RESUMEN

The aim of this study was to determine the potential for dietary uptake by trophic transfer using the explosive 2,4,6-trinitrotoluene (TNT) and the substantially more hydrophobic dichlorodiphenyltrichloroethane (DDT) utilizing the amphipods Leptocheirus plumulosus as prey and the fish Cyprinodon variegatus as predator. Bioaccumulation did not change significantly over time for TNT but apparent steady-state was not reached for DDT at exposure termination after 7 days of dietary exposure. The bioaccumulation factor was 0.09 mg/mg for TNT and 0.34 mg/mg for DDT, confirming the low potential of TNT to bioaccumulate in fish.

Asunto(s)

RESUMEN

Mosaicism for trisomy 13 and triploidy was detected by amniocentesis performed at 18 weeks' gestation because of fetal anomalies. Pregnancy continued and a live-born male was delivered vaginally at 37 weeks. The infant had features common to both trisomy 13 and triploidy: intrauterine growth retardation (IUGR), small abnormal ears, cleft palate, and a small jaw. In addition, he had complete cutaneous syndactyly of fingers 3 and 4 and partial syndactyly of the toes, as seen in triploidy. Mixoploidy for trisomy 13 and triploidy was confirmed postnatally in blood, skin, and placenta. Examination of chromosome heteromorphisms and DNA markers suggested the presence of two maternal contributions in the triploid cell line. In addition, the extra chromosome 13 in the trisomic cell line was derived from the mother.

Asunto(s)

RESUMEN

Over the past three decades, there has been an increasing interest in cases of profound muscle weakness in critically ill, mechanically ventilated patients. Potential causes for these acute weakness syndromes are multiple and include disorders of the peripheral nerves, the neuromuscular junction, and muscle (Sliwa, 2000). This article will provide an overview of one potential cause of an acute weakness syndrome affecting peripheral nerves, critical illness polyneuropathy (CIP). A case study concerning a 32-year-old male who suffered multiple traumatic injuries, and who was treated for more than two years, is presented to illustrate the course of the syndrome. He required extensive interdisciplinary involvement to achieve independence in spite of ongoing neurological impairments.

Asunto(s)

RESUMEN

OBJECTIVE: To determine the effects of sulfasalazine (SASP) and its metabolites sulfapyridine (SP) and 5-amino salicylic acid (5ASA) on steady state mRNA levels of inflammatory cytokines [interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha)], matrix metalloproteinases [collagenase (MMP1), stromelysin (MMP3), gelatinase 72 kDa (MMP2)], tissue inhibitors of metalloproteinase (TIMP 1 and TIMP 2), and the TNF-alpha receptor in rheumatoid synovial fibroblasts. METHODS: Cells were dosed with each compound for 24 h in the presence or absence of PMA inducer and messenger RNA (mRNA) extracted and subjected to Northern blot analysis. Messenger RNA levels were quantitated by densitometry and normalized to GAPDH or 18S rRNA. RESULTS: We observed some modest effects of sulfasalazine and its metabolites on steady state mRNA levels including: (1) repressed mRNA levels for TNF-alpha [approximately 40% with 3x (drug median serum concentration) all 3 drugs], stromelysin (approximately 24% with 3x all 3 drugs and approximately 31% with 3x 5ASA), and collagenase (approximately 27% with 3x 5ASA); (2) elevated mRNA levels for TIMP 2 (3.5 kb transcript) (51% with 3x SP and 44% with 3x 5ASA), gelatinase (approximately 20% with 3x SP and 3x 5ASA), stromelysin (approximately 40% with 3x and 1x SASP), IL-1beta (approximately 31% with 0.1x 5ASA); and (3) no effect on mRNA levels for TNF-alpha receptor and TIMP 1. CONCLUSION: (1) SASP and its metabolites showed varied effects on steady state mRNA concentrations for gene transcripts that fell into 3 categories: (a) repressed, (b) elevated, (c) no effect on mRNA levels. (2) No apparent linear dose response effect was observed for SASP or its metabolites, although a generalized suppression of mRNA levels at all doses was seen in some cases. (3) No predominant suppressive effect (> or = 50%) of mRNA levels by any of the drugs was observed for any of the genes studied; however, TIMP 2 mRNA levels increased 51% with 3x SP and 44% with 3x 5ASA.

Asunto(s)

RESUMEN

Many Gulf War veterans complain of a variety of symptoms including skin rashes and joint pain which may have a common immunological basis. Other Gulf War veterans have post-traumatic stress disorder (PTSD), an anxiety disorder associated with chronic stress. Whether or not chronic stress may affect the capacity to resist disease has not been fully delineated, but recent work suggests that a dysregulated balance of cytokines produced by T helper cells of the immune system may play a role in stress-related illnesses. It is known that a balanced immune response (cell-mediated and humoral immunity) is an important defense mechanism. Although the mechanism(s) by which a change in immune system balance occurs is not clear, it may be secondary to stress-induced changes in hormones such as cortisol and catecholamines, both of which have been implicated in altering levels of cellular or humoral immunity. For these reasons, we are investigating the function of both the cellular and humoral arms of the immune system as well as the cytokine patterns associated with these different functions in symptomatic Gulf War veterans and control groups consisting of asymptomatic Gulf War veterans and symptomatic non-Gulf War veterans.

