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Biomedical subjects

R Silverman

Publications and source records attributed to R Silverman.

At least 55 records · Page 3Linked to original sources
PubMed1993

Magnetic resonance imaging in inflammatory bowel disease.

Magnetic resonance (MR) images were acquired in 28 consecutive inflammatory bowel disease (IBD) patients undergoing medical treatment. The protocol employed included i.v. gadopentatate dimeglumine, pre- and post-contrast breath-hold Fast Low Angle Shot (FLASH), and fat-suppressed spin echo imaging. The percent contrast enhancement (% CE) of the fat-suppressed images was compared with severity of inflammation based on endoscopic and/or surgical findings. The %CE of the contrast-enhanced images was 169% +/- 63 in cases of severe inflammation (n = 16), 97% +/- 38 in moderate inflammation (n = 8), and 49% +/- 26 in mild inflammation (n = 4). Significant correlations were found between the clinicopathologic findings and (a) % CE, r = 0.74 (p = 0.0001); (b) length of affected bowel segment, r = 0.49 (p = 0.007); and (c) bowel wall thickness, r = 0.42 (p = 0.02). In a subsequent comparison, %CE was correlated with length of affected bowel and bowel wall thickness. The best correlation was bowel wall thickness, r = 0.53 (p < 0.004). Good correlation was found between MR findings and pathology/histology findings in the determination of bowel wall thickness, length of diseased bowel, and severity of inflammation in 10 patients who underwent bowel resection. The results of this study show that MR images demonstrate the extent and severity of inflammatory changes in the GI tract, which correlate with endoscopic and histological findings.

Adult↗
PubMed1993

MRI in the diagnosis of Crohn's disease in two pregnant women.

Two pregnant women considered symptomatic for inflammatory bowel disease were referred for magnetic resonance imaging (MRI) for assistance in establishing a diagnosis. Breath-hold gradient echo and contrast-enhanced T1-weighted fat-suppressed spin echo sequences were used. The MR appearance of the terminal ileum was consistent with Crohn's disease in both patients. The diagnosis of Crohn's disease was subsequently confirmed histologically. MRI is a safe, noninvasive modality that may be useful in confirming a suspected diagnosis of inflammatory bowel disease, especially in patients who cannot be evaluated with standard techniques.

Adult↗
PubMed1993

Magnetic resonance imaging evaluation of the local extent of colorectal mass lesions.

Magnetic resonance imaging (MRI) was conducted in 21 patients with known or suspected colorectal mass lesions. Imaging was carried out at 1.5 T using Fast Low Angle Shot (FLASH) and fat-suppressed (T1FS) gadolinium enhanced sequences. The lesions studied included adenocarcinoma (n = 16), lipoma (n = 2), villous adenoma with foci of adenocarcinoma (n = 1), malignant melanoma (n = 1), and rectal lymphoma (n = 1). Correlation was made with surgical findings in 14 patients, 10 of whom had tumors resected. Bowel wall involvement, tumor size, and extension demonstrated on MR images was correlated with histopathology findings. No significant differences were found (p > 0.05) among those parameters when compared to MR information from T1FS images. Lymph nodes were demonstrated on MR images but distinction between benign and malignant nodes could not be made.

Adenocarcinoma↗
PubMed1993

A comparison of the immunosuppressive effects of cyclosporine A and cyclosporine G in vivo and in vitro.

