Blood pressure biofeedback treatment, organ damage and sympathetic activity in mild hypertension

BACKGROUND: Although biofeedback treatment is reported to be useful for patients with mild hypertension as an adjunct to medication, it is not certain whether the presence of organ damage affects its efficacy. The aim of this study is to clarify the clinical effects of biofeedback on mild hypertension in the absence and presence of organ damage. METHODS: Eleven mildly hypertensive outpatients without damage to the heart, brain, retina or kidney (4 men and 7 women), aged 40-65 years, and 11 mildly hypertensive outpatients with target organ damage and matching variables for age, sex and medication were included in this study. They underwent biofeedback treatment once a week for a total of four sessions. Results: As a result of these sessions, mean blood pressures (MBP) in the organ-damage-negative (-) group and in the organ-damage-positive (+) group were significantly reduced by 12 +/- 11 and 12 +/- 8, respectively. The decrease was still significant 3 months after the treatment in the organ-damage (-) group, whereas no significant change was found 1 or 3 months after the treatment in the organ-damage (+) group. Throughout these sessions, the ratio of low frequency to high frequency of heart rate variance as well as systolic and MBP gradually decreased in each group (p < 0.01); this ratio of heart rate variance was smaller, and the alpha-wave amplitude on the electroencephalogram was larger in the organ-damage (-) group (p < 0.05). CONCLUSION: These results suggested that biofeedback intervention may be effective in mild hypertension, especially when the patient is organ damage (-). Sympathetic activity seems to play an important role in the differentiated response.     

Activation of monocytes during inflammatory bowel disease.

Inflammatory bowel diseases lead to a systemic acute-phase response. Monocyte activation plays a central role during systemic acute-phase response via secretion of inflammatory cytokines. We determined the activation of peripheral-blood monocytes in patients with inflammatory bowel diseases by measuring their interleukin-6 (IL-6) secretion. Blood was obtained from patients with active Crohn's disease before treatment [mean Crohn's disease activity index (CDAI) = 332 +/- 34] and from patients after treatment with prednisolone (mean CDAI index = 139 +/- 20). The mean serum IL-6 levels measured by a hybridoma growth assay (B9) were 23 +/- 4 U/ml before therapy and fell to 16 +/- 3 U/ml after treatment with prednisolone. Healthy persons and patients with inactive Crohn's disease usually had serum IL-6 levels below the detection limit of 4 U/ml. An ex vivo whole-blood system was used to measure IL-6 secretion by peripheral-blood monocytes with and without stimulation. Spontaneous IL-6 secretion in this system was about 9 U/ml in patients with Crohn's disease and below the detection limit of 4 U/ml in healthy controls. Moderate stimulation of blood cells [100 pg/ml lipopolysaccharide (LPS)] from patients with active Crohn's disease before and after treatment led to mean IL-6 concentrations of 1,160 +/- 514 and 131 +/- 54 U/ml, respectively. Maximal stimulation of peripheral blood before and after therapy by LPS (100 ng/ml) led to mean IL-6 concentrations of 5,570 +/- 1,660 and 6,220 +/- 1,630 U/ml, respectively. Thus, administration of glucocorticoids led to a rapid down-regulation of IL-6 synthesis by peripheral-blood monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding

BACKGROUND AND METHODS: We compared propranolol therapy and endoscopic ligation for the primary prevention of bleeding from esophageal varices. This prospective, controlled trial included consecutive eligible patients who had large varices (>5 mm in diameter) that were at high risk for bleeding. The patients were assigned to either propranolol therapy, at a dose sufficient to decrease the base-line heart rate by 25 percent, or variceal ligation, to be performed weekly until the varices were obliterated or so reduced in size that it was not possible to continue treatment. RESULTS: Of the 89 patients, 82 of whom had cirrhosis of the liver, 44 received propranolol and 45 underwent variceal ligation. The mean (+/-SD) duration of follow-up in each group was 14+/-9 and 13+/-10 months, respectively. The mean time required to achieve an adequate reduction in the heart rate was 2.5+/-1.7 days; the mean number of sessions needed to complete variceal ligation was 3.2+/-1.1. After 18 months, the actuarial probability of bleeding was 43 percent in the propranolol group and 15 percent in the ligation group (P=0.04). Twelve patients in the propranolol group and four in the ligation group had bleeding. Three of the four in the ligation group had bleeding before their varices had been obliterated. Nine patients in the ligation group had recurrent varices, a mean of 3.7 months after the initial treatment. Five patients in each group died; bleeding from the varices was the cause of death of four patients in the propranolol group and of three in the ligation group. There were no serious complications of variceal ligation; in the propranolol group, treatment was stopped in two patients because of side effects. CONCLUSIONS: In patients with high-risk esophageal varices, endoscopic ligation of the varices is safe and more effective than propranolol for the primary prevention of variceal bleeding.     

