'The Doctor doesn't need to see you now': reduction in general practice appointments following group pain management.

Background: Patients living with chronic, non-malignant, musculoskeletal pain are frequent visitors to general practice (GP) services, placing a large burden on resources. Pain management programmes (PMPs) are recommended for chronic pain patients and aim to teach self-management techniques. While there is evidence for their clinical effectiveness, few studies have explored whether there is a reduction in primary care healthcare use after attending a PMP.

Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs.

Machupo virus, the cause of Bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no Food and Drug Administration-approved vaccines or therapeutics. This study evaluated the guinea pig as a model using the Machupo virus-Chicava strain administered via aerosol challenge. Guinea pigs (Cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology.

Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure.

Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash.

Experimental aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs.

Eight guinea pigs were aerosolized with guinea pig-adapted Zaire ebolavirus (variant: Mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. Guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. Intracytoplasmic inclusion bodies were observed in many alveolar macrophages.

Can a pain management programme approach reduce healthcare use? Stopping the revolving door.

Patients with chronic musculoskeletal pain are frequent users of healthcare. Whilst evidence suggests that a multidisciplinary pain management programme (PMP) approach is effective in reducing patients' levels of distress and disability, there is little research examining the cost-effectiveness of such an approach. The present study sought to address this by examining the impact a PMP had on patients' pain-related secondary care healthcare use.

Advances, challenges and a developing synthesis of ecological community assembly theory.

Ecological approaches to community assembly have emphasized the interplay between neutral processes, niche-based environmental filtering and niche-based species sorting in an interactive milieu. Recently, progress has been made in terms of aligning our vocabulary with conceptual advances, assessing how trait-based community functional parameters differ from neutral expectation and assessing how traits vary along environmental gradients. Experiments have confirmed the influence of these processes on assembly and have addressed the role of dispersal in shaping local assemblages.

Neuropathy-induced osteopenia in rats is not due to a reduction in weight born on the affected limb.

Changes in bone mineral density (BMD) are associated with clinical neuropathies. Following nerve injury in the rat, there is a loss of BMD, which may be related to nerve injury or reduced mechanical loading. The purpose of this study was to investigate if altered mechanical loading is solely responsible for the observed loss of BMD in neuropathic pain models.

Development and pharmacological characterization of a rat model of osteoarthritis pain.

Osteoarthritis (OA) is an age-related joint disease characterized by degeneration of articular cartilage and is associated with chronic pain. Although several experimental models of OA have been employed to investigate the underlying etiologies of the disease, there has been relatively little investigation into development of animal models of OA to study the pain associated with the condition. In the present study, we investigated OA induced by injection of either iodoacetate or papain into the knee joint of rats, and assessed the joint degeneration with radiographic analyses and measured pain behavior using hind limb weight bearing.

New tools for laparoscopic division of the pancreas: a comparative animal study.

We tested the hypothesis that the pancreas can be safely divided laparoscopically using non-suture devices. Twelve pigs were randomized into 4 groups: 1) laparoscopic distal pancreatectomy (LDP) using an ultrasonic scalpel; 2) LDP using an ultrasonic scalpel with pancreatic stump suture reinforcement; 3) LDP using a 35-mm laparoscopic linear vascular stapler; 4) LDP using a prototype 35-mm radio-frequency laparoscopic linear vascular stapler. There were no serious complications related to distal pancreatectomy.

Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome.

Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in fibrillin-1 (encoded by FBN1 in humans and Fbn1 in mice), a matrix component of extracellular microfibrils. A distinct subgroup of individuals with Marfan syndrome have distal airspace enlargement, historically described as emphysema, which frequently results in spontaneous lung rupture (pneumothorax; refs. 1-3).

Toxicity of intracranial and intraperitoneal O6-benzyl guanine in combination with BCNU delivered locally in a mouse model.

Purpose: The DNA-repair protein, O6-alkylguanine-DNA alkyl transferase, may account for resistance of CNS tumors to DNA-alkylating drugs, such as bis-(2-chloroethyl)-1-nitrosourea (BCNU). The therapeutic effects of BCNU can be potentiated by inhibiting the repair protein with an alkylated guanine analog, O6-benzyl guanine (O6BG). To investigate potential toxicity of this inhibition, we examined the effects of O6BG in mice treated with intracranial (i.

Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome.

Marfan syndrome is associated with early death due to aortic aneurysm. The condition is caused by mutations in the gene (FBN1) encoding fibrillin-1, a major constituent of extracellular microfibrils. Prior observations suggested that a deficiency of microfibrils causes failure of elastic fiber assembly during late fetal development.

Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice.

The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer.

The oncogenic properties of the HMG-I gene family.

The HMG-I gene family encodes high mobility group proteins originally identified as nonhistone chromosomal binding proteins. HMG-I and -Y proteins are alternatively spliced products of the same mRNA; HMG-C is encoded by a separate gene. The HMG-I proteins function as architectural chromatin-binding proteins that bind to the narrow groove of AT-rich regions in double-stranded DNA.

Brown bullhead (Ameiurus nebulosus) skin carcinogenesis.

Alternative models using fish species have been tested in liver toxicity and carcinogenesis bioassays. Similar models have not been developed for skin. The brown bullhead (Ameiurus nebulosus) has shown potential as a model for skin carcinogenesis studies due to its sensitivity to environmental chemical pollutants.

HMG-I/Y, a new c-Myc target gene and potential oncogene.

