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Biomedical subjects

S L Silverman

Publications and source records attributed to S L Silverman.

34 records · Page 2Linked to original sources

Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome). A Department of Veterans Affairs Cooperative Study.

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.

Adult↗

Identification of conserved amino acids in the human granulocyte-macrophage colony-stimulating factor receptor alpha subunit critical for function. Evidence for formation of a heterodimeric receptor complex prior to ligand binding.

A superfamily of growth factor and cytokine receptors has recently been identified, which is characterized by four spatially conserved cysteine residues, a tryptophan-serine motif (WSXWS) in the extracellular domain, and a proline-rich cytoplasmic domain. The high affinity human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (hGM-CSFR) consists of two subunits, alpha (hGM-CSFR alpha) and beta (hGM-CSFR beta), both of which are members of the receptor superfamily. In this study, we prepared mutations in conserved amino acids of the receptor subunit necessary for GM-CSF binding (hGM-CSFR alpha) and analyzed mutant receptors for low affinity binding, internalization, and high affinity binding when complexed with the beta subunit. Mutations in the cytoplasmic domain did not affect GM-CSF binding or receptor internalization. Mutation of a single conserved serine residue within the WSXWS motif diminishes cell surface receptor expression but not ligand binding. Mutation of either the second or third conserved cysteine residue of hGM-CSFR alpha resulted in complete loss of low affinity binding; however, co-expression of the cysteine 2 mutant with hGM-CSFR beta yielded a high affinity receptor complex. Since neither the cysteine 2 mutant nor the beta subunit can bind ligand alone, this result suggests that hGM-CSFR alpha and hGM-CSFR beta exist in a preformed heterodimeric protein complex on the plasma membrane.

Amino Acid Sequence↗

Rachitic syndrome after disodium etidronate therapy in an adolescent.

A 12-year-old patient with a severe traumatic brain injury developed heterotopic ossification (HO) with rapidly decreasing range of motion in multiple joints despite intensive passive range of motion exercises and the use of nonsteroidal antiinflammatory drugs (NSAIDs). His alkaline phosphatase was markedly elevated. Etidronate, 20mg/kg/d was used to control the ossification. After 7 months of continual etidronate use, the patient developed periarticular pain with widened growth plates, suggesting a rachitic syndrome. Serum laboratory panel including calcium, phosphorous, alkaline phosphatase, and vitamin D were normal. After 3 months off etidronate, radiological studies showed growth plate calcification, though not before development of bilateral slipped femoral capital epiphyses. Further improvement and resolution of all complications occurred 5 months after discontinuation of etidronate. Rachitic syndromes secondary to didronel use in a clinical setting has not been previously reported. Other possible causes for a rachitic syndromes were not present. Alternate treatments for children with or at risk for HO should be considered.

Brain Injuries↗

The clinical consequences of vertebral compression fracture.

Vertebral compression fractures (VCFs) may be defined radiographically or as a clinical event. The prevalence of these fractures in women aged 50 and over has been estimated at 26% when defined as a reduction in vertebral height greater than 15%. Retrospective reviews of case records have shown a clinical detection rate of VCF in white women of 153/100,000 person years. Of these clinically detected VCFs, 84% were associated with pain. VCF may be defined as a clinical event characterised by loss of height and acute pain. The pain of acute fracture usually lasts 4 to 6 weeks with intense pain at the site of fracture. Chronic pain may also occur in patients with multiple compression fractures, height loss and low bone density but is probably due to structural changes or osteoarthritis. Radiographic VCF may not be symptomatic. The greater the deformity, the greater the likelihood of pain and disability. As height is lost, patients experience discomfort from the rib cage pressing downward on the pelvis. Patients develop a thoracic kyphosis, a lumbar lordosis, and a protuberant abdomen with prominent horizontal skinfold creases. The reduced thoracic space may result in decreased exercise tolerance and reduced abdominal space may give rise to early satiety and weight loss. Sleep disorders may also occur. Patients lose self esteem. Self care may become difficult. They are often depressed. They become fearful of further fracture. They have distorted body image and poor health perception. Patients with one vertebral fracture are at increased risk of peripheral fracture and further vertebral fracture. The aims of acute management are to reduce symptoms and mobilise the patient as quickly as possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

Glucocorticoid-induced osteoporosis: a cross-sectional study.

