to the reference form with respect to the extent of bioavailability, AUC0-8, and AUC0-(last) of the parent drug. The CI of Cmax of allopurinol slightly exceeded the upper limit of 130%, so that bioequivalence was not confirmed with regard to the rate of bioavailability of the parent compound. The CI values of both AUC and Cmax of the active metabolite were tighter than those of allopurinol. In addition, the CI values of Cmax of oxipurinol were smaller than those of the corresponding AUC. As a consequence the test drug can clearly be accepted as bioequivalent, based on metabolite data. Since the active metabolite is of greater therapeutic significance than the parent drug, assessment of the bioequivalence of allopurinol preparations needs to be based on oxipurinol rather than allopurinol. Our data provide further evidence that establishing compound-specific criteria is required for bioequivalence evaluation in drugs with a single active metabolite.

To determine the elimination phenotype of the uricosuric agent benzbromarone 100 mg of the drug was administered as a single oral dose to 11 volunteers on a formula diet; plasma concentration-time profiles of the parent drug and the main metabolites M1 (1'-hydroxybenzbromarone) and M2 (6-hydroxy-benzbromarone) were measured by high-performance liquid chromatography for 168 h. Of the 11 subjects 2 showed higher plasma concentrations and delayed elimination of benzbromarone and metabolite M1 but reduced formation of metabolite M2 compared to the other 9 subjects. However, the plasma concentration-time profiles of the metabolites in these two slow eliminators, termed type 2, differed from those of a poor eliminator characterized during a previous study; the latter, termed type 1, eliminated benzbromarone as well as both metabolites M1 and M2 slowly. The differences in the elimination of benzbromarone and its metabolites are probably caused by differences in the activities of the cytochrome P450 mono-oxygenase isozymes. The results show that determination of the phenotype solely by measurement of the 24-h benzbromarone plasma concentration does not unequivocally characterize slow benzbromarone eliminators; additional plasma concentration-time profiles of the parent drug and metabolites are necessary. Metabolite M2 is characterized as 6-hydroxybenzbromarone; the formation and elimination of the chiral metabolite M1 is enantioselective.

In this paper a simple phenomenological description of the effects of coherent quantum and incoherent mutual exchange of two deuteron nuclei in solid state transition metal complexes on their ²H NMR spectra is given. This description is based on the quantum-mechanical density matrix formalism developed by Alexander and Binsch. Only the nuclear spin system is treated quantum mechanically. The quantum exchange interaction in NMR is included in the nuclear spin Hamiltonian, and the interaction with the surrounding bath and incoherent exchange processes are treated as phenomenological rate processes described by rate constants. The incoherent exchange corresponds formally to 180° rotations or jumps of the D−D vector around an axis perpendicular to this vector and averages the different quadrupole splitting of the two deuterons. In principle the dideuteron pair will exist in several rovibrational states. However, if the interconversion among these states is fast, the dideuteron exchange can be described by an average exchange coupling or tunnel frequency X12 and a single average rate constant k12 of the incoherent exchange. It is shown that the incoherent exchange gives rise to a relaxation of rate −2k12 between coherences created between states of different symmetry. The ²H NMR line shape of a dideuteron pair in the solid state as a function of tunnel and incoherent exchange rate is studied numerically. For single crystals, the effects of coherent and incoherent exchange are strongly different, in particular if the rate constants are on the order of the quadrupole splitting. The spectra of nonoriented powder samples are more similar to each other. Nevertheless, our calculations show that there are still pronounced differences, which should allow the distinction between coherent and incoherent exchange even in nonoriented samples.

The influence of the disaccharidase inhibitor acarbose on carbohydrate tolerance was investigated in healthy subjects during substitution of fibre-free formula diets for normal food. Two separate experiments showed that acarbose was highly efficient in retarding and diminishing the postprandial rise in blood glucose and serum insulin when administered with these diets for 10 to 14 days. Acarbose decreased the area under the postprandial curves of blood glucose from 1.836 to -504 mg/dl×min in Study 1, and from 587 to -302 mg/dl×min in Study 2. The area under the serum insulin curves was reduced from 5.022 to 1.440 µU/ml×min in Study 1, and from 7.990 to 918 µU/ml×min in Study 2. In addition, acarbose greatly diminished the interindividual variation in postprandial serum insulin concentration. Its efficacy in reducing the glycaemic response to a test meal in both experiments was found to depend on the time of initiation of therapy; in contrast, the serum insulin response was only time-dependent in Study 2. Use of fibre-free diets to standardise experimental conditions proved to be a valuable tool in investigating these details.

