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Milnacipran, a new serotonin and noradrenaline reuptake inhibitor: an overview of its antidepressant activity and clinical tolerability.

Milnacipran (Ixel) is a new antidepressant with essentially equal potency for inhibiting the reuptake of both serotonin and noradrenaline, with no affinity for any neurotransmitter receptor studied. A review of the studies comparing milnacipran, placebo and active comparator antidepressants provides clear-cut evidence of its efficacy in both severe and moderate depression in hospitalized and community settings. Meta-analyses of the original data of controlled trials involving 1032 patients, comparing milnacipran with imipramine or selective serotonin reuptake inhibitors (SSRIs), show that milnacipran provides antidepressant efficacy similar to that of imipramine and significantly superior to that of the SSRIs. An analysis of a database of over 3300 patients shows that both the general and cardiovascular tolerability of milnacipran are superior to those of the tricyclic antidepressants (TCAs) with fewer cholinergic side-effects. The tolerability of milnacipran was comparable to that of the SSRIs, with a higher incidence of dysuria with milnacipran, and a higher frequency of nausea and anxiety with the SSRIs. Milnacipran is a new therapeutic option in depression, which offers a clinical efficacy in the range of the TCAs combined with a tolerability equivalent to that of the SSRIs.

Adrenergic Uptake Inhibitors↗

Acute central and renal haemodynamic responses to tertatolol and propranolol in patients with arterial hypertension following head injury.

We compared the central and renal haemodynamic effects of tertatolol, a new non-cardioselective beta-adrenergic blocking drug without partial agonist activity, with those of an equipotent dosage of propranolol in two groups of 10 patients each with acute cerebral injury who had developed systemic hypertension. After tertatolol, 5 mg orally, mean arterial pressure was unchanged, heart rate decreased by 22% (P less than 0.01) and cardiac index by 24% (P less than 0.01), while renal blood flow remained unchanged (-5%, NS). After 160 mg propranolol orally, mean arterial pressure was unchanged, heart rate decreased by 12% (P less than 0.01), cardiac index by 16% (P less than 0.01) and renal blood flow by 17% (P less than 0.01). There was a moderate rise in norepinephrine levels after tertatolol only. Thus in this particular model of acute hypertension, tertatolol acted as a potent beta-blocking agent but differed from propranolol by preserving renal perfusion.

Adolescent↗

Cardiovascular and renal effects of the beta-blocker SE2395 in conscious normotensive dogs.

The cardiac and renal hemodynamic effects of SE2395, a beta-blocking agent, were examined after intravenous administration (50 micrograms/kg) in normotensive conscious dogs. Beta-blocking action of SE2395 was evidenced by a reduction in heart rate and cardiac output without change in the mean arterial pressure. An increase in glomerular filtration rate (inulin clearance) and a slight enhancement in effective renal plasma flow (para-aminohippurate clearance) were observed without attendant decreases in plasma renin activity. An increase in urinary sodium excretion was also observed; urinary prostaglandin E2 excretion was, however, unchanged. We conclude that at effective beta-blocking dosage SE2395 does not induce any detrimental effect on renal function in conscious dogs.

Adrenergic beta-Antagonists↗

Assessment of antihypertensive effect by blood pressure monitoring: applications to bisoprolol and lisinopril in a double-blind study.

The aim of this study was to evaluate the antihypertensive effect of drugs according to the initial ambulatory blood pressure (BP) level. After a 15-day placebo run-in period, 105 patients with moderate essential hypertension (mean age, 52 years) underwent 24-h BP monitoring (spacelabs: 1 measure/15 min). Patients were subdivided into two groups: the "High" group, with 24-h mean values of systolic BP (SBP) > 137 or diastolic BP (DBP) > 87 mm Hg, and the "Low" group, with SBP < or = 137 and DBP < or = 87 mm Hg. All patients received, in a random and double-blind design, either bisoprolol (10 mg q.d.) or lisinopril (20 mg q.d.) for 8 weeks. At the end of this active treatment period, office and ambulatory BP measurements were performed. Casual measurements revealed similar BP decreases in all subgroups receiving bisoprolol and lisinopril; BP monitoring showed that the antihypertensive effect depended on the baseline mean 24-h value; -15/-12 mm Hg for bisoprolol and -18/-13 mm Hg for lisinopril in the High group; -7/-6 mm Hg for bisoprolol and -6/-6 mm Hg for lisinopril in the Low group. This study shows that the antihypertensive effect depended on initial ambulatory BP values, with a lower BP decrease in the Low group. Assessment of the antihypertensive effect on ambulatory BP is useful in clinical trials.

Adrenergic beta-Antagonists↗

Fast gradient echo magnetic resonance imaging of the normal diaphragm.

