Showing papers by "University of Bonn published in 1992"

Laufband locomotion with body weight support improved walking in persons with severe spinal cord injuries

Abstract: After low transection of the spinal cord mammalian quadrupeds can be trained to walk on a driven surface indicating that coordinating neuronal circuits persist in the spinal cord segments caudal to the lesion. We trained 8 persons with incomplete spinal cord lesion on a Laufband (driven treadmill) for 1 1/2 to 7 months (5 days a week, 30-60 minutes daily) starting 5 to 20 months after injury and found significant improvement in the utilisation of the paralysed limbs during locomotion. Locomotion is described in one additional patient who had trained independently on parallel bars for several years. Five patients had complete functional paralysis in one lower limb when tested in a resting position. In EMG recordings voluntary activity (ie activity induced upon command) was absent or residual in the main flexor and extensor muscles of this limb. In contrast, during locomotion flexion and extension movements were performed and phasic EMG activity was present. In these 5 patients, and in all others reported here, skin sensibility and proprioception are preserved to different degrees in all limbs. In the course of locomotive training of 4 severely paralysed patients the initially habituating flexion reflexes could be entrained in the paralysed limbs as was the case for knee extension during stance. Subsequently, initial body weight support (BWS) of 40% could be reduced to 0%. The distance covered on the Laufband (0-104 m in the first week) increased significantly (200-410 m) in the last week of training as did speed (0-10 to 14-23 m/min). More importantly, this training subsequently allowed patients to walk on a static surface for 100 to 200 meters while voluntary activity remained absent in the paralysed limb when tested at rest. Similar progress was achieved in the 4 less severely paralysed patients. The one patient who had trained independently on parallel bars for several years is described walking on a static surface for 40 meters with the help of a walker, though he had one completely and one near completely paralysed lower limb. It appears that bipedal stepping with consequent knee extension and stabilisation can be taught after unilateral complete or near complete loss of voluntary activity, suggesting the manifestation of complex reflex motor patterns at the spinal level.

Crustacean neuropeptides: structures, functions and comparative aspects.

Abstract: In this article, an attempt is made to review the presently known, completely identified crustacean neuropeptides with regard to structure, function and distribution. Probably the most important progress has been made in the elucidation of a novel family of large peptides from the X-organ-sinus gland system which includes crustacean hyperglycemic hormone (CHH), putative molt-inhibiting hormone (MIH) and vitellogenesis (=gonad)-inhibiting hormone (VIH). These peptides have so far only been found in crustaceans. Renewed interest in the neurohemal pericardial organs has led to the identification of a number of cardioactive/myotropic neuropeptides, some of them. unique to crustaceans. Important contributions have been made by immunocytochemical mapping of peptidergic neurons in the nervous system, which has provided evidence for a multiple role of several neuropeptides as neurohormones on the one hand and as local transmitters or modulators on the other. This has been corroborated by physiological studies. The long-known chromatophore-regulating hormones, red pigment concentrating hormone (RPCH) and pigment-dispending hormone (PDH), have been placed in a broader perspective by the demonstration of an additional role as local neuromodulators. The scope of crustacean neuropeptide research has thus been broadened considerably during the last years.

Enzyme stabilization be ectoine-type compatible solutes: protection against heating, freezing and drying

Abstract: The aim of this study was to elucidate the protective effect of the new compatible solutes, ectoine and hydroxyectoine, on two sensitive enzymes (lactic dehydrogenase, phosphofructokinase). The solutes tested also included (for reasons of comparison) other compatible solutes such as glycine betaine and a number of disaccharides (sucrose, trehalose, maltose). All compatible solutes under investigation displayed remarkable stabilizing capabilities. However, the degree of protection depended on both the type of solute chosen and the enzyme used as a test system. The most prominent protectants were trehalose, ectoine and hydroxyectoine, which are very often found in nature (singly or in combinationn) as part of the compatible solute “cocktail” of moderately halophilic eubacteria.

