Reflex sympathetic dystrophy: result of autonomic denervation?

1. To investigate the nature of sympathetic dysfunction in the pathogenesis of reflex sympathetic dystrophy, the microcirculatory vasoconstrictive responses to dependency were investigated in the skin of the hand of 76 reflex sympathetic dystrophy patients with unilateral disease by means of laser Doppler flowmetry (in perfusion units) and capillary microscopy. The patients were divided into three stages according to their perception of skin temperature (stage I in the case of a stationary warmth sensation, stage II in the case of an intermittent warmth and cold sensation, and stage III in the case of a stationary cold sensation). The vasoconstrictive responses were induced by lowering of the affected hand. 2. As compared to controls, the mainly sympathetically mediated vasoconstrictive response at thermoregulatory level of the skin microcirculation, as measured by laser Doppler flowmetry, was attenuated at stage I (1.82 versus 1.41, P < 0.05), stage II (1.82 versus 1.09, P < 0.0001) and stage III (1.82 versus 1.14, P < 0.01), suggesting the involvement of sympathetic denervation at all stages of the reflex sympathetic dystrophy syndrome. This sympathetic denervation may also account for the observed increase in thermoregulatory skin blood flow at stage I as compared to controls (152 versus 81, P < 0.01). 3. Since sympathetic denervation has been reported to cause increased sensitivity of vascular structures to catecholamines, the decrease in thermoregulatory skin blood flow at stages II (54 versus 81, P < 0.05) and III (31 versus 81, P < 0.05), both as compared to controls, may result from hypersensitivity to catecholamines of skin microvessels. 4. The sympathetically independent vasoconstrictive response at the nutritive level of skin microcirculation, as measured by capillary microscopy, was impaired only at stage III as compared to controls (1.04 versus 2.06, P < 0.05). This divergence in microvascular reactivity upon dependency of the nutritive and thermoregulatory subsystems also supports the hypothesis of sympathetic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Non-invasive assessment of vascular reactivity in forearm skin of patients with primary Raynaud's phenomenon and systemic sclerosis

We have non-invasively assessed neurovascular control mechanisms in forearm skin of 10 healthy control subjects, eight patients with primary Raynaud's phenomenon (PRP) and 10 patients with systemic sclerosis (SSc) by iontophoresing acetylcholine (endothelial dependent), sodium nitroprusside (endothelial independent) and adrenaline, and measuring subsequent blood flow responses by dual-channel laser Doppler. Because basal forearm blood flow is low, adrenaline response was assessed by attenuation of reperfusion hyperaemia following 60 s of upper arm occlusion. Reperfusion hyperaemia prior to adrenaline iontophoresis differed significantly between groups (F2.21 = 4.3, P = 0.03), being lowest in the SSc and highest in the PRP group. However, the degree of attenuation of this hyperaemia by adrenaline did not differ between groups and all groups demonstrated similar vasodilatory responses to acetylcholine and to sodium nitroprusside. These findings may reflect that abnormalities in vascular tone in patients with Raynaud's phenomenon are local to the digits, or that vasoactive agents not examined in this study play a key role.     

Change in colonic motility after extrinsic autonomic denervation in dogs

Changes in colonic motility were compared in dogs undergoing autonomic denervation of the paraaortic and presacral (group A), paraaortic (group B), or mesocolonic region (group C), and sham operation (group D). Five bipolar recording electrodes were placed into the seromuscular layer of the colon and rectum. The numbers of continuous electrical response activity and contractile electrical complex after an intragastric olive oil injection were smaller in group A than in the other groups (P < 0.05) from three weeks through six months after denervation. This difference was significant even in the proximal colon. These data suggest that the pelvic plexus may play an important role in colonic motility including the proximal colon. The damage to the plexus did not recover for at least six months after denevation. Pelvic plexus injury may thus be one of possible explanations for the prolonged change in bowel habit after anterior resection of the rectum.     

Electrophysiological tests of autonomic function in patients with idiopathic autonomic failure syndromes

Three electrophysiological tests of autonomic function were performed in patients with autonomic nervous system dysfunction to define test sensitivities and specificities. The skin sympathetic response, Valsalva ratio, and heart rate variation with deep breathing were studied in 10 patients with multiple system atrophy (MSA) and in 7 patients with pure (also called progressive or primary) autonomic failure (PAF); control subjects were 17 normal individuals of similar age. Thirteen patients had abnormal skin sympathetic responses, and 16 had abnormal Valsalva ratios. Fourteen patients had an abnormal variation of the heart rate with deep breathing. Taking the three tests together, binary logistic regression for distinguishing between patients and normal subjects correctly classified 91% of the 33 individuals for whom there were complete data with sensitivity of 88% and specificity of 94%. However, only 69% of the patients could be correctly classified by a logistic regression for discriminating between MSA and PAF. Electromyography (EMG) studies showed that 7 of 8 patients with MSA but only 2 of 7 patients with PAF (both multiparous women) had denervation of the rectal sphincter muscle. The EMG study is, therefore, valuable in men, but has a high false positive rate in women, probably because of pudendal nerve injury from parturition.     

