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Biomedical subjects

E D Silverman

Publications and source records attributed to E D Silverman.

At least 127 records · Page 7Linked to original sources

Drug therapy for juvenile arthritis.

Juvenile arthritis includes a variety of rheumatic disorders with varied articular and extraarticular manifestations. The heterogeneity of JA cannot be overemphasized in a rational approach to therapy. Fortunately, most children with JA improve significantly with first-line treatment, especially those with pauciarticular disease. Only a small number of these patients go on to require second-line treatment, usually because of the evolution of their condition into the polyarticular type. Patients with polyarticular, RF-positive disease and patients with early-onset polyarthritis in association with systemic-onset disease both have poor prognoses in terms of ultimate joint function, and should receive second-line treatment early in their therapy. Injectable gold is the drug of choice for the former patients, if an initial trial of NSAIDs has failed. Patients with polyarticular onset, RF-negative disease generally have a better prognosis than other patients with polyarticular involvement. One may wait considerably longer before introducing a second-line agent for these patients. An antimalarial agent may be a reasonable choice for these patients, especially those with limited polyarticular involvement (5 to 10 active joints). This latter principle may also be applied to patients who evolve from pauciarticular to polyarticular involvement. In all such cases, penicillamine is almost never used as first choice. If the patient is a young child, the difficulty with injecting gold and the hazards of antimalarial agents may limit the use of these treatments. In situations such as this, auranofin or sulfasalazine may be the drug of choice. Cytotoxic/antimetabolic therapy should be reserved for those children who have continued active disease despite full courses of two SAARDs, or for those who have been unable to take SAARDs because of their side effects. Corticosteroid therapy should be used only when specifically indicated, and every attempt should be made to wean the patient from it as soon as feasible. The aim of therapy is to ensure that patients enter their remission in the best condition possible. For this to be assured, a sensible approach to drug therapy is mandatory.

Adolescent↗

Effect of 1,25-dihydroxyvitamin D3 in vivo on circulating T lymphocytes.

Previous in vitro and animal studies have suggested that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has important immunoregulatory properties. In this study, immune parameters were monitored in 16 patients the day before and 14 days after starting therapy with this hormone. Despite the absence of changes in the total white cell count, lymphocyte count and T lymphocyte count, CD4/CD8 ('helper/suppressor') ratio of T lymphocytes increased by 57% from the normal into the elevated range. Furthermore, a downward trend was seen in the percentage of stimulated lymphocytes expressing the interleukin-2 receptor. We conclude that in vivo administration of 1,25(OH)2D3 may have immunoregulatory effects in man. Whether these changes are the result of changes in intracellular or extracellular calcium concentration, parathyroid hormone concentration, or the concentration of 1,25(OH)2D3 itself remains to be answered.

Adult↗

Chronic recurrent multifocal osteomyelitis and psoriasis--a report of a new association and review of related disorders.

In summary, we have described two patients with CRMO and psoriasis, and have reviewed the musculoskeletal manifestations associated with pustular eruptions of the palms and soles. In view of the frequent occurrence of PPP in patients with CRMO, we suggest that the occurrence of psoriasis in our two patients is more than coincidence, and that noninfectious, inflammatory lesions of bone may be another musculoskeletal manifestation of psoriasis. This rare association, as well as the association of PPP with disorders associated with new bone formation, may shed new insights on the relatively common finding of periosteal elevation associated with psoriatic arthritis and the occasional severe juxta-articular osteolytic destructive bone lesions seen in psoriatic arthritis.

Acne Vulgaris↗

A six-month open safety assessment of a naproxen suspension formulation in the therapy of juvenile rheumatoid arthritis.

The safety of naproxen suspension was assessed in an open study in children with juvenile rheumatoid arthritis. Fifty-eight patients aged 1 to 13 (mean, 4.5 years) were studied. Based on the patient's condition, naproxen was prescribed at dosages ranging from 9 to 20 mg/kg/day. Follow-up assessments were made during regular clinic visits, as often as deemed necessary by the physician. Forty-four patients completed a minimum of six months' treatment. One patient was lost to follow up and 13 were withdrawn early: three because of unsatisfactory therapeutic response, one because of disease remission, five because of taste complaints, and four because of other side effects. The side effects were mostly gastrointestinal and were mild to moderate in severity. Investigators' subjective evaluations indicated that 84% of the patients who completed six months' treatment had good or excellent therapeutic responses at termination. The study results demonstrated that naproxen suspension is a well-tolerated anti-inflammatory agent for young children with juvenile rheumatoid arthritis.

Adolescent↗

Occurrence of Kawasaki disease and systemic lupus erythematosus in a single patient.

