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Biomedical subjects

J Heller

Publications and source records attributed to J Heller.

At least 109 records · Page 6Linked to original sources
PubMed1995

Preliminary effects of in vitro lipid exposure on absorbable poly(ortho ester) films.

Bioabsorbable films show promise in preventing postoperative interfacial tissue adhesion. Absorbable polymers in film form are generally more sensitive to chemical environments, due to their large surface area to volume ratio. The in vivo environment contains lipids such as cholesterol, triglycerides, and phospholipids, which are known to affect the degradation of permanent and absorbable polymeric biomaterials. Preliminary investigations of in vitro lipid exposure of bioabsorbable poly(ortho ester) (POE) films for implant use are described. POE has been studied previously for use in controlled drug delivery and fracture fixation. Six-week in vitro exposure of 65:35 POE films to a cholesterol emulsion (1 g/L) showed no apparent difference in hydrolytic degradation rates of mechanical properties or mass loss compared to deionized water exposed films. Decreases of 28 and 6% in inherent viscosity were observed after 5 weeks for cholesterol and deionized water exposed films, respectively, suggesting cholesterol may have some effect. Further examination of the data, due to sample variation, revealed that clear, uniform films showed only minor changes in mass loss and mechanical properties after 6 weeks in either of the in vitro media. But slightly cloudy films possessing microscopic bubbles showed accelerated degradation in both media, indicating the effect of cholesterol was inconclusive due to sample variation. Control of the microbubble formation process could have utility in controlling hydrolytic degradation of POE films.

Biocompatible Materials↗
PubMed1995

A study of reversibly inactivated lipases for use in a morphine-triggered naltrexone delivery system.

A key component of an implant that can be triggered by external morphine to release naltrexone is an inactivated enzyme that can be activated by morphine and which can then rapidly remove a protective coating surrounding a bioerodible polymer containing dispersed naltrexone. In this article we describe a lipase that has been conjugated with O3-carboxymethylmorphine, morphine-beta-3-glucuronide and O3-carboxypropylmorphine. The enzyme conjugate was then inactivated by complexation with affinity-purified goat polyclonal antimorphine antibodies. Antibody lipase interactions were measured by pH Stat and ELISA techniques. Affinity constants of the antibodies determined by radioimmunoassay using tritium-labeled morphine were 4.10 x 10(6), 3.18 x 10(6) and 3.38 x 10(7), respectively. While a concentration of 10(-5)M morphine was required to restore lipase activity, it is likely that a combination of correct morphine tether and correct affinity-purified antibody can increase sensitivity to the desired 10(-8)10(-9)M morphine level. Thus, a functioning device can almost certainly be constructed. However, it is unlikely that reactivation times of 1-2 h necessary for clinical usefulness in treatment of narcotic addiction can be achieved.

Animals↗
PubMed1995

Information flow and temporal coding in primate pattern vision.

We perform time-resolved calculations of the information transmitted about visual patterns by neurons in primary visual and inferior temporal cortices. All measurable information is carried in an effective time-varying firing rate, obtained by averaging the neuronal response with a resolution no finer than about 25 ms in primary visual cortex and around twice that in inferior temporal cortex. We found no better way for a neuron receiving these messages to decode them than simply to count spikes for this long. Most of the information tends to be concentrated in one or, more often, two brief packets, one at the very beginning of the response and the other typically 100 ms later. The first packet is the most informative part of the message, but the second one generally contains new information. A small but significant part of the total information in the message accumulates gradually over the entire course of the response. These findings impose strong constraints on the codes used by these neurons.

Animals↗
PubMed1995

Development of a drug delivery system for the treatment of periodontal disease based on bioerodible poly(ortho esters).

