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Biomedical subjects

R Kluger

Publications and source records attributed to R Kluger.

At least 19 recordsLinked to original sources
PubMed2007

Influence of high tibial osteotomy on bone marrow edema in the knee.

To determine the influence of high tibial osteotomy on subchondral bone marrow edema in medial osteoarthritis of the varus knee, full leg-length radiographs and magnetic resonance imaging were performed in 20 patients (20 knees) before surgery, 1 year postoperatively, and at a mean of 7 years postoperatively. The extent of bone marrow edema in the medial compartment was quantified with magnetic resonance imaging in two planes using the formula for a prolate ellipsoid as follows: length x width x depth x pi/6. We used the Japanese Orthopaedic Association knee score for clinical evaluation. At the last followup, all knees with valgus alignment (10/10) showed reduced edema. In contrast, bone marrow edema increased or remained unchanged in four of 10 knees with neutral or varus alignment. The percentage of satisfactory results was 100% (10/10) in valgus knees and only 30% (3/10) in neutral or varus knees. Extent of bone marrow edema at the followup correlated with the mechanical axis and knee score. Because of the prognostic value of bone marrow abnormalities in the medial compartment observed on magnetic resonance imaging, early lateral closing wedge osteotomy should be considered in patients with varus malalignment and bone marrow edema even in mild cases of medial osteoarthritis.

Adult↗
PubMed2006

10,000 reasons to step out--exercise patterns and pedometer evaluation of consultant anaesthetists.

Major international bodies recommend that adults should accumulate at least 30 minutes of moderate intensity physical activity every day. Ten thousand steps a day has been found to approximate 30 minutes of exercise. A questionnaire regarding exercise patterns was sent to all (584) Victorian consultant anaesthetists, and 30 consultants wore a pedometer for one week, during working hours only. The questionnaire response rate was 59.4% (347). Of these respondents, 58% indicated that they had a formal exercise program. There were no significant differences between people with a set exercise program and those without, with respect to age, gender, working hours or smoking. Those with a set exercise program exercised a median of four times per week and the commonest exercise listed was gymnasium attendance (40%). The main reasons cited for having a regular exercise program were maintenance of physical health (77%), mental health (71%) and weight control (35%). The main reasons for not having an exercise program were fatigue (40%), too busy (70%), family commitments (67%) or just not interested (18%). The overall median steps per day for the pedometer group was 4770 with a range of 1667 to 9630, fitting into the classification of 'sedentary'. In summary this study has shown that a significant number of anaesthetists do not achieve adequate physical activity in or out of working hours and has identified some reasons for this behaviour. This will hopefully provide motivation and information for the implementation of useful strategies to increase the level of physical activity performed by anaesthetists.

Adult↗
PubMed2003

Removal of the surface layers of human cortical bone allografts restores in vitro osteoclast function reduced by processing and frozen storage.

A major complication of cortical bone grafting is nonunion at the host-graft junction. Many factors are thought to be involved in successful engraftment including the quality of the graft and the host response to it. In particular, the recipient osteoclasts (OCs) play a critical role by resorbing the engrafted bone. Thus, effective engraftment may depend on the inherent biological properties of the bone graft, which subsequently correlates with early and effective OC resorption. Normally, bone grafts are stored and processed by freezing, freeze-drying, irradiation, and lipid extraction. We sought to determine whether processing and storage affected bone quality, as evaluated by OC bone resorption. Cortical bone specimens from six human donors were either fresh, frozen at -75 degrees C, or had undergone combinations of freezing at -75 degrees C, freeze-drying, lipid extraction, irradiation, and treatment with hydrogen peroxide. Bone slices of 0.5-mm thickness taken from the surface, beneath the surface, and at a depth of 7.5 mm were incubated with isolated rabbit OCs and resorption lacunae were measured. We observed highest OC activity with fresh bone followed by frozen, partially processed, and fully processed bone. When allografts were stored at -75 degrees C for 12 months, there was up to a 4.2-fold reduction in OC activity on the surface layer. Additionally, we found reduced OC activity upon the outer surface bone compared to the inner layers. Removal of more than 0.5 mm of frozen and processed bone significantly improved OC activity. These results imply that inner bone layers of stored and processed bone allografts are protected against degradation of bone matrix components, except when frozen for extended periods of time. Taken together, these data suggest that bone allografts should be stored for less than 1 year and require the removal of at least 0.5 mm from their surface prior to transplantation.

