Search

Background This review of scholarly work in health care knowledge translation advances understanding of implementation components that support the complete and timely integration of new knowledge. We adopt a realist approach to investigate what is known from the current literature about the impact of, and the potential relationships between, context, complexity and implementation process. Methods Informed by two distinct pathways, knowledge utilization and knowledge translation, we utilize Rogers’ Diffusion of Innovations theory (DOI) and Harvey and Kitson’s integrated- Promoting Action on Research Implementation in Health Service framework (PARIHS) to ground this review. Articles from 5 databases; Medline, Scopus, PsycInfo, Web of Science, and Google Scholar and a search of authors were retrieved. Themes and patterns related to these implementation components were extracted. Literature was selected for inclusion by consensus. Data extraction was iterative and was moderated by the authors. Results A total of 67 articles were included in the review. Context was a central component to implementation. It was not clear how and to what extent context impacted implementation. Complexity was found to be a characteristic of context, implementation process, innovations and a product of the relationship between these three elements. Social processes in particular were reported as influential however; descriptions of how these social process impact were limited. Multiple theoretical and operational models were found to ground implementation processes. We offer an emerging conceptual model to illustrate the key discoveries. Conclusions The review findings indicate there are dynamic relationship between context, complexity and implementation process for enhancing uptake of evidence-based knowledge in hospital settings. These are represented in a conceptual model. Limited empiric evidence was found to explain the nature of the relationships.

There is little published information on effective treatment of Kaposi’s sarcoma (KS) in children in low-income countries. We prospectively treated 12 patients with an institutional review board-approved protocol consisting of four monthly courses of doxorubicin (Adriamycin), bleomycin and vincristine sulphate (ABV), with highly active antiretroviral therapy (HAART) plus co-trimoxazole prophylaxis for those who were HIV-positive, with additional vincristine if remission was not achieved after 4 months. Maintenance HAART plus co-trimoxazole was given to all HIV-positive patients. A fine-needle aspirate and CD4+ count were done if possible, and staging was performed according to Mitsuyasu. Eight of ten HIV-positive patients with stage III - IVB disease, and both HIV-negative patients with stage I disease, were in remission after 473 - 1 490 (mean 939) days. One patient died after absconding during treatment, and one died from neutropenia-related pulmonary infection. ABV with or without HAART is an effective treatment option for children with KS.

Deer mice (Peromyscus maniculatus) are the principal host species of Sin Nombre (SN) virus, the primary etiologic agent of hantavirus cardiopulmonary syndrome in North America. The disease is a cytokine-mediated immunopathology characterized by pulmonary mononuclear infiltrates without discernible viral pathology. Infected deer mice remain life-long carriers and virus is found in many organs, including the lungs, but without pathology. It is unclear how deer mice respond to SN virus because no tools exist to examine the immune response in infected animals. As an initial step in examining host responses to SN virus, we have cloned partial cDNAs of deer mouse interferon-gamma (IFN-gamma), interleukin-10 (IL-10), tumor necrosis factor (TNF) and lymphotoxin-alpha (LTalpha). IL-10, TNF and LTalpha sequences are highly conserved compared to orthologs of other mammalian species, while IFN-gamma is substantially less conserved. Phylogenetic analyses indicate that the amino acid sequences of IFN-gamma and TNF may be useful in resolving relationships at the subfamily level within the rodent family Muridae. While all four sets of analyses were able to reconstruct clade Rodentia, they were not able to resolve the relationships among the mammalian orders represented in this study. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis of concanavalin A-stimulated splenocytes determined that maximal IFN-gamma and TNF expression occurred rapidly while IL-10 and LTalpha expression was maximal at 24 h.

