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Biomedical subjects

T W Wright

Publications and source records attributed to T W Wright.

At least 19 recordsLinked to original sources
PubMed2003

Characterization of transmission of Pneumocystis carinii f. sp. muris through immunocompetent BALB/c mice.

By using mouse models, it has been shown that Pneumocystis carinii f. sp. muris can be transmitted to immunocompetent mice that are exposed to immunosuppressed mice with active P. carinii pneumonia. We sought to determine whether P. carinii f. sp. muris could be transmitted between normal mice. The rationale for these experiments was to demonstrate whether the normal host could serve as the reservoir of organisms that produce Pcp when the organism is acquired by the immunosuppressed host. Under the conditions of these experiments, normal mice are able to be infected by brief cohousing with P. carinii-infected SCID mice. There was active replication of organisms in the normal host such that the organism could be transmitted to other normal mice, again with active replication. Mice that had seroconverted after exposure to P. carinii-infected SCID mice were more resistant to infection when reexposed. Infection in normal mice was well tolerated with minimal effects on dynamic lung compliance. We speculate, based on these results, that transmission from normal host to normal host, as an asymptomatic or minimally symptomatic infection, could be a way to maintain this opportunistic pathogen in the environment.

Animals↗
PubMed2001

Ulnar nerve excursion and strain at the elbow and wrist associated with upper extremity motion.

Significant excursion of the ulnar nerve is required for unimpeded upper extremity motion. This study evaluated the excursion necessary to accommodate common motions of daily living and associated strain on the ulnar nerve. The 2 most common sites of nerve entrapment, the cubital tunnel and the entrance of Guyon's canal, were studied. Five fresh-frozen, thawed transthoracic cadaver specimens (10 arms) were dissected and the nerve was exposed at the elbow and wrist only enough to be marked with a microsuture. Excursion was measured with a laser mounted on a Vernier caliper fixed to the bone and aligned in the direction of nerve motion. A Microstrain (Burlington, VT) DVRT strain device was applied to the nerve at both the elbow and wrist. Nerve excursion associated with motion of the shoulder, elbow, wrist, and fingers (measured by goniometer) was measured at the wrist and elbow. An average of 4.9 mm ulnar nerve excursion was required at the elbow to accommodate shoulder motion from 30 degrees to 110 degrees of abduction, and 5.1 mm was needed for elbow motion from 10 degrees to 90 degrees. When the wrist was moved from 60 degrees of extension to 65 degrees of flexion, 13.6 mm excursion of the ulnar nerve was required at the wrist. When all the motions of the wrist, fingers, elbow, and shoulder were combined, 21.9 mm of ulnar nerve excursion was required at the elbow and 23.2 mm at the wrist. Ulnar nerve strain of 15% or greater was experienced at the elbow with elbow flexion and at the wrist with wrist extension and radial deviation. Any factor that limits excursion at these sites could result in repetitive traction of the nerve and possibly play a role in the pathophysiology of cubital tunnel syndrome or ulnar neuropathy at Guyon's canal.

Cubital Tunnel Syndrome↗
PubMed2001

Radiographic assessment of uncemented humeral components in total shoulder arthroplasty.

Seventy-two total shoulder arthroplasties performed using Neer II press-fit humeral components and followed for an average of 4.1 years (range, 2-7.8 years) were analyzed radiographically. A humeral component was considered radiographically at risk for clinical loosening when a radiolucent line > or =2 mm in width was present in > or =3 zones or tilt or subsidence was identified on sequential radiographs by 2 of 3 or 3 of 3 independent observers. Forty components (55.6%) were judged to be at risk. There were no identifiable characteristics associated with the development of an at-risk humeral component except longer average follow-up of the at-risk group (4.7 years vs 3.3 years, P =.001). Humeral components at risk had a higher rate of endosteal erosion (P =.04) and greater number of zones with sclerosis. Radiographic changes around Neer II uncemented humeral components are common. Data from this study can be used as 1 benchmark to compare with alternate methods of humeral component fixation.

Adult↗
PubMed2001

Pulmonary inflammation disrupts surfactant function during Pneumocystis carinii pneumonia.

