A double-blind, placebo-controlled study of intranasal apomorphine spray as a rescue agent for off-states in Parkinson''s disease

Physico-chemical and morphologic parameters of skin layers and subcutaneous tissue in lymphedematous limb were studied in vivo using magnetic resonance imaging. High resolution images were obtained with a depth resolution of about 70 microm, using a specific surface gradient coil specially designed for skin imaging and connected to a standard whole-body imager at 1.5 T. Twenty-one patients with unilateral lower extremity lymphedema (11 primary and 10 secondary) were examined. Skin thickness, relaxation times, and relative proton density were calculated in lymphedematous limbs and in contralateral extremities. In diseased limbs, the average skin thickness (2.17 mm) was significantly larger (p = 1.5 x 10(-4)) than that of contralateral limb (1.14 mm). Major cutaneous alterations due to lymphedema took place in dermis. In lymphedematous dermis, the significant increase of relaxation time values could be due to a shift in the equilibrium of water inside this tissue in relation to the interactions between macromolecules and water molecules. In lymphedematous epidermis our results showed an increase in the number of free water protons. Information about water and fat distribution in lymphedema was also obtained using chemical shift weighted images. Our results demonstrated a water retention diffusely spread over the entire dermis, and an important fluid retention located in the interlobular spacing and beside the superficial fascia. Inside the subcutis, the mean thickness of the superficial fat lobules was increased more than that of the deep fat lobules. From all the various measurements we could not distinguish primary from secondary lymphedema.     

Selegiline (L-deprenyl) and L-dopa treatment of Parkinson's disease: a double-blind trial

To confirm the clinical utility of selegiline (L-deprenyl), a selective inhibitor of monoamine oxidase B, as an anti-Parkinson's disease (PD) agent, the first Japanese multi-center, double-blind comparative study of this drug was conducted. The subjects were patients who had responded poorly or suffered with other problems related to L-dopa treatment. A total of 112 patients in two groups, one given selegiline at a dose of 7.5 mg/day (Group D, n = 60) and another given a placebo (Group P, n = 52), were compared over an 8-week treatment period. The percentage patients showing "moderate improvement" or better was 34.5% in Group D, while that in Group P was 11.5% (P < 0.01). In the assessment of overall safety, 66.7% in Group D showed no adverse reactions, which was not significantly different from the result of 78.9% for Group P.     

Prevention of supraventricular tachyarrhythmias after open heart operation by low-dose sotalol: a prospective, double-blind, randomized, placebo-controlled study

BACKGROUND: The aim of this prospective, double-blind, placebo-controlled trial was to assess the preventive effect and safety of low-dose sotalol after heart operation. METHODS: Two hundred fifty-five consecutive patients referred for elective coronary artery bypass grafting (n = 220) or aortic valve operation (n = 35) were randomized to receive either 80 mg of sotalol twice daily (n = 126) or matching placebo (n = 129) for 3 months, with the first dose given 2 hours before operation. RESULTS: There were no significant baseline differences between the groups. Overall, supraventricular tachyarrhythmias occurred in 36% of patients (82% atrial fibrillation). Hospital stay was 11.6 +/- 5 days in patients with supraventricular arrhythmias, versus 9.5 +/- 2.4 days in patients without it (p < 0.0001). Low-dose sotalol reduced the rate of supraventricular arrhythmias from 46% (placebo) to 26% (sotalol; p = 0.0012), or by 43%. On the fourth postoperative day, heart rate was lower in the sotalol group (74 +/- 12 beats/min versus 85 +/- 15 beats/min; p < 0.0001) but the QT interval corrected for the heart rate was not prolonged (sotalol group, 0.44 +/- 0.03 second; placebo group, 0.43 +/- 0.03 second; p = not significant). Study medication had to be discontinued because of side effects in 5.6% of sotalol and 3.9% of placebo patients (p = not significant), with one possible proarrhythmic event occurring in a patient receiving sotalol. CONCLUSIONS: Because more than 90% of supraventricular arrhythmic episodes occurred within 9 days after operation and 70% of all possibly sotalol related side effects occurred after day 9, the findings in this study imply that prophylactic treatment with sotalol may be limited to the first 9 postoperative days.     