Failure of erythropoietin treatment in a case with primary autonomic failure

All prisons provide healthcare services which aim to meet the needs of prisoners. The goal of the service is to give prisoners access to the same quality and range of health care as the NHS gives the general public. However, within the prison environment priorities centre around order, control and discipline and therefore an ethos of health care needs to be developed. Custody reduces the prisoner's opportunity for self-care and independent action as inmates have to consult nursing or medical staff for even the most simple remedies. Nursing staff in the prison service can play a significant part in primary health care, mental disorder and health promotion. Nurses have the knowledge, skills and attitudes needed to deal with this diverse and vulnerable prison population and to promote a positive interface between custody and care.     

Possible erythromelalgia-like syndrome associated with nifedipine in a patient with Raynaud's phenomenon

OBJECTIVE: To describe a patient who was diagnosed with Raynaud's phenomenon, was prescribed immediate-release nifedipine, and developed a possible erythromelalgia-like syndrome. CASE SUMMARY: A 24-year-old white woman with a history of esophageal spasms and Raynaud's phenomenon was prescribed nifedipine 10 mg po qid. Approximately 1 hour after the patient had taken the fourth dose of nifedipine, she experienced acute erythema and a burning sensation in her feet and lower limbs, light-headedness, and palpitations. Because of a reportedly abnormally low blood pressure, the patient took diphenhydramine 50 mg po and proceeded to the clinic. On arrival, abnormal vital signs were BP 140/48 mm Hg and HR 130 beats/min. Without any other medical intervention, approximately 30 minutes later her blood pressure and heart rate had returned to baseline at 122/60 mm Hg and 96 beats/min, respectively. The nifedipine was permanently discontinued and the patient's symptoms completely resolved over 24 hours. DISCUSSION: The characteristic symptoms of erythromelalgia include burning pain, increased skin temperature, and erythema of the extremities, usually to the feet, lower legs, and, less often, the hands. Erythromelalgia-like syndromes secondary to the administration of many medications have been reported. Several nifedipine-related reports describe an erythromelalgia-like syndrome similar to our reported case. CONCLUSIONS: Because the patient was not taking any other medications and the symptoms started with the administration of nifedipine and were relieved after its discontinuation, nifedipine was thought to be the cause of the erythromelalgia-like syndrome.     

Clinical diversity of Raynaud's phenomenon in childhood: report of six cases

Six pediatric patients with Raynaud's phenomenon are reported. Three patients had clinical and immunological evidence for a connective tissue disease; one had primary Raynaud's phenomenon associated with antinuclear antibodies and two had Raynaud's phenomenon secondary to exposure to lead and to a vibrating instrument, respectively. The diagnostic and therapeutic implications of these observations will be discussed.     

Cyanotic Raynaud's phenomenon with conventional but not with liposomal amphotericin B: three case reports

Despite its common adverse effects intravenous (i.v.) amphotericin B is an indispensable antifungal drug in childhood oncology. We report here on three cases of painful cyanotic Raynaud's phenomenon after i.v. administration or inhalation of amphotericin B. A liposomal i.v. preparation of amphotericin B was well tolerated by the infants. Spasms of peripheral vessels mediated by thromboxane A2 could be responsible for the Raynaud's phenomenon. Hence, inhibitors of prostaglandin synthesis are suggested for therapy.     

Cerebrovascular and cardiovascular responses to graded tilt in patients with autonomic failure

