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Biomedical subjects

R Hirsch

Publications and source records attributed to R Hirsch.

At least 55 records · Page 3Linked to original sources

Occurrence of antibiotics in the aquatic environment.

The recent monitoring of drug residues in the aquatic environment has gained much interest as many pharmaceutical compounds can frequently be found in sewage treatment plant (STP) effluents and river water at concentrations up to several microgram/l. This article describes the analysis of various water samples for 18 antibiotic substances, from the classes of macrolid antibiotics, sulfonamides, penicillins and tetracyclines. Samples were preconcentrated via lyophilization and quantified using HPLC-electrospray-tandem-mass spectrometry. The investigated STP effluents and surface water samples showed frequent appearance of an erythromycin degradation product, roxithromycin and sulfamethoxazole with concentrations up to 6 micrograms/l. Neither tetracyclines nor penicillins could be detected at concentration levels above 50 and 20 ng/l, respectively. From the large number of ground water samples that were taken from agricultural areas in Germany, no contamination by antibiotics was detected except for two sites. This indicates that intake from veterinary applications to the aquatic environment is of minor importance.

Agriculture↗

Association of the course of collagen-induced arthritis with distinct patterns of cytokine and chemokine messenger RNA expression.

OBJECTIVE: To quantitate changes in cytokine and chemokine messenger RNA (mRNA) levels during the development and progression of collagen-induced arthritis (CIA) in mice. METHODS: Mice with CIA were scored for arthritis and killed at weekly intervals. Cytokine and chemokine mRNA levels were determined by RNase protection assays of total paw RNA. RESULTS: Arthritic paws exhibited mRNA levels of interleukin-1beta (IL-1beta), IL-2, macrophage inflammatory protein 2 (MIP-2), IL-6, IL-1 receptor antagonist, RANTES, tumor necrosis factor alpha (TNFalpha), TNFbeta, MIP-1alpha, IL-11, transforming growth factor beta1 (TGFbeta1), TGFbeta2, and TGFbeta3 that were increased above mRNA levels in paws of normal, unimmunized mice and that exhibited distinct temporal patterns of mRNA expression. Clinically uninvolved paws also exhibited an increase in mRNA levels of IL-11, RANTES, TNFalpha, TNFbeta, and MIP-1alpha. CONCLUSION: The observed differential temporal cytokine and chemokine mRNA expression patterns suggest that specific cytokines and chemokines have defined roles at various times during the course of autoimmune arthritis. Since most of these cytokines and chemokines are found in human rheumatoid arthritis (RA) synovium and synovial fluids, these findings may have relevance to RA.

Animals↗

Severity of hand osteoarthritis and its association with upper extremity impairment in a population of disabled older women: the Women's Health and Aging Study.

Most severity indices of osteoarthritis (OA) include measures of physical function which render them unsuitable for assessing the impact of OA on disability. Data from 1002 moderate to severely disabled community-dwelling women > or = 65 years were used to develop hand OA severity indices which are independent of functional status. Baseline exams and strength tests were conducted by trained nurse examiners. Each distal and proximal interphalangeal joint, and first carpometacarpal joint (20 joints in all) was scored for the presence of a) bony enlargement or deformity, and b) pain on motion or tenderness on palpation. Severity indices were then created: Deformity index (DEF) = sum of joints with bony changes (0-20); Pain/Tenderness index (PT) = sum of joints with pain or tenderness (0-20); and Combined Deformity/Pain index = sum of DEF and PT (0-40). These indices were then validated against grip and pinch strength. All three indices showed a significant trend for weaker grip strength as severity index scores increased. When the 25th, 50th and 75th percentiles were used to divide each severity index into levels of involvement, a threshold effect was observed with significantly poorer grip strength performance above the 75th percentile for each index. Similar results were seen for pinch strength. In conclusion, these hand OA severity indices, based on examination findings alone, help distinguish disease status, and may provide a valuable research tool for investigating the role of hand OA in impairment and disability.

Aged↗

Thrombosis of bileaflet tricuspid valve prosthesis: clinical spectrum and the role of nonsurgical treatment.