The inhibitory effect of terfenadine and flurbiprofen on early and late-phase bronchoconstriction following allergen challenge in atopic asthma

We have studied the effect of cyclo-oxygenase inhibition and H1-receptor antagonism on the early and late bronchoconstrictor responses to inhaled allergen in mild atopic asthmatics. In the first phase of the study histamine inhalation challenge tests were performed in seven mild, atopic asthmatics 2 h after treatment with placebo or flurbiprofen (50, 100 or 150 mg). Flurbiprofen in these single doses had no effect on histamine reactivity. Ten atopic asthmatics participated in the second phase of the study in which the time course of the bronchoconstrictor response to inhalation of allergen was observed on four separate occasions after treatment with (a) placebo, (b) flurbiprofen, 150 mg, (c) terfenadine 180 mg, and (d) the combination of flurbiprofen and terfenadine. On each occasion subjects inhaled a concentration of allergen (Dermatagaphoides pteronyssinus, grass pollen) that had previously been shown to produce a 30% fall in FEV1 (PC30 allergen). The mean maximum fall in FEV1 during the early reaction was 33.2 +/- 3.3% from the post-saline baseline value following placebo and this was reduced to 27.5 +/- 5.3% after flurbiprofen (n.s.), 20.3 +/- 3.2% after terfenadine (P less than 0.05), and 23.1 +/- 2.3 after the treatment combination (P less than 0.05). Seven subjects developed late asthmatic reactions (LAR) after placebo and in these subjects the mean maximum fall in PEFR during the LAR was reduced from 22.6 +/- 3.1% after placebo to 16.7 +/- 3.2% after flurbiprofen (P less than 0.05), 15.2 +/- 2.3% after terfenadine (P less than 0.05) and 11.5 +/- 3.1% after the treatment combination (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

A 3 year, prospectively-designed study of late selective multifetal pregnancy reduction

The aim of our study was to evaluate the pregnancy outcomes of late selective multifetal reduction (MFPR). We performed a 3 year, prospectively-designed study in which 28 patients underwent MFPR at a mean gestational age of 20.2 +/- 3.9 weeks (range 14-29 weeks). The indications for MFPR included: multiple gestation (> or = 3) (57%), structural anomaly (29%), and chromosomal abnormality (14%). The procedure was performed using ultrasonographically-guided intracardiac injection of potassium chloride. The mean gestational age at delivery was 36.6 +/- 2.2 weeks (range 31-40 weeks). Nine patients (32%) delivered before 36 weeks of gestation. The mean birth weight was 2370 +/- 614 g (range 1510-3250 g). Discordancy was evident in four twins (14%), and intrauterine growth retardation in four pregnancies. One case (3.5%) presented with oligohydramnios, and one with pregnancy- induced hypertension. One case of late abortion due to passive cervical dilatation 4 weeks after the MFPR was observed. Procedure-related amnionitis followed by late abortion occurred in one case. A total of 57% of the patients delivered vaginally and 43% delivered by Caesarean section. We concluded that late selective MFPR is associated with favourable perinatal outcome. Late MFPR may facilitate the detection of structural and chromosomal anomalies prior to the procedure, and the accomplishment of selective reduction of the affected fetus.      

Insect-sting challenge in 138 patients: relation between clinical severity of anaphylaxis and mast cell activation.