Asunto(s)

RESUMEN

The role of stress and immunological abnormalities, as well as the neuroendocrine regulation of these two variables, in illnesses in Gulf War veterans (GWVs) is unknown. Many GWV patients complain of skin and joint problems, that is, disorders that may have a common immunological basis. Post-traumatic stress disorder (PTSD), an anxiety disorder associated with chronic stress, is diagnosed in approximately 10% of the Alabama GWVs. Chronic stress can lead to a reduced capacity to resist disease. Recent work suggests that a dysregulated balance of cytokines produced by T helper cells of the immune system can play a significant role in stress-related illnesses. Indeed, a balanced immune response (cell-mediated and humoral immunity) is an important defense mechanism, and cytokines can regulate this balance. It is therefore plausible that stress-induced changes in hormones (such as cortisol and catecholamines) and cytokines, both of which have been implicated in altering levels of cellular or humoral immunity, may play a role in GWV illnesses.

Asunto(s)

RESUMEN

We report the prenatal diagnosis of an apparently balanced de novo complex chromosome rearrangement (CCR) which involved nine breakpoints on four different chromosomes. Fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY) were performed as an adjunct to G-banding for characterization of the abnormal chromosomes. The 22-week female fetus showed minor dysmorphic features including dolichocephaly, broad fingernails, tibial bowing, clubfoot, thoracolumbar scoliosis and hypoplastic toenails. Autopsy revealed gall-bladder hypoplasia and an atrial septal defect. Chromosome analysis of fetal tissue confirmed the presence of the complex rearrangement.

Asunto(s)

Asunto(s)

RESUMEN

Dichorionic placentation is observed in both monozygotic (MZ) and dizygotic (DZ) twinning, while monochorionic placentation is unique to MZ twinning. Examinations of monochorionic twin placentas frequently reveal the presence of vascular anastomoses between the two fetal circulations; such anastomoses rarely occur in dichorionic placentas. Consequently, abnormalities resulting from placental vascular communications are almost exclusively observed in MZ twin pairs with monochorionic placentas. We report opposite-sex DZ twins in which vascular anastomoses occurred within a fused dichorionic placenta and were associated with vascular disruptions in one twin. The liveborn male twin had amelia, cutis aplasia, and XX/XY blood chimerism; the female twin died in utero.

Asunto(s)

RESUMEN

A correlation was found between the expression of a specific Mycoplasma fermentans surface antigen (Pra, proteinase-resistant antigen) and the site of isolation of the organism from the infected host. Strains which expressed Pra were most frequently associated with cells of bone marrow origin, and strains which lacked expression of Pra were most commonly isolated from the respiratory tract, genital tract, and arthritic joints, i.e., epithelial cell surfaces. Pra was previously shown to be resistant to degradation by proteinases and was hypothesized to play a protective role at the organism surface and perhaps to influence which host tissue site was colonized by the organism. The methods used for this phenotyping scheme required isolation and growth of the mycoplasma in quantities sufficient for immunoblot analysis using monoclonal antibodies. We wanted to determine a more rapid and less cumbersome technique to supplement this method for determining the Pra phenotype directly in clinical specimens. Here we describe PCR studies to investigate the movement of a previously identified M. fermentans insertion sequence (IS)-like element. These data showed a correlation between a specific IS genotype and the Pra+ phenotype. Production of a 160-bp product using a single set of IS-based primers was associated with expression of Pra. The genomic IS location resulting in the 160-bp product was determined by using Southern blot analysis and was found to be a stable insertion site characteristic of genotype I strains. Additional analyses of sequences within and flanking the IS insertion sites revealed another pair of PCR primer sites which resulted in the consistent production of a 450-bp amplicon. The stability of this site was dependent on the absence of the IS-like element between the primer sites. The production of this 450-bp amplicon correlated with the Pra mutant phenotype and was characteristic of genotype II strains. The data showed that the sequence within the IS may be unstable and that reliable genotyping sequences are more easily found in the stable genomic sites which flank the IS element.

Asunto(s)

RESUMEN

Alcohol fuels produced from biomass can improve air quality, enhance energy security, create employment opportunities, and reduce waste disposal problems. Opportunities in California exist to produce alcohols from waste streams from various sectors of the economy. Government agencies have promoted waste-to-alcohol activities, but efforts have been inconsistent and intermittent. Often these efforts have been hindered by contradictory but mandate-driven policies. A prudent approach to coordinate statewide efforts includes the development of an integrated statewide policy to examine barriers that impede private sector business efforts to produce alcohols from biomass. A multi-agency task force to promote research, development, commercialization, and marketing efforts for biomass-produced alcohols is desirable.