Poly(ortho esters) prepared by the condensation of 1,2,6-hexanetriol and an alkyl orthoacetate are viscous, semisolid materials at room temperature that can be injected using a blunt needle. When tetracycline was incorporated into these materials, complete release occurred within about 24 hours, but when small amounts of Mg(OH)2 were incorporated into the polymer release could be extended to many weeks, and a loading of 0.5 wt% resulted in sustained release of about 10 days. When adhesion was tested using bovine teeth, cohesive failure of the pure polymer occurred at a force of about 392 mN cm-2 and cohesive failure of a polymer incorporating 10 wt% tetracycline and 1 wt% (Mg(OH)2 occurred at about 118 mN cm-2. The combination of injectability, dentoadhesiveness and ability to control accurately the release of incorporated antibiotics makes these materials promising candidates for bioerodible delivery systems useful in the treatment of periodontitis. Toxicological studies are currently in progress.

Acetates↗
PubMed1995

Biocompatibility and in vivo morphine diffusion into a placebo morphine-triggered naltrexone delivery device in rabbits.

Two key factors in developing a clinically useful triggered naltrexone delivery system are device biocompatibility and ability of morphine to diffuse from the blood into the device in concentrations useful to trigger delivery. Two types of devices were implanted subcutaneously into rabbits and their biocompatibility was investigated. One device consisted of the outer semipermeable regenerated cellulose acetate tubing, closed at both ends with double knots and filled with poly(N-vinyl pyrrolidone) as osmotic filler. The other device was a placebo device that contained within the regenerated cellulose acetate tubing, also closed at both ends with double knots, all device components except naltrexone. Both devices were biocompatible. When the regenerated cellulose acetate device filled with osmotic filler was implanted in rabbits which were subsequently dosed at day 7 and day 14 post-implant with 150 mg kg(-1) morphine sulphate, the concentration of morphine in the device was only about 10-fold less than that measured in rabbit blood. Thus, enough morphine diffuses into the device to make triggering in a real-life situation feasible.

Animals↗
PubMed1995

Does desmopressin improve hemostasis and reduce blood loss from aortic surgery? A randomized, double-blind study.

PURPOSE: The purpose of this study was to determine the effect of desmopressin acetate (DDAVP) on blood loss, transfusion requirements, and thromboembolic complications in patients undergoing elective aortic operations. METHODS: A randomized, double-blind trial was carried out during a 3-year period with patients receiving 20 micrograms DDAVP or identical-appearing placebo at the time of aortic cross-clamp placement. In addition to major bleeding and thromboembolic end points, bleeding times and platelet counts were monitored serially. RESULTS: Forty-three patients were randomized to receive DDAVP, and 48 were assigned to a placebo. An equivalent proportion of patients with aneurysm and patients with occlusive disease was in each group. In spite of mild prolongation in the postoperative bleeding times and moderate thrombocytopenia, DDAVP had no beneficial effect on blood loss or transfusion requirements. Total blood transfusion amount (mean +/- standard deviation) for patients receiving DDAVP was 3.1 +/- 3.0 U compared with 2.7 +/- 3.0 U for those receiving placebo. For all patients the period associated with the greatest blood loss was the time between heparin administration with cross-clamp application and reversal of heparin with protamine sulfate. The incidence of major thromboembolic complications was similar in both groups. CONCLUSION: Thrombocytopenia and mild platelet dysfunction are common after aortic operation, but DDAVP does not improve hemostasis or lessen transfusion requirements. This study does not rule out a beneficial effect of DDAVP in patients who are undergoing more complex aortic operations or who have major hemostatic aberrations.

Aged↗
PubMed1995

A comparison of the effect of feeding a low-protein diet and of pharmacological intervention on the course of ablation nephropathy in the rat.

In Wistar rats just after weaning, 5/6 of renal parenchyma were removed surgically. Thereafter, the rats were fed either a "high-protein" (21%) or two types of a "low-protein" (6%) diet; in one of the latter the lack of protein was substituted by saccharide, in the other by fat, making the substitution "isocaloric" in either case. In all three diet groups, subgroups were formed drinking either tap water or water containing either the ACE inhibitor enalapril (Ena) or the calcium antagonist diltiazem (Dil), or both (Ena + Dil). In the high-protein diet group, increases in the weight of kidney remnants, in proteinuria and in systolic blood pressure (SBP) were seen. This was prevented by feeding either type of the low-protein diet but also by Ena and Ena + Dil. Ena and Ena + Dil not only prevented the increase in SBP but actually lowered it significantly. Dil alone also had a SBP-lowering action but offered no protection from kidney hypertrophy and proteinuria. No additive protective action of Ena + Dil or Ena + low protein or Ena + Dil + low protein was seen, suggesting that a bottom limit of these protective action was reached by the low-protein diet alone. There was no substantial difference between either type of the low-protein diet except a small and transient decrease in body weight in the first week of fat-rich diet administration.