We studied 70 patients (48 women and 22 men) with either rheumatic disease (n = 25) or lung disease (n = 45) who had been treated with glucocorticoids for at least 6 months (mean cumulative dose, 24.2 +/- 27.1 g of prednisone; mean current dose, 11.0 +/- 8.6 mg/d, mean duration of therapy, 8.1 years. We measured bone mineral density (BMD) of the hip (femoral neck) and spine (L2-L4) using dual-photon absorptiometry and BMD of the distal one third radius using single-photon absorptiometry. Compared with age-matched controls, the study population had decreased BMD of the spine (87.0%), hip (87.2%), and radius (90.6%). Current dose, cumulative dose, and duration of therapy were not correlated with BMD in the spine or hip in the total study population. The most significant correlations with low bone mass at the hip and spine were short height and low weight. There was a high incidence of hypercalciuria (30%) as compared with an age- and sex-matched control group (6.4%). Glucocorticoids are known to decrease vertebral and radial bone density. We conclude that glucocorticoids also decrease hip bone density as measured at the femoral neck. The high incidence of hypercalciuria may have implications for therapy of glucocorticoid-induced osteoporosis.

Absorptiometry, Photon↗

The importance of aspects of treatment for fibromyalgia (fibrositis). Differences between patient and physician views.

Thirty-five individuals with fibromyalgia (fibrositis), 22 of their physicians, and 49 rheumatologists on an Arthritis Foundation referral list rated the importance of 24 aspects of fibromyalgia treatment. These encompassed symptom control, psychosocial factors, information, and physical therapy. Respondents with fibromyalgia rated their satisfaction with the way each aspect of treatment had been managed by their physician, and each completed a health status questionnaire. Fibromyalgia patients viewed 8 of the 24 aspects of treatment as significantly more important than did their own physician, and 18 of the 24 as significantly more important than did area rheumatologists. Satisfaction with the way treatment had been managed was generally low. Some evidence suggested that patients' health status was affected positively by the extent to which their physician viewed certain aspects of treatment as important. The results are expected to be useful in the design of fibromyalgia education programs for both lay and health professional audiences.

Adult↗

Decreased incidence of hip fracture in Hispanics, Asians, and blacks: California Hospital Discharge Data.

We examined the incidence of hip fracture in Non-Hispanic White, Hispanic, Black, and Asian Americans for the years 1983 and 1984 using a data base which contains a summary of all hospitalizations for the State of California. We found a consistently lower risk for hip fracture after age 60 in Hispanic, Black, and Asian American females than in White females who were not Hispanic. Overall age-adjusted hip fracture rates in Hispanic, Black, and Asian females were 49.7, 57.3, and 85.4, respectively, and 140.7/100,000 in White females who were not Hispanic. These differences were not found in males, although Whites (not Hispanic) had the highest incidence of hip fractures among males.

Black or African American↗

Thrombocytopenia and intravenous heroin use.

Five young male heroin users presented with a syndrome resembling acute immune thrombocytopenic purpura. Although a viral, autoimmune, or toxic origin cannot be conclusively excluded at present, data are most consistent with the hypothesis that the thrombocytopenia was due to a drug-related immunologic mechanism that resulted in peripheral platelet destruction. Epidemiologic considerations suggest the common agent involved in their illnesses was present in the heroin they used. Although glucocorticoid therapy was followed by clinical recovery in four of the five patients (one was lost to follow-up), it is not certain that this represented a causal relation.

Adult↗

A musculoskeletal syndrome in intravenous heroin users: association with brown heroin.

During a recent 5-month period, 16 intravenous heroin users were hospitalized with a previously unrecognized complication of drug abuse. The characteristic symptoms were similar in all patients and included fever, paraspinal myalgias, and periarthritis. There was no evidence of bacterial infection, hepatitis, or drug abstinence as the cause of these musculoskeletal symptoms. Continued heroin use was associated with progressive musculoskeletal symptoms, while discontinuation of heroin use resulted in complete recovery. Antibiotics did not affect the outcome, and the syndrome was self-limited in all hospitalized patients. The pathogenesis of this syndrome is unknown but may be related to the heroin, which was described as brown by the patients, or an adulterant.

Adult↗

Mitogen induced cellular cytotoxicity (MICC) in multiple myeloma.

Mitogen induced cellular cytotoxicity (MICC) was noted to be markedly increased in patients with multiple myeloma as compared to normal controls and to patients with chronic lymphocytic leukemia (CLL). Enhanced MICC was present at various effector-to-target cell ratios and at several mitogen concentrations. Removal of adherent, phagocytic cells by carbonyl iron, glass wool, or rayon columns abolished the MICC response from the peripheral blood of both multiple myeloma patients and normal controls. Thus, the effector cell mediating MICC may be monocytic in origin and closely resembles the suppressor cell for immunoglobulin synthesis described in patients with multiple myeloma. Our data suggest that the MICC assay with chicken red blood cells as targets may provide a convenient method for identifying pathologic conditions where this cytotoxic effector cell population plays an active role.

Adult↗