Evaluation of a modified ACR20 scoring system in patients with rheumatoid arthritis receiving treatment with etanercept.

OBJECTIVE: To evaluate a modified American College of Rheumatology 20 (mACR20) scoring system for patients with rheumatoid arthritis. METHODS: The data were evaluated from one study on patients with methotrexate (MTX)-naive early rheumatoid arthritis (ERA) and another study on patients with DMARD-refractory late rheumatoid arthritis (LRA). For mACR20 scoring, acute-phase reactant measurements were excluded, and 20% improvement from baseline was determined by 2 or 3 of the 4 remaining ACR components. RESULTS: For full joint counts with data from patients with ERA, marked differences favoured 25 mg etanercept (ETN) over 10 mg ETN by using the unmodified ACR20 (69% v 55%), the mACR20(3 of 4) (63% v 49%) and the mACR20(2 of 4) (72% v 58%). An assessment of 28 joints showed similar findings. In the trial on patients with LRA, considerably more patients in both ETN groups achieved a clinical response compared with placebo by using the ACR20, the mACR20(3 of 4) and the mACR20(2 of 4), whether using full or 28 joint counts. The mACR20(3 of 4) and full joint counts with data on patients with ERA showed a marked difference between the MTX and 10 mg ETN groups (63% v 49%), which was not observed with the ACR20. CONCLUSION: Patterns of improvement indicated by mACR20 scores were consistent with standard ACR20 scores.

Two sniffing strategies in palinurid lobsters.

Most studies of lobster chemoreception have focused on the model systems of Panulirus argus (Palinuridae) and Homarus americanus (Nephropidae). We compare antennule morphology across lobsters and conduct the first kinematic study of antennule flicking in a palinurid species other than P. argus. High-speed video analysis shows that Palinurus elephas flicks at a rate more than an order of magnitude higher than in P. argus. However, both species flick their antennular flagella at a Reynolds number (Re) of approximately one, such that an asymmetry in the speed of the flick phases causes both species to have a leaky closing flick phase and a non-leaky opening phase. The antennular flagella of P. argus are nearly seven times longer than those of P. elephas, and, when compared across palinurid genera, Panulirus species sample far greater areas of water over greater spatial and time scales than do any other palinurid genera. Palinurid lobsters appear to have two sniffing strategies: low flick rates over a large area of water (e.g. P. argus) or high flick rates over a small area of water (e.g. P. elephas). P. argus is a highly informative model system in which to study aquatic chemoreception; however, its antennule anatomy and kinematics suggest a separate strategy, unique to Panulirus species, for sensing chemical plumes in fluid environments.

Fluid dynamic design of lobster olfactory organs: high speed kinematic analysis of antennule flicking by Panulirus argus.

Many organisms use olfactory appendages bearing arrays of microscopic hairs to pick up chemical signals from the surrounding water or air. We report a morphometric and high speed kinematic analysis of the olfactory organs (lateral flagella of the antennules, which bear chemosensory aesthetasc hairs) of the spiny lobster, Panulirus argus. Panulirus argus sample specific locations by executing a rapid series of antennule flicks at one position, moving the antennule to a different spot and then performing another series of flicks. Odorant delivery to an aesthetasc depends on the water motion near it, which depends on its Reynolds number (Re, proportional to both the diameter and speed of the hair). High speed video enabled us to resolve that during a series of flicks, an antennule moves down rapidly (aesthetasc Re = 2) and up more slowly (Re = 0.5), pausing briefly ( approximately 0.54 s) before the next downstroke. The antennules of P. argus operate in a range of Re values and inter-aesthetasc spacings in which penetration of fluid between the hairs in an array is especially sensitive to changes in speed. Therefore, when antennules flick 'old' water is flushed out of the aesthetasc array during the leaky downstroke and is not picked up again during the less leaky upstroke, hence the antennules can take discrete samples. Thus, by operating in this critical Re range these antennules should be particularly effective at sniffing.

Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein.