Fifteen HBsAg kits from 14 manufacturers were assessed. Their sensitivity was evaluated by testing 150 HBsAg-positive sera, sera from four donors who were low-level HBsAg carriers, and sequential specimens from 22 seroconverting individuals together with dilutions of six of these specimens. The British HBsAg Working Standard (0.5 IU mL-1) and the NIBSC/UKBTS HBsAg Monitor Sample (0.125 IU mL-1) were also tested. Five assays failed to detect one of the 150 routine HBsAg-positive sera. Four assays (Auszyme Monoclonal; Monolisa Ag HBs 2nd generation; Murex HBsAg; Ortho HBsAg Test Systems 3) were able to detect HBsAg in all but one of the six sera from low-level carriers, whereas one assay (MicroTrak II HBsAg) detected only one of the six. The most sensitive kit (Monolisa Ag HBs 2nd generation) detected HBsAg in 79 specimens from the seroconversion panels; four other kits detected HBsAg in at least 70 specimens, seven in 60-69, two in 50-59 and the least sensitive in 31. Further analysis of the findings on seroconverters indicated a median reduction in the duration of HBsAg detection of 5 days or more for four assays when compared with the most sensitive assay. One kit (Auszyme Monoclonal) detected HBsAg in 15 of the 18 dilutions prepared from the seroconversion specimens, whereas three kits detected HBsAg in fewer than 10 dilutions. Two kits gave negative reactions with the British HBsAg Working Standard on all of five occasions and six were consistently unreactive with the NIBSC/UKBTS HBsAg Monitor Sample; only three kits (Bioelisa, Enzygnost, Murex) were always reactive. There is therefore substantial variation in sensitivity among the HBsAg kits currently available.

The ceroid-lipofuscinoses are a group of inherited neurodegenerative diseases of human beings characterized by the accumulation of a fluorescent lipopigment in neurons and other cells within the body. There is usually atrophy of both brain and retina with preferential loss of particular neurons. Biochemically, the diseases divide into at least two groups, i.e. those that accumulate subunit c of mitochondrial ATP synthase and those that do not. Dolichol pyrophosphate linked oligosaccharides are also present in storage material. As the underlying biochemical anomalies are not known, the various clinicopathological entities are classified on clinical grounds, by age of onset and, to a lesser extent, by the course of the disease. The best recognized diseases are infantile, late infantile, early juvenile, juvenile and adult onset forms but other variants occur indicating considerable heterogeneity within the group. The infantile, late infantile and juvenile diseases are not allelic. Analogous diseases occur in a variety of animal species. That in the sheep has been extensively studied as a model of the human disease and is the prototype subunit c storage disease.

The childhood spinal muscular atrophies (SMAs) are the most common, serious neuromuscular disorders of childhood second to Duchenne muscular dystrophy. A single locus for these disorders has been mapped by recombination events to a region of 0.7 centimorgan (range, 0.1-2.1 centimorgans) between loci D5S435 and MAP1B on chromosome 5q11.2-13.3. By using PCR amplification to screen yeast artificial chromosome (YAC) DNA pools and the PCR-vectorette method to amplify YAC ends, a YAC contig was constructed across the disease gene region. Nine walk steps identified 32 YACs, including a minimum of seven overlapping YAC clones (average size, 460 kb) that span the SMA region. The contig is characterized by a collection of 30 YAC-end sequence tag sites together with seven genetic markers. The entire YAC contig spans a minimum of 3.2 Mb; the SMA locus is confined to roughly half of this region. Microsatellite markers generated along the YAC contig segregate with the SMA locus in all families where the flanking markers (D5S435 and MAP1B) recombine. Construction of a YAC contig across the disease gene region is an essential step in isolation of the SMA-encoding gene.

The childhood-onset SMA locus has been mapped to chromosome 5q13, in a region bounded by the proximal locus, D5S6, and the closely linked distal loci, DSS112 and MAP1B. We now describe a highly polymorphic, tightly linked microsatellite marker (D5S435) that is very likely the closest proximal marker to the SMA locus. Multipoint linkage analysis firmly establishes the following order of markers at 5q13: centromere-D5S76-D5S6-D5S435-MAP1B/D5S112-D5S39-telomere. The data indicate that SMA resides in an approximately 0.7-cM (range 0.1-2.1) region between D5S435 and MAP1B. This finding reduces by approximately fourfold the genetic region that most likely harbors the SMA locus and will facilitate the physical mapping and cloning of the disease gene region.