During Pneumocystis carinii pneumonia (PCP) in mice, the degree of pulmonary inflammation correlates directly with the severity of lung function deficits. Therefore, studies were undertaken to determine whether the host inflammatory response contributes to PCP-related respiratory impairment, at least in part, by disrupting the pulmonary surfactant system. Protein and phospholipid content and surfactant activity were measured in the lavage fluid of infected mice in either the absence or presence of an inflammatory response. At 9 weeks postinfection with P. carinii, nonreconstituted SCID mice exhibited no signs of pulmonary inflammation, respiratory impairment, or surfactant dysfunction. Lavage fluid obtained from these mice had protein/phospholipid (Pr/PL) ratios (64% +/- 4.7%) and minimum surface tension values (4.0 +/- 0.9 mN/m) similar to those of P. carinii-free control mice. However, when infected SCID mice were immunologically reconstituted, an intense inflammatory response ensued. Pr/PL ratios (218% +/- 42%) and minimum surface tension values (27.2 +/- 2.7 mN/m) of the lavage fluid were significantly elevated compared to those of the lavage fluid from infected, nonreconstituted mice (P < 0.05). To examine the specific role of CD8(+) T-cell-mediated inflammation in surfactant dysfunction during PCP, mice with defined T-cell populations were studied. P. carinii-infected, CD4(+)-depleted mice had elevated lavage fluid Pr/PL ratios (126% +/- 20%) and elevated minimum surface tension values (16.3 +/- 1.0 mN/m) compared to normal mice (P < 0.05). However, when infected mice were additionally depleted of CD8(+) cells, Pr/PL ratios were normal and surfactant activity was improved. These findings demonstrate that the surfactant pathology associated with PCP is related to the inflammatory process rather than being a direct effect of P. carinii. Moreover, CD8(+) lymphocytes are involved in the mechanism leading to surfactant dysfunction.

Animals↗
PubMed2000

Molecular characterization of KEX1, a kexin-like protease in mouse Pneumocystis carinii.

Expression screening of a Pneumocystis carinii-infected mouse lung cDNA library with specific monoclonal antibodies (mAbs) led to the identification of a P. carinii cDNA with extensive homology to subtilisin-like proteases, particularly fungal kexins and mammalian prohormone convertases. The 3.1 kb cDNA contains a single open reading frame encoding 1011 amino acids. Structural similarities to fungal kexins in the deduced primary amino acid sequence include a putative proenzyme domain delineated by a consensus autocatalytic cleavage site (Arg-Glu-Lys-Arg), conserved Asp, His, Asn and Ser residues in the putative catalytic domain, a hydrophobic transmembrane spanning domain, and a carboxy-terminal cytoplasmic domain with a conserved tyrosine motif thought to be important for localization of the protease in the endoplasmic reticulum and/or Golgi apparatus. Based on these structural similarities and the classification of P. carinii as a fungus, the protease was named KEX1. Southern blotting of mouse P. carinii chromosomes localized kex1 to a single chromosome of approximately 610 kb. Southern blotting of restriction enzyme digests of genomic DNA from P. carinii-infected mouse lung demonstrated that kex1 is a single copy gene. The function of kexins in other fungi suggests that KEX1 may be involved in the post-translational processing and maturation of other P. carinii proteins.

Amino Acid Sequence↗
PubMed2000

Pressure mapping of the radioulnar carpal joint: effects of ulnar lengthening and wrist position.

The purpose of this study was to investigate the effects of ulnar lengthening and wrist position on force transmission through the radioulnar carpal joint in a forced dorsiflexed wrist position. Eight cadaveric arms were subjected to a 30 kg compressive load directed down the forearm towards the wrist. A pressure sensor recorded forces across the wrist joint with the triangular fibrocartilage complex intact and excised. The biomechanics of the distal radioulnar joint were altered by changes in ulnar length and wrist position. Pressures at the ulnolunate articulation increased as the ulna was lengthened and were significantly lower when the triangular fibrocartilage complex was excised. An inverse relationship between triangular fibrocartilage complex thickness and ulnar variance was shown. Greater increases in ulnolunate pressure were observed in more positive ulnar variant wrists.

Biomechanical Phenomena↗
PubMed2000

Acromioplasty: comparison of outcome in patients with and without workers' compensation.