To determine the ability of fast gradient-recalled echo (GRE), breath-hold magnetic resonance imaging (MRI) to depict all regions of the diaphragm, 13 volunteers were scanned in coronal and sagittal planes. The central to anterior left hemidiaphragm and the posterior lumbar portions were each demonstrated in 12 subjects (92%). The crura were visible crossing anterior to the aorta in the sagittal plane in eight subjects (62%) and in the coronal plane in six subjects (46%). In the sagittal plane, the right crus was evident in eight subjects (62%). Muscular portions of the diaphragm in contact with the liver or body wall were less frequently discernible, and the central tendon could not be confidently resolved. Several artifacts occurred that interfered with visualization of the diaphragm. These observations indicate that many regions of the diaphragm can be seen with fast GRE, breath-hold MRI, but there are some limitations in depicting the diaphragm in its entirety.

Adult↗

Biophysics of cochlear implant/MRI interactions emphasizing bone biomechanical properties.

OBJECTIVE/HYPOTHESIS: The forces exerted during a 1.5-Tesla MRI evaluation on the internal magnet of a cochlear implant (CI) raise concern about the safety for CI recipients. This study determines the magnitude of force required to fracture the floor of a CI receiver bed. METHOD: Recessed CI beds were drilled to maximum uniform thinness into formalin-fixed and fresh-frozen human calvaria specimens. A Med-El stainless steel CI template mounted to the piston of an electrohydraulic testing device was used to fracture the floor of the implant beds. Force and displacement were measured as a function of time using a digital data acquisition system. RESULTS: Mean force to first failure, displacement to first failure, and minimum thickness, respectively, were: group 1 (formalin-fixed, 0.3-0.4-mm thick [n = 22]), 34.08 N (8.21-59.64 N, standard deviation [SD] 15.41 N), 1.09 mm (0.40-2.16 mm, SD 0.51 mm), 0.36 mm (0.3-0.4 mm, SD 0.05 mm); group 2 (formalin-fixed, 0.5-0.9 mm thick [n = 21]), 52.82 N (20.28-135.53 N, SD 25.29 N), 1.08 mm (0.50-2.28 mm, SD 0.47 mm), 0.58 mm (0.5-0.9 mm, SD 0.12 mm); group 3 (fresh-frozen [n = 9]), 134.13 N (86.44-190.70 N, SD 34.92 N), 1.96 mm (1.47-2.46 mm, SD 0.35 mm), 0.42 mm (0.3-0.6 mm, SD 0.11 mm). CONCLUSIONS: The mean magnitude of force required to fracture the floor of a CI bed is significantly greater than those that are generated when a Med-El Combi 40+, CII Bionic Ear CI, or Nucleus Contour CI is placed into a 1.5-Tesla MRI unit.

Adult↗

Effect of magnetic resonance imaging on internal magnet strength in Med-El Combi 40+ cochlear implants.

OBJECTIVE: Magnetic resonance imaging (MRI) has been contraindicated when cochlear implants containing an internal magnet are in place because of concerns regarding torque, force, demagnetization, artifacts, induced voltages, and heating. The objective was to determine the magnetic field strength of Med-El Combi 40+ cochlear implant internal magnets after MRI studies. STUDY DESIGN/METHODS: Two fresh cadavers were used to study demagnetization using a repeated measures design and a magnetometer. Pre- and postMRI measurement of magnetic field strength was completed. Five sets of sagittal T1-weighted, axial T1-weighted, and axial T2-weighted sequences were performed on a cadaver at 0.2 Tesla in the device-up and device-down positions. In the other cadaver, 15 sets of sagittal T1-weighted, axial T1-weighted, and axial T2-weighted sequences were performed on a cadaver at 1.5 Tesla were conducted, 5 each with the head oriented at 80, 90, and 100 degrees rotated around the yaw plane (rotated around the z-axis). Subsequently, three cochlear implant patients completed 0.2 Tesla MRIs. For these patients, subjective and objective assessment of cochlear implant performance was performed. SETTING: Academic medical center. RESULTS: In the cadaver studies, analysis of variance showed no significant difference in the magnetic field strength after the 0.2 or 1.5 Tesla scans. There was no significant difference in the magnetic field strength for the three patients undergoing 0.2 Tesla MRIs and no adverse consequences, including no changes in telemetry, auditory sensations, nonauditory sensations, and sound quality. CONCLUSIONS: No significant demagnetization of the internal magnet occurred during repeated 1.5 Tesla MRI scans with the head orientations used in this study. In the cochlear implant patients, no significant demagnetization of the internal magnet occurred after a 0.2 Tesla MRI.