Rudi J. Raedsch R, Gerteis C. Schlenker T, Plachky J. Walter-Sack I, Sabouraud A, Scherrmann JM, Kommerell B. Plasma kinetics and biliary excretion of colchicine in patients with chronic liver disease after oral administration of a single dose and after long-term treatment. Scand J Gastroenterol 1994; 29:346-351.Plasma kinetics and biliary excretion of colchicine in patients with chronic liver disease were evaluated after oral administration of a single dose and after long-term treatment. A single oral dose of 1 mg colchicine led to a mean peak concentration of 3.60 ± 1.04 ng/ml at a peak time of 2.16 ± 0.34 h and a mean area under the plasma concentration time curve, extrapolated from time 0 to infinity, of 24.90 ± 8.47 ng h/ml. Comparable values were obtained after repeated administration. Distribution half-life was 2.83 ± 0.74 h, and terminal plasma elimination half-life was 9.81 ± 2.08 h; the mean apparent volume of distribution and the mean apparent plasma clearance were 1448 ± 4061 and 175.3 ± 47.61/h. respectively. Colchicine concentrations in bile (2025 ± 1368 ng/ml) were clearly higher than in plasma. Long-term treatment with colchicine (1 mg/day) in patients with various stages of primary biliary cirrhosis (PBC) was associated with colchicine concentrations varying from <0.15 to 2.0 ng/ml, with a slight tendency to higher concentrations in PBC stages III-IV than I-II. Although about 20% of colchicine is excreted in bile within 24 h, accumulation of colchicine may appear only in patients with advanced liver disease and cholestasis.

We have investigated the disposition and plasma uric acid lowering effect of oxipurinol in ten healthy individuals following oral administration of three different formulations of oxipurinol and of allopurinol in equimolar doses. The reduction of plasma uric acid was clearcut up to 48 h. As estimated from plasma AUC0-8, Cmax, tmax, tlag, and urinary drug excretion, a conventional rapid release preparation of oxipurinol sodium was clearly superior to oxipurinol as free acid and to enteric coated microtablets of oxipurinol sodium. Plasma oxipurinol concentrations following a single dose of the conventional formulation of oxipurinol sodium were approximately 25% lower than those observed after an equimolar dose (300 mg) of allopurinol, but mean Cmax reached the value reported to be necessary for 90% inhibition of xanthine oxidase. Since prolonged administration will result in accumulation of oxipurinol because of its slow elimination, this type of oxipurinol formulation can be expected to meet the therapeutic requirements for a drug to lower plasma uric acid.

Following oral administration of the uricosuric drug benzbromarone two major metabolites appear in the circulation, 1'-hydroxy-benzbromarone (M1), and a second product (M2) of unknown structure. The plasma concentrations of the parent drug and of M1 and M2 have now been compared in two different elimination phenotypes, 10 subjects who eliminated the drug rapidly (S1–10) and one individual (S11) whose elimination capacity was impaired, presumably due to genetic variation (S11). The AUC (0–96) of the parent drug in S11 was 145 gmg · ml-1 h, and in the other individuals it averaged 18.3 (11.4–24.5) µg · ml-1 h. The plasma elimination half life of benzbromarone was 3.34 (1.77–5.24) h in the rapid eliminators, and 13.08 h in the subject with the elimination defect. The mean plasma elimination half life of the metabolites in S1–10 amounted to 20.1 (11.9–41.2) h for M1, and 17.2 (12.9–30.7) h for M2. In S11 the plasma elimination half life of M1 was prolonged to 76.6 h, and of M2 to 75.4 h. Thus, the elimination defect in S11 was not restricted to the parent drug, but it also involved the two major metabolites M1 and M2. This might be a consequence of a hepatic enzyme deficiency, or be due to impairment of drug excretion.