Splicing of the c-src N1 exon in neuronal cells depends in part on an intronic cluster of RNA regulatory elements called the downstream control sequence (DCS). Using site-specific cross-linking, RNA gel shift, and DCS RNA affinity chromatography assays, we characterized the binding of several proteins to specific sites along the DCS RNA. Heterogeneous nuclear ribonucleoprotein (hnRNP) H, polypyrimidine tract binding protein (PTB), and KH-type splicing-regulatory protein (KSRP) each bind to distinct elements within this sequence. We also identified a new 60-kDa tissue-specific protein that binds to the CUCUCU splicing repressor element of the DCS RNA. This protein was purified, partially sequenced, and cloned. The new protein (neurally enriched homolog of PTB [nPTB]) is highly homologous to PTB. Unlike PTB, nPTB is enriched in the brain and in some neural cell lines. Although similar in sequence, nPTB and PTB show significant differences in their properties. nPTB binds more stably to the DCS RNA than PTB does but is a weaker repressor of splicing in vitro. nPTB also greatly enhances the binding of two other proteins, hnRNP H and KSRP, to the DCS RNA. These experiments identify specific cooperative interactions between the proteins that assemble onto an intricate splicing-regulatory sequence and show how this hnRNP assembly is altered in different cell types by incorporating different but highly related proteins.

Fibromyalgia, hypermobility, and breast implants.

OBJECTIVE: To examine possible relationships among fibromyalgia (FM, American College of Rheumatology 1990 criteria), hypermobility, and breast implants. METHODS: The medical records of 2,500 female patients (ages 25-65) who had been seen for the first time in a rheumatology practice in Atlanta, GA, during 1986-92 were abstracted and analyzed. In each analysis, patients whose records indicated that the patient met the full case criteria were compared with patients whose records had no indication of the disease. Patients whose medical records indicated the clinical onset of FM prior to breast implantation were identified. RESULTS: Univariate and multivariate regression analyses were performed, adjusting for age, income, and the presence of connective tissue disease or rheumatoid arthritis. Significant associations were found between hypermobility and FM (adjusted OR 2.20, 95% CI 1.73, 2.80) and between hypermobility and breast implantation (adjusted OR 1.80, 95% CI 1.19, 2.69). No association was found between breast implantation and subsequent FM (adjusted OR 0.74, 95% CI 0.42, 1.32). CONCLUSION: Hypermobility was found to be independently associated with both FM and with breast implantation, but FM and breast implantation were not found to be independently associated with each other.

Term domain distribution analysis: a data mining tool for text databases.

In this paper, we give a case history illustrating the real-world application of a useful technique for data mining of text databases. The technique, which we call Term Domain Distribution Analysis (TDDA), consists of keeping track of term frequencies for specific finite domains and announcing significant differences from standard frequency distributions over these domains as a hypothesis. TDDA is part of a larger framework, the Digital Filter Model, for data mining of text documents. In the case study presented, the domain of terms was the pair {right, left}, over which we expected a uniform distribution. In analyzing term frequencies in a thoracic lung cancer database, the TDDA technique led to the surprising discovery that primary thoracic lung cancer tumors appear in the right lung more often than the left lung, with a ratio of 3:2. Treating the text discovery as a hypothesis, we verified this relationship against the medical literature in which primary lung tumor sites were reported, using a standard chi 2 statistic. We subsequently developed a working theoretical model of lung cancer that may explain the discovery. This discovery and our model may change how oncologists view the mechanisms of primary lung tumor location.

Connective tissue disease in people exposed to organic chemical solvents: systemic sclerosis (scleroderma) in dry cleaning plant and aircraft industry workers.

