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A comparison of diltiazem and metoprolol in hypertension. Swedish Diltiazem-Metoprolol Multicentre Study Group.

A double-blind, parallel-group multicentre study has been done to compare the antihypertensive properties, effects on serum lipoproteins and adverse effect profiles of diltiazem and metoprolol given as monotherapy to primary hypertensive patients. 128 patients were included from 10 participating centers. Following a placebo wash-out period of 5 weeks, patients were randomized either to diltiazem or metoprolol treatment according to a forced titration regimen. Each dose was given for a 4-week period in a stepwise regimen. A total of 119 patients, 59 and 60 in the two groups, completed the study. Supine and standing BPs were reduced in a similar, dose-dependent fashion by diltiazem and metoprolol. In the former supine BP fell from 161/101 to 151/91 mmHg at the highest dose level. In the latter patients, supine BP at the highest dose level was reduced from 161/102 to 155/94 mmHg. Target pressures (DBP less than or equal to 90 mmHg and/or DBP reduction of greater than or equal to 10%) were reached in 63% and 48% of the patients, respectively. HDL-cholesterol was increased in diltiazem-treated patients and decreased in those on metoprolol. Otherwise, serum lipoproteins did not differ significantly between treatments. The incidence and severity of dose-dependent adverse effects did not differ significantly between treatments, although moderate to distressing side effects were reported more commonly by metoprolol-treated patients. Ankle oedema and breathlessness tended to be more common on diltiazem therapy, while tiredness, increased sweating and sleep disturbances appeared to be experienced more frequently by metoprolol-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Sequence of centromere separation: differential replication of pericentric heterochromatin in multicentric chromosomes.

The dicentric and multicentric chromosomes in L cells and a brain tumor cell line of mouse display only one site of kinetochore formation associated with the 'active' centromere. The accessory or 'inactive' centromeres show premature separation. These cell lines were treated with 10(-6) M 5-bromodeoxyuridine (BrdUrd) followed by anti-BrdUrd antibody to study the pattern of replication of pericentric heterochromatin flanking the active vs inactive centromeres. Regardless of its quantity, heterochromatin around the inactive centromere replicates earlier than that associated with the active centromere. There appears to be a relationship between the timing of separation of a centromere and the timing of replication of pericentric heterochromatin. The premature replication of heterochromatin associated with an inactive centromere may be responsible for its premature separation and, hence, inactivity.

Animals↗

Multicentric Castleman's disease in a patient with primary Sjögren's syndrome.

A 38-year-old woman suffering from primary Sjögren's syndrome for 2 years developed angiofollicular hyperplasia (multicentric Castleman's disease). In Sjögren's syndrome (SS) a number of findings indicate the presence of a B-cell hyperactivity that may evolve to a lymphoproliferative disorder. This report adds another pathological event to the complex spectrum of lymphoproliferative diseases in SS.

Adult↗

Glioblastoma multiforme in three family members, including a case of true multicentricity.

Three cases of glioblastoma multiforme are described, occurring in two brothers and the sister of their father. One of the cases was found at autopsy to represent true multicentric glioblastoma, with five widely separated lesions affecting both hemispheres. It is postulated that there may be an association between factors responsible for multiple foci of transformation and a familial tendency to develop glioma.

Aged↗

A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy.

A multicentre retrospective study was carried out on the characteristics and course of myasthenia gravis (MG) in Italy. Data from 1152 patients, fairly representative of the myasthenic population seeking medical advice, were analysed for diagnostic criteria, clinical aspects and therapeutic approaches. Mean follow-up was 4.9 years. The disease was correctly diagnosed within 2 years of the onset in 80% of cases. Onset of symptoms peaked in the second and third decade in females and fell between 20 and 59 years in males. At first observation 87% of the patients had generalized MG. Maximal worsening was observed within 3 years in 77% of patients. At the last follow-up, 35% of cases were symptom-free (pharmacological remission 24%, remission without treatment 11%). The more severe the disease at the first observation and at the maximal worsening of symptoms, the lower was the proportion of remissions. Steroids were given in 54% and immunosuppressants in 18%. Thymectomy was performed in 72%, mostly in women, younger than age 40, and with generalized MG. Thymectomy seemed to improve the course of the disease, mostly in patients operated on shortly after diagnosis and those with generalized mild-to-moderate disease and with a normally involuted thymus. MG was lethal in 4% of patients, principally men, older than 40, in grade 3 or worse at first observation, with a short history of disease, and with thymona.

Adolescent↗

Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study).

