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Biomedical subjects

M Sobel

Publications and source records attributed to M Sobel.

At least 55 records · Page 3Linked to original sources
PubMed1994

Objective tinnitus in patients with atherosclerotic carotid artery disease.

Atherosclerotic carotid artery disease (ACAD) as a cause of objective-pulsatile tinnitus has not been adequately addressed in the literature. This report presents the authors' experience in 12 patients with pulsatile tinnitus arising from ACAD. Ipsilateral carotid bruit was detected in all patients and objective tinnitus was present in eight cases. The intensity of the carotid bruit was louder than the objective tinnitus in all patients. Carotid artery stenosis was confirmed in all patients with noninvasive vascular flow mapping. Atherosclerotic carotid artery disease should be highly suspected in patients with pulsatile-objective tinnitus who are older than 50 years and have associated cardiovascular risk factors. Pulsatile tinnitus in these patients can be the first manifestation of ACAD. Duplex ultrasound study of the carotid arteries can confirm the diagnosis. Consultation with a vascular surgeon is essential in selected cases.

Aged↗
PubMed1993

Heparin-von Willebrand factor binding as assessed by isothermal titration calorimetry and by affinity fractionation of heparins using synthetic peptides.

The ability of proteins to bind heparin, a heterogeneous sulfated glycosaminoglycan, likely depends on the conformational uniqueness of specific binding domains. Based on the motif of a consensus heparin-binding synthetic peptide, a 23-residue sequence (Y565-A587) of human von Willebrand factor (vWF) was previously identified which binds heparin with affinity comparable to that of the native protein (Sobel, M., Soler, D. F., Kermode, J. C., and Harris, R. B. 1992 J. Biol. Chem. 267, 8857-8862). This peptide undergoes a conformational change upon binding heparin. Isothermal titration calorimetry has now been used to further quantify this binding reaction. In experiments done at 25 degrees C, Y565-A587 bound heparin with about the same affinity (Kd = 9.0 x 10(-7) M) as a "core" sequence peptide encompassing residues K569-I580. Binding between these peptides and heparin is overwhelmingly enthalpically favored and is dependent on the formation of productive electrostatic bonds; hydrophobic interactions do not play a significant role in mediating binding. Furthermore, when immobilized on Sepharose in a manner which does not compromise essential cationic residues, the vWF domain peptides are effective affinity ligands. They bind a species of heparin which possesses significantly enhanced affinity for native vWF. The Kd for binding between the high-affinity heparin and Y565-A587 is about threefold lower than that determined with crude, unfractionated heparin. Thus, the vWF peptides are a useful model for studying the physiological role of heparin binding to the native protein.

Amino Acid Sequence↗
PubMed1993

Structural characterization of heparin's binding domain for human platelets.

The structural features of heparin that are involved in binding to human platelets were investigated by a competitive binding approach. A range of heparin-derived glycosaminoglycans (GAGs) with relatively defined structure were prepared by different methods of depolymerization of pharmaceutical heparin, followed by fractionation according to molecular weight and net charge. Competitive binding to platelets was dependent on molecular weight but not on the net charge of the GAGs. The method for depolymerization significantly affected the binding activity of the resulting GAG. Heparinase I and nitrous acid depolymerization produced GAGs with lower binding affinity for platelets than those GAGs derived from the treatment with periodate followed by alkali. The IC20 (concentration producing 20% inhibition of binding) was 0.05 microM for unfractionated heparin, 0.11 microM for a periodate treated GAG, and 2 microM for comparably sized GAGs (M(r) approximately 6,000-8,000) derived by heparinase I or nitrous acid treatment. Thus, the disaccharide units GlcNSO3-6S--IdoA-2S or GlcNSO3--IdoA-2S [(2-deoxy-2-sulfoamido-6-O-sulfo-alpha-D-glycopyranosyl)-(1- 4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic acid) or (2-deoxy-2-sulfoamido-alpha-D-glycopyranosyl)-(1-4)-O-(2-O-s ulfo-alpha-L-idopyranosyluronic acid)] may be crucial elements for binding to the platelet, because these are known to be preserved during periodate/alkali treatment, but readily decomposed by heparinase I and nitrous acid. Understanding this structural specificity for platelet binding may be useful for the development of heparins with high or low platelet reactivity.

Binding Sites↗
PubMed1993

Acute exacerbation of carpal tunnel syndrome after radial artery cannulation.