Animals↗
PubMed2000

Decomposition of 2-(1-hydroxybenzyl)thiamin. Ruling out stepwise cationic fragmentation.

[reaction: see text] The rapid fragmentation of 2-(1-hydroxybenzyl)thiamin (1) is initiated by transfer of a proton from C2alpha to give an enamine. The subsequent irreversible process can be written as a concerted (or stepwise) rearrangement involving migration of the hydroxyl hydrogen to the methylene bridge. An attractive alternative is internal addition of C2alpha to the pyrimidine, generating a carbocation. However, addition of azide to the reaction solution, which could trap the carbocation, has no effect on the rate or products of reaction.

Azides↗
PubMed2000

Mechanism of site-directed protein cross-linking. protein-directed selectivity in reactions of hemoglobin with aryl trimesates.

Site-directed cross-linking of hemoglobin has become an efficient way to produce a structurally defined altered protein with desirable functional properties. The reagent trimesoyl tris(3, 5-dibromosalicylate) (1) introduces a bis amide cross-link derived from the epsilon-amino groups of the side chains of the two beta-Lys-82 residues in human hemoglobin. The basis of its specificity was investigated using a set of analogues of 1 (2-12). There are marked differences in the reaction patterns of these compounds with amino groups in hemoglobin compared to reactions with n-propylamine. The compounds that effectively modify the protein contain a carboxyl group ortho to the phenolic oxygen of the ester, while materials with meta or para carboxyl groups give little or no reaction. In contrast, the reactions with n-propylamine are slowest with the ortho carboxyl materials. Addition of the unreactive compound 5 to a solution containing hemoglobin reduces the ability of 1 to modify the protein, showing that the unreactive compound binds but does not react. On the basis of these observations and the known reaction patterns of salicylates, it is clear that the environment in the protein controls the reaction, regardless of the inherent reactivity of the reagent. We propose that the carboxyl group positions the reagent critically within the protein. Only the ortho arrangement permits transfer of the acyl function to the nucleophile.

Chromatography, High Pressure Liquid↗
PubMed2000

Acute laryngeal oedema and the yellow nail syndrome.

A complication of yellow nail syndrome after pleurodesis is presented. After endotracheal extubation the patient developed delayed acute laryngeal oedema requiring re-intubation. We postulate that the combination of lymphatic defect and airway trauma from the double lumen endotracheal tube were contributory to the oedema. If endotracheal intubation is performed, these patients should be observed for 48 h.

Journal Article↗
PubMed2000

Elevated levels of lipoprotein(a) in familial bone marrow edema syndrome of the hip.

There is controversy whether bone marrow edema syndrome represents a distinct transient disease or reflects an early reversible phase of spontaneous osteonecrosis of the hip. Hypofibrinolysis on the basis of elevated plasma levels of plasminogen activator inhibitor or lipoprotein(a) or both has been reported to favor the development of bone marrow edema syndrome and nontraumatic avascular necrosis. The current authors report on the familial occurrence of transient bone marrow edema syndrome of the hip in three female family members. Plasma concentrations of lipoprotein(a) were elevated in all three patients, whereas serum levels of plasminogen activator inhibitor were within normal ranges. This first familial description of transient bone marrow edema syndrome of the hip strongly suggests that a genetically determined elevation of lipoprotein(a) may be an important predisposing factor in these patients.

Adult↗
PubMed1999

[Years of training: a new risk factor in acute badminton injuries].