Dramatic response to levamisole and low-dose prednisolone in 23 patients with oral lichen planus: a 6-year prospective follow-up study

The purpose of this prospective study was to evaluate the short-term and long-term clinical efficacy of levamisole used with low-dose prednisolone in patients with refractory oral lichen planus. Twenty-three patients with OLP who had been treated unsuccessfully with other modalities were given 150 mg/day levamisole and 15 mg/day prednisolone for 3 consecutive days each week. Twelve patients showed dramatic remission of signs and symptoms within 2 weeks, whereas 11 had partial remission. All 23 reported significant pain relief and showed no evidence of erosive oral lichen planus after 4 to 6 weeks of treatment. All 23 also remained free from symptoms for 6 to 9 months after the treatment ended. There were few side effects from this treatment besides minor skin rash, headache, and insomnia from the levamisole in three cases. We conclude that the addition of levamisole to prednisolone may produce improved results in the management of erosive oral lichen planus.     

Mitochondrial impairment as an early event in the process of apoptosis induced by glutathione depletion in neuronal cells: relevance to Parkinson''s disease

OBJECTIVE: To examine the effect of ZD7155, an angiotensin II receptor antagonist, on blood pressure, heart rate and occupancy of tissue angiotensin II receptor in two-kidney, one-clip Goldblatt hypertensive rats. METHODS: Goldblatt hypertension was produced in Sprague-Dawley rats. ZD7155 was administered orally at 3 mg/kg and blood pressure and heart rate were monitored for up to 48 h. In a second series of experiments, the rats were administered increasing doses of ZD7155 and monitored for 1 h. For each time and dose, rats were killed and their blood and tissues were collected. Tissue angiotensin II receptor binding was assessed by quantitative autoradiography in vitro. For a separate group of rats, the pressor response to 0.1 microg/kg angiotensin II was monitored before and after the administration of 3 mg/kg ZD7155. RESULTS: After oral administration of ZD7155, blood pressure was rapidly lowered and this lowering was sustained for up to 48 h. This effect was accompanied by sustained inhibition of angiotensin II receptor binding in the aorta, kidney and adrenal gland, together with an increase in plasma renin activity. Increasing doses of ZD7155 dose-dependently reduced blood pressure and inhibited angiotensin II receptor binding in the tissues. Degrees of inhibition varied among the different tissues and had different time courses. ZD7155 inhibited the pressor response to angiotensin II remarkably for 24 h. CONCLUSIONS: ZD7155 is a potent antihypertensive agent in two-kidney, one-clip Goldblatt hypertensive rats and this effect is accompanied by sustained inhibition of tissue angiotensin II binding.     

Autologous platelet concentrate as an adjunct in macular hole healing: a pilot study

PURPOSE: A pilot study was undertaken to assess the efficacy of autologous platelets in macular hole healing. PATIENTS AND METHODS: Eight eyes of eight patients with stage 3 or 4 macular holes, two of which had failed to heal after previous vitrectomy and gas tamponade, were included. The procedure consisted of pars plana vitrectomy with removal of posterior cortical vitreous, stripping of associated epimacular membranes, 15% perfluoroethane-air tamponade, and instillation of autologous platelet concentrate onto the posterior pole. Strict postoperative facedown positioning was observed for 12 days. Postoperative evaluation included visual acuity measurement, biomicroscopic macular appearance and scanning laser ophthalmoscope examination. The follow-up period ranged from 3 to 13 months (mean, 7 months). RESULTS: Of eight eyes, flattening of the surrounding retina and closure of the hole were achieved in seven (87.5%). Visual acuity improved two lines or more in four eyes (50%) Four eyes (50%) reached a postoperative visual acuity of 20/50 or more. Increased nuclear sclerosis was observed in six eyes (75%), and retinal detachment occurred in two eyes (25%). CONCLUSIONS: Autologous platelet concentrate administered peroperatively in full-thickness macular holes seems to be a safe and effective adjunct to vitrectomy with removal of posterior hyaloid and gas tamponade. A larger multicenter randomized prospective study is underway to verify these encouraging results before advocating the use of autologous platelets in macular hole surgery.     

Individual differences in circadian rhythm parameters and short-term tolerance to shiftwork: a follow-up study

The relationship between individual differences in the phase and amplitude of circadian rhythms and tolerance to shiftwork has been the subject of several studies. Those studies recorded circadian rhythms and shiftwork tolerance at approximately the same time. The present study aimed to examine the predictive relationships between the amplitude, phase, and mesor of 24 h rhythms obtained before exposure to shiftwork, and subsequent indices of tolerance measured after one and three years of shiftwork. The results revealed some stable relations between the various rhythm parameters and subsequent tolerance measures. Workers who had a higher mesor of positive moods, and a lower mesor of negative moods and fatigue, before entering shiftwork tended to tolerate shiftwork better. Further, those whose heart rate rhythm showed an earlier acrophase had better subsequent sleep quality scores, while those with a smaller amplitude of their temperature, negative mood and fatigue rhythms showed better night-shift tolerance.     