Analysis of Variance↗
PubMed1995

[Effect of light intensity on binocular distance perception].

Empirical investigations of perceived binocular distance often use an experimental setting in which real point-like light sources are presented in a completely dark surround. The results obtained, however, may be a consequence of the joint influence of binocular and monocular depth cues. Here, for the first time, the effect of (monocular) illumination cues on the locus of perceived equidistance is experimentally investigated by manipulating the luminous intensity of the stimuli. In a computer-controlled setup, small light-emitting diodes were presented in complete darkness. Five subjects judged the perceived distance of stimuli, which appeared in four directions and at five levels of luminous intensity, with respect to a fixed standard. Adaptive methods were used to determine perceived equidistance. Although the results show a significant effect of illumination cues, their influence on the locus of perceived equidistance turned out to be far less than previously supposed. For three subjects it was practically negligible.

Adult↗
PubMed1995

[Ineffectiveness of ACE inhibitors (enalapril) on glomerular damage in rats after a 5/6 nephrectomy and a high-salt diet].

Wistar rats with surgically removed 5/6 of renal parenchyma were fed either standard (0.35% salt content) or a high-salt (2%) diet. Half of the animals of each group drunk plain water while the other half was provided water enriched with the angiotensin-converting enzyme inhibitor enalapril (ENA) at a dose of 5 mg/kg/day. In rats receiving standard diet, ENA had a significant inhibitory effect on the consequences of ablation: the rats had normal blood pressure, low proteinuria, and high endogenous creatinine clearance compared to water-drinking controls. The high-salt diet significantly enhanced the sequelae of ablation: a high blood pressure and proteinuria, low clearance, which ENA was unable to prevent in these animals. No plausible explanation for the absence of ENA's beneficial effect is available: one can speculate that, under conditions of high-salt intake, the activity of the renin-angiotensin system is suppressed leaving no place for ENA to exert its effect. We also believe that the highly adverse effect of a high-salt diet in chronic renal failure is due to growth factors other than angiotensin II.

Animals↗
PubMed1995

[Do the kidneys play an important role in the pathogenesis of "essential" hypertension?].

The Prague Hypertensive Rat (PHR) is a model of genetic hypertension derived from the Wistar strain, in which a normotensive parallel, the Prague Normotensive Rat (PNR), was also bred from the same parent pair. Thus, it is possible to transfer organs between both parallels without signs of rejection and without the use of immunosuppressive drugs. Unilateral nephrectomy and transplantation of one kidney within the PHR and PNR groups did not affect the systolic blood pressure (SBP). Transplantation of one kidney from PNR to a bilateral nephrectomized (BNX) PHR normalized the high SBP; and transplantation of one kidney from PHR to BNX PNR led to an elevation of SBP: hypertension "travels" with the kidney. When the development of high SBP in PHR was prevented for 2 months after weaning by antihypertensive drugs, transplantation of one kidney from these rats to BNX PNR always induced a sustained hypertension in the recipient. If a PHR was left with one original kidney in situ after transplantation of a "normotensive" kidney, the high blood pressure persisted until the original "hypertensive" kidney was removed. These results support the view that the kidney of PHR produces a "hypertensinogenic" substance, the secretion of which is genetically determined and is not influenced by the magnitude of the SBP.

Animals↗
PubMed1995

[The effect of Tenziomin on function, morphology and lectin binding in rat kidney remnants after experimental subtotal nephrectomy].