In this study we compared the immunosuppressive effects of cyclosporine (Cs) A and G, both in vitro (human and rabbit) and in vivo (rabbit). The 50% inhibitory concentration (IC50) of CsG was up to three times greater than that of CsA for mitogen and alloantigen-induced lymphocyte proliferation (IC50 CsA 1 degree MLC = 19 +/- 4 micrograms/L vs. IC50 CsG = 60 +/- 7 micrograms/L; P < 0.01). Kinetic studies in both human and rabbit systems showed that the effectiveness of both drugs was similarly reduced when added at later times after culture initiation. The effects of CsA and CsG in combination on immune responses appeared to be antagonistic at higher and additive at lower drug doses. We also compared the ability of CsA and CsG to displace 3H-CsA from PBMC. The 50% displacement concentration (DC50) for CsG was up to three times greater than that for CsA (DC50 CsA = 1.44 +/- 2.49 x 10(-7) M vs. DC50 CsG = 3.9 +/- 5.4 x 10(-7) M; P < 0.05), suggesting that CsG does not bind as well to PBMC as CsA. In vivo studies using skin allografts confirmed in vitro findings. Both CsA and CsG at 5 and 10 mg/kg/day significantly (P < 0.01) prolonged graft survival compared with control animals. However, at these doses and even at 15 mg/kg/day CsG, CsA was more efficacious at prolonging skin graft survival in rabbits (P < 0.01), e.g., mean survival time (MST, days) 10 mg/kg/day CsA = > 20.5 vs. MST 15 mg/kg/day CsG = 15.0. These results suggest that both in vitro and in vivo in rabbits CsG is less immunosuppressive than CsA.

Animals↗
PubMed1993

Lessening the burden of diabetes. Intervention strategies.

OBJECTIVE: To evaluate the impact of primary and secondary interventions on the development of complications from diabetes, we modeled the effects of primary and secondary interventions for diabetes on a single well-studied complication, diabetic retinopathy. RESEARCH DESIGN AND METHODS: A model was developed to predict cumulative incidence of retinopathy in IDDM and NIDDM. Risk functions are based on duration of diabetes. The effects of intervention strategies were simulated by altering the retinopathy risk. The effects of the simulations were assessed using cumulative incidence. RESULTS: Simulations of delaying the onset of IDDM from 2 to 8 yr and decreasing the retinopathy rates by 20-80% were performed for each type of retinopathy. Simulating primary prevention shifted the cumulative incidence curves to the right, and simulating secondary intervention shifted the curves downward. Primary prevention was less effective than secondary prevention. This difference was more apparent for IDDM than for NIDDM, where disease duration and exposure to retinopathy risk were shorter. All interventions shifted the development of retinopathy to later in life. CONCLUSIONS: The greatest effect on cumulative incidence of all forms of retinopathy occurs when primary and secondary interventions are combined.

Adult↗
PubMed1992

Tractional elevations of the retina in patients with diabetes.

Tractional retinoschisis and tractional retinal detachment are both complications of proliferative diabetic retinopathy. The two conditions are frequently confused because they are similar in diagnostic features. We determined the respective incidence of tractional retinoschisis and tractional retinal detachment in 200 eyes with tractional elevations of the retina in patients with diabetes. In 39 eyes, the diagnosis was unequivocally tractional retinoschisis because the retinal elevation maintained its concave contour despite the development of retinal holes. In 65 eyes, tractional retinal detachment was diagnosed with equal certainty, either because pigment lines were present or because the elevation, after a retinal hole developed, rapidly became convex and extended to the ora serrata. The remaining 96 eyes, in which retinal holes or pigment lines were absent, were classified by other features that had been tested for significance in the already diagnosed eyes. On that basis, the diagnosis was retinoschisis in 46 eyes and retinal detachment in 50 eyes.

Diabetes Mellitus, Type 1↗
PubMed1989

Thrombogenicity of total parenteral nutrition solutions: I. Effect on induction of monocyte/macrophage procoagulant activity.