A survey of persons soliciting sex in an area known to be frequented by prostitutes in Albuquerque, NM, included 43 females and 66 males. Seroprevalence rates found in this population-based study were as follows: human immunodeficiency virus type 1 (HIV-1), 3%; hepatitis B, 39%; hepatitis C, 45%. Increased age, intravenous drug use, and condom use were independent risk factors for hepatitis B. Female gender and intravenous drug use were independent risk factors for hepatitis C. Neither sharing injection equipment nor engaging in receptive anal intercourse was independently associated with hepatitis B or C.

Rheumatoid Arthritis (RA) synovial membranes were examined by single and dual immunohistological techniques with a number of monoclonal antibodies against lymphocyte and macrophage related antigens. CD4 positive T lymphocytes frequently expressed MHC Class II antigens and were found in sublining collections in close association with activated macrophages as well as B lymphocytes. CD8 positive T cells surrounded these collections as well as being scattered throughout the membrane and also frequently expressed MHC Class II antigens. IL2 receptor (IL2r) expression on T cells and CD5 expression on B cells were rarely seen in these synovial membranes. Similar immunohistological architecture was found in synovial membranes from patients with psoriatic arthritis (PA) and Reiter's Syndrome (RS). Normal synovium contained few T cells, with few cells expressing MHC Class II antigens. Synovium from osteoarthritis (OA) patients also demonstrated similar immunohistological changes to those found in inflammatory arthritides, suggesting that there are only quantitative rather than qualitative differences between the synovial membrane immunohistological architecture from patients with inflammatory and noninflammatory arthritides.

BackgroundDeer mice (Peromyscus maniculatus) are among the most common mammals in North America and are important reservoirs of several human pathogens, including Sin Nombre hantavirus (SNV). SNV can establish a life-long apathogenic infection in deer mice, which can shed virus in excrement for transmission to humans. Patients that die from hantavirus cardiopulmonary syndrome (HCPS) have been found to express several proinflammatory cytokines, including lymphotoxin (LT), in the lungs. It is thought that these cytokines contribute to the pathogenesis of HCPS. LT is not expressed by virus-specific CD4+T cells from infected deer mice, suggesting a limited role for this pathway in reservoir responses to hantaviruses.ResultsWe have cloned the genes encoding deer mouse LTα and LTβ and have found them to be highly similar to orthologous rodent sequences but with some differences in promoters elements. The phylogenetic analyses performed on the LTα, LTβ, and combined data sets yielded a strongly-supported sister-group relationship between the two murines (the house mouse and the rat). The deer mouse, a sigmodontine, appeared as the sister group to the murine clade in all of the analyses. High bootstrap values characterized the grouping of murids.ConclusionNo conspicuous differences compared to other species are present in the predicted amino acid sequences of LTα or LTβ; however, some promoter differences were noted in LTβ. Although more extensive taxonomic sampling is required to confirm the results of our analyses, the preliminary findings indicate that both genes (analyzed both separately and in combination) hold potential for resolving relationships among rodents and other mammals at the subfamily level.

Most thyroid cysts are benign; however, they require aspiration if symptomatic or atypical on ultrasound scanning, and ablation with ethanol injection if recurrent. We have systematically studied the use of new safety technologies for surgical procedures, which protect both the surgeon and the patient. Here, we describe the use of one such technology, the reciprocating procedure device, which enables simpler, safer, more efficient and less painful thyroid cyst aspiration and therapeutic ablation.

In response to increasing pressure on inpatient services and a meta-analysis indicating that cisplatin (C) is superior to carboplatin, we report a phase II trial of gemcitabine (G) and split-dose C in advanced non-small cell lung cancer (NSCLC) in an outpatient setting. Patients with stage IIIB/IV NSCLC received: G/C 1250/40 mg/m(2); G and C were given on day (d) 1 and d8 in a 21d cycle. Patients with performance status 0-2, adequate bone marrow function and calculated glomerular filtration rate (GFR)50 ml/min were eligible. Forty-two patients were enrolled: 25 male; median age 62 (range 37-78) years. There were 26 patients (62%) with stage IV disease. One hundred and thirty-eight cycles of chemotherapy were delivered. Chemotherapy was well tolerated, allowing maintenance of planned dose intensity (DI) with mean dose delivered of 780.1 mg/m(2) (93%) and 25.6 mg/m(2) (96%) for G and C, respectively. The overall response rate was 43%. Median survival was 12.5 months with a median follow-up of 13.5 months. One year survival rate was 51%. G plus C both given on d1 and d8 (q21d) is a very active, well tolerated and convenient outpatient schedule, which maintains DI.