One hundred thirty-eight patients with a previous anaphylactic reaction to a yellow jacket or a honeybee sting, as well as eight volunteers, were subjected to an in-hospital sting challenge. Plasma levels of histamine, tryptase, and prostaglandin D2 (PGD2) during sting challenge were studied in relation to clinical symptoms. Prechallenge levels (mean +/- SD) of histamine, tryptase, and PGD2 were 2 +/- 1 nmol/L, 0.3 +/- 0.3 U/L, and 320 +/- 223 ng/L, respectively. In the volunteers and in none except for one of the nonreacting patients, these levels did not change significantly after challenge. In contrast, mean increases in the group of 18 patients with a mild reaction were significant for histamine and tryptase at one or more time points after the challenge. (Five patients demonstrated no increase in histamine; nine demonstrated no increase in tryptase.) Except for histamine levels in one patient, these increases were considerably more in all 17 patients with a severe reaction, starting from the first anaphylactic symptoms. Fifteen minutes later, peak values were reached of 1275 +/- 2994 nmol of histamine per liter (range, 3 to 12800 nmol/L; median, 11 nmol/L) and 406 +/- 1062 U of tryptase per liter (range, 1.8 to 4400 U/L; median, 17 U/L). This rise in levels inversely correlated with the mean arterial pressure. Plasma levels of PGD2 in severely reacting patients did not differ significantly from those in patients with a mild or no reaction. In conclusion, only 28% of patients with a history of Hymenoptera anaphylaxis developed an anaphylactic reaction after an in-hospital challenge.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of short-term treatment with gaboxadol on sleep maintenance and initiation in patients with primary insomnia

STUDY OBJECTIVE: To perform an early evaluation of the efficacy and safety of gaboxadol in the treatment of primary insomnia. METHODS: 26 adults (18-65 years) with DSM-IV criteria for primary insomnia were randomly assigned gaboxadol (5 mg, 15 mg) or placebo in a double-blind, crossover study. After a 3-night polysomnographic (PSG) screen, treatment was administered 30 min before bedtime on 2 consecutive nights during 3 separate sessions including PSG. Efficacy analyses (n = 23) were based on the average of Nights 1 and 2, and compared gaboxadol versus placebo. Baseline was the average of Nights 2 and 3 of the screening session. Both gaboxadol doses significantly (P < 0.05) improved mean total sleep time (mean +/- SD: baseline = 368.0 +/- 51.1 min, 15 mg = 420.3 +/- 24.5 min, 5 mg = 419.8 +/- 20.4 min, placebo = 408.7 +/- 30.4 min). Both gaboxadol doses reduced mean wake after sleep onset, although statistical significance was only achieved with 5 mg (baseline = 61.6 +/- 35.4 min, 15 mg = 38.0 +/- 21.1 min, 5 mg = 34.6 +/- 14.3 min, placebo = 43.4 +/- 22.9 min). Gaboxadol 15 mg also significantly reduced mean latency to persistent sleep (baseline = 55.6 +/- 27.0 min, 15 mg = 23.6 +/- 15.1 min, placebo = 30.0 +/- 19.1 min) and enhanced slow wave duration (baseline = 72.4 +/- 20.8 min, 15 mg = 114.0 +/- 37.5 min, placebo = 93.9 +/- 31.3 min) with no significant effects on REM sleep duration. Patient reports (Leeds Sleep Evaluation Questionnaire) of reduced time to sleep and increased sleep quality showed significant improvement with gaboxadol 15 mg. No next-day residual effects were observed with either dose of gaboxadol (assessed 2 h and 9 h after lights on). All adverse events were mild or moderate. CONCLUSION: Gaboxadol 15 mg was effective and generally well tolerated in the short-term treatment of patients with primary insomnia. Gaboxadol also enhanced slow wave sleep duration and had no significant effects on REM sleep duration. These findings suggest that gaboxadol may be a useful treatment for insomnia.     