The etiology of connective tissue disease appears to be multifactorial and includes genetic factors, autoimmune responsiveness and environmental elements. This survery in a clinical rheumatology practice has investigated the relationship of environmental occupational organic solvent exposure and the presence of connective tissue disease. Two hundred and seventynine consecutive patients with various connective tissue diseases were classified according to the American College of Rheumatology criteria for systemic lupus erythematosus, systemic sclerosis (scleroderma), and rheumatoid arthritis and clinically as dermatomyositis/polymyositis, mixed connective tissue disease, and Sjogren's syndrome. Comprehensive questionnaires were used regarding diagnosis, occupational history and chemical and other substance exposure.There was a striking increase in exposure to organic chemical solvents in the population of people with systemic sclerosis. Twelve of 33 people with scleroderma gave a history of organic chemical exposure versus 22 of the other 246 people (p = .00001); 3 of 33 with systemic sclerosis were exposed to perchloroethylene versus 2 of the other 246 (p = .00076), 2 scleroderma patients to trichloroethane versus 1 of the other 246 (p = .0031), and 2 scleroderma patients each to petroleum solvent and fluorocarbon solvent versus 0 of the other 246 (p = .00011) for each. Four of these 33 scleroderma patients worked in dry cleaning plants versus one of the other 246 (p < .00001), and 2 scleroderma subjects had been cleaning airplane parts versus 2 of the other 246 (p = .00076).These observations support a hypothesis for a role of occupational exposure in some patients with scleroderma. Prospective epidemiologic studies are needed. Clinicians should question new patients about such exposures and may wish to counsel them about avoiding exposures. However, no data have yet suggested that stopping the exposures made patients healthier.

Breast implants, rheumatoid arthritis, and connective tissue diseases in a clinical practice.

This study was designed to assess the relationship between breast implants and certain rheumatologic diseases (rheumatoid arthritis and diffuse connective tissue diseases). The study base was a rheumatological practice in Atlanta, Georgia that started in 1982 and began computerizing its records in 1985. The computerized records through May 1992 included 4229 women patients, 150 with breast implants and 721 with a diagnosis of rheumatoid arthritis (RA) and/or one of the connective tissue diseases (CTDs). Of the 721 patients who had been diagnosed as having rheumatoid arthritis (RA) and/or one of the connective tissue diseases (CTDs), 392 had rheumatoid arthritis, 344 had connective tissue disease, 15 had both rheumatoid arthritis and a connective tissue disease, and 33 had more than one connective tissue disease. Of the patients with connective tissue disease, 179 had systemic lupus erythematosus, 64 had scleroderma, 49 had Sjögren's syndrome, 36 had dermatomyositis or polymyositis, and 49 had mixed connective tissue disease. Data were analyzed by univariate and multivariate techniques including logistic regression. Significant variables included age at first visit, income strata, and period of first visit. Analyses were performed for each clinical diagnosis, for all connective tissue diseases together (CTDs), and for those with rheumatoid arthritis and/or connective tissue disease (RA/CTD). Analyses were performed on the total data base and on the records of new patients (1986-1992). The adjusted odds ratio for breast implants among women who entered the practice in 1986-1992 and were diagnosed as having rheumatoid arthritis and/or one of the connective tissue diseases (RA/CTDs) was 0.45 (0.22-0.90), for those with rheumatoid arthritis was 0.61 (0.28-1.49), for those with any of these specific diffuse connective tissue diseases was 0.34 (0.11-1.06) compared to those without the disease. For systemic lupus erythematosus, the odds ratio of 0.24 (0.03-1.75) was based on a single case who had the disease 5 yr before the implant. For Sjögren's syndrome, the odds ratio was 1.67 (0.39-7.13) based on two cases, one of whom had the disease 5 yr before the implant. The calculated odds ratios for scleroderma, dermatomyositis/polymyositis, and mixed connective tissue disease were zero since no cases were diagnosed among the patients with breast implants. This study found no evidence that women with breast implants are at an increased risk for having rheumatoid arthritis or other diffuse connective tissue disease.

An acoustic basis for maternal recognition in timber wolves (Canis lupus)?