Captopril (Tenziomin) treated rats after subtotal (5/6) nephrectomy showed conspicuously better function of kidney tissue remnants than untreated animals. Histology was the same in both groups--focal glomerulosclerosis, anisocytosis and anisokaryosis of tubular epithelial cells, hyperplasia of proximal tubuli. Proteinuria was substantially lower in treated animals. Lectin histochemistry showed differences between superficial and juxtamedullary nephrons in glycoprotein contents and function. An important finding was selective binding of WGA lectin in brush border of proximal convoluted tubuli of juxtamedullary nephrons. Differences in lectin binding between nephrectomized and intact control animals were rather quantitative than qualitative.

Animals↗
PubMed1994

[The effect of a low-protein diet and certain pharmaceutical agents on the course of ablation nephropathy in rats].

BACKGROUND: The beneficial effect of a low-protein diet on the course of renal failure after ablation nephropathy in the rat is known; also calcium channel antagonists (CaA) and angiotensin I converting enzyme inhibitors (ACEI) have a protective effect. Because even simple energy restriction retards the development of spontaneous or ablation-induced glomerulosclerosis the authors decided to replace the lacking dietary protein in the low protein diet by starch (disaccharide) and by fat (cereal oil) and compare these two low-protein diets as to their effect on the development of chronic renal failure (CRI) caused by surgical removal of 5/6 of renal parenchyma (5/6 NX). METHODS AND RESULTS: In Wistar rats just after weaning, 5/6 of renal parenchyma were removed surgically. Thereafter, the rats were fed either a "high-protein" (21%) or two types of a "low-protein" (6%) diet, in one of the latter, the lack of protein was substituted by saccharide, in the other by fat making the substitution "isocaloric" in either case. In all three diet groups, subgroups drinking either tap water or water containing either the ACE-inhibitor enalapril (ena) or the calcium antagonist diltiazem (dil) or both (ena+dil) were formed. On the high-protein diet, an increase in the weight of kidney remnants, in proteinuria and in systolic blood pressure (SBP) was seen. This was prevented by feeding either type of the low-protein diet but also by ena and ena+dil. Ena and ena+dil not only prevented the increase in SBP but actually lowered it significantly. Dil alone also had a SBP-lowering action but offered no protection from kidney hypertrophy and it significantly. Dil alone also had a SBP-lowering action but offered no protection from kidney hypertrophy and proteinuria. No additive protective action of ena+dil or ena+low-protein or ena+dil+low-protein was seen suggesting that the lower limit of these protective actions was reached by the low-protein diet alone. There was no substantial difference between either type of low-protein diet except a small and transient decrease in body weight in the first week on a fat-rich diet. CONCLUSIONS: In the described experiments and with the set-up used the low-protein diet had no effect on the plasma creatinine and urea levels nor on creatinine clearance. The weight of the kidney remnants and proteinuria were significantly higher in animals on a high-protein diet who drank water or water with diltiazem. These changes were suppressed by administration of angiotensin converting enzyme inhibitors either alone or combined with diltiazem. A low- protein diet (both types tested) as well as angiotensin converting enzyme inhibitors improve the course of chronic renal failure in ablation nephropathy in the rat; the authors did not prove an additive effect of the combination of this diet with angiotensin converting enzyme inhibitors.

Animals↗
PubMed1994

Evaluation of absorbable poly(ortho esters) for use in surgical implants.

Recent reports describe an unfavorable noninfective inflammatory response to acidic degradation products in clinical applications of bone fixation devices fabricated from bulk hydrolyzing polyglycolides and polylactides (PGA and PLA). The work described here suggests that poly(ortho esters) (POEs) offer an alternative. By comparison, hydrophobic POEs degrade predominately via surface hydrolysis, yielding first a combination of nonacidic degradation products, followed by alcoholic and acidic products gradually over time. POE specimens proved acutely nontoxic in United States Pharmacopeia tests of cellular, intracutaneous, systemic, and intramuscular implant toxicity. Hot-molded specimens degraded slowly in saline, retaining 92% initial stiffness (1.6 GPa flexion) and retaining 80% initial strength (66 MPa flexion) in 12 weeks. Degradation was almost unaffected by decreasing saline pH from 7.4 to 5.0. This demonstrated the relative hydrophobicity of POEs, since incorporation of small amounts of acid within the polymer markedly increases the degradation rate. Degradation rates were increased substantially by dynamic mechanical loading in saline. This may be true for other degradable polymers also, but no data could be found in the literature. Presumably, tensile loading opens microcracks, allowing water to enter. Solvent cast POE films were strong in tension (30 + MPa tensile yield) and reasonably tough (12-15% elongation to yield). Higher molecular weight films (41-67 kDa) showed no degradation in mechanical properties after 31 days in physiological buffer at body temperature. A 27-kDa film offered similar initial strength and stiffness but began showing mechanical degradation at 31 days. The films showed a decrease in weight with exposure time but no change in either molecular weight or water absorption at 31 days, further supporting the observation that POE degrades by surface hydrolysis rather than by bulk hydrolysis.