Soluble interleukin-2 receptors in plasma cell dyscrasias

Levels of the soluble form of the interleukin-2 receptor (sIL-2R) were evaluated in the peripheral blood of 69 patients with plasma cell dyscrasias. A close relationship was seen between serum sIL-2R levels and clinical features. Among patients with normal BUN and creatinine levels, the mean (+/- 1SD) level of sIL-2R in 44 patients with multiple myeloma (MM) was higher than that of normal controls (457 +/- 227 U/ml vs 288 +/- 124 U/ml, P = 0.01). The mean level of sIL-2R in eight patients with primary macroglobulinemia was 722 +/- 251 U/ml. In MM, those with active or refractory disease showed a significantly higher mean level of sIL-2R than those in the remission phase (577 +/- 240 U/ml vs 335 +/- 103 U/ml, P = 0.01). There was a negative correlation between sIL-2R and hemoglobin levels in MM patients (r = -0.45, P = 0.01). Five patients with complications of renal insufficiency had elevated levels of sIL-2R. In a longitudinal study of a patient with plasmacytoma and an extremely high sIL2-R level, the sIL-2R level showed a strong relationship with tumor burden. Patients with high sIL-2R levels generally had a poor prognosis than those with normal levels. Thus a high sIL-2R level may be an indicator of a poor prognosis in MM.     

An open clinical trial of benazepril--a new ACE inhibitor in mild-moderate hypertension

Benazepril hydrochloride, a new non-sulfhydryl ACE inhibitor (ACEI) was studied in a titrated dose of 10 mg-20 mg once a day for 6 weeks in 42 mild to moderate adult hypertensive patients with sitting diastolic blood pressure (SDBP) 95-114 mm Hg. The pre-drug SDBP(mean +/- SE) of 102.5 +/- 0.8 mm Hg showed a significant reduction to 87.5 +/- 0.93 mm Hg at the end of treatment. BP was controlled (SDBP < or = 90 mm Hg) in 34 (81%) patients and a drop of at least 10 mm Hg from the pre-treatment SDBP value was noted in 34 (81%) patients. Common adverse reaction was cough in 8(19%) patients. Clinically significant changes in laboratory evaluations were not seen in any patient. Study showed that benazepril in a dose range of 10 to 20 mg per day is an effective agent for treatment of mild to moderate hypertension.     

Cytokine production and serum levels in systemic sclerosis.

Serum levels of various cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL1-beta), and interleukin 2 (IL2), and of soluble IL2 receptors (sIL2R) were determined in 30 patients with definite systemic sclerosis (SSc). Spontaneous and lipopolysaccharide-or mitogen-induced production of the cytokines, TNF-alpha, IL1-beta, and IFN-gamma, by peripheral blood mononuclear cells (PBMNC) of these SSc patients was measured by immunoassays. The patients were divided into three groups: 12 with limited cutaneous disease (lcSSc), 7 with diffuse cutaneous disease (dcSSc) < 3 years duration, and 11 with dcSSc > 3 years duration. None were treated with cytotoxic drugs or biologic response modifiers. Sera of patients with SSc had elevated sIL2R levels, and only low levels of IL2 (1-2 U/ml) were detected in 10/29 sera tested. Spontaneous production of TNF-alpha and IL1-beta by PBMNC of patients with SSc (829 pg/ml +/- 215 SEM and 728 pg/ml +/- 186, respectively) was significantly higher than that by normal PBMNC obtained from 30 volunteers (25 +/- 10 and 34 +/- 6 pg/ml, respectively) and tested at the same time as patients' PBMNC. The largest increases in spontaneous release of TNF-alpha or IL1-beta were seen in patients with early dcSSc. No significant difference in spontaneous IFN-gamma production by patient or control PBMNC was detected. On the other hand, the mean level of mitogen-induced IFN-gamma production by PBMNC was significantly depressed in patients with SSc (103 U/ml +/- 18 vs 255 +/- 33 U/ml in controls). In vitro-induced production of TNF-alpha or IL1-beta by patients' PBMNC was comparable to that of normal PBMNC. These data indicate that in vivo-activated PBMNC of patients with SSc spontaneously secrete excessive amounts of fibrogenic cytokines, which are involved in modulation of connective tissue synthesis.     

Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction

We performed a double-blind randomized trial comparing high doses of subcutaneous heparin (12,500 units every 12 hours) with low doses (5000 units every 12 hours) for 10 days in the prevention of left ventricular mural thrombosis in 221 patients with acute anterior myocardial infarction. Left ventricular mural thrombosis was observed by two-dimensional echocardiography on the 10th day after infarction in 10 of 95 patients (11 percent) in the high-dose group and in 28 of 88 patients (32 percent) in the low-dose group (P = 0.0004). One patient in the high-dose group and four in the low-dose group had nonhemorrhagic strokes (P = 0.17). One patient in the low-dose group had a fatal pulmonary embolism. There was no difference in the frequency of hemorrhagic complications, which occurred in six patients in the high-dose group and four in the low-dose group. The mean (+/- SEM) plasma heparin concentration was 0.18 +/- 0.017 U per milliliter in the high-dose group and 0.01 +/- 0.005 U per milliliter in the low-dose group (P less than 0.0001). In the high-dose group, the mean plasma heparin concentration was 0.10 +/- 0.029 U per milliliter among patients with abnormal two-dimensional echocardiograms, as compared with 0.19 +/- 0.019 U per milliliter among patients with normal echocardiograms (P = 0.01). We conclude that heparin administered subcutaneously in a dosage of 12,500 units every 12 hours to patients with acute anterior transmural myocardial infarction is more effective than a lower dosage (5000 units every 12 hours) in preventing left ventricular mural thrombosis.     

Clinical and mycological benefits of topical application of honey, olive oil and beeswax in diaper dermatitis

Twelve infants suffering from diaper dermatitis were treated four times daily for 7 days with a mixture containing honey, olive oil and beeswax. The severity of erythema was evaluated on a five-point scale. Three infants had severe erythema and ulceration, four had moderate erythema, and five had moderate erythema with maceration. The initial mean lesion score of 2.91 +/- 0.79 declined significantly (p < 0.05) to 2.0 +/- 0.98 (day 3), 1.25 +/- 0.96 (day 5) and 0.66 +/- 0.98 (day 7). Candida albicans was isolated initially from four patients, but from only two patients after treatment. This topical treatment was safe and well-tolerated, and demonstrated clinical and mycological benefits in the treatment of diaper dermatitis.     

A method to assess biochemical activity of liver cells during clinical application of extracorporeal hybrid liver support

Biochemical activity of a hybrid liver support system based on porcine liver cells was investigated in patients suffering from acute liver failure, coma stage III-IV Patient plasma was drawn systemically and after circulation through the bioreactor at four hour intervals. A method is used that takes into account the rate of plasma flow and the differences in plasma concentration systemically and after circulation through the liver support system to determine the net release or uptake of metabolites such as ammonia, urea and glucose. Urea release (mean 2.28+/-0.37 micromol/h/g cells) and ammonia uptake (mean 0.17+/-0.11 micromol/h/g cells) was seen during treatment, an active role of the system in glucose metabolism was observed. All patients were bridged successfully to liver transplantation.     

Venous congestive myelopathy: a mimic of neoplasia.

Venous congestive myelopathy is a progressive disorder frequently associated with arteriovenous fistulas, usually dural. By causing diffuse spinal cord enlargement and enhancement on imaging, it may simulate a neoplasm and prompt a biopsy. We evaluated the biopsy findings in seven such patients (M=5, F=2, mean age 59+/-11 years) who presented variably with progressive lower extremity weakness (86%), bowel and bladder dysfunction (86%), sensory changes (86%) or pain (29%). Preoperative magnetic resonance imaging showed spinal cord enlargement with T2-hyperintensity (86%) and contrast enhancement (57%) at the cervical (14%), thoracolumbar (57%), and/or conus medullaris (57%) level. Prebiopsy spinal angiogram, performed in two patients, was negative. Spinal cord biopsy showed architecturally distorted parenchyma with gliosis and thick hyalinized vessels (100%), variable myelin loss (71%), mild glial atypia (57%), hemosiderin deposition (71%), Rosenthal fibers (43%), vascular thrombosis (29%), and necrosis (29%), features highly suggestive of venous congestive myelopathy. Postbiopsy spinal angiograms were performed in five patients. A dural arteriovenous fistula was identified by selective angiography in three patients, including the two with a negative preoperative angiogram. Additional postbiopsy angiographic studies in two patients were negative, and two patients were followed up without angiography. Mean follow-up after biopsy was 13.6 months. Histologic changes characteristic of venous congestive myelopathy may be seen in spinal cord biopsies with or without an associated fistula. Recognition of this entity by surgical pathologists is important, leading to the correct identification of a non-neoplastic lesion as well as of a surgically treatable disease.     