Short-term beneficial effect of deprenyl monotherapy in early Parkinson''s disease: a quantitative assessment

We report a case of giant ectopic pelvic spleen combined with an accessory spleen and confirmed by liver-spleen scan, angiography, magnetic resonance imaging, and surgical findings. In various reviews of the literature, no ectopic pelvic spleen larger than this one has been reported.     

High- versus low-dose ACE inhibition in chronic heart failure: a double-blind, placebo-controlled study of imidapril

OBJECTIVES: To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril. BACKGROUND: The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect. METHODS: In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II-III: +/-80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones. RESULTS: At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p < 0.05). Exercise time increased 45 s in the 10-mg group (p = 0.02 vs. placebo), but it did not significantly change in the 5-mg (+16 s), and 2.5-mg (+11 s) imidapril group, compared to placebo (+3 s). Physical working capacity also increased in a dose-related manner. Plasma brain and atrial natriuretic peptide decreased (p < 0.05 for linear trend), while (nor)epinephrine, aldosterone and endothelin were not significantly affected. Renin increased in a dose-related manner, but plasma ACE activity was suppressed similarly (+/-60%) on all three doses. CONCLUSIONS: Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.     

Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study

BACKGROUND & AIMS: Although bacterial bowel flora may be one of the contributing factors in the pathogenesis of chronic mucosal inflammation, antibiotic treatment has no established role in ulcerative colitis. The aim of the study was to evaluate the role of ciprofloxacin in the induction and maintenance of remission in ulcerative colitis in patients responding poorly to conventional therapy with steroids and mesalamine. METHODS: Ciprofloxacin (n = 38; 500-750 mg twice a day) or placebo (n = 45) was administered for 6 months in a double-blind, randomized study with a high but decreasing dose of prednisone and maintenance treatment with mesalamine including follow-up for the next 6 months. Clinical assessment and colonoscopic evaluation were performed at 0, 3, 6, and 12 months. Treatment failure, the primary end point, was defined as both symptomatic and endoscopic failure to respond. RESULTS: During the first 6 months, the treatment-failure rate was 21% in the ciprofloxacin-treated group and 44% in the placebo group (P = 0.02). Endoscopic and histological findings were used as secondary end points and showed better results in the ciprofloxacin group at 3 months but not at 6 months. CONCLUSIONS: Addition of a 6-month ciprofloxacin treatment for ulcerative colitis improved the results of conventional therapy with mesalamine and prednisone.     

Prophylactic iron supplementation after Roux-en-Y gastric bypass: a prospective, double-blind, randomized study

OBJECTIVE: To determine whether prophylactic oral iron supplements (320 mg twice daily) would protect women from iron deficiency and anemia after Roux-en-Y gastric bypass. DESIGN: Prospective, double-blind, randomized study in which 29 patients received oral iron and 27 patients received a placebo beginning 1 month after Roux-en-Y gastric bypass. SETTING: Tertiary care medical center. PATIENTS AND INTERVENTIONS: Complete blood cell count and serum levels of iron, total iron binding capacity, ferritin, vitamin B12, and folate were determined preoperatively and at 6-month intervals postoperatively in 56 menstruating women who had Roux-en-Y gastric bypass. MAIN OUTCOME MEASURE: Incidence of iron deficiency and other hematological abnormalities in each treatment group. RESULTS: Hemoglobin, hematocrit, and vitamin B12 levels were significantly decreased compared with preoperative values in both groups. Conversely, folate levels increased significantly over time in both groups. Oral iron consistently prevented development of iron deficiency in the iron group. Ferritin levels did not change significantly in the iron group. However, in placebo-treated patients, ferritin levels 2 years postoperatively were significantly decreased compared with preoperative levels. There was no difference in the incidence of anemia between the 2 groups. However, the incidence of microcytosis was substantially greater (P=.07) in placebo-treated than iron-treated patients. CONCLUSIONS: Prophylactic oral iron supplements successfully prevented iron deficiency in menstruating women after Roux-en-Y gastric bypass but did not consistently protect these women from developing anemia. On the basis of these results we now routinely recommend prophylactic iron supplements to menstruating women who have Roux-en-Y gastric bypass.     