Anti-oxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes mellitus, thus providing a rationale of potential therapeutic value for diabetic patients. The effects of the anti-oxidant alpha-lipoic acid (thioctic acid) were studied in a 3-week multicentre, randomized, double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy; ALADIN) in 328 non-insulin-dependent diabetic patients with symptomatic peripheral neuropathy who were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (1200, 600, or 100 mg ALA) or placebo (PLAC). Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) were scored at baseline and at each visit (days 2-5, 8-12, and 15-19) prior to infusion. In addition, the Hamburg Pain Adjective List, a multidimensional specific pain questionnaire, and the Neuropathy Symptom and Disability Scores were assessed at baseline and day 19. According to the protocol 260 (65/63/66/66) patients completed the study. The total symptom score in the feet decreased from baseline to day 19 by -4.5 +/- 3.7 (-58.6%) points (mean +/- SD) in ALA 1200, -5.0 +/- 4.1 (-63.5%) points in ALA 600, -3.3 +/- 2.8 (-43.2%) points in ALA 100, and -2.6 +/- 3.2 (-38.4%) points in PLAC (ALA 1200 vs PLAC: p = 0.003; ALA 600 vs PLAC: p < 0.001). The response rates after 19 days, defined as an improvement in the total symptom score of at least 30%, were 70.8% in ALA 1200, 82.5% in ALA 600, 65.2% in ALA 100, and 57.6% in PLAC (ALA 600 vs PLAC; p = 0.002). The total scale of the Pain Adjective List was significantly reduced in ALA 1200 and ALA 600 as compared with PLAC after 19 days (both p < 0.01). The rates of adverse events were 32.6% in ALA 1200, 18.2% in ALA 600, 13.6% in ALA 100, and 20.7% in PLAC. These findings substantiate that intravenous treatment with alpha-lipoic acid using a dose of 600 mg/day over 3 weeks is superior to placebo in reducing symptoms of diabetic peripheral neuropathy, without causing significant adverse reactions.

Adolescent↗

A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population.

A cross-sectional multicentre study of randomly selected diabetic patients was performed using a standardised questionnaire and examination, to establish the prevalence of peripheral neuropathy in patients attending 118 hospital diabetes clinics in the UK. Vibration perception threshold was performed in two centres to compare with the clinical scoring systems. A total of 6487 diabetic patients were studied. 53.9% male, median age 59 years (range 18-90 years). 37.4% Type 1 (insulin-dependent) diabetes mellitus, with a median duration of diabetes 8 years (0-62 years). The overall prevalence of neuropathy was 28.5% (27.4-29.6%) (95% confidence interval) in this population. The prevalence in Type 1 diabetic patients was 22.7% (21.0-24.4%) and in Type 2 (non-insulin-dependent) diabetic patients it was 32.1% (30.6-33.6%). The prevalence of diabetic peripheral neuropathy increased with age, from 5% (3.1-6.9%) in the 20-29 year age group to 44.2% (41.1-47.3%) in the 70-79 year age group. Neuropathy was associated with duration of diabetes, and was present in 20.8% (19.1-22.5%) of patients with diabetes duration less than 5 years and in 36.8% (34.9-38.7%) of those with diabetes duration greater than 10 years. Mean vibration perception threshold measured at the great toe was 21.1 +/- 13.5 SD volts and correlated with the neuropathy disability score, r = 0.8 p < 0.001. In conclusion, diabetic peripheral neuropathy is a common complication associated with diabetes. It increases with both age and duration of diabetes, until it is present in more than 50% of Type 2 diabetic patients aged over 60 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A multicentre trial of the aldose-reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy.

The effects of the aldose-reductase inhibitor, tolrestat, on chronic symptomatic diabetic sensorimotor neuropathy were studied during a placebo-controlled, randomised, 52-week multicentre trial. Of the four tolrestat doses investigated, only the highest dose group, 200 mg once daily, showed subjective and objective benefit over baseline and placebo, and further analyses are confined to this group (n = 112) and placebo (n = 107). Painful and paraesthetic symptoms were analysed separately: improvement in paraesthetic symptoms were seen at one year (p = 0.04), though painful symptoms improved on both placebo and active therapies. Significant improvement in both tibial and peroneal motor nerve conduction velocities were seen at 52 weeks. Tolrestat 200 mg once daily was significantly better than placebo in producing concordant improvements in both motor nerve conduction velocities and paraesthetic symptom scores at 24 weeks (p = 0.01), 42 weeks (p = 0.01) and 52 weeks (p = 0.02). Long-term benefit [concordant improvement at 24 weeks maintained until 52 weeks] was seen in 28% of treated patients compared to 5% on placebo (p = 0.001). It is concluded that some sustained improvement in symptomatic diabetic neuropathy may be obtained following aldose-reductase inhibition with tolrestat 200 mg once daily.

Aldehyde Reductase↗

Multicentre comparison between slow-release furosemide and bendroflumethiazide in congestive heart failure.