The incidence of badminton injuries is low compared with other sports, but acute injuries are generally more severe. Little is known about the risk of competitive badminton players to get an acute badminton injury. The purpose of this study was to define for the first time "years of playing badminton on a competitive level" as a risk factor for acute badminton injuries. 179 badminton injuries of 102 Austrian competitive badminton players, some of them being elite players in the european championships, were retrospectively registered. The years 1993, 1994 and 1995 were covered by our investigation. Injury incidences were defined as injuries/1000 h and were calculated separately for the 0. through the 21st year of competitive badminton. The incidence of acute badminton injuries increased constantly from the 0 to the 7th year of competitive badminton. The 6th and 7th year of competitive badminton showed a threefold increased incidence of acute badminton injuries when compared with the first year and the late years of the career as a competitive badminton player. We found no correlation between the incidence of acute badminton injuries and age, gender, hours played per year or time of warming up. We conclude that players being engaged in competitive badminton for 5 to 8 years represent a high risk population for acute badminton injuries. In contrast players at the beginning and towards the end of the competitive career showed a markedly lower risk for acute badminton injuries. We recommend additional training efforts concerning technical skills and endurance as well as proper rehabilitation of sports injuries for the high risk group of badminton players.

Adolescent↗
PubMed1998

Effect of modifying O2 diffusivity and delivery on glomerular and tubular function in hypoxic perfused kidney.

Is O2 diffusivity within renal capillaries rate limiting for O2 delivery to hypoxic renal tubules? Equations based on diffusion theory and developed here predict that soluble hemoglobin (Hb) increases O2 diffusivity by a factor of 1 + [442 Hb%/(P50 + PO2)], where P50 is the partial pressure of O2 at which the Hb is half saturated. To examine the effect of P50 and Hb concentrations on renal function, we perfused isolated rat kidneys with Hb-P35 (P50 = 35 mmHg) and Hb-P11 (P50 = 11 mmHg). Venous PO2 was lower with Hb-P11 (10 +/- 1 vs 16 +/- 1 mmHg with arterial PO2 = 35 mmHg and 28 +/- 2 vs. 40 +/- 2 mmHg with arterial PO2 = 140 mmHg; P < 0.001). Perfusate P50 did not influence vascular resistance, glomerular filtration rate, O2 consumption, Na reabsorption, protein excretion, or free water clearance. Percent glucose and phosphate excretion were lower with Hb-P11 than with Hb-P35 (P < 0.001). Urine glucose was 0.17 mmol/l with Hb-P11 and 0.77 mmol/l with Hb-P35 (P < 0.001). Hb-P35 (2%) doubled O2 delivery and lowered glucose and phosphate excretion to the level obtained with 1% Hb-P11. Thus Hb-P11 delivered O2 twice as effectively as Hb-P35 to high-affinity sodium glucose and phosphate cotransporters in the late proximal tubule (S3 segment). Hb-P11 may also have shunted O2 from the outer cortex to the outer medulla and facilitated O2 diffusion where PO2 was low. We conclude that diffusivity is a limiting factor in delivery of O2 to hypoxic tubules.

Animals↗
PubMed1998

Intraoperative transoesophageal echocardiography: impact on adult cardiac surgery.

Although multiple case reports have demonstrated the capability of transoesophageal echocardiography (TOE) to detect unsuspected cardiac pathology with important therapeutic implications, few studies have examined the effect of real-time interpretation of routine TOE on clinical management of a typical series of cardiac surgery patients. To assess the impact of intraoperative TOE on cardiac surgical management, we conducted a prospective observational study on 238 consecutive patients undergoing intraoperative TOE during adult cardiac surgery. Potentially important new diagnostic information was detected in 39 of 184 (21%) routine and in 53 of 54 requested TOE examinations, and led directly to different surgical procedures in 11 of 184 (6%) routine and in 12 of 54 (22%) requested TOE examinations. Our data suggests that intraoperative TOE may be a valuable tool in the routine management of adult cardiac surgical patients.

Adult↗
PubMed1997

Allosteric intermediates indicate R2 is the liganded hemoglobin end state.

Hemoglobin has been a long-standing paradigm for understanding protein allostery. Here, the x-ray structures of two chemically crosslinked, fully liganded hemoglobins, alpha2beta82CA82beta and alpha2beta82ND82beta, are described at 2.3 A and 2.6 A resolution, respectively. Strikingly, these crosslinked hemoglobins assume intermediate conformations that lie between those of R and the controversial liganded hemoglobin state R2 rather than between R and T. Thus, these structures support only a T left and right arrow R left and right arrow R2 allosteric pathway and underscore the physiological importance of the R2 conformation.

