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Biomedical subjects

G Steiner

Publications and source records attributed to G Steiner.

At least 145 records · Page 8Linked to original sources
PubMed1995

Tricalcium phosphate and osteogenin: a bioactive onlay bone graft substitute.

The disadvantages of autogenous bone grafts has prompted a search for a dependable onlay bone graft substitute. A combination of tricalcium phosphate, a resorbable ceramic, and osteogenin, an osteoinductive protein, was evaluated as an onlay bone graft substitute in a rabbit calvarial model. Twenty-eight tricalcium phosphate implants (15 mm diameter x 5 mm; pore size, 100-200 microns) were divided into experimental and control groups and placed on the frontal bone of 14 adult New Zealand White rabbits. In the experimental animals, 185 micrograms of osteogenin was added to each implant. In the control animals, the implants were placed untreated. Implants were harvested at intervals of 1, 3, and 6 months, and evaluated using hematoxylin and eosin histology, microradiography, and histomorphometric scanning electron microscope backscatter image analysis. At 1 month there was minimal bone ingrowth and little tricalcium phosphate resorption in both the osteogenin-treated and control implants. At 3 months, both the osteogenin-treated and control implants showed a modest increase in bone ingrowth (8.85 percent versus 5.87 percent) and decrease in tricalcium phosphate (32.86 percent versus 37.08 percent). At 6 months, however, the osteogenin-treated implants showed a statistically significant increase in bone ingrowth (22.33 percent versus 6.96 percent; p = 0.000) and decrease in tricalcium phosphate (27.25 percent versus 37.80 percent; p = 0.004) compared with the control implants. The bone within the control implants was mostly woven at 6 months, whereas the osteogenin-treated implants contained predominantly mature lamellar bone with well-differentiated marrow. All implants maintained their original volume at each time interval studied. The tricalcium phosphate/osteogenin composite, having the advantage of maintaining its volume and being replaced by new bone as the tricalcium phosphate resorbs, may be applicable clinically as an onlay bone graft substitute.

Animals↗
PubMed1995

Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans.

Changes in VLDL triglyceride and VLDL apo B production were determined semiquantitatively in healthy young men by examining the effect of altering plasma insulin and/or FFA levels on the change in the slopes of the specific activity of VLDL [3H]triglyceride glycerol or the 131I-VLDL apo B versus time curves. In one study (n = 8) insulin was infused for 5 h using the euglycemic hyperinsulinemic clamp technique. Plasma FFA levels declined by approximately 80% (0.52 +/- 0.01 to 0.11 +/- 0.02 mmol/liter), VLDL triglyceride production decreased by 66.7 +/- 4.2% (P = 0.0001) and VLDL apo B production decreased by 51.7 +/- 10.6% (P = 0.003). In a second study (n = 8) heparin and Intralipid (Baxter Corp., Toronto, Canada) were infused with insulin to prevent the insulin-mediated fall in plasma FFA levels. Plasma FFA increased approximately twofold (0.43 +/- 0.05 to 0.82 + 0.13 mmol/liter), VLDL triglyceride production decreased to a lesser extent than with insulin alone (P = 0.006) (-31.8 +/- 9.5%, decrease from baseline P = 0.03) and VLDL apo B production did not decrease significantly (-6.3 +/- 13.6%, P = NS). In a third study (n = 8) when heparin and Intralipid were infused without insulin, FFA levels rose approximately twofold (0.53 +/- 0.04 to 0.85 +/- 0.1 mmol/liter), VLDL triglyceride production increased by 180.1 +/- 45.7% (P = 0.008) and VLDL apo B production increased by 94.2 +/- 28.7% (P = 0.05). We confirm our previous observation that acute hyperinsulinemia suppresses VLDL triglyceride and VLDL apo B production in healthy humans. In addition, we have demonstrated that elevation of plasma FFA levels acutely stimulates VLDL production in vivo in healthy young males. Elevating plasma FFA during hyperinsulinemia attenuates but does not completely abolish the suppressive effect of insulin on VLDL production, at least with respect to VLDL triglycerides. Therefore, in normal individuals the acute inhibition of VLDL production by insulin in vivo is only partly due to the suppression of plasma FFA, and may also be due to an FFA-independent process.

