Biomedical subjects

G R Williams

Publications and source records attributed to G R Williams.

At least 73 records · Page 4Linked to original sources

PubMed1998

Anteroposterior instability of the distal clavicle after distal clavicle resection.

Resection of the lateral end of the clavicle disrupts the acromioclavicular articulation and creates the potential for abnormal postoperative motion. Seventeen isolated distal clavicle resections were reviewed to assess translation of the acromioclavicular articulation in the anteroposterior plane and its relationship to patient outcome. Stress radiographs were used to quantitate the translation of the distal clavicle and the amount of bone resected. Radiographs of the contralateral shoulder served as a control. Patients completed a questionnaire on shoulder function and pain and were examined preoperatively and postoperatively. The total translation (anterior plus posterior) in the anteroposterior plane averaged 8.7 mm (range, 3-21 mm) for surgically treated shoulders and was significantly greater than that for the contralateral shoulders (mean, 3.2 mm; range, 1-6 mm). Patients' postoperative visual analog pain scales correlated with the magnitude of anteroposterior translation. The amount of translation and the postoperative pain scores did not correlate with the apparent joint space seen on radiographs after surgery. The correlation of pain scores with the amount of translation shows that excessive anteroposterior instability of the distal clavicle can cause postoperative shoulder pain and poor surgical outcome.

Acromioclavicular Joint↗

PubMed1998

Impingement syndrome and rotator cuff disease as repetitive motion disorders.

The relationship between repetitive motion and subacromial impingement and rotator cuff disease is controversial and poorly understood. The potential etiology is multifactorial and involves patient related factors (age, supraspinatus outlet anatomy, and preexisting rotator cuff pathology) and worker related factors (arm position, lifting requirements, numbers of repetitions). Radiographic and magnetic resonance imaging abnormalities may represent preexisting disease that could have predisposed the patient to the development of impingement syndrome, but should be interpreted cautiously within the context of the remainder of the clinical picture. Treatment often involves temporary or permanent modifications of the work environment.

Biomechanical Phenomena↗

PubMed1997

Prevalence and features of joint hypermobility among adolescent athletes.

OBJECTIVE: To determine the prevalence of joint hypermobility in a group of adolescent, interscholastic athletes. DESIGN: Cross-sectional; descriptive or observational. SETTING: Free preparticipation physical examinations for sports. SUBJECTS: Two hundred and sixty-four athletes (150 male, 114 female; average age, 15.5 years) comprised the entire set of athletes who came to our clinic for free physical examinations. INTERVENTION AND MAIN OUTCOME MEASURES: We screened 264 athletes using the widely accepted Carter-Wilkinson-Beighton method, which examines range of motion at the knees, trunk, fingers, thumbs, and elbows bilaterally and employs a 0 to 9 scoring scheme (5 = hypermobile). We also used an "injury allowance," whereby if an athlete screened positive for only one side of a bilateral test but had a history of injury to the corresponding side, he or she was given an injury allowance point. RESULTS: Thirty-two scored 5 or higher, with another 2 screening positive for hypermobility by the injury allowance, for a total of 34 hypermobile athletes (12.9%). There was a highly significant difference between sexes (P < .001), with 25 female (22%) and 9 male subjects (6%) testing positive. CONCLUSIONS: The overall prevalence of hypermobility and the significant sex difference found in this group of adolescent athletes were similar to nonathletes populations of comparable age. Research on nonathletes has been relied on by many to recommend that hypermobile persons avoid strenuous physical activity; however, research on athletes is less than conclusive. Given that a significant segment of young athletes, especially females, may be hypermobile, prospective studies are warranted to investigate this question before we can justify depriving hypermobile youths of the many known benefits of regular or strenuous exercise.

Adolescent↗

PubMed1997

Trefoil factor family domain peptides.

Within the past 15 years a new family of peptides has been identified, known as trefoil factor family (TFF) domain peptides; they are associated with mucin-secreting epithelial cells and synthesised predominantly in the gastrointestinal tract. They share a highly conserved physical structure, and their role in mucosal defence and healing is becoming increasingly clear, more recently a tumour suppressor function has been postulated. Outside the gastrointestinal tract, members of this group of peptides have also been identified in the normal hypothalamus and pituitary, and in normal breast tissue where it is responsive to oestrogen stimulation. Evidence of peptide expression has been found in a range of urological, gynaecological, gastrointestinal, pulmonary and breast carcinomas, and in the last two it appears to carry prognostic significance. The present review aims to summarise the rapidly expanding data on the role of these peptides in epithelial inflammation, repair and neoplasia.

