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Biomedical subjects

R Greenwald

Publications and source records attributed to R Greenwald.

At least 19 recordsLinked to original sources
PubMed2001

Biologic properties of non-antibiotic, chemically modified tetracyclines (CMTs): a structured, annotated bibliography.

The first paper reporting on a potentially important medical property of a non-antimicrobial tetracycline appeared in 1987. Since then, a literature of over 75 papers has supported the therapeutic potential of this class of compounds. In this review, this literature is grouped and organized with commentary on the data which has been published to date. The biomedical applicability of these discoveries obviously covers a wide range of medical conditions and clearly justifies their continued development.

Animals↗
PubMed2001

Lack of effect of doxycycline on disease activity and joint damage in patients with rheumatoid arthritis. A double blind, placebo controlled trial.

OBJECTIVE: To investigate the effects of doxycycline on disease activity and joint destruction in patients with rheumatoid arthritis (RA). METHODS: A 36 week double blind, placebo controlled crossover trial was conducted. Patients (n = 66) received 50 mg doxycycline or placebo twice a day during 12, 24, or 36 weeks. Patient assessments were performed before the treatment was administered, at 6, 12, 24 and 36 weeks of treatment, and finally at 4 weeks after cessation of treatment. Patient assessments, swollen and tender joint counts, duration of morning stiffness, erythrocyte sedimentation rate, and Modified Disease Activity Score were used as measures of disease activity. Effects on joint destruction were assessed by urinary excretion of the pyridinolines hydroxylysylpyridinoline and lysylpyridinoline and by scoring radiographic damage of hands and feet before and after treatment. RESULTS: The changes of clinical or laboratory disease activity measures, pyridinoline excretion, or progression of radiographic joint damage during doxycycline or placebo treatment did not differ significantly. CONCLUSION: The results indicate that 50 mg doxycycline twice a day provided no therapeutic benefit for patients with RA.

Adolescent↗
PubMed2000

Toward a more ecologically valid measure of speech understanding in background noise.

In an attempt to develop a more ecologically valid measure of speech understanding in a background of competing speech, we constructed a quasidichotic procedure based on the monitoring of continuous speech from loudspeakers placed directly to the listener's right and left sides. The listener responded to the presence of incongruous or anomalous words imbedded within the context of two children's fairy tales. Attention was directed either to the right or to the left side in blocks of 25 utterances. Within each block, there were target (anomalous) and nontarget (nonanomalous) words. Responses to target words were analyzed separately for attend-right and attend-left conditions. Our purpose was twofold: (1) to evaluate the feasibility of such an approach for obtaining electrophysiologic performance measures in the sound field and (2) to gather normative interaural symmetry data for the new technique in young adults with normal hearing. Event-related potentials to target and nontarget words at 30 electrode sites were obtained in 20 right-handed young adults with normal hearing. Waveforms and associated topographic maps were characterized by a slight negativity in the region of 400 msec (N400) and robust positivity in the region of 900 msec (P900). Norms for interaural symmetry of the P900 event-related potential in young adults were derived.

Adult↗
PubMed1998

The potential role of doxycycline in the treatment of osteoarthritis of the temporomandibular joint.

Collagenase and gelatinase are matrix metalloproteinases (MMPs) which play an important role in tissue destruction in arthritic joints. Studies have demonstrated that tetracyclines can inhibit MMPs and prevent tissue destruction independent of their antimicrobial activity. The purpose of this pilot study is to assess the potential therapeutic role of Doxycycline in patients with advanced osteoarthritis of the temporomandibular joint (TMJ). This ongoing investigation includes patients with a diagnosis of osteoarthritis of the TMJ based on clinical and diagnostic imaging findings, symptoms (localized TMJ pain, limited mobility, dysfunction) for a minimum of 36 months, and failure of previous non-surgical and surgical modalities to alleviate the symptoms. A synovial fluid sample is collected by a saline injection and aspiration technique, followed by diagnostic arthroscopy. Patients are placed on Doxycycline 50 mg BID for three months and then undergo repeat diagnostic arthroscopy and synovial fluid collection. The samples are stored at -80 degrees C. Collagenase activity is determined by a combination of SDS-polyacrylamide gel electrophoresis and fluorography and calculated based on the percentage of collagen alpha chains that are degraded into alphaA breakdown products. Three patients have completed the three-month course of Doxycycline thus far, and 5 joints with osteoarthritis have been analyzed. All patients were female (mean age = 35, mean duration of symptoms = 132 months) and had undergone previous bilateral arthroscopies. One patient had undergone unilateral arthroplasty. The mean collagenase activity showed 55% collagen lysis prior to Doxycycline treatment and 19% after three months of therapy. The mean gelatinase activity was 28% prior to Doxycycline treatment and 7% after three months of therapy. The mean interincisal opening was 33 mm initially and 41 mm after three months of Doxycycline. Subjectively, two of the three patients reported significant improvement in their overall symptoms, which they had not experienced over the previous three years. One patient did not experience any change in symptoms, in spite of a marked reduction in collagenase activity from 86.4% to 9.6%. Because of the very small numbers of patients enrolled in this pilot study so far, no statistically significant differences could be appreciated. However, the dramatic reduction in collagenase activity in these patients, with a long history of TMJ symptoms from osteoarthritis, suggests the potential promising role of Doxycycline in the management of osteoarthritis, and further investigation is warranted.

