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Biomedical subjects

R J Levy

Publications and source records attributed to R J Levy.

At least 127 records · Page 7Linked to original sources
PubMed1979

gamma-Carboxyglutamate excretion and warfarin therapy.

The urinary excretion of gamma-carboxyglutamic acid (Gla), the amino acid involved in the vitamin K-dependent calcium binding of prothrombin and clotting factors VII, IX, and X, was studied in warfarin-anticoagulated patients. An isotope dilution procedure was developed for the measurement of free urinary Gla with the use of prior anion-exchange chromatography to separate and concentrate the free Gla from whole urine and subsequent automated amino acid analysis. Eight subjects on stable warfarin anticoagulant therapy and 11 comparable control subjects with normal coagulation were examined. Urinary Gla excretion was reduced in patients on warfarin anticoagulant therapy (p = 0.001) and the urinary Gla level correlated (r = -0.73, p = 0.001) with plasma prothrombin time. It is concluded that decreased urinary Gla in warfarin-treated patients is related to coagulation status and may be a clinically useful parameter.

1-Carboxyglutamic Acid↗
PubMed1978

Birthweight of infants with congenital heart disease.

A subnormal birth weight distribution was noted in a population of infants seen during the first year of life for major congenital heart disease (CHD). When arranged according to cardiac diagnostic categories, 17 of the 21 major cardiac lesions were associated with subnormal birth weight distribution. Major extracardiac anomalies present in 19.9% of all infants appeared not to influence the birth weight distributions of either the total population of 19 of 21 cardiac lesion categories. An increased incidence (6.1%) of small-for-dates infants was observed in the study population. Extra-cardiac anomalies occurred in 28% of the small-for-dates infants. Survival to 1 year of age was 42.8% for the total population with CHD and 49.2% in the small-for-dates group.

Abnormalities, Multiple↗
PubMed1978

Growth after surgical repair of simple D-transposition of the great arteries.

The effect of the Mustard procedure on growth was assesed in 45 patients with simple D-transposition of the great arteries (DTGA) surviving for at least one year after operation. Growth failure (below the third percentile for height, weight, or both) was found in 25 of the 45 patients preoperatively and in 8 patients postoperatively. The principal factors associated with poor growth before repair were advancing age, increased pulmonary and systemic flow, and subpulmonic stenosis. In those patients without postoperative growth failure, growth had returned to the normal range within two years. All patients wit retarded growth after the Mustard procedure had had preoperative growth failure as well. In addition, all 8 patients with postoperative growth failure had one or more amjor residual hemodynamic abnormalities, whereas residual lesions were present in only 10 of 37 patients with normal postoperative growth.

Age Factors↗
PubMed1978

Determinants of growth in patients with ventricular septal defect.

Growth status was studied in 1210 patients with ventricular septal defects (VSD) participating in the Joint Study on the Natural History of Congenital Heart Defects. A total of 793 patients were managed medically and 194 underwent successful surgical repair. Admission measurements revealed height and weight status to be subnormal and related to physiological severity and age. Successful repair resulted in significant increase in weight but not height. Medical therapy was associated with little change in the subnormal growth pattern. Multivariate analysis revealed determinants of admission height for all patients with VSD to be presence of extracardiac anomalies, birthweight below 2.5 kg, admission age greater than 2 years, history of heart failure and pulmonary/systemic pressure ratio. The same determinants were noted for admission weight with addition of pulmonary/systemic flow ratio. It is conluded that the severe growth disturbance in patients with VSD is only in part due to abnormal postnatal hemodynamics. Intrauterine and genetic factors and low birthweight also play a role and help explain the incomplete growth response after successful surgery.

Age Factors↗
PubMedDate not supplied

Immune response with biodegradable nanospheres and alum: studies in rabbits using staphylococcal enterotoxin B-toxoid.

