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W Maloney

Publications and source records attributed to W Maloney.

13 recordsLinked to original sources
PubMed2001

Receptor activator of NF-kappa B and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis.

The receptor activator of NF-kappaB (RANKL) is the essential signal required for full osteoclast (OC) development, activation, and survival. RANKL is highly expressed in areas of trabecular bone remodeling and inflammatory bone loss, is increased on marrow stromal cells or osteoblasts by osteotropic hormones or cytokines, and is neutralized by osteoprotegerin (OPG), a soluble decoy receptor also crucial for preventing arterial calcification. Vascular endothelial cells (VEC) are critically involved in bone development and remodeling and influence OC recruitment, formation, and activity. Although OCs develop and function in close association with bone VEC and sinusoids, signals mediating their interactions are not well known. Here, we show for the first time that human microvascular endothelial cells (HMVEC) express transcripts for both RANKL and OPG; inflammatory cytokines tumor necrosis factor-alpha and interleukin-1alpha elevate RANKL and OPG expression 5-40-fold in HMVEC (with an early OPG peak that declines as RANKL rises), and RANKL protein increases on the surface of tumor necrosis factor-alpha-activated HMVEC. Cytokine-activated HMVEC promoted the formation, fusion, and bone resorption of OCs formed in co-cultures with circulating human monocytic precursors via a RANKL-mediated mechanism fully antagonized by exogenous OPG. Furthermore, paraffin sections of human osteoporotic fractured bone exhibited increased RANKL immunostaining in vivo on VEC located near resorbing OCs in regions undergoing active bone turnover. Therefore, cytokine-activated VEC may contribute to inflammatory-mediated bone loss via regulated production of RANKL and OPG. VEC-derived OPG may also serve as an autocrine signal to inhibit blood vessel calcification.

Base Sequence↗
PubMed2001

In vitro generation of scaffold independent neocartilage.

A novel serum-free culture system was developed in an attempt to generate a three-dimensional hyalinelike neocartilage independent of polymer scaffolds. Neocartilage disks as much as 1.5 mm thick were produced, which were characterized by synthesis of the normal articular cartilage collagens and proteoglycans. In contrast to growth in serum-containing media, chondrocytes from juveniles maintained in static culture under defined serum-free conditions deposited an extracellular matrix that accumulated in the form of tissue disks. Electron microscopic evaluation of neocartilage disks revealed collagenous matrices characteristic of articular cartilage from human infants. The neocartilage did not show terminal chondrocyte differentiation as shown by the absence of Type X collagen production and lack of cellular hypertrophy. Although chondrocytes from preadolescent donor cartilage recapitulated embryonic development in the absence of exogenous factors, chondrocytes from articular cartilage from adults failed to produce neocartilage when grown under identical conditions. This is the first demonstration that autocrine morphogens are sufficient to guide production of hyaline cartilage in vitro. In addition to providing a unique model system to compare the healing response of mature and immature articular chondrocytes, this technology may be of clinical importance in the development of new biomaterials for repair of articular cartilage defects.

Adolescent↗
PubMed1998

Prediction of postoperative knee flexion in Insall-Burstein II total knee arthroplasty.

Postoperative knee flexion in patients undergoing Insall-Burstein-II total knee arthroplasty at 2 years was evaluated regarding two basic questions: what groups of patients gain or lose the most flexion and what groups of patients have the best or worst postoperative flexion. Thirteen preoperative variables (maximum flexion, flexion arc, tibiofemoral angle, quadriceps strength, extensor lag, Knee Society score, Knee Society patient assessment, gender, age, height, weight, diagnosis, and surgeon) and four postoperative variable (leg length change, tibiofemoral angle, distance from patella to the joint line, and the tibial prosthesis anteroposterior translation on a lateral radiograph) were used in an attempt to explain postoperative flexion. The analysis was performed on 164 consecutive Insall-Burstein-II total knees in which the data were gathered prospectively on a time oriented medical record database. A regression tree analysis was used to identify several groups of patients, characterized by preoperative factor values, who had markedly above average performance on postoperative flexion. The preoperative factors identified include preoperative flexion, flexion arc, tibiofemoral angle, extensor lag, diagnosis, and age. The only postoperative variable of significance was tibiofemoral angle. Among the potential determinants of postoperative flexion that failed to appear predictive were the Knee Society scores and surgeon. Preoperative flexion is known to be a critical determinant of postoperative flexion in total knee replacement. However, in the current study, preoperative flexion accounted for only half of the difference between the best (122 degrees) and the worst (88 degrees) group, as determined with regression tree analysis.