Serial Testing of Postural Control After Acute Lateral Ankle Sprain

OBJECTIVE: To identify subjects' changes in postural control during single-leg stance in the 4 weeks after acute lateral ankle sprain. DESIGN AND SETTING: We used a 2 x 2 x 3 (side-by-plane-by-session) within-subjects design with repeated measures on all 3 factors. All tests were performed in a university laboratory. SUBJECTS: Seventeen young adults (9 men, 8 women; age, 21.8 +/- 5.9 years; mass, 74.9 +/- 10.5 kg; height, 176.9 +/- 7.1 cm) who had sustained unilateral acute mild or moderate lateral ankle sprains. MEASUREMENTS: Measures of center-of-pressure excursion length, root mean square velocity of center-of-pressure excursions (VEL), and range of center-of-pressure excursions (RANGE) were calculated separately in the frontal and sagittal planes during 5-second trials of static single-leg stance. RESULTS: We noted significant side-by-plane-by-session interactions for magnitude of center-of-pressure excursions in a given trial (PSL) (P =.004), VEL (P =.011), and RANGE (P =.009). Both PSL and VEL in the frontal plane were greater in the injured limbs compared with the uninjured limbs on day 1 and during week 2 but not during week 4, whereas sagittal-plane differences existed during all 3 testing sessions. Injured-limb, frontal-plane RANGE scores were greater than uninjured values at day 1 but not during weeks 2 or 4. No significant differences in sagittal-plane RANGE scores were seen. CONCLUSIONS: Postural control was significantly impaired in the injured limbs at day 1 and during week 2 after lateral ankle sprain but not during week 4. Consistent improvement in postural control measures on both injured and uninjured limbs was seen throughout the 4 weeks after ankle sprain.     

Pulmonary tuberculosis and serum IgE

Several recent studies indicate that mycobacterium or viral infection may reduce IgE levels or suppress atopy or both. The present study was undertaken to investigate whether Mycobacterium tuberculosis infection and its successful treatment down-regulate serum total IgE levels, a marker of a Th2 response, due to enhancement of a Th1 response in adult patients with tuberculosis (TB). We prospectively studied the changes in serum total IgE and DTH response to tuberculin, a marker of a Th1 response in 10 healthy controls, 20 patients with pulmonary TB, and 19 asthma patients without TB. Measurement of serum total IgE and tuberculin skin tests were performed before initiation of treatment and after successful completion of 6 months treatment in TB patients, and at the corresponding intervals in controls and asthmatics. The initial serum total IgE concentrations were significantly higher in TB patients than in healthy controls (282 +/- 26 U/ml (mean +/- s.e.m.) in TB patients versus 126 +/- 56 U/ml in controls; P = 0.03). However, serum total IgE concentrations significantly decreased (282 +/- 26 U/ml before versus 151 +/- 12 U/ml after treatment; P = 0.03) and tuberculin indurations significantly increased (23.6 +/- 1.8 mm before versus 29.6 +/- 2.1 mm after treatment; P = 0.04) in TB patients. In contrast, initial serum IgE concentrations and tuberculin indurations did not differ significantly from post-observation data in both healthy controls and asthmatics (P>0.30). The present study confirmed that immune responses to M. tuberculosis down-regulate a Th2 immune response, and might contribute to the decreased prevalence of allergic disorders.     

