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.     

Management of older patients presenting after a fall--an accident and emergency department audit.

BACKGROUND: It is common for older patients to present to accident and emergency (AE) departments after a fall. Management should include assessment and treatment of the injuries and assessment and correction of underlying risk factors in order to prevent recurrent falls. OBJECTIVES: To determine management of older patients presenting after a fall to the AE department of Groote Schuur Hospital in Cape Town, South Africa. METHOD: Hospital records were reviewed for a random sample of 100 patients aged 65 years and older presenting to the AE department after a fall, between December 2001 and May 2002. RESULTS: The mean age of the sample was 78.6 years (range 65-98 years); 72% of subjects were female. History of a previous fall, and history of drug or alcohol intake, were recorded in less than 20% of cases. Blood pressure and pulse rate were recorded in approximately 90% of cases, and pulse rhythm and postural blood pressure in 2%. Examination of the musculoskeletal system was done in 86% of cases and that of other systems in less than 50%; cognitive assessment was conducted in less than 30%. Radiological investigations were performed in 89% of cases, glucose and haemoglobin in 32%, renal profile and electrocardiogram in 5%, and urinalysis in 4%. Three-quarters of the patients were referred for further management: 52% to orthopaedic surgery, 12% to other surgical subspecialties, 6% to the general medical department, and 6% to other hospitals and clinics. No referrals were made to geriatric medicine, physiotherapy or occupational therapy. CONCLUSIONS: In managing elderly patients after a fall, the AE department focused on injuries sustained. Little effort was made to establish and manage risk factors, hence to prevent recurrent falls. Guidelines are needed for the management of such patients in AE departments.     

A Randomized Pilot Study of Behavioral Treatment to Increase Calorie Intake in Toddlers With Cystic Fibrosis

This pilot study examined a behavioral treatment to increase calorie intake in toddlers with cystic fibrosis. Eight toddlers were randomly assigned to behavioral plus nutrition (BEH) or nutrition intervention (NTR) conditions. Calorie intake and weight were measured at pre- and posttreatment. The BEH group showed a trend for changes in calorie intake pre- to posttreatment (p = .07; 40% increase). Results for the BEH and NTR groups did not differ significantly. Most participants achieved weight gains consistent with normal growth. Seventy-five percent had not shown this pattern during the year prior to intervention. These results support the feasibility and potential for behavioral interventions in this age group.     

The Relationship Between Daily Life Stress and Gastrointestinal Symptoms in Women with Irritable Bowel Syndrome

Research on irritable bowel syndrome (IBS), a functional disorder of the gastrointestinal (GI) system, has linked GI symptoms to stress. This study examined the relationship between daily stress and GI symptoms across women and within woman in IBS patients (n = 26), IBS nonpatients (IBS-NP; n = 23), and controls (n = 26), controlling for menstrual cycle phase. Women (ages 20–45) completed daily health diaries for two cycles in which they monitored daily GI symptoms and stress levels. The Life Event Survey (LES) was used as a retrospective measure of self-reported stress. The across-women analyses showed higher mean GI symptoms and stress in the IBS and IBS-NP groups relative to controls but no group differences in LES scores. The within-woman analyses found a significant and positive relationship between daily stress and daily symptoms in both the IBS-NP and the IBS groups. Controlling for menstrual cycle had no substantial impact on the results.     

Dopa-responsive parkinsonism secondary to right temporal lobe haemorrahage.

A 46-year-old man developed a symmetrical parkinsonian syndrome 7 weeks after large right temporal intracerebral haemorrhage resulting from a ruptured arteriovenous malformation. His signs included bradykinesia, rigidity, start hesitation, and poor postural reflexes, without a resting tremor. He also had signs of a Parinaud's syndrome. Computed tomography and magnetic resonance imaging of the brain demonstrated changes in the right temporal lobe associated with the haemorrhage but no abnormality of the basal ganglia or midbrain. Levodopa therapy produced a dramatic improvement within a few days of commencement. We postulate that the parkinsonism resulted from midbrain compression secondary to transtentorial herniation. Although parkinsonism is a rare complication of lobar intracerebral haemorrhage, it is important to recognise as it may be potentially treatable.     