Animals↗

PubMed1997

Keratin expression in anal carcinoma: an immunohistochemical study.

The keratin expression of 40 frozen tissue specimens of anal carcinoma was investigated using a panel of 17 monoclonal antibodies to 14 individual keratins. The tumours were divided into three histological subgroups showing pure squamous, squamous and basaloid, or squamous and glandular differentiation. A further assessment of the tumour grade was made. The overall profile was of expression of keratins 4, 13, 17, 18 and 19 across the majority of the tumours, with the minority expressing keratins 1 and 10, and keratin 7. Dedifferentiation was associated with loss of expression of keratinocyte keratins, particularly the cornification markers keratin 1 and 10, and K6 and 16 associated with keratinocyte hyperproliferation and differentiation. This correlated with acquisition of the simple epithelial keratins 7 and 8. Compared with the tumours as a whole, well differentiated squamous tumours (the most easily identifiable histological group) showed consistent positivity for keratins 6 and 16, expressed suprabasally, while simple keratins 18 and 19 were also found. Independent of grade, mixed tumours showed more widespread positivity for simple epithelial keratins 7, 8 and 18 and loss of expression of cornification keratins 1 and 10 and K6 and 16 compared with pure squamous tumours. The relatively limited keratin profile of pure squamous tumours, predominantly consisting of keratinocyte keratins, suggests that these malignancies are less likely to originate from the region of the anal canal where the keratin profile is heterogeneous, i.e. the anal transitional zone.

Anus Neoplasms↗

PubMed1997

The vitamin D analog, KH1060, is rapidly degraded both in vivo and in vitro via several pathways: principal metabolites generated retain significant biological activity.

Vitamin D analogs are valuable drugs with established and potential uses in hyperproliferative disorders. Lexacalcitol (KH1060) is over 100 times more active than 1alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3], as judged by in vitro antiproliferative and cell differentiating assays. The underlying biochemical reasons for the increased biological activity of KH1060 are unknown, but are thought to include 1) metabolic considerations in addition to explanations based upon 2) enhanced stability of KH1060-liganded transcriptional complexes. In this study we explored the in vivo and in vitro metabolism of KH1060. We established by physicochemical techniques the existence of multiple side-chain hydroxylated metabolites of KH1060, including 24-, 24a-, 26-, and 26a-hydroxylated derivatives as well as side-chain truncated forms. KH1060 metabolism could be blocked by the cytochrome P450 inhibitor, ketoconazole. KH1060 was not an effective competitor of C24 oxidation of 1alpha,25-(OH)2D3. Certain hydroxylated metabolites of KH1060 retained significant biological activity in vitamin D-dependent reporter gene systems (chloramphenicol acetyltransferase). Likewise, those metabolites accumulating in the target cell culture models in metabolism studies, particularly 24a-hydroxy-KH1060 and 26-hydroxy-KH1060, retained biological activities superior to those of 1alpha,25-(OH)2D3 in native gene expression systems in vitamin D target cells (osteopontin and P450cc24). We conclude that KH1060 is rapidly metabolized by a variety of cytochrome P450-mediated enzyme systems to products, many of which retain significant biological activity in vitamin D-dependent assay systems. These results provide an explanation for the considerable biological activity advantage displayed by KH1060 compared with 1alpha,25-(OH)2D3 in various in vitro assay systems.

Animals↗

PubMed1997

Thyroid hormone, vitamin D and retinoid receptor expression and signalling in primary cultures of rat osteoblastic and immortalised osteosarcoma cells.

3,5,3'-Tri-iodothyronine (T3), 1 alpha,25(OH)2-vitamin D3 (D3) and retinoids activate related nuclear receptors which interact by heterodimerisation to regulate gene expression. Actions of each hormone are discrete and may be specified by changes in the relative concentrations of their receptors (T3R, vitamin D receptor (VDR), retinoic acid receptor (RAR), retinoid X receptor (RXR)). T3, D3 and retinoids are essential for skeletal development and maintenance and we have previously shown complex interactions amongst their signalling pathways in osteosarcoma cells. In these studies we demonstrate that similar T3R, VDR, RAR and RXR proteins are co-expressed in both osteoblast lineage cell primary cultures and osteosarcoma cells by Western blotting. We investigated whether hormone interactions in bone result from changes in receptor stoichiometry. Cells were treated with combinations of T3, D3, 9-cis retinoic acid (9-cis RA) and all-trans retinoic acid (RA) that are known from previous studies to produce complex cell specific responses. No alteration in expression of any receptor protein was seen in response to any hormone combination in three phenotypically distinct osteosarcoma cell lines. Thus, in contrast to studies of overexpressed receptors in vitro, changes in the physiological concentrations of endogenous T3R, VDR, RAR and RXR do not specify discrete hormone actions in osteoblastic cells. Other unidentified factors are likely to modulate hormone action in these bone cells.