The human gp200-MR6 molecule has previously been shown to have either an antagonistic or agonistic effect on IL-4 function, demonstrated by inhibition of IL-4-induced proliferation of T cells or mimicking of IL-4-induced maturation of epithelium, respectively. We now show that gp200-MR6 ligation can also mimic IL-4 and have an anti-proliferative pro-maturational influence within the immune system, causing up-regulation of co-stimulatory molecules on B lymphocytes. Biochemical analysis and cDNA cloning reveal that gp200-MR6 belongs to the human macrophage mannose receptor family of multidomain molecules. It comprises 1722 amino acids in toto (mature protein, 1695 amino acids; signal sequence, 27 amino acids) organized into 12 external domains (an N-terminal cysteine-rich domain, a fibronectin type II domain and 10 C-type carbohydrate recognition domains), a transmembrane region and a small cytoplasmic C terminus (31 amino acids) containing a single tyrosine residue (Y1679), but no obvious kinase domain. Strong amino acid sequence identity (77%) suggests that gp200-MR6 is the human homologue of the murine DEC-205, indicating that this molecule has much wider functional activity than its classical endocytic role. We also show that the gp200-MR6 molecule is closely associated with tyrosine kinase activity; the link between gp200-MR6 and the IL-4 receptor may therefore be via intracellular signaling pathways, with multifunctionality residing in its extracellular multidomain structure.

Influences on parent perceptions regarding the practice of integrating students with significant cognitive disabilities into general education classrooms were examined. Findings confirmed that perceptions were significantly influenced by characteristics of the parent and the child as well as by factors associated with the child's placement history. Further, factors influencing these perceptions differed according to varying dimensions of inclusion being considered. We argue that the efficacy of any specific type of educational model cannot be determined without a consideration of the complex dynamics involved in the interplay between individual child characteristics, parent and family values, and the perceived role of the school.

Febrile nonhemolytic transfusion reactions frequently accompany platelet transfusions and may be due to accumulation of cytokines mediating inflammation during storage of platelet concentrates (PCs). We wished to determine whether PCs collected using the COBE(R) SpectraTM Apheresis System (Version 4) were sufficiently leukocyte reduced (LR) to limit cytokine accumulation during storage.Cytokine accumulation - interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) - and release of platelet alpha-granule - P-selectin, transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor AB (PDGF-AB), von Willebrand factor (vWf) - or dense granule (serotonin) markers were investigated during a 7-day storage period comparing apheresis-collected, LR PCs (LR PCs) and random donor platelets prepared from whole blood (WB).Leukocyte counts were reduced 99.95% comparing LR PCs (5.7 x 10(5)/l) and WB PCs (1.09 x 10(9)/l). Little or no accumulation of leukocyte-derived cytokines was observed in LR PCs during storage in contrast to WB PCs. A reduction in the release of platelet alpha-granule proteins, such as P-selectin, TGF-beta1 and PDGF-AB, was observed on day 0 for LR PCs compared to WB PCs with little or no difference observed from day 3 to 7. Plasma vWf levels were higher in LR PCs compared to WB PCs on days 0-7.Leukocyte levels in PCs collected with the COBE Spectra Apheresis System are sufficiently low to limit cytokine production during 7 days of storage.

