Increased postural sway in control subjects with poor orthostatic tolerance.

OBJECTIVES: This study sought to evaluate postural sway in control subjects with good and poor orthostatic tolerance (OT). BACKGROUND: Some asymptomatic volunteers, when subjected to a progressive orthostatic stress test, show early presyncope. We hypothesized that normal subjects with poor OT do not usually faint because they adopt a strategy of increased lower limb movement, which helps maintain venous return. METHODS: In 12 asymptomatic subjects with good OT and 11 with poor OT, assessed by the combined orthostatic stress of head-up tilting and lower body suction, we determined postural sway using a force platform after 1, 5, and 10 min of motionless standing. RESULTS: The subjects with poor tolerance had greater distances and velocities of sway in the anteroposterior direction but not the mediolateral direction. There was a significant negative correlation between postural sway and orthostatic tolerance. CONCLUSIONS: We have shown that in normal subjects with poor OT during a passive orthostatic stress test, their leg movements tend to be greater when standing. These movements are likely to enhance venous return and may at least partly explain why, despite their poor test results, they do not normally faint.     

Abnormalities of coagulation in hypertensive patients with reduced creatinine clearance

PURPOSE: The prothrombotic state that occurs in uremic patients may increase their cardiovascular risk. We studied hypertensive patients with mild-to-moderate impairment of renal function to determine if they had evidence of abnormalities in the coagulation system. SUBJECTS AND METHODS: Renal function was assessed in 382 patients with essential hypertension, in whom 24-hour creatinine clearance, urinary protein excretion, and microalbuminuria were measured. We evaluated the function of the coagulation system by measurement of platelet counts, prothrombin time, partial thromboplastin time, and plasma antithrombin III, fibrinogen, D-dimer, and prothrombin fragment 1 + 2 levels. RESULTS: Impaired renal function, defined as a creatinine clearance of 30 to 89 mL per minute per 1.73 m(2) of body surface area, was found in 168 (44%) of the patients. Age, blood pressure, duration of hypertension, and plasma levels of fibrinogen, D-dimer, prothrombin fragment 1 + 2, and lipoprotein(a) were significantly greater in these patients than in those with normal renal function; these differences persisted after adjustment for potential confounders. Creatinine clearance was significantly and inversely correlated with levels of plasma fibrinogen (Spearman's rho = -0.26, P <0.001), D-dimer (rho = -0.33, P <0.001), and prothrombin fragment 1 + 2 (rho = -0.20, P <0.001). Levels of plasma fibrinogen (P = 0.009) and D-dimer (P = 0.003) were correlated with renal function independent of age, blood pressure, duration of hypertension, triglyceride level, urinary protein excretion, and erythrocyte sedimentation rate. Lipoprotein(a) levels were correlated with fibrinogen (rho = 0.16, P = 0.003) and D-dimer (rho = 0.26, P <0.001) levels. CONCLUSIONS: Increased plasma levels of fibrinogen, D-dimer, and prothrombin fragment 1 + 2 are present in hypertensive patients with mildly decreased creatinine clearance, suggesting that the coagulation system is activated in these patients.     

Functional imaging of pain in patients with primary fibromyalgia

OBJECTIVE: To examine the function of the nociceptive system in patients with fibromyalgia (FM) using functional magnetic resonance imaging (fMRI). METHODS: Two groups of women, 9 with FM and 9 pain-free, volunteered to participate. In Experiment 1, we assessed psychophysical responses to painful stimuli and prepared participants for fMRI testing. For Experiment 2, subjects underwent fMRI scanning while receiving painful and nonpainful heat stimuli. Conventional and functional MR images were acquired using a 1.5 T MR scanner. Scanning occurred over 5 conditions. Condition 1 served as a practice session (no stimuli). Conditions 2 and 5 consisted of nonpainful warm stimuli. Conditions 3 and 4 consisted of an absolute thermal pain stimulus (47 degrees C) and a perceptually equivalent pain stimulus delivered in counterbalanced order. RESULTS: Experiment 1 indicated that subjects with FM were significantly more sensitive to experimental heat pain than controls (p < 0.001). In Experiment 2, fMRI data indicated that the FM group exhibited greater activity than controls over multiple brain regions in response to both nonpainful and painful stimuli (p < 0.01). Specifically, in response to nonpainful warm stimuli, FM subjects had significantly greater activity than controls in prefrontal, supplemental motor, insular, and anterior cingulate cortices (p < 0.01). In response to painful stimuli, FM subjects had greater activity in the contralateral insular cortex (p < 0.01). Data from the practice session indicated brain activity in pain-relevant areas for the FM group but not for controls. CONCLUSION: Our results provide further evidence for a physiological explanation for FM pain.     