BACKGROUND: Thrombosis of a mechanical tricuspid valve prosthesis is a potentially hazardous event. This study aimed to explore the incidence and the clinical presentation of tricuspid valve thrombosis occurring in bileaflet valves and to evaluate the diagnostic and the therapeutic approach. METHODS AND RESULTS: Tricuspid valve thrombosis was sought in 22 late survivors with the CarboMedics valve in a follow-up period of 36.0 +/- 20.8 months. Limited leaflet motion and/or a visible thrombus were considered diagnostic of valve thrombosis. Eight episodes of tricuspid valve thrombosis were diagnosed among 5 patients (12.1 episodes per 100 patient-years). Anticoagulation was inadequate in 3 patients and fair in 2. Florid right heart failure occurred in 3 episodes. Common physical findings included increased jugular venous pulse (5 patients), diastolic tricuspid murmur (4 patients), and peripheral edema (4 patients). The diagnosis was suspected in all clinically and by transthoracic echocardiography and confirmed by fluoroscopy and/or transesophageal echocardiography. In 4 patients, both leaflets were involved. No thrombi were visualized. Three patients received thrombolytic therapy in 4 episodes (complete success in 3, partial success in 1) without hemorrhagic or embolic complications. One patient responded to aggressive anticoagulant therapy. One patient required an emergent repeat surgery. In 1 patient, valve thrombosis recurred thrice. CONCLUSIONS: In patients with fair or poor anticoagulation, a bileaflet valve in the tricuspid position is associated with a high incidence of valve thrombosis. Hinge entrapment requires only a small amount of thrombotic material. Valve thrombosis may be asymptomatic. Involvement of both leaflets is usually required to produce symptoms. A nonsurgical approach (thrombolysis or intensified anticoagulation) is usually successful. Patients should be instructed about heralding signs of valve thrombosis.

Adult↗

Low back pain and disability in older women: independent association with difficulty but not inability to perform daily activities.

BACKGROUND: Low back pain is a highly prevalent chronic condition, yet little is known about the disabling effects of this common problem in older adults. This study examines the relationship between the presence and severity of low back pain and disability in older women. METHODS: The study population was 1,002 disabled older women participating in a population-based prospective study of disablement. Key outcome measures of disability included level of difficulty and inability to perform the following daily activities: light housework, shopping, walking one-quarter mile, climbing stairs, lifting, and activities of daily living (ADLs). RESULTS: Forty-two percent of participants reported they had low back pain for at least one month in the year before baseline. The prevalence of severe back pain decreased markedly with age (10% of those > or = 85 yr versus 23% in each of the two younger 10 yr age groups). After multivariate adjustments, women with severe back pain were 3 to 4 times more likely than other women to have a lot of difficulty with light housework or shopping. There was also an increased likelihood of difficulty with mobility tasks and basic ADLs among those with severe back pain. No associations were found between back pain and being unable to perform any of the daily activities studied, indicating possible differences in disablement processes leading to functional difficulties versus functional incapacity. CONCLUSIONS: There was a strong association between back pain and functional difficulties in older women, pointing to the need for further research using longitudinal methods.

Activities of Daily Living↗

Self-assessment in a problem-based learning curriculum in dentistry.

The creation of sound self-judgement for students is an integral goal in any educational sphere. Student clinicians in dentistry must learn sufficient skills to be able to self-assess their performance very accurately, because after graduation, the nature of dental procedures means that others are seldom in a position to evaluate the quality of their work. Over recent years, the Department of Dentistry at the University of Adelaide has been developing a self-assessment procedure, initially as a pilot study in the subject oral diagnosis, and currently in all years of the course. This paper describes how self-assessment has been demonstrated to work initially in the pilot subject, and currently across the whole course. The paper also describes how the criteria for assessment and the levels of performance expected for each grade are established and how student performance is monitored. Finally, evidence is presented to indicate acceptance by the students of self-assessment as a valuable and integral part of their learning in dentistry.

Curriculum↗

Foot pain and disability in older women.

