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At least 433 records · Page 24Linked to original sources
PubMed1996

Assessment of the efficacy of sacroiliac corticosteroid injections in spondylarthropathies: a double-blind study.

Despite previously carrying out a first open study of sacroiliac injection of long-acting corticosteroid, it was not possible to evaluate the role of a placebo effect. We therefore performed a double-blind study in 10 patients/13 articulations, suffering painful sacroiliitis. At 1 month, 5/6 sacroiliac joints injected with corticosteroid described a relief of > 70%, in comparison to 0/7 of the placebo group (P < 0.05). Dolometry showed a marked decrease in the corticosteroid group from (mean +/- S.E.M.) 6.8 +/- 0.6 to 1.3 +/- 0.3, and decreases were mild in the placebo group: 7.0 +/- 0.6 to 5.2 +/- 0.5 (P < 0.005). Six of the seven sacroiliac joints of the placebo group and two patients with failure and relapse of the corticosteroid group were reinjected with corticosteroid. At 1 month, 12/14 (85.7%) were assessed as having a good result. Results were still significant at 3 months (62%) and 6 months (58%). Tolerance was good or very good in 86% of the cases, and we did not report any notable complication. This technique is safe and very efficient, and it has to be considered more widely in patients with contraindications or complications with NSAID, or if the medical treatment is unable to control sufficiently the active sacroiliitis.

Adrenal Cortex Hormones↗
PubMed1998

Altered DNA repair and dysregulation of p53 in IRF-1 null hepatocytes.

The tumor suppressor proteins IRF-1 and p53 are involved in response pathways after DNA damage. In different cell types, IRF-1 and p53 can cooperate to produce cell cycle arrest (embryo fibroblasts) or can independently trigger apoptosis (lymphoid cells). p53 may also regulate DNA repair, but there is no information on IRF-1 and repair. The cell lineage dependency of these effects precludes extrapolation of findings to other tissues of relevance to human cancer. Here, we report the consequences of IRF-1 deficiency for apoptosis, cell cycle arrest, and DNA repair in primary hepatocytes after DNA damage and extend previous work on the role of p53 in hepatocytes. IRF-1-deficient hepatocytes showed reduced DNA repair activity compared with wild-type, as assessed by unscheduled DNA synthesis after UV irradiation (10J/m2) and by host reactivation of a UV-damaged reporter construct. p53-deficient hepatocytes also showed reduced unscheduled DNA synthesis after UV, but there was no impairment of specific repair in host reactivation assays. IRF-1 deficiency did not affect the p53-dependent G1/S arrest after UV irradiation. Hepatocyte apoptosis after UV treatment, previously reported to be independent of p53, was also independent of IRF-1. However, IRF-1 deficiency produced dysregulation of p53, manifested as increased transactivation of a p53-reporter plasmid in undamaged hepatocytes, and accelerated p53 stabilization after DNA damage. Hence, in hepatocytes, IRF-1 is not required for growth arrest or apoptosis after DNA damage, but the results suggest for the first time a role in DNA repair regulation.

Animals↗
PubMed1987

High-grade malignant cutaneous plasmacytoma metastatic to the central nervous system. A case report with electron microscopy, immunohistological, and neuropathological studies.

A case of high-grade malignant extramedullary plasmacytoma (EMP), unusual in its initial cutaneous localization and major involvement in the central nervous system rapidly resulting in death, is reported. Light- and electron-microscopic studies of a skin nodule revealed a high proportion of immature and mature plasmacytes. Immunohistological study revealed that both cells synthesized different amounts of a monotypic cytoplasmic kappa light chain. Neuropathological study revealed extensive infiltration of the leptomeninges and perivascular spaces as far as the deep parenchyma. In several places, effraction of vessels resulted in parenchymatous, tumor-like, plasmacytic infiltration. The findings of this case were compared with those of the few previously reported cases of EMP with initial cutaneous or intracranial localization, and with those of immunoblastic sarcoma occurring in some cases of myeloma.

Brain Neoplasms↗
PubMed2001

In vivo proton (H1) magnetic resonance spectroscopy for cervical carcinoma.