Acute carpal tunnel syndrome that follows radial artery cannulation has been described. To determine the incidence and predisposing factors, we prospectively studied 151 patients who had perioperative radial artery cannulation. Postoperatively 9 of the 151 patients had symptoms of carpal tunnel syndrome with positive Phalen and Tinel signs on the side on which the radial artery catheter had been inserted. Eight of 12 patients with a prior history of carpal tunnel syndrome had acute exacerbation of symptoms postoperatively. By contrast, only 1 of 139 patients with no prior history of the disorder had symptoms. Fourteen patients had multiple arterial artery punctures or perforations of the posterior wall of the radial artery. In three of these, postoperative symptoms of carpal tunnel syndrome developed but did not reach statistical significance. The only patient with postoperative acute carpal tunnel syndrome but no prior history of the syndrome had multiple arterial punctures. The use of perioperative anticoagulation, the use of wrist-extension splints, and the duration of radial artery cannulation did not influence acute exacerbation of carpal tunnel syndrome. Patients with a prior history of carpal tunnel syndrome are at increased risk of recurrent symptoms after radial artery cannulation. We found no statistically significant relationship between traumatic cannulations and the development of symptoms of carpal tunnel syndrome.

Acute Disease↗
PubMed1993

Microvasculature of the tibialis anterior tendon.

Subcutaneous rupture of the tibialis anterior tendon is an uncommon condition for which the etiology is unclear. The existence of a hypovascular zone has been proposed as an etiology for rupture of the tibialis anterior tendon. To investigate this possibility, the microvascular anatomy of the tibialis anterior tendon was studied using a modified Spalteholz technique. The vascular supply to the tibialis anterior tendon arises from proximal and distal ventral vinculae. Muscular branches of the anterior tibial artery, proximally, and the medial tarsal arteries, distally, form an intratendinous, longitudinal, competent blood supply. The tendon also receives a rich vascular blood supply from the synovial sheath. The blood supply appears adequate throughout the course of the tibialis anterior tendon, and no hypovascular region was noted at the common site of rupture 1 to 3 cm proximal to its insertion. No relationship was noted between increasing age and alteration in blood supply.

Adolescent↗
PubMed1993

A comparative study of heparin responses in arterial and venous thromboembolism using molecular markers for thrombosis.

BACKGROUND: Compared with the therapy of venous thromboembolism, there is little consensus regarding guidelines for heparin anticoagulation of patients with arterial thrombosis. This study aimed to identify the quantitative differences in the activation of the coagulation cascade and platelets in these two syndromes and to characterize their specific biological responses to heparin therapy. METHODS AND RESULTS: Eighteen patients receiving intravenous heparin to treat venous (n = 9) or arterial (n = 9) thromboembolism were prospectively studied for an average of 4 days each. Clinical responses to treatment, activated partial thromboplastin time (aPTT), and molecular markers for thrombosis were measured regularly. Although both groups received equivalent doses of heparin (approximately 1100 units/h), the resulting aPTTs and plasma heparin activity were significantly lower in the arterial patients (P < .05 and P < .01, respectively). The plasma levels of beta-thromboglobulin (a marker for platelet activation and granule release) were significantly higher in the arterial patients (109 +/- 9.5 versus 79 +/- 7.1 ng/mL, mean +/- SEM, P < .05). In vivo fibrin formation, as evidenced by plasma levels of fibrinopeptide A, was less effectively suppressed in the patients with arterial versus venous thrombosis (18.5 +/- 3.2 versus 10.4 +/- 2 ng/mL, P < .05). Prothrombin fragments 1 + 2, a marker for prothrombinase complex activity, was nearly normal in both heparinized groups. CONCLUSIONS: The anticoagulant response to heparin is blunted in patients with arterial thrombosis, at least in part by the antagonistic actions of increased platelet activation. Comparing arterial with venous thrombosis, higher doses of heparin on the average may be required to achieve comparable aPTTs, plasma heparin activity, and comparable suppression of fibrin formation.

Aged↗
PubMed1993

Chronic ankle instability as a cause of peroneal tendon injury.

Chronic lateral ankle pain and instability can be associated with a split in the peroneus brevis tendon. This case reports a peroneus brevis split that was centered over the sharp posterior edge of the fibula and was associated with laxity of the superior peroneal retinaculum, and chronic ankle instability. The mechanism of the split was easily demonstrated during surgery by everting the foot and pulling longitudinally on the peroneus longus tendon. The interrelationship of lateral ankle instability with superior retinacular laxity and resultant peroneus brevis splits can account for posttraumatic lateral ankle pain. Surgical treatment must identify and correct the underlying pathology and should attempt to repair or debride the peroneus brevis tendon, reconstruct the superior peroneal retinaculum, flatten the posterior edge of the fibula by removing the sharp bony prominence, and address any associated lateral ankle instability with either a modified Chrisman-Snook, Anderson, or modified Brostrom-Gould procedure.

Adult↗
PubMed1992

Design and synthesis of a helix heparin-binding peptide.