Non-ideal mixing in the phlogopite-annite binary: constraints from experimental data on Mg−Fe partitioning and a reformulation of the biotite-garnet geothermometer

Abstract: The existing experimental data [Ferry and Spear 1978; Perchuk and Lavrent'eva 1983] on Mg−Fe partitioning between garnet and biotite are disparate. The underlying assumption of ideal Mg−Fe exchange between the minerals has been examined on the basis of recently available thermochemical data. Using the updated mixing parameters for the pyrope-almandine asymmetric regular solution as inputs [Ganguly and Saxena 1984; Hackler and Wood 1984], thermodynamic analysis points to non-ideal mixing in the phlogopite-annite binary in the temperature range of 550°C–950°C. The non-ideality can be approximated by a temperature-independent, one constant Margules parameter. The retrieved values for enthalpy of mixing for Mg−Fe biotites and the standard state enthalpy and entropy changes of the exchange reaction were combined with existing thermochemical data on grossular-pyrope and grossular-almandine binaries to obtain geothermometric expressions for Mg−Fe fractionation between biotite and garnet. [T in K] $$\begin{gathered} {\text{T(HW) = [20286 + 0}}{\text{.0193P - \{ 2080(X}}_{{\text{Mg}}}^{{\text{Gt}}} {\text{)}}^{\text{2}} {\text{ - 6350(X}}_{{\text{Fe}}}^{{\text{Gt}}} {\text{)}}^{\text{2}} \hfill \\ {\text{ - 13807(X}}_{{\text{Ca}}}^{{\text{Gt}}} {\text{)(1 - X}}_{{\text{Mn}}}^{{\text{Gt}}} {\text{) + 8540(X}}_{{\text{Fe}}}^{{\text{Gt}}} {\text{)(X}}_{{\text{Mg}}}^{{\text{Gt}}} {\text{)(1 - X}}_{{\text{Mn}}}^{{\text{Gt}}} {\text{)}} \hfill \\ {\text{ + 4215(X}}_{{\text{Ca}}}^{{\text{Gt}}} {\text{)(X}}_{{\text{Mg}}}^{{\text{Gt}}} {\text{ - X}}_{{\text{Fe}}}^{{\text{Gt}}} {\text{)\} + 4441}}{{{\text{(2X}}_{{\text{Mg}}}^{{\text{Bt}}} {\text{ - 1)]}}} \mathord{\left/ {\vphantom {{{\text{(2X}}_{{\text{Mg}}}^{{\text{Bt}}} {\text{ - 1)]}}} {{\text{[13}}{\text{.138}}}}} \right. \kern- ulldelimiterspace} {{\text{[13}}{\text{.138}}}} \hfill \\ {\text{ + 8}}{\text{.3143 InK}}_{\text{D}} {\text{ + 6}}{\text{.276(X}}_{{\text{Ca}}}^{{\text{Gt}}} ){\text{(1 - X}}_{{\text{Mn}}}^{{\text{Gt}}} )] \hfill \\ {\text{T(GS) = [13538 + 0}}{\text{.0193P - \{ 837(X}}_{{\text{Mg}}}^{{\text{Gt}}} )^{\text{2}} {\text{ - 10460(X}}_{{\text{Fe}}}^{{\text{Gt}}} )^2 \hfill \\ {\text{ - 13807(X}}_{{\text{Ca}}}^{{\text{Gt}}} )(1{\text{ - X}}_{{\text{Mn}}}^{{\text{Gt}}} {\text{) + 19246(X}}_{{\text{Fe}}}^{{\text{Gt}}} ){\text{(X}}_{{\text{Mg}}}^{{\text{Gt}}} ){\text{(1 - X}}_{{\text{Mn}}}^{{\text{Gt}}} ) \hfill \\ {\text{ }}{{{\text{ + 5649(X}}_{{\text{Ca}}}^{{\text{Gt}}} ){\text{(X}}_{{\text{Mg}}}^{{\text{Gt}}} {\text{ - X}}_{{\text{Fe}}}^{{\text{Gt}}} ){\text{\} + 7972(2X}}_{{\text{Mg}}}^{{\text{Bt}}} {\text{ - 1)]}}} \mathord{\left/ {\vphantom {{{\text{ + 5649(X}}_{{\text{Ca}}}^{{\text{Gt}}} ){\text{(X}}_{{\text{Mg}}}^{{\text{Gt}}} {\text{ - X}}_{{\text{Fe}}}^{{\text{Gt}}} ){\text{\} + 7972(2X}}_{{\text{Mg}}}^{{\text{Bt}}} {\text{ - 1)]}}} {{\text{[6}}{\text{.778}}}}} \right. \kern- ulldelimiterspace} {{\text{[6}}{\text{.778}}}} \hfill \\ {\text{ + 8}}{\text{.3143InK}}_{\text{D}} {\text{ + 6}}{\text{.276(X}}_{{\text{Ca}}}^{{\text{Gt}}} )(1{\text{ - X}}_{{\text{Mn}}}^{{\text{Gt}}} )] \hfill \\ \end{gathered} $$ The reformulated geothermometer is an improvement over existing biotite-garnet geothermometers because it reconciles the experimental data sets on Fe−Mg partitioning between the two phases and is based on updated activity-composition relationship in Fe−Mg−Ca garnet solid solutions.

