PubMed Health⌕ Search

Biomedical subjects

J Gruber

Publications and source records attributed to J Gruber.

At least 19 recordsLinked to original sources
PubMed2006

Ultrasonographic and radiographic results from a two-year controlled trial of immediate or one-year-delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis.

OBJECTIVE: To compare the impact of immediate and delayed introduction of anti-tumor necrosis factor therapy on inflammation and structural damage in methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA). METHODS: Twenty-four patients with erosive early RA (duration < 3 years) who were receiving MTX were randomized to receive infliximab 5 mg/kg or placebo infusions at weeks 0, 2, and 6, and then every 8 weeks through week 46. Beginning at week 54 and thereafter, all patients received infliximab 5 mg/kg. Metacarpophalangeal joints were scanned using high-frequency ultrasonography and power Doppler imaging. Radiographs were evaluated using the modified Sharp/van der Heijde scoring system. RESULTS: From baseline to week 54, total synovial thickness was significantly improved in the infliximab + MTX group compared with the placebo + MTX group (median reduction 95.8% versus 37.5%; P = 0.005), as was the total color Doppler area (CDA; vascularity assessment) (median reduction 100% and 47.1%, respectively; P = 0.025). From week 0 to week 110, no significant between-group difference was observed in the change from baseline for total synovial thickening or the total CDA. At week 54, greater progression in the Sharp/van der Heijde score was apparent in patients receiving placebo + MTX compared with those receiving infliximab + MTX. Although radiographic progression in the placebo + MTX group was greatly reduced in the second year (after initiation of infliximab therapy), marked differences were observed between the infliximab + MTX group (median change in the Sharp/van der Heijde score 4.0) and the placebo + MTX group (median change 14.5) from baseline to week 110 (P = 0.076). CONCLUSION: The results indicate that the efficacy of 2 years of combination therapy with infliximab + MTX for inhibiting cumulative structural damage was superior to that of 1 year of treatment with MTX alone followed by the addition of infliximab.

Antibodies, Monoclonal↗
PubMed2006

Acute inflammatory syndrome induced by mycophenolate mofetil in a patient following kidney transplantation.

Mycophenolate mofetil (MMF) is increasingly used to prevent acute and chronic rejection following kidney transplantation and in autoimmune diseases. Here, we report on a patient after kidney transplantation, who developed an acute inflammatory syndrome characterized by fever and oligoarthritis within 1 week after increasing the MMF dosage. MMF was discontinued resulting in a complete resolution of the syndrome within 48 h. We demonstrated in vitro that the patient's phorbol myristate acetate (PMA-) and formyl Met-Leu-Phe (fMLP-) stimulated polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MMF. This report demonstrates that MMF can also induce acute inflammatory syndrome in patients following kidney transplantation and that this syndrome might be due to a paradox, pro-inflammatory reaction of PMNs.

Aged↗
PubMed2004

Hysteroscopy in the evaluation of patients with recurrent pregnancy loss: a cohort study in a primary care population.

BACKGROUND: The purpose of this study was to determine the prevalence of structural uterine defects (SUD) in patients with recurrent pregnancy loss (RPL) attending a large family medicine practice and to determine the effectiveness of the therapeutic intervention. METHODS: This prospective cohort study from October 1995 to October 1998 included 23 patients aged 23 to 35 years (mean, 28.1) with an otherwise unexplained history of three or more 1st- or 2nd-trimester miscarriages and no live births. None of the couples were tobacco or alcohol users, all of them and had normal cytogenetic examinations and testing. Their jobs were unrelated to chemical handling. All patients had a complete history taken and underwent physical examination and hysteroscopy with directed biopsy. They had normal values for complete blood count, sedimentation rate, urinalysis and culture (gonorrhea, Chlamydia, syphilis, hepatitis B, HIV), lupus anticoagulant, anticardiolipin antibodies, spermiogram, progesterone, and pelvic ultrasound. RESULTS: Fourteen patients (60.9%) had a normal hysteroscopy (with biopsies). Nine patients (39.1 %) had SUD, as follows: Five patients (21.8%) had intrauterine adhesions, two patients (8.7%) had a septated uterus, one patient (4.3%) had submucosal myoma, and one patient (4.3%) had multiple factors. After appropriate therapy of the SUD, seven patients (77.8%) achieved successful pregnancy and two patients (22.2%) had recurrent miscarriage. In the normal hysteroscopy group, eight patients (57.1%) had recurrent miscarriages, two patients (14.3%) had infertility, and four patients (28.6%) achieved successful pregnancy with no further therapy. CONCLUSIONS: The prevalence of SUD in our studied population was 39.1 %. After appropriate treatment, the rate of live-birth pregnancies in these patients was 77.8%. Because SUD are the most treatable cause of RPL, these patients should be identified early after other potential causes of RPL are eliminated.

