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Biomedical subjects

M D McKee

Publications and source records attributed to M D McKee.

At least 37 records · Page 2Linked to original sources
PubMed2000

Fractures of capitellum and trochlea.

The principles of management of capitellar and trochlear fractures are similar to any other intra-articular fracture. Accurate anatomic reduction, rigid internal fixation, and early mobilization of the elbow are prerequisites for a good functional result. Small fragments with minimal subchondral bone, not amenable to rigid internal fixation, are best treated by surgical resection. This article outlines the diagnosis, treatment, controversies, postoperative results, and complications of these rare elbow fractures.

Adult↗
PubMed2000

Identification and localization of lysozyme as a component of eggshell membranes and eggshell matrix.

The avian eggshell is a composite biomaterial composed of non-calcifying eggshell membranes and the overlying calcified shell matrix. The calcified shell forms in a uterine fluid where the concentration of different protein species varies between the initial, rapid calcification and terminal phases of eggshell deposition. The role of these avian eggshell matrix proteins during shell formation is poorly understood. The properties of the individual components must be determined in order to gain insight into their function during eggshell mineralization. In this study, we have identified lysozyme as a component of the uterine fluid by microsequencing, and used western blotting, immunofluorescence and colloidal-gold immunocytochemistry to document its localization in the eggshell membranes and the shell matrix. Furthermore, Northern blotting and RT-PCR indicates that there is a gradient to the expression of lysozyme message by different regions of the oviduct, with significant albeit low levels expressed in the isthmus and uterus. Lysozyme protein is abundant in the limiting membrane that circumscribes the egg white and forms the innermost layer of the shell membranes. It is also present in the shell membranes, and in the matrix of the calcified shell. Calcite crystals grown in the presence of purified hen lysozyme exhibited altered crystal morphology. Therefore, in addition to its well-known anti-microbial properties that could add to the protective function of the eggshell during embryonic development, shell matrix lysozyme may also be a structural protein which in soluble form influences calcium carbonate deposition during calcification.

Animals↗
PubMed2000

Operative treatment of nonunions about the elbow.

Nonunions about the elbow present a great challenge to the orthopaedic surgeon. Recent advances have enabled the surgeon to achieve much improved results. The current study outlines the treatment of nonunions of the distal humerus, proximal ulna (including olecranon, Monteggia, and coronoid nonunions), and radial head and neck nonunions. The historic problems of treating these nonunions included the use of inadequate fixation, the poor understanding of the role of soft tissue surgery in the treatment of the stiff elbow, and the failure of previous postoperative rehabilitation protocols. Advances made in the techniques of soft tissue treatment, modern methods of stable internal fixation, and early postoperative rehabilitation all have made an exceptional difference in the surgeon's ability to treat these most complex problems. The current study will provide the reader with a greater understanding of nonunions about the elbow, clinical and technical details for their treatment, and the expected results after treatment.

Arthroplasty, Replacement↗
PubMed2000

Use of a hinged external fixator for elbow instability after severe distal humeral fracture.

The authors report the case of a forty-year-old man who developed acute elbow instability after fixation of an open, comminuted distal humeral fracture. Treatment with a hinged, external elbow fixator was successful in reestablishing elbow stability and a functional range of elbow motion. To the best of the authors' knowledge, the use of this device for acute elbow instability after distal humeral fracture fixation has not been previously reported.

Acute Disease↗
PubMed2000

Osteopontin.

Osteopontin (OPN) is a highly phosphorylated sialoprotein that is a prominent component of the mineralized extracellular matrices of bones and teeth. OPN is characterized by the presence of a polyaspartic acid sequence and sites of Ser/Thr phosphorylation that mediate hydroxyapatite binding, and a highly conserved RGD motif that mediates cell attachment/signaling. Expression of OPN in a variety of tissues indicates a multiplicity of functions that involve one or more of these conserved motifs. While the lack of a clear phenotype in OPN "knockout" mice has not established a definitive role for OPN in any tissue, recent studies have provided some novel and intriguing insights into the versatility of this enigmatic protein in diverse biological events, including developmental processes, wound healing, immunological responses, tumorigenesis, bone resorption, and calcification. The ability of OPN to stimulate cell activity through multiple receptors linked to several interactive signaling pathways can account for much of the functional diversity. In this review, we discuss the structural features of OPN that relate to its function in the formation, remodeling, and maintenance of bones and teeth.