The HMG-I/Y gene encodes the HMG-I and HMG-Y proteins, which function as architectural chromatin binding proteins important in the transcriptional regulation of several genes. Although increased expression of the HMG-I/Y proteins is associated with cellular proliferation, neoplastic transformation, and several human cancers, the role of these proteins in the pathogenesis of malignancy remains unclear. To better understand the role of these proteins in cell growth and transformation, we have been studying the regulation and function of HMG-I/Y.

Regulation of left-right patterning in mice by growth/differentiation factor-1.

The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of structurally related polypeptides that are capable of regulating cell growth and differentiation in a wide range of embryonic and adult tissues. Growth/differentiation factor-1 (Gdf-1, encoded by Gdf1) is a TGF-beta family member of unknown function that was originally isolated from an early mouse embryo cDNA library and is expressed specifically in the nervous systemin late-stage embryos and adult mice. Here we show that at early stages of mouse development, Gdfl is expressed initially throughout the embryo proper and then most prominently in the primitive node, ventral neural tube, and intermediate and lateral plate mesoderm.

Oxygen-independent upregulation of vascular endothelial growth factor and vascular barrier dysfunction during ventilated pulmonary ischemia in isolated ferret lungs.

Vascular endothelial growth factor (VEGF) is a potent mediator of endothelial barrier dysfunction, and is upregulated during ischemia in many organs. Because ventilated pulmonary ischemia causes a marked increase in pulmonary vascular permeability, we hypothesized that VEGF would increase during ischemic lung injury. To test this hypothesis, we measured VEGF expression by Northern and Western blot analysis in isolated ferret lungs after 45 (n = 12) or 180 (n = 12) min of ventilated (95% or 0% O(2)) ischemia.

Use of non-mammalian species in bioassays for carcinogenicity.

The high costs of bioassays for carcinogenicity in rodents have sparked interest in the use of non-mammalian species as possible alternatives. Invertebrate and lower vertebrate species have been used for many years in bioassays for teratogenicity, toxicity and carcinogenicity involving exposure to a range of genotoxic compounds. Carcinogenicity tests have shown that the development of neoplasia in non-mammalian species is predictable and reproducible and that the results are affected by species, age, chemical class and dose.

Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1.

Dissecting aortic aneurysm is the hallmark of Marfan syndrome (MFS) and the result of mutations in fibrillin-1, the major constituent of elastin-associated extracellular microfibrils. It is yet to be established whether dysfunction of fibrillin-1 perturbs the ability of the elastic vessel wall to sustain hemodynamic stress by disrupting microfibrillar assembly, by impairing the homeostasis of established elastic fibers, or by a combination of both mechanisms. The pathogenic sequence responsible for the mechanical collapse of the elastic lamellae in the aortic wall is also unknown.

Targetting of the gene encoding fibrillin-1 recapitulates the vascular aspect of Marfan syndrome.

Aortic aneurysm and dissection account for about 2% of all deaths in industrialized countries; they are also components of several genetic diseases, including Marfan syndrome (MFS). The vascular phenotype of MFS results from mutations in fibrillin-1 (FBN1), the major constituent of extracellular microfibrils. Microfibrils, either associated with or devoid of elastin, give rise to a variety of extracellular networks in elastic and non-elastic tissues.

Cytochrome P450 isoenzyme activities in cultured rat and mouse liver slices.

1. The objective of this study was to determine the basal and inducible activities of several cytochrome P450 (CYP) isozymes and monitor the acinar and hepatocyte morphology in precision cut, cultured rat and mouse liver slices. 2.

Diagnostic criteria for degenerative, inflammatory, proliferative nonneoplastic and neoplastic liver lesions in medaka (Oryzias latipes): consensus of a National Toxicology Program Pathology Working Group.

Diagnostic criteria are presented for degenerative, inflammatory, nonneoplastic proliferative, and neoplastic lesions in the liver of medaka (Oryzias latipes), a small fish species frequently used in carcinogenesis studies. The criteria are the consensus of a Pathology Working Group (PWG) convened by the National Toxicology Program. The material examined by the PWG was from Medaka exposed to N-nitrosodiethylamine for 28 days, removed to clean water, and sacrificed 4, 6, or 9 mo after initiation of exposure.

Experimental chemical carcinogenesis in fish.

Experimental carcinogenesis using fish species as alternative models is a dynamic field of research. The 1940's expansion of synthetic chemical producing industries coincided with a number of pollution-associated fish neoplasia epizootics, with polycyclic aromatic hydrocarbons as significant components of contaminated sediment in several cases. Epizootics of primarily liver and skin neoplasia in benthic species near coastal urban or industrial areas indicated the sensitivity of fish species to known mammalian carcinogens.

Reactivity of tissue-specific antigens in N-methyl-N'-nitro-N-nitrosoguanidine-induced neoplasms and normal tissues from medaka (Oryzias latipes).

To further characterize the distribution of tissue-specific antigens in fish neoplasms, juvenile medaka were exposed to 30 mg/L of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 1 hr and allowed to grow out for up to 16 mo. Using a streptavidin peroxidase technique, keratin, vimentin, and neurofilament intermediate filament proteins, and actin and S-100 proteins were labeled in MNNG-induced neoplasms and normal medaka tissues using specific monoclonal or polyclonal antibodies. In vascular tumors, rhabdomyosarcoma, and teratoma, muscle tissues were positive for actin.