Proton magnetic resonance spectroscopy (MRS) may be a useful tool in both the initial diagnosis of cervical carcinoma and the subsequent surveillance after radiation therapy, particularly when other standard diagnostic methods are inconclusive. Single voxel magnetic resonance (MR) spectral data were acquired from 8 normal volunteers, 16 patients with cervical cancer before radiation therapy, and 18 patients with cervical cancer after radiation therapy using an external pelvic coil at a 1.5-T on a Signa system. The presence or absence of various resonances within each spectrum was evaluated for similarities within each patient group and for spectral differences between groups. Resonances corresponding to lipid and creatine dominated the spectrum for the eight normal volunteers without detection of a choline resonance. Spectra from 16 pretreatment patients with biopsy-proven cervical cancer revealed strong resonances at a chemical shift of 3.25 ppm corresponding to choline. Data acquired from the 18 posttreatment setting studies was variable, but often correlated well with the clinical findings. Biopsy confirmation was obtained in seven patients. H1 MRS of the cervix using a noninvasive pelvic coil consistently demonstrates reproducible spectral differences between normal and neoplastic cervical tissue in vivo. However, signal is still poor for minimal disease recurrence. Further study is needed at intervals before, during, and after definitive irradiation with biopsy confirmation to validate the accuracy of MRS in distinguishing persistence or recurrence of disease from necrosis and fibrosis.

Adult↗
PubMed1996

Magnetic resonance imaging of cerebrospinal fluid volume and the influence of body habitus and abdominal pressure.

BACKGROUND: Although the cerebrospinal fluid (CSF) is the pathway of anesthetic delivery and the diluent for neuraxially administered drugs, little is known about its volume, including variability among individuals, longitudinal distribution, or influence of body habitus. Models made to investigate subarachnoid anesthetic distribution lack valid dimensions. CSF volume was measured in volunteers, and the effect of obesity and abdominal compression on CSF volume was evaluated using magnetic resonance imaging. METHODS: Low thoracic and lumbosacral axial magnetic resonance images of 25 healthy volunteers were obtained at 8-mm intervals by fast spin-echo sequence, which highlights CSF. A repeat image series was performed in 15 subjects during external abdominal compression. In two subjects, images were obtained without compression for the entire vertebral column. Dural sac and spinal cord areas were determined in a blinded fashion for each image using video/digital analysis. Area of the sac minus area of the cord constituted area of CSF and roots ("CSF/root"); this area multiplied by 8 mm resulted in CSF/root volume per section. RESULTS: There is great interindividual variability in CSF/root volume. From the T11-T12 disc to the sacral terminus of the dural sac, the mean volume for all subjects is 49.9 +/- 12.1 ml (mean +/- SD; range 28.0-81.1 ml). This volume was significantly less in relatively obese subjects (42.9 +/- 9.5 ml) than in nonobese subjects (53.5 +/- 12.9 ml). Abdominal compression decreased CSF/root volume by 3.6 +/- 3.2 ml. Sections through intervertebral foramina showed the biggest decrease with abdominal compression, with a lesser change in sections with veins and no change in the absence of these anatomic features. Total vertebral CSF/root volume in two subjects was 94.84 and 120.01 ml, respectively. CONCLUSIONS: CSF volume is widely variable between individuals. The decreased CSF volume that results from increased abdominal pressure, such as with obesity or pregnancy, may produce more extensive neuraxial blockade through diminished dilution of anesthetic. The mechanism by which increased abdominal pressure decreases CSF volume is probably inward movement of soft tissue in the intervertebral foramen, which displaces CSF.

Abdomen↗
PubMed1998

Development of a method to separate lipoprotein-bound and lipoprotein-depleted tissue factor pathway inhibitor. Measurement of free tissue factor pathway inhibitor activity.

The aim of this study was to develop a method to separate lipoprotein-bound from lipoprotein-free tissue factor pathway inhibitor (TFPI) and to measure the TFPI chromogenic activity and antigen in both fractions. This was performed by ultracentrifugation of plasma, after increasing its density to 1.21 g/ml with potassium bromide. Blood was taken from nine volunteers before and after an injection of low-molecular-weight heparin. The ultracentrifugation procedure was adequate, since the mean cholesterol recovery was 91% and only 2% of the cholesterol remained in the lipoprotein-depleted fraction. No free TFPI protein was found in the lipoprotein-rich fraction. Moreover, the amount of free TFPI in the lipoprotein-depleted fraction was close to that found in plasma. Using this method, we confirmed that heparin does not induce an increase in bound TFPI and that the moderate increase in total TFPI antigen in plasma is entirely caused by the enhancement of free TFPI. We then applied the TFPI chromogenic assay to the lipoprotein-depleted fraction to assess the activity of free TFPI. The activity was 0.11+/-0.03 and 0.36+/-0.08 U/ml before and after heparin, respectively (a 3.6-fold increase) while the activity of bound TFPI did not increase at all. We suggest that this method may be an alternative to gel filtration for measuring free TFPI activity, and might be of value in the search for TFPI abnormalities in patients with thrombosis.