Acromioplasty was performed on 24 shoulders in 23 patients who had a diagnosis of impingement syndrome/rotator cuff tendinopathy. Ten patients were female and 13 were male; mean age was 52.3 years. Patients were divided into two groups, depending on whether they were receiving workers' compensation benefits. Clinical outcomes were evaluated preoperatively and at follow-up postoperatively using the University of California Los Angeles (UCLA) Shoulder Rating Scale. All patients had bursectomy, anterior inferior acromioplasty, and coracoacromial ligament release. The two groups showed significantly different postoperative results in terms of pain, function, strength of forward flexion, and total score, with the workers' compensation group consistently having a lower functional score. Pain did improve significantly for workers' compensation patients over the course of treatment, but relief was not nearly as complete as in the noncompensated group. A positive response to a shoulder bursa steroid injection, even if temporary, was a good predictor of final outcome after an acromioplasty.

Acromion↗
PubMed1999

Wrist ligament strain during external fixation: a cadaveric study.

The purpose of this study was to evaluate the change in strain (elongation) that occurs in 2 extrinsic ligaments of the wrist (volar radioscaphocapitate and dorsal radiotriquetral) as the wrist is sequentially distracted with an external fixator. Six fresh cadaver specimens were dissected to expose the dorsal radiotriquetral and volar radioscaphocapitate ligaments. A differential variable reluctance transducer strain gauge was applied to both ligaments and the wrist was serially distracted in increments of 5 mm with an Agee WristJack (Hand Biomechanics Laboratory, Sacramento, CA). The distraction increments were measured on the WristJack. X-rays were obtained at each level of distraction. At 10 mm of WristJack distraction, the strain in both the volar radioscaphocapitate and dorsal radiotriquetral ligaments increased to greater than 20%. An increase to a 0.63 carpal height index resulted in an increase in strain of 20%. This increased strain may contribute to wrist stiffness.

External Fixators↗
PubMed1999

Nonunion of the distal radius.

We report five cases of nonunion of the distal radius. There were three women and two men. The mean age was 44 years (range, 34-56). All five patients were heavy tobacco smokers and three had a history of alcohol abuse. In three patients, union of the distal radius was obtained. Two had a persistent nonunion which was salvaged with a total wrist fusion.

Adult↗
PubMed1999

Chemokine gene expression during Pneumocystis carinii-driven pulmonary inflammation.

Severe combined immunodeficient (SCID) mice lack functional lymphocytes and therefore develop Pneumocystis carinii pneumonia. However, when infected SCID mice are immunologically reconstituted with congenic spleen cells, a protective inflammatory cascade is initiated. Proinflammatory cytokines are produced, and lymphocytes and macrophages are recruited specifically to alveolar sites of infection. Importantly, uninfected regions of the lung remain free from inflammatory involvement, suggesting that there are specific mechanisms that limit inflammation in the infected lung. Therefore, to determine whether chemokines are involved in targeting the P. carinii-driven inflammatory response, steady-state mRNA levels of several chemokines were measured in the lungs of both reconstituted and nonreconstituted P. carinii-infected SCID mice. Despite significant organism burdens in the lungs of 8- and 10-week-old SCID mice, there was no evidence of elevated chemokine gene expression, which is consistent with the lack of an inflammatory response in these animals. However, when 8-week-old infected SCID mice were immunologically reconstituted, signs of focal pulmonary inflammation were observed, and levels of RANTES, MCP-1, lymphotactin, MIP-1alpha, MIP-1beta, and MIP-2 mRNAs were all significantly elevated. Chemokine mRNA abundance was elevated at day 10 postreconstitution (PR), was maximal at day 12 PR, and returned to baseline by day 22 PR. In situ hybridization demonstrated that during the peak of inflammation, RANTES gene expression was localized to sites of inflammatory cell infiltration and P. carinii infection. Thus, these observations indicate that chemokines play a role in the focal targeting of inflammatory cell recruitment to sites of P. carinii infection after the passive transfer of lymphocytes to the host.

Animals↗
PubMed1999

Immune-mediated inflammation directly impairs pulmonary function, contributing to the pathogenesis of Pneumocystis carinii pneumonia.

