Guillain-Barré syndrome as differential diagnosis of intervertebral disk-induced nerve root compression

INTRODUCTION: Diagnosis of Guillian-Barré Syndrome usually is not difficult, but diagnostic failure occurs for the variable initial presentation. Diagnosis is based on physical examination showing loss of motor strength in more than one limb and loss of deep tendon reflexes. Ventilatory assistance, pharmacologic maintenance of cardiovascular homeostasis, corticosteroids, IgG and plasma exchange are the dominant therapeutic measures. CASE: This article reports on a case of a 59-year old surgeon suffering from degenerative disc disease in the lumbar spine. The patient developed a severe course of the Guillian-Barré Syndrome with persisting motor weakness of the legs. CONCLUSION: If the primary problem at presentation is limb and back pain the pathology appears to be in the musculoskeletal rather than in neurological system. The awareness of this presentation of Guillian-Barré-Syndrome will eliminate delay in diagnosis.     

Household budget survey nutritional data in relation to mortality from coronary heart disease, colorectal cancer and female breast cancer in European countries. DAFNE I and II projects of the European Commission. Data Food Networking.

OBJECTIVE: We have undertaken a study to examine whether Household Budget Survey (HBS)-derived nutritional patterns are related to mortality from diseases with strong nutritional components, namely coronary heart disease, colorectal cancer and cancer of the female breast. DESIGN: Ecological correlation study. In the context of the Data Food Networking projects of the European Union, raw data from the national HBS of 10 European countries were provided. For each of the 10 participating countries, daily food availability per capita around 1990 was calculated. Individual foods were aggregated into 12 major food groups that were linked with the diseases under consideration. Mortality data were available from a World Health Organisation database. We have used a composite score to summarise the postulated influence of diet. SETTING: Ten European countries circa 1990. RESULTS: The correlation coefficients between the composite score and the age-adjusted mortality from each of the studied diseases were: + 0.51 (P approximately 0.14) for colorectal cancer; +0.72 (P approximately 0.02) for female breast cancer; and +0.60 (P approximately 0.07) for coronary heart disease, after adjustment for tobacco smoking. CONCLUSIONS: We conclude that dietary information from HBS is sufficiently reliable to reveal correlations with mortality rates from chronic diseases with fairly strong nutritional roots. HBS data could be used, with little cost, for monitoring secular trends in dietary patterns with a view to their health implications.     

Interspecies pharmacokinetic comparisons and allometric scaling of napsagatran, a low molecular weight thrombin inhibitor

The objective of this work was to assess the pharmacokinetics of napsagatran, a low molecular weight thrombin inhibitor, after intravenous administration in a variety of laboratory animals, and prospectively to help design the first pharmacokinetic studies in man. Napsagatran is actively excreted into the bile and urine of various species and pronounced species-differences in its pharmacokinetics are observed. It is, therefore, an interesting compound to use in tests of the limitations of presently available inter-species scaling methods. The present data suggest that allometric exponent values which are consistent with the values expected for physiological processes and small organic molecules are not necessarily associated with successful predictions in man when active transport processes are involved in the disposition of the compounds. For example, compared with the values observed in man, the clearance (CL), non-renal clearance (CL(nr)) and the volume of distribution at steady state (Vd(ss)) were over-predicted by 3-, 7- and 2-fold, respectively, by use of allometry. Of the species tested, the cynomolgus monkey seemed to be the most useful for predicting kinetics in man when the approach based on concentration-time transformations was used. Thus, for half-life (t(1/2)), CL and Vd(ss), the observed mean values of 1.7 h, 459 mL min(-1) and 24 L kg(-1) in man were very close to the values predicted from the cynomolgus monkey (1.7 h, 652 mL min(-1) and 22 L kg(-1), respectively). The results show that there are large inter-species differences for kidney and liver excretion of napsagatran. This is probably because of the involvement of active transport processes, which compromised the kinetic extrapolation from animal to man, although a more thorough investigation of the transporters involved in the disposition of napsagatran is necessary to enable better understanding of the species differences observed.     

Regulation of substantia nigra pars reticulata neuronal activity by excitatory amino acids

Midbrain non-dopaminergic neurons of the substantia nigra pars reticulata play an important role in the basal ganglia circuitry. The regulation of their electrical activity by excitatory amino acid (EAA) inputs was investigated using in vivo electrophysiological methods in chloral hydrate-anaesthetized rats. We first determined the subtypes of EAA receptors present on reticulata neurons, using microiontophoretic application of selective agonists: kainic acid (KA), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), N-methyl-D-aspartic acid (NMDA), and trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD). Each agonist activated reticulata neurons and the apparent rank order of efficacy was: KA> or =AMPA=NMDA>trans-ACPD. Using pressure or iontophoretic microejections of ionotropic and metabotropic receptor antagonists, we then investigated EAA receptor subtypes involved in the spontaneous firing rate of reticulata neurons. Kynurenic acid and (+/-)-2-amino-5-phosphonopentanoic acid (AP-5) markedly decreased the spontaneous firing rate of reticulata neurons, while 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) was much less effective. The metabotropic receptor antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) failed to affect the spontaneous electrical activity. In contrast to CNQX, microapplications of AP-5 sometimes produced total inhibition. This powerful effect may reflect the potential importance of NMDA receptors in regulating the activity of some reticulata neurons. These results indicate that both functional ionotropic (NMDA and non-NMDA) and metabotropic EAA receptors are present on non-dopaminergic substantia nigra pars reticulata neurons. Moreover, in the anaesthetized animal, the spontaneous firing rate of these neurons, mediated by EAA inputs, seems mainly due to the tonic activation of ionotropic, but not metabotropic, receptors.     