Elaboration of heparin-protein-binding interactions is necessary to understand how heparin modulates protein function. The heparin-binding domain of some proteins is postulated to be a helix structure which presents a surface of high positive charge density. Thus, a synthetic 19-residue peptide designed to be alpha-helical in character was synthesized, and its interaction with heparin was studied. The peptide was shown to be 75% helix by circular dichroism (CD) spectrometry in neutral pH buffer (at 2 degrees C); helicity increased to nearly 85% under high ionic strength conditions or to nearly 100% in 75% ethanol. Increasing the temperature of the solution caused a change in the spectral envelope consistent with a coil transition of the peptide. The midpoint of the transition (i.e., the temperature at which the helix content was determined to be 50%) was 25 degrees C, and the determined van't Hoff enthalpy change (delta HvH) was 3.2 kcal/mol of peptide. By CD, heparin increases the helix content of the peptide to 100% and increases the apparent thermal stability of the peptide by about 1 kcal/mol. The melting point for the helix/coil transition of the heparin-peptide complex was 50 degrees C. The thermal coefficient of the transition (approximately 300 deg.cm2.dmol-1.degree C-1) was essentially the same for the peptide alone or the peptide-heparin complex. Dissociation of the complex under high ionic strength conditions was also observed in the CD experiment. Biological assays showed less heparin-binding activity than expected (micromolar KD values), but this was attributed to the absence of critical lysyl residues in the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Localization and characterization of a heparin binding domain peptide of human von Willebrand factor.

Human von Willebrand factor, a plasma glycoprotein which plays a critical role in regulating hemostasis, binds heparin, but the physiological importance and mode of this interaction is poorly understood. Using the motif of an amino acid sequence of a consensus heparin binding synthetic peptide, a 23-residue sequence (Tyr565-Ala587) of human von Willebrand factor was identified that retains the consensus motif and binds heparin with affinity comparable with native von Willebrand factor and the consensus peptide. In a fluid phase binding assay, the Tyr565-Ala587 peptide competed effectively with von Willebrand factor for binding heparin. Synthesis and testing of peptides overlapping Tyr565-Ala587, as well as adjacent cationic regions, showed this core sequence to be the optimal linear binding domain. Far ultraviolet circular dichroism spectrometry of the Tyr565-Ala587 peptide suggested that the peptide undergoes conformational change upon binding heparin. The Tyr565-Ala587 peptide thus encompasses part (or all) of a functionally important heparin binding domain of von Willebrand factor. Further study of this and related peptides may be useful for exploring how heparin may influence von Willebrand factor-mediated platelet hemostasis.

Amino Acid Sequence↗
PubMed1992

Measuring and managing quality of surgery. Statistical vs incidental approaches.

New rules for quality assurance provoked a comparison of effects of two approaches used concurrently for 14 years. In an incidental approach, a multidisciplinary conference reviewed all postoperative complications as they occurred and attributed each to one of six causes. Remedies were instituted and data were filed. In a statistical approach, death and complication rates were computed annually and compared with previous years' rates and with rates reported to Congress as national norms. Statistics suggested acceptable quality in each specialty but calculations were tedious and differences achieved significance too rarely or too slowly to identify problems, protect patients, and improve care. The incidental approach was popular and produced immediate improvements in patient care. Conferees attributed one half of complications to errors. Frequent acknowledgment of susceptibility to error may contribute to the safety and quality shown by our statistics.

Humans↗
PubMed1992

Late results of suprarenal Greenfield vena cava filter placement.

Placement of the Greenfield filter above the renal veins was necessary in 71 (9%) of 821 total patients in the filter registries of two institutions. The status of 60 patients (85%) could be verified, with follow-up data ranging from 18 months to 16 years (average, 53 months). Of 24 deaths (34%), none was from recurrent embolism or renal failure; death was most commonly associated with a malignant neoplasm. The recurrent embolism rate was 4%, identical to the infrarenal experience. Duplex evaluation of the filters in 22 patients, representing the majority (61%) of living patients, showed that all the filters were patent. Sixteen patients (41%) had lower-extremity edema that predated filter insertion, and in no patient did the results of noninvasive venous studies worsen. Filter fracture (two patients) or distal migration (two patients) had no clinical sequelae, and there was no evidence of renal dysfunction. For thrombus extending to the level of the renal veins or within them and for pregnant patients or women of childbearing age, suprarenal placement of the Greenfield filter is safe and effective, with no filter obstruction seen in follow-up extending to 16 years.

Adolescent↗
PubMed1992

Custom total shoulder arthroplasty in inflammatory arthritis. Preliminary results.

