Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury. Tumor necrosis factor-alpha (TNFalpha) is protective in LPS-induced preconditioning yet exacerbates neuronal injury in ischemia. Here, we define dual roles of TNFalpha in LPS-induced ischemic tolerance in a murine model of stroke and in primary neuronal cultures in vitro, and show that the cytotoxic effects of TNFalpha are attenuated by LPS preconditioning. We show that LPS preconditioning significantly increases circulating levels of TNFalpha before middle cerebral artery occlusion in mice and show that TNFalpha is required to establish subsequent neuroprotection against ischemia, as mice lacking TNFalpha are not protected from ischemic injury by LPS preconditioning. After stroke, LPS preconditioned mice have a significant reduction in the levels of TNFalpha (approximately threefold) and the proximal TNFalpha signaling molecules, neuronal TNF-receptor 1 (TNFR1), and TNFR-associated death domain (TRADD). Soluble TNFR1 (s-TNFR1) levels were significantly increased after stroke in LPS-preconditioned mice (approximately 2.5-fold), which may neutralize the effect of TNFalpha and reduce TNFalpha-mediated injury in ischemia. Importantly, LPS-preconditioned mice show marked resistance to brain injury caused by intracerebral administration of exogenous TNFalpha after stroke. We establish an in vitro model of LPS preconditioning in primary cortical neuronal cultures and show that LPS preconditioning causes significant protection against injurious TNFalpha in the setting of ischemia. Our studies suggest that TNFalpha is a twin-edged sword in the setting of stroke: TNFalpha upregulation is needed to establish LPS-induced tolerance before ischemia, whereas suppression of TNFalpha signaling during ischemia confers neuroprotection after LPS preconditioning.     

Dietary modulation of small intestinal glutamine transport in intestinal brush border membrane vesicles of rats

The effects of a glutamine-enriched diet on the transport of glutamine across brush border membrane vesicles (BBMV) from the rat jejunum were studied to gain further insight into the effects of diet on regulating gut glutamine utilization. Following fasting, rats were randomized to one of three nutritionally complete elemental diets supplemented with glutamine, glutamate, or glycine (control). Brush border membrane vesicles were prepared by a Mg2+ aggregation/differential centrifugation technique and uptake of radioactive [3H]glutamine by the BBMV was studied using a rapid mixing/filtration technique. BBMVs from all test diet groups were enriched in alkaline phosphatase 14-fold. [3H]Glutamine uptake courses for all groups demonstrated sodium dependency, overshoots, and similar 2-hr equilibrium values. Vesicles from animals fed the glutamine-enriched diet had a 75% increase in glutamine uptake compared to those of the control diet and a 250% increase compared to those of the glutamate-enriched diet (P less than 0.05). alpha-Methylamino isobutyric acid and glycine did not significantly inhibit total [3H]glutamine uptake, whereas asparagine and glutamine inhibited total [3H]glutamine uptake compared to the mannitol control. The brush border appears to possess the glutamine selective System N transporter, the activity of which can be stimulated by providing dietary glutamine.     

Nitric oxide treatment for fulminant pulmonary hypertension.

A 3 year old child with known pulmonary haemosiderosis suffered acute circulatory collapse secondary to raised pulmonary vascular resistance. Nitric oxide inhalation produced a profound improvement in circulatory parameters and gaseous exchange. Nitric oxide may have a therapeutic role in acute pulmonary hypertensive crisis.     

Family caregiver stress: clinical assessment and management

This intervention study compares the effectiveness of two approaches on caregiving stress reduction. Caregivers' psychobiological symptom experience and coping were profiled over time by identifying the types of stress-related symptoms most frequently experienced. Following pretesting (and selected matching procedures) using family functioning, coping, stress and mental status instruments, random assignment of caregivers was made to one of four groups: educative/didactic, psychotherapeutic/support, placebo, or control. Patients were tested at the end of eight weekly 2-hour sessions and again at 1-, 3-, 6-, and 12-month intervals after treatment. Although both the educative and psychotherapeutic groups were effective interventions for the reduction of strain, the psychotherapeutic/support group was the most effective over time, both at posttest and at the 3-month intervals. Neither group intervention was more effective than the control groups in reducing other types of stress, including anxiety, somatization, or depression. The psychobiological symptoms experienced by caregivers peaked at crisis periods in the caregiving trajectory, or when multiple demands were made of the caregiver during any one point in time.     

Aspergillus brain abscess. A case report

The history and findings in a patient with erythroleukaemia who developed a fungal brain abscess during the agranulocytic phase of induction treatment is reported. The radiological features of fungal infection are reported, with emphasis on the importance of clinical judgement in making the diagnosis. The autopsy findings further illustrate the increasing importance of this previously very rare condition.     

Reduction of the median mandibulotomy with the fixed mandibular implant.

A technique is presented whereby a median mandibulotomy of an atrophic edentulous mandible is performed to gain access to an oropharyngeal tumor and is subsequently reapproximated with a four-pin FMI. The procedure allows reduction of the osteotomy site and provides intraoral implants that increase the stability and retentive properties of a mandibular prosthesis.     

Bilateral fracture dislocation of the sacroiliac joint

 We present a rare case of a 27-year-old man sustaining a bilateral fracture dislocation of the sacroiliac joints without disruption of the anterior pelvis, following a fall from a height. Reconstructed images in the coronal plane and three-dimensional CT images were invaluable in the diagnosis and assessment of this injury.     

An evaluation of educational outreach to general practitioners as part of a statewide cervical screening program.

OBJECTIVES: The purpose of this study was to determine the acceptability, effectiveness, and cost of a face-to-face educational outreach intervention in the context of a program aimed at increasing cervical screening in Victoria, Australia. METHODS: All identified general practitioners in a specified intervention area were offered a visit by a general practitioner educator. Practitioners completed a questionnaire evaluating the acceptability of the visit. Odds ratios for a woman being screened in the 3 months following the visits were determined. RESULTS: Fifty-nine general practitioners (69.4%) accepted the offer of a visit. Most found both the process and the content of the intervention to be acceptable. The intervention and nonintervention regions did not differ either before or after the intervention. In both regions, there was a statistically significant increase in number of Pap tests performed. There was no difference in the change in screening between the two regions. Costs were estimated at Au$34 per general practitioner visited. CONCLUSIONS: This strategy cannot be recommended for widespread use in a cervical screening program.     

Becoming a mother — an analysis of women's experience of early motherhood

This paper presents the results of a qualitative study conducted by midwife researchers into women's experience of new motherhood. Data were collected using focus groups involving 55 first-time mothers and analysed using grounded theory method. The analysis produced six categories: 'realizing', 'unready', 'drained', 'aloneness', 'loss' and 'working it out'. The core category, 'becoming a mother', integrates all other categories and encapsulates the process of change experienced by women. Also explained are factors mediating the often distressing experience of becoming a mother. The analysis provides a conceptualization of early motherhood enabling the development of strategies for midwives, nurses and others helping women negotiate this challenge.