The clinical severity of Pneumocystis carinii pneumonia (PCP) correlates closely with the appearance of pulmonary markers of inflammation. Therefore, a model system was developed whereby physiological studies could be performed on live mice to determine the extent to which pulmonary inflammation contributes to respiratory impairment during PCP. P. carinii-infected severe combined immunodeficient mice displayed little evidence of pulmonary inflammation and exhibited normal oxygenation and dynamic lung compliance. When comparably infected littermates were immunologically reconstituted, however, an intense immune-mediated inflammatory response was observed that resulted in significant decreases in both lung compliance and oxygenation. As the pneumonia resolved pulmonary function returned toward normal. To begin to define the cell populations contributing to inflammation-associated respiratory impairment during PCP, similar studies were performed in CD4(+) T cell-depleted mice. Mice depleted of both CD4(+) and CD8(+) cells developed infection, but they demonstrated neither abnormal lung compliance nor increased respiratory rate and displayed no markers of lung injury. In contrast, mice depleted of only CD4(+) T cells exhibited severe pulmonary inflammation and injury, decreased oxygenation and lung compliance, and increased respirations. Respiratory compromise was associated with the presence of activated CD8(+) cells and neutrophils in broncho-alveolar lavage fluid. These observations provide direct experimental evidence that the host's response to P. carinii directly impairs pulmonary function and contributes to the pathogenesis of PCP. Furthermore, CD8(+) T cells likely contribute to the respiratory compromise observed during PCP.

Animals↗
PubMed1998

Vascular anatomy of the ulna.

The vascular anatomy of the ulna was studied. Ten fresh-frozen upper extremity specimens were injected with India ink and latex solution. The extraosseous anatomy was dissected. The intraosseous anatomy was evaluated after treatment with the modified Spalteholtz technique. The proximal periarticular portion of the ulna was supplied by numerous, very small periarticular branches running in the capsule. A major intramedullary nutrient vessel arose from the ulnar artery or ulnar recurrent artery in all specimens and entered at the base of the coronoid. The ulnar artery gave off a common interosseous artery that branches into posterior and anterior interosseous vessels that course distally on the interosseous membrane. The interosseous vessels were critical for they supply the only observed vascular branches to the ulna diaphysis. The anterior interosseous vessel supplied on average 7 branches (range, 3-11 branches) to the ulna diaphysis spaced at generally regular 2-cm intervals, with the number of branches decreasing in the distal third. The posterior interosseous artery supplied an average of 11 branches (range, 9-14 branches) to the ulna diaphysis spaced at 1-cm intervals. The distal ulna metaphysis was supplied by terminal branches of the anterior interosseous artery. The ulnar head was supplied by small branches off the ulnar artery proper. In summary, the blood supply to the ulna diaphysis was dependent on segmental vessels provided by the anterior and posterior interosseous vessels. No dominant intramedullary vessel was observed in the diaphysis. The interosseous vessels should be protected when treating a ulna fracture or a nonunion, or when performing an osteotomy.

Cadaver↗
PubMed1998

Induction of fibrinogen expression in the lung epithelium during Pneumocystis carinii pneumonia.

Pneumocystis carinii is an important pulmonary pathogen responsible for morbidity and mortality in patients with AIDS. The acute-phase response (APR), the primary mechanism used by the body to restore homeostasis following infection, is characterized by increased levels of circulating fibrinogen (FBG). Although the liver is the primary site of increased FBG synthesis during the APR, we unexpectedly discovered that FBG is synthesized and secreted by lung alveolar epithelial cells in vitro during an inflammatory stimulus. Therefore, we sought to determine whether lung epithelial cells produce FBG in vivo using animal models of P. carinii pneumonia (PCP). Inflammation was noted by an influx of macrophages to P. carinii-infected alveoli. Northern hybridization revealed that gamma-FBG mRNA increased two- to fivefold in P. carinii-infected lung tissue, while RNA in situ hybridization demonstrated increased levels of gamma-FBG mRNA in the lung epithelium. Immunoelectron microscopy detected lung epithelial cell-specific production of FBG, suggesting induction of a localized inflammatory response resembling the APR. A systemic APR was confirmed by a two- to fivefold upregulation of the levels of hepatic gamma-FBG mRNA in animals with PCP, resulting in a corresponding increase in levels of FBG in plasma. Furthermore, immunoelectron microscopy revealed the presence of FBG at the junction of cell membranes of trophic forms of P. carinii organisms aggregated along the alveolar epithelium. These results implicate FBG in the pathogenesis of PCP in a manner similar to that of the adhesive glycoproteins fibronectin and vitronectin, which are known to participate in intra-alveolar aggregation of organisms and adherence of P. carinii to the lung epithelium.