In this study, the adjuvant effect of the sustained release biodegradable nanospheres (100-150 nm in diameter) has been compared with alum. Nanospheres were formulated using a biodegradable polylactic polyglycolic acid copolymer (PLGA, 50:50) containing Staphylococcal Enterotoxin B (SEB) toxoid as a model vaccine antigen. Systemic immune response of the nanospheres containing toxoid was studied in rabbits by subcutaneous immunization. The data demonstrated that approximately 30% of the toxoid activity was lost following its encapsulation into nanospheres. Under in vitro conditions, nanospheres demonstrated sustained release of the toxoid. However, only 20% of the antigenic toxoid was released over the first 2 weeks of the release study. Immunization of animals with equal doses of toxoid, either using nanospheres or alum induced a comparable systemic immune response (IgG, IgM and IgA). The immune response reached a maximum level at 7 weeks post-immunization, which then gradually declined with time. The booster dose of toxoid at 19 weeks, either using alum or nanospheres induced similar immune response in both the groups, but was greater than the primary immune response. The studies, thus, suggest that biodegradable nanospheres could be used as a vaccine adjuvant.

Adjuvants, Immunologic↗
PubMedDate not supplied

Enhanced immune response with a combination of alum and biodegradable nanoparticles containing tetanus toxoid.

The purpose of the study was to determine the synergistic adjuvant effect of sustained release biodegradable nanoparticles in combination with alum. Nanoparticles containing tetanus toxoid (TT) were formulated using a biodegradable polymer, polylactic polyglycolic acid co-polymer (50:50, molecular weight 100000). The immunization studies were carried out subcutaneously in rats. The results were expressed as mean serum anti-TT IgG levels. I'he nanoparticles demonstrated a TT loading of 4% w/w with mean particle diameter of 238 +/- 31 nm. The TT encapsulated in nanoparticles was released slowly under in vitro conditions, with 67.5% cumulative release occurring in 20 days. A single injection of TT-nanoparticles (TT dose = 10 Lf) mixed with TT-Alum (TT dose= 5 Lf) induced a four-fold greater mean serum anti-TT IgG response than a single injection of TT nanoparticles alone (TT dose=15Lf) (2235 +/- 310 vs. 539 +/- 49 microg/ml, mean +/- sem, p = >0.001). In addition, the mean immune response induced with the single injection of combination of nanoparticles and alum was comparable to the two injections of TT-alum alone (5 Lf each dose) given at 3 week intervals IgG = 1998 +/- 333 microg/ ml). Furthermore, the combination induced a peak immune response (IgG = 4215 +/- 546 microg/ml) as early as the first time point at 3 weeks post-immunization. In the case of a TT-alum alone, the animals showed a weaker immune response at 3 weeks and required a second dose of TT-alum to enhance the antibody response. The data thus suggest that the combination of TT-nanoparticles and TT-alum acts as a much better adjuvant than nanoparticles or alum alone. A rapid induction of immune response is useful to curb the spread of communicable diseases in the case of an outbreak.

Adjuvants, Immunologic↗
PubMedDate not supplied

Al+++ binding studies and metallic cation effects on bioprosthetic heart valve calcification in the rat subdermal model.

