Maternal stress increases fetal brain and neonatal cerebral cortex 5-hydroxytryptamine synthesis in rats: a possible mechanism by which stress influences brain development.

Previous studies have shown that maternal stress modifies 5-hydroxytryptamine (5-HT) receptor binding in several brain regions of the adult offspring and alters the intensity of the behavioral responses to 5-HT receptor agonists. We now report that the same stress, crowding combined with daily saline injections during the final week of pregnancy, elevates maternal plasma free tryptophan level without significantly affecting total tryptophan. The increased maternal plasma tryptophan was associated with significantly increased fetal brain levels of tryptophan, 5-HT and 5-hydroxyindoleacetic acid. These increases were maintained after birth until at least postnatal day 10. Since 5-HT is recognised as having a role in the control of neuron development during the perinatal period, we suggest that the stress-induced increase in fetal brain 5-HT synthesis may play a part in the mechanisms by which prenatal stress alters adult behavior.     

A randomized controlled trial of antibiotics on symptom resolution in patients presenting to their general practitioner with a sore throat.

BACKGROUND: Sore throat is a common symptom presented to general practitioners (GPs), and there remains controversy about the appropriate use of antibiotics. AIM: To compare, in a randomized controlled trial, the effectiveness of penicillin, cefixime and placebo on symptom resolution in patients presenting with a sore throat in general practice. METHOD: Twenty-two GPs in Avon recruited 154 patients, aged 16-60 years, presenting to their GP with a sore throat, and for whom the GP would normally prescribe an antibiotic. Patients were randomized to one of three groups: penicillin V 250 mg four times a day; cefixime 200 mg daily; and placebo. Each was prescribed for five days. The main outcome measures were a diary of symptom resolution over seven days and eradication of group A beta-haemolytic streptococcus (GABHS). RESULTS: Of the 103 (67%) patients who completed symptom diaries, 40 were allocated to receive penicillin, 29 cefixime and 34 placebo. In the analysis including all patients, symptom resolution was greater by day 3 in the cefixime group than in the placebo group. Penicillin did not improve symptom resolution by day 3 compared with placebo, and cefixime was not statistically significantly different from penicillin. There were significant differences in the proportion of patients using analgesia at day 3, with the proportion being lowest in the cefixime group. The results for the subgroup of patients without GABHS were similar to those for all patients; in particular, the only statistically significant difference was between cefixime and placebo. Although numbers were too small for statistical significance, among patients with GABHS the effects of penicillin and cefixime were similarly raised in relation to placebo. CONCLUSION: Compared with placebo, cefixime can improve the rate of resolution of symptoms in patients with a sore throat who are selected for antibiotic treatment by their GP. The unexpected finding that cefixime was of benefit compared with placebo for patients without GABHS suggests that bacteria other than GABHS may be important in the pathogenesis of sore throat.     

Alteration in the pattern of macrophage subtypes in chronic osteomyelitis compared with acute joint infection

Summary Macrophage subtypes were detected in cryostat sections of biopsies from patients with chronic osteomyelitis, acute joint infections and normal bone marrow, using monoclonal antibodies against different macrophage populations. The resident macrophage subtype 25F9, the glucocorticoid-inducible macrophage RM 3/1 and the inflammatory type 27E10 were found in abundance in acute infections. They were also present in tissue sections of uninflamed bone marrow. By contrast, in about 50% of the biopsies from patients with chronic osteomyelitis a reduced number of macrophage subtypes, or even the lack of one or more macrophage subpopulations was found. The unusual absence of macrophage phenotypes seems to be restricted to the area of osteomyelitis because in the tissues of inflamed sinuses in these patients, the macrophage subtypes were present. These findings suggest a disturbance at the level of the macrophages which may contribute to the persistence of the inflammatory process in osteomyelitis.

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Résumé L'utilisation d'anticorps monoclonaux contre différentes sous-populations de macrophages a permis de mettre en évidence, à l'examen de coupes cryostatiques, des sous-types de macrophages. Ces derniers ont été retrouvés dans les moelles osseuses normales comme dans les biopsies provenant de malades atteints d'ostéomyélite chronique et d'arthrite aiguë. Le sous-type résident 25F9, le macrophage glycocorticoïde inductible RM 3/1 et le sous-type inflammatoire 27E10 ont été trouvés en abondance dans les infections aiguës. Ils étaient également présents dans des coupes de moelle osseuse non inflammatoire. Inversement dans près de 50% des cas le nombre de ces sous-populations était considérablement diminué, et même certaines d'entre elles avaient complétement disparu, sur les pièces biopsiques d'ostéomyélite chronique. L'absence inhabituelle de certains types de macrophages semble être limitée à la zone ostéitique car on les retrouve dans le tissu inflammatoire des fistules. Cette étude semble montrer que l'atteinte de ces sous-populations serait responsable de la chronicité de l'ostéomyélite.