Prevention of postoperative nausea and vomiting with ondansetron: a prospective, randomized, double-blind study in 90 patients

Cortical variation in mammals and other terrestrial vertebrates, re-examined by current comparative methodology (out-group analysis), indicates that separate lateral (olfactory), dorsal and medial (hippocampal) pallial or cortical formations arose with the origin of vertebrates. Although the exact origin of mammalian isocortex (so-called neocortex) is still disputed, it appears that the earliest mammals already had a six-layered isocortex with ten to 20 functional subdivisions. Among placental mammals, at least, isocortex has expanded numerous times, producing additional cortical subdivisions. Because these expansions were independent transformations of a simpler cortex, they produced subdivisions that are not homologous.     

Loop diuretics in the management of acute renal failure: a prospective, double-blind, placebo-controlled, randomized study

BACKGROUND: Studies on the role of loop diuretics in patients with acute renal failure (ARF) are largely retrospective, anecdotal, and poorly controlled. We report the results of a prospective, randomized, placebo-controlled, double-blind study examining the effect of loop diuretics on renal recovery, dialysis, and death in patients with ARF. METHODS: Ninety-two patients with ARF were enrolled into the study. All received intravenous dopamine, 2 micrograms/kg body weight/min throughout, 20% mannitol, 100 ml every 6 h for the first 3 days, and, in a double-blind manner, either torasemide, frusemide, or placebo, 3 mg/kg body weight i.v. every 6 h for 21 days or until renal recovery or death. RESULTS: Renal recovery, the need for dialysis, and death were no different in the three groups. Patients given a loop diuretic had a significant rise in urine flow rate in the first 24 h compared to placebo (P = 0.02). Based on the urine flow rate during the first post-medication day patients were divided into two groups--oliguric (< 50 ml/h) and non-oliguric (> or = 50 ml/h). Non-oliguric patients had a significantly lower mortality than oliguric patients (43% vs 69%, P = 0.01). However, they were less ill (APACHE II score 17.2 vs 20.6, P = 0.008) and had less severe renal failure at entry (creatinine clearance 14 ml/min vs 4 ml/min, P < 0.0001). CONCLUSION: The use of loop diuretics in oliguric patients with ARF can result in a diuresis. There is no evidence that these drugs can alter outcome.     

Recovery, Inc., as an adjunct to treatment in an era of managed care

As capitation increasingly limits professional mental health services, self-help organizations may play an expanding role. Recovery, Incorporated, is an internationally active mental health self-help organization developed in the late 1930s by Abraham A. Low, M.D. The author reviews concepts about mental illness and health developed since Low's time, such as locus of control, learned helplessness, defense theory, and Antonovsky's salutogenic model. He describes how these concepts support many of the principles developed by Low, in particular the idea that optimal health is achieved when a person assumes responsibility for his or her failure or success. In the structured format that Low designed for Recovery, Inc., meetings, members learn to identify self-defeating and illness-promoting thoughts and impulses and counter them with self-endorsing thoughts and wellness-promoting actions. The author suggests that professionals should become familiar with self-help organizations in their communities, promote relevant research, and facilitate referral to these groups.     

Ultrasonography as an aid to diagnosis and treatment in a rural African hospital: a prospective study of 1,119 cases

For the development of a totally implantable ventricular assist system (VAS), we have been developing the vibrating flow pump (VFP), which can generate oscillated blood flow with a relative high frequency (10-50 Hz) for a totally implantable system. In this study, the effects of left ventricular assistance with this unique oscillated blood flow were analyzed by the use of nonlinear mathematics for evaluation as the whole circulatory regulatory system, not as the decomposed parts of the system. Left heart bypasses using the VFP from the left atrium to the descending aorta were performed in chronic animal experiments using healthy adult goats. The ECG, arterial blood pressure, VFP pump flow, and the flow of the descending aorta were recorded in the data recorder during awake conditions and analyzed in a personal computer system through an A-D convertor. By the use of nonlinear mathematics, time series data were embedded into the phase space, the Lyapunov numerical method, fractal dimension analysis, and power spectrum analysis were performed to evaluate nonlinear dynamics. During left ventricular assistance with the VFP, Mayer wave fluctuations were decreased in the power spectrum, the fractal dimension of the hemodynamics was significantly decreased, and peripheral vascular resistance was significantly decreased. These results suggest that nonlinear dynamics, which mediate the cardiovascular dynamics, may be affected during left ventricular (LV) bypass with oscillated flow. The decreased power of the Mayer wave in the spectrum caused the limit cycle attractor of the hemodynamics and decreased peripheral resistance. Decreased sympathetic discharges may be the origin of the decreased Mayer wave and fractal dimension. These nonlinear dynamic analyses may be useful to design optimal VAS control.     

