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Biomedical subjects

B E Cohen

Publications and source records attributed to B E Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1995

Proximal third tibial shaft fractures. Should they be nailed?

Thirty-two extraarticular fractures of the proximal third of the tibia were treated with locked intramedullary nails. There were 10 closed and 22 open injuries. Treatment consisted of a reamed nail in each of the 5 closed fractures, and an unreamed nail in the remaining 27 fractures. Thirty of the 32 fractures eventually healed; however, 9 (28%) underwent exchange nailing and 4 (13%) required bone grafting. At final followup, 27 of 32 fractures (84%) had angulation of 5 degrees or greater in the frontal or sagittal plane. Nineteen of the 32 fractures (59%) had 1 cm or more of displacement at the fracture site. In 8 fractures (25%), there was loss of fixation, most commonly associated with placement of a single proximal locking screw. Fractures of the proximal third of the tibial shaft do not appear to respond as favorably to intramedullary nailing as do fractures in the distal 2/3 of the tibia. Valgus, apex anterior angulation, and residual displacement at the fracture site are common after nailing. Surgical errors of a medialized nail entry point and a posteriorly and laterally directed nail insertion angle contributed to malalignment. Based on their findings, the authors have limited the use of intramedullary nailing for proximal third tibial shaft fracture and consider alternate forms of fixation (plate or external fixation).

Adolescent↗
PubMed1995

Comparison of the leishmanicidal activity of fungizone, liposomal AmB and amphotericin B incorporated into egg lecithin-bile salt mixed micelles.

We compared leishmanicidal activity of five formulations of amphotericin B (AmB). AmB used as Fungizone immediately caused cell lysis, at lower concentrations partial, and at higher concentrations total; the non-lysed cells reassuming growth. AmB formulated with egg-lecithin and bile salt at doses equivalent to those of Fungizone was not active, whereas at higher doses it resulted in a delayed but complete inhibition of cell growth. The activity of liposomal AmB was comparable to that of Fungizone. The time of initial leishmanicidal activity of the five formulations tested can be ascribed to the rate of free, monomeric AmB delivered. Features that are characteristic of the anticellular effect of AmB formulated with egg lecithin and bile salts, a delay in activity, a requirement for higher concentration and total inhibition of cell growth, were also noted.

Amphotericin B↗
PubMed1994

Application of the 3M microvascular anastomotic device in non-vascular tubular structures.

In this study, the 3M microvascular anastomotic system was utilized for the first time to perform an end-to-end anastomosis in a non-vascular tubular structure, which was compared to the conventional microvascular suture method. The bicornuate rat uterus was the preferred structure because of its anatomic similarity to the human fallopian tube. Thirty Sprague-Dawley rats underwent 3M and conventional end-to-end anastomoses of their bicornuate uteri. At different intervals, the animals were explored and biopsies were taken for examination under light microscopy. Overall patency rate with the 3M technique was 68 percent vs. 96 percent with the conventional technique. Complication rates were 40 percent with the 3M device and 12 percent with the conventional method. This study concludes that, if this method is to be used on non-vascular tubular structures, further modifications to the system and additional research are mandatory, in order to recommend this technique for clinical application.

Anastomosis, Surgical↗
PubMed1994

Acute intraoperative arterial elongation: histologic, morphologic, and vascular reactivity studies.

This study focuses on the histomorphologic damage produced by an acute elongation process, as well as on quantifying the alterations in arterial contractility following the application of this technique. Light microscopy and scanning electron microscopy studies were prepared from expanded and non-expanded pig superficial femoral arteries (SFA) harvested immediately following expansion, and again at 24- and 72-hr intervals. Histologically, the expanded vessels showed minor, patchy, endothelial slough, but not fragmentation of the internal or external elastic lamina. At 24 hr, the endothelium showed reactive changes, but no evidence of smooth-muscle necrosis of the tunica media was observed. At 72 hr, healing of the endothelium was evident by SEM. Similar specimens, also from the SFA, were harvested and placed in organ chambers immediately following expansion and 24 hr later, to measure contractility when exposed to alpha-adrenergic agonists. The vessels were exposed to the contractile agonists, phenylephrine and 5-hydroxytryptamine, which evoked similar concentration-dependent increases in tension in both the expanded group and the controls. From these observations, the authors conclude that acute intraoperative elongation of arteries results in only minor endothelial damage, without affecting the inherent contractility of the vessel wall.