Amino Acid Sequence↗
PubMed2000

Fixation of fractures of the shaft of the humerus by dynamic compression plate or intramedullary nail. A prospective, randomised trial.

We randomised prospectively 44 patients with fractures of the shaft of the humerus to open reduction and internal fixation by either an intramedullary nail (IMN) or a dynamic compression plate (DCP). Patients were followed up for a minimum of six months. There were no significant differences in the function of the shoulder and elbow, as determined by the American Shoulder and Elbow Surgeons' score, the visual analogue pain score, range of movement, or the time taken to return to normal activity. There was a single case of shoulder impingement in the DCP group and six in the IMN group. Of these six, five occurred after antegrade insertion of an IMN. In the DCP group three patients developed complications, compared with 13 in the IMN group. We had to perform secondary surgery on seven patients in the IMN group, but on only one in the DCP group (p = 0.016). Our findings suggest that open reduction and internal fixation with a DCP remains the best treatment for unstable fractures of the shaft of the humerus. Fixation by IMN may be indicated for specific situations, but is technically more demanding and has a higher rate of complications.

Adult↗
PubMed2000

Functional outcome after open supracondylar fractures of the humerus. The effect of the surgical approach.

We reviewed 26 patients who had had internal fixation of an open intra-articular supracondylar fracture of the humerus. All operations were performed using a posterior approach, 13 with a triceps split and 13 with an olecranon osteotomy. The outcome was assessed by means of the Mayo Elbow score, the Disability of the Arm, Shoulder and Hand (DASH) score and the SF-36 Physical Function score. Patients with an olecranon osteotomy had less good results.

Adolescent↗
PubMed2000

The effect of surgery for rotator cuff disease on general health status. Results of a prospective trial.

BACKGROUND: Previous studies of the effect of rotator cuff surgery have concentrated on limb-specific or surgeon-based outcome criteria. We conducted a prospective trial to determine the effect of surgery for rotator cuff disease on general health status. METHODS: Seventy-one patients (fifty of whom were men and twenty-one of whom were women) with a mean age of 56.1 years were enrolled in the study. In addition to routine clinical and radiographic evaluation, all patients completed the Short Form-36 (SF-36) health-status questionnaire and five limb-specific questionnaires preoperatively and at six, twelve, eighteen, and twenty-four months postoperatively. All patients had a standard open acromioplasty and resection of the subacromial bursa. Thirty-one patients had repair of an associated rotator cuff tear. Sixty-seven patients (94 percent) completed the study; the remaining four patients were lost to follow-up. RESULTS: The preoperative SF-36 scores for physical function (60.6, p = 0.02), role function-physical (20.8, p = 0.001), pain (38.6, p = 0.003), physical component summary (37.0, p = 0.001), and mental component summary (45.6, p = 0.02) were significantly decreased compared with normative data. The preoperative limb-specific scores also were low. At the time of the most recent follow-up evaluation, there was improvement that approached or reached significance both in the limb-specific scores (p < or = 0.0026) and in the general-health-status scores for pain (p = 0.0001), role function-physical (p = 0.06), vitality (p = 0.01), and physical component summary (p = 0.01). The presence of a rotator cuff tear had a significant negative effect on limb-specific scores both preoperatively (p = 0.04) and postoperatively (p = 0.05). Although operative treatment of rotator cuff disease led to improved scores, patients who had filed a Workers' Compensation claim had lower limb-specific and SF-36 scores both preoperatively (p = 0.02 and p = 0.01, respectively) and postoperatively (p = 0.01 and p = 0.005, respectively). CONCLUSIONS: Surgery for chronic rotator cuff disease reliably and significantly improves general health status.