Abortion, Habitual↗
PubMed2004

Comparison of ultrasonographic assessment of synovitis and joint vascularity with radiographic evaluation in a randomized, placebo-controlled study of infliximab therapy in early rheumatoid arthritis.

OBJECTIVE: To investigate sensitive ultrasonographic imaging methods for detection of synovial thickness and vascularity to discriminate between patients with early rheumatoid arthritis (RA) receiving infliximab + methotrexate (MTX) versus placebo + MTX over 18 weeks, and to compare the relationship between synovial thickening and vascularity at baseline and radiologic damage to joints of the hands and feet at 54 weeks. METHODS: Patients with early RA (duration <3 years) receiving stable dosages of MTX were randomly assigned to receive blinded infusions of 5 mg/kg infliximab (n = 12) or placebo (n = 12) at weeks 0, 2, 6, and then every 8 weeks until week 46. At baseline and week 18, clinical assessments were performed, and metacarpophalangeal joints were assessed by high-frequency ultrasonography and power Doppler ultrasonography measurements. Radiographs of the hands and feet taken at baseline and at 54 weeks were evaluated using the van der Heijde modification of the Sharp method (vdH-Sharp score). RESULTS: Using changes in the total vdH-Sharp score over 54 weeks and changes in synovial thickening and joint vascularity at 18 weeks, we were able to distinguish those patients receiving infusions of infliximab + MTX from those receiving placebo + MTX. Sonographic measurements of synovial thickening and vascularity at baseline in the placebo + MTX group demonstrated clear relationships with the magnitude of radiologic joint damage at week 54. Infliximab + MTX treatment abolished these relationships. CONCLUSION: The delay or reversal of inflammatory and joint-destructive mechanisms in patients with early RA was already apparent following 18 weeks of treatment with infliximab + MTX and was reflected in radiologic changes at 54 weeks.

Antibodies, Monoclonal↗
PubMed2004

Large-vessel arteritis and myelodysplastic syndrome: report of two cases.

Myelodysplastic syndrome (MDS) is frequently associated with autoimmune diseases such as polymyalgia, arthritis, and rarely, with systemic vasculitis. The pathogenesis of these autoimmune complications remains unknown, but there is increasing evidence of profound immune dysregulation in MDS. In the few cases reported so far, vasculitides associated with MDS affected mainly cutaneous vessels. Here we describe two cases of acute large-vessel vasculitis in association with MDS. The first patient is a 67-yr-old male presenting with a massive large-vessel arteritis as primary manifestation of refractory anemia with excess of blasts type 1 (RAEB-1). The second patient is a 60-yr-old male, who presented with acute thoracic aortitis after a 2-yr history of refractory anemia with ringed sideroblasts (RARS). Both patients received immunosuppressive treatment with steroids, leading to rapid improvement of systemic inflammatory symptoms, vessel wall injury and peripheral blood counts. Whereas the first patient displayed sustained favorable hematologic responses under long-term steroid therapy, there was a rapid transformation into secondary acute myeloid leukemia in the second patient. We conclude that large-vessel vasculitis should be added to the list of potential autoimmune complications in MDS. In this clinical setting, steroid therapy may alleviate inflammatory symptoms and result in beneficial hematologic responses.