A 5-year-old girl who developed systemic lupus erythematosus 3 1/2 years after having had Kawasaki disease was found to be homozygous at both class I and class II MHC loci. This homozygosity suggests that she may also be homozygous for an MHC or non-MHC linked gene that could allow for the appearance of 2 diseases with similar immunoregulatory abnormalities, as occurs in the MRL/1pr/1pr mouse model. Although this is the first report of the occurrence of a second immunologic disorder in a patient with a history of Kawasaki disease, North American children who developed Kawasaki disease early in life are only now reaching the age when other inflammatory disorders become relatively common. Therefore, this group of children will have to be closely observed for the development of other inflammatory disorders.

Child↗

Insulin-like growth factors I and II in children with systemic onset juvenile arthritis.

Systemic onset juvenile arthritis (JA) has been associated with growth failure in children whether or not treated with adrenocorticosteroids. Growth hormone secretion has been reported to be normal, but production of insulin-like growth factors has not been studied. We measured serum concentrations of insulin-like growth factor I and II in a group of children with systemic JA at different times, and during treatment with only nonsteroidal antiinflammatory therapy or while receiving prednisone. Mean concentrations of insulin-like growth factor I and II were below normal for age whether or not prednisone was being given. Growth failure during periods of active disease was observed in both groups. Only 4 of 11 prepubertal children in whom growth rates were measured grew 4.5 cm or more/year. However, longitudinal studies of individual children showed that lowest growth rates occurred while taking prednisone and that growth rates were not correlated to insulin-like growth factor levels.

Arthritis, Juvenile↗

Scintigraphic evaluation of duodenogastric reflux. Problems, pitfalls, and technical review.

Bile reflux has been implicated in the pathogenesis of gastritis, gastric ulcer, and esophagitis. Radionuclide techniques provide the only non-invasive method to detect duodenogastric reflux. To analyze the problems that occur with attempts at quantitation, 55 patients were prospectively evaluated (45 patients with reflux esophagitis or Barrett's esophagus and ten patients with clinical symptoms of bile reflux, four of whom had Bilroth II surgery) with Tc-99m DISIDA, using a fasting technique with gallbladder stimulation by sincalide. Visual duodenogastric reflux occurred in 16 of 55 patients. Overlap of small bowel with the stomach is the major problem for accurate quantitation and occurred in 20 of 55 patients (36%). Overlap of left lobe of the liver occurred in 40 of 55 patients (73%), but its contribution to gastric activity was slight and could be easily subtracted. Reflux was intermittent in six of the 16 positive studies (38%), and continuous computer acquisition is needed to detect its maximum value. Primarily because of the problem of small bowel overlap, scintigraphic evaluation of duodenogastric reflux is only, at best, semi-quantitative. A review of the technical variables used in this examination, as well as potential problems that can occur, is provided.

Adult↗

Barrett esophagus: decreased esophageal clearance shown by radionuclide esophageal scintigraphy.

Radionuclide esophageal scintigraphy is a sensitive test of esophageal function, but its usefulness is not well documented in Barrett esophagus. This technique was prospectively studied in 27 patients with histologically proved Barrett esophagus and 17 patients with biopsy-confirmed reflux esophagitis. The esophageal transit time and percentage of emptying were calculated. The only quantitative parameter of radionuclide esophageal scintigraphy to show a significant difference between the two conditions was the percentage of emptying, which was abnormal in 48% of patients with Barrett esophagus versus 31% of patients with reflux esophagitis. In the latter group, the mean percentage of emptying approached normal (89.5%), while in the former group it was decreased to 82.1% (P less than .05). Neither emptying parameter correlated with length of Barrett esophagus. These data support the hypothesis of inherent esophageal dysmotility in Barrett esophagus. Half of the patients with this condition have impaired esophageal clearance and may benefit from drug therapy.

Adult↗

Spontaneous secretion of a proteoglycan releasing factor by mononuclear cells in juvenile arthritis.

Patients with juvenile arthritis (JA) spontaneously produced a substance which accelerated proteoglycan loss from cultured articular cartilage. Peripheral blood mononuclear cells (PBMC) from 15 patients with JA were cultured for varying days, and cell-free PBMC conditioned media were added to articular cartilage cultures. Release of proteoglycan and collagen from cartilage was quantified by analysis of chondroitin sulfate and hydroxyproline content, respectively, after 4 days of culture. Conditioned media from PBMC of patients with systemic onset JA (3/3) and 5/7 patients with polyarticular JA increased release of proteoglycan when added to cartilage cultures. Mitogen stimulation of the PBMC was unnecessary for activity and addition of mitogen did not alter proteoglycan release. The PBMC conditioned media from the other patients (2/7) with polyarticular JA, from patients (3/3) with systemic onset JA which had progressed to polyarticular JA, and from patients with pauciarticular JA, did not enhance proteoglycan release without mitogen stimulation. PBMC of normal children produced media which enhanced proteoglycan release after mitogen stimulation. No conditioned medium accelerated proteoglycan release if cartilage was freeze killed before culture and none tested reduced cartilage collagen content.