BACKGROUND AND PURPOSE: Patients with autonomic nervous system failure often experience symptoms of orthostatic intolerance while standing. It is not known whether these episodes are caused primarily by a reduced ability to regulate arterial blood pressure or whether changes in cerebral autoregulation may also be implicated. METHODS: Eleven patients and eight healthy age- and sex-matched control subjects were studied during a graded-tilt protocol. Changes in their steady state middle cerebral artery mean flow velocities (MFV), measured by transcranial Doppler, brain-level mean arterial blood pressures (MABPbrain), and the relationship between the two were assessed. RESULTS: Significant differences between patients and control subjects (P < .05) were found in both their MFV and MABPbrain responses to tilt. Patients' MFV dropped from 60 +/- 10.2 cm/s in the supine position to 44 +/- 14.0 cm/s at 60 degrees head-up tilt, whereas MABPbrain fell from 109 +/- 11.7 to 42 +/- 16.9 mm Hg. By comparison, controls' MFV dropped from 54 +/- 7.8 cm/s supine to 51 +/- 8.8 cm/s at 60 degrees, whereas MABPbrain went from 90 +/- 11.2 to 67 +/- 8.2 mm Hg. Linear regression showed no significant difference in the MFV-MABPbrain relationship between patients and control subjects, with slopes of 0.228 +/- 0.09 cm.s-1.mm Hg-1 for patients and 0.136 +/- 0.16 cm.s-1.mm Hg-1 for control subjects. CONCLUSIONS: The present study found significant differences between patients and control subjects in their MFV and MABPbrain responses to tilt but no difference in the autoregulatory MFV-MABPbrain relationship. These results suggest that patients' decreased orthostatic tolerance may primarily be the result of impaired blood pressure regulation rather than a deficiency in cerebral autoregulation.     

Attenuated cardiac sympathetic responsiveness during dynamic exercise in patients with heart failure

BACKGROUND: Cardiac norepinephrine (NE) spillover is increased in patients with chronic heart failure. This elevation is partly due to augmented NE release but also to reduced capacity for cardiac NE removal processes. In patients with mild to moderate heart failure, it is not known whether the described alteration in cardiac sympathetic function also affects cardiac NE spillover during intense sympathetic activation and whether other organs respond in proportion to the heart. METHODS AND RESULTS: Twenty-two patients with heart failure and 15 age-matched healthy subjects were studied. Whole-body and regional (NE) spillovers from the heart and kidneys were assessed at baseline and during supine cycling exercise (10 minutes) with the use of steady-state infusions of tritiated NE (isotope dilution). Cardiac performance was evaluated by means of catheterization of the right side of the heart. Cardiac NE spillover was higher (P < .05) at baseline in the patient group than in healthy subjects, whereas renal and whole-body NE spillovers were similar between the study groups. During exercise, cardiac NE spillover increased 13-fold (P < .05) in healthy subjects but only 5-fold (P < .05) in the cardiac failure group, the latter reaching a lower peak value (P < .05). In contrast, there was no difference between the study groups in either renal or whole-body NE spillover responsiveness to exercise. CONCLUSIONS: Patients with mild to moderate heart failure demonstrated a selective attenuation of cardiac sympathetic responsiveness during dynamic exercise. This attenuation may convey reduced inotropic and chronotropic support to the failing heart.     

Hemodynamic and autonomic effects of intravenous saterinone in patients with chronic heart failure

In this study, the hemodynamic and neurohumoral/autonomic effects of intravenous saterinone (a selective phosphodiesterase type III inhibitor, with additional alpha 1-blocking properties) were evaluated. In a double-blind, placebo-controlled design, 36 patients with moderate to severe heart failure were studied (saterinone, n = 24; placebo, n = 12). Invasive hemodynamic measurements, by using right-heart catheterization, were performed, as well as measurement of plasma neurohormones and analysis of heart rate variability (HRV), to study drug influences on neurohumoral activation and autonomic tone. Systemic vascular resistance significantly decreased during saterinone infusion, accompanied by a decrease in systemic blood pressure (both p values < 0.05) and an increase in heart rate (p = 0.05). Filling pressures also decreased during saterinone, but this was statistically significant only for pulmonary capillary wedge pressure, whereas the cardiac index remained unaffected. Plasma neurohormones (norepinephrine, epinephrine, and renin activity) were not significantly influenced by saterinone. HRV analysis revealed no significant effect of saterinone on autonomic tone. These results suggest that intravenous saterinone has a significant vasodilating effect in patients with moderate to severe chronic heart failure (CHF), without exerting an adverse effect on the autonomic nervous system, as demonstrated by assessment of plasma neurohormones and HRV analysis.     

