Absence of IFNγ expression induces neuronal degeneration in the spinal cord of adult mice

Background  

Interferon gamma (IFNγ) is a pro-inflammatory cytokine, which may be up-regulated after trauma to the peripheral or central nervous system. Such changes include reactive gliosis and synaptic plasticity that are considered important responses to the proper regenerative response after injury. Also, IFNγ is involved in the upregulation of the major histocompatibility complex class I (MHC class I), which has recently been shown to play an important role in the synaptic plasticity process following axotomy. There is also evidence that IFNγ may interfere in the differentiation and survival of neuronal cells. However, little is known about the effects of IFNγ absence on spinal cord neurons after injury.     

Influence of inorganic nutrition on growth and PSP toxin production of Alexandrium minutum (Dinophyceae) from Cork Harbour, Ireland.

The physiological response of the PSP toxin producing dinoflagellate Alexandrium minutum isolated from the Irish coast was assessed after modulating the initial concentrations of nitrate and phosphate in batch cultures. The cell growth in cultures of strain CK.A02 was primarily controlled by nitrate availability. In all experiments, only gonyautoxins 2 and 3 (GTX2 and 3) were synthesized along the different growth phases, with GTX3 dominating ( approximately 80%) at all stages, making the GTX2-3 toxin profile a possible population marker of A. minutum in Cork Harbour. The cellular toxin quotas remained low and relatively stable at around 2pgcell(-1), except when high N:P ratios were initially used for culture inoculations; in these conditions PSP toxins accumulated up to 14pgcell(-1). Due to the composition of the toxin profile, the toxicity of strain CK.A02 was generally relatively low (from 1.1 to 1.7pg STX eqcell(-1)) in comparison with strains from other geographic areas except when phosphate limiting culture conditions were applied (maximum of 12.5pg STX eqcell(-1)). Results showed that sufficient soluble protein quotas were necessary to observe the intra-cellular accumulation of PSP toxins in phosphate limiting conditions, highlighting also the requirement of adequate nitrogen supplies. The possible existence of localized toxicity hot spots in the field, linked to the accumulation of PSP toxins within A. minutum cells as a metabolic response to adverse environmental conditions, could potentially increase risks for shellfish farming operations.     

Fibreoptic bronchoscopy without general anaesthetic.

We have used flexible fibreoptic bronchoscopy using sedation and local anaesthesia in 50 children aged 2-19 years (median 10) using an Olympus BFP20 instrument. Indications were opportunistic pneumonias (n = 11), persistent atelectasis (n = 11), recurrent pneumonia (n = 7), miscellaneous lower airway disease (n = 7), recurrent wheezing (n = 3), haemoptysis (3), to diagnose infection or rejection of heart-lung transplants (n = 3), stridor (n = 2), suspected airway compression (n = 1), evaluation of tracheostomy (n = 1), and suspected foreign body (n = 1). In 43 cases (86%) the diagnosis was related to the primary indication. In five (10%) unrelated abnormalities were found, and five (10%) were normal. In 13 (26%) treatment was altered as a result of flexible fibreoptic bronchoscopy. Complications were transient respiratory arrest (n = 2), hypoxia (n = 2), pneumonia (n = 2), and laryngospasm (n = 1). All complications were followed by complete recovery. Our results suggest that flexible fibreoptic bronchoscopy is safe. Advantages over rigid bronchoscopy include greater visual range, fewer complications, and the avoidance of a general anaesthetic. Though invasive it can yield important diagnostic and therapeutic information.     

Lung function from infancy to school age in cystic fibrosis

The aim was to investigate pulmonary mechanics in patients with cystic fibrosis during infancy and again in early childhood to see whether infant tests predicted status at school age. Plethysmographic measurements of thoracic gas volume and airways resistance were made in 29 patients at 6 months and again at 5 years 10 months. Maximum flow at functional residual capacity was measured during infancy for comparison with maximum expiratory flow rates during childhood. While many patients had normal measurements during infancy, pulmonary function had deteriorated by school age. Thoracic gas volume at school age was significantly related to the values in infancy, but other measurements made during childhood were independent of infant values. The relations between measurements in infancy and early childhood described here provide a background against which the role of external factors on pulmonary function in young children with cystic fibrosis can be investigated.     