Botulinum toxin A has been used to treat wrist and finger spasticity mainly through injection of the forearm flexor muscles. This case study describes its first reported use in managing spastic lumbricals of the hand. A 19-year-old male had significant flexion deformity and hypertonicity of the left wrist and hand, particularly the second through fifth metacarpophalangeal joints, after traumatic brain injury. By using the 0-4 Ashworth scale, spasticity of the lumbricals across the second to fourth metacarpophalangeal joints was rated 2, with persistent clonus of the finger flexors as confirmed by electromyography to the middle and ring fingers, even after botulinum toxin A injection of the flexor digitorum sublimis and profundus muscles. By using the electromyography-guided technique, botulinum toxin A was injected into the first lumbrical of the index finger (12 units), second and third lumbricals of the middle and ring fingers, respectively (15 units each), and fourth lumbrical of the little finger (10 units). At follow-up, clinical and electromyographic examination revealed a significant reduction in tone and clonus of the injected lumbricals. Ashworth scores of the lumbricals from the index to little finger improved to 1. Botulinum toxin A injection of the lumbricals can be beneficial in managing spasticity of these muscles. It is well tolerated and effective at doses of 10 to 15 units. Lumbrical injection of botulinum toxin A is a useful adjunct in our percutaneous armamentarium for managing the spastic hand.

Neurologic complications of Hodgkin's disease (HD) include both metastatic and non-metastatic involvement of the nervous system. There are at least five paraneoplastic syndromes associated with HD but chorea has not been described. We report the first choreiform disorder as a paraneoplastic complication of HD and only the second case of paraneoplastic chorea in the literature.

The high incidence of colorectal cancer in Western society is believed to be strongly related to diet. Mutation of the p53 gene is a late event in colorectal carcinogenesis, and thus, the majority of pre-malignant adenomas express wild-type p53. As loss of p53 protein function is an important step in colorectal carcinogenesis, we investigated whether naturally occurring lumenal factors can modulate the expression of p53 in non-tumorigenic human colonic adenoma cell lines. Levels of p53 protein and mRNA were measured in adherent cells which had been incubated with growth-inhibitory concentrations of sodium butyrate (a by-product of dietary fibre fermentation) or sodium deoxycholate (a bile acid) for up to 48 hr. We report that both butyrate and deoxycholate can down-regulate the expression of wild-type and mutant p53. In contrast, incubation for 48 hr with the endogenous inhibitory growth factor TGFbeta1 did not alter p53 protein expression. Thus, in addition to cellular mechanisms which regulate p53 function, such as post-translational stabilisation, nuclear exclusion, negative feedback inhibition of p53 mRNA translation or binding of p53 by cellular proteins, p53 protein levels also may be regulated by changes in the level of p53 gene transcription. Furthermore, we show that lumenal factors are able to affect directly the expression of p53 protein in colonic epithelial cells.

To determine, using autopsy eyes, whether diode laser energy adjustments are indicated in patients with thin sclera.In the laboratory, the superior 180 degrees of sclera at the limbus was dissected to the level of barely visible anterior uvea and the opposite 180 degrees of sclera served as the control in three human cadaver eyes. A contact G-probe was placed at the limbus, and settings of a diode laser were increased in increments from 1.0 to 9.0 J at 4 burns per setting in each location.On gross examination, circular hypopigmented lesions were seen in the ciliary body (CB) beginning at 3.0 J in thin sclera and at 5.0 J in normal sclera. On light microscopic examination of thin scleral sections, CB damage began at 2.9 J and CB/ciliary body epithelium (CBE) damage occurred beginning at 3.5 J. In normal sclera, minimal CB/CBE changes occurred at 6.0 to 7.5 J. No scleral damage was visible in either the experimental or the control groups.Cycloablation energy adjustments are indicated on eyes with abnormally thin sclera to achieve similar histologic end points using the diode laser.

Incessant supraventricular tachycardia can cause a dilated cardiomyopathy. This article discusses the case of a 55-year-old woman whose cardiomyopathy was reversed when she underwent successful radiofrequency catheter ablation of a unifocal atrial tachycardia.

To quantify inorganic pyrophosphate (PPi) production from extracellular adenosine triphosphate (ATP) by human serum or plasma.Serial measurements of ATP hydrolysis (t1/2) were performed by the luciferase method from a starting concentration of 1 microM in serum or platelet-poor plasma incubated under physiologic conditions. ATP was then pumped into another sample of each specimen using the rate constant derived from the ATP t1/2 of that specimen. Trace (32P) gamma ATP was added at the start of the infusion; conversion to (32P) inorganic orthophosphate (Pi) and to (32P) PPi was determined by precipitation of Pi as reduced phosphomolybdate before and after treatment with yeast pyrophosphatase.ATP was hydrolyzed by all serum and plasma specimens; the rate of hydrolysis in serum and plasma from the same blood sample was nearly identical. PPi was the major product, averaging 71%.PPi is the major product of ATP catabolism in serum and platelet-poor plasma.