Nail fold capillaroscopy findings in patients with primary fibromyalgia

Summary The nail fold capillary morphology and blood flow were examined by capillaroscopy in 10 patients with primary fibromyalgia. Only slight morphological anomalies such as moderate enlargement of capillary loops and variations in calibre were found. No obvious correlation emerged between capillary morphology and the duration of the disease, smoking, or history of Raynaud's phenomenon. Three patients with a history of Raynaud's phenomenon showed sluggish capillary flow correlated with subnormal skin temperature during registration. The findings suggest that marked generalized capillary abnormality such as that often involving the nail fold capillaries in many connective tissue disorders is not a prominent feature of primary fibromyalgia.     

Comparative effects of clonidine and dihydroergotamine on venomotor tone and orthostatic tolerance in patients with severe hypoadrenergic orthostatic hypotension

PURPOSE: Clonidine, an alpha(2)-adrenergic agonist, raises blood pressure in patients with autonomic failure, in whom failure of reflex neurogenic venoconstriction leads to severe orthostatic hypotension. Because animal studies suggest that postjunctional alpha(2)-adrenoreceptors are located mainly on venous capacitance rather than arterial resistance vessels, we tested the hypothesis that venoconstriction is the main mechanism by which clonidine raises blood pressure in patients with autonomic failure. SUBJECTS AND METHODS: We measured forearm venous and arterial tone using plethysmography in 4 patients with autonomic failure before and after acute administration of clonidine (0.4 mg orally) or dihydroergotamine (0.15 mg intravenously), a known venoconstrictor agent. We also recorded supine intraarterial pressure at rest and during graded orthostatic stress with lower body negative pressure. RESULTS: Clonidine and dihydroergotamine caused similar increases in supine (mean +/- SD) arterial pressure (+23 +/- 11 mm Hg vs. and +27 +/- 5 mm Hg) and forearm vascular resistance (+36% +/- 13% vs. +28% +/- 9%). However, the drugs had different effects on forearm venous tone, which increased by 38% +/- 9% with dihydroergotamine (P = 0.01 vs. control) but was unaffected by clonidine (change = 0% +/- 14%). A single dose of clonidine was less effective than a single dose of dihydroergotamine in maintaining arterial pressure during graded orthostatic stress. CONCLUSION: In contrast with what has been hypothesized, clonidine appears to function mainly as an arterial constrictor in patients with hypoadrenergic orthostatic hypotension. Further studies are needed to determine if venoconstrictor agents are of greater therapeutic benefit in this condition than are pure arterial vasoconstrictors.     

Comparisons of spontaneous pain and tenderness in patients with primary fibromyalgia

Summary Pain was assessed in 47 patients with fibromyalgia in the University Rheumatology Clinic in Basle with the aid of three different techniques. First, a simple visual analog scale was used, later a body diagram on which patients could indicate pain separately in different regions of the body (pain score) and, finally, dolorimetric measurements at 56 typical PFS tender points. After four weeks of therapy, pain was again scored by patients using these techniques. The changes in assessment were compared with the aid of Spearman correlation. Data recorded with the aid of the body diagram correlated better with dolorimetric findings than did the results obtained from a simple visual analog scale. The severity of the disease can be more objectively assessed using these three techniques than it can using only the visual analog scale. In particular, the pain score and dolorimetry make possible a clear assessment of the value of therapeutic regimens.With the support of the Deutscher Akademischer Austauschdienst e.V., D-5300 Bonn-Bad Godesberg.     

Evidence of neuromuscular hyperexcitability features in patients with primary fibromyalgia

The presence of clinical and electromyographic (EMG) features of neuromuscular hyperexcitability (NMHE) and of the commonly associated neurovegetative disturbances (NVD) were investigated in 49 patients with primary fibromyalgia (PF) and in a control group of 33 patients with rheumatoid arthritis (RA). At least two clinical features of NMHE were present in 39%, and at least three NVD in 63% of PF patients. In contrast, only 1 RA control had two NMHE features (p greater than 0.005) and three NVD (p less than 0.001). Moreover, a significant post-ischemic spontaneous EMG hyperactivity was observed in 11 PF patients, and in only 1 control with RA (p less than 0.05). Finally, in patients with PF the number of tender points were correlated with psychological tests for depression (p less than 0.02), and the number of NVD. The present study shows that in patients with PF there is a large prevalence of NMHE complaints and NVD. The potential underlying pathogenetic mechanisms are also discussed.     