Anticoagulants↗
PubMed2001

Polymorphisms of the tissue factor pathway inhibitor gene and the risk of restenosis after coronary angioplasty.

Intracoronary stent implantation is associated with a significantly lower risk of restenosis compared with balloon angioplasty. However, restenosis still occurs in some cases. Experimental studies suggest that the tissue factor pathway is involved in this phenomenon. We investigated a possible relationship between three previously identified polymorphisms of the tissue factor pathway inhibitor (TFPI) gene and restenosis in 443 patients who underwent angioplasty, with or without stent implantation. The effect of the intron 7-33T<--C polymorphism and that of the combined intron 7 and promoter genotype on plasma TFPI levels was also investigated in 58 healthy subjects. DNA analysis was performed by polymerase chain reaction amplification of genomic DNA extracted from white blood cells, followed by digestion with the restriction enzymes Hind III, Nde I and Mae III for the detection of promoter, intron 7 and exon IX polymorphisms, respectively. The minimal luminal diameter, percent stenosis, acute gain, late loss and loss index did not differ according to the genotype before, immediately after or 6 months after angioplasty, regardless of stent implantation. Interestingly, subjects with the intron 7 CC genotype had significantly higher total TFPI levels than those with the TT genotype before and after an enoxaparin injection. Moreover, subjects with the -287TT/Int7TT combined genotype had the lowest plasma TFPI levels. Despite significant variations in plasma TFPI levels, we found no evidence that three polymorphisms of the TFPI gene influence the risk of restenosis. These results do not exclude the possibility that other polymorphisms in the TFPI gene may influence this risk.

Aged↗
PubMed2003

Combined factor V leiden (G1691A) and prothrombin (G20210A) genotyping by multiplex real-time polymerase chain reaction using fluorescent resonance energy transfer hybridization probes on the Rotor-Gene 2000.

Several methods have been developed to detect common single point mutations in the factor V and prothrobin genes that are risk factors for thrombophilia. Most are based on PCR followed by restriction enzyme digestion and electrophoresis (RFLP), but gel analysis has certain limitations, and alternative detection methods, including real-time PCR, have therefore been developed. In this study we developed and evaluated a combined factor V Leiden and prothrombin (G20210A) genotyping method based on multiplex real-time PCR with fluorescent resonance energy transfer (FRET) hybridization probes on the Rotor-Gene 2000. Two hundred subjects were screened for the two mutations. The FRET assay clearly discriminated among wild-type, homozygous and heterozygous status for the two mutations, and the results were in full agreement with those of the RFLP assay. This robust FRET probe-based assay also has a higher throughput capacity than conventional methods, handling up to 72 samples in 90 min.

DNA↗
PubMedDate not supplied

Cortical activation response to acoustic echo planar scanner noise.

PURPOSE: Our goal was to determine the distribution of auditory and language cortex activation in response to acoustic echo planar scanner noise with functional MRI (fMRI). METHOD: Acoustic scanner noise and spoken text, reproduced on high output cassette tape, were separately delivered at equivalent intensities to six normal hearing adult volunteers through earphones during fMRI data acquisition. In nine other subjects, taped scanner noise was delivered in five successive iterations of the task to assess the consistency of cortical activation to the noise stimulus. Gyri of the auditory and language system were divided into 10 different subregions for analysis of cortical activation. The number of activated pixels and proportion of volunteers activating each cortical subregion were determined using a cross-correlation analysis. RESULTS: Cortical activation to taped acoustic scanner noise was present within the transverse temporal gyrus (primary auditory cortex) in all subjects, but activation was highly variable between subjects in auditory association and language relevant cortex. Auditory association cortex activation was seen in the planum polari, planum temporali, and middle temporal gyrus/superior temporal sulcus regions in one-half to two-thirds of the volunteers. There was no significant difference in the distribution of cortical activation within individual subjects across five successive iterations of the scanner noise task. Listening to spoken text consistently activated primary and association auditory cortex bilaterally as well as language relevant cortex in some cases. The mean number of activated pixels was significantly greater for text listening than acoustic scanner noise in auditory association and language relevant cortical subregions (p < 0.01), although the distribution of activity was similar between the two tasks. CONCLUSION: This preliminary investigation suggests that the complex sounds produced by the echo planar pulse sequence can activate relatively large regions of auditory and language cortex bilaterally, with the extent of activation outside the primary auditory cortex being variable between subjects. However, the distribution of activation within individual subjects was relatively constant across several iterations of the scanner noise stimulus.