The effects of slow-release furosemide and bendroflumethiazide in the ambulatory treatment of mild to moderate congestive heart failure were compared in a controlled multicentre study using a randomized, double-blind procedure. In the first trial, slow-release furosemide 60 mg daily was compared with 2.5 mg bendroflumethiazide; in the second trial the daily doses were 30 mg and 2.5 mg, respectively. There were 47 patients in Trial I and 39 in Trial II. The randomised allocation to the treatment regimen was made after a four-week period on bendroflumethiazide 2.5 mg daily, and treatment was continued for 12 weeks. Clinical and laboratory data were recorded before, during and at the end of the trial. Adverse effects were few and minor in both medication groups, and there were no significant intergroup differences. It was concluded slow-release furosemide 30 mg or 60 mg daily was as effective as bendroflumethiazide 2.5 mg daily for maintenance treatment in mild to moderate congestive heart failure.

Adult↗

Multicentre comparison of the antihypertensive effect of acebutolol and hydrochlorothiazide in uncomplicated mild-moderate hypertension in the elderly.

To evaluate the efficacy of acebutolol, 400-600 mg/day in elderly hypertensive patients, and to compare it with hydrochlorothiazide 25-50 mg/day, 45 patients with mild-moderate uncomplicated hypertension were treated for 6 weeks in a multicentre, single-blind, randomized, crossover trial. Acebutolol decreased supine systolic blood pressure from 186.5 to 162.7 mmHg and diastolic blood pressure from 107.4 to 92.4 mmHg. Hydrochlorothiazide decreased systolic blood pressure from 185.0 to 166.4 and diastolic blood pressure from 107.2 to 96.4. There was no difference between the effects of acebutolol and hydrochlorothiazide on blood pressure during the trial. Both drugs proved to be safe and effective antihypertensive agents, provided the major contraindications for their use were taken into account. Beta-blockade by acebutolol was highly effective in treating mild-moderate arterial hypertension in the elderly.

Acebutolol↗

Clinical evaluation of labetalol alone and combined with chlorthalidone in essential hypertension: a double-blind multicentre controlled study.

In a multicentre, double-blind, crossover, placebo-controlled study, the antihypertensive effect of labetalol 100 mg and chlorthalidone 10 mg, given alone or in combination, has been assessed in 32 hypertensive patients. The combination had a greater effect in reducing blood pressure than did its separate components. This was particularly evident after exercise. Heart rate increased during chlorthalidone therapy, decreased during labetalol therapy, and a summation effect was observed during treatment with the combination. In most cases additivity was observed, as no interaction between the single components was observed, except for heart rate after exercise, and for diastolic blood pressure in the upright position. No interaction was observed either in the biochemical indices or in the clinical side-effects.

Adult↗

Renal oncocytoma. A review of the literature and report of an unusual multicentric case.

Renal oncocytoma is a rare tumour of the kidney composed exclusively of large polygonal cells with eosinophilic, granular cytoplasm. Ultrastructurally they are distinguished by the presence of large numbers of mitochondria and histochemically by abundant oxidative enzymes and adenosine triphosphate. Macroscopically these tumours are usually light brown in colour and commonly exhibit a dense central area of fibrous scarring, with fibrous trabeculae extending from this central zone in a stellate fashion. Renal oncocytomas are commoner in males than females (sex ratio 2:1) and although the age range at presentation is wide, there is a peak incidence in the seventh decade. The prognosis following surgical removal is excellent, despite the fact that many of these tumours are large. Invasion of the perirenal fat and the renal vein and metastatic spread to regional lymph nodes is documented, but death from metastatic disease is rare. The great majority of renal oncocytomas reported are solitary. We describe a multicentric renal oncocytoma, the sixth so far reported.

Adenoma↗

Multicentre comparative trial of tienilic acid and hydrochlorothiazide in hypertensive patients.

To compare the clinical and metabolic effects of a new diuretic uricosuric agent, tienilic acid, with those of hydrochlorothiazide, a multicentre double-blind trial was performed in 56 hypertensive patients. Twenty-eight patients were randomly assigned to take tienilic acid and 28 to take hydrochlorothiazide. The diuretic and anti-hypertensive actions of the two compounds were similar. No significant differences were observed between tienilic acid and hydrochlorothiazide in their effects on urinary and serum electrolytes, hepatic and renal function tests, and fasting lipids. The patients who received tienilic acid showed a significant fall in serum uric acid, mediated by the uricosuric effect. The availability of an agent combining diuretic, antihypertensive and hypouricemic effects offers promise in the treatment of arterial hypertension.

Adolescent↗

Arwin in peripheral arterial circulatory disorders: controlled multicentre trials.