Although thrombosis is a frequent complication of total parenteral nutrition (TPN), its pathogenesis has received little scientific attention. We have studied, in vitro, the effects of the component solutions of TPN on the induction and modulation of human monocyte procoagulant activity, an initiator of coagulation. Human peripheral blood mononuclear cells were cultured with (a) 200 microliters of dextrose solution (10%, 15%, 20%, 25%, and 50%), (b) 200 microliters of amino acid solution (full, one-half, and one-quarter strength), and (c) 200 microliters of isosmolar 10% lipid emulsion (LE). Cocultures of LE and 20% dextrose, LE and full-strength amino acid solution, and LE and bacterial lipopolysaccharide were also studied. Cells cultured with lipopolysaccharide or medium alone constituted positive and negative controls, respectively. In addition, cocultures of LE and 20% dextrose, LE and full-strength amino acid solution, and LE and lipopolysaccharide were also studied. Cells were incubated for intervals of 12-72 h, washed, frozen, and assayed for monocyte procoagulant activity (MPCA). Milliunits of MPCA were derived from a standard thromboplastin curve. In addition, spontaneous MPCA levels were measured in healthy volunteers (n = 4) and "home" total parenteral nutrition patients (n = 4) before and after a 2-h infusion of 500 ml of LE. Our results show that, in vitro, hypertonic dextrose and full-strength amino acid solutions induce significant levels of MPCA. Induction of MPCA by dextrose was lymphocyte-independent. Although a significant increase in MPCA by full-strength amino acid solution was seen in cultures of isolated monocytes, a lymphocyte requirement was demonstrated for full MPCA. In contrast, LE significantly inhibited the induction of MPCA by 20% dextrose and full-strength amino acid solution. This inhibitory activity was at the monocyte level. Subfractionation of the LE into triglyceride and phospholipid phases showed the inhibitory capacity to reside in the former. In vivo, patients on home total parenteral nutrition expressed higher spontaneous MPCA levels than normal controls. Ten percent lipid emulsion infusion abolished MPCA expression in both groups. These corroborative in vitro and in vivo data suggest a mechanism for the thrombogenicity of total parenteral nutrition solutions and that the inhibitory properties of LE may be of practical advantage in preventing thrombosis.

Adult↗
PubMed1988

Factitious hypoglycemia due to surreptitious administration of insulin. Diagnosis, treatment, and long-term follow-up.

Ten patients had factitious hypoglycemia due to surreptitious insulin injections diagnosed and were followed for up to 15 years (median, 5 years; range, 2 months to 15 years). When available, demonstration of anti-insulin antibodies was the most helpful diagnostic test. Decreased plasma C-peptide levels corroborated the diagnosis. Young women (nine of ten) with knowledge of the medical profession or relatives with diabetes mellitus predominated in the sample. Five of the patients had a history of insulin-requiring diabetes mellitus. Two patients eventually committed suicide despite the best efforts at therapy. Only three of ten patients made a successful transition into productive life after the diagnosis of factitious hypoglycemia was established. Factitious hypoglycemia remains a difficult diagnosis to make, and the long-term outcome after the diagnosis is established is unpredictable. All efforts have to be made to confirm the diagnosis before the patients are approached. The confrontation is to be made by an experienced team of health care professionals who have gained the patient's confidence through an understanding but firm manner. Long-term therapy must be planned and initiated before the patient's discharge.

Adult↗
PubMed1987

Localization of a peptide sequence contained in the precursor to gonadotropin releasing hormone (GnRH).

The precursor protein that contains the sequence for the neurohormone gonadotropin releasing hormone (GnRH) also contains an additional fragment (amino acids 14-26, designated pHGnRH14-26) that can release luteinizing hormone (LH) and follicle stimulating hormone (FSH) in vitro. An immunocytochemical study was carried out to determine if this sequence could be found in its processed form in hypothalamic nerve terminals. In rats, ewes and rhesus monkeys pHGnRH14-26 was demonstrated in both neuronal cell bodies and in axon terminals. In mice, immunoreactivity was present in terminals only. No reaction was found in the hamster hypothalamus. Double label immunocytochemical studies for GnRH and pHGnRH14-26 showed that both sequences could be found in the rat septal-preoptic-hypothalamic continuum in some but not all neuronal cell bodies. Control experiments strongly suggest that the 14-26 immunoreactivity represents the fragment after it has been cleaved from the precursor protein and that this peptide could be available for release into the hypophysial portal system.

Amino Acid Sequence↗
PubMed1987

Impaired coronary vasodilator responsiveness as a cause of lactate production during pacing-induced ischemia in patients with angina pectoris and normal coronary arteries.