In a study of the relation between foot pain and disability, a cross-sectional analysis was performed using baseline data (1992-1995) from the Women's Health and Aging Study, a population-based study of 1,002 disabled women aged 65 years and older living in Baltimore, Maryland. Chronic and severe foot pain, defined as pain lasting 1 month or longer in the previous year, plus pain in the previous month rated severe (7-10 on a scale of 0 to 10), was reported by 14% of the women. Severe foot pain was more common in women who were younger (aged 65-74 years), obese, or had hand or knee osteoarthritis. Walking speed and five repeated chair stands were slower in women with foot pain. After adjustment for age, body mass index, race, education, self-rated health, smoking status, comorbidities, and number of other pain sites, severe foot pain was independently associated with increased risk for walking difficulty (adjusted odds ratio = 1.69, 95% confidence interval 1.10-2.59) and disability in activities of daily living (adjusted odds ratio = 1.91, 95% confidence interval 1.21-3.01). These findings suggest that severe foot pain may play a key role in disability in older women. Further studies are warranted to confirm these results longitudinally and to determine whether interventions to alleviate foot pain could reduce or prevent disability in older women.

Aged↗

Adenovirus-mediated granulocyte-macrophage colony-stimulating factor improves lung pathology of pulmonary alveolar proteinosis in granulocyte-macrophage colony-stimulating factor-deficient mice.

Mutation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene by homologous recombination causes progressive pulmonary alveolar proteinosis (PAP) in GM-CSF-deficient mice (GM-/-). The present study tested whether adenovirus-mediated expression of GM-CSF alters the progression of PAP in GM-/- mice. Adult mice were pretreated with an anti-T cell receptor (TCR) antibody to block T cell-mediated immune response, followed by intratracheal instillation of deltaE1-E3 replication-deficient adenovirus expressing mouse GM-CSF (Av1mGM). Mice were killed 1, 3, and 5 weeks after treatment to assess lungs for GM-CSF, surfactant protein B (SP-B), alveolar macrophage maturation, and type II cell proliferation. GM-CSF was detected in BAL fluid from GM-/- mice 1 week after Av1mGM treatment, and GM-CSF mRNA was detected by RT-PCR through 5 weeks. Five weeks after Av1mGM treatment, PAP was improved and SP-B decreased as assessed by ELISA and immunostaining. Increased numbers of alveolar macrophages stained with alpha-naphthyl acetate esterase (alpha-NAE) following treatment with Av1mGM. Local expression of GM-CSF with a recombinant adenovirus ameliorated PAP in the GM-/- mice in association with enhanced maturation of alveolar macrophages.

Adenoviridae↗

Inhibition of collagen-induced arthritis in mice by viral IL-10 gene transfer.

Autoimmune arthritides are characterized by an imbalance between pro- and anti-inflammatory cytokines. Viral IL-10 (vIL-10) shares many of the anti-inflammatory properties of mouse and human IL-10, but lacks their immunostimulatory properties and may therefore offer superior immunosuppression. Viral IL-10 has a short half-life; however, genetic modification of cells in vivo offers a potential means of achieving prolonged therapeutic titers. To determine the effects on collagen-induced arthritis of vIL-10 gene transfer, DBA/1 mice were administered i.v. or intra-articular injections of Av(vIL-10), a replication-deficient adenovirus encoding vIL-10. The i.v. injection of Av(vIL-10) before disease onset delayed the onset and reduced the severity of collagen-induced arthritis, but treatment of established disease was ineffective. The preventative effects were not due to decreased anti-type II collagen Ab production. Rather, T cells from mice treated with Av(vIL-10) demonstrated a decreased in vitro proliferative response to type II collagen, and a delay was observed in up-regulation of synovial mRNA for the proinflammatory cytokines IL-2 and IL-1beta. Intra-articular injection of Av(vIL-10) into knee joints did not reduce arthritis in the knees, but inhibited the development of arthritis in the paws. Humoral and cellular immune responses against Av(vIL-10) were observed. These results demonstrate that vIL-10 can significantly alter the course of autoimmune arthritis and emphasize the complexities of using gene transfer as a method of drug delivery for arthritis.

Adenoviridae↗

Determination of antibiotics in different water compartments via liquid chromatography-electrospray tandem mass spectrometry.