Arthritis↗

Scintigraphic detection of metoclopramide esophageal stimulation in progressive systemic sclerosis.

Supine radionuclide esophageal scintigraphy (RES) and manometry were used to prospectively evaluate metoclopramide effect on esophageal function and pressure amplitudes in 14 patients (12 females and two males; median time since diagnosis: 2 yr) with progressive systemic sclerosis (PSS). Quantitation of RES included calculation of percent emptying at 30 sec, and standard manometric measurements were obtained. RES and manometry were performed before and 10 min following the i.v. administration of metoclopramide. RES showed a significant increase in mean percent emptying from 36% to 46% after drug administration (p less than 0.01), while mean lower esophageal pressure (end-expiratory) increased from 2 to 11 mm of Hg (p less than 0.001). Manometry failed to reveal a significant increase in either distal or proximal mean esophageal contractile amplitude, and no correlation was found between the increase in percent emptying at RES and the change in lower esophageal pressure in the individual patient. RES is the only quantitative method presently available to evaluate bolus propagation in the esophagus, and it documented improved esophageal function after metoclopramide administration in a PSS population. When drug therapy is directed at augmentation of esophageal emptying, RES is an ideal method to evaluate drug response.

Adult↗

Naproxen-associated renal failure in a child with arthritis and inflammatory bowel disease.

Renal failure occurred in a 14-year-old girl with peripheral arthritis associated with inflammatory bowel disease while she was being treated with naproxen. She had previously received aspirin and tolmetin sodium and had no complications. A renal biopsy showed a severe tubulointerstitial nephritis. Although her renal function improved somewhat with corticosteroid treatment, it worsened when the steroids were discontinued. This case emphasizes that renal failure can develop insidiously in children on nonsteroidal anti-inflammatory drug therapy and that such children must be monitored closely for signs of nephrotoxicity.

Adolescent↗

Beta-adrenergic receptors on human suppressor, helper, and cytolytic lymphocytes.

Using the radioligand beta-adrenergic blocker [125I]cyanopindolol (ICYP), we have characterized the beta-adrenergic receptors on Leu 3+ (T helper [TH]), Leu 2+, 9.3- (T suppressor [Ts]) and Leu 2+, 9.3+ (T cytolytic [Tc]) subsets of human lymphocytes. Peripheral blood T cells were isolated by rosetting, and then subsets were purified by their affinities to monoclonal antibodies against their Leu 3 and 9.3 markers. ICYP binding to the subsets was saturable with time and with concentration; the binding was stereoselective and reversible by beta-adrenergic antagonists. A biological response produced by beta agonists increased intracellular concentrations of cAMP and corresponded to the number of binding sites. Each subset of cells had a number of binding sites, which was characteristic for the given subset. The data indicate that the density of distribution of beta-adrenergic receptors was not homogeneous on the precursors of phenotypically and functionally distinct T cells (Ts approximately 2900, Tc approximately 1800 and TH approximately 750 binding sites). The displacement studies using beta-adrenergic agonists were performed on the cytolytic and suppressor T cell subsets, suggesting that the receptors were mainly of the beta-2 type. The immunobiological significance of such selective distribution of numbers and subtypes of beta-adrenergic receptors on distinct T cell subsets is under investigation.

Epinephrine↗

Solid-phase gastric emptying in patients with Barrett's esophagus.

Delayed gastric emptying as a pathophysiologic factor in patients with gastroesophageal reflux (GER) is controversial. In order to further evaluate this question, we studied a population with severe reflux, specifically, patients with Barrett's esophagus. Solid-phase gastric emptying was measured in 17 patients and in 17 healthy volunteers using radionuclide imaging. Gastric emptying was variable among these patients with 70% normal, 18% rapid, and only 12% slow studies. From these observations, we conclude that delayed gastric emptying is unlikely to be a major factor in the pathogenesis of Barrett's esophagus.

Adult↗

Progressive systemic sclerosis: radionuclide esophageal scintigraphy and manometry.

Radionuclide esophageal scintigraphy (RES) and manometry were used for prospective evaluation of esophageal involvement and disease severity in 11 patients (nine women and two men; median time since diagnosis, 1 year) with progressive systemic sclerosis (PSS). Quantitation of RES included calculation of the percentage of emptying at 30 seconds, while manometry provided measurements of proximal, distal, and lower esophageal sphincter (LES) pressures. The findings of both RES and manometry were abnormal in all 11 patients. There was a high correlation between the percentage of emptying and either distal esophageal pressure (r = .86, P less than .01) or LES pressure (r = .79, P less than .01). No significant correlation was found between the percentage of emptying and proximal esophageal pressure (r = .28, P = .39). RES is a safe, simple procedure that is readily accepted by patients and can be used in place of manometry for the detection and staging of esophageal involvement in PSS.

Adult↗