Efficacy of a combined treatment with plasma exchange and cytostatics in macroglobulinemia

Monthly plasma exchange (PE) sessions have been carried out in 3 patients with advanced Waldenstr?m macroglobulinemia, in order to reduce electrophoretic M band under 2g/100 ml. When PE was combined to low doses of cytostatics (n = 18), 3 procedures per session were required to obtain a mean 57.4 +/- 12.3% IgM reduction, from 4.2 +/- 1.2 to 1.7 +/- 0.5 g/100 ml. A mean 61.5 +/- 13.1% IgM reduction, from 5.5 +/- 1.3 to 2.1 +/- 1 g/100 ml, was obtained in 64 procedures carried out as the only therapy in 12 sessions, with 5.3 procedures requirement per monthly session. IgM percent reduction 24 hours after PE was greater with combined treatment (45 +/- 9.7 vs. 28.9 +/- 15.4%; p = 0.001). The advantage of a combined treatment is therefore either a lowered PE requirement or a tapered maintenance cytostatic dosage.     

Effect of exercise on coronary endothelial function in patients with coronary artery disease

BACKGROUND: Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease. METHODS: We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography. RESULTS: In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group). CONCLUSIONS: Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.     

Spontaneous pallidal neuronal activity in human dystonia: comparison with Parkinson's disease and normal macaque

Dystonia is a movement disorder defined by sustained muscle contractions, causing twisting and repetitive movements and abnormal postures. To understand the abnormalities in pallidal discharge in dystonia, we have analyzed the spontaneous activity of 453 neurons sampled from the internal or external pallidum (GPi or GPe) of 22 patients with dystonia, 140 neurons from 11 patients with Parkinson's disease (PD), and 157 neurons from two normal non-human primates (NHPs; Macacca mulatta). All recordings were performed without systemic sedation. Mean GPi discharge rate in dystonia was 55.3 +/- 1.3 (SE) Hz. This was significantly lower than in the normal NHPs (82.5 +/-2.5 Hz) and lower than in PD patients (95.2 +/- 2.3 Hz). Mean GPe discharge rate in dystonia (54.0 +/- 1.9 Hz) was lower than in the normal NHPs (69.7 +/- 3.3 Hz) and was indistinguishable from that in PD patients (56.6 +/- 3.5 Hz). Mean GPi discharge rate was inversely correlated with dystonia severity. GPi showed increased oscillatory activity in the 2- to 10-Hz range and increased bursting activity in both dystonia and PD as compared with the normal NHPs. Because the abnormalities in discharge patterns were similar in dystonia compared with PD, we suggest that bursting and oscillatory activity superimposed on a high background discharge rate are associated with parkinsonism, whereas similar bursting and oscillations superimposed on a lower discharge rate are associated with dystonia. Our findings are most consistent with a model of dystonia pathophysiology in which the two striatal cell populations contributing to the direct and indirect intrinsic pathways of the basal ganglia both have increased spontaneous activity.     

Angiotensin-converting enzyme in hypercalcaemic disorders

Serum angiotensin-converting enzyme (SACE) was elevated (mean +/- S.D. 55.2 +/- 19.8 U/ml) in 11 patients with hypercalcaemia due to sarcoidosis, whereas it was within the normal limits ((20.0 +/- 5.2 U/ml) in 23 patients with other hypercalcaemic conditions. Among these, 16 had primary hyperparathyroidism and a SACE level of 18.6 +/- 4.7 U/ml, significantly lower than in healthy controls (24.4 +/- 6.2 U/ml). In 7 patients with hypercalcaemia due to malignancies or prolonged immobilization SACE was 21.8 +/- 5.9 U/ml. A weakly positive correlation was found between SACE and S-calcium in hypercalcaemic sarcoidosis patients but not in the other patients or in a control group of 144 consecutive sarcoidosis patients. sarcoidosis with hypercalcaemia seems to be associated with a very high prevalence of elevated SACE. Especially when sarcoidosis is suspected to be the cause of hypercalcaemia, SACE measurement may be useful as a rapid diagnostic guide.