Aged↗
PubMed1998

Cellular profile and cytokine production at prosthetic interfaces. Study of tissues retrieved from revised hip and knee replacements.

The tissues surrounding 65 cemented and 36 cementless total joint replacements undergoing revision were characterised for cell types by immunohistochemistry and for cytokine expression by in situ hybridisation. We identified three distinct groups of revised implants: loose implants with ballooning radiological osteolysis, loose implants without osteolysis, and well-fixed implants. In the cemented series, osteolysis was associated with increased numbers of macrophages (p = 0.0006), T-lymphocyte subgroups (p = 0.03) and IL-1 (p = 0.02) and IL-6 (p = 0.0001) expression, and in the cementless series with increased numbers of T-lymphocyte subgroups (p = 0.005) and increased TNF alpha expression (p = 0.04). For cemented implants, the histological, histochemical and cytokine profiles of the interface correlated with the clinical and radiological grade of loosening and osteolysis. Our findings suggest that there are different biological mechanisms of loosening and osteolysis for cemented and cementless implants. T-lymphocyte modulation of macrophage function may be an important interaction at prosthetic interfaces.

Aged↗
PubMed1997

Loosening and osteolysis of cemented joint arthroplasties. A biologic spectrum.

The purpose of this study was to characterize the cell types (using immunohistochemistry) and cytokine expression (using in situ hybridization) of tissues surrounding well fixed and loose cemented prostheses undergoing revision. Clinical and radiographic data were gathered prospectively for a series of cemented total joint replacements undergoing revision. Three groups were identified: (1) loose implants with osteolysis (10 specimens), (2) loose implants without osteolysis (11 specimens), and (3) well fixed implants (7 specimens). At surgery, a specimen was harvested from the bone cement interface. Immunohistochemical staining was performed using monoclonal antibodies to identify macrophages and lymphocyte subgroups. Human antisense probes were selected to identify the mRNA for specific cytokines using in situ hybridization. The percentage of positively staining cells was determined for each antibody or probe using a grid counting technique. Tissues from loose cemented prostheses with osteolysis contained significantly greater numbers of macrophages and T lymphocytes compared with tissues from loose and well fixed cemented prostheses without osteolysis. The number of interleukin-1 and interleukin-6 positive cells was highest in specimens with osteolysis and lowest in specimens from well fixed prostheses. These cytokines modulate the growth and differentiation of cells in the immune system and the monocyte and macrophage system and mediate the remodeling of bone and mesenchymal tissues. Specific cell populations and cytokine profiles appear to be involved in periprosthetic osteolysis; this information may be useful in planning strategies for prevention and treatment.

Aged↗
PubMed1995

Encephalomyeloradiculopathy of infectious or parainfectious etiology--a new entity?

Between 19 March 1990 and 24 December 1992, six persons in Nova Scotia presented with a unique neurological illness. A prodrome of fever and headache was followed by neurogenic bladder, transverse myelitis, and encephalopathy in association with mononuclear pleocytosis of the CSF and nerve-conduction study findings consistent with polyradiculopathy. The spinal cords of three of the patients appeared abnormal on myelograms or magnetic resonance imaging studies. No microbial agent was isolated or demonstrated serologically. All of the patients were treated with antimicrobial agents and corticosteroids. Three recovered completely, but neurogenic bladder persisted in the remaining three. We suggest that this group of patients manifested an encephalomyeloradiculopathy that is likely a new clinical entity of infectious or parainfectious etiology.

Adolescent↗
PubMed1994

Etiology of osteolysis around porous-coated cementless total hip arthroplasties.