To quantify inorganic pyrophosphate (PPi) production from extracellular adenosine triphosphate (ATP) by human synovial fluids (SF).Serial measurements of ATP hydrolysis rate (t1/2) were performed by the luciferase method from a starting concentration of 500 nM in 21 pathologic and one normal cell-free SF samples incubated under physiologic conditions. ATP was then pumped into a sample of each fluid, using the rate constant derived from the t1/2 of that fluid, to provide steady state levels simulating those reported in SF. Trace [32P] gamma ATP was added at the start of the infusion; conversion to [32P] Pi and to [32P] PPi was determined by precipitation of Pi as reduced phosphomolybdate before and after treatment with yeast inorganic pyrophosphatase. Finally, the pumping experiment was repeated and PPi production was calculated from direct measurement of PPi at time zero and at 60 min. PPi hydrolysis was measured in each fluid by [32P] Pi precipitation from [32P] PPi tracer added at time zero.ATP was hydrolyzed by all SF. The mean t1/2 (seconds) in 8 osteoarthritis (OA) samples was 72 s, in 5 calcium pyrophosphate dihydrate (CPPD) 30 s (p0.02), in 3 rheumatoid arthritis (RA) 1160 s, in normal 86 s, in 3 olecranon bursal (OB) 54 s, and in 2 total knee replacement fluid samples 17 and 121 s. The major product of ATP hydrolysis was PPi in all but 2 fluids (1 RA, 1 OB), even at lower than steady state levels. At simulated in vivo steady state ATP levels, mean conversion of APT to PPi was stoichiometric in OA and CPPD fluids. PPi hydrolysis was4% in all noninflammatory fluids.PPi is the major product of extracellular ATP catabolism in most SF. Hydrolysis rates were significantly faster in SF containing CPPD crystals. Mean PPi production by these fluids at simulated in vivo steady state levels was 6-fold that of OA SF (p0.01). Hydrolysis of extracellular ATP by ectonucleotide pyrophosphohydrolases can account for all PPi produced by joint issues previously estimated from [32P] PPi pool and turnover studies in human knee joints.

Described is an epidemiological investigation of hookworm infections in a rural community in Zimbabwe, where Necator americanus is the only human helminth species present. Among a cohort of 120 individuals the overall prevalence of infection was 78%. Intensity of infection was quantified both as egg counts (range: 0-2563 eggs per g of stool) and worm burden (range: 0-100 worms). Although both these measures provide useful quantitative data, they are tedious to determine in large-scale epidemiological studies and may present social and logistic difficulties. As an alternative screening method, we therefore investigated isotype-specific responses to adult worm antigens of N. americanus. The results show that specific IgG4 responses correlate positively and significantly with both measures of intensity and may be a useful marker of hookworm infection.

SUMMARY Data from a previous study suggested that peripheral blood monocytes in patients with rheumatoid arthritis (RA) may be activated. Therefore, in this study we sought further evidence of ‘presynovial’ activation of monocytes. Our results show that phenotypic changes are demonstrable in peripheral blood monocytes in patients with RA, including increased expression of CR3 (CDllb/CD18) and FcRI (CD64). However, changes are most extensive in synovial monocytes/macrophages and especially for HLA-DR and intercellular adhesion molecule-1 (ICAM-1) (CD54). We conclude that monocyte/macrophage activation is most evident within the joint, and that ‘presynovial’ changes occur but are of limited extent.

SUMMARYAntibody responses to Ascaris lumbricoides worm antigens were examined by ELISA in a case-control study of 2 groups of Bangladeshi children, one of which had been shown over a period of 12 months to be consistently lightly infected (controls) and the other consistently heavily infected (cases). The children showed a wide range in intensity of infection; children identified as cases were on average 4 times more heavily infected than the controls. There were no significant differences in weight, height, mid-upper arm circumference and skinfold thickness between the case or control subjects at the time blood samples for analyses by ELISA were collected. Children with repeatedly heavy infections with A. lumbricoides had higher concentrations of antibody isotypes to the antigens of A. lumbricoides than children who are repeatedly lightly infected. IgG1, IgG4 and IgE to worm antigens occurred in significantly higher concentrations in heavily infected subjects. This suggests that these antibody responses simply reflect the intensity of infection and may not play a significant role in protecting against heavy infections.