Quantitative correlation between the residual activity of beta-hexosaminidase A and arylsulfatase A and the severity of the resulting lysosomal storage disease.

Abstract: A previously suggested model for the correlation between residual activity of a lysosomal enzyme and the turnover rate of its substrate(s) has been extended to a discussion of substrate accumulation rates in individual cells and whole organs. With these considerations, much of the observed variability in age of onset and clinical phenotype, as well as the phenomenon of pseudodeficiency, can be understood as the consequences of small differences in the residual activity of the affected enzyme. In order to experimentally verify the basic assumptions on which this model rests, studies were performed in cell culture. The radiolabeled substrates ganglioside GM2 and sulfatide were added to cultures of skin fibroblasts with different activities of β-hexosaminidase A or arylsulfatase A, respectively, and their uptake and turnover measured. In both series of experiments, the correlation between residual enzyme activity and the turnover rate of the substrate was essentially as predicted: degradation increased steeply with residual activity, to reach the control level at a residual activity of approximately 10–15% of normal. All cells with an activity above this critical threshold had a normal turnover. Comparison of the results of these feeding studies with the clinical status of the donor of each cell line basically confirmed our notions but also revealed the limitations of the cell culture approach.

The detector simulation program for the OPAL experiment at LEP

Abstract: The Monte Carlo program for the OPAL experiment at the LEP ee collider is described. This program is based on the GEANT simulation package. The general organization of the program is outlined, and a description is given of the techniques used for simulating the various subdetectors of OPAL. The performance of the program is illustrated by comparisons with recent data recorded by OPAL at LEP. (Submitted to Nucl. Instr. and Meth.) School of Physics and Space Research, University of Birmingham, Birmingham, B15 2TT, UK Dipartimento di Fisica dell' Universit a di Bologna and INFN, Bologna, 40126, Italy CNAF-INFN, Bologna, Italy Physikalisches Institut, Universitat Bonn, D-5300 Bonn 1, FRG Department of Physics, University of California, Riverside, CA 92521 USA Cavendish Laboratory, Cambridge, CB3 0HE, UK Carleton University, Dept of Physics, Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada Centre for Research in Particle Physics, Carleton University, Ottawa, Ontario K1S 5B6, Canada CERN, European Organisation for Particle Physics, 1211 Geneva 23, Switzerland Enrico Fermi Institute and Department of Physics, University of Chicago, Chicago Illinois 60637, USA Fakult at f ur Physik, Albert Ludwigs Universitat, D-7800 Freiburg, FRG Universitat Hamburg/DESY, II Inst. f ur Experimental Physik, 2000 Hamburg 52, FRG Physikalisches Institut, Universitat Heidelberg, Heidelberg, FRG Queen Mary and West eld College, University of London, London, E1 4NS, UK University College London, London, WC1E 6BT, UK Department of Physics, Schuster Laboratory, The University, Manchester, M13 9PL, UK Department of Physics and Astronomy, University of Maryland, College Park, Maryland 20742, USA Laboratoire de Physique Nucl eaire, Universit e de Montr eal, Montr eal, Quebec, H3C 3J7, Canada Rutherford Appleton Laboratory, Chilton, Didcot, Oxfordshire, OX11 0QX, UK DPhPE, CEN Saclay, F-91191 Gif-sur-Yvette, France International Centre for Elementary Particle Physics, University of Tokyo, Tokyo 113, Japan Brunel University, Uxbridge, Middlesex, UB8 3PH UK Nuclear Physics Department, Weizmann Institute of Science, Rehovot, 76100, Israel Present address: EPFL, Lausanne, Switzerland Present address: Applied Silicon Inc, Ottawa, Canada Present address: Rutherford Appleton Laboratory, Chilton, Didcot, Oxfordshire, OX11 0QX, UK On leave from Birmingham University, Birmingham B15 2TT, UK Present address: Culham Laboratory, Culham, Oxfordshire, UK Present address: Meiji Gakuin University, Yokohama 244, Japan