Aged↗
PubMed2004

In situ analysis of metal melts in metallurgic vacuum devices by laser-induced breakdown spectroscopy.

We report on rapid in situ analysis of liquid metal melts under reduced ambient pressure by laser-induced breakdown spectroscopy (LIBS) using a transportable system. LIBS denotes a method in which characteristic optical emission line intensities of excited species in laser-generated plasma plumes are used for a quantitative chemical analysis of target materials. It is a fast, noncontact method that can be carried out under various atmospheric conditions, allowing large working distances between the sample under investigation and the detection system. For these reasons, LIBS is applicable in particular for process control in metallurgy under reduced ambient pressure. This was demonstrated for two types of vacuum devices under production conditions at a steel mill. The results of these experiments, including calibration curves for Cr, Ni, and Mg in liquid steel, are presented. The influence of variations in the ambient pressure on the results of the LIBS analysis is discussed within the frame of a generalized shock-wave model for the expansion of the laser-induced plasma plume.

Journal Article↗
PubMed2003

Rheological microscopy: local mechanical properties from microrheology.

We demonstrate how tracer microrheology methods can be extended to study submicron scale variations in the viscoelastic response of soft materials; in particular, a semidilute solution of lambda-DNA. The polymer concentration is depleted near the surfaces of the tracer particles, within a distance comparable to the polymer correlation length. The rheology of this microscopic layer alters the tracers' motion and can be precisely quantified using one- and two-point microrheology. Interestingly, we found this mechanically distinct layer to be twice as thick as the layer of depleted concentration, likely due to solvent drainage through the locally perturbed polymer structure.

Bacteriophage lambda↗
PubMed2001

Transitional subsidies for health insurance coverage.

Losing or leaving a job often means losing health insurance. Of all those who have lost private insurance and become uninsured, one-third have either left or lost a job in the recent past. Continuation of coverage subsidies under the Consolidated Omnibus Budget Reconciliation Act (COBRA) of 1985 mitigate only slightly this problem due to the high costs of the group coverage that must be purchased. This paper discusses a proposal to build on the successes of COBRA to extend insurance to this important population. The key components are: a doubling of the length of COBRA entitlement to 36 months; eligibility for workers in all firms, not just those with more than 20 employees, but with a waiting period of one to two years; the establishment of a new COBRA-LOAN program that would offer government loans to help enrollees pay the cost of COBRA while they searched for new opportunities; and forgiveness of repayments after the entitlement period for those with low incomes.

Adult↗
PubMed2000

Endothelial cell apoptosis in systemic sclerosis is induced by antibody-dependent cell-mediated cytotoxicity via CD95.

OBJECTIVE: Apoptosis of endothelial cells is a key event in the pathogenesis of systemic sclerosis (SSc). The aim of the present study was to analyze in vitro the mechanism causing endothelial cell apoptosis in SSc. METHODS: Human dermal microvascular endothelial cells (HDMEC) or human umbilical vein endothelial cells (HUVEC) were cultured with native or heat-inactivated serum from SSc patients or controls with or without interleukin-2-activated natural killer (NK) cells or peripheral blood mononuclear cells. SSc and control sera were tested for the presence or absence, respectively, of anti-endothelial cell antibodies (AECA) by indirect immunofluorescence. Apoptosis was detected by the TUNEL technique. RESULTS: Native sera alone had no effect. Apoptosis induction was observed on HDMEC, but not on HUVEC, in the presence of AECA-positive SSc sera and activated NK cells, and could be inhibited by an anti-Fas ligand antibody. Inhibition of the perforin/granzyme pathway with concanamycin A had no effect on apoptosis induction in this in vitro model. Immunofluorescence analysis of cryosections from SSc skin showed Fas (CD95) expression by endothelial cells, supporting the in vitro findings. CONCLUSION: The results suggest that endothelial cell apoptosis in SSc is induced by antibody-dependent cell-mediated cytotoxicity via the Fas pathway. These data not only provide insight into the pathogenesis of SSc, but also may open new ways to rational therapy for this disease.