The plasma benzbromarone concentration-time profile in a healthy subject who retained the compound much longer than other individuals is described. The data suggested that determination of the 24 h plasma concentration of the parent drug after a single oral dose of 100 mg benzbromarone would be an appropriate procedure to determine the elimination phenotype. Based on this procedure, 148 of 153 healthy individuals (97%) in a population study were found to eliminate benzbromarone rapidly. In one subject the 24 h benzbromarone plasma concentration was very similar to the that observed in the individual who had been more fully characterized. Four participants gave intermediate results. The data are compatible with a bimodal or trimodal distribution of different benzbromarone elimination phenotypes.

Severely ill patients often require total parenteral nutrition including intravenous liqid emulsions concurrently administered with lipophilic drugs. Therefore we investigated whether therapeutic application of a mixed medium chain/long chain triglyceride infusion affects the disposition of midazolam necessary for sedation in patients on artificial respiration. The concentrations of midazolam were measured in unfractionated plasma, and in lipoprotein fractions isolated from ex vivo blood samples, including determination of triglycerides and cholesterol; the albumin level was also analysed.

To evaluate phenprocoumon elimination its possible biliary excretion was evaluated in addition to the known pathway of renal elimination.

Summary Benzbromarone is one of the main uricosuric drugs currently used. We determined plasma concentrations of benzbromarone, bromobenzarone, and benzarone and 24 hour uric acid excretion in ten healthy individuals following fasting application of two different non-micronised benzbromarone brands. In addition we explored the influence of adjusting urinary pH to near neutral values and of concomitant food intake. Benzbromarone was more rapidly absorbed from the test preparation than from the reference preparation; the extent of systemic availability did not differ significantly. Urinary pH adjustment had no clearcut effect, whereas food intake retarded drug absorption (even though not significant because of the variability of the data). Binding of benzbromarone to plasma proteins exceeded 99%. Bromobenzarone and benzarone were not detectable and are unlikely to be major metabolites of benzbromarone. Instead we found two other compounds suggestive of metabolites, one of them being monohydroxilated benzbromarone. The plasma concentrations of the parent compound in one subject exceeded those of the rest of the group, possibly indicating genetic differences in drug metabolism. The uricosuric effect was not related to benzbromarone plasma concentrations.

Summary Diarrhea represents the most frequent health problem of Western tourists visiting subtropical and tropical areas. Antibiotic prophylaxis has been suggested by some authors but may not be generally advisable because of adverse drug effects. In the present study we investigated the prophylaxis of traveler's diarrhea using a combination of tannalbuminate and ethacridin-lactate. During a 16-day cruise in Egypt, 77 tourists were assigned to either placebo or prophylactic doses of tannalbuminate (500 mg) and ethacridin-lactate (50 mg), 1 tbl. b.i.d., in a randomized double-blind fashion. The number of bowel movements, consistency of stools, and clinical symptoms like nausea, abdominal cramps, vomiting, and fever were monitored daily. In the placebo group (n=43) 35 tourists developed diarrhea (81.4%), whereas in the verum group (n=34) only 18 tourists (52.9%) had diarrhea (p<0.0125). In the travelers receiving verum and developing diarrhea the clinical symptoms were less pronounced than in the placebo group. These results demonstrate that the events of traveler's diarrhea may be reduced; moreover, symptoms are attenuated by medical prophylaxis with tannalbuminate and ethacridin-lactate.