Anastomosis, Surgical↗
PubMed1994

Effect of ketoconazole on lethal action of amphotericin B on Leishmania mexicana promastigotes.

The effect of ergosterol depletion by ketoconazole on the leishmanicidal activity of the pore-forming antibiotic amphotericin B (AmB) was investigated. Leishmania mexicana promastigotes were lysed within minutes by the addition of micromolar concentrations of AmB (0.5 microM) but became insensitive to AmB after growth in the presence of ketoconazole (0.25 microM, 90 h). Lipid chromatographic analysis indicated that under such conditions, ketoconazole depleted the major Leishmania sterols, dehydroepisterol and ergosterol. Plasma membrane vesicles prepared from ketoconazole-treated promastigotes exhibited a much reduced enhancement of their salt permeability after the addition of AmB at concentrations as high as 5 microM. This finding clearly indicates that upon ketoconazole treatment, the capacity of pore formation by the antibiotic is substantially impaired. The reduction of desmethyl sterols by ketoconazole was accompanied by a significant increase of 14-alpha-methyl sterols, but exogenous cholesterol remained unchanged. This ability of Leishmania promastigotes to incorporate cholesterol from the external medium may explain why ketoconazole-treated cells exhibited a much decreased but significative response to AmB when they were exposed to high AmB concentrations (2.5 or 5.0 microM). Parallel measurements by using a fluorescence energy transfer method indicated that binding of AmB to ketoconazole-treated Leishmania promastigotes and heat-transformed leishmanias was also decreased but to different extents, a finding that may be related to the differences in their sterol content. The results obtained clearly indicate that the specific interaction of AmB with desmethyl sterols, such as dehydroepisterol, ergosterol, and even exogenous cholesterol, is an absolute requirement for the lethal action exerted by this polyene antibiotic on L. mexicana promastigotes.

Amphotericin B↗
PubMed1993

Clinical applications of acute intraoperative arterial elongation.

This study reports four clinical cases in which acute intraoperative, extraluminal, arterial elongation was utilized. This technique was developed to facilitate end-to-end anastomoses across vascular defects traditionally bridged with vein grafts. In the reported cases, arterial defects, ranging from 17 to 25 mm, were closed primarily following the application of this technique. Follow-up, ranging from 3 to 34 months, has demonstrated patency in all cases. The authors believe this technique can be used clinically as a reliable alternative to vein grafting for the reconstruction of certain arterial defects.

Adolescent↗
PubMed1992

A sequential mechanism for the formation of aqueous channels by amphotericin B in liposomes. The effect of sterols and phospholipid composition.

The kinetics of formation of amphotericin B (AmB) aqueous pores in ergosterol-containing DMPC or egg-PC liposomes was investigated using a stopped-flow method. The formation of aqueous pores by AmB occurred very rapidly (in milliseconds to seconds depending of the AmB concentration), and it was always preceded by the formation of transient, non-aqueous pre-pore structures. As anticipated, these non-aqueous pre-pore structures made the liposomes more permeable to urea without at the same time leading to a decrease of the reflection coefficient of urea or to an enhancement of glucose permeability. However, when liposomes were composed of egg-PC and cholesterol, the formation of non-aqueous and aqueous channels by AmB occurred after a lag time of several minutes. Such a time lag for AmB action was not observed in cholesterol-containing DMPC liposomes, an indication that the phospholipid composition is an important parameter in the formation of non-aqueous channels by AmB. Both non-aqueous and aqueous channels were always formed at lower concentrations of AmB in liposomes containing ergosterol while higher concentrations were needed in cholesterol-containing liposomes. Measurements of the permeabilizing effect of AmB on liposomes prepared without sterols indicate that non-aqueous channels were formed in DMPC (but not in egg-PC) at polyene concentrations identical to that found for cholesterol-containing liposomes. No evidence of the formation of aqueous channels by AmB was found in pure DMPC liposomes. These data are consistent with the concept that AmB forms non-aqueous channels without the direct participation of sterol molecules. The initially formed non-aqueous channels subsequently interact with the sterols in the membrane to form aqueous channels, having an enlarged diameter. This sequential mechanism for the formation of AmB aqueous pores in liposomes provides a rationale for the understanding of the effect of both the phospholipid composition and type of sterol in the interaction of AmB with natural membranes and artificial bilayers.