Al+++ preincubation has been shown to inhibit calcification of glutaraldehyde pretreated bovine pericardium calcification in the rat subdermal model. This study was designed to assess in vitro the Al+++ (10(-1) M, 10(-2) M, 10(-3) M preincubations) binding characteristics of glutaraldehyde pretreated bovine pericardium. In vivo studies assessed the ability of AlCl3 (10(-1) M, 10(-2) M, 10(-3) M) preincubations to inhibit calcification after 21 and 60 days in the rat subdermal model. Other in vivo studies investigated the ability of other metallic cations (Fe+++, La+++, and Ga+++) used as a pretreatment to inhibit glutaraldehyde pretreated bovine pericardium calcification after a 21 day rat subdermal implant. Lyophylized glutaraldehyde pretreated bovine pericardium samples were analyzed for Al+++ by neutron activation. In vitro results showed the greatest glutaraldehyde pretreated bovine pericardium Al+++ uptake in specimens incubated in 0.1M AlCl3. Maximal Al+++ uptake occurred by 1 hour. Glutaraldehyde pretreated bovine pericardium Al+++ levels after incubation in 10(-1) M, 10(-2) M, and 10(-3) M AlCl3 for 1 hour were 351.4 +/- 15.8 nM/mg, 96.4 +/- 17.4 nM/mg, and 24.6 +/- 4.9 nM/mg, respectively versus 394.5 +/- 48.0 nM/mg, 105.3 +/- 2.3 nM/mg, 40.0 +/- 8.8 nM/mg, respectively for 3 days. In vivo 21 day rat (50-60 g, male, Sprague-Dawley) subdermal implants of 0.1 M AlCl3, FeCl3, FeCl3 plus citrate, LaCl3, and GaNO3 pretreated glutaraldehyde pretreated bovine pericardium showed calcification inhibition by Al+++, Fe+++, and Fe+++ plus citrate (Ca++ = 5.5 +/- 0.2 micrograms/mg, 13.6 +/- 4.6 micrograms/mg, 5.9 +/- 1.7 micrograms/mg, respectively) compared to control (Ca++ = 63.6 +/- 5.7 micrograms/mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMedDate not supplied

Assessment of the in vitro transport parameters for ethanehydroxy diphosphonate through a polyurethane membrane. A potential refillable reservoir drug delivery device.

Calcification (CALC) is the most frequent cause of failure in bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated porcine aortic valve or bovine pericardium. Site specific controlled administration of ethanehydroxy diphosphonate (EHDP), using numerous carriers, has been successful in inhibiting CALC of BHV tissue in an accelerated rat subdermal model, without adverse effects on serum calcium, bone development, or overall somatic growth. The current study was designed to evaluate refillable reservoir devices fabricated from polyurethane (Biomer Woburn, MA) with regard to their transport properties relative to EHDP. The refillable reservoirs were evaluated for EHDP release in vitro at 22 degrees C (under perfect sink conditions) into both a physiologic receptor phase (N-2 hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer, pH = 7.4) with (1.5 mM) or without Ca2+ present. Transport parameters for EHDP diffusion through the polyurethane membranes used to fabricate the reservoirs were significantly different for the two receptor phases evaluated. The mean diffusion coefficients (D) for EHDP through the polyurethane membrane into each receptor phase were not significantly different. However, an approximately 3.5-fold reduction was observed in the mean value of the partition coefficient (K) for EHDP when EHDP was evaluated for release into a receptor phase that contained 1.5 mM Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Local cyclosporine immunotherapy of heart transplants in rats enhances survival.

High-dose systemic cyclosporine (CyA) administration frequently results in severe side effects. To evaluate a means of limiting the adverse effects of CyA, we implanted CyA-collagen matrices (0.2 or 1 mg/kg/day released) around the cardiac homografts at the time of rat heterotopic (neck) heart transplantation. Control animals received empty collagen (nondrug) matrix implants. A fourth group received CyA matrix (1 mg/kg/day released), implanted in a distal subdermal leg pouch at the time of heart transplantation. Rejection was determined by the absence of contraction in the transplanted heart. No animal received any other immunosuppression. Parallel groups of animals had whole blood, heart, and kidney CyA levels measured on the sixth posttransplant day. Local immunosuppression with high-dose CyA in a controlled-release matrix resulted in a significant survival advantage (mean survival time, 17.1 days; control, 6.9 days; p less than 0.001). The lower dose of CyA also demonstrated significant survival benefits (10.1 days), with clinically negligible blood CyA levels and very low kidney CyA levels. Both doses of epicardial local release CyA were well absorbed locally, resulting in very high CyA levels in cardiac tissue. Local immunotherapy of transplanted hearts with CyA was shown to be an effective means of preventing rejection. If this technology can be developed, this approach may prove advantageous clinically, both in extending transplantation and in minimizing systemic side effects of immunosuppression.