Adult↗
PubMed1995

High expression of a CD38-like molecule in normal prostatic epithelium and its differential loss in benign and malignant disease.

PURPOSE: We characterize an undescribed antigen on prostatic epithelial cells, which is recognized by anti-CD38. MATERIALS AND METHODS: Normal (3 cases), benign hyperplastic (10) and carcinomatous (10) prostatic tissues were analyzed using immunohistochemistry, immuno-electron microscopy and the Western blot test. RESULTS: Comparison of prostatic and lymphatic CD38 antigen revealed identical bands at 45 kD. Electron microscopy demonstrated anti-CD38 reactivity on the cytoplasmic membrane and within the secretory vacuoles. Double labeling with anti-cytokeratin types 5/15 and 8/18 confirmed that basal and secretory normal prostatic epithelial cells express CD38. By contrast, a complete loss was found in malignant (52.8%), tumor-surrounding nonmalignant (16.3%) and benign prostatic hyperplasia derived glands (3.7%). CONCLUSIONS: CD38 is a novel prostatic antigen. Its role in intracellular calcium mobilization may contribute to smooth muscle cell contraction and/or sperm motility.

ADP-ribosyl Cyclase↗
PubMed1995

Origin of triacylglycerol moiety of plasma very low density lipoproteins in the rat: structural studies.

We have compared the molecular species composition of the glycerolipids of rat liver and rat plasma very low density lipoproteins (VLDL). There were differences in the stereospecific distribution of the fatty acids in the triacylglycerols (TG) of the liver and of VLDL. While chiral and reversed phase chromatography with mass spectrometry (LC/MS) revealed great similarities in positional distribution and molecular association of the fatty acids between the sn-1,2-diacylglycerol (DG) moieties of the VLDL and liver TG, the corresponding sn-2,3-DG were distinctly different. The free hepatic sn-1,2-DG and the sn-1,2-DG moiety contained within hepatic phosphatidic acid showed a maximum 60% homology to the sn-1,2-DG contained within the TG of the liver and of VLDL. By contrast, the smaller pool of hepatic free sn-2,3-DG was nearly identical to the sn-2,3-DG moiety contained in the TG of the liver. These differences between hepatic and VLDL TG indicate that direct transfer of hepatic triacylglycerols is not a major mechanism of VLDL TG formation. On the other hand, the results suggest that stored hepatic TG are largely hydrolyzed to sn-1,2-DG and then reesterified to TG before being secreted as VLDL TG. Although an involvement of 2-monoacylglycerol pathway could not be excluded, it probably plays a minor role in VLDL TG formation. Our data suggest that a minimum of 60% of the VLDL TG could have been derived via hydrolysis to DG and reesterification, and a maximum of 40% could have originated via the conventional phosphatidic acid pathway.

Animals↗
PubMed1995

Soluble receptors for tumor necrosis factor and interleukin-2 in serum and synovial fluid of patients with rheumatoid arthritis, reactive arthritis and osteoarthritis.