Adult↗
PubMed2000

Epstein-Barr virus-associated Hodgkin's lymphoma and legionella pneumophila infection complicating treatment of juvenile rheumatoid arthritis with methotrexate and cyclosporine A.

We describe the case of a 53-month-old girl with juvenile rheumatoid arthritis (JRA), complicated by the occurrence of Hodgkin's lymphoma and Legionella pneumophila infection during immunosuppressive treatment with methotrexate (MTX) and cyclosporine A (CSA). The girl had received variable anti-inflammatory combination therapy, including MTX for 28 months and CSA for 3 months. Thirty-six months after the onset of arthritis, the girl presented with an enlargement of the lymph nodes of the mediastinum, the hilum of the lungs, and the abdomen. Concomitantly, a diagnosis of Legionella pneumonia was rendered. Autopsy showed Epstein-Barr virus (EBV)-associated nodular sclerosing Hodgkin's lymphoma. The neoplastic cells were positive for CD15, CD 30, and latent membrane protein 1 (LMP 1). The present case is the second reported to occur in a child, and it lends support to the hypothesis that immunosuppressive treatment may contribute to an increased risk of the development of EBV-associated lymphoproliferative disorders (LPD) in pediatric patients suffering from JRA.

Arthritis, Rheumatoid↗
PubMed1999

A phase I/II trial of neoadjuvant chemotherapy with cisplatin and vinorelbine followed by accelerated irradiation for patients with inoperable nonsmall cell lung carcinoma.

BACKGROUND: Both locoregional and distant disease control remains poor in the treatment of Stage III nonsmall cell lung carcinoma (NSCLC). This trial was conducted to evaluate the tolerance and responses of patients with NSCLC given a neoadjuvant regimen of cisplatin and vinorelbine chemotherapy followed by accelerated thoracic radiotherapy. METHODS: Forty-two patients with Stage IIIA and IIIB NSCLC were entered into the study. Treatment consisted of cisplatin 100 mg/m2 given on Days 1 and 29 and vinorelbine 30 mg/m2 given weekly for 5 weeks, with a planned 50% dose reduction to 15 mg/m2 planned for Week 2. This was followed by thoracic irradiation of 60 gray (Gy) in 30 fractions of 2 Gy over 4 weeks (once daily during Weeks 1 and 2 and twice daily during Weeks 3 and 4). RESULTS: With a median follow-up time of 12.2 months (27-65 months for survivors), the median survival was 12.2 months (16.6 months for patients with no prior weight loss and 7.8 months for those with prior weight loss). The response rate after induction chemotherapy was 46.1%, increasing to 74.4% after radiation therapy (8 complete responses and 21 partial responses). The rate of progression was 13 of 18 (72%) for those who responded to chemotherapy (4 distant, 9 local) and 18 of 21 (86%) for those who did not respond to chemotherapy (14 distant, 7 local). The most frequent acute Grade 3 toxicity was nausea (21.4%). CONCLUSIONS: Accelerated thoracic irradiation after induction chemotherapy is well tolerated and yields therapeutic results that compare favorably with those reported for other regimens of chemotherapy and standard fractionated radiotherapy. The data from this study suggest that the responses of patients with clinically apparent disease to induction chemotherapy might indicate a likelihood of controlling microscopic distant metastases.

Adult↗
PubMed1999

2-Amino-3-substituted-6-[(E)-1-phenyl-2-(N-methylcarbamoyl)vinyl]imid azo[1,2-a]pyridines as a novel class of inhibitors of human rhinovirus: stereospecific synthesis and antiviral activity.