For the determination of 18 antibiotics in water samples down to the lower ng/l range, an analytical multi method is presented. The analytes belong to different groups of antibiotics such as penicillins, tetracyclines, sulfonamides and macrolid antibiotics. Samples were enriched using a universal freeze-drying procedure or a solid-phase extraction facultatively. Analysis was performed by liquid chromatography with electrospray-tandem MS detection. Chromatography required different columns and eluents. Mean recovery rates were in excess of 70%, however, with one exception and a quantitation limit of 50 ng/l for the tetracyclines and 20 ng/l for all other antibiotics were set.

Anti-Bacterial Agents↗

Hip osteoarthritis prevalence estimates by three radiographic scoring systems.

OBJECTIVE: To estimate and compare the age- and sex-specific prevalence of radiographic hip osteoarthritis (RHOA) in a population-based study of the Pima Indians, using 3 atlas-based methods for assessing features of RHOA. METHODS: Pelvic radiographs from 755 Pima Indians age > or = 45 years enrolled in a population-based study were read using the Kellgren/Lawrence (K/L) grading scale (grade 0-4) and 2 validated individual-radiographic-features (IRF) scales (grades 0-3 for narrowing and osteophytes). RESULTS: The age- and sex-specific prevalence of RHOA among Pima Indians assessed using the K/L scale was < 10% in all age and sex groups. The prevalence of grade > or = 2 osteophytes assessed using the 2 IRF scales were similar to each other in all age and sex groups. However, differences between the 2 IRF scoring systems were found for the prevalence of grade > or = 2 joint space narrowing. CONCLUSION: Pima Indians have an age- and sex-specific prevalence of RHOA similar to that found in the US population. Our finding of different joint space narrowing prevalence by the 2 IRF grading scales supports the use of the same atlas-based case definitions for determining disease prevalence for comparative studies.

Age Distribution↗

Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States.

OBJECTIVE: To provide a single source for the best available estimates of the national prevalence of arthritis in general and of selected musculoskeletal disorders (osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, the spondylarthropathies, systemic lupus erythematosus, scleroderma, polymyalgia rheumatica/giant cell arteritis, gout, fibromyalgia, and low back pain). METHODS: The National Arthritis Data Workgroup reviewed data from available surveys, such as the National Health and Nutrition Examination Survey series. For overall national estimates, we used surveys based on representative samples. Because data based on national population samples are unavailable for most specific musculoskeletal conditions, we derived data from various smaller survey samples from defined populations. Prevalence estimates from these surveys were linked to 1990 US Bureau of the Census population data to calculate national estimates. We also estimated the expected frequency of arthritis in the year 2020. RESULTS: Current national estimates are provided, with important caveats regarding their interpretation, for self-reported arthritis and selected conditions. An estimated 15% (40 million) of Americans had some form of arthritis in 1995. By the year 2020, an estimated 18.2% (59.4 million) will be affected. CONCLUSION: Given the limitations of the data on which they are based, this report provides the best available prevalence estimates for arthritis and other rheumatic conditions overall, and for selected musculoskeletal disorders, in the US population.

Adolescent↗

Familial aggregation of osteoarthritis: data from the Baltimore Longitudinal Study on Aging.

OBJECTIVE: To evaluate the familial aggregation of osteoarthritis (OA) in a cohort of healthy volunteers drawn from a community setting. METHODS: Hand radiographs obtained between 1978 and 1991 and bilateral standing knee radiographs obtained between 1984 and 1991 were read for changes of OA, using Kellgren-Lawrence (K-L) scales. The hand sites were distal interphalangeal (DIP) joints, proximal interphalangeal (PIP) joints, and first carpometacarpal (CMC1) joints. For each joint group, the presence of OA in at least 1 joint in a joint group, the number of affected digits in each joint group, and the sum of the K-L grade across all joints were analyzed. Polyarticular OA was recorded if there were OA findings in 2 of 3 hand joint groups plus 1 or both knees. Data from 167 families with hand radiographs, 157 families with knee radiographs, and 148 families with both hand and knee radiographs were analyzed for sib-sib correlations. RESULTS: After adjustment for age, sex, and body mass index, clinically relevant sib-sib common correlations were found for OA of the DIP, PIP, and CMC1 joints, for OA at 2 or 3 hand sites, and for polyarticular OA (r = 0.33-0.81) when OA was defined according to the number of affected joints or as the sum of the K-L grade across all joints. CONCLUSION: These results from a cohort of volunteers drawn from a community setting and ascertained without regard to OA status demonstrate familial aggregation of OA and contribute to the evidence for heritability of OA.