OBJECTIVE: To compare levels of soluble tumor necrosis factor receptor (TNF-R) and soluble interleukin 2 receptor (sIL-2R) in sera and synovial fluids (SF) of patients with rheumatoid arthritis (RA), reactive arthritis (ReA), and osteoarthritis (OA) in order to investigate the usefulness of soluble cytokine receptors for differentiation diagnosis and their involvement in the pathophysiology of rheumatic diseases. METHODS: Soluble TNF-R (55 kDa), sIL-2R, and TNF-alpha were measured by ELISA in sera and SF of patients with RA, ReA, and OA and correlated with serological and clinical disease activity variables. RESULTS: Serum TNF-R was significantly (p < 0.0001) elevated in RA (4.6 +/- 2.1 ng/ml, mean +/- SD) compared to ReA (2.5 +/- 0.6 ng/ml), OA (2.2 +/- 0.7 ng/ml), and healthy controls (2.0 +/- 0.4 ng/ml). In SF mean TNF-R levels were 21 +/- 9.3 ng/ml in RA, 12.5 +/- 5.1 ng/ml in ReA, and 8.7 +/- 3.7 ng/ml in OA (p < 0.0001 for RA vs ReA or OA; p < 0.02 for ReA vs OA). SF levels were significantly higher in rheumatoid factor (RF) positive than in RF negative patients with RA. In patients with RA, correlations were found between TNF-R and TNF-alpha in SF (r = 0.32, p < 0.01), and between TNF-R and early morning stiffness (r = 0.4, p < 0.003 in serum; r = 0.29, p < 0.05 in SF). However, there was no correlation with disease activity variables such as Ritchie index, erythrocyte sedimentation rate (ESR) or C-reactive protein. Serum levels of IL-2R were elevated in RA and ReA, but a significant difference was found only for RA versus OA and controls (p < 0.0005), whereas in SF significant differences existed between all 3 patient groups (RA/ReA: p < 0.004; RA/OA: p < 0.0001; ReA/OA: p < 0.0003); both in serum and SF, levels of RF positive patients with RA were higher than those of RF negative patients. In patients with RA, IL-2R correlated weakly with ESR (r = 0.24, p < 0.05), iron concentration (r = -0.35, p < 0.005), and CRP (r = 0.24, p < 0.05). CONCLUSION: In RA, in contrast to ReA and OA, TNF-R and IL-2R were not only elevated in the joint fluid but also in serum. This indicates general activation of the immune system in RA, but not in ReA and OA. Therefore the soluble receptors, especially TNF-R, might become useful diagnostic variables to distinguish RA from ReA and OA.

Adult↗
PubMed1995

Dyslipoproteinemias in diabetes.

The risk of macrovascular disease in those with diabetes is several-fold greater than that in the general population. One of the many groups of factors that might contribute to this is the dyslipoproteinemias. Among the dyslipoproteinemias in diabetes, the most frequently observed abnormality is hypertriglyceridemia. Levels of low-density lipoprotein (LDL) and of plasma cholesterol in those with diabetes are similar to those observed in people without diabetes. However, in diabetes there may be qualitative modifications in LDL (as well as in other lipoproteins) that increase their atherogenicity. At present there is one study, the Diabetes Atherosclerosis Intervention Study (DAIS), specifically designed to examine whether correcting the dyslipoproteinemia of diabetes will reduce the angiographic progression of coronary artery disease. Until results are available from studies that are designed to investigate the lipid hypothesis in those with diabetes, recommendations for the treatment of dyslipoproteinemias in diabetes will be based on pathophysiologic reasoning and on extrapolation from interventions studies conducted in nondiabetic individuals.

Arteriosclerosis↗
PubMed1994

Flow cytometric assessment of human MIC2 expression in bone marrow, thymus, and peripheral blood.