An in-den recording system was used to monitor the vocalizations and behavior of adult wolves tending to a litter of pups during the first five postnatal weeks. Two female adults, one of them the mother, tended to the pups on nonoverlapping schedules. The distributions of the fundamental frequencies of the adults' squeak vocalizations were largely nonoverlapping, suggesting that this feature may be available as an acoustic cue to individual recognition. Squeaks emitted outside the den, and which were associated with pup exit responses, had fundamental frequencies wholly within the range of the mother's, raising the possibility that the pups used this as a cue for maternal recognition.

Cognitive rehabilitation of adults with severe and persistent mental illness: a group model.

The authors report on a group treatment approach developed for adults with schizophrenia who live in a Community Mental Health Center supported group home. The goals of the group intervention included cognitive rehabilitation and the development of effective communication and social skills. A variety of outcome measures used to evaluate the effectiveness of treatment revealed that the group modality promoted improved functioning in cognitive processing, social skills, and verbal communication. Although the results of the study can only be viewed as suggestive due to a small sample size and lack of a control group, the authors present a detailed group treatment format that can be utilized and further developed by people working with a severe and persistent mentally ill population.

A prospective randomized comparison of two gonadotrophin-releasing hormone agonists, nafarelin acetate and buserelin acetate, in in-vitro fertilization-embryo transfer.

We tested the efficacy of a new gonadotrophin-releasing hormone agonist (GnRHa), nafarelin acetate, in in-vitro fertilization (IVF), and compared the results with those of another widely used GnRHa, buserelin acetate; both were in the form of nasal spray. Therapy was used in a long protocol in the luteal phase in two groups of women with similar aetiology of infertility. There was no significant difference in patient response, measured by cycle cancellation, number of oocytes retrieved, fertilization rate and cleavage rate. Pregnancy rates were similar in nafarelin acetate and buserelin acetate treated women, namely 22% and 24% pregnancies per cycle, and 28.8% and 32.1% pregnancies per transfer, respectively. Side-effects were few and comparable in both groups. The only difference noted was that women receiving nafarelin acetate required significantly fewer ampoules of human menopausal gonadotrophin, making a significant difference in the expense involved. We conclude that on the basis of our experience, nafarelin acetate is an efficient and safe gonadotrophin-releasing hormone agonist, effective in IVF therapy.

Self-perception variables that mediate AIDS-preventive behavior in college students.

Three psychological variables--self-efficacy, control and meaning, and perceived risk--were tested in a structural model predicting AIDS-preventive behavior. Results revealed a good model fit, indicating that these psychological variables did play a role in mediating AIDS-preventive behavior in college students. A multivariate analysis of variance and individual analyses of variance conducted for men and women also revealed gender differences on individual items of self-efficacy, perceived risk, and AIDS-preventive behavior. This study underscores the importance of identifying and assessing the psychological determinants of AIDS-preventive behavior.

The impact of long-term gonadotropin-releasing hormone analogue treatment on preclinical abortions in patients with severe endometriosis undergoing in vitro fertilization-embryo transfer.

OBJECTIVE: To examine the relationship between endometriosis and preclinical abortions and to evaluate the effect of gonadotropin-releasing hormone analogue (GnRH-a) therapy on these pregnancies. DESIGN AND PATIENTS: Of 67 women with severe endometriosis referred to us for in vitro fertilization-embryo transfer (IVF-ET), 32 underwent ovarian stimulation for oocyte retrieval with menotropins (protocol A), whereas the other 35 were admitted for the procedure after a 6-month period of hormonal suppression with a GnRH agonist (protocol B). The clinical impact of the preclinical and clinical pregnancies in both treatment protocols were evaluated on the basis of oocyte classification and embryo quality score. SETTING: All patients were treated in our IVF Unit. MAIN OUTCOME MEASURE: Clinical pregnancy was used as our main outcome measure of success. RESULTS: A significantly higher number of preclinical pregnancies (P less than 0.0001) occurred in patients treated by protocol A. After GnRH-a treatment, the preclinical pregnancy rate declined significantly (P less than 0.0001), whereas the clinical pregnancy rate per cycle and per transfer rose significantly (P less than 0.0001 and P less than 0.0001, respectively). Furthermore, clinical pregnancies had a significantly better mean embryo quality score in comparison with preclinical pregnancies (P less than 0.0001). CONCLUSIONS: It is concluded that combining GnRH-a therapy before IVF-ET provides an improved treatment modality for preclinical abortions and infertility associated with severe endometriosis.