Adult↗
PubMed1997

The function of costimulatory molecules and the development of IL-4-producing T cells.

The development of IL-4-producing effector T cells during a type 2 immune response requires signaling through B7 ligands, but probably not CD40 ligands. Here, William Gause and colleagues review the still controversial role of CD28 and CTLA-4 on T cells, and B7-1 and B7-2 on antigen-presenting cells, and provide a model to incorporate recent findings.

Abatacept↗
PubMed1996

Chemically modified tetracyclines inhibit inducible nitric oxide synthase expression and nitric oxide production in cultured rat mesangial cells.

Tetracyclines inhibit matrix metalloproteinases (MMP) and attenuate connective tissue degradation in a wide variety of human and animal disorders. Chemically modified tetracyclines (CMT) have been synthesized in which the antibacterial potency has been eliminated but in which the anti-MMP efficacy is retained. Nitric oxide (NO) modulates MMP synthesis and activity in mesangial cells in vitro. Therefore, we examined whether CMT inhibit iNOS gene and protein expression and NO production in cultured rat mesangial cells. Mesangial cells were maintained in media containing IFN-gamma and LPS for 24-72 h. Test media contained either no further additives or CMT-1, 3, 5, or 8 at concentrations of 1, 2.5, 5, and 10 micrograms/ml. iNOS gene and protein expression were assessed and NO production was determined by the Griess reaction. Incubation of mesangial cells with CMT-3 and CMT-8 resulted in time- and dose-dependent inhibition of NO production that was maximal at 48 h (< 20% of control) and at a drug concentration of 5 micrograms/ml (P < 0.05). Addition of CMT-1 had a modest (40%) inhibitory effect and CMT-5 did not alter NO production. The impact of CMT on NO production was directly related to their potency as collagenase inhibitors. Moreover, CMT-induced changes in NO synthesis were associated with parallel alterations in steady-state iNOS mRNA abundance and protein expression. These agents may be useful to ameliorate NO-dependent glomerular inflammation.

Animals↗
PubMed1993

Meprin activity in rats with experimental renal disease.

Activity of renal meprin, a membrane-bound proteinase in the proximal tubule brush border, was measured in normal rats and in two disease groups: chronic puromycin aminonucleoside nephropathy for 12 weeks and streptozocin-induced diabetes for 6 months. Enzyme activity in kidney homogenates was assayed using azocasein as substrate. The mean activity of mephrin was 3.22 +/- 0.34 U/g kidney weight in normal rats. In diabetic animals, enzyme activity was 8.58 +/- 2.11 U/g kidney weight, P < 0.01. In contrast, meprin activity was decreased in rats with puromycin-induced glomerulopathy, 2.13 +/- 0.17 U/g kidney weight, P < 0.01. These findings indicate that meprin activity is elevated in experimental diabetes. Diminished activity of this luminal membrane enzyme in puromycin aminonucleoside nephropathy may contribute to renal injury in this disease model associated with massive urinary protein excretion.

Animals↗
PubMed1991

Scleroderma-like fasciitis without eosinophilia after L-tryptophan ingestion.

A 53-year-old man developed severe sclerodermatous skin changes and a neuromyopathic process, consistent with the eosinophilia-myalgia syndrome, 2 months after discontinuation of L-Tryptophan (L-Try). His peripheral eosinophil count was within normal limits upon presentation and remained so throughout the illness. Currently the Centers for Disease Control surveillance definition requires peripheral eosinophilia greater than 1000 cells/mm3. Eosinophilia-myalgia syndrome may need to be part of a differential diagnosis even in the absence of peripheral eosinophilia.

Diagnosis, Differential↗
PubMed1987

Delayed postbacteremic prosthetic joint infection.

Deep infection of a prosthetic joint is a devastating complication. One proposed mechanism of late prosthetic joint infection involves hematogenous spread from an extraarticular focus of infection. Two cases clearly demonstrate hematogenously acquired prosthetic joint infections, one caused by Clostridium perfringens and the other by Streptococcus pneumoniae. These cases were unusual in that a long asymptomatic period intervened between the primary bacteremic illness and the subsequent prosthetic infection. Patients with prosthetic joints who develop bacteremic infection at extraarticular sites should be treated promptly and aggressively with appropriate antibiotics. Prophylactic antibiotics should be strongly considered in the patient with a prosthetic joint who undergoes procedures likely to be associated with a bacteremia. Transient arthralgias at the time of bacteremia may represent the onset of the joint infection and should not be overlooked or attributed a priori to the patient's underlying arthritic or medical condition.

Aged↗
PubMed1986

Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association.

For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.

Adult↗
PubMed1986

Rheumatoid iliopsoas bursitis presenting as unilateral leg edema.

A 66-year-old woman with rheumatoid arthritis presented with unilateral leg edema attributable to an enlarged iliopsoas bursa with presumed impedance of lymphatic drainage. The adjacent hip joint was not severely involved by arthritis. Ultrasonography and computed tomography were used to delineate the bursal mass and demonstrate communication with the joint space.

Aged↗
PubMed1980

Endoscopic therapy of the "sump" syndrome.

Choledochoduodenostomy may be followed by the "sump syndrome." This previously required surgical intervention. We describe the successful application of endoscopic therapy in two patients with this syndrome.

Cholangitis↗