Twenty-three patients with inflammatory arthritis and rotator cuff deficiency have undergone 27 custom-fit total shoulder arthroplasties. The design used included a short-stem humeral component and a metal-backed glenoid component with an offset keel. The glenoid component was custom-fit to provide maximum coverage of the glenoid surface. The average age of the patients at the time of surgery was 55 years (range, 20-75 years). All patients had inflammatory arthritis, 16 were on steroids, and all had some degree of rotator cuff involvement ranging from small to complete tears. The average length of follow-up study was 5 years (range, 3-7 years). The average preoperative shoulder score was 36 points (range, 15-50 points) with an average pain score of 7 (of 30) points. Postoperatively, the shoulder score improved to 85 points with a pain score of 28 points. Twenty-one shoulders scored a good to excellent result. Two patients required reoperation, both for recurrent rotator cuff tears, one of which occurred after a fall. Radiographic analysis revealed no incidence of humeral radiolucency and six cases of glenoid radiolucency. Only two of these were progressive and both were associated with irreparable rotator cuff tears. Thus, in the early follow-up, this design of glenoid has decreased the incidence of glenoid radiolucency in this difficult patient population.

Adult↗
PubMed1992

Brachial plexus injury caused by impalement.

Open injuries of the brachial plexus are rare. One such case, that of a 68-year-old impaled on a fence spike, is presented here. Certain principles to guide evaluation and treatment are discussed. Concomitant injury to the pleura or to vascular structures requires immediate attention; the extent and type of plexus damage may be determined from physical findings and the nature of injury. The results of plexus reconstruction are variable and routine exploration may be detrimental. The Brooks classification is reviewed.

Aged↗
PubMed1992

Collateral ligament reconstruction of the unstable metatarsophalangeal joint: an in vitro study.

Anatomic reconstruction of the collateral ligaments of the lesser metatarsophalangeal joints is proposed for certain cases of metatarsophalangeal instability. The suggested reconstruction involves replication of the attachments of the collateral ligaments. As an example of such a reconstruction, the interosseous tendon was used in this study as a graft for anatomic replacement of the collateral ligaments. The tendon was left attached distally where its attachments include the volar plate and proximal phalanx, thereby resembling the distal attachment of the collateral ligament. The proximal portion of the tendon was inserted into the metatarsal head, replicating the attachment of the collateral ligament at that location. Preliminary testing of such a reconstruction shows that it can re-establish stability caused by loss of the collateral ligaments. Such a procedure may be applicable in select cases of crossover toe deformity and straight vertical instability.

Humans↗
PubMed1992

The dynamics of peroneus brevis tendon splits: a proposed mechanism, technique of diagnosis, and classification of injury.

The etiology of peroneus brevis splits is unclear. Because longitudinal splits in the peroneus brevis tendon do not necessarily effect the integrity or strength of the tendon, it is difficult to ascertain whether or not injury to the peroneus brevis tendon is present. Recent clinical, anatomic, and histologic reports have suggested that the split develops from prolonged mechanical attrition within the fibular groove as a result of ankle trauma with resultant lateral ankle instability and incompetency of the superior peroneal retinaculum with resultant subluxation of the peroneal tendons. This cascade of events may result in splitting of the peroneus brevis tendon. The purpose of this paper was to report the investigation of the mechanism by which peroneus brevis splits develop, to describe a technique of diagnosis, and to propose a classification of injury. Peroneus brevis splits are the result of a dynamic mechanical insult at the fibular groove. Laxity of the superior peroneal retinaculum combined with peroneus longus mechanical compression causes the peroneus brevis to splay out and eventually split over the sharp posterior edge of the fibula. Anatomic factors, such as a shallow fibular groove (congenital convex groove) or the presence of an anomalous low-lying peroneus brevis muscle belly or peroneus quartus tendon, may also play a role in this mechanism by interfering with the competence of the superior peroneal retinaculum.

Adult↗
PubMed1992

Microvascular anatomy of the peroneal tendons.

The etiology of longitudinal splitting of the peroneus brevis tendon is unclear. It has been hypothesized that compressive load applied to the tendon as it passes through the fibular groove may compromise the vascularity of the tendon with resultant inhibition of the repair response and degeneration of tendon structure. To investigate this possibility, a study of the microvascularity of the peroneal tendons was undertaken. Twelve fresh, frozen cadaveric limbs were injected with India ink. The vascularity of the peroneal tendons was examined in situ and the tendons were harvested and cleared using a modified Spalteholz technique. The vascularity of the cleared tendons was evaluated utilizing a dissecting microscope. The vascular supply of the peroneal tendons arises from two posterolateral vincula, one for the peroneus longus tendon and one for the peroneus brevis tendon. These vincula are supplied by branches of the posterior peroneal artery. A zone of hypovascularity within the peroneus brevis or peroneus longus tendon correlating with the site of peroneus brevis splits was not found. There was no relationship between increasing age of specimens and alteration in vascular supply.

Adolescent↗