RESUMEN

The term eosinophilia myalgia syndrome (EMS) was coined in 1989 after a cluster of cases with symptoms of incapacitating myalgias and eosinophilia were reported. This syndrome has been only defined as varying degrees of myalgias and peripheral eosinophilia. Case reports of EMS are protean and do not show a consistent clinical picture, raising the question of whether this reflects a single disorder or is a conflation of various disorders. There have been only two studies evaluating the association of EMS with 1-tryptophan. These two included only 23 patients with EMS. Apart from the obvious statistical fragility inherent in such small studies, each is further weakened by differences in the mechanisms by which patients and controls were selected. Furthermore, the continued reports of EMS after 1-tryptophan was removed from the market raise additional questions about the association. Nonetheless, there has been an inordinate reliance on a history of 1-tryptophan ingestion in making the diagnosis of EMS. When presented case studies, clinicians were much more likely to make the diagnosis of EMS when a history of 1-tryptophan ingestion was included. These observations underscore the need for careful application of well-considered diagnostic criteria to the study of new syndromes and their potential associations.

Asunto(s)

Asunto(s)

RESUMEN

Anecdotal, reports have raised the issue of an association between silicone breast implants and the development of rheumatic diseases. Fortunately, this issue has now been extensively addressed by controlled studies, which demonstrate no association between breast implants and rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Moreover, several studies that now have addressed the issue of "atypical connective tissue disease" indicate no association between a number of rheumatic complaints and silicone breast implants. Additionally, several controlled studies show no evidence of chronic inflammation in patients with silicone breast implants. These observations should be reassuring to women with breast implants and the individuals who care for them.

Asunto(s)

RESUMEN

Breast implants containing silicone have been used for approximately 30 years for breast augmentation or reconstruction. In general, the implants have been well tolerated and reports have indicated a high degree of patient satisfaction. Nonetheless, there have been anecdotal reports of patients with musculoskeletal complaints that have been attributed to silicone breast implants. To investigate this further, we prospectively examined 70 women with silicone breast implants who had complaints that they or their referring physicians thought were related to their implants. On clinical examination, the majority of the patients had fibromyalgia, osteoarthritis, or soft-tissue rheumatism. One patient had rheumatoid arthritis, which predated her implants, and one had Sjõgren's syndrome. Because many of our patients had myalgic symptoms, we further evaluated these patients by measuring circulating levels of soluble factors including interleukin-6, interleukin-8, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, and soluble interleukin-2 receptor, which have been previously found to be elevated in patients with inflammatory diseases. We found that the levels of these molecules in women with silicone breast implants were not different from those seen in normal subjects and were significantly less than those seen when examining chronic inflammatory disorders such as rheumatoid arthritis or systemic lupus erythematosus. In summary, our clinical and laboratory evaluation of symptomatic breast implant patients argues against an association of silicone breast implants with a distinctive rheumatic disease or a systemic inflammatory disorder. Given these findings and the clinical picture, it is our impression that most symptomatic women with silicone breast implants have well-delineated noninflammatory musculoskeletal syndromes. Moreover, these data fail to support the concept that their symptoms are due to a systemic inflammatory response related to their implants.

Asunto(s)

RESUMEN

A chimeric Adenovirus-Simian Virus 40 (AdSV40) containing the large T antigen was used to transform rheumatoid synovial fibroblasts. A rheumatoid synovial fibroblast cell line was established by infection of primary rheumatoid arthritis (RA) synovial fibroblasts at Passage 10 with AdSV40 recombinants followed by selection in semisoft agarose cultures. The transformed cells grew anchor independent, exhibited continuous proliferation (> 65 passages) in monolayer culture, and formed multiple visible foci. The transformed synovial fibroblasts showed expression of the simian virus 40 large T antigen in the nucleus as determined by immunofluorescence staining. In addition, indirect immunofluorescence staining demonstrated that the transformed cells stained specifically with a fibroblast-specific antibody 1B10. Studies involving expression of metalloproteinases showed that collagenase and stromelysin were induced by phorbal 12-myristate 13-acetate (PMA), and such an induction was repressed by dexamethasone typical of primary RA fibroblasts. Levels of mRNAs for IL-1 beta, TNF-alpha, and c-jun were increased by PMA, and the mRNA transcripts of these genes were also repressed by addition of dexamethasone to the culture media. Our results indicate that transformed RA synovial fibroblasts display a similar gene expression pattern in response to PMA and dexamethasone as observed for untransformed primary RA synovial fibroblasts. These transformed rheumatoid arthritis synovial fibroblast cells provide an ideal cell culture model in which to test the efficacy of novel arthritis gene therapy reagents.

Asunto(s)

RESUMEN

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy. METHODS: Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments. RESULTS: While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients.

Asunto(s)

RESUMEN

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy. METHODS: Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.

Asunto(s)

RESUMEN

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy. METHODS: One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA.

Asunto(s)

Asunto(s)