ABSTRACT
BACKGROUND: The relationship between bullous pemphigoid (BP) and neurological disease has been the subject of numerous recent studies and BP antigens and their isoforms have been identified in the central nervous system (CNS). Whilst epidemiological data support this association, little is known about the pathomechanism behind this link and the immunological characteristics of patients with BP and neurological disease, other than multiple sclerosis (MS), has not been studied. OBJECTIVE: We aimed to compare the cutaneous immune response in BP patients with and without neurological disease, to investigate whether or not there is a distinctive immunopathological profile in patients with concomitant BP and neurological disease. METHODS: Seventy-two patients with BP were included and divided into two groups; those with neurological disease (BP+N, n = 43) and those without (BP-N, n = 29). Patients in BP+N group had a confirmed neurological disease by a hospital physician, neurologist or psychiatrist with positive neurological imaging where appropriate, or a Karnofsky score of 50 or less due to mental impairment. All sera were analysed with indirect immunofluorescence (IIF) using serial dilutions up to 1:120000, immunoblotting (IB) and Enzyme-linked immunosorbent assay (ELISA) for BP180 and BP230. RESULTS: Median antibody titres by IIF were 1:1600 vs. 1:800 for BP-N and BP+N, respectively, although the difference did not reach statistic significance (P = 0.93, Mann-Whitney U-test). ELISA values for both BP180 and BP230 did not differ significantly between the two groups. Similarly, autoantibodies to specific antigens as identified by ELISA and IB were not related to the presence of neurological disease. CONCLUSION: The results of this study indicate that patients with BP and neurological disease exhibit an immune response to both BP180 and BP230, thus the link between the CNS and the skin is not dependent on a specific antigen, but possibly both antigens or their isoforms may be exposed following a neurological insult, and play a role in generation of an immune response.
Subject(s)
Nervous System Diseases/immunology , Nervous System Diseases/pathology , Pemphigoid, Bullous/immunology , Pemphigoid, Bullous/pathology , Aged , Aged, 80 and over , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique, Indirect , Humans , Male , Middle AgedSubject(s)
Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Dermatologic Agents/therapeutic use , Glucocorticoids/therapeutic use , Pemphigoid, Bullous/drug therapy , Dermatology , Diagnosis, Differential , Humans , Immunosuppressive Agents/therapeutic use , Pemphigoid, Bullous/diagnosis , Societies, Medical , United KingdomSubject(s)
Autoimmune Diseases of the Nervous System/complications , Encephalitis/complications , Pemphigoid, Bullous/complications , Anti-Inflammatory Agents/therapeutic use , Autoimmune Diseases of the Nervous System/drug therapy , Encephalitis/drug therapy , Encephalitis/immunology , Female , Humans , Methylprednisolone/therapeutic use , Middle Aged , Pemphigoid, Bullous/drug therapyABSTRACT
Current recommendations on the management of acute myocardial infarction and the use of thrombolysis are reviewed.
Subject(s)
Angioplasty, Balloon, Coronary , Myocardial Infarction/therapy , Acute Disease , Algorithms , Angioplasty, Balloon, Coronary/methods , Anticoagulants/therapeutic use , Clinical Trials as Topic , Clopidogrel , Drug Therapy, Combination , Fibrinolytic Agents/therapeutic use , Heparin/therapeutic use , Humans , Myocardial Infarction/diagnosis , Platelet Aggregation Inhibitors/therapeutic use , Randomized Controlled Trials as Topic , Risk Factors , Thrombolytic Therapy/methods , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic use , Treatment OutcomeABSTRACT
The threshold for activation of the humoral renal antihypertensive system, presumably residing in the renomedullary interstitial cells (RIC), is substantially reset upwards in the spontaneously hypertensive rat (SHR). Depressor reactions, normally elicited by an increased renal perfusion pressure, can be inhibited either by high frequency renal nerve stimulation or blockade of nitric oxide synthesis, i.e. manoeuvres decreasing renal blood flow at this high perfusion pressure. The present study was designed to explore the effects on regional renal haemodynamics of blocking NO synthesis with N-omega-nitro-L-arginine (L-NNA) in chloralose anaesthetized SHR and Wistar rats. Mean arterial blood pressure (MAP), heart rate (HR), renal blood flow (RBF), cortical blood perfusion (CBP) and papillary blood perfusion (PBP) were measured in renally innervated and denervated SHR (Si n = 8, Sd n = 8) and in Wistar rats (Wi n = 10, Wd n = 10). An innervated non-treated Wistar group served as control (Ci n = 12). The laser Doppler technique was used to record CBP and PBP. MAP increased in all groups receiving L-NNA while HR, RBF and CBP simultaneously decreased. The relative decreases in RBF were more marked into the two SHR groups than in the corresponding Wistar groups. After L-NNA PBP also decreased in all four groups despite the increased MAP and more so in the Si group; Wi -19 +/- 8 (P < 0.05), Wd -17 +/- 6 (P = 0.07), Si -50 +/- 9 (P < 0.01) and Sd -25 +/- 9% (P < 0.05). We conclude that NO is important for maintaining PBP especially in SHR. The more marked decrease in PBP in the innervated SHR suggests a NO/renal nerve interaction in the control of renomedullary blood flow in SHR. This finding may be of importance for the regulation of the humoral renal depressor mechanism.
Subject(s)
Hemodynamics/drug effects , Kidney/drug effects , Nitric Oxide/pharmacology , Animals , Arginine/pharmacology , Blood Pressure/drug effects , Heart Rate/drug effects , Laser-Doppler Flowmetry , Male , Rats , Rats, Inbred SHR , Rats, Wistar , Time FactorsABSTRACT
Intrarenal blood flow regulation probably affects long-term blood pressure homeostasis. We have previously shown that 5 Hz renal sympathetic stimulation inhibits a humoral renal depressor mechanism, otherwise activated when increasing perfusion pressure to an isolated kidney in a cross-circulation set-up. This inhibition was suggested to occur as a result of a reduction of renomedullary blood flow. Little is known about nervous blood flow regulation within the medulla. Therefore in this study, total renal (RBF), cortical (CBF) and papillary (PBF) blood flows were separately measured by ultrasonic and laser-Doppler techniques in Wistar rats during graded renal sympathetic stimulations. Periods of 15 min stimulation at 0.5, 2 and 5 Hz were performed in random order. RBF decreased at 0.5 Hz by 1%, at 2 Hz by 16% (P < 0.001) and at 5 Hz by 49% (P < 0.001). In a similar fashion (r = 0.73, P < 0.001), CBF decreased by 1%, 10% (P < 0.001) and 37% (P < 0.001), respectively. By contrast, PBF increased by 2% at 0.5 Hz and 4% at 2 Hz, while it decreased at 5 Hz, by 4% (P < 0.05, compared with 2 Hz). It seems therefore, that superficial renocortical and total renal blood flows are closely regulated by renal sympathetic nerves with increasing vasoconstriction at higher frequencies, while medullary blood flow, on the other hand, seems to be under strong local control, tending to offset neurogenic flow restrictions.