Artifacts↗

Subepidermal autoimmune bullous skin diseases associated with B-cell lymphoproliferative disorders.

The development of several types of autoimmune disorders is well known in the course of B-cell lymphoproliferative diseases. In order to investigate whether these autoimmune diseases may target cutaneous antigens, especially those of the dermal-epidermal junction, we conducted a retrospective analysis of all cutaneous direct immunofluorescence studies performed in patients with B-cell neoplasia who presented with cutaneous lesions requiring a skin biopsy. Patients with linear deposits of immunoglobulin or C3 molecules at the dermal-epidermal junction were studied further, using immunoblotting and immunoelectron microscopy. Patients with no overt hematologic malignancies but with cutaneous lesions requiring direct immunofluorescence were studied as a control population. During the study period, the diagnosis of autoimmune blistering diseases of the dermal-epidermal junction was established in 9/102 (8.9% +/- 2%) patients with a B-cell lymphoid disorder, compared with 288/8,189 (3.5% +/- 0.04%) patients without underlying hemopathy (p < 0.01). Among the 9 patients, 7 were studied in detail. Immunologic studies demonstrated epidermolysis bullosa acquisita in 6 patients and cicatricial pemphigoid in 1. Autoimmune blistering diseases, especially epidermolysis bullosa acquisita, are part of the spectrum of autoimmune disorders associated with B-cell neoplasia.

Aged↗

Single photon emission computerized tomography (SPECT) in detecting neurodegeneration in Huntington's disease.

Single photon emission computerized tomography (SPECT) studies were performed on 34 manifest Huntington's disease (HD) patients at various stages of clinical pathology ranging from early chorea to late dystonia with or without signs of dementia and 12 pre-symptomatic patients with abnormal terminal CAG expansions. Thirty HD patients with obvious clinical signs and seven pre-symptomatic patients without signs or symptoms of HD displayed selective caudate hypoperfusion by direct visual inspection. Such qualitative, selective striatal hypoperfusion patterns can be indicative of early and persistent metabolic changes in striatal neuropathology. SPECT studies can be useful in documenting early pre-clinical changes in patients with abnormal terminal CAG expansions and in confirming the presence of caudate pathology in patients with clinical signs of HD.

Adult↗

Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil and cisplatin.

INTRODUCTION: Adenocarcinoma of the pancreas remains one of the most difficult malignancies to treat. Its incidence has steadily increased over the past four decades, and its prognosis is still dismal. AIM To assess tumor control and the palliative benefit of 5-fluorouracil (5-FU), cisplatin (CDDP), and radiotherapy in patients with advanced pancreatic cancer. METHODOLOGY: Systemic chemotherapy consisted of 5-FU (600 mg/m ), given as a 22-hour infusion on days 1 to 5, and CDDP (100 mg/m ), given as a 90-minute infusion on day 2. Treatment courses were repeated identically on day 21. Radiotherapy was delivered using megavolt irradiation of 25-MV photons with a two- or four-field isocentric technique. RESULTS: Twenty-seven patients were treated with this radiochemotherapy (RCT). Twenty-one patients (78%) completed initial treatment. The median dose of radiation therapy delivered was 42.5 Gy. At the time of evaluation (1 month after the end of the RCT), no grade 4 (WHO) toxicity was observed; 12 patients had improved or stable body weight; pain was improved for 20 patients, with 11 experiencing no pain; and analgesic consumption decreased for 18 patients, of whom 11 stopped intake. The clinical benefit response was 7/27 (26%). Median survival and time to progression were, respectively, 9 and 4.4 months. CONCLUSION: This RCT regimen had a good impact on clinical benefit in locally advanced pancreatic carcinoma, without severe side effects.

Adenocarcinoma↗

Dorsal scalloping by calcified disc herniation.

SUMMARY OF BACKGROUND DATA: Disc herniation responsible for scalloping of vertebral body had been reported only at the lumbar level. RESULTS: The authors report on an unusual etiology of dorsal scalloping. A voluminous and calcified dorsal disc herniation was responsible for this, and within the center of the mass there was an unexpected hypersignal on nuclear magnetic resonance imaging. CONCLUSION: Scalloping does not preclude disc herniation, even at the dorsal level. Hyperintensity in T1-weighted images can reveal calcifications, as indicated in previous studies.

Calcinosis↗

Super-acute aseptic spondylitis as the first manifestation of round calcifying nucleopathy in a 77-year-old man. A case report.