In a cross-sectional study of helminth infections in a rural village in The Gambia, West Africa, hookworm, probably Necator americanus and Ascaris lumbricoides were found to be the most prevalent helminths present at prevalence levels of 30% and 25% respectively. Other parasites present were Trichuris trichiura (2.4%) and Schistosoma mansoni (1.5%). The mean egg counts of N. americanus and A. lumbricoides in all age groups and in the total population were low. Egg counts between age and sex groups were not statistically significant. The frequency distributions of both N. americanus and A. lumbricoides were overdispersed with the majority of the sample population producing none or few eggs, and a small minority producing relatively large amounts of eggs. Large variance: mean ratios within age groups and the total study population suggested a high degree of aggregation of the parasites in this community.

Rheumatoid arthritis primarily involves the synovial membrane of the joints, together with that of the tendon sheaths and bursae. These structures are targeted in a selective and symmetrical manner. The inflammatory cell infiltrate is usually dominated by mononuclear phagocytes. These are recruited into the synovial lining as type A synoviocytes. A proportion of the mononuclear cell population has proven to be specialized antigen-presenting accessory cells. The T and B lymphocyte infiltrate is quite variable in intensity, but may become highly organized. Polymorphonuclear leukocytes pass rapidly into the joint space. The cellular characteristics of rheumatoid nodules have some similarities with those of the synovial membrane. In a minority of patients, immunoglobulin production and circulating immune complex formation reaches levels which precipitate the appearance of a complement mediated vasculitis. This may lead to tissue damage in remote organs.

In conclusion, we estimate the incidence of carpal tunnel surgery to be between 400,000 and 500,000 cases annually in the United States, with economic costs in excess of $2 billion per year. The costs incurred in workers' compensation cases are almost three times those of other workers and five times those of nonworkers. Despite an increase in medial costs for endoscopic carpal tunnel release, the procedure has a potential to decrease overall costs by lowering productivity and wage reimbursement losses. With better surveillance and data collection systems, workers at risk can be identified and the incidence of occupational carpal tunnel syndrome reduced through appropriate worksite intervention.

Endothelial cells (ECs) synthesize and release von Willebrand factor (vWf) either constitutively or from Weibel-Palade bodies by a regulated pathway. Although stimulated release of vWf from ECs occurs following exposure to thrombin, histamine, interleukin, tissue necrosis factor and fibrin in vitro, these agents are unlikely to be present in physiologically relevant concentrations during the initial stages of primary hemostasis. Alternatively, agents known to be released from the dense granules of activated platelets at the sites of vascular injury may provide the initial physiological stimuli for vWf release from ECs in vivo. We have examined the effects of the platelet secretagogues ADP, AMP, ATP and serotonin on the release of vWf from ECs and demonstrated enhanced release in all cases. The extent and time at which optimum vWf release was observed depended on the agonist and its concentration. At 3 nM, optimum release occurred after 4 hours with ADP (330%/ml) or 1 h with AMP (153%/ml) or ATP (450%/ml). At 30 nM, optimum release was seen after 1 hour with ADP (315%/ml) or AMP (595%/ml) and after 15 min with ATP (938%/ml). With serotonin, optimal release was seen by 30 min at 0.3 microM (1034%/ml) and after 1 h at 1 microM (745%/ml) although the response after 15 min was nearly equivalent (667%/ml). The doses giving 50% of maximal response (ED50) after 1 h were 6.5 nM (ADP), 15.2 nM (AMP) and 2.4 nM (ATP) and 20 nM for ATP or 75 nM for serotonin after 15 or 30 min respectively. ADP also enhanced PGI2 release from ECs in a dose- and time-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunologically distinct subgroups of patients with rheumatoid arthritis (RA)--those with the autoantibody rheumatoid factor (seropositive RA) and those without (seronegative RA)--were compared on a variety of clinical and self-report measures in a consecutive series of women with disease of 7 years' or less duration. The groups were comparable on clinical, pain, functional, and psychosocial variables. However, the seronegative RA group reported elevated levels of preonset negative life event stress. Postonset life event stress and disease activity were significantly correlated for the seronegative RA group, but not for the seropositive RA group. Results suggest that stress factors may be more important in the etiology and maintenance of seronegative RA and that the seronegative RA group may possibly derive particular benefit from psychological techniques to enhance stress management skills.

