Health-related quality of life and its predictive role for analgesic effect in patients with painful polyneuropathy.

Painful polyneuropathy is a common neuropathic pain condition. The present study describes health-related quality of life (HRQL) in a sample of patients with painful polyneuropathy of different origin and the possible predictive role of HRQL for analgesic effect. Ninety-three patients with a diagnosis of painful polyneuropathy were included in the analysis. Data were obtained from three randomised, placebo-controlled cross-over studies testing the effect of different drugs on polyneuropathic pain (St. John's wort, venlafaxine/imipramine and valproic acid). Patients completed a HRQL questionnaire (SF-36) after a drug-free baseline period and at the end of each treatment period. At baseline, all eight SF-36 scores were lower than in the normal population. No significant differences were found between SF-36 scales during placebo and treatment with valproic acid and St. John's wort. Those two drugs had not shown a pain relieving effect in former analysis. The SF-36 scale of bodily pain (BP) was improved by venlafaxine treatment (p=0.023). General health (GH) and vitality (VT) were improved under treatment with imipramine (GH: p=0.006, VT: p=0.015). In a multivariate logistic regression analysis, baseline SF-36 scores predicted subsequent response to pharmacological treatment. Results show an impaired HRQL in painful polyneuropathy and suggest that HRQL may predict response to analgesic treatment.     

Intravenous Lidocaine Relieves Spinal Cord Injury Pain: A Randomized Controlled Trial

Background: Neuropathic pain in spinal cord injury is a common challenging therapeutic condition. The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine.

Methods: Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were randomized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min. Twelve patients reported evoked pain, and 12 patients had no evoked pain. Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing.

Results: Lidocaine significantly reduced spontaneous pain in all patients (P < 0.01) and in each of the two groups with (P < 0.01) and without (P = 0.048) evoked pain, with no difference in number of responders (pain reduction >= 33%) between the patients with (n = 6) and without (n = 5) evoked pain. Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia, pinprick hyperalgesia, or pain evoked by repetitive pinprick.     

Hyperosmolarity selectively enhances IgE-receptor-mediated histamine release from human basophils

Increased osmotic pressure has been reported to cause non-cytotoxic histamine release (HR) from human basophils, as well as a potentation of HR induced by anti-IgE. In this study, the effects of hyperosmolar Na–K-acetate (300–600 mOsm/kg H₂O) on HR was studied in washed human blood cells from newborns, adult volunteers and patients with severe atopic dermatitis. These three patient groups represesented 3 very distinct populations with respect to total plasma IgE content, medians were <0.2 IU/ml, 20.5 IU/ml and 2508 IU/ml, respectively. Increasing osmolarity to 500 mOsm/kg H₂O caused little HR in the absence of other stimuli, whereas at 600 mOsm/kg H₂O a significant increase in spontaneous HR was seen. The HR induced by anti-IgE and Concanavalin A, acting through the IgE-receptor, was increased approximately twofold at 500 mOsM/kg H₂O. Responses were highly correlated to results at 300 mOsm/kg H₂O. The use of 600 mOsm/kg H₂O buffers caused a further increase in most, but not all blood samples. The potentiation of IgE-receptor-mediated HR when using hyperosmolar media was clearly independent of plasma IgE contents, and did not change the concentration-response to anti-IgE. In contrast, HR induced by the IgE-receptor-independent stimuli, Formyl-met-leu-phe and calcium ionophore A 23187, were not enhanced at all by incrased osmotic pressure. We conclude, that hyperosomolar media selectively enhance IgE-receptor-mediated HR. The use of hyperosmolar media may therefore be beneficial in a diagnostic application of washed blood HR assays use in allergy diagnosis.     

Diurnal variations of serum erythropoietin at sea level and altitude

This study tested the hypothesis that the diurnal variations of serum-erythropoietin concentration (serum-EPO) observed in normoxia also exist in hypoxia. The study also attempted to investigate the regulation of EPO production during sustained hypoxia. Nine subjects were investigated at sea level and during 4 days at an altitude of 4350 m. Median sea level serum-EPO concentration was 6 (range 6–13) U·l^–1. Serum-EPO concentration increased after 18 and 42 h at altitude, [58 (range 39–240) and 54 (range 36–340) U·l^–1, respectively], and then decreased after 64 and 88 h at altitude [34 (range 18–290) and 31 (range 17–104) U·l^–1, respectively]. These changes of serum-EPO concentration were correlated to the changes in arterial blood oxygen saturation (r = –0.60,P = 0.0009), pH (r = 0.67,P = 0.003), and in-vivo venous blood oxygen half saturation tension (r = –0.68,P = 0.004) but not to the changes in 2, 3 diphosphoglycerate. After 64 h at altitude, six of the nine subjects had down-regulated their serum-EPO concentrations so that median values were three times above those at sea level. These six subjects had significant diurnal variations of serum-EPO concentration at sea level; the nadir occurred between 0800–1600 hours [6 (range 4–13) U·l^–1], and peak concentrations occurred at 0400 hours [9 (range 8–14) U·l^–1,P = 0.02]. After 64 h at altitude, the subjects had significant diurnal variations of serum-EPO concentration; the nadir occurred at 1600 hours [20 (range 16–26) U·l^–1], and peak concentrations occurred at 0400 hours [31 (range 20–38) U·l^–1,P = 0.02]. This study demonstrated diurnal variations of serum-EPO concentration in normoxia and hypoxia, with comparable time courses of median values. The results also suggested that EPO production at altitude is influenced by changes in pH and haemoglobin oxygen affinity.     

A chimeric T cell receptor with super-signaling properties

A key question yet to be resolved concerns the structure and function relationship of the TCR complex. How does antigen recognition by the TCR-alphabeta chains result in the activation of distinct signal transduction pathways by the CD3-gammadeltaepsilon/zeta complex? To investigate which part of the TCR-beta chain is involved in TCR signaling, we exchanged different domains of the constant regions of the TCR-beta chain with the corresponding TCR-gamma chain domains. We show here that hybridoma cells expressing a chimeric TCR-beta chain (betaIII) containing intracellular and transmembrane TCR-gamma amino acids, together with a wild-type TCR-alpha (alphawt) chain, were 10 times more sensitive to antigenic stimulation compared to cells expressing TCR-alphawt/betawt chains. This super-signaling phenotype of the betaIII chain was observed in two different TCRs. One specific for an alloantigen (I-A(bm12)) and one for an autoantigen (I-A(b)/MOG(35-55)). We found that this chimeric alphawt/betaIII TCR had normal association with CD3-gammadeltaepsilon and zeta chains. To investigate the effect of the chimeric betaIII chain in transgenic T cells, we made MOG(35-55)-specific TCR transgenic mice expressing either the alphawt/betawt or chimeric alphawt/betaIII TCR. Similar to what was observed in hybridoma cells, transgenic alphawt/betaIII T cells showed a super-signaling phenotype upon antigenic stimulation. Further studies may help us understand the effect of increased TCR signaling on autoimmunity and may lead to the identification of signaling molecules that can be targeted to stop the progression of autoimmune disorders such as multiple sclerosis.     

Alpers'' disease

Observations on skin reflectance were made on 309 endogamous Indian families, for constitutive (medial upper arm) and facultative skin colour (forehead) to investigate which of the two colours is under a rigid control of genetic action. An assessment of data by coefficient of correlation "r" show that facultative colour is inherited more strictly than the constitutive colour.
Received 4 July, accepted 3 October 1983