Acute-Phase Reaction↗
PubMed1998

Electromyography of the shoulder: an analysis of passive modes of exercise.

Passive shoulder motion is standard early rehabilitation in patients undergoing rotator cuff repair. A number of rehabilitation protocols exist to obtain this goal. This article evaluated different rehabilitation protocols using electromyographic analysis of the rotator cuff muscles to determine if the different protocols promote passive motion. Ten healthy volunteers underwent EMG to investigate the relative activity of the rotator cuff muscles during various exercises used postoperatively following shoulder surgery. The exercises tested were continuous passive motion machine (CPM), pulley, pendulum, self-assisted bar raise using the contralateral arm for power, self-assisted internal and external rotation, therapist-assisted elevation in plane of the scapula, and therapist-assisted internal and external rotation. The relative activity of the supraspinatus, infraspinatus, anterior deltoid, and trapezius muscles were measured and expressed as a percentage of maximal activity. For all muscle groups tested, the pulley exercise showed significantly more activity than the CPM machine. In the supraspinatus muscle, the pulley exercise averaged 17.6% of maximal activity and 8.7% for the self-assisted bar raise using contralateral arm power compared with 5.0% for the CPM machine. In general, therapist-assisted exercises and Codman's pendulum exercises showed activity that was not significantly different from the CPM machine. These results indicate that CPM and therapist-assisted passive range of motion, by being more passive, may increase the safety margin for obtaining early passive range of motion without disrupting the rotator cuff repair.

Adolescent↗
PubMed1997

Analysis of cytokine mRNA profiles in the lungs of Pneumocystis carinii-infected mice.

Severe combined immunodeficient (scid) mice lack functional CD4+ lymphocytes, and therefore develop life-threatening Pneumocystis carinii infection. However, when scid mice are immunologically reconstituted with spleen cells, including CD4+ cells, a protective inflammatory response is mounted against the organism. To determine whether these lymphocytes induce elevated cytokine mRNA levels in response to P. carinii infection, steady-state levels of cytokine mRNAs were measured in the lungs of both reconstituted and unaltered scid mice. Despite significant numbers of organisms and the presence of functional alveolar macrophages in the lungs of 8- and 10-wk-old scid mice, there was neither evidence of pulmonary inflammation, nor increased proinflammatory cytokine expression. However, when 8-wk-old scid mice were immunologically reconstituted, signs of intense, focal pulmonary inflammation were observed, and levels of interleukin (IL)-1alpha, IL-1beta, IL-3, IL-6, interferon-gamma (IFN-gamma), tumor necrosis factor (TNF)-alpha, and TNF-beta mRNAs were all significantly elevated. Cytokine expression was increased at day 10 post-reconstitution (PR), maximal at day 12 PR, and returned to baseline by day 22 PR. In situ hybridization demonstrated that at day 12 PR, increased IL-1beta and TNF-alpha expression was localized to sites of intense inflammation and focal P. carinii colonization. Many of the cells expressing high levels of IL-1beta and TNF-alpha in these regions were in direct contact with organisms, or contained degraded organisms within their cytoplasm. Thus, even though functional macrophages are present in scid mice, CD4+ T cells are required for proinflammatory cytokine expression, which is associated with the generation of a protective inflammatory response at sites of P. carinii infection.

Animals↗
PubMed1997

Treatment of humeral diaphyseal nonunions in patients with severely compromised bone.

Twenty-eight patients were treated for humeral shaft nonunions. Host factors associated with humeral nonunion included a high rate of significant medical problems and significant local tissue trauma from the initiating injury. Comminuted fractures and fractures that were either long oblique or spiral in configuration were also heavily represented in this series. Midshaft was the most common anatomic location (n = 17). Previous surgery had been unsuccessful in 22 of the patients. All the humeral nonunions were treated by either standard AO compression plate technique with iliac crest bone grafting or, in patients with severely compromised bone from osteoporosis or multiple fixation attempts, a reconstruction using an intramedullary fibular graft and dynamic compression plate with screws, obtaining four cortices of fixation (quadricortical). This construction was also augmented with iliac crest bone graft. In this difficult subgroup of patients, our technique of intramedullary quadricortical fixation yielded an 89% union rate (17/19). Patients with humeral union were satisfied and had functional range of motion of the shoulder and elbow.

Adolescent↗