Acromion↗
PubMed2000

Functional outcome following surgical treatment of intra-articular distal humeral fractures through a posterior approach.

BACKGROUND: While surgical repair is considered the standard of care of displaced intra-articular distal humeral fractures, most investigators have assessed its results with use of surgeon-based and/or radiograph-based outcome measures. The purpose of our study was to determine the functional outcome of fixation of displaced intra-articular distal humeral fractures with use of a standardized evaluation methodology consisting of objective testing of muscle strength and use of patient-based questionnaires (both limb-specific and general health-status questionnaires). METHODS: We identified twenty-five patients (fourteen male and eleven female), with a mean age of forty-seven years, who had an isolated, closed, displaced, intercondylar, intra-articular fracture of the distal part of the humerus repaired operatively through a posterior approach and fixed with plates on both the medial and the lateral column. All patients returned for follow-up that included recording of a complete history, physical examination, radiographic examination, completion of both a limb-specific questionnaire (Disabilities of the Arm, Shoulder and Hand [DASH]) and a general health-status questionnaire (Short Form-36 [SF-36]), and objective muscle-strength testing. RESULTS: The mean duration of follow-up was thirty-seven months (range, eighteen to seventy-five months). The mean flexion contracture was 25 degrees (range, 5 to 65 degrees), and the mean arc of flexion-extension was 108 degrees (range, 55 to 140 degrees). Significant decreases in mean muscle strength compared with that on the normal side were seen in both elbow flexion measured at 90 degrees (74 percent of normal, p = 0.01) and elbow extension measured at 45 degrees (76 percent of normal, p = 0.01), 90 degrees (74 percent of normal, p = 0.01), and 120 degrees (75 percent of normal, p = 0.01). The mean DASH score was 20 points, indicating mild residual impairment. The SF-36 scores revealed minor but significant decreases in the role-physical and physical function scores (p = 0.01 and 0.03, respectively) but no alteration of the mental component or mean scores. Six patients (24 percent) had a reoperation; three of them had removal of prominent hardware used to fix the site of an olecranon osteotomy. CONCLUSIONS: The surgical repair of an intra-articular distal humeral fracture is an effective procedure that reliably maintains general health status as measured by patient-based questionnaires. Our study quantified a decrease in the range of motion and muscle strength of these patients, which may help to explain the mild residual physical impairment detected by the limb-specific outcome measures and physical function components of the general health-status measures.

Adult↗
PubMed1999

Molecular cloning and ultrastructural localization of the core protein of an eggshell matrix proteoglycan, ovocleidin-116.

The role of avian eggshell matrix proteins in shell formation is poorly understood. This calcitic biomaterial forms in a uterine fluid where the protein composition varies during the initial, calcification, and terminal phases of eggshell deposition. A specific antibody was raised to a 116-kDa protein, which is most abundant in uterine fluid during active eggshell calcification. This antiserum was used to expression screen a bacteriophage cDNA library prepared using mRNA extracted from pooled uterine tissue harvested at the midpoint of eggshell calcification. Plasmids containing inserts of differing 5'-lengths were isolated with a maximum cDNA sequence of 2.4 kilobases. Northern blotting and reverse transcriptase-polymerase chain reaction demonstrated that the 2. 35-kilobase message was expressed in a uterine-specific manner. The hypothetical translational product from the open reading frame corresponded to a novel 80-kDa protein, which we have named ovocleidin-116. After removal of the predicted signal peptide, its N-terminal sequence corresponded almost exactly with that determined from direct microsequencing of the 116-kDa uterine protein (this work) and with that previously determined for the core protein of a 120-kDa eggshell dermatan sulfate proteoglycan (Corrino, D. A., Rodriguez, J. P., and Caplan, A. I. (1997) Connect. Tissue Res. 36, 175-193). Ultrastructural colloidal gold immunocytochemistry of ovocleidin-116 demonstrated its presence in the organic matrix, in small vesicles found throughout the mineralized palisade layer, and the calcium reserve assembly of the mammillary layer. Ovocleidin-116 thus is a candidate molecule for the regulation of calcite growth during eggshell calcification.