The cell-surface expression of the MIC2 antigen defined by the monoclonal antibody 12E7 was investigated on human leukocytes in bone marrow (BM), thymus, and peripheral blood (PB) using multiparameter flow cytometry and cell sorting. In contrast to preceding reports, we found that the MIC2 antigen is not restricted to T cells and monocytes. We show that it is also expressed in the B cell and in the granulocytic lineage, the levels of expression being related to distinct maturational stages. CD34+ cells of BM were found to express the antigen at high levels. Along the granulocytic maturation pathway from CD34+CD33+ blasts to mature granulocytes, MIC2 densities appeared progressively reduced with a considerable decline at the myelocyte stage. In B lymphopoiesis, the earliest CD34+ CD10+ B-cell precursor (BCP) cells, further subdivided by expression of CD19, displayed the highest MIC2 density of BM leukocytes. All later BCP stages showed lower MIC2 expression levels, with a remarkable reduction concomitant with loss of the CD34 antigen at the CD10+CD20- surface mu-chain- stage, and a subsequent slight upregulation along with maturation to CD10-CD20high surface mu-chain+ BCPs. The brightest MIC2 expression of all cells tested was displayed by the most immature thymic T-lineage cells characterized by the antigenic profile CD34weakor- CD7++ surface CD3-CD1a(weak) CD4weak CD8-or weak. Common thymocytes stained slightly less intense with 12E7, whereas all subsequent stages of T-lineage cells in thymus, PB, or BM showed markedly reduced MIC2 levels. Mature peripheral CD4+ as well as CD8+ T cells displayed a bimodal distribution of MIC2. In the CD4+ population, the distinct MIC2 levels were related to the well-studied functional subdivision by differential expression of CD45 isoforms, the helper-inducer/memory subset showing higher MIC2 expression than helper-suppressor/naive CD4+ T cells. Similarly high MIC2 densities were found on CD16+ natural killer cells and on CD14+ monocytes, whereas mature peripheral B cells exhibited low or intermediate expression, and granulocytes exhibited no or only dim expression. These results document that the MIC2 antigen (1) is expressed on all leukocyte lineages; (2) is differentially expressed during T- and B-lymphoid, as well as granulocytic maturation; (3) shows highest expression in the most immature lymphocytic and granulocytic developmental stages; and (4) is also differentially expressed on functional T-cell subsets. We speculate that these observations imply a functional significance of MIC2 in the network of hematopoietic adhesion pathways.

12E7 Antigen↗
PubMed1994

The dyslipoproteinemias of diabetes.

Atherosclerosis is the most frequent complication of diabetes. There are many potentially atherogenic factors in diabetes that may underlie this problem. Of these, one is the group of dyslipoproteinemias. In diabetes there are both qualitative and quantitative changes in the plasma lipoproteins. Based on pathophysiological and epidemiological data, these may be among the many factors that can result in early macrovascular disease. Furthermore, at least one of the dyslipoproteinemias--hypertriglyceridemia--is associated with insulin resistance and therefore could aggravate glucose intolerance. Thus, on theoretical grounds it is reasonable to postulate that treating the dyslipoproteinemias of diabetes would reduce atherosclerotic disease. However, to date there have been no intervention studies specifically designed to test this postulate in the diabetic population. One such study, the Diabetes Atherosclerosis Intervention Study, is currently in progress.

Aged↗
PubMed1994

Postprandial lipoproteins and progression of coronary atherosclerosis.

The relations between triglyceride-rich lipoproteins, alimentary lipaemia and coronary heart disease (CHD) have remained obscure and much debated. We studied the basal and postprandial plasma levels of chylomicron remnants and very low density lipoproteins (VLDL) of varying particle size in 32 male postinfarction patients (mean (S.D.) age 48.8 (3.2) years) and in 10 age-matched control men. The selective quantification of postprandial intestinal and hepatic lipoproteins was accomplished by determining apolipoproteins B-48 and B-100 in lipoprotein subfractions of Svedberg flotation (Sf) rates > 12 before and 3, 6 and 12 h after an oral fat load. Since all patients had undergone two coronary angiographies with an intervening time interval of around 5 years, lipoprotein fractions were examined in relation to the global severity as well as the rate of progression of coronary lesions. The postprandial plasma levels of small chylomicron remnants (Sf 20-60 apolipoprotein B-48) were found to relate distinctly to the rate of progression of coronary lesions between the angiographies (r = 0.51, P = 0.01). Adjustment for the possible confounding effect of the HDL cholesterol and dense LDL apolipoprotein B concentrations did not substantially alter the strength of this association. Neither the increment of plasma triglyceride during the postprandial period nor the concentrations of other lipoprotein fractions closely reflected the amount of small chylomicron remnants in the circulation or correlated with progression of coronary lesions. Our data suggest that small chylomicron remnants are implicated in the progression of coronary artery disease.