Animals↗

PubMed1997

Treatment of complications of shoulder arthrodesis.

A reconstructive osteotomy was performed to correct symptomatic malposition after arthrodesis of the shoulder in nine of fourteen patients who had complications related to the arthrodesis. The clinical position of the arm in relation to the trunk was determined with the method described by Rowe. Malposition was primarily the result of fusion in more than 15 degrees of either flexion or abduction, or both, coupled with improper rotation, defined as rotation of less than 40 degrees or more than 60 degrees. Reconstructive osteotomy eliminated pain and improved the ability of the patient to perform six activities of daily living. The complications necessitating operative treatment after the arthrodesis in the remaining five patients included failure of the arthrodesis site to unite (three patients), a wound hematoma at the iliac-crest donor site (one patient), and a superficial wound infection (one patient). Two additional complications - a fracture through a screw-hole in the humerus and a fracture distal to the internal fixation device - occurred after the reconstructive osteotomies for malposition. All of the complications resolved with treatment. Arthrodesis of the shoulder is a technically demanding procedure that can lead to serious complications that necessitate operative intervention. Careful attention to operative technique and to the position of the arthrodesis are essential.

Activities of Daily Living↗

PubMed1997

Glenohumeral joint translations before and after total shoulder arthroplasty. A study in cadavera.

UNLABELLED: The purpose of the present study was to examine the motions of natural and prosthetically reconstructed glenohumeral joints without capsular contracture in the laboratory to obtain a better understanding of joint motion as it may relate to failure of the implant. Seven joints from fresh-frozen human cadavera were instrumented with a six-degrees-of-freedom magnetic tracking device to study patterns of translation and rotation with and without the application of simulated muscle forces (active and passive models). The specimens were tested before and after reconstruction of the joint with use of modified operative techniques and implants that had from zero to five millimeters of radial mismatch between the humeral head and glenoid components. The natural and reconstructed joints had similar patterns of translation, with larger rotations and translations observed in the passive model. On the average, the active translations of the natural joints were best reproduced by the reconstructed joints with less conforming articulations. The mean active translation in the natural joints was 1.5 millimeters along the anterior-posterior axis and 1.1 millimeters along the superior-inferior axis. The active translations in the reconstructed joints were observed to increase consistently as the conformity of the components decreased: the mean active anterior-posterior translations ranged from 0.3 millimeter for conforming components to 1.7 millimeters for components with a five-millimeter radial mismatch, and the mean active superior-inferior translations ranged from 0.4 to 1.1 millimeters. The patterns of translation during passive motions were less consistent, presumably because of the influence of capsular ligaments and because the translations were large enough for the articular surface of the humeral head to lose contact with the articular surface of the glenoid component. CLINICAL RELEVANCE: Glenohumeral translations during active motions were found to depend on articular conformity, which indicates that the choice of implants may have important consequences for normal motions. Totally conforming designs may impose a degree of restraint to translations that is higher than that in the natural joint. The patterns of translation may influence the longevity of the joint replacement with respect to stability, loosening of the glenoid component, and wear of the components.

Aged↗

PubMed1997

Repair of soft tissue to bone using a biodegradable suture anchor.

The medial collateral ligaments of 18 New Zealand rabbits were surgically detached from bone. In one knee, the ligament was repaired using a biodegradable suture anchor composed of a co-polymer of lactic and glycolic acid. The contralateral medial collateral ligament was not repaired. Animals were sacrificed at 4, 8, and 12 weeks after the operation, and the knee that had the ligament repair was compared with the contralateral control knee. All knees were tested manually tested for stability to valgus stress and then prepared for histologic examination. Medial collateral ligaments repaired using the biodegradable suture anchor demonstrated stability to valgus stress and anatomic healing at the bone-tendon junction. Resorption of the implant was virtually complete by 12 weeks. All specimens demonstrated less inflammatory reaction to the suture anchor than to the attached Vicryl suture. This contrasts with the control group, which was grossly unstable and demonstrated scarring in this nonanatomic position. These results demonstrate efficacy of this particular material of biodegradable implant and justify further investigative efforts.