     

Corticosteroids and Inhaled Salbutamol in Patients with Reversible Airway Obstruction Markedly Decrease the Incidence of Bronchospasm after Tracheal Intubation

Background: In patients with bronchial hyperreactivity, airway instrumentation can evoke life-threatening bronchospasm. However, the best strategy for the prevention of bronchospasm has not been defined. Therefore, in a randomized, prospective, placebo-controlled study, the authors tested whether prophylaxis with either combined salbutamol-methylprednisolone or salbutamol alone (1) improves lung function and (2) prevents wheezing after intubation.

Methods: Thirty-one patients with partially reversible airway obstruction (airway resistance > 180%, forced expiratory volume in 1 s [FEV1] < 70% of predicted value, and FEV1 increase > 10% after two puffs of salbutamol), who were naive to anti-obstructive treatment, were randomized to receive daily for 5 days either 3 x 2 puffs (0.2 mg) of salbutamol alone (n = 16) or salbutamol combined with methylprednisolone (40 mg/day orally) (n = 15). Lung function was evaluated daily. Another 10 patients received two puffs of salbutamol 10 min before anesthesia. In all patients, wheezing was assessed before and 5 min after tracheal intubation.

Results: Within 1 day, both salbutamol and salbutamol-methylprednisolone treatment significantly improved airway resistance (salbutamol, 4.3 +/- 2.0 [SD] to 2.9 +/- 1.3 mmHg [middle dot] s [middle dot] l-1; salbutamol-methylprednisolone, 5.5 +/- 2.9 to 3.4 +/- 1.7 mmHg [middle dot] s [middle dot] l-1) and FEV1 (salbutamol, 1.79 +/- 0.49 to 2.12 +/- 0.61 l; salbutamol-methylprednisolone, 1.58 +/- 0.66 to 2.04 +/- 1.05 l) to a steady state, with no difference between groups. However, regardless of whether single-dose salbutamol preinduction or prolonged salbutamol treatment was used, most patients (8 of 10 and 7 of 9) experienced wheezing after intubation. In contrast, only one patient receiving additional methylprednisolone experienced wheezing (P = 0.0058).     

Intraarterial sodium nitroprusside infusion in the treatment of severe ergotism

Treatment of migraine with ergot alkaloids may produce systemic vasospasm in patients, especially as a result of automedication and overconsumption but also due to individual hypersensitivity. Peripheral vasoconstriction may lead to gangrene of the extremities, necessitating amputation. Various treatments have been tried against ischemic complications during ergotism with varied and unpredictable results. We report two recent cases of severe acute peripheral ischemia due to ergotamine abuse successfully treated with continuous systemic sodium nitroprusside infusion. The doses used during intraarterial injection are well below those known to be toxic. Consequently, the adverse effects of cyanide toxicity can be avoided. We think that intraarterial infusion of sodium nitroprusside, associated with forced diuresis and the administration of hydroxycobalamin, constitutes the treatment of choice of extreme peripheral ischemia of ergotism.     

Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur.

A closed femur fracture pain model was developed in the C57BL/6J mouse. One day after fracture, a monoclonal antibody raised against nerve growth factor (anti-NGF) was delivered intraperitoneally and resulted in a reduction in fracture pain-related behaviors of approximately 50%. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis. INTRODUCTION: Current therapies to treat skeletal fracture pain are limited. This is because of the side effect profile of available analgesics and the scarcity of animal models that can be used to understand the mechanisms that drive this pain. Whereas previous studies have shown that mineralized bone, marrow, and periosteum are innervated by sensory and sympathetic fibers, it is not understood how skeletal pain is generated and maintained even in common conditions such as osteoarthritis, low back pain, or fracture. MATERIALS AND METHODS: In this study, we characterized the pain-related behaviors after a closed femur fracture in the C57BL/6J mouse. Additionally, we assessed the effect of a monoclonal antibody that binds to and sequesters nerve growth factor (anti-NGF) on pain-related behaviors and bone healing (mechanical properties and histomorphometric analysis) after fracture. RESULTS: Administration of anti-NGF therapy (10 mg/kg, days 1, 6, and 11 after fracture) resulted in a reduction of fracture pain-related behaviors of approximately 50%. Attenuation of fracture pain was evident as early as 24 h after the initial dosing and remained efficacious throughout the course of fracture pain. Anti-NGF therapy did not modify biomechanical properties of the femur or histomorphometric indices of bone healing. CONCLUSIONS: These findings suggest that therapies that target NGF or its cognate receptor(s) may be effective in attenuating nonmalignant fracture pain without interfering with bone healing.