Amphotericin B↗
PubMed1992

[Psychosocial characteristics of phenylketonuric women: birth defect prevention].

Women with phenylketonuria (PKU) are at high risk for having offspring with mental retardation, microcephaly, heart defects and low birth weight. These adverse outcomes can be prevented by a low-phenylalanine diet started before conception and continued throughout pregnancy. In view of the frequency of poor dietary compliance in women with PKU, a psychosocial model was developed that delineates developmental stages with specific behavioral goals for them to follow. In the present study 15 women with PKU over the age of 16 were followed for 3 years and compared to groups of their healthy acquaintances and of diabetic women. Structured interviews and standard questionnaires were used to study factors hypothesized as being related to the subjects' adjustment and to achievement of their PKU-related behavioral goals. After 1 year most of the PKU subjects were not planning a pregnancy, making their main behavioral goal the prevention of an unplanned pregnancy. Their knowledge of the risks of maternal PKU and family planning was unsatisfactory. PKU subjects had more conservative attitudes about sex and contraception than the controls. The psychosocial profile of PKU subjects pinpointed their special needs and indicated the kinds of specific intervention that might help them adhere to the recommended treatment and prevent birth defects in their offspring.

Adolescent↗
PubMed1992

CO2 laser-assisted repair of esophageal lacerations.

This study was designed to evaluate the feasibility of CO2 laser-assisted repair of esophageal injuries. Nine-millimeter longitudinal incisions were made in the cervical esophagus of 40 Sprague-Dawley rats. The rats were divided into two groups. Twenty rats in Group 1 had their incisions closed in two layers (mucosa and muscularis) with the I.L. Med Unilase microsurgical CO2 laser (LAREL), using 80 mW of power with a spot size of 200 mu (power density = 255). Twenty rats in Group 2 had their incisions closed in two layers using 8-0 Vicryl conventional suture technique (CST). Postoperatively, an intraluminal methylene blue injection evaluated patency and leakage. Histologic analysis was performed at 3 days, 2 weeks, 1 month, and 6 months. Patency rates of LAREL and CST were comparable. No fistulas or strictures were found with either technique. Laser-assisted repair of esophageal lacerations (LAREL) was found to be faster and easier than CST. The question arises whether small esophageal tears can be safely repaired through the endoscope. This study demonstrates the feasibility of tissue welding the esophagus. Further research is mandatory to study the applicability of this technique in the clinical setting.

Animals↗
PubMed1992

Acute intraoperative arterial lengthening for closure of large vascular gaps.

This study demonstrates the feasibility of acute extraluminal expansion to elongate arteries intraoperatively in order to overcome defects too large to be repaired primarily. Twenty Sprague-Dawley rats were divided into two groups: an expander-elongation group and a nonexpanded control group of 10 rats each. Arterial resections were performed ranging from 6 to 22 mm. A miniaturized tissue expander was used to stretch vessels in three consecutive cycles over a 15- to 20-minute period (expander-elongation group). Defects twice as long as those which could be overcome by mobilization alone (nonexpanded control group) could be closed following the application of this technique without thrombosis. Initial laboratory findings and the application of this method in a clinical case are presented.