Summary This study concerns the incidence of side effects occurring in connection with the prescription of co-trimoxazole which, according to the observations of medical practitioners, were suspected of being drug related. It is based on reports from 260 doctors in the Nordbaden/Rheinlandpfalz area between 1981 and 1984, as well as on those from hospital doctors concerning 33,300 in-patients at the Department of Internal Medicine at the University Hospital of Heidelberg from 1980 to 1983. General practitioners' reports: Of 3,739 side effects reported over a three and a half year period, 180 were related to drugs containing co-trimoxazole. Side effects were 3.3 times as frequent with the “forte” dosage as compared to the 80 mg trimethoprim/400 mg sulfamethoxazole preparation. The most frequently cited unwanted reactions concerned the skin (n=63, of which two were Quincke oedema and three were urticarious reactions) and the gastrointestinal tract (n=52), as well as disturbance of well being (n=30). Gastro-intestinal disturbances appeared to occur more frequently after a higher than after a lower dosage. Clinicians' reports: During the period of observation an average of 12.6% of all in-patients were treated with drugs containing co-trimoxazole. The total number of cases of side effects due to this drug amounted to 255. Serious reactions included: two anaphylactic reactions; two thrombocytopenias below 80,000/mm3; and two cases of Lyell's syndrome (one of which could not be confirmed beyond all doubt). Side effects occurred more often after i.v. than after oral application. Whilst nausea and vomiting were more frequent after oral treatment, diarrhoea occurred to a large extent after i.v. administration. In-patients for whom co-trimoxazole was prescribed suffered on average 3.8% of side effects following treatment with the most frequently prescribed co-trimoxazole preparation. This corresponds to the figures given in the existing literature. These figures cover approximately 170,000 patient years for the general population within the survey (prescription of co-trimoxazole not known) and 1,200 patient years for the in-patients (12% of whom received treatment with co-trimoxazole). No incidence of death caused by co-trimoxazole was reported.

The structure of the amide bonds of gluconamide has been elucidated and compared to acetanilide by the combined application of ¹³C and ¹⁵N double- and triple-resonance solid-state NMR spectroscopy. The length of the amide bond has been determined from the dipolar spectrum using a SEDOR type experiment, and the orientation of the principal axis systems of both the ¹³C and ¹⁵N chemical shift tensors have been determined by employing dipolar chemical shift NMR spectroscopy in conjunction with CSA spectroscopy. The groups exhibit for amide bonds typical approximately 120° bond angles between −CO, −CN, −CR, and −NC, −NH, −NR. Comparing the structure of the gluconamide with the corresponding structure of the acetanilide, two major differences are visible:  the orientations of the CSA tensors in the amide plane with respect to the CN-bond direction are different (12° for the ¹³C tensor and 10° for the ¹⁵N tensor), and the directions of least shielding and intermediate shielding are interchanged in the gluconamide as compared to the acetanilide. Since the chemical shielding tensors of the ¹⁵N are strongly influenced by hydrogen bonding, these different orientations are an indication of the different hydrogen bond structure of the gluconamide as compared to the acetanilide.

The primary objective of treatment in women with severe hypertension and pre-eclampsia is to prevent complications such as encephalopathy and haemorrhage. In many countries dihydralazine is considered the drug of choice for treating hypertension in pregnancy, because it now has been used safely for about 30 years, and the introduction of a new drug in pregnancy is a difficult task with partially unknown hazards. In some other countries combined alpha- and beta-blockers are also used. Taking into account that some patients with pre-eclampsia do not respond to dihydralazine and the drug has serious side-effects like headache and reflex tachycardia, there is some need for developing alternative treatment strategies using drugs that are more adequate for pregnancy than dihydralazine.

The interaction of allopurinol (300 mg/day) and hydrochlorothiazide (50 mg/day) was studied in seven healthy male volunteers during prolonged coadministration of the two drugs using defined dietary conditions. A formula diet was administered with the allopurinol throughout the 24-day study, while hydrochlorothiazide was added during days 11–21. After the addition of hydrochlorothiazide both plasma uric acid and plasma oxipurinol rose for 6 days – 24% and 30%, respectively, compared to steady-state levels during allopurinol alone (P < 0.01 each). In neither substance were variations in renal excretion significant. By the end of combined treatment (day 21), the changes induced by hydrochlorothiazide had already been reversed to a considerable extent. It is concluded that both in normal individuals and in patients with normal renal clearance of uric acid the effect of hydrochlorothiazide on the plasma concentration and renal excretion of oxipurinol is small. When taking both drugs, there is no increased risk during long-term treatment, and a risk is even questionable during the first days.