Multiple-dose pharmacokinetics, safety, and tolerability of bosentan, an endothelin receptor antagonist, in healthy male volunteers.

The multiple-dose pharmacokinetics, safety, and tolerability of oral bosentan, a selective endothelin receptor antagonist, were investigated in healthy male volunteers. In study A, an ascending-dose, double-blind, placebo-controlled trial, doses of 100, 200, 500, and 1000 mg bosentan or placebo were given once daily for 8 days as tablets (100 and 500 mg dose strength). In study B, a double-blind, placebo-controlled trial, 500 mg tablets of bosentan or placebo tablets were given once daily for 8 days with two additional single intravenous dose administrations of 250 mg bosentan 48 hours before the first and 24 hours after the last oral dose. The drug was very well tolerated. No effects on pulse rate, ECGs, or clinical laboratory tests were observed. Marginal effects on blood pressure were seen in subjects only when standing. The oral bioavailability of bosentan was 43% to 48%, with a small interindividual variability of 20%. Doses above 500 mg did not lead to significant further increases in plasma levels of bosentan. From the first to the last day of the oral treatment phase, plasma concentrations of bosentan decreased by 30% to 40% due to a 2-fold increase in plasma clearance. Absorption and plasma protein binding did not change. The 24-hour urinary excretion of 6 beta-hydroxycortisol was increased in parallel by approximately 1.7-fold, indicating induction of cytochrome P450 3A isozymes. The two metabolites of bosentan reached plasma concentrations well below those of bosentan and will most likely not contribute to the pharmacological activity.     

Contribution of patient and hospital characteristics to adverse patient incidents.

The 1974 medical malpractice "crisis" brought about extensive legislation and insurance regulation in the United States. Hospitals in many states are now required to support risk management programs that include investigation and systematic analyses of adverse patient incidents. However, no research supports the hypothesis that systematic analysis of adverse patient incidents can identify contributory factors. In this study, a simple prediction model was used to estimate relationships between adverse incidents and selected patient and environmental characteristics in a large hospital. While some of the incident-characteristic relationships were significant, none of the estimated equations yielded results that could be logically translated into policy recommendations for the hospital. These results point to the need for further research. The benefits that positive research results would have for patients, hospitals, an the bill-paying public are obvious. Additional negative results would suggest that many legislative bodies and regulatory agencies were presumptions in requiring hospitals to conduct analyses of incidents.     

Differential typology among patients with hard and soft suicide methods

Two samples of patients admitted during one year after suicide attempts were compared: patients of the University Surgical Department in Heidelberg and a random sample of those who were admitted to the detoxication ward of the University Department for Internal Medicine. The frequency of patients who used "hard" methods was 10% of those using "soft" methods. Patients with hard suicide methods displayed more social desintegration, were more often psychiatrically ill, had a shorter presuicidal phase, a shorter time span from decision to execution of the suicidal attempt, more negative self-esteem and more chronic suicidality. Aggressiveness was low in both groups. Although the number of patients with "hard" suicidal methods is small and does not justify a special service in the Surgical Hospital, these patients need particularly careful supervision because of their psychopathological and psychosocial profile.     

Contaminated sediments from tributaries of the Great Lakes: Chemical characterization and carcinogenic effects in medaka (Oryzias latipes)

Sediments from four inshore industrial sites and a reference site in the Great Lakes were extracted with organic solvents to produce a crude extract, which was separated on alumina into two fractions: predominantly polycyclic aromatic hydrocarbons; and predominantly nitrogencontaining polycyclic aromatic compounds. Crude extracts were redissolved in acetone and analyzed by gas chromatography and gas chromatography-mass spectrometry. The acetone-redissolved crude extracts from the four industrialized sites contained 5.6–313.3 g total polycyclic aromatic compounds/g sediment and 3.0–36.4 g other compounds/g sediment. In addition to the typical EPA priority pollutants, a substantial amount (228.7 g/g sediment) of alkyl-polycyclic-aromatic compounds was detected in sediments from one of the industrialized sites. Extracts from the reference site contained 1.55 g total polycyclic aromatic compounds/ g sediment. Medaka (Oryzias latipes) were exposed to multiple pulse doses of acetone-redissolved extracts and fractions. Medaka were also exposed to a known carcinogen, methylazoxymethanol acetate, to verify that chemicals produced tumors in the test fish. Acetone-redissolved extracts and fractions from contaminated sediments were toxic to medaka. Fin erosion and non-neoplastic liver abnormalities were more prevalent in medaka after exposure to acetoneredissolved extracts and fractions from contaminated sediments. Neoplasms previously associated with chemical exposure in wild fishes were induced in medaka exposed to acetone-redissolved extracts and fractions from two of the contaminated sites, but not from the reference site or controls. These findings further support the hypothesis that chemical contaminants in sediments are involved in epizootics of neoplasms in wild fishes at contaminated sites.