Branching of twins near an austenite—twinned-martensite interface

Abstract: We study the role of surface energy in determining twin width near an austenite—twinned-martensite interface. We find that there are two distinct regimes, depending on the relative values of the elastic moduli, surface energy density and grain size. In the first regime the twin width w is constant, of order L 1/2, where L is the grain size. In the other regime the twin width is not constant; rather, it varies as l 2/3, where l is the distance to the austenite. Most prior analyses have captured only the first regime, and it seems to be the one most commonly observed. However, twin branching consistent with our second regime has been observed in some materials.

Finding approximate separators and computing tree width quickly

Abstract: We show that for any fixed k, there is a linear-time algorithm which given a graph G either: (i) finds a cutset X of G with |X| ≤ k such that no component of G–X contains more than 3/4|G–X| vertices, or (ii) determines that for any set X of vertices of G with |X| ≤ k, there is a component of G–X which contains more than 2/3|G–X| vertices.This approximate separator algorithm can be used to develop and O(n log n algorithm for determining if G has a tree decomposition of width at most k (for fixed k) and finding such a tree decomposition if it exists.

Expression of Cx26, Cx32 and Cx43 gap junction proteins in normal and neoplastic human tissues.

Abstract: This report concerns the expression of the gap-junction proteins Connexin (Cx)26, 32 and 43 in different malignant and non-malignant human tissues. Affinity-purified polyclonal antibodies against Cx26, 32 and 43 were used for immunohistochemical as well as immunoblot analysis. Cx32, the major gap-junction protein in rat and mouse liver, was detected in human liver and kidney. By contrast, Cx43 was expressed in epithelial and mesenchymal tissues and Cx26 was detected in different epithelia. Whereas all of the benign tumors studied, and some malignant ones, showed stable expression of gap-junction proteins, breast cancer, renal-cell cancer and sarcomas showed a significant decrease in gap-junction proteins as opposed to normal tissue. Cx43, not detected in human normal liver, was found in human hepatocellular carcinoma and Cx26, not detected in human adult skin, was observed in tissue samples of basal-cell carcinoma. In immunoblot analysis, Cx32 antibodies recognized a 27-kDa protein in human liver and hepatocellular carcinoma. A 43-kDa polypeptide was detected in human kidney, renal-cell carcinoma, normal breast, connective tissue of invasive-duct carcinoma of the breast and hepatocellular carcinoma.

Molecular cloning and functional expression of mouse connexin40, a second gap junction gene preferentially expressed in lung.