Animals↗

PubMed1997

Surgical treatment of postoperative deltoid origin disruption.

Although it is well recognized that deltoid disruption after shoulder surgery is associated with poor function, little information is available regarding results of surgical treatment for this problem. Twenty-four patients underwent direct repair or rotational deltoidplasty reconstruction of a detached muscle origin after shoulder surgery. The original surgical procedure was rotator cuff repair in 12, acromioplasty in four, and lateral acromionectomy with or without rotator cuff repair in eight. The average duration of symptoms before deltoid reconstruction was 17 months. The mean followup was 39 months (range, 13-84 months). Twelve patients reported moderate to severe pain, whereas 12 had minimal pain. Two patients required a shoulder fusion for intractable pain. Overall, one (4%) excellent, seven (29%) good, and 16 (67%) unsatisfactory results were observed. A poor outcome was associated with a prior lateral acromionectomy, involvement of the middle deltoid, a massive rotator cuff tear with weakness in external rotation, and a residual postoperative defect larger than 2 cm. In select cases, repair or deltoidplasty can improve function and pain.

Acromion↗

PubMed1996

Antiproliferative responses to two human colon cancer cell lines to vitamin D3 are differently modified by 9-cis-retinoic acid.

1 alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] exerts antiproliferative actions in colorectal cancer, but their underlying molecular mechanisms have not been determined. 1,25(OH)2D3 regulates target gene transcription via a specific nuclear vitamin D receptor (VDR), which mediates hormone action preferentially as a heterodimer with 9-cis-retinoic acid receptors (RXRs). We investigated the actions of 1,25(OH)2D3 and 9-cis-retinoic acid (RA) in two human colon cancer cell lines, HT-29 and Caco-2. Both expressed mRNAs encoding VDR, RXR alpha, and RXR gamma, and VDR was regulated posttranscriptionally in Caco-2 cells. There was an antiproliferative response of both cell lines to 1,25(OH)2D3. 9-cis-RA exerted antiproliferative effects on Caco-2 cells but blocked 1,25(OH)2D3 actions in HT-29 cells. The 1,25(OH)2D3-responsive gene 25-hydroxyvitamin D3 24-hydroxylase was induced in both cell lines b 1,25(OH)2D3 but in only HT-29 cells by 9-cis-RA. 1,25(OH)2D3 and 9-cis-RA cotreatment enhanced 24-hydroxylase expression in HT-29 cells only. The 24-hydroxylase enzyme is known to result in catabolism of 1,25(OH)2D3 and attenuation of its actions. Increased 24-hydroxylase activity in HT-29 cells, but not in Caco-2 cells, in response to 9-cis-RA may account for some of the complex cell-specific responses demonstrated in these studies.

Antineoplastic Agents↗

PubMed1996

Properties of HPV-positive and HPV-negative anal carcinomas.

Evidence of human papillomavirus (HPV) can be found in up to 85 per cent of anal carcinomas. In the vulva, a discrete subset of HPV-positive carcinomas which show koilocytic morphology and distinct clinical features has recently been identified (warty carcinoma). The morphological and prognostic features of HPV-positive and HPV-negative anal carcinomas were compared in this study of the tumour distribution of HPV DNA. Vulval and anal neoplasia are similar in many ways and we have also looked to see if their similarity extends to 'warty' morphology in relation to HPV status. Thirty-five resection specimens of anal carcinoma were examined with biotin-labelled probes for HPV 6, 11, 16, and 18 DNA, using a non-isotopic in situ hybridization (ISH) technique. No tumour was found to contain HPV 6, 11, or 18. Twenty-four (72 per cent) showed positivity for HPV 16 DNA. Staining was homogeneous and independent of local squamous, basaloid, or ductal differentiation. The majority of tumours showed staining suggestive of episomal, non-productive HPV infection. HPV-positive tumours were more likely to occur in the anal canal than perianally and to show a mixed squamous and basaloid appearance. No difference between the two groups was found in patient age, presence of adjacent dysplasia, ductal differentiation, or prognosis. There was no correlation between condylomatous tumour morphology and HPV 16 DNA positivity; thus, a subset equivalent to vulval warty carcinoma could not be identified.

Anus Neoplasms↗

PubMed1996

Kinematics of the glenohumeral joint: influences of muscle forces, ligamentous constraints, and articular geometry.