Animals↗
PubMed1994

Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products.

Bioabsorbable polymer implants may provide a viable alternative to metal implants for internal fracture fixation. One of the potential difficulties with absorbable implants is the possible toxicity of the polymeric degradation products especially if they accumulate and become concentrated. Accordingly, material evaluation must involve dose-response toxicity data as well as mechanical properties and degradation rates. In this study the toxicity and rates of degradation for six polymers were determined, along with the toxicity of their degradation product components. The polymers studied were poly(glycolic acid) (PGA), two samples of poly(L-lactic acid) (PLA) having different molecular weights, poly(ortho ester) (POE), poly(epsilon-caprolactone) (PCL), and poly(hydroxy butyrate valerate) (5% valerate) (PHBV). Polymeric specimens were incubated at 37 degrees C in 0.05 M Tris buffer (pH 7.4 at 37 degrees C) and sterile deionized water. The solutions were not changed during the incubation intervals, providing a worst-case model of the effects of accumulation of degradation products. The pH and acute toxicity of the incubation solutions and the mass loss and logarithmic viscosity number of the polymer samples were measured at 10 days, 4, 8, 12, and 16 weeks. Toxicity was measured using a bioluminescent bacteria, acute toxicity assay system. The acute toxicity of pure PGA, PLA, POE, and PCL degradation product components was also determined. Degradation products for PHBV were not tested. PGA incubation solutions were toxic at 10 days and at all following intervals. The lower molecular weight PLA incubation solutions were not toxic in buffer but were toxic by 4 weeks in water.(ABSTRACT TRUNCATED AT 250 WORDS)

Biodegradation, Environmental↗
PubMed1994

The effect of kinin and prostaglandin inhibitors on the renal response to angiotensin-converting enzyme inhibition: a micropuncture study in the dog.

It has been suggested that angiotensin-converting enzyme (ACE) inhibition is accompanied by enhanced bradykinin and prostaglandin activities, which may contribute to the renal haemodynamic actions of ACE inhibitors. Therefore we investigated renal function by clearance and micropuncture techniques in dogs maintained either on normal or low-salt diet before and after ACE inhibition with an i.v. bolus of 0.1 mg/kg ramiprilat followed by an infusion of 5 micrograms kg-1 min-1. Subgroups each comprising six dogs were also treated with either HOE-140, a bradykinin B2 receptor antagonist, or the cyclooxygenase inhibitor indomethacin. In general, renal effects of ramiprilat were more pronounced in dogs fed on low salt than in those on normal diet. In dogs on low salt, the mean arterial pressure decreased by 20% 20 min after ramiprilat application, whereas the total renal blood flow rose by 71% from 4.71 to 8.06 ml min-1 g kidney weight-1 and the glomerular filtration rate (GFR) by 28% from 0.74 to 0.95 ml min-1 g-1. Single-nephron glomerular blood flow and single-nephron GFR rose by 55% and 23% respectively. The total and the single-nephron filtration fraction decreased by 25% and 23% respectively. There were no substantial changes in glomerular and peritubular capillary and tubular pressures, but a significant increase in the ultrafiltration coefficient, Kf, by 103% from 3.55 nl/mmHg to 7.19 nl/mmHg (26.7-54.0 nl/kPa) was observed. Afferent and efferent arteriolar resistances decreased in parallel by 55% and 47%.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