Allosteric Regulation↗
PubMed1996

A doubly cross-linked human hemoglobin. Effects of cross-links between different subunits.

Human deoxyhemoglobin cross-linked with trimesyl tris(3,5-dibromosalicylate) produces the previously reported cross-linked hemoglobin in which the epsilon amino groups of the two beta chain 82 lysyl residues are joined by a trimesyl bridge. Further specific modification of this protein directed to the alpha subunits with bis(3,5-dibromosalicyl)fumarate gives a doubly cross-linked material in which the epsilon-amino groups of the two alpha chain 99 lysyl residues are now joined by a fumaryl bridge. The singly cross-linked beta chain species binds oxygen cooperatively with a high oxygen affinity (P50 = 4.8 torr at pH 7.4). The addition of the second cross-linking reduces the oxygen affinity to 15.9 torr, which compares with 13.0 torr for the singly cross-linked alpha chain species. The doubly cross-linked hemoglobin retains significant cooperativity with a Hill coefficient of 2.3 compared with 3.0 for unmodified hemoglobin. Because some of the groups responsible for the Bohr effect are acylated, this doubly cross-linked hemoglobin exhibits 25% of the normal Bohr effect and less than 20% of the normal chloride effect. The use of two distinct cross-links within the same tetramer provides a material for physical and structural analysis as well as for further modifications for specific applications. The results indicate that the cross-link introducing the lowest oxygen affinity in the two singly cross-linked species appears to control the overall affinity in this doubly cross-linked species.

Hemoglobins↗
PubMed1996

Automated ST-segment analysis during cesarean delivery: effects of ECG filtering modality.

STUDY OBJECTIVES: To determine the effect of different electrocardiographic (ECG) filtering modalities on ST-segment changes during cesarean delivery. We compared the use of narrow and standard bandwidth ECG filtering modes in assessing ECG-detected ischemic changes in healthy patients undergoing routine, elective cesarean delivery. DESIGN: Prospective, nonrandomized clinical trial. SETTING: Academic medical center. PATIENTS: 20 healthy parturients undergoing elective cesarean delivery with regional anesthesia. INTERVENTION: Continuous 5-lead ECG monitoring was performed in all 20 study parturients. The same incoming ECG signal was divided by a special cable and displayed on two Marquette 7010 monitors. Leads I, II, and V5 were analyzed. One of the monitors filtered the signal with a 0.07 to 100 Hz filter (DIAG), the other with a 0.3 to 40 Hz filter (MON). The ST segment was analyzed continuously by electronic comparison with a template established as a baseline at the beginning of the case. This continuous output was led in digital form every 15 seconds to an IBM PC computer for data analysis. MEASUREMENTS AND MAIN RESULTS: In each of the leads analyzed, the mean MON versus DIAG different showed a bias, with MON showing consistently lower (ie, more negative) readings than DIAG. Using different criteria for ST depression (> 0.25, > 0.5, or > 1.0mm), we categorized patients as showing more ST depression on either MON or DIAG. With the 0.25 mm criterion, ST depression was identified significantly more often in MON then DIAG in leads H and V5 (p < 0.05). Using the other criteria, the differences were similar, but were not statistically significant. In general, very few instances of ST depression were identified in lead I. No patient had sequelae indicative of intraoperative myocardial ischemia, such as chest pain, dyspnea, persistent ectopy, or hemodynamic instability. CONCLUSIONS: In patients at low risk for myocardial ischemia, narrow bandwidth (monitor mode) ECG filtering reveals greater degrees of ST-segment depression than does standard (diagnostic mode) ECG filtering. Studies examining ST-segment phenomena would be facilitated by including a description of the ECG filtering-technique.

Angina Pectoris↗
PubMed1995

Allosteric transition intermediates modelled by crosslinked haemoglobins.