Anastomosis, Surgical↗
PubMed1992

Effects of aggregation and solvent on the toxicity of amphotericin B to human erythrocytes.

In aqueous suspensions of amphotericin B (AmB), a polyene antibiotic and antifungal agent, three forms of AmB coexist: monomers, water-soluble oligomers, and non-water-soluble aggregates. The toxicity of the water-soluble self-associated form of AmB compared with that of the non-water-soluble self-associated form was tested by measuring induction of K+ leakage from human erythrocytes, using different suspensions containing the antibiotic and phosphate-buffered saline. These suspensions were obtained from various stock solutions of the antibiotic in dimethyl formamide or dimethyl sulfoxide. Their circular dichroism spectra around 340 nm, indicative of the degree of AmB self-association, were strongly dependent on the concentration of organic solvent in the suspensions. The nonsoluble self-associated form was separated from the water-soluble form by centrifugation. The nonsoluble form was favored by a high concentration of AmB of the stock solution. The kinetics of AmB-induced K+ leakage from human erythrocytes also appeared to be strongly dependent on the AmB concentration of the stock solution being much weaker with concentrated stock solutions. It was concluded that the only form of AmB toxic to human erythrocytes is the water-soluble self-associated form (in contrast with fungal cells on which the monomeric form is also active). This result may be important in the design of new less toxic AmB derivatives and in the understanding of the mechanism of action of liposomal AmB.

Amphotericin B↗
PubMed1992

Analysis of risks and aesthetics in a consecutive series of tissue expansion breast reconstructions.

A consecutive series of 73 patients underwent tissue expansion for breast reconstruction between 1980 and 1986. The cases were reviewed, and preoperative risk factors, postoperative complications, and aesthetic results were assessed. Cigarette smoking correlated with a higher incidence of complications and unfavorable results. Similar correlations were found among patients with histories of significant medical disorders or alcohol abuse, although patient numbers were small in these categories. Subpectoral and suprapectoral placement of expanders yielded similar complication rates and aesthetic results. Surgical techniques contributing to improved aesthetic results are described.

Adult↗
PubMed1991

Compound heterozygosity in nonphenylketonuria hyperphenylalanemia: the contribution of mutations for classical phenylketonuria.

Hyperphenylalaninemia (HPA) results from defective hydroxylation of phenylalanine in the liver, in most cases because of defective phenylalanine hydroxylase. HPA is highly variable, ranging from moderate elevation of plasma phenylalanine with no clinical consequences to a severe disease, classical phenylketonuria (PKU). Non-PKU HPA was found in excess of PKU in Israel, while the opposite is true in Europe. To study the genetic basis of non-PKU HPA, we performed haplotype analysis at the phenylalanine hydroxylase locus in 27 families with non-PKU HPA. All individuals with this condition were compound heterozygotes. In six of these families, in which both PKU and non-PKU HPA were segregating, haplotype analysis showed that non-PKU HPA resulted from compound heterozygosity for a PKU mutation and a second mutation, with milder effect, which is probably expressed only when it interacts with the severe mutation. The involvement of PKU mutations in non-PKU HPA was further demonstrated in Jewish Yemenite families with non-PKU HPA, in which the individuals with this condition were carriers of the single PKU allele which exists in this community. In addition, two previously known PKU point mutations (R261Q and R408W) were found in individuals with non-PKU HPA. These mutations are associated, in our population, with the same haplotypes as those with which it is associated in Europe. Based on the above-mentioned genetic model for non-PKU HPA, successful prenatal diagnosis of this condition was performed in one family.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

A single origin of phenylketonuria in Yemenite Jews.