Fresh versus frozen thawed semen for initial and late insemination in IVF cycles.

Frozen thawed semen has been associated with reduced semen quality and as a result diminished pregnancy rates. In vitro fertilization (IVF) can supply the true measure of the functional fertilizing capacity of fresh versus frozen-thawed semen. One hundred and six patients in an IVF program who underwent donor insemination were divided into two groups. Group I included 51 women in whom initial insemination with donor fresh or frozen semen was performed. They were compared to 65 group II women in whom late insemination with donor fresh or frozen semen was performed after initial insemination with husband semen had failed to fertilize the eggs. There was no statistically significant difference between groups I and II on initial insemination; however, statistically significant difference in fertilization (P less than 0.006) and pregnancy rates (P less than 0.001) between the two groups were achieved when late insemination was carried out. Consequently, we prefer initial insemination with frozen-thawed donor semen in cases indicated.

Hypermobility and deconditioning: important links to fibromyalgia/fibrositis.

In this study 210 patients who were identified as having fibromyalgia/fibrositis were evaluated for hypermobility of joints. The patients were then instructed to perform an exercise program, and thereafter their compliance with the program and its effect on their symptoms were evaluated. The data were then analyzed using the Student's t test and Pearson's correlation coefficient. Patients who exercised during the study had improvement. Because the hypermobile patients as a group exercised more than the nonhypermobile group, they showed greater improvement than the nonhypermobile group (58% versus 30%). Patients with fibromyalgia/fibrositis who have articular hypermobility are more likely to exercise, which will improve their symptoms. The ability to show the objective findings of hypermobility to a person with fibromyalgia/fibrositis, a diagnosis based on subjective symptoms and signs, facilitates management of the patient. These tangible signs help the patient accept and adjust to the diagnosis of fibromyalgia/fibrositis.

Very early pregnancy wastage in in vitro fertilization and embryo transfer (IVF-ET).

The occurrence and incidence of early pregnancy wastage in an in vitro fertilization and embryo transfer (IVF-ET) program have been studied in 750 patients. In 297 (39.6%) a pregnancy was diagnosed; of these, 14.8% were biochemical and 24.8% clinical pregnancies. In the latter group 23.6% aborted, while 75.8% had clinical ongoing pregnancies. The mean embryo quality score of the biochemical pregnancy group was similar to that of the clinical ongoing pregnancy group but statistically different from that of the clinical abortion group (P less than 0.005). Furthermore, the clinical ongoing pregnancy rate in women with previous biochemical pregnancy was 24.7%, a significantly higher percentage compared to clinical ongoing pregnancies achieved in IVF-ET cycles (P less than 0.05). It is possible that biochemical pregnancy does not represent an index for infertility but rather an intact stage of reproduction leading toward implantation. The high clinical pregnancy rate in subsequent cycles may probably serve as an encouraging sign or a marker for future clinical pregnancy.

Transvaginal ultrasonic needle-guided aspiration of endometriotic cysts before ovulation induction for in vitro fertilization.

Controversy still exists concerning the optimal treatment of endometriomata in endometriosis and its related infertility. Forty-one women with endometriomata who failed to conceive during previous in vitro fertilization and embryo transfer (IVF-ET) cycles (protocol A) were readmitted for ovum pickup following transvaginal ultrasonic needle-guided aspiration of the endometriomata (protocol B). Following aspiration a significantly higher number of oocytes was recovered (P less than 0.0006); subsequently, more embryos were transferred, and significantly higher clinical pregnancy rates per cycle (P less than 0.0001) were achieved. This difference may be directly related to the reduction of extensive ectopic endometrial tissue (endometriomata) with improved ovarian response, follicular accessibility, and, most probably, improved oocyte quality.