Abstract: From a mouse genomic library, a clone has been isolated that codes for a connexin-homologous sequence of 358 amino acids. Because of its theoretical molecular mass of 40.418 kD it is named connexin40 (Cx40). Based on both protein and nucleotide sequence, mouse Cx40 is more closely related to mouse Cx43 (alpha subgroup of connexins) than to mouse Cx32 (beta subgroup). The highest overall homology detected, however, was to chick Cx42 (67% amino acid and 86% nucleotide identity), raising the possibility that Cx40 may be the mouse analogue. The coding region of Cx40 is uninterrupted by introns and is detected as a single copy gene in the mouse genome. High stringency hybridization of Northern blots with the coding sequence of Cx40 identified a single transcript of 3.5 kb that is at least 16-fold more abundant in lung-similar to mouse Cx37-than in other adult tissues (kidney, heart, and skin). In embryonic kidney, skin, and liver the level of the Cx40 transcript is two- to fourfold higher than in the corresponding adult tissues. Microinjection of Cx40 cRNA into Xenopus oocytes induced functional cell-to-cell channels between pairs. These channels show a symmetrical and markedly cooperative closure in response to transjunctional voltage (Boltzmann parameters of Vo = +/- 35 mV; A = 0.32) which is also fast relative to other connexin channels recorded similarly (tau = 580 ms at Vj of +/- 50 mV). Although Cx40-expressing oocytes did not couple efficiently with oocytes expressing endogenous connexins, they did couple well to Cx37-expressing oocytes. The heterotypic channels which formed had voltage-gating properties modified from those of the original homotypic forms. Transfection of mouse Cx40 DNA, under control of the SV-40 early promoter, into coupling-deficient human HeLa or SK-Hep-1 cells resulted in expression of the expected transcript and restoration of fluorescent dye transfer in transfected clones.

Autosomal recessive polycystic kidney disease

Abstract: Autosomal recessive polycystic kidney disease is a rare inherited disorder which usually becomes clinically manifest in early childhood, whereas autosomal dominant polycystic kidney disease usually is a disorder of adult onset. With increasing knowledge and improving diagnostic techniques, it becomes evident that the spectrum of both entities is much more variable than generally known. The presentation of autosomal recessive polycystic kidney disease at later ages and survival into adulthood have been reported. The diagnostic criteria, clinical course, genetics and differential diagnosis of autosomal recessive polycystic kidney disease will be presented.

Attenuation of pathological tremors by functional electrical stimulation. I: Method.

Abstract: In this study we explored the possibility of suppressing pathological tremors using closed-loop functional electrical stimulation (FES) to activate the tremorogenic muscles out-of-phase. A displacement signal monitored with a transducer was filtered so as to be "tuned" to the tremor frequency at the wrist or elbow. The filtered signal was used to amplitude-modulate the electrical stimulation. The design process was based on measurements of the open-loop frequency response characteristics of the forearm and hand to stimulation of the elbow and wrist flexors and extensors in a number of subjects. These data allowed us to identify closed-loop configurations, which attenuated 2-5 Hz tremors substantially, while only minimally attenuating functional movements in the 0-1 Hz range. There was a fairly delicate balance between efficacy and the risk of instability. However, designs were identified that offered enough tremor suppression and adequate immunity to muscle/load variations for the technique to be considered seriously for clinical application.

Structure and dynamic of a natterjack toad metapopulation (Bufo calamita).

Abstract: The migratory and reproductive behaviour ofBufo calamita was studied at four neighbouring breeding sites in the northern Rhineland, Germany, from 1986 to 1991. Radio telemetry and marking systems based on toe-clipping and on microchips were used to follow the tracks of toads and for individual recognition. Emphasis lay on estimates of (1) the exchange of reproductive individuals between neighbouring sites, and (2) the reproductive success at each site. Allozyme electrophoresis served to assess the genetic diversity of local populations. More than 90% of all reproductive males showed a lifelong fidelity to the site of first breeding, whereas females did not prefer certain breeding sites. Due to the female-biased exchange of individuals among neighbouring sites the genetic distance between local populations was generally low but increased with geographical distance. This pattern of spatial relations is consistent with the structure of a metapopulation. Morever, up to three mass immigrations of males per breeding period, replacing previously reproductive individuals, suggested the existence of temporal populations successively reproducing at the same locality. Genetic distances were considerably greater between temporal populations than between local ones, indicating partial reproductive isolation. In fact, an exchange of reproductive individuals between the temporal populations at each site was not detected, but gene flow due to the recruitment of first-breeders originating from offspring other than their own seems probable. Thus, natterjack metapopulations consist of interacting local and temporal populations. The reproductive success differed considerably among the four sites and also between the temporal populations. Three out of four local populations had low reproductive success as well as the latest temporal population. The persistence of these populations depended entirely on the recruitment of juveniles from the only self-sustaining local population. This “rescue-effect” impeded local extinction. The discussion focuses on the modifications required to fit the classical metapopulation concept to the empirical findings and their consequences for the dynamics of amphibian metapopulations.