Adult↗
PubMedDate not supplied

Acoustic echoplanar scanner noise and pure tone hearing thresholds: the effects of sequence repetition times and acoustic noise rates.

PURPOSE: Our goal was to determine the effects of acoustic echoplanar scanner noise on pure tone hearing thresholds in normal volunteers and to determine the influence of echoplanar sequence repetition time on threshold effects. METHOD: With use of a calibrated audiometer, pure tones ranging from 125 to 8,000 Hz were delivered monaurally to 10 normal-hearing volunteers in a quiet MR scanner suite and in the presence of acoustic scanner noise produced by three separate single shot blipped echoplanar pulse sequences varying only in repetition time (TR = 1,000, 2,000, or 3,000 ms), with all other parameters including the number of slices held constant. The magnitude of noise-induced threshold changes and the slopes of the threshold curves produced by each of the three echoplanar pulse sequences were then analyzed using multiple comparisons and a least significant difference method. The shapes of the threshold curves produced in each background state were best fit using a quadratic effect for frequency in a mixed effects linear model and compared using F test statistics. RESULTS: All of the volunteers demonstrated entirely normal hearing thresholds throughout the full range of tonal frequencies tested (< 25 dB) when no acoustic scanner noise was present in the scanner suite. Pure tone hearing thresholds significantly increased (p < 0.01) in the presence of acoustic scanner noise, with the magnitude of change inversely proportional to the repetition time and therefore the rate of periodic noise production by the echoplanar sequence used. The shape of the threshold curve in the presence of noise produced by the 1,000 ms TR sequence was not equivalent across the frequency spectrum tested but had a quadratic distribution with peak effects at 750-2,000 Hz. As the repetition time was increased and the periodic noise rate decreased, the magnitude of the noise-induced threshold changes significantly lessened (p < 0.01) and the quadratic distributions of the threshold curves changed significantly (p < 0.01), tending toward a more planar configuration. CONCLUSION: Background acoustic echoplanar scanner noise can significantly increase pure tone thresholds in the optimal frequency hearing range (125-8,000 Hz). However, the threshold effects are not equivalent across the frequency spectrum, and the magnitude of threshold changes is dependent on the rate at which periodic acoustic scanner noises are produced for a given sequence repetition time.

Acoustic Stimulation↗
PubMedDate not supplied

Magnetization transfer imaging of skeletal muscle in autosomal recessive limb girdle muscular dystrophy.

PURPOSE: The purpose of this work was to characterize magnetization transfer (MT) contrast of skeletal muscles in limb girdle muscular dystrophy (LGMD). METHOD: The calf muscles of five LGMD patients and 10 normal volunteers were imaged with an off-resonance MT suppression pulse applied to T1-weighted images. MT suppression ratios were calculated for anterior tibialis, posterior tibialis, soleus, and gastrocnemius muscles in the LGMD and control groups. The relationship between MT of individual muscles and the duration of LGMD symptoms was determined. RESULTS: Strong MT contrast was observed in normal calf muscles, with mean (+/-SD) suppression ratios ranging from 37.9% (+/-3.0) to 41.1% (+/-2.1). In diseased muscle, MT signal suppression ranged from 11 to 38%, demonstrating an inverse relationship between symptom duration and suppression ratios. MT contrast in the LGMD patients, as a reflection of muscle tissue integrity, was preserved in posterior or anterior tibialis, soleus, and gastrocnemius muscles, respectively. Suppression ratios were dramatically reduced in muscles with gross fatty infiltration but also were reduced in muscle tissues without visual evidence of fatty infiltration. CONCLUSION: MT imaging provides a quantitative measure of pathologic changes occurring within the skeletal muscles of patients with LGMD relative to normal and may be useful in evaluating disease extent, progression, and response to new therapies as they become available.

Adolescent↗
PubMedDate not supplied

Intensity-dependent activation of the primary auditory cortex in functional magnetic resonance imaging.