Subgroups of patients with angina pectoris and normal coronary arteries are known to have pacing-induced lactate production and, therefore, myocardial ischemia. To examine the mechanism of this pacing-induced ischemia, the effect of incremental atrial pacing on coronary blood flow and metabolism was studied in 27 patients with angina and normal coronary arteries. Seventeen patients continued to exhibit normal lactate extraction even at heart rates up to 160 beats/min (Group 1), whereas in 10 patients (Group 2) lactate extraction changed to production at the highest pacing rate. Coronary blood flow increased in Group 1 patients by 18, 41 and 75%, respectively, as heart rate was increased by 20 beat/min increments from 100 to 160 beats/min. In contrast, coronary blood flow increased by only 8, 7 and 14%, at the three respective pacing rates in Group 2. Between the heart rates of 100 and 160 beats/min, coronary vascular resistance decreased 32% in Group 1 patients but was unchanged in Group 2 patients. There was no significant change in the ratio of myocardial O2 consumption/rate-pressure product in Group 1 patients, but this ratio decreased from 0.91 +/- 0.26 ml O2 X min-1 X (mm Hg X beats/min)-1 to 0.53 +/- 0.11 (p less than 0.05) in Group 2 patients as heart rate increased from baseline to 160 beats/min. Thus, patients with angina and normal coronary arteries who develop ischemia with pacing have a decreased coronary vasodilator response that interferes with their ability to increase myocardial oxygen supply to match the higher demand.

Adult↗
PubMed1987

Immune responses in small intestinal transplantation in the rat: correlation of histopathology and monocyte procoagulant activity.

No predictive serologic marker exists for rejection or graft versus host disease (GVHD) reactions in small intestinal transplantation (SIT). SIT was performed in Lewis (Lew) and Lew X Brown Norway Fl hybrid (LBN) rats in the following combinations: group 1, Lew X Lew; group 2 (isolated rejection), LBN X Lew, and group 3 (isolated GVHD), Lew X LBN. Procoagulant activity (PCA), an index of monocyte immune activation, was measured in the peripheral blood mononuclear cells of graft recipients to assess its value as an immunologic monitor. Histologic findings and PCA were evaluated on days 1, 2, and 3 and every 2 to 3 days after SIT. No pathologic findings of graft or host tissue developed in group 1 (n = 14). Histologic rejection (blunted villi and mononuclear cell infiltration) was seen beginning on day 5 in group 2 (n = 19); early GVHD (loss of nodal and splenic architecture) was first noted on days 5 and 6 in group 3 (n = 17). PCA elevation in SIT was seen to precede histologic evidence of rejection or graft versus host disease in this model and may constitute an important marker for these immunologic events.

Animals↗
PubMed1984

Down-regulation and recycling of insulin receptors. Effect of monensin on IM-9 lymphocytes and U-937 monocyte-like cells.

Receptor down-regulation is the result of various cellular processes including receptor internalization, new synthesis, and recycling. Monensin, a monocarboxylic acid ionophore, has been used to characterize the role of recycling in the metabolism of insulin receptors on two cultured human cell lines, U-937 and IM-9, which have different rates of internalization. The U-937 monocyte-like cell internalizes insulin receptors readily. Incubation with monensin at low doses (10(-6) to 10(-7) M) for 2 h did not affect subsequent surface insulin binding. However, the drug markedly enhanced insulin-induced down-regulation. Monensin had little effect on ligand internalization in this cell line as demonstrated by quantitative morphometric analysis. The IM-9 lymphocyte, a slow internalizer, was less sensitive to monensin exposure. Prolonged exposure (12 h) to this compound of either cell line resulted in apparent inhibition of insertion into the surface membrane of both newly synthesized and recycled receptors. When solubilization was used to quantitate total cell receptors, there was essentially no difference in intact cell binding (i.e. surface receptors) and total cell binding in IM-9 cells when insulin-induced down regulation alone was compared to insulin and monensin. By contrast for the U-937 cells there was only a small further decrease in binding when monensin was added to insulin in the solubilized cells compared to the marked augmentation of down-regulation when monensin was added to insulin in intact cells. These data demonstrate that cells with a rapid internalization rate have an associated active recycling process. By contrast cells with a slow internalization rate have a similarly slow recycling rate. This is consistent with relatively equal rates of receptor biosynthesis and plasma membrane insertion in both cell types.

Cell Line↗