Animals↗
PubMedDate not supplied

Long-term efficacy of Al3+ for prevention of bioprosthetic heart valve calcification.

AI3+ preincubation has been shown in 21 and 60 day implants to inhibit calcification of glutaraldehyde preserved bovine pericardium (GPBP) in the rat subdermal model. This study was designed to assess the long-term anticalcification efficacy of GPBP AI3+ preincubation. Rat (50-60 gm, male, CD Sprague-Dawley) subdermal implants of GPBP, pretreated with 0.01 M or 0.1 M AICI3, were carried out for 21, 60, 90, and 120 days. Each explanted GPBP was analyzed for Ca2+ by atomic absorption spectroscopy and for AI3+ by atomic absorption spectroscopy or neutron activation irradiation. Results showed profound long-term (implant duration 120 days) inhibition of calcification after GPBP preincubation in 0.1 M AICI3 (Ca2+ = 21.8 +/- 12.6 micrograms/mg), compared to control (Ca2+ = 329.0 +/- 20.3 micrograms/mg). After preincubation in 0.1 M AICI3 and 21 day rat subdermal implantation, GPBP AI3+ levels declined from 9033 +/- 680 micrograms/g (control = 6.3 +/- 3.7 micrograms/g) to 2700 +/- 156 micrograms/g; however, there was no further significant decline in GPBP AI3+ levels after long-term implantation of 120 days (2618.4 +/- 349 micrograms/g). The authors conclude that GPBP preincubation in 0.1 M AICI3 markedly inhibited pathologic calcification to 7% of control values in the rat model after long-term (120 day) subdermal implantation.

Aluminum↗
PubMedDate not supplied

Local controlled release of 1-hydroxyethylidene diphosphonate using silicone-rubber matrices. Effects of sterilization on in vitro release and in vivo efficacy.

Calcification (CALC) is the most frequent cause of the clinical failure of bioprosthetic heart valves (BHVs). Controlled release of disodium ethanehydroxydiphosphonate (EHDP) has been demonstrated to inhibit subdermal BHV calcification at effective low local doses, avoiding adverse effects. However, the eventual circulatory use of controlled release EHDP necessitates addressing several critical issues that may affect efficacy. These include the effects of sterilization on EHDP release and the efficacy of sustained release matrices containing CaEHDP, which is less soluble than NaEHDP. The effects of CaEHDP-NaEHDP incorporation and steam sterilization on controlled release of EHDP from silicone-rubber matrices was studied both in vitro and in vivo using a rat subdermal model and sheep tricuspid valve replacements. Autoclaved EHDP matrices (20% wt/wt) released 88.9% +/- 7.84 of contained drug after 140 days in vitro, compared with control (87.6% +/- 10.3 cumulative release). Autoclaved EHDP matrices completely inhibited BHV CALC in 60 day rat subdermal implants (8.84 +/- 3.68 micrograms Ca++/mg tissue), comparable to nonsterilized EHDP-loaded matrices (7.06 +/- 2.00 micrograms Ca++/mg tissue). Nontreated CALC levels were 183 +/- 7.60 micrograms Ca++/mg tissue. Na-CaEHDP co-incorporation into silicone rubber matrices markedly prolonged controlled release with the 1:1 Na-CaEHDP mixture demonstrating an extrapolated release duration of approximately 20 years, assuming the total amount of dispersed drug was released. Data from tricuspid valve replacements in sheep demonstrate erratic control calcification (41.3 +/- 14.9 micrograms Ca++/mg tissue), but complete suppression of BHV calcification with Na2EHDP controlled release (5.74 +/- 1.35 micrograms Ca++/mg tissue) after 150 days.

Animals↗