The structural end-points of haemoglobin's transition from its low-oxygen-affinity (T) to high-oxygen-affinity (R) state, have been well established by X-ray crystallography, but short-lived intermediates have proved less amenable to X-ray studies. Here we use chemical crosslinking to fix these intermediates for structural characterization. We describe the X-ray structures of three haemoglobins, alpha 2 beta 1S82 beta, alpha 2 beta 1Tm82 beta and alpha 2 beta 1,82Tm82 beta, which were crosslinked between the amino groups of residues beta Val1 and beta Lys82 by 3,3'-stilbenedicarboxylic acid (S) or trimesic acid (Tm) while in the deoxy state, and saturated with carbon monoxide before crystallization. alpha 2 beta 1S82 beta, which has almost normal oxygen affinity, is completely in the R-state conformation; however, alpha 2 beta 1Tm82 beta and alpha 2 beta 1,82Tm82 beta, both of which have low oxygen affinity, have been prevented from completing their transition into the R state and display many features of a transitional intermediate. These haemoglobins therefore represent a snapshot of the nascent R state.

Allosteric Regulation↗
PubMed1995

Influence of jet direction on pulmonary vein flow patterns in severe mitral regurgitation.

Pulmonary vein flow patterns measured with transesophageal echocardiography have been used recently to assess the severity of mitral valve regurgitation. This study was designed to determine whether regurgitant jet direction selectively influences the pattern of flow in right and left pulmonary veins. Thirty-seven patients undergoing mitral valve repair or replacement for severe valvular regurgitation were studied intraoperatively with biplane transesophageal echocardiography. Regurgitant jets were classified by color flow mapping as central or wall, with the latter further classified as septal, lateral, anterior, or posterior in the two orthogonal scan planes. Pulmonary vein flow patterns were measured with pulsed wave Doppler ultrasonography and categorized as showing normal, blunted, or reversed systolic flow. Right and left pulmonary vein flow patterns were identical in the majority of patients studied (78%). Eight patients had discordant flow patterns. In seven of eight patients, the more abnormal pattern was seen in the right pulmonary vein, despite the fact that the regurgitant jets were directed centrally in four of these seven patients. Since discordant pulmonary vein flow patterns occurred in 5 of 15 patients (33%) with central jets, but in only 3 of 22 patients (14%) with eccentric wall jets, it is unlikely that mitral regurgitation jet direction per se causes predictable and selective unilateral alteration in pulmonary vein flow patterns.

Adolescent↗
PubMed1994

Inactivation of D-3-hydroxybutyrate dehydrogenase by fumaroyl bis(methyl phosphate).

Fumaroyl bis(methyl phosphate) reacts with the NADH-dependent enzyme, D-3-hydroxybutyrate dehydrogenase, leading to irreversible inactivation. The bifunctional reagent cross-links the subunits of the enzyme. The inactivation is subject to saturation and protection by substrate, consistent with the reaction occurring at the active site. The stoichiometry of inactivation indicates two active sites undergo reaction with each equivalent of reagent. These results indicate that the dimeric enzyme has contiguous active sites. The reagent is likely to react with an active site lysine, consistent with previous suggestions.

Binding Sites↗
PubMed1994

Cross-linking hemoglobin by design: lessons from using molecular clamps.

The development of a red cell substitute by chemical modification of hemoglobin has been approached as a systematic, iterative process. Acyl phosphate methyl esters were designed as anionic electrophiles to permit selective acylation of amino groups in the cationic site of hemoglobin which binds polyanions. Kinetic studies with systematically substituted acyl phosphates and amines show that the reaction is controlled by a reversible addition step followed by an irreversible elimination step. Acyl phosphate methyl esters which are derivatives of rigid dicarboxylic acids introduce cross-links in human hemoglobin between amino groups in the beta subunits (epsilon-NH2-Lys-82, alpha-NH2-Val-1) and permit correlation of oxygen binding properties with cross-link structure. The data suggest that the cross-link maintains cooperativity while reducing overall oxygen affinity by lowering the affinity of the R form for oxygen rather than by perturbing the R,T equilibrium of native hemoglobin. Materials produced from deoxyhemoglobin with a cross-link between positions 1 and 82 of the two beta units have appropriate oxygen affinity for red cell substitutes. The use of a trifunctional cross-linker, trimesyl tris(methyl phosphate) selectively produces hemoglobin with the desired 1-82 connection in good yield. The reagent is readily prepared and the properties of this chemically modified hemoglobin are suitable for trial as a red cell substitute, closely resembling those of optimized materials produced by recombinant technology. Further work is producing new chemicals and providing structural information.

Binding Sites↗