A series of 2-amino-3-substituted-6-[(E)-1-phenyl-2-(N-methylcarbamoyl)vinyl]+ ++imid azo[1,2-a]pyridines 1a-i, structurally related to Enviroxime and its analogous benzimidazoles, was designed and prepared for testing as antirhinovirus agents. The imidazo ring in this class of compounds was constructed starting from the aminopyridine after tosylation and subsequent treatment with the appropriate acetamides. The key steps in the synthesis include the development and use of a new Horner-Emmons reagent for the direct incorporation of methyl vinylcarboxamide. The reaction was stereospecific in the substrates 5a-f leading exclusively to the desired E-isomer and avoiding the use of reverse-phase preparative HPLC for the separation of both possible isomers before antiviral activity evaluation. The isopropylsulfonyl group, known as the best substituent at the 1-position in the benzimidazole SAR in terms of activity, was introduced in this new series of imidazo[1,2-a]pyridines via halogen-metal exchange and subsequent treatment with isopropyl isopropanethiolsulfonate. Compounds 1a-i were evaluated in plaque reduction assay and in a cytopathic effect assay. Compounds 1b-d,h exhibited a strong antirhinovirus activity, and no apparent cellular toxicity was visible. The substitution at the 3-position was required for activity. Surprisingly the isopropylsulfonyl in this family of compounds did not enhance the activity as in the case of benzimidazoles. Instead, compound 1i was 4 times less active than its phenyl and sulfide partners. The chemistry as well as the biological evaluation are discussed.

Antiviral Agents↗
PubMed1999

Physician fees and procedure intensity: the case of cesarean delivery.

While there is a large literature investigating the response of treatment intensity to Medicare reimbursement differentials, there is much less work on this question for the Medicaid program. The answers for Medicare may not apply in the Medicaid context, since a smaller share of a physician's patients will be Medicaid insured, so that income effects from fee changes may be dominated by substitution effects. We investigate the effect of Medicaid fee differentials on the use of cesarean delivery over the period 1988-1992. We find, in contrast to the backward-bending supply curve implied by the Medicare literature, that larger fee differentials between cesarean and normal childbirth for the Medicaid program leads to higher cesarean delivery rates. In particular, we find that the lower fee differentials between cesarean and normal childbirth under the Medicaid program than under private insurance can explain between one half and three-quarters of the difference between Medicaid and private cesarean delivery rates. Our results suggest that Medicaid reimbursement reductions can cause real reductions in the intensity with which Medicaid patients are treated.

Cesarean Section↗
PubMed1999

Membrane phospholipid composition affects function of potassium channels from rabbit colon epithelium.

We tested the effects of membrane phospholipids on the function of high-conductance, Ca(2+)-activated K(+) channels from the basolateral cell membrane of rabbit distal colon epithelium by reconstituting these channels into planar bilayers consisting of different 1:1 mixtures of phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylinositol (PI). At low ambient K(+) concentrations single-channel conductance is higher in PE/PS and PE/PI bilayers than in PE/PC bilayers. At high K(+) concentrations this difference in channel conductance is abolished. Introducing the negatively charged SDS into PE/PC bilayers increases channel conductance, whereas the positively charged dodecyltrimethylammonium has the opposite effect. All these findings are consistent with modulation of channel current by the charge of the lipid membrane surrounding the channel. But the K(+) that permeates the channel senses only a small fraction of the full membrane surface potential of the charged phospholipid bilayers, equivalent to separation of the conduction pathway from the charged phospholipid head groups by 20 A. This distance appears to insulate the channel entrance from the bilayer surface potential, suggesting large dimensions of the channel-forming protein. In addition, in PE/PC and PE/PI bilayers, but not in PE/PS bilayers, the open-state probability of the channel decreases with time ("channel rundown"), indicating that phospholipid properties other than surface charge are required to maintain channel fluctuations.

Animals↗
PubMed1999

Construct and longitudinal validity of a modified Huang clinical scoring system in adult cystic fibrosis patients.