Increased orthostatic tolerance following moderate exercise training in patients with unexplained syncope

OBJECTIVE: To determine whether a programme of simple, moderate exercise training increases blood volume and improves orthostatic tolerance in patients with attacks of syncope or near syncope related to orthostatic stress. DESIGN: An open study in 14 patients referred with unexplained attacks of syncope, who were shown to have a low tolerance to an orthostatic stress test. Measurements were made of plasma and blood volumes, orthostatic tolerance to a test of combined head up tilt and lower body suction, and baroreceptor sensitivity by applying subatmospheric pressures to a chamber over the neck. Cardiorespiratory fitness was assessed from the relation between heart rate and oxygen uptake during a graded treadmill exercise test. Assessments were made before and after undertaking an exercise training programme (Canadian Air Force 5BX/XBX). RESULTS: After the training period, 12 of the 14 patients showed evidence of improved cardiorespiratory fitness. All 12 patients were symptomatically improved; they showed increases in plasma and blood volumes and in orthostatic tolerance, and decreases in baroreceptor sensitivity. Despite the improved orthostatic tolerance, values of blood pressure both while supine and initially following tilting were lower than before training. CONCLUSIONS: Exercise training has a role in the management of patients with syncope and poor orthostatic tolerance. It improves symptoms and increases orthostatic tolerance without increasing resting blood pressure.     

Abnormalities of hypothalamic-pituitary-thyroid axis in patients with primary empty sella

Primary empty sella (PES) is a very frequent neuroradiological finding in the general population, that can induce hypopituitarism. Some studies focused on the association of PES with GH deficiency (GHD) or hypogonadotropic hypogonadism (HH), while data regarding the involvement of hypothalamic-pituitary-thyroid (HPT) axis, despite sporadic reports of central hypothyroidism, or the occurrence of hypoadrenalism (HA) are scanty. In this study, thyroid function and TSH response to exogenous TRH injection (TRH/TSH) were investigated in 43 patients [10 men and 33 women; aged (mean +/- SD), 48+/-12 yr] with PES: 22 patients had total and 21 partial PES. Forty healthy subjects (9 men and 31 women; aged 46+/-12 yr) were enrolled as a control group. Central hypothyroidism was found only in 2/43 cases, whereas one patient showed primary hypothyroidism. In euthyroid patients, mean serum TSH levels were significantly lower than controls (TSH: 1.0+/-0.7 vs 1.4+/-0.6 mU/l, p<0.01) and 79% of them showed abnormal TRH/TSH responses (TRH test was performed in 34 euthyroid patients: 17 cases with total and 17 cases with partial PES), but mean serum free T4 (FT4) and free T3 (FT3) values were not significantly lower than controls (FT4: 15.9+/-0.4 vs 15.0+/-2.1 pmol/l, p=NS; FT3: 5.3+/-1.2 vs 5.8+/-1.5 pmol/l, p=NS). Moreover, no significant differences were evident in mean serum TSH, FT4 and FT3 between patients with total and partial PES (TSH: 1.1+/-0.7 vs 0.9+/-0.8 mU/l, p=NS; FT4: 16.3+/-2.6 vs 15.7+/-2.2 pmol/l, p=NS; FT3: 5.4+/-1.3 vs 5.2+/-0.8 pmol/l, p=NS) and the TRH/TSH peak was impaired or exaggerated/delayed in 9 and 3 patients with total and in 12 and 3 cases with partial PES. No significant differences in the prevalence of abnormal TRH/TSH responsiveness were found between patients with partial or total PES (chi2=1.6, p=NS). Other impairment of pituitary function was detected in 23/43 patients: GHD was present in 15 cases, HH in 11 and central HA in 5 patients. Isolated or combined hypopituitarism was present in 17 and in 6 patients, respectively. In conclusion, pituitary dysfunction is very frequent in patients with PES, but central hypothyroidism occurs rarely. The entity of arachnoid herniation into the sellar fossa does not play a significant role on the degree of HPT axis dysfunction.     

Salt supplement increases plasma volume and orthostatic tolerance in patients with unexplained syncope.

OBJECTIVE: To determine whether in patients presenting with posturally related syncope administration of salt increases plasma volume and improves orthostatic tolerance. Patients with poor tolerance of orthostatic stress tend to have lower than average plasma and blood volumes. DESIGN: A double blind placebo controlled study in 20 patients and an open study in 11 of the effects of giving 120 mmol/day of sodium chloride. PATIENTS: 31 patients presenting with episodes of syncope who had no apparent cardiac or neurological disease. Plasma volume was determined by Evans blue dye dilution, orthostatic tolerance by time to presyncope in a test of combined head-up tilt and lower body suction, and baroreceptor sensitivity by the effect of neck suction on pulse interval. RESULTS: 8 weeks after treatment, 15 (70%) of the 21 patients given salt and three (30%) of the placebo group showed increases in plasma and blood volumes and in orthostatic tolerance, and decreases in baroreceptor sensitivity. Improvement was related to initial salt excretion in that patients who responded to salt had a daily excretion below 170 mmol. The patients in the placebo group who improved also showed increases in salt excretion. CONCLUSIONS: In patients with unexplained syncope who had a relatively low salt intake administration of salt increased plasma volume and orthostatic tolerance, and in the absence of contraindications, salt is suggested as a first line of treatment.     

