Delayed wound healing in Mac-1–deficient mice is associated with normal monocyte recruitment

The Mac-1 integrin is an important mediator of migration and inflammatory activation of neutrophils and monocytes. However, the role of Mac-1 in modulating macrophage emigration and activation and its subsequent impact on cutaneous wound healing have not been fully elucidated. To examine the significance of Mac-1 to murine wound healing, we measured epithelialization and granulation tissue formation in partial-thickness ear wounds and full-thickness head wounds, respectively, in Mac-1-deficient mice. Wounds were histologically analyzed at postwounding days 3, 5, and 7. The gap measured between the leading edges of inward-migrating granulation tissue was significantly increased in knockout mice compared with control animals at day 5 (3.8+/-0.3 vs. 2.6+/-0.5 mm; p<0.001) and day 7 (2.2+/-0.4 vs. 0.96+/-0.73 mm; p=0.005). Epithelial gap measurements were also increased in knockout mice vs. wild-type controls at days 3 (0.62+/-0.02 vs. 0.54+/-0.07 mm; p<0.05) and 5 (0.58+/-0.06 vs. 0.39+/-0.08 mm; p<0.001). Immunohistochemistry showed equal numbers of macrophages in knockout and control wounds. These findings show that Mac-1 is required for normal wound healing but that the attenuation in the deposition of granulation tissue and wound epithelialization in Mac-1 knockout mice is not associated with decreased monocyte migration into the wound.     

Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics.

BACKGROUND: A subgroup of children with obsessive-compulsive and tic disorders are proposed to have an infectious trigger. The purpose of this study was to investigate the relationship between group A streptococcal titers and symptom fluctuations in children with a clinical course resembling that described for pediatric autoimmune neuropsychiatric disorders associated with streptococcus. METHODS: Twenty-five children with obsessive-compulsive disorder and/or tic disorder were evaluated for neuropsychiatric severity and group A streptococcal antibody titers (streptolysin O, deoxyribonuclease B, and carbohydrate A) at 6-week intervals for > or = six consecutive evaluations (total visits=277). RESULTS: Children with large symptom fluctuations (n=15) were compared with children without dramatic fluctuations (n=10). Co-movements of obsessive-compulsive/tic severity and group A streptococcal antibodies were assessed. In subjects with large symptom changes, positive correlations were found between streptococcal titers and obsessive-compulsive severity rating changes (p=.0130). These subjects were also more likely to have elevated group A streptococcal titers during the majority of observations (p=.001). Tic symptom exacerbations occurred more often in the fall/winter months than spring/summer months (p=.03). CONCLUSIONS: Patients with marked obsessive-compulsive/tic symptom changes may be characterized by streptococcal titer elevations and exhibit evidence of seasonal tic exacerbations.     

Effects of amyotrophic lateral sclerosis serum on cultured chick spinal neurons

We used a quantitative immunoassay to examine the effects of human serum and immunoglobulins on neurofilament protein expression in cultures of chick spinal neurons. Compared with cultures grown in the presence of serum from healthy controls or patients with other neurologic disorders, ALS serum lowered the level of neurofilament proteins. Effects were similar with or without muscle-derived neurotrophic factors; there was no specificity for motor neurons. No neurotoxic activity was found in immunoglobulin fractions, and there was no evidence of circulating antibodies that might neutralize muscle-derived neurotrophic factors or induce cytolysis of spinal neurons.     

Alleles of RUNX2/CBFA1 gene are associated with differences in bone mineral density and risk of fracture.

The aim of this study was to determine if DNA polymorphism within runt-related gene 2 (RUNX2)/core binding factor A1 (CBFA1) is related to bone mineral density (BMD). RUNX2 contains a glutamine-alanine repeat where mutations causing cleidocranial dysplasia (CCD) have been observed. Two common variants were detected within the alanine repeat: an 18-bp deletion and a synonymous alanine codon polymorphism with alleles GCA and GCG (noted as A and G alleles, respectively). In addition, rare mutations that may be related to low BMD were observed within the glutamine repeat. In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The effect was maximal at the ultradistal (UD) radius (p = 0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture, suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis.     

Percutaneous transhepatic placement of biliary endoprostheses: results in 100 consecutive patients.

One hundred patients with malignant biliary obstruction underwent palliative therapy by means of percutaneous transhepatic placement of 114 biliary endoprostheses. All patients were then followed up for at least 18 months or until death. Retrospective evaluation of the 95 patients who died showed an average survival time of 5.0 months. The five remaining patients have survived an average of 29.8 months. During the 1st week after stent insertion, a second manipulation was performed to improve stent function in nine patients. Overall, 14 (12.3%) of the stents became obstructed and six (5.2%) migrated; 86 patients required no further therapy for biliary obstruction or stent malfunction. The 30-day mortality rate was 12%; none of the deaths were directly attributable to a complication of the stent placement procedure.     

Predicting drug-resistant patients who respond to add-on therapy with levetiracetam.

INTRODUCTION: Levetiracetam (LEV) is approved for use as add-on therapy in adult patients with partial epilepsy. It is apparent from clinical trials that up to 8% of previously drug-resistant patients may be rendered seizure-free by adding-on levetiracetam. As yet there is no way of predicting these unexpectedly responsive patients. We set out to identify our previously refractory patients who had demonstrated unexpected responsiveness to add-on therapy with levetiracetam, and compared these to patients who had not responded to the drug. We then attempted to characterise any clinical features that differentiated these groups of patients. METHODS: We included all patients with a history of present or previous exposure to levetiracetam who had been unresponsive to at least two other prior anti-epileptic drugs (AEDs) and recorded their demographic and clinical data. We divided response into (a) 'seizure-free' (seizure-free for a minimum of 6 months after commencing LEV); (b) 'partial > 50%' (greater than 50% reduction in seizures for a minimum of 6 months after commencing LEV); (c) 'honeymoon' (seizure-free for less than 6 months after commencing LEV and then returned towards baseline frequency); and (d) 'no-response'. For the purpose of analysis we considered the 'seizure-free' and 'partial > 50%' groups as 'responders', and the 'no response' group as 'non responders'. RESULTS: 344 patients were included in the analysis. Fifty-six patients (16.3%) were rendered seizure-free on levetiracetam. Idiopathic generalised epilepsy and post-traumatic partial epilepsy were more common in the responder than the non-responder group (p = 0.005 and 0.05 respectively). Lamotrigine was used significantly more often in combination with levetiracetam in responders than non-responders (p = 0.003). The mean daily dose of levetiracetam was lower in responders than non-responders. DISCUSSION: A higher than expected number of previously drug resistant patients was rendered seizure-free by add-on therapy with levetiracetam. Those who respond best appear to do so at relatively low doses and our data suggest the possibility of a beneficial pharmacodynamic interaction between levetiracetam and lamotrigine. We were unable to identify any clinical factors that clearly predicted which patients would become seizure-free and we hypothesise that response may be determined by genetic or molecular factors. All drug-resistant patients, including those being assessed for surgery, should be considered for a trial of levetiracetam, regardless of their epilepsy classification.