STUDY DESIGN: This is a report of an unusual case of very late onset, symptomatic, round calcifying nucleopathy. OBJECTIVE: To describe this unusual case of calcifying nucleopathy in a 77-year-old man who had no previous back problems, but had a history of diffuse skeletal hyperostosis. SUMMARY OF BACKGROUND DATA: The resorption of calcifying nucleopathy associated with reactional spondylitis is a classic occurrence in children but is rare in adults. METHODS AND RESULTS: Spondylitis was diagnosed on the basis of pain, a transient Babinski's sign, and systemic inflammation. Radiographs, a bone scan, and magnetic resonance imaging revealed a large calcified nucleopathy of the T12-L1 disc associated with spondylitis of T12. The calcification disappeared within 3 weeks, and recovery was clinically and biologically complete after treatment consisting of only rest and analgesics. CONCLUSION: A diagnosis of resorption of a round calcifying nucleopathy is not to be excluded in the elderly patient. This event can mimic an infectious spondylitis clinically and biologically.

Aged↗

Possible use of arthrodesis for intractable sacroiliitis in spondylarthropathy: report of two cases.

STUDY DESIGN: Two cases of successful sacroiliac joint arthrodesis for medically intractable aseptic sacroiliitis are reported. SUMMARY OF BACKGROUND DATA: Although successful arthrodesis of the sacroiliac joint had been reported previously for septic sacroiliitis, no report had shown the procedure to be effective for spondylarthropathy. METHODS: Two women with spondylarthropathy involving very painful sacroiliac arthritis for 18 and 24 months had been relieved only transiently by several injections of steroids into the sacroiliac joint under fluoroscopy and by Bermuda casts. Both patients underwent sacroiliac joint arthrodesis. RESULTS: Both patients showed dramatic improvement after sacroiliac joint arthrodesis. Moreover, no relapses had occurred, respectively, after 2 and 3 years of follow-up evaluation despite continuing spondylarthropathy in other joints. CONCLUSIONS: After a careful selection of patients, including positive blocks in the sacroiliac joint, arthrodesis of sacroiliac joint might be considered for so-called "intractable" aseptic sacroiliitis.

Adult↗

Autoimmunity after allogeneic bone marrow transplantation. A study of 53 long-term-surviving patients.

Various autoantibodies were screened in 53 long-term survivors after allogeneic bone marrow transplantation. Among them, 40 displayed chronic graft-versus-host disease, with clinical features reminiscent of collagen diseases, especially scleroderma, Sjögren's syndrome, and autoimmune hepatitis. Antinuclear, anti-smooth muscle, antimitochondria, anti-liver kidney microsome, and antiepidermal antibodies were found at a frequency of 62.2%, 49.0%, 11.3%, 5.6%, and 11.3%, respectively. The screening for native anti-DNA, anti-extractable nuclear antigen, anticentromere, and anti-salivary gland duct antibodies was negative. The presence or absence of acute GVHD made no difference in the frequency of autoantibodies. No correlation between cutaneous hepatic involvement, sicca syndrome, scleroderma status, and autoantibodies could be established. Despite clinical features mimicking collagen vascular diseases, the biological autoimmune profile of GVHD was different. The precise role of autoimmunity in chronic GVHD remains to be defined.

Antibodies, Antinuclear↗

Cancer of the ampulla of Vater: results of a 20-year population-based study.

BACKGROUND: Relatively little attention has been given to the epidemiology and management of cancer of the ampulla of Vater. SETTING: A series of 111 patients with a cancer of the ampulla of Vater diagnosed over a 20-year period (1976-1995) in a well-defined French population was used to analyse its incidence, management and prognosis as well as to determine time trends. Prognosis was determined by using crude and relative survival rates. Factors predictive of survival were also identified using a relative survival model in a multivariate analysis. RESULTS: Age-standardized incidence rates were 3.8 per 1000000 inhabitants in men and 2.7 per 1000000 inhabitants in women. Incidence increased over time in men from 1.9 during the first period (1976-1980) to 5.9 during the last period (1991-1995). In women, incidence rates remained stable. A resection for cure was performed in 52 cases (48.1%). Overall, 9.9% of these cancers were classified TNM stage I and 54.1% stage IV. There was no significant variation in treatment modalities and in stage at diagnosis over the study period. The overall operative mortality rate was 7.5%. Relative survival rates were 58.9% at 1 year, 30.9% at 3 years and 20.9% at 5 years. Five-year relative survival rates varied from 72.8% in TNM stage I cancers to 6.6% in TNM stage IV cancers. Age, treatment procedure and stage at diagnosis significantly influenced the prognosis of cancer of the ampulla of Vater. In a multivariate analysis, stage at diagnosis remained the major prognostic factor (P<0.01). CONCLUSIONS: Although its incidence is increasing in men, cancer of the ampulla of Vater remains a rare tumour in both sexes. No improvements in the management and care of patients have been achieved. Further studies are needed to enhance the understanding of this cancer.

Adenocarcinoma↗