Flashlamp-excited dye laser therapy of idiopathic vulvodynia is safe and efficacious

Objective: The management of chronic vulvovaginal pain, not explicable on specific histologic grounds, presents a major problem in referral centers for lower genital tract diseases.Study design: This article reports on a two-step protocol in a sample of 175 medical nonresponders, drawn from a 2-year cohort of 725 women with vulvovaginal pain. The first maneuver was the use of a flashlamp-excited dye laser to selectively photocoagulate symptomatic subepithelial blood vessels in 168 women; the second was the microsurgical removal of chronically painful Bartholin's glands in 52 women not responsive or not suited to flashlamp-excited dye laser photothermolysis.Results: Dye laser response rates werer independent of whether patients manifested macroscopic focl of painful erythema (“vestibular adenitis”) or just colposcopically apparent hyperemia-ectasia of the individual blood vessels (“pruritic papillomatosis”) (55% vs 45% after a single surgical procedure; 76% vs 65% after serial retreatment; p not significant). Conversely, response rates were much lower among women in whom pressure on the Bartholin's glands produced sharp, lancinating pain (15% vs 66% after a single surgical procedure; 22% vs 93% after serial retreatment; p < 0.001). Forty-two (85%) of 50 patients with flashlamp-excited dye laser failure had deep pain; however, the impasse to progress was broken by gland removal. Final response rates were 92.5% (complete response 62%; partial response 30%) in the “surface-only” group and 80.3% in the “surface-plus-deep” group (χ² = 14.9; p < 0.001). The major complication was acute bacterial cellulitis, occurring in the first postoperative week. Modification of the treatment protocol to include topical antibiotics with an occlusive dressing reduced the cellulitis rate from 17.2% to 2.5%. In four women (1.8%) Koebner-like exophytic condylomas also developed within 1 month of flashlamp-excited dye laser surgery.Conclusion: The availability of a safe, efficacious, and relatively noninvasive treatment should reduce the need for resective surgery in most patients with idiopathic vulvodynia. 1995; 172; 1684–1701.)     

Duodenal perforation associated with tolazoline.

A neonate, managed with tolazoline for pulmonary hypertension after repair of a congenital diaphragmatic hernia, developed a duodenal perforation. The role of tolazoline in this condition is discussed, and possible measures to reduce its gastrointestinal side effects are proposed.     

Corpus callosum abnormalities in psychopathic antisocial individuals

CONTEXT: Psychopathic antisocial individuals have previously been characterized by abnormal interhemispheric processing and callosal functioning, but there have been no studies on the structural characteristics of the corpus callosum in this group. OBJECTIVES: To assess whether (1) psychopathic individuals with antisocial personality disorder show structural and functional impairments in the corpus callosum, (2) group differences are mirrored by correlations between dimensional measures of callosal structure and psychopathy, (3) callosal abnormalities are associated with affective deficits, and (4) callosal abnormalities are independent of psychosocial deficits. DESIGN: Case-control study. SETTING: Community sample. PARTICIPANTS: Fifteen men with antisocial personality disorder and high psychopathy scores and 25 matched controls, all from a larger sample of 83 community volunteers. MAIN OUTCOME MEASURES: Structural magnetic resonance imaging measures of the corpus callosum (volume estimate of callosal white matter, thickness, length, and genu and splenium area), functional callosal measures (2 divided visual field tasks), electrodermal and cardiovascular activity during a social stressor, personality measures of affective and interpersonal deficits, and verbal and spatial ability. RESULTS: Psychopathic antisocial individuals compared with controls showed a 22.6% increase in estimated callosal white matter volume (P<.001), a 6.9% increase in callosal length (P =.002), a 15.3% reduction in callosal thickness (P =.04), and increased functional interhemispheric connectivity (P =.02). Correlational analyses in the larger unselected sample confirmed the association between antisocial personality and callosal structural abnormalities. Larger callosal volumes were associated with affective and interpersonal deficits, low autonomic stress reactivity, and low spatial ability. Callosal abnormalities were independent of psychosocial deficits. CONCLUSIONS: Corpus callosum abnormalities in psychopathic antisocial individuals may reflect atypical neurodevelopmental processes involving an arrest of early axonal pruning or increased white matter myelination. These findings may help explain affective deficits and previous findings of abnormal interhemispheric transfer in psychopathic individuals.     

Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis

Vaccination with naked DNA represents a therapeutic strategy currently under consideration in multiple sclerosis (MS). In this study, we tested the potential therapeutic effect of vaccination with a naked DNA construct encoding proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensitization for experimental autoimmune encephalomyelitis (EAE) actively-induced in SJL mice with PLP139-151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local muscle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, exacerbated form of disease (in comparison to control mice), while late sensitization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a Th1-type cytokine response was noted. In contrast, sensitization >10 weeks post-DNA vaccination led to peripheral tolerance as evidenced by a decrease in T cell proliferation and cytotoxic T cell response, no Th2 response, and no increase in apoptosis. These data are novel in that they demonstrate a differential effect of DNA vaccination and have important implications for its use as a mechanism to enhance or modulate immune reactivity.