The kinetics of allopurinol and hydrochlorothiazide were investigated in seven healthy male subjects during prolonged coadministration of two drugs. Subjects were maintained on an isoenergetic, purine-free formula diet with RNA supplementation for 24 days. Allopurinol (300 mg) was given orally on days 1–24. Hydrochlorothiazide (50 mg daily) was added to days 11–21. On day 43 a single oral dose of 50 mg hydrochlorothiazide was administered. Plasma concentration-time profiles of allopurinol and its main metabolite oxipurinol were obtained on days 1, 10, and 21; hydrochlorothiazide profiles were assessed on days 21 and 43. In addition, 24-h plasma concentrations of oxipurinol were measured repetitively, and 24 h urine samples were collected for the determination of allopurinol, oxipurinol, and hydrochlorothiazide. For oxipurinol, meanCmax was not altered on hydrochlorothiazide treatment (13.8 ± 1.4 µg/ ml and 14.7 ± 2.6 µg/ml, respectively); mean AUC0–24 was 259 and 290 µg h-1 ml-1, respectively. The small difference in AUC0–24 values does not explain the increase in plasma uric acid concentration during hydrochlorothiazide treatment, nor do the variations in allopurinol and hydrochlorothiazide kinetics.

Über die Auswirkungen einer medikamentösen Langzeittherapie auf eine Vielzahl von Parametern — gemessen bei großen Patienten-Kolletiven unter standar disierten Bedingungen und im Vergleich zu Kontrollen — wissen wir immer noch wenig. Dies gilt besonders für Deutschland, aber auch international. Häufig werden nur bestimmte Zielgrößen aus der Palette der möglichen Analysen herausgegriffen. Aus diesem Grund bleibt die Vergleichbarkeit der betrachteten Kohorten ungewiß, so daß die Bewertung von Veränderungen vereinzelter Parameter schwerfällt. Jede Bemühung, die bekanntgewordenen Detailbefunde durch systematische Untersuchungen zu erhärten und erklärbar zu machen, ist deshalb zu begrüßen. Dies gilt um so mehr, als solche breit angelegten Untersuchungen auch Aussagen darüber zulassen, welche klinisch-chemischen Parameter und auch körperlichen Befunde unter Langzeittherapie einer laufenden Kontrolle bedürfen. Dies ist ein wichtiger Beitrag zur Sicherheit der Behandlung mit Arzneimitteln. Eine effiziente und risikoarme Pharmakotherapie ist nicht zuletzt auch unter ökonomischen Gesichtspunkten optimal.

Summary Fiber-free formula diets are widely used for medical and experimental purposes. In healthy individuals no major changes of fasting blood glucose have been reported, whereas oral glucose tolerance tests indicate a deterioration of carbohydrate tolerance following ingestion of liquid diets containing certain sugars. We examined carbohydrate tolerance in normal subjects during prolonged administration of a fiber-free semisolid diet containing polysaccharides instead of sugars. In the first experiment, diet A (55% starch, 40% highly polyunsaturated fat, P/S 5.4, 15% protein) served as the sole source of energy for 4 weeks. During this time a progressive deterioration of carbohydrate tolerance was observed, indicated by a gradual increase of the postprandial glycemic response (area under the curve) from -316 to +3874 mg/dl × min without significant alteration of postprandial serum insulin concentrations. For the second study, nutrient relations of the diet were modified (diet B: 45% starch, 40% saturated fat, P/S 0.3, 15% protein). The changes of carbohydrate tolerance during 1 week of feeding diet B were similar to those seen in the first experiment. However, follow-up observations during a subsequent pharmacological trial showed that the changes of postprandial blood glucose curves were reversed within 2 weeks. This was associated with an enhanced serum insulin response. The reason for the different durations of the metabolic effects of diets A and B are not obvious from our data. The time course may have been influenced by the different nutrient intake. Fasting blood glucose concentrations were not sensitive enough to detect the deterioration of carbohydrate tolerance.

Two patients with acute disseminated encephalomyelitis after repeated injection of extracts from several different plants are described. There was no evidence of prior infection or vaccination. Both patients recovered rapidly after treatment with methylprednisolone. Acute disseminated encephalomyelitis should be considered a rare complication of parenteral therapy with herbal extracts.