Apolipoprotein B-100↗
PubMed1994

Comparison of the effect of hyperinsulinemia on acyl-CoA:cholesterol acyltransferase activity in the liver and intestine of the rat.

UNLABELLED: Recent studies have suggested that cholesteryl ester synthesis plays a critical role in the assembly of VLDL apo B and triacylglycerol in the liver. Chronic hyperinsulinemia is associated with increased TG production and since cholesteryl ester synthesis depends on acyl CoA:cholesterol acyltransferase (ACAT), we investigated the possibility that chronic hyperinsulinemia might increase ACAT activity. We also measured ACAT activity in the intestinal mucosa, where it has been suggested to play a role in induction of diabetes-associated hypercholesterolemia. Chronically hyperinsulinemic rats were produced by injecting insulin (2 weeks, 6U/day). To prevent profound hypoglycemia, these rats were given 10% sucrose in place of drinking water. Acute hyperinsulinemia was produced by injecting a single dose of 0.5 U insulin ip. Chronic hyperinsulinemia led to a significant increase in free cholesterol, cholesteryl esters, triacylglycerols and phospholipids in the whole liver (27%, P < 0.05; 60%, P < 0.05; 70%, P < 0.01; 37%, P < 0.01, respectively) and an increase in hepatic microsomal triacylglycerol (P < 0.05). In contrast, the microsomal lipids of the intestinal mucosa decreased significantly. In chronically hyperinsulinemic rats there was no change in hepatic ACAT, while ACAT in the intestine actually decreased (26%-50%, P < 0.01). CONCLUSIONS: since the effect of chronic hyperinsulinemia on hepatic ACAT did not parallel that seen previously on VLDL secretion, the effect of chronic hyperinsulinemia on VLDL production cannot be explained by its effect on hepatic ACAT. However, chronic hyperinsulinemia was associated with reduced ACAT activity in the intestine and this might result in decreased lipoprotein production in the hyperinsulinemic intestine.

Animals↗
PubMed1994

Phenotype and function of peripheral and prostatic lymphocytes in patients with benign prostatic hyperplasia.

In a previous report, we demonstrated intense lymphocytic infiltration of all benign prostatic hypertrophy (BPH) tissues analyzed in conjunction with HLA-DR expression on normally MHC-class-II-negative prostate epithelial cells. The composition of these infiltrates (70 to 80% CD3+ T-cells, but no granulocytes) resembles the situation seen in immune responses against altered self or self rather than against foreign antigens (infection). In the present study, phenotypic and functional immunoassays were used in order to investigate whether T-cells in BPH are indeed activated, and whether this activation is systemic or restricted locally to the prostate. Analysis of T-cell activation marker expression and proliferation requirements provided substantial evidence that these infiltrating lymphocytes, in contrast to their peripheral counterparts, are chronically activated. Since local accumulation of activated lymphocytes can cause tissue destruction, high concentrations of cytokines, and consequently tissue rebuilding, this process might contribute to the pathogenesis of BPH.

Adult↗
PubMed1994

Multidimensional distraction osteogenesis: the canine zygoma.

The principle of distraction osteogenesis, well-established in the enchondral bones of the axial skeleton, has recently been applied to the membranous bones (mandible, cranium) of the craniofacial skeleton in the experimental animal and in the human. In the craniofacial skeleton, however, the technique has been used only to lengthen bone in a direction along its major axis, i.e., unidimensional distraction. A canine model is presented to demonstrate the feasibility of distracting membranous bone away from its dominant axis, i.e., multidimensional distraction. Four mongrel dogs, 5 months of age, were the subjects of this study. Two osteotomies were made in the zygomatic arch, and the bone-lengthening device was fixed to the zygoma. After 7 days of external fixation, the osteotomized segment was lengthened 1 mm/day away from the long axis of the bone for 15 days. External fixation was then maintained for a minimum of 4 weeks, after which the dogs were sacrificed. Craniofacial CT with three-dimensional reconstruction documented multidimensional bone lengthening, and histologic analysis of the specimen confirmed the presence of new cortical bone in the expanded areas. Refinement in technique and miniaturization and internalization of the bone-lengthening device may allow for more precise changes in the amount and direction of lengthening, thus making distraction osteogenesis more widely applicable for use in the human craniofacial skeleton.

