The effects of subcutaneous saline injections on growth and keratinization of mouse tail epidermis.
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To investigate prospectively serious adverse events associated with sumatriptan injection, we studied 12,339 typical migraineurs for up to 12 months each. This study imitated the ordinary clinical use of sumatriptan injection except that: (a) a short, written informed consent was required, (b) there was a centralized, automated dispensing service that audited each patient's product use, (c) patients were sometimes reviewed by telephone, and (d) drug supply and medical consultation were without charge. All adverse events were recorded regardless of etiology. There were 25 fatalities during the study, none being attributable to sumatriptan injection. Of six strokes in the study, two occurred soon after treatment of a migraine attack with sumatriptan injection; whether these were migraine-related or drug-related is discussed. None of the three myocardial infarctions was due to sumatriptan injection use. We conclude that sumatriptan injection is well tolerated when used in accordance with labeling.
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Glutamate and GABA are important nociception modulating transmitters in specific brain regions, i.e. the spinal cord, the thalamic nuclei and the periaqueductal gray (PAG). However, quantitative and topographical changes in glutamate and GABA release in these brain regions during peripheral inflammation episodes have not been characterized in awake animals. To address this issue, an in vivo microdialysis study was carried out in freely moving rats in order to analyze PAG extracellular glutamate and GABA concentrations following unilateral formalin injection into the dorsal skin of the right hind-paw. Both glutamate and GABA release decreased after the injection of formalin during phase I and phase II of hyperalgesia. Because naloxone prevented the decrease of GABA and glutamate release induced by formalin, this study shows that, in vivo, a nociceptive stimulation may activate opioidergic fibres into the PAG. The increased release of endogenous opioids may, in turn, inhibit the activity of the GABAergic neurons (i.e. opioid disinhibition). Formalin injection also decreased extracellular glutamate concentration. However, we found that intra-PAG perfusion with tetrodotoxin only decreased GABA, but not glutamate dialysate values. Although it should be reasonable to speculate that opioids also inhibit glutamate fibres, further investigation is needed to clarify whether or not the dialysate glutamate we measured reflects change in the metabolism or neurotransmitter pool of this amino acid.
We performed a crossover study of apomorphine-induced motor response reproducibility in 10 parkinsonian patients with the "on-off" phenomenon. On 2 separate days, each patient received two successive identical s.c. apomorphine injections, the second injection being randomly administered either 10 or 80 min after the end of the first apomorphine-induced motor benefit. Latency (12.3 +/- 4.5 min) and duration (61.9 +/- 13.3 min) of motor effects were similar in all tests. A transient worsening of the parkinsonian state after a motor improvement induced by apomorphine occurred in most of the patients. Therefore, the duration and severity of the "off" period after a motor improvement does not seem to influence the efficacy of a second apomorphine administration.
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Three patients are reported who developed cutaneous atrophy in the upper arm following a single injection of a long-acting corticosteroid preparation into the deltoid region.
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STUDY OBJECTIVE: To evaluate the safety and pharmacokinetics of recombinant, soluble human CD4 (rCD4) in subjects with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. The protein rCD4 binds to envelope protein, gp120, of the human immunodeficiency virus (HIV) and blocks HIV infection of CD4 lymphocytes in vitro. DESIGN: Phase 1 trial with dose escalation. SETTING: Two university-affiliated hospital clinics. SUBJECTS: Of 42 subjects enrolled, 29 had AIDS and 13 had AIDS-related complex. INTERVENTIONS: The rCD4 was administered by rapid intravenous infusion on day 1, followed by a 3-day washout, then once a day for 10 days, followed by a 7-day washout, and then three times a week for 8 weeks. Doses of 1, 10, 30, 100, and 300 micrograms/kg body weight per day of rCD4 were administered intravenously to 6 subjects at each dose level. Twelve additional patients received 300 micrograms/kg.d of rCD4: 6 by intramuscular and 6 by subcutaneous injection. All subjects were monitored for toxicity. Immunologic and virologic variables were also monitored. MEASUREMENTS AND MAIN RESULTS: Administration of rCD4 was not associated with important toxicity as determined by clinical monitoring or by serum chemistry, hematologic, or immunologic variables. No subjects required dose reduction or discontinuation of therapy due to rCD4-related toxicity. No consistent or sustained changes in CD4 lymphocyte populations or HIV antigen levels were observed. The volume of distribution of rCD4 was small, and clearance remained constant over the dose range studied. The bioavailability of intramuscular injection and subcutaneous injection was 51% and 45%, respectively. CONCLUSIONS: At the dose levels used in this study, rCD4 appears safe and well tolerated. Serum concentrations of rCD4 were achieved that were comparable to concentrations shown to have antiviral activity in vitro. Further studies are indicated to determine whether rCD4 or related molecules will be useful in treating HIV infection.
Insulin injection technique has far greater bearing on glycaemic control than is often recognised. This article discusses the optimal needle length for different injection sites and highlights other crucial aspects, such as needle re-use, importance of adequate mixing of cloudy insulin, and the way pen devices should be stored.
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The tissue reactions of non-tumor-bearing F1 (DBA/2 X C57B16) mice to i.v. and s.c. injected BCG were studied in animals sacrificed at planned intervals following the injection. No appreciable changes were observed prior to day 6, when the thymic cortex and medulla began to show hyperplasia of epithelial cells; many of them had PAS positive cytoplasm and some of these cells were contiguous with the walls of small blood vessels and large cystic spaces containing PAS-positive secretions. The thymic cortical lymphocytes showed, on day 6, a pronounced pyroninophilia and increased mitotic activity without increase in thymic weight. These changes were considerably more striking in the i.v. than in the s.c. injected animals. On the same day a pronounced multifocal lymphocytic infiltration involving the red pulp and the parafollicular and periarteriolar zones of the spleen were observed. It was more pronounced in the i.v. than in the s.c. injected animals. The thymic changes were seen only in animals killed on day 6 and day 10, but were no longer observed on day 14. Beginning with day 14 a pronounced histiocytic granulomatous reaction was observed in the liver. On day 18, this granulomatous reaction was also seen in the spleen, lymph nodes, and lungs of i.v. injected animals. It persisted until day 45. In the s.c. injected animals histiocytic granulomas were seen only at the site of injection and in the regional lymph nodes.
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