The effect of Arwin on peripheral arterial occlusive disease has been studied in two multicentre trials. In the first, in cases of severe peripheral arterial circulatory disorders of the lower extremities with permanent rest pain (stages III and III + IV according to Fontaine) Arwin had a better intravenous therapeutic effect than anticoagulant treatment. A further trial was done to investigate whether subcutaneous administration of Arwin would have an effect superior to classical conservative therapy with vasodilator drugs in this type of disease. The results were assessed by sequential analysis. Arwin was again shown to be a much better treatment. Problems of medical documentation and statistics are discussed in relation to the value of sequential analysis.

Ancrod↗

Hypotensive effect of oxprenolol in mild to moderate hypertension: a multicentre controlled study.

In a multicentre, double-blind, between-patient study the hypotensive effect of oxprenolol was investigated in 329 patients with mild to moderate hypertension. A factorial experimental design with three factors was chosen: oxprenolol--none or daily doses of 20, 40, 60 and 80 mg; dihydralazine and hydrochlorothiazide, respectively, none or 30 mg daily. Each treatment was given for 4 weeks after an adequate period of withdrawal from any other possible hypotensive therapy and one week of placebo wash-out. Irresponsive of the association with dihydralazine and/or hydrochlorothiazide, oxprenolol had a hypotensive effect linearly related to dose for standing systolic (P less than 0.05) and diastolic (P less than 0.01) pressure, and for lying diastolic (P less than 0.05) pressure. The additional of dihydralazine enhanced the time-course of the hypotensive effect of oxprenolol, particularly the 80 mg dose level. In general, the combination of oxprenolol with dihydralazine and hydrochlorothiazide caused larger reductions in blood pressure, particularly with oxprenolol 80 mg. In the latter group, the eventual falls in blood pressure were 30.5 and 14.4 mmHg for lying systolic and diastolic, respectively; and 32.1 and 20.0 mmHg for the standing systolic and diastolic pressures. The drug was well tolerated; major side effects (heart failure and bronchospasm) occurred in three patients.

Clinical Trials as Topic↗

The effects of prazosin and propranolol in combination with thiazide diuretics on blood pressure and serum lipids: a multicentre study.

We have carried out randomized 12-week multicentre study to compare the effects of prazosin and propranolol on blood pressure and serum lipids in 70 patients with essential hypertension after a 4 week minimum period of treatment with thiazide diuretics. After 12 weeks treatment with prazosin (n = 40, 1.5-12.0 mg per day) or propranolol (n = 30, 30-120 mg per day) with diuretics there was a significant blood pressure reduction from 165.1/97.9 mmHg to 151.2/90.6 mmHg and from 167/96.5 mmHg to 153/91.9 mmHg, respectively. In the 12th week a significant decrease was noted in triglyceride and in low-density lipoprotein cholesterol (LDL + VLDL-C), but no significant effects were seen in high-density lipoprotein cholesterol (HDL-C) in patients receiving prazosin. On the other hand, a significant decrease in lecithin cholesterol acyltransferase (LCAT) was seen in patients receiving propranolol. Twenty-six of 40 patients receiving prazosin were given an additional 12 weeks of treatment. Twenty-two of 30 patients initially treated with propranolol were switched from propranolol to prazosin after 13 weeks and given prazosin up to the 24th week. At 24 weeks, the blood pressure was 149/93.0 mmHg in the prazosin group and 155/89.2 mmHg in the group which switched from propranolol to prazosin. Triglyceride remained reduced in the prazosin group at the 24th week. In the group which switched from propranolol to prazosin, triglyceride decreased significantly over the next 12 weeks.

Benzothiadiazines↗

Italian multicentre study of carpal tunnel syndrome: study design. Italian CTS Study Group.

In September 1996, during a carpal tunnel syndrome (CTS) symposium, the Italian CTS Study Group was funded. The group designed a strict clinical and neurophysiological protocol for performing a wide multicentre study on idiopathic CTS in hands. In addition to the traditional evaluations, the group also adopted a validated patient-oriented measurement in order to obtain comprehensive and reliable data for the clinical picture. The study was designed to: (1) better assess the clinical picture of the CTS population, especially using new measurement tools (patient-oriented); (2) evaluate the sensitivity of an electrodiagnostic protocol; (3) re-evaluate the validity of a neurophysiological classification; and (4) evaluate the influence of social status and quantify some of the aspects regarding economic and social costs. The study design is described.

Carpal Tunnel Syndrome↗

Psychosocial adversity in an adolescent psychiatry inpatient cohort: WHO ICD-10 findings from a multicentre prospective study.

Sixteen Axis 5 ICD-10 codes were applied to a prospective multicentre study of 276 adolescent psychiatric inpatients. Frequency distributions were obtained for the whole cohort and separately for each of the seven main ICD-9 psychiatric diagnoses. Certain abnormal psychosocial situations were associated with particular diagnoses, and many significant correlations were found between Axis 5 codes. Factor analysis with varimax rotation produced four factors accounting for 46% of the total variance.

Adolescent↗