Intrapleural streptokinase versus urokinase in the treatment of complicated parapneumonic effusions: a prospective, double-blind study

Intrapleural administration of fibrinolytics has been shown in small numbers of patients with complicated parapneumonic effusions (CPE) and pleural empyema to be effective and relatively safe. Although streptokinase (SK) is recommended as the fibrinolytic of choice, there are no comparative studies among fibrinolytics. We therefore compared the efficacy, safety, and the cost of treatment two of the most used thrombolytics, SK and urokinase (UK). Fifty consecutive patients with CPE or empyema were randomly allocated to receive either SK (25 patients) or UK, in a double-blind fashion. All patients had inadequate drainage through chest tube (< 70 ml/24 h). Both drugs were diluted in 100 ml normal saline and were infused intrapleurally through the chest tube in a daily dose of 250,000 IU of SK or 100,000 IU of UK. The chest tube was clamped for 3 h after instillation. Response was assessed by clinical outcome, fluid drainage, chest radiography, pleural ultrasound, and/or computed tomography. Clinical and radiologic improvement was noted in all but two patients in each group, who required surgical intervention. The mean volume drained during the first 24 h after instillation was significantly increased; 380 +/- 99 ml for the SK group (p < 0.001) and 420.8 +/- 110 ml for the UK group (p < 0.001). The total volume (mean +/- SD) of fluid drained after treatment was 1,596 +/- 68 ml for the SK group, and 1,510 +/- 55 ml for the UK group (p > 0.05). The SK instillations (mean +/- SD) were 6 +/- 2.16 (range, 3 to 10) and those of UK 5.92 +/- 2.05 (range, 3 to 8). High fever as adverse reaction to SK was observed in two patients. The total cost of the drug in the UK group was two times higher than that of SK ($180 +/- 47 for SK and $320 +/- 123 for UK). The mean total hospital stay after beginning fibrinolytic therapy was 11.28 +/- 2.44 d (range, 7 to 15) for the SK group and 10.48 +/- 2.53 d (range, 6 to 18) for the UK group (p = 0.32). We conclude that intrapleural SK or UK is an effective adjunct in the management of parapneumonic effusions and may reduce the need for surgery. UK could be the thrombolytic of choice given the potentially dangerous allergic reactions to SK and relatively little higher cost of UK.     

Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study

Two populations of hydrogen protons exist in magnetic resonance imaging: free protons and bound protons. Bound protons do not contribute to normal MR signal because they resonate somewhat off the center frequency of water. A special pulse sequence called magnetization transfer contrast (MTC) was developed to compensate for this off-resonance limitation. A saturation transfer of bound protons occurs during MTC, enabling a transfer of energy to the free proton pool and thereby contributing to the overall MR signal. This article describes MTC, reviews its applications and explains how it improves lesion conspicuity, small vessel detail and background suppression.     

Oculoplethysmography: an adjunct to arteriography in the diagnosis of extracranial carotid occlusive disease

A four and a half year study documents that oculoplethysmography, in conjunction with carotid phonoangiography, fulfills the criteria of an effective noninvasive adjunct to arteriography in the diagnosis of extracranial carotid occlusive disease. The risk and expense of unnecessary arteriographic studies can be reduced and accuracy of arteriographic technics and interpretations can be enhanced by routine application of oculoplethysmography.     

Subcutaneous versus intravenous low-dose IL-2 therapy after autologous transplantation: results of a prospective, non-randomized study

Medorinone 5-methyl-1,6-napthyridin-2(1H)-one and some of its analogs having varying degrees of cardiotonic potency have been studied by molecular orbital and electric field mapping methods. Ground state geometries of the molecules were optimized using the MNDO molecular orbital method. Hybridization displacement charges (HDC) combined with L?wdin charges as well as Mulliken charges were used for electric field mapping around the molecules. Electric fields near the O2 site of medorinone and its analogs correlate well with their observed cardiotonic potencies. This result is in agreement with certain pharmacological models for cardiotonics.