Animals↗
PubMed1994

VLDL production is decreased to a similar extent by acute portal vs. peripheral venous insulin.

Acute changes in very low-density lipoprotein (VLDL) triglyceride (TG) and VLDL apolipoprotein (apo) B production were examined in 11 healthy young males in response to insulin delivered either by the peripheral venous route or secreted directly by the pancreas. Steady rates of pancreatic insulin secretion were achieved for 5 h by a programmed intravenous tolbutamide infusion, while euglycemia was maintained with a dextrose infusion. Insulin secretory rate was calculated from peripheral C-peptide levels by deconvolution, and, in a subsequent study, exogenous insulin was infused peripherally to match this pancreatic insulin secretory rate in each subject. Changes in VLDL TG and VLDL apo B production were determined semiquantitatively on each occasion by examining the change in slope of the specific activity (SA) of 3H-labeled triglyceride glycerol ([3H]TGG) and 131I-VLDL apo B vs. time curves, respectively, occurring with acute hyperinsulinemia. Plasma-free fatty acids (FFA), TG, apo B, and VLDL TG/VLDL apo B ratio decreased to a similar extent in both studies after the onset of hyperinsulinemia. VLDL TG production decreased significantly in both the tolbutamide (-47.1 +/- 7.3%, P < 0.002) and the exogenous insulin infusion study (-52.8 +/- 12.4%, P < 0.005). VLDL apo B production also decreased significantly in both studies (-58.9 +/- 7.5%, P = 0.0007 and -52.1 +/- 6.8%, P < 0.006, respectively), and there were no significant differences between studies. Tolbutamide was shown to have no independent effect on VLDL TG or VLDL apo B production in four insulin-deficient diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Activation of coagulation factor VII during alimentary lipemia.

Dietary studies have established a connection between plasma lipoproteins and coagulation factor VII. The present study was undertaken to specifically examine whether factor VII is activated during alimentary lipemia and to investigate the relations of factor VII mass and activity state with fasting and postprandial lipoproteins and free fatty acids (FFAs). Factor VII levels were therefore determined in plasma samples taken before and after intake of a standardized, oral fat load of a mixed-meal type in 33 men (mean age +/- SD, 48.8 +/- 3.2 years) with a previous myocardial infarction at a young age and 10 healthy, age-matched control subjects. A panel of methods for factor VII determination was used to ensure that changes in all potentially existing forms of the factor during alimentary lipemia would be included. Substantial activation of factor VII was found to occur during alimentary lipemia, whereas the number of factor VII molecules remained constant or even appeared to decrease after the test meal. Activation of factor VII was more pronounced in control subjects than patients, and the proportion of activated factor VII molecules was higher in control subjects. Interestingly, factor VII activation, which correlated quantitatively with the degree of postprandial triglyceridemia, seemed to be related to FFA production during lipolysis of triglyceride-rich lipoproteins that were generated in response to fat intake. Postheparin plasma lipoprotein lipase activity was lower in patients, which could offer one explanation why factor VII activity was lower during alimentary lipemia in these subjects despite their exaggerated postprandial triglyceridemia. Thus, activation of coagulation factor VII during alimentary lipemia may result in a procoagulant state that is likely to promote the formation of a coronary thrombus in individuals with established coronary artery disease.

Adult↗
PubMed1994

A new method for comparing portal and peripheral venous insulin delivery in humans: tolbutamide versus insulin infusion.