Small cell undifferentiated carcinoma of the pancreas is a rare type of pancreatic neoplasm.The authors report the clinical and pathologic aspects of a patient with this malignant lesion and an extensive serologic and immunohistochemical survey of potential ectopically produced hormones or tumor markers.Neuron-specific enolase (NSE) emerged as a tumor marker.NSE could be valuable in the diagnosis and management of other patients with this rare disease.

Left ventricular hypertrophy (LVH) is frequently present in patients referred for radionuclide ventriculography (RVG) for evaluation of left ventricular function. During interpretation of these studies, the nuclear medicine physician may have the subjective impression that increased septal thickening is present because of the abnormally prominent separation of the right and left ventricular blood pools. To examine the diagnostic reliability of this finding, we retrospectively reviewed the RVG studies of 43 consecutive patients and correlated the finding of subjectively increased septal thickness with established echocardiographic (ECHO) criteria and commonly used electrocardiographic (ECG) indices of LVH. Using standard ECHO measurements of septal thickness as a gold standard, RVG interpretation of septal thickening demonstrated a sensitivity of 0.69, specificity of 0.70, and accuracy of 0.70. When compared with standard ECG criteria for LVH, RVG performed quite favorably in the diagnosis of LVH confirmed by ECHO left ventricular mass index. We conclude that scintigraphic evidence of LVH should be reported when RVG studies are interpreted.

The Pediatric Examination of Educational Readiness (PEER) is an assessment instrument specifically designed for use by pediatricians in assessing the development of preschool children. The present study investigated the psychometric properties of the PEER. Specifically, factor analyses of items from the Developmental Attainment and Associated Observation components of the test were performed. The PEER was administered to 69 preschool children. Three major factors were identified as making up the Developmental Attainment portion of the test: perceptual-motor, verbal-cognitive, and gross motor. The Associated Observations component was found to be composed of only one factor, attention. Children's performance on only two of these four factors was associated with their performance on the McCarthy Scales, the Woodcock-Johnson skills cluster, and the Minnesota Child Development Inventory. Discussion focused on the validity and utility of the PEER.

We investigated rheumatoid subcutaneous nodules using monoclonal antibodies recognizing functional determinants on mononuclear phagocytes (Mph) and lymphocytes. Mph at the center of rheumatoid nodules showed strong expression of the leukocyte intergrins CR3 and p150,95 which would be consistent with the presence of a central chemotactic stimulus. Mph expression of FcR1, a gamma interferon regulated molecule, was decreased in 5/13 cases despite strong expression of MHC class II. There was a variable unstructured infiltrate of T lymphocytes, a majority of which were CD8 positive. Lymphocytes showed increased MHC class II expression but interleukin 2 receptor expression was low. We discerned no relationship between the number, distribution or phenotype of the T cell infiltrate and the phenotype of the predominant Mph population.

A self-report measure of rheumatoid arthritic activity developed from the articular index described by Thompson, Silman, Kirwan, and Currey (1987), was tested for reliability, validity, and sensitivity to therapeutic change. Concurrent validity was demonstrated by a significant correlation, (ICC = 0.83) between the self-report measure and a standard Thompson index completed by a rheumatologist. Test-retest reliability was demonstrated by significant correlations (ICC = 0.88, ICC = 0.77) between repeated administrations of the self-report form in 2 independent samples. The self-report measure demonstrated sensitivity to therapeutic change when completed by patients both before and after intraarticular corticosteroid injection. The rheumatologist's index correlated significantly with C-reactive protein but the self-report form did not.