Adult↗

Rheumatoid arthritis in the Pima Indians: the intersection of epidemiologic, demographic, and genealogic data.

OBJECTIVE: To describe the clinical features and familial distribution of rheumatoid arthritis (RA) in the Pima Indians. METHODS: From 1965 through 1990, all cases of RA as defined by the American College of Rheumatology (formerly, the American Rheumatism Association) 1987 criteria or all cases of seropositive, erosive disease as defined by the Rome criteria were identified in individuals who were age 20 years and older and were of 50% or more Pima/Tohono-O'odham heritage. Radiographs were reviewed by 2 musculoskeletal radiologists who were blinded to case status. Kinship coefficients were used to evaluate familial aggregation. RESULTS: Eighty-eight RA cases were identified from this population-based sample. Over 66% of the cases had seropositive disease, over 60% had erosive disease, and over 40% had subcutaneous nodules. Of the 88 RA cases, 40 were members of families with more than 1 RA case. The remainder were simplex cases. CONCLUSION: In this population, clinical markers of severe RA were present in a majority of cases. The presence of familial aggregation for RA in the Pima Indians suggests underlying genetic factors in disease pathogenesis.

Adult↗

Altered susceptibility to collagen-induced arthritis in transgenic mice with aberrant expression of interleukin-1 receptor antagonist.

OBJECTIVE: To determine the effect of overexpression or deletion of interleukin-1 receptor antagonist (IL-1Ra) in collagen-induced arthritis (CIA). METHODS: Mice overexpressing the IL-1Ra gene under the control of its endogenous promoter, mice lacking IL-1Ra, and normal littermate controls were immunized with bovine type II collagen (CII) and compared in terms of features of CIA. RESULTS: Mice overexpressing IL-1Ra had a significant reduction in the incidence and severity of CIA. After CII immunization, IL-1Ra messenger RNA was overexpressed in the spleens, but not in the paws, of transgenic mice. Minimal differences were observed in the humoral or cellular immune responses to CII. Mice lacking IL-1Ra had a significantly earlier onset of CIA, with increased severity. CONCLUSION: Endogenous expression of IL-1Ra is a critical determinant of susceptibility to CIA. These findings suggest potential therapeutic interventions for autoimmune arthritis.

Animals↗

Establishing the level of digitization for wrist and hand radiographs for the third National Health and Nutrition Examination Survey.

In the third National Health and Nutrition Examination Survey (NHANES III) conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention, radiographs of the hands and knees were taken of participants 60 years and older as part of the study of arthritis and musculoskeletal conditions. The purpose of the study was to decide the digitizing resolution to be used for these radiographs. A set of wrist and hand radiographs (N = 49) was graded by two radiologists for degree of bone erosions and served as a "gold standard." The radiographs were then digitized at three resolution levels; low-resolution 150 microns (2001 x 1634 x 12 bit matrix); intermediate-resolution 100 microns (3000 x 2400 x 12 bit matrix); and high-resolution 50 microns (4900 x 3000 x 12 bit matrix). A comparison of the digital images versus the gold standard reading was made at the three resolutions by two radiologists. Kappa statistics suggested fair (K > .4) to excellent (K > .75) agreement between the gold standard and the images at all levels. Intraclass correlation coefficient suggested high agreement between readers (ICC > .5), with minimal individual reader effect. Variance component estimates showed that the major contribution (78-83%) to scoring came from variability in the images themselves, not from the readers. The 100 microns resolution was selected over the 150 and 50 microns on the basis of practical considerations such as storage requirements, display time, and easier manipulation of the digital images by the readers.

Arizona↗