Levels of complexity in the microstructure of mammalian enamel and their application in studies of systematics.

Abstract: Description and analysis of the complex structure of enamel can be facilitated through the application of a system of hierarchical levels of structural complexity. Five interdependent levels are distinguished. These are the levels of: 1) crystallites, 2) prisms, 3) enamel types, 4) schmelzmuster, and 5) dentition. This system provides a basis for analysis of both variation of particular structures and variation of structural types throughout a mammal's dentition. Optimally, in wide ranging systematic and biomechanical studies, all levels of structural complexity should be considered, but lack of information about one level does not prevent significant analyses at other levels.

Lower eigenvalue estimates for Dirac operators

Abstract: We derive upper eigenvalue estimates for generalized Dirac operators on closed Riemannian manifolds. In the case of the classical Dirac operator the estimates on the first eigenvalues are sharp for spheres of constant curvature.

Effects of chronic amiodarone therapy on defibrillation threshold.

Abstract: In a prospective and parallel, randomized study, the long-term stability of epicardial defibrillation threshold was evaluated in 22 patients, using a patch-patch lead configuration at the time of implantation and generator replacement The concomitant antiarrhythmic drug treatment consisted of either mexiletine (720 mg/day) or amiodarone (400 mg/day) and was administered to patients in a randomized and parallel manner During a mean follow-up of 24 +/- 6 months, the defibrillation threshold increased significantly from 143 +/- 28 to 179 +/- 53 J (p < 005) for the entire patient group The increase in the chronic defibrillation threshold was due to a marked increase in defibrillation energy needs in the subgroup of patients receiving amiodarone Whereas no significant change in the defibrillation threshold was documented in the subgroup of patients receiving mexiletine, the mean defibrillation threshold increased from 141 +/- 30 to 209 +/- 54 J (p < 0001) in those receiving amiodarone In all patients with increased defibrillation thresholds, reevaluation showed a reduction in the defibrillation threshold after discontinuation of antiarrhythmic drug therapy The only variable associated with an increase in the chronic defibrillation threshold was amiodarone treatment These findings suggest that the defibrillation threshold should be measured at each generator replacement and in case of a change in antiarrhythmic drug treatment In particular, if amiodarone treatment is initiated, it is recommended that the defibrillation threshold should be reevaluated to ensure an adequate margin of safety

The structure of pneumococcal lipoteichoic acid. Improved preparation, chemical and mass spectrometric studies.