Developmental patterns of intermediate filament gene expression in the normal hamster brain

We have examined the patterns of expression of the major intermediate filament (IF) protein mRNAs during development of the hamster brain. Quantitative northern blotting was used to examine changes in the levels of mRNAs for the low, middle and high molecular weight neurofilament proteins (NF-L, NF-M, NF-H) as well as peripherin, vimentin and glial fibrillary acidic protein (GFAP). Total RNA was isolated from hamster brains at embryonic (E) days 12 and 14 and postnatal (P) days 1, 3, 5, 7, 9, 11, 13, 15, 20, 28 and 60-90 (adult), and probed with specific IF cDNAs. Northern blotting revealed that NF-L and NF-M mRNAs were present at very low levels in embryonic brain and that significant expression of these genes only occurred postnatally when the levels increased dramatically until P28 and then declined again in the adult. Increases in NF-H mRNA levels were somewhat delayed relative to those of NF-L and NF-M. NF-H mRNA was not seen at embryonic stages and was expressed at very low levels prior to P9; after that time the levels increased rapidly until P28 and then declined in the adult. Two of the type III IF genes, peripherin and vimentin, followed a pattern of expression opposite that of the NF genes. Both peripherin and vimentin mRNAs were present in embryonic brain and were expressed at higher levels during early postnatal stages than at later times. The magnitude and rate of reduction in vimentin gene expression in the postnatal interval was much greater than that of peripherin. GFAP mRNA levels were extremely low prior to P9 after which a robust increase occurred, followed by a decline in the adult. We discuss the implication of the dramatic changes in IF isotype expression in brain to the pathways of both neuronal and glial development in vivo.     

Infants with single umbilical artery studied in a national registry. General epidemiological characteristics

Summary. In this paper, registry data on infants born in Sweden between 1983 and 1986 are reviewed to describe the epidemiological characteristics of infants with single umbilical artery (SUA). During this period 372 066 births were registered with information on the number of umbilical vessels. Our data set contains 1782 SUA infants. The incidence at birth was: in multiple births 0.8%, in infants with chromosome anomalies 6.1% and in singletons without a known chromosome anomaly 0.46%. Incidence was higher in girls than in boys. There were no consistent seasonal variations in the date of presumed conception. Low birthweight (<2500 g) and preterm birth (<37 weeks) were seen more frequently in SUA singleton infants than in infants with three vessels. At any given gestation, SUA infants had a lower mean birthweight than infants with three vessels. The risk of having a SUA infant was increased in women over 40 years, and slightly increased at or above parity of three.     

Prognostic relevance of histological grade and its components in node-negative breast cancer patients.

Available results highlight the lack of good level of evidence studies on the pure prognostic value of histological grade. In the present study, the prognostic relevance of histological grade and of its three components, tubule formation, nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients with node-negative breast cancer treated with locoregional therapy alone until early relapse. Histological grade was determined blindly by two observers and discordance between evaluations was resolved after joint review using a multihead microscope. No relation was observed between histological grade and any of its three components and disease-free survival. Conversely, a significant relation was observed between histological grade and distant metastasis-free survival (at 6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P=0.013) as well as overall survival (98, 90 and 86%, P=0.001). A breakdown analysis as a function of the three components showed that neither tubule formation nor nuclear pleomorphism was associated with prognosis, and only mitotic count strongly influenced both distant metastasis-free survival (91, 82 and 74%, P=0.014) and overall survival (97, 87 and 85%, P=0.011). Histological grade suffers from a much higher subjectivity than any other microscopic evaluation of biomarkers as it is the sum of three different morphological features. Within the Italian Network for Quality Assessment of Tumor Biomarkers program we observed that histological grade is an independent prognostic variable, but also that this role is ascribable only to the number of mitotic figures. In conclusion, due to the ever smaller size of diagnosed breast cancers, resulting in less cancer tissue for biofunctional and molecular analysis, mitotic count evaluated under strict quality control conditions seems to be an accurate and feasible prognostic variable.