We describe a new noninvasive method for comparing insulin secreted acutely by the pancreas vs. a matched peripheral venous insulin infusion in humans. An intravenous tolbutamide infusion algorithm was developed that produced sustained steady rates of portal insulin secretion over 5 h in 11 healthy young men. Plasma glucose levels were maintained in the euglycemic range by adjusting the rate of an iv dextrose (20%) infusion. The pancreatic insulin secretory rate was calculated from peripheral C-peptide levels by deconvolution using standard parameters for a two-compartment mathematical model for C-peptide distribution and metabolism. On a subsequent occasion in the same subject, exogenous insulin was infused peripherally at a rate that matched the earlier tolbutamide-induced pancreatic insulin secretory rate, and euglycemia was maintained with a variable 20% dextrose infusion. The assumption that tolbutamide, when used in this fashion, has no independent insulin-like or insulin-potentiating effect at either low or high levels of peripheral insulinemia, does not affect insulin clearance, and does not suppress peripheral glucagon levels was validated in four patients with insulin-dependent diabetes mellitus. Mean peripheral immunoreactive insulin was significantly higher in the insulin infusion study than in the tolbutamide study (286 +/- 31 vs. 156 +/- 21 pmol/L; P = 0.0001). The dextrose infusion rates required to maintain euglycemia were also higher in the insulin infusion study (0.44 +/- 0.03 vs. 0.32 +/- 0.03 mmol/kg.min; P = 0.003). The MCR of insulin was greater in the tolbutamide infusion vs. the exogenous insulin infusion study (32.6 +/- 2.9 vs. 19.8 +/- 2.2 mL/kg.min; P = 0.0003), probably due to the hepatic first pass effect on insulin clearance when insulin is delivered by the portal route. This noninvasive method can be used in future studies to examine the relative importance of direct hepatic vs. peripheral effects of insulin in controlling hepatic glucose and lipid production.

Adult↗
PubMed1994

Comparison of the efficacy and safety of trandolapril and nifedipine SR in mild-to-moderate hypertension. Investigator Study Group.

After a single-blind, 4-week placebo run-in period, 161 patients were randomized to trandolapril 2 mg once daily (n = 54), nifedipine slow-release (SR) 20 mg twice daily (n = 55), or a combination of both drugs (n = 52) for 16 weeks. Morning predosing supine diastolic blood pressure (DBP) was the primary efficacy measurement. After 16 weeks the intention-to-treat analysis showed no significant difference in supine DBP (mean +/- SEM) between trandolapril (-12.4 +/- 1.5 mm Hg) and nifedipine SR (-15.3 +/- 1.4 mm Hg; p = 0.1). However, the combination therapy was more effective (-18.9 +/- 1.3 mm Hg). Normalized blood pressure at 16 weeks was seen with 54% on trandolapril, 63% on nifedipine SR, and 77% on the combination. Adverse events, possibly related to drug, were more common with nifedipine SR (34%) than with trandolapril (17%; p < 0.05), and in comparison with the combination (21%). Drug-related treatment emergent events, reported by more than 3% of patients (fatigue, palpitations, edema, migraine), were seen only in the nifedipine SR and combination groups. Trandolapril 2 mg proved a well-tolerated and effective antihypertensive agent, comparable to nifedipine SR 40 mg. Furthermore, the combination of the two drugs was shown to enhance the antihypertensive effect of the two compounds alone. Adverse events were less common with trandolapril and the combination than with nifedipine SR alone.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Clinical utility and serological connections of anti-RA33 antibodies in systemic lupus erythematosus.

OBJECTIVE: To determine whether the autoantibody anti-RA33, first identified in patients with rheumatoid arthritis, could define a subset of patients with lupus. METHODS: Sera from 30 patients with systemic lupus erythematosus (SLE), including serial bleeds from 8 patients were tested for anti-RA33 antibodies by immunoblotting. The results were compared to a wide range of SLE clinical features using the British Isles Lupus Assessment Group system and serological abnormalities. RESULTS: 12 of the 30 patients had RA33 antibodies. Their presence was associated with erosive arthropathy, and a lack of dermatological involvement in patients less likely to be Caucasian. CONCLUSION: The presence of anti-RA33 antibodies appears to identify a subset of patients with SLE.

Antigens, Nuclear↗