Hyperoxia improves autonomic function in individuals with long-duration type 1 diabetes and macroalbuminuria.

AIM: Acute oxygen inhalation and slow deep breathing improve measures of autonomic function transiently in individuals with short-duration type 1 diabetes. Our aims were to examine these interventions and changes in autonomic function in individuals with long-duration type 1 diabetes and to explore interactions with the presence of macroalbuminuria or existing cardiovascular autonomic neuropathy. METHODS: Individuals with type 1 diabetes (n = 54) were exposed to acute oxygen inhalation, slow deep breathing and a combination of both (hereafter 'the combination'). Primary outcomes were change in baroreflex sensitivity and heart rate variability. Associations between changes in outcomes were evaluated using mixed effects models. RESULTS: Mean age ± sd was 60 ± 10 years and diabetes duration was 38 ± 14 years. Changes are presented as per cent difference from baseline with 95% confidence intervals. Acute oxygen inhalation, slow deep breathing and the combination increased baroreflex sensitivity by 21 (10, 34)%, 32 (13, 53)% and 30 (10, 54)%, respectively. Acute oxygen inhalation trended towards increasing heart rate variability 8 (-1, 17)% (P = 0.056), and slow deep breathing and the combination increased heart rate variability by 33 (18, 49)% and 44 (27, 64)% respectively. Macroalbuminuria or cardiovascular autonomic neuropathy did not modify results. CONCLUSION: Autonomic function is improved transiently in individuals with long-duration type 1 diabetes and normoalbuminuria or macroalbuminuria by acute oxygen inhalation and slow deep breathing. There is a risk of survival bias. Autonomic dysfunction might be a reversible condition, and hypoxia might represent a target of intervention.

Glutamate dysregulation in the trigeminal ganglion: a novel mechanism for peripheral sensitization of the craniofacial region.

In the trigeminal ganglion (TG), satellite glial cells (SGCs) form a functional unit with neurons. It has been proposed that SGCs participate in regulating extracellular glutamate levels and that dysfunction of this SGC capacity can impact nociceptive transmission in craniofacial pain conditions. This study investigated whether SGCs release glutamate and whether elevation of TG glutamate concentration alters response properties of trigeminal afferent fibers. Immunohistochemistry was used to assess glutamate content and the expression of excitatory amino acid transporter (EAAT)1 and EAAT2 in TG sections. SGCs contained glutamate and expressed EAAT1 and EAAT2. Potassium chloride (10 mM) was used to evoke glutamate release from cultured rat SGCs treated with the EAAT1/2 inhibitor (3S)-3-[[3-[[4-(trifluoromethyl)ben zoyl]amino]phenyl]methoxy]-L-aspartic acid (TFB-TBOA) or control. Treatment with TFB-TBOA (1 and 10 µM) significantly reduced the glutamate concentration from 10.6 ± 1.1 to 5.8 ± 1.4 µM and 3.0 ± 0.8 µM, respectively (p<0.05). Electrophysiology experiments were conducted in anaesthetized rats to determine the effect of intraganglionic injections of glutamate on the response properties of ganglion neurons that innervated either the temporalis or masseter muscle. Intraganglionic injection of glutamate (500 mM, 3 µl) evoked afferent discharge and significantly reduced muscle afferent mechanical threshold. Glutamate-evoked discharge was attenuated bythe N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate (APV) and increased by TFB-TBOA, whereas mechanical sensitization was only sensitive to APV. Antidromic invasion of muscle afferent fibers by electrical stimulation of the caudal brainstem (10 Hz) or local anesthesia of the brainstem with lidocaine did not alter glutamate-induced mechanical sensitization. These findings provide a novel mechanism whereby dysfunctional trigeminal SGCs could contribute to cranial muscle tenderness in craniofacial pain conditions such as migraine headache.

[Chronic lymphocytic and myeloid leukemia in the same patient]. / Kronisk lymfatisk og myeloid leukaemi hos samme patient.

A patient with chronic lymphocytic leukemia (CLL) treated with chlorambucil and prednisone developed chronic myelocytic leukemia (CML) five years later. An association between the two chronic leukemias has only rarely been reported. In the majority of cases the CLL preceded CML after which the malignancies coexisted morphologically in bone marrow and peripheral blood. In this case we report a suppression of CLL related symptoms and blood findings after the emergence of CML. However, immunophenotypic studies demonstrated a minor remaining population of CLL cells in the peripheral blood.

Antibodies to pigeon antigens in pigeon breeders. Detection of antibodies by an enzyme-linked immunosorbent assay.

Antibodies to whole pigeon serum (PS) and pigeon dropping extract (PDE) were investigated in pigeon breeders and controls by an enzyme-linked immunosorbent assay (ELISA). The optimal antigen concentration was in the range of 3-30 microgram protein/ml for both PS and PDE. PDE antibody titres greater than or equal to 10240 were found in three (75%) of four patients with pigeon breeders' disease (PBD) and in 19 (13.6%) of 140 other pigeon breeders (P = 0.011). PS antibody titres greater than or equal to 10240 occurred in all four (100%) PBD patients and in only seven (5.0%) of 140 other breeders (P = 0.0002). In 85 blood donors antibodies in low titres against PS and PDE occurred in 4.7% and 7.1%, respectively. By immunodiffusion three or more precipitin lines were found more often in PBD patients than in other breeders (P = 0.0006), and the highest ELISA antibody titres occurred in patients with precipitating antibodies. No correlation between P blood group phenotypes or anti-P1 antibodies and respiratory symptoms or antibodies to pigeon antigens could be demonstrated.