Amino Acid Sequence↗
PubMed1999

Calcification of vascular smooth muscle cell cultures: inhibition by osteopontin.

Calcification of vascular tissue is a common complication in aging, atherosclerosis, diabetes, renal failure, aortic stenosis, and prosthetic valve replacement. Osteopontin is a noncollagenous adhesive protein routinely found at sites of dystrophic calcification and synthesized at high levels by macrophages in calcified aortic valves and atherosclerotic plaques. In the present study, we have characterized the calcification of bovine aortic smooth muscle cell (BASMC) cultures in vitro and have studied the effects of exogenous osteopontin on mineral deposition. Induction of calcification in BASMC cultures was alkaline phosphatase-dependent and was characterized by a multilayer cell morphology. Mineral deposition occurred in the basal matrix of multilayered areas as indicated by von Kossa staining, and transmission electron microscopy and electron diffraction identified the mineral as apatite. Ultrastructural analysis of the cultures showed the presence of extracellular matrix vesicles, calcifying collagen fibrils, and nodular-type calcifications similar to those found in calcified heart valves and atherosclerotic plaques. Purified osteopontin (0.05 to 5 microgram/mL) dose dependently inhibited calcification of BASMC cultures, whereas vitronectin and fibronectin had no effect. In contrast to the inhibitory mechanism of levamisole on mineral deposition, osteopontin did not inhibit alkaline phosphatase activity or reduce phosphorus levels in the culture medium. Addition of calcium to the cultures overcame the inhibitory effect of osteopontin on BASMC culture calcification and resulted in decreased levels of calcium in the culture medium and increased levels in the cell layer. Moreover, using high-resolution, colloidal-gold immunocytochemistry, osteopontin was found intimately associated with growing apatite crystals. These data indicate that the effect of osteopontin, although calcium-dependent, was not mediated by simple calcium chelation but most likely by direct interaction of osteopontin with crystal surfaces. These studies suggest that BASMCs can be used to model vascular calcification in vitro and that soluble osteopontin released near sites of vascular calcification may represent an adaptive mechanism aimed at preventing vascular calcification.

Adaptation, Physiological↗
PubMed1999

Changes in the fine specificity of gp100(209-217)-reactive T cells in patients following vaccination with a peptide modified at an HLA-A2.1 anchor residue.

In a recent clinical trial, HLA-A2+ melanoma patients were vaccinated with a peptide derived from the melanoma Ag gp100, which had been modified at the second position (g9-209 2M) to enhance MHC binding affinity. Vaccination led to a significant increase in lymphocyte precursors in 10 of 11 patients but did not result in objective cancer responses. We observed that some postvaccination PBMC cultures were less reactive with tumor cells than they were with g9-209 peptide-pulsed T2 cells. In contrast, g9-209-reactive tumor-infiltrating lymphocyte cultures generally reacted equally with tumor cells and g9-209 peptide-pulsed T2 cells. To investigate this difference in T cell reactivity, T cell cloids derived from the PBMC of three patients vaccinated with g9-209 2M were compared with T cell cloids isolated from g9-209-reactive TIL cultures. All of the T cell cloids obtained from TIL reacted with HLA-A2+, gp100+ melanoma cell lines as well as with g9-209 and g9-209 2M peptide-pulsed targets. In contrast, only 3 of 20 PBMC-derived T cell cloids reacted with melanoma cell lines in addition to g9-209 and to g9-209 2M peptide-pulsed targets. Twelve of twenty PBMC-derived cloids reacted with g9-209 and g9-209 2M peptide-pulsed targets but not with melanoma cell lines. And 5 of 20 PBMC-derived cloids recognized only the g9-209 2M-modified peptide-pulsed targets. These results suggest that immunizing patients with the modified peptide affected the T cell repertoire by expanding an array of T cells with different fine specificities, only some of which recognized melanoma cells.

Amino Acid Sequence↗
PubMed1999

Quantitation of T-cell receptor frequencies by competitive PCR: generation and evaluation of novel TCR subfamily and clone specific competitors.