PURPOSE: The purpose of this study was to investigate the activation patterns of the primary auditory cortex in response to varying intensities of pure tone stimuli. METHOD: A 1,000-Hz pure tone stimulus was delivered monaurally to the right ear of 12 normal-hearing right-handed volunteers in 20-second on-off cycles. Stimuli were applied at 20 and 50 dB hearing level (HL) above threshold in 12 subjects and at 0, 20, 40, and 50 dB HL above threshold in 6 subjects. Functional magnetic resonance imaging (fMRI) data were obtained using a 1.5-T scanner and echoplanar imaging. Activated pixels were identified in the transverse temporal gyrus (TTG) of both hemispheres in response to pure tone stimuli at each intensity level using cross-correlation analysis (0.6; P < 0.0001). RESULTS: Of the 24 right and left TTGs imaged (n = 12), activation to pure tone stimuli at 20 and 50 dB HL above threshold was seen in 46% and 79% of TTGs, respectively, with bilateral hemispheric activation in 27% and 64% of subjects, respectively. The mean numbers of activated voxels were 4.0 and 13.0, respectively. Of the 12 right and left TTGs imaged at 0, 20, 40, and 50 dB HL above threshold, activation was seen in 33%, 42%, 58%, and 75% of TTGs, respectively. The mean numbers of activated voxels were 5.8, 3.2, 9.8, and 15.3, respectively. There was a nonsignificant trend toward contralateral (left) dominant TTG activation with increased tone intensity. CONCLUSION: Our results show an increased likelihood of TTG activation, increased TTG activation volume, and increased bilateral hemisphere TTG activation with increasing pure tone intensity. Our results suggest that the primary auditory cortex reflects or is directly involved in the central processing of sound intensity and that varying the intensity of even simple stimuli can alter the patterns of fMRI activation in auditory cortex.

Acoustic Stimulation↗
PubMedDate not supplied

Two-dimensional excitation short echo time chemical shift imaging at 0.5 tesla.

Detection of short T2 metabolites such as glutamate and glutamine (glx) in the brain can be improved by minimizing the echo time (TE) of the pulse sequence. By combining two dimensions of localization during a single radiofrequency (RF) pulse, an elliptic excitation chemical shift imaging sequence (EECSI) that further reduces TE by a factor of 2 relative to a TE-optimized point resolved spectroscopy sequence chemical shift imaging sequence was developed. An additional set of outer volume saturation pulses is included to minimize the contamination from scalp and marrow space lipids. The sequence runs with conventional gradient hardware (1 G/cm, 17 T/m/s slew rate) at 0.5 T. The increase in the fitted areas of beta,gamma multiplet of glutamate and glx in a brain-mimicking phantom was by a factor of 1.66. In the thalamus of healthy volunteers, glx was increased by 1.44. Combined with the field strength-related improvements in glutamate and glx detection previously demonstrated at 0.5 T, EECSI offers further improvements for imaging glutamate and glx in vivo.

Brain↗
PubMedDate not supplied

Visual object agnosia and pure word alexia: correlation of functional magnetic resonance imaging and lesion localization.

We present a case of a 64-year-old, right-handed female with a metastatic breast cancer lesion involving the left posterior inferior temporal lobe causing complete loss of the ability to recognize visually common objects and words. After her symptoms resolved on corticosteroid therapy, functional magnetic resonance imaging (fMRI) mapping demonstrated strong left-hemispheric dominance for word recognition and right-hemispheric dominance for object recognition. The case illustrates the relationships among ventral occipito-temporal cortical activation, lesion localization, and lesion-induced deficits of higher visual function. The relationship between hemispheric dominance determined by fMRI and risk of postoperative deficit depends on the specific visual function of interest.

Agnosia↗
PubMed1996

Preclinical pharmacology of milnacipran.

Milnacipran (Ixel) is a new antidepressant which has been developed for its selective inhibition of both serotonin and noradrenaline reuptake and its lack of affinity for neurotransmitter receptors. It inhibits virtually equipotently the reuptake of serotonin and noradrenaline both in vitro and in vivo, as demonstrated by the antagonism of centrally acting monoamine displacers. It has no effect on dopamine reuptake. In addition, milnacipran has been shown by intracerebral microdialysis to increase the extracellular levels of both serotonin and noradrenaline after acute administration. Milnacipran is devoid of interactions at any known neurotransmitter receptor or ion channel. In particular, and unlike tricyclic antidepressants, it does not act at noradrenergic, muscarinic or histaminergic receptors. Contrary to tricyclic antidepressants, chronic administration of milnacipran does not modify beta-adrenoceptor binding or second messenger function. Milnacipran is active on various animal models of depression such as the forced swimming test in the mouse, learned helplessness in the rat and the olfactory bulbectomized rat model. This pharmacological profile, associated with an excellent bioavailability in man, was predicted to be that required for a powerful and well-tolerated antidepressant. Subsequent clinical development has shown this prediction to be well founded.