Rapid distal small bowel transit associated with sympathetic denervation in type I diabetes mellitus

BACKGROUND: The pattern of progression of a meal from the stomach to the caecum in diabetes mellitus is controversial and the differential roles of transit through the jejunum and the ileum have not been investigated in diabetes. AIMS: To determine gastric emptying and transit rates through proximal and distal regions of the small bowel in type I diabetic patients. SUBJECTS: The study included six diabetic patients with evidence of autonomic neuropathy (DM-AN group), 11 diabetics without autonomic dysfunction (DM group), and 15 control volunteers. METHODS: Gastric emptying and small bowel transit of a liquid meal were evaluated scintigraphically in these subjects. Transit through regions of interest corresponding to the proximal and distal small intestine up to the caecum was determined and correlated with gastric emptying rates, cardiovascular measurements of autonomic function, and the occurrence of diarrhoea. RESULTS: Gastric emptying and transit through the proximal small bowel were similar in the three groups. The meal arrived to the caecum significantly earlier in DM-AN patients (median; range: 55 min; 22-->180 min) than in the DM group (100 min; 44-->180 min, p < 0.05) or in controls (120 min; 80-->180 min, p < 0.02). Accumulation of chyme in the distal small bowel was decreased in DM-AN patients, who showed values for peak activity (30%; 10-55%) significantly lower than in the DM group (49%; 25-77%, p = 0.02) and controls (50%; 30-81%, p = 0.02). In DM patients (n = 17), the time of meal arrival to the caecum was significantly correlated with both orthostatic hypotension (coefficient of contingency, C = 0.53, p < 0.01) and diarrhoea (C = 0.47, p < 0.05), but not with gastric emptying rates. CONCLUSIONS: Patients with type I diabetes mellitus and sympathetic denervation have abnormally rapid transit of a liquid meal through the distal small bowel, which may play a part in diarrhoea production.     

Scintigraphic assessment of regionalized defects in myocardial sympathetic innervation and blood flow regulation in diabetic patients with autonomic neuropathy

OBJECTIVES: This study sought to evaluate whether regional sympathetic myocardial denervation in diabetes is associated with abnormal myocardial blood flow under rest and adenosine-stimulated conditions. BACKGROUND: Diabetic autonomic neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death, potentially by altering electrical stability or impairing myocardial blood flow, or both. The effects of denervation on cardiac blood flow in diabetes are unknown. METHODS: We studied 14 diabetic subjects (7 without DAN, 7 with advanced DAN) and 13 nondiabetic control subjects without known coronary artery disease. Positron emission tomography using carbon-11 hydroxyephedrine was used to characterize left ventricular cardiac sympathetic innervation and nitrogen-13 ammonia to measure myocardial blood flow at rest and after intravenous administration of adenosine (140 microg/kg body weight per min). RESULTS: Persistent sympathetic left ventricular proximal wall innervation was observed, even in advanced neuropathy. Rest myocardial blood flow was higher in the neuropathic subjects (109 +/- 29 ml/100 g per min) than in either the nondiabetic (69 +/- 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79 +/- 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left ventricular myocardial blood flow was significantly less in the neuropathic subjects (204 +/- 73 ml/100 g per min) than in the nonneuropathic diabetic group (324 +/- 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44% (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic subjects, respectively. Assessment of the myocardial innervation/blood flow relation during adenosine infusion showed that myocardial blood flow in neuropathic subjects was virtually identical to that in nonneuropathic diabetic subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than that in the nonneuropathic diabetic subjects in the proximal innervated segments. CONCLUSIONS: DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.     

Workplace bullying in NHS community trust: staff questionnaire survey

OBJECTIVES: To determine the prevalence of workplace bullying in an NHS community trust; to examine the association between bullying and occupational health outcomes; and to investigate the relation between support at work and bullying. DESIGN: Questionnaire survey. SETTING: NHS community trust in the south east of England. SUBJECTS: Trust employees. MAIN OUTCOME MEASURES: Measures included a 20 item inventory of bullying behaviours designed for the study, the job induced stress scale, the hospital anxiety and depression scale, the overall job satisfaction scale, the support at work scale, and the propensity to leave scale. RESULTS: 1100 employees returned questionnaires-a response rate of 70%. 421 (38%) employees reported experiencing one or more types of bullying in the previous year. 460 (42%) had witnessed the bullying of others. When bullying occurred it was most likely to be by a manager. Two thirds of the victims of bullying had tried to take action when the bullying occurred, but most were dissatisfied with the outcome. Staff who had been bullied had significantly lower levels of job satisfaction (mean 10.5 (SD 2. 7) v 12.2 (2.3), P<0.001) and higher levels of job induced stress (mean 22.5 (SD 6.1) v 16.9 (5.8), P<0.001), depression (8% (33) v 1% (7), P<0.001), anxiety (30% (125) v 9% (60), P<0.001), and intention to leave the job (8.5 (2.9) v 7.0 (2.7), P<0.001). Support at work seemed to protect people from some of the damaging effects of bullying. CONCLUSIONS: Bullying is a serious problem. Setting up systems for supporting staff and for dealing with interpersonal conflict may have benefits for both employers and staff.