T cell receptor (TCR) V gene usage has been used to characterize the immune response to bacteria, viruses, allografts, self antigens, tumor antigens, and superantigens. Sensitive methods to detect changes in the frequency of TCR subfamilies or clonotypes might be useful in evaluating the efficacy of vaccines against infectious agents, immunotherapy treatments for cancer patients, or the status of autoimmune diseases. Two HLA-A2 restricted CTL clones expressing BV17 were isolated from a tumor infiltrating lymphocytes (TIL) culture of a patient with metastatic melanoma. One clone recognized the MART-1(27-35) peptide and the other clone recognized the gp100(209-217) peptide. The frequency of each of these CTL clones in an expanding TIL culture was measured using a novel competitive RT-PCR (cRT-PCR) strategy. cRT-PCR uses a single primer pair to amplify template cDNA simultaneously with a modified DNA competitor molecule. A rapid two-step PCR technique followed by a single cloning step was used to generate a TCR BV17 subfamily specific competitor or competitors specific for the MART-1(27-35) reactive CTL clone (CO-41) and the gp100(209-217) reactive CTL clone (CO-4). Each competitor contained a segment of the TCR BC region that served as an internal reference standard. Using the BV17 competitor we were able to accurately and reproducibly measure cDNA templates at a frequency as low as 1/100,000 using cDNA samples of known TCRBV subfamily composition. This competitor was used to monitor the frequency of BV17 expressing T cells in the TIL and PMBC of a patient with metastatic melanoma. We determined that the frequency of BV17 expressing T cells increased from 4.5% of the culture on day 35 to 60.7% of the culture on day 58. Expansion of the BV17 subfamily was due predominantly to the expansion of the CO-4 clone. This method can be used to meaningfully quantify the precursor frequency of T cell mRNA in prepared samples via TCR subfamily or TCR sequence specific primers.

Cell Line↗
PubMed1999

Do foot injuries significantly affect the functional outcome of multiply injured patients?

OBJECTIVE: To assess the functional outcome of multiply injured trauma patients with foot injuries and to determine which outcome measures are most appropriate for this assessment. DESIGN: Prospective, matched pair analysis. SETTING: University-affiliated Level I trauma center with a prospectively entered trauma database. PATIENTS: Twenty-eight multiply injured patients with foot injuries were randomly identified in our prospective trauma database (Group 1). The patients in Group 1 were randomly matched in a blinded fashion to twenty-eight multiply injured patients without foot injuries who were selected from the entire group of patients in our trauma database (Group 2). The patients were matched by age, sex, length of follow-up, and Injury Severity Score. MAIN OUTCOME MEASURES: Three outcome tools were used: the Short Form 36 (SF-36), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the modified Boston Children's Hospital Grading System. RESULTS: The outcome of multiply injured patients with foot injuries was significantly worse than that of patients without foot injuries when using any of the three outcome measures (SF-36, p = 0.008; WOMAC, p = 0.00007; modified Boston Children's score, p = 0.001). The outcome of patients with foot injuries was worse than that of those without foot injuries in five of the eight components of the SF-36 score (physical functioning, p = 0.0004; role physical, p = 0.01; bodily pain, p = 0.01; social functioning, p = 0.01; role emotional, p = 0.006). The outcome of patients with foot injuries was worse than that of patients without foot injuries in all three components of the WOMAC (pain score, p = 0.0004; stiffness score, p = 0.007; physical function score, p = 0.00006). For the patients with foot injuries, there was strong correlation across all three scales (SF-36 vs. WOMAC, r = 0.84; SF-36 vs. modified Boston Children's Hospital, r = 0.88; WOMAC vs. modified Boston Children's Hospital, r = 0.78). CONCLUSIONS: The SF-36, WOMAC, and modified Boston Children's Hospital Grading System are all useful in assessing the outcome of multiply injured patients with foot injuries. The outcome of these patients is poor when using any of these measures. Foot injuries cause significant disability to multiply injured patients. More attention should be given to these injuries, and more aggressive management should be considered to improve the outcome of this group of multiply injured patients.

Adolescent↗