The prosthetic components and tissues retrieved from 12 hips with osteolysis in association with well-fixed cementless porous-coated total hip prostheses (5 Porous Coated Anatomic, 6 Harris-Galante Porous, and 1 Omniflex) were examined using a variety specific techniques including electron microscopy, standard histology, immunohistochemistry, and particle identification. The patients were young and active. Extensive osteolysis developed in all 12 femurs and 3 acetabula between 36 and 84 months after arthroplasty (mean, 63 months). All of the polyethylene liners were noted to be worn substantially (mean volumetric wear, 1140 +/- 810 mm3). The wear was unrelated to the head diameter in this small number of cases. In all 12 cases, the articulating surfaces were wear polished and contained numerous fine multidirectional scratches, suggesting 3-body abrasive wear mechanisms in addition to adhesive wear liberating very small (micron to submicron) wear particles. In 4 cases, surface delamination and flaking of polyethylene were also found, suggesting fatigue wear liberating larger wear particles. Nine of 10 cobalt alloy heads showed numerous fine scratches with sharp edges presumably from 3-body abrasive wear. Corrosion and fretting at the femoral head-neck junction in 5 cases, burnishing of the femoral stem against bone in 4 cases, and metal staining of tissues opposite the porous coatings in 7 cases provided evidence for the liberation of fine metal particles from outside the articulation. Histologic and immunohistochemical studies of tissue in the regions of osteolysis in all cases showed numerous focal aggregates of KP1 antibody positive activated macrophages containing large amounts of submicron intracellular particles of polyethylene (presumably related to the 3-body abrasive wear polishing) and giant cells within a fibrous stroma. In 5 cases, some of the macrophages also contained submicron metal particles but smaller in numbers. T lymphocytes, plasma cells, and mast cells that might indicate hypersensitivity were found in 4 of the 12 cases (33%), and none of the cases had B lymphocytes. These data suggest that abrasive wear at the articulation leads to the liberation of abundant fine particulate wear debris of polyethylene into the tissues around cementless prostheses. Small amounts of particulate metal debris are also liberated from corrosion and fretting of the metal components and can contribute to accelerated 3-body abrasive wear at the articulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1983

The treatment response scale: a retrospective method of assessing response to neuroleptics.

The 10-item Treatment Response Scale (TRS) was used to rate the charts of schizophrenic inpatients for prior response to neuroleptic treatment. Interrater reliability, interitem agreement, and agreement of each item with total TRS scores were good. The validity of the TRS was assessed against changes in independent measurements with the Brief Psychiatric Rating Scale. The results indicate that findings from a systematic chart review correlate substantially with clinical assessment of response.

Antipsychotic Agents↗
PubMedDate not supplied

Effects of hip center location on the moment-generating capacity of the muscles.

We have developed a three-dimensional biomechanical model of the human lower extremity to study how the location of the hip center affects the moment-generating capacity of four muscle groups: the hip abductors, adductors, flexors, and extensors. The model computes the maximum isometric force and the resulting joint moments that each of 25 muscle-tendon complexes develops at any body position. Abduction, adduction, flexion, and extension moments calculated with the model correspond closely with isometric joint moments measured during maximum voluntary contractions. We used the model to determine (1) the hip center locations that maximize and minimize the moment-generating capacity of each muscle group and (2) the effects of superior-inferior, anterior-posterior, and medial-lateral displacement of the hip center on the moment arms, maximum isometric muscle forces, and maximum isometric moments generated by each muscle group. We found that superior-inferior displacement of the hip center has the greatest effect on the force- and moment-generating capacity of the muscles. A 2 cm superior displacement decreases abduction force (44%), moment arm (12%), and moment (49%), while a 2 cm inferior displacement increases abduction force (20%), moment arm (7%) and moment (26%). Similarly, a 2 cm superior displacement decreases flexion force (27%), moment arm (6%), and moment (22%), while inferior displacement increases all three variables. Anterior-posterior displacement alters the moment-generating capacity of the flexors and extensors considerably, primarily due to moment arm changes. Medial-lateral displacement has a large effect on the moment-generating capacity of the adductors only. A 2 cm medial displacement decreases adduction moment arm (20%), force (26%) and moment (40%). These results demonstrate that the force- and moment-generating capacities of the muscles are sensitive to the location of the hip center.

Adult↗
PubMedDate not supplied

Posttachycardia T-wave changes.

A 25-year-old previously healthy man presented to the emergency department with a tachydysrhythmia. After pharmacological intervention, the patient's rhythm converted to normal sinus and symmetrically inverted T-wave changes were noted. Although asymptomatic after conversion, the patient was admitted to the hospital and monitored for two days to rule out cardiac ischemia correlating with the T-wave changes. The patient was ultimately discharged in good health. A review of the emergency medical literature fails to reveal examples of post-tachycardic T-wave changes that may simulate myocardial ischemia but be of no clinical significance.

Adult↗