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.     

On language laterality in normal dextrals and sinistrals: Results from the Bilateral Object Naming Latency Task

Rasmussen and Milner [N.Y. Acad. Sci. Vol. 299, pp. 355–379, 1977] published data on late-lesioned (after age 6) epileptic patients who had suffered left hemisphere lesions. They estimated that left hemisphere dominance occurred in 96% of dextrals and 70% of sinistrals. These figures have been regarded as valid estimates for normal dextrals and sinistrals. We administered the Bilateral Object Naming Latency Task, a verbal tachistoscopic task with very good psychometric properties, to 188 dextral and 72 sinistral normals. Results showed that 93.6% of the dextrals and 80.3% of the sinistrals were left hemisphere dominant. A consideration of results from a number of carefully conducted dichotic listening studies suggests, as do present results, that the 70% left-dominance estimate of Rasmussen and Milner for normal sinistrals may be too low by about 10%. It is suggested that ‘bilateral dominance’, present in 15% of the epileptic sinistrals of Rasmussen and Milner, may be much less common in normal sinistrals.     

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.

     

Parasternal mediastinal sonography: sensitivity in the detection of anterior mediastinal and subcarinal tumors

Twenty-seven patients with anterior mediastinal and subcarinal mediastinal tumors confirmed by CT and 30 control subjects were prospectively investigated by sonography performed via a parasternal approach in both decubitus positions. The sonograms and CT scans were interpreted blindly by two investigators and the results of the two procedures were compared. In the group of 30 controls, sonography via the right parasternal approach showed the anterior mediastinum in 29 (97%) and the subcarinal space in 27 (90%). Fifteen (94%) of 16 anterior mediastinal tumors and 16 (94%) of 17 subcarinal tumors were identified sonographically. These results show that parasternal sonography is a sensitive technique for the detection of tumors in the anterior mediastinal and subcarinal mediastinal spaces.     

Sperm antibodies.

Anti-sperm antibodies (ASA) occur in 1% to 30% of infertile couples. Mechanisms by which ASA impair fertility include prevention of fertilization by decreasing acrosome reaction and/or zona pellucida binding, and postfertilization effects. Treatment for ASA involves assisted reproductive technologies.     

Neurotoxicity and carcinogenicity of N-methylolacrylamide in F344 rats and B6C3F1 mice

Toxicology and carcinogenicity studies of N-methylolacrylamide were conducted by administering the chemical by gavage in water to both sexes of F344/N rats and B6C3F1 mice 5 times per week for 16 d, 13 wk, or 2 yr. In 16-d studies, rats receiving doses of 200 mg/kg or higher and mice receiving 400 mg/kg died. In 13-wk studies, all rats given 100 mg/kg or higher doses died. Rats receiving 50 mg/kg or higher doses developed hindlimb ataxia progressing to paralysis. In neurobehavioral assessments, decreased forelimb and hindlimb grip strength occurred in rats at doses as low as 12.5 mg/kg. Landing footspread was also increased in dosed rats compared to controls. Axon filament and myelin sheath degeneration in the spinal cord and/or peripheral nerves occurred in rats receiving doses of 25 mg/kg or higher. Necrosis in the granular cell layer of the cerebellum was seen in rats given 200 mg/kg. Mice receiving 200 mg/kg in 13-wk studies died. Decreased grip strength was noted in mice at doses as low as 25 mg/kg, and rotarod performance was also affected by N-methylolacrylamide administration, but no neuropathology was seen microscopically. Testicular weights were decreased at doses as low as 12.5 mg/kg, and hepatocellular necrosis, thymic lymphocyte necrosis, and hemorrhage, necrosis, and mineralization of the zona reticularis of the adrenal gland were seen in mice that died (200 mg/kg). In 2-yr studies, survival and weight gains in male and female rats receiving doses of 6 or 12 mg/kg/d were minimally affected. No biologically important clinical signs or neoplastic or nonneoplastic lesions were attributed to N-methylolacrylamide administration to rats, suggesting that higher doses could have been tolerated. In mice, survival was not different between dosed and control groups (0, 25, or 50 mg/kg/d). Body weights were higher by as much as 25% in dosed compared to control groups. No compound-related clinical signs were observed, but increases in neoplasms of the harderian gland, liver, and lung were clearly related to chemical administration in both sexes of mice. Benign granulosa-cell neoplasms of the ovary were also increased in dosed female mice.     

Management und Kontrolle einer Influenzapandemie Konzeptionelle Überlegungen für einen deutschen Influenzapandemieplan

The World Health Organization (WHO) and the majority of the influenza experts assume that an influenza pandemic might reemerge again at any time. Therefore WHO has called upon all member states to set up a national pandemic preparedness plan. For Germany such a plan is long overdue. In order to gain as much time as possible early identification of the pandemic virus is of highest priority. Furthermore progression of a pandemic is influenced by the time needed to develop a subtype specific vaccine as well as by the vaccines availability. However, in case of a pandemic a shortage of vaccines and prophylactic pharmaceuticals cannot be avoided. Therefore, decisions have to be made in order to establish priorities concerning the vaccination and the prophylactic and/or therapeutic antimicrobial treatment of selected sub-populations. There is also a need to lay down measures ensuring the distribution of vaccines and antiviral drugs, adequate health care and ambulance service, and the organization of dignified funerals of the deceased. It is also necessary to enter into an early agreement with vaccine manufacturers on a guaranteed supply of respective batches of vaccine doses. In addition procedures should be established to allow an increase in vaccine production in case of a pandemic. There is also a need for early agreements with the manufacturers of antiviral agents and for a decision concerning the establishment of a national stockpile to guarantee an adequate supply. Some measures must already be taken in the inter-pandemic period. Those are: enhancement of surveillance and research, development of new vaccines and new methods of vaccine production, licensing of new vaccines in case of a pandemic and establishment of a national influenza committee. Problems like the effectiveness of antiepidemic measures, such as immigration control and the closing of schools, must be solved in advance of a pandemic.     

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).