Adrenergic Uptake Inhibitors↗
PubMed1996

Milnacipran and selective serotonin reuptake inhibitors in major depression.

In drug development the move from tricyclic antidepressants (TCAs) to selective serotonin reuptake inhibitors (SSRIs) involved not only the loss of the direct receptor interactions responsible for the adverse side effects of TCAs, but also the ability to inhibit the reuptake of noradrenaline. Selectivity for the single neurotransmitter, serotonin, may explain why SSRIs tend to be less efficacious than the TCAs, especially in more serious forms of depression. The advent of selective serotonin and noradrenaline reuptake inhibitors (SNRIs) has tended to confirm the idea that an action on both monoamine systems is important for maximal antidepressant efficacy. This paper reviews clinical trials comparing the new SNRI milnacipran with the SSRIs fluoxetine and fluvoxamine. A meta-analysis of the principal trials shows greater response rates (the proportion of patients with a decrease in symptom scores of 50% or more) with milnacipran (50 mg twice a day) than with fluoxetine (20 mg once a day), or fluvoxamine (100 mg twice a day) (milnacipran: 64%; SSRIs: 50%). Remission rates (the proportion of patients with Hamilton Depression Rating Scores of 7 or below) were also higher with milnacipran than with SSRIs (39 versus 28%). In one study, in which 100 mg milnacipran was given once a day in the evening, the higher response rate obtained with fluoxetine appears to be largely attributable to an inappropriate milnacipran dosage regimen. Data from a pharmacovigilance database including all patients participating in clinical trials with milnacipran (n = 5732) showed that, compared with the SSRIs, milnacipran produced fewer gastrointestinal side effects, such as nausea, and less anxiety. Milnacipran was, however, associated with a higher incidence of headache, dry mouth and dysuria. The results of these studies suggest that milnacipran is superior in efficacy to SSRIs and is equally well tolerated. Milnacipran, therefore, appears to offer a therapeutic advantage over the SSRIs.

Adrenergic Uptake Inhibitors↗
PubMed1996

Efficacy and tolerability of milnacipran: an overview.

The relative benefits and risks of milnacipran, a novel antidepressant which selectively inhibits the reuptake of serotonin and noradrenaline, have been evaluated in comparative trials against tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs). A total of 2462 patients with major depressive disorders have been investigated. At the optimal dose (50 mg twice a day), the efficacy of milnacipran was equivalent to that of the TCAs, with response rates of approximately 65% in both cases. Milnacipran was consistently effective against all of the principal elements of depression (anxiety, cognitive function, sleep and psychomotor retardation), and did not produce sedation or the emergence of suicidal thoughts. The Clinical Global Impression (CGI-3) score, a measure of the overall therapeutic impact of a treatment, was significantly higher with milnacipran than with TCAs (1.98 versus 1.84, p < 0.05). TCAs were associated with a higher frequency of adverse events than milnacipran, particularly with respect to anticholinergic-like effects; dysuria was the only adverse event occurring twice as frequently with milnacipran than with TCAs. Compared with TCAs, milnacipran was also associated with a lower incidence of cardiovascular adverse events. No haematological abnormalities occurred during treatment with milnacipran, and the incidence of abnormal liver function tests tended to be lower with milnacipran than with TCAs. In comparisons with SSRIs, milnacipran produced significantly higher response rates. The CGI-3 scores were significantly higher in milnacipran-treated patients (2.64 versus 2.32, p < 0.05). The adverse event profiles of the two treatments were similar, as was the incidence of abnormal liver function tests. These studies suggest that milnacipran offers clinical advantages over TCAs in terms of tolerability, and over SSRIs in terms of efficacy. In particular, the lack of cardiovascular adverse events appears to offer advantages in cases of deliberate overdose. To date, 15 such overdoses have occurred; none was fatal and each had a favourable outcome. The reproducible pharmacokinetic characteristics of milnacipran present further advantages over both groups of agents, due to lack of drug accumulation and a low risk of drug interactions.

Adrenergic Uptake Inhibitors↗