Inter-relations between clinical parameters and muscle function in patients with primary fibromyalgia

In forty-four female patients with primary fibromyalgia, muscle function was related to clinical parameters such as age, height, number of tenderpoints, subjective scores of physical capacity and number of subjective symptoms. Muscle function was determined as the dynamic muscle strength measured with an isokinetic dynamometer. Muscle function was found to be low in primary fibromyalgia patients with pronounced muscle tenderness compared to matched controls. Furthermore the reduction in muscle function increased with increasing number of tenderpoints and subjective symptoms. In primary fibromyalgia patients correlations between muscle strength and age/height were either not present or were weaker than in the control subjects. It is concluded that voluntary dynamic muscle strength is a useful parameter for measuring disease impact in primary fibromyalgia patients.     

Vitamin D deficiency and treatment in Iraqi patients with primary fibromyalgia syndrome

Aim of the workTo establish the frequency of vitamin D deficiency in patients with primary fibromyalgia syndrome (FMS) in Basrah, Iraq, and to evaluate the effectiveness of vitamin D supplements in managing disease symptoms.Patients and methods160 FMS patients and 160 matched healthy controls were studied. Serum vitamin D levels were measured. Patients were randomly assigned to one of three treatment groups: Group 1 receiving antidepressant (amitriptyline 10 mg/day); group 2 treated with vitamin D (cholecalciferol 50,000 IU/week) and group 3 received both. All treatments were followed-up for 3 months.ResultsThe frequency of vitamin D deficiency was high (95%). The mean age of patients was 34.3 ± 9.5 years and 92.5% were females. The widespread pain index (WPI) scores significantly improved after 12 weeks in groups 2 and 1 (5.3 ± 3.4 and 7.9 ± 3.4 respectively) compared to baseline (11.9 ± 2.8 and 13.4 ± 2.6 respectively; p = 0.003). The WPI scores of the patients in group 3 improved early into week 4 (3.3 ± 2.7) and continued to improve at weeks 8 and 12 (2.7 ± 2.6 and 1.96 ± 1.6). There were clinically significant improvement in the patients in all treatment groups, most notably in the symptoms severity score (SSS) of fatigue, waking unrefreshed and cognitive impairment. Effects were greatest in the group treated with vitamin D and antidepressants.ConclusionVitamin D deficiency is common in FMS patients and it is associated with worsening of symptoms. Vitamin D supplementation in deficient FMS patients is associated with significant improvement. Screening of FMS patients for hypovitaminosis D is recommended.     

Impairment of cerebral autoregulation in diabetic patients with cardiovascular autonomic neuropathy and orthostatic hypotension.

AIMS: Impaired cerebrovascular reactivity and autoregulation has been previously reported in patients with diabetes mellitus. However, the contribution of cardiovascular diabetic autonomic neuropathy and orthostatic hypotension to the pathogenesis of such disturbances is not known. The purpose of this study was to evaluate cerebral blood flow velocity in response to standing in patients with diabetes and cardiovascular autonomic neuropathy with or without orthostatic hypotension. METHODS: We studied 27 patients with diabetes--eight had cardiovascular autonomic neuropathy and orthostatic hypotension (age 46.4 +/- 13.5 years, diabetes duration 25.0 +/- 11.0 years), seven had autonomic neuropathy without hypotension (age 47.3 +/- 12.7 years, diabetes duration 26.4 +/- 12.1 years), and 12 had no evidence of autonomic neuropathy (age 44.1 +/- 13.8 years, diabetes duration 17.1 +/- 10.2 years)-and 12 control subjects (age 42.6 +/- 9.7 years). Flow velocity was recorded in the right middle cerebral artery using transcranial Doppler sonography in the supine position and after active standing. RESULTS: Cerebral flow velocity in the supine position was not different between the groups studied. Active standing resulted in a significant drop of mean and diastolic flow velocities in autonomic neuropathy patients with orthostatic hypotension, while there were no such changes in the other groups. The relative changes in mean flow velocity 1 min after standing up were -22.7 +/- 16.25% in patients with neuropathy and orthostatic hypotension, +0.02 +/- 9.8% in those with neuropathy without hypotension, -2.8 +/- 14.05% in patients without neuropathy, and -9.2 +/- 15.1% in controls. CONCLUSIONS: Patients with diabetes and cardiovascular autonomic neuropathy with orthostatic hypotension show instability in cerebral blood flow upon active standing, which suggests impaired cerebral autoregulation.