This study reports on the evaluation of a modified Huang scoring system in adult cystic fibrosis patients for construct and longitudinal validity. Two studies were performed. In the first study, the scoring system was applied to 59 adult cystic fibrosis patients prospectively followed at the Montreal Chest Institute. The total score and all the subscores distinguished between patients with the expected mild degree of disease severity seen in patients colonized with only Staphylococcus aureus, compared to the more advanced disease severity seen in patients colonized with Pseudomonas aeruginosa or multiple resistant pseudomonads. The relationship between disease severity assessed by forced expiratory volume in one second per cent predicted and the nonpulmonary function subscores was significant and linear (for the radiological subscore, r2=0.694, p<0.0001) and curvilinear (for the clinical and complications subscores, r2=0.622, p=0.0192 and r2=0.508, p=0.0009 respectively). In the second study, 20 patients retrospectively recorded were added to the prospective group. There was a good association between changes in nonpulmonary function subscores and changes in spirometry over a mean follow-up period of 779+/-204 days, at all levels of disease severity. The contribution of changes in clinical and complications subscores to the changes in total score became progressively more significant with more advanced disease severity. In conclusion, significant evidence for the construct validity of the scoring system as a discriminative instrument and for the longitudinal validity as an evaluative instrument was demonstrated. It may prove of value in assessing outcome of therapeutic interventions in clinical trials in patients with cystic fibrosis.

Adult↗
PubMed1999

Social Security, retirement incentives, and retirement behavior: an international perspective.

Escalating rates of early retirement are imposing fiscal pressure on retirement systems around the world. In some developed countries, the labor-force participation rates of men ages 60-64 have fallen by 75 percent over the last three decades. One explanation for this striking decline is social security program provisions which create disincentives to continued labor-force participation by older workers. There are substantial differences among developed nations in the labor-force participation of older workers. While two-thirds of 60-year-old American males are working, only one-quarter of men that age are working in Belgium. Over the entire 55-65 age range, 63 percent of American males are working, compared with only 40 percent of French males and 33 percent of Belgians males. There is strong evidence that the early retirement provisions of social security systems in developed countries determine the modal age of retirement. There is a strong relationship between early retirement ages and labor-force withdrawal rates; for example, in France, 60 percent of those working at the early entitlement age of 60 leave the labor force at that age. The core of this analysis is the construction of "implicit tax/subsidy rates" on additional work at older ages through each nation's social security system. These rates measure the change in a worker's retirement wealth entitlement from delaying retirement for one year, relative to the amount that would have been earned over that year. The U.S. Social Security system has an actuarial adjustment for delayed benefits claiming and other features that avoid financial incentives to leave the labor force at age 62 for a married worker, there is a slight disincentive to work for single workers and high wage earners. However, at ages 65 and older there is a stronger incentive to leave the labor force, with implicit tax rates on work of 19 percent for married workers and 33 percent for single workers. By comparison, other nations do not have actuarially fair adjustments, and as a result impose substantial taxes on additional work at older ages. In several countries, implicit tax rates on work at older ages approach or exceed 100 percent. This is because by delaying retirement, workers forgo benefits which often replace close to their full wage, in addition to having to pay the high payroll taxes required to finance generous social security benefits. There is a striking correlation across nations between high implicit tax rates on additional work and low labor-force participation rates among older workers. This suggests that social security program incentives are an important determinant of retirement. These findings have important policy implications for reforming social security programs in the United States and abroad. Policymakers must consider how program reforms will affect incentives for continued work at older ages.

Actuarial Analysis↗
PubMed1999

[Electromyography biofeedback therapy in fibromyalgia].

Nineteen patients with fibromyalgia underwent a course of treatment with EMG-biofeedback (EMG-BFB) technique. On completion of treatment, there was a statistically significant lowering of sensitivity to pain at pressure points typical for fibromyalgia (p = 0.017), which could be observed also 2 months after completion of treatment. In addition, there was a reduction both in the affective (p = 0.04) and in the sensory (p = 0.007) components of pain. Furthermore, there was a statistically significant improvement in the accompanying disease parameters of sleep disturbance (p = 0.004) and head ache (p = 0.031). Since EMG-BFB training might contribute not only to a reduction of pain and muscle tension but also to an improvement of quality of life, it can be recommended as part of a multimodal pain therapy in fibromyalgia patients.

Adult↗