Phenylketonuria (PKU) is a metabolic disease caused by recessive mutations of the gene encoding the hepatic enzyme phenylalanine hydroxylase (PAH). The incidence of PKU varies widely across different geographic areas, and is highest (about 1 in 5,000 live births) in Ireland and western Scotland, and among Yemenite Jews. A limited number of point mutations account for most of the PKU cases in the European population. Here we report that a single molecular defect--a deletion spanning the third exon of the PAH gene--is responsible for all the PKU cases among the Yemenite Jews. Examination of a random sample of Yemenite Jews using a molecular probe that detects the carriers of this deletion indicated a high frequency of the defective gene in this community. Although the deleted PAH gene was traced to 25 different locations throughout Yemen, family histories and official documents of the Yemenite Jewish community showed that the common ancestor of all the carriers of this genetic defect lived in San'a, the capital of Yemen, before the eighteenth century.

Alleles↗
PubMed1990

Increased calcium permeability is not responsible for the rapid lethal effects of amphotericin B on Leishmania sp.

The mode of action of the polyene antibiotic amphotericin B (AmB), the drug of choice for the treatment of systemic fungal infections and visceral leishmaniasis, is still unclear. An increase in intracellular Ca2+ concentration [( Ca2+]i), toxic in many cases, has been postulated as a possible lethal mechanism for AmB. Cell permeabilization to ethidium bromide (EB) was used as a criterion of viability. Kinetics of the DNA-EB fluorescent complex formation was studied in ergosterol-containing Leishmania promastigotes. Intracellular Ca2+ concentration was measured using quin-2 fluorescence in parallel aliquots. It is shown in this work that AmB can act as an efficient Ca2+ ionophore. However, the rapid permeabilization effect induced by AmB on these cells was not dependent on an increase in [Ca2+]i. On the contrary, it was found that leishmanicidal effect of AmB was enhanced in the absence of external calcium. Furthermore, A23187 a Ca2+ ionophore did not provoke cell permeabilization to EB.

Amphotericin B↗
PubMed1990

Laser-assisted microsurgical anastomoses in traumatized blood vessels.

Technological advances have made CO2 laser-assisted microvascular anastomoses (LAMA) feasible. This study seeks to compare results of LAMA versus CSMA (conventional suture microsurgical anastomosis) in traumatized vessels. Using a rat model, femoral arteries and veins were either crushed and transected or divided by avulsion and then repaired by either LAMA or CSMA. LAMA resulted in higher patency rates than CSMA at early postoperative observation periods. With time, the patency rates improved in both groups and, by the end of the study, the patency rates were equivalent. These findings indicate that the laser technique may be a better option when working with traumatized vessels because of the critical nature of early patency rates. The improved results may be due to a reduction of suture material at the anastomotic site when using the laser technique. Some physiologic aspects of vessel thrombosis, recanalization, and the role of collateral circulation are discussed.

Anastomosis, Surgical↗
PubMed1990

Enhanced action of amphotericin B on Leishmania mexicana resulting from heat transformation.

A comparative study of the effect of the polyene antibiotic amphotericin B (AmB) on the viability of Leishmania mexicana promastigotes before and after their transformation by heat into amastigotelike forms was carried out. The kinetics of cell death were followed by spectrofluorometry with the nucleic acid-binding compound ethidium bromide. It was found that the rapid killing effect that is exerted by AmB on Leishmania promastigotes was even faster after their transformation into amastigotelike forms. Binding studies of AmB to Leishmania membranes by circular dichroism indicated that heat transformation modified it from noncooperative to cooperative binding, decreasing the amount of antibiotic that bound to the membranes. Thus, the increased rate of ethidium bromide incorporation into transformed cells was not related either to the amount of AmB bound or to an increased amount of ergosterol in the membrane (the ergosterol/phospholipid ratio was four times smaller after heat shock). An increase in the Mg2+ content of the external aqueous solution was able to prevent the AmB-induced incorporation of ethidium bromide into Leishmania promastigotes to a greater extent (Ki = 13.8 mM) than it was into heat-transformed cells (Ki = 64 mM), suggesting that there were significant changes at the Leishmania cell surface on heat transformation. The significance of these results for understanding the mechanism of action of AmB on sensitive organisms is discussed.

Amphotericin B↗