Abstract: Pneumococcal lipoteichoic acid was extracted and purified by a novel, quick and effective procedure. Structural analysis included methylation, periodate oxidation, Smith degradation, oxidation with CrO3, and fast-atom-bombardment mass spectrometry. Hydrolysis with 48% (by mass) HF and subsequent phase partition yielded the lipid anchor (I), the dephosphorylated repeating unit of the chain (II) and a cleavage product of the latter (III). The proposed structures are: (I) Glc(beta 1----3)AATGal(beta 1----3)Glc(alpha 1----3)acyl2Gro, (II) Glc(beta 1----3)AATGal(alpha 1----4)GalNAc(alpha 1----3)GalNAc(beta 1----1)ribitol and (III) Glc(beta 1----3)AATGal(alpha 1----4)GalNAc(alpha 1----3)GalNAc, where AATGal is 2-acetamido-4-amino-2,4,6-trideoxygalactose, and all sugars are in the pyranose form and belong to the D-series. Alkaline phosphodiester cleavage of lipoteichoic acid, followed by treatment with phosphomonoesterase, resulted in the formation of II and IV, with IV as the prevailing species: [sequence: see text] The linkage between the repeating units was established as phosphodiester bond between ribitol 5-phosphate and position 6 of the glucosyl residue of adjacent units. The chain was shown to be linked to the lipid anchor by a phosphodiester between its ribitol 5-phosphate terminus and position 6 of the non-reducing glucosyl terminus of I. The lipoteichoic acid is polydisperse: the chain length may vary between 2 and 8 repeating units and variations were also observed for the fatty acid composition of the diacylglycerol moiety. Preliminary results suggest that repeating units II and IV are enriched in separate molecular species. All species were associated with Forssman antigenicity, albeit to a various extent when related to the non-phosphocholine phosphorus. Owing to its unique structure, the described macroamphiphile may be classified as atypical lipoteichoic acid.

Recovery from hemophilia B Leyden: an androgen-responsive element in the factor IX promoter

Abstract: One form of the inherited, X-linked, bleeding disorder, hemophilia B, resolves after puberty. Mutations at -20 and -26 in the clotting factor IX promoter impair transcription by disrupting the binding site for the liver-enriched transcription factor LF-A1/HNF4. The -26 but not the -20 mutation also disrupts an androgen-responsive element, which overlaps the LF-A1/HNF4 site. This explains the improvement seen in patients with the -20 mutation and the failure of the -26 patient to recover.

Comparative efficacy of antidepressants.

Abstract: Selective serotonin reuptake inhibitors (SSRIs) are a recently developed class of drugs with significantly greater antidepressant efficacy than placebo. Generally, in double-blind comparative trials, all SSRIs demonstrated antidepressant efficacy similar to that of the 'standard' tricyclic antidepressants amitriptyline and imipramine; a meta-analysis of controlled trials found the efficacy of the SSRIs to be equivalent to that of the 2 tricyclics. Nevertheless, because of small patient numbers included in most studies that compare SSRIs with other antidepressants, no definitive statements about relative efficacy can be made. In these studies it is simply possible to state that no statistically significant differences were identified between SSRIs and the comparative antidepressants. Importantly, differences in clinical characteristics exist between the SSRIs-differences in elimination half-life (t1/2 beta) between fluoxetine and/or its metabolite (total t1/2 beta = 330 hours) and other SSRIs (t1/2 beta range = 15 to 30 hours), for example. This has implications in terms of potential drug interactions and must be considered when patients have to be switched to treatment with monoamine oxidase inhibitors. Studies with fluvoxamine have been conducted in both in- and outpatients, whereas trials with other SSRIs have been confined largely to outpatient populations. Fluvoxamine has been associated with a high incidence of nausea (37%), although this may have resulted from high initial dosages (rather than upward dose titration protocols) used in early trials. Of further interest, fluoxetine doses of 20mg may be sufficient to produce a satisfactory antidepressant response, and this SSRI may be particularly useful in patients with chronic retarded depression. More clinical data are required before the efficacy of sertraline and citalopram relative to standard antidepressants can be clearly defined. Preliminary data indicate that SSRIs are effective in the treatment of panic disorder, obsessive-compulsive disorder (OCD), eating (e.g. anorexia and bulimia) and personality disorders (e.g. anger, impulsiveness) and substance abuse (e.g. alcoholism); early results with fluvoxamine in the treatment of panic disorder and OCD, and with fluoxetine in the treatment of bulimia, personality disorders and alcohol abuse, have been encouraging. SSRIs have a more favourable tolerability profile than tricyclic antidepressants and, unlike the tricyclics, are not associated with anticholinergic adverse effects, sedation, cardiotoxicity or weight gain. SSRIs are associated with a relatively high incidence of nausea, particularly if high doses are used at the start of treatment. However, the incidence of nausea appears to decrease as treatment is continued.(ABSTRACT TRUNCATED AT 400 WORDS)