Despite recent interest in the study of shoulder kinematics, there is considerable controversy in the literature regarding translations at the glenohumeral joint. The purpose of this study was to investigate the key factors that control shoulder motions, thus leading to a better understanding of joint function. Translation and rotation patterns were studied in fresh-frozen glenohumeral joints of human cadavers with a six-degrees-of-freedom magnetic tracking device. Shoulders were positioned from maximal internal to external rotation at several arm positions (various elevations and planes of motion). In order to determine the effect of muscle forces, joints were positioned both actively and passively. Additionally, articular surface geometry and ligament origin-insertion wrap lengths were measured to assess their influences on joint kinematics. When joints were positioned passively, large translations were observed at the extremes of motion. With active positioning, muscle forces tended to limit humeral head translations, principally by restricting rotational ranges of motion. However, when data from the passive model were reanalyzed by considering only the rotational ranges of motion seen actively, no significant differences in translation were found between the two models. Joint conformity was found to have a significant influence on translations during active positioning but not during passive positioning. Glenohumeral ligament wrap lengths, however, correlated with translations when joints were positioned passively but not when positioned actively. Findings from this study emphasize the importance of muscle forces in keeping the humeral head centered in the glenoid. Although large translations are possible, they can be achieved only with increases in rotational ranges of motion associated with the removal of muscle force. Additionally, joint conformity appears to play a role in controlling translations during active motions, whereas capsular constraints become more important during passive motions.

Aged↗

PubMed1996

Damage to the photoreceptor cells of the rabbit retina from 56Fe ions: effect of age at exposure, 1.

Optic and proximate tissues of New Zealand white (NZW) rabbits at ages (approximately 3.5 years) near the middle of their median lifespan (5-7 years) were given 0.5-3.5 Gy of 465 MeV u-1 56Fe ions in the Bragg plateau region of energy deposition at a linear energy transfer (LET infinity) of 220 +/- 31 keV micrometer-1. Dose-dependent losses of retinal photoreceptor cells (rods) occurred until 1-2 years after irradiation, the period of this interim report. Similar cumulative losses of photoreceptor cells were seen during the period 1-2 years post-irradiation for rabbits given comparable exposures when young (6-9 weeks old). Since losses of photoreceptor cells at early times had not been determined previously, the current experiment, which was designed to simulate the responses of mature astronauts, redressed that deficiency.

Age Factors↗

PubMed1996

Anatomic, histologic, and magnetic resonance imaging abnormalities of the shoulder.

Six fresh frozen, human cadaver shoulders were evaluated for gross anatomic, magnetic resonance imaging, and histologic abnormalities. The shoulders underwent routine magnetic resonance imaging with and without intraarticular Gadolinium using a standard surface shoulder coil. The shoulders were dissected in a systematic fashion to yield 18 anatomic specimens from the supraspinatus and infraspinatus tendon as well as the glenoid labrum. These specimens were studied histologically using hematoxylin and eosin and Goldner's trichrome stains. Gross anatomic and magnetic resonance image abnormalities of the rotator cuff corresponded to histologic changes consistent with tendon degeneration. However, there was a poor correlation between gross anatomic, magnetic resonance image, and histologic changes of degeneration in the glenoid labrum. In general, histologic degeneration was more severe than abnormalities seen either grossly or on magnetic resonance images.

Adult↗

PubMed1996

Open medial subtalar dislocation associated with fracture of the posterior process of the talus.

A case of medial subtalar dislocation associated with fracture of the posterior process of the talus is described. Although this injury pattern is uncommon, it is important to recognize the associated fracture, as it involves a weightbearing articular surface. In this case, the flexor hallucis longus also prevented anatomic closed reduction necessitating open reduction and internal fixation.

Adult↗

PubMed1996

Evaluation of the Neer system of classification of proximal humeral fractures with computerized tomographic scans and plain radiographs.

The intraobserver reliability and inter-observer reproducibility of the Neer classification system were assessed on the basis of the plain radiographs and computerized tomographic scans of twenty fractures of the proximal part of the humerus. To determine if the observers had difficulty agreeing only about the degree of displacement or angulation (but could determine which segments were fractured), a modified system (in which fracture lines were considered but displacement was not) also was assessed. Finally, the observers were asked to recommend a treatment for the fracture, and the reliability and re-producibility of that decision were measured. The radiographs and computerized tomographic scans were viewed on two occasions by four observers, including two residents in their fifth year of postgraduate study and two fellowship-trained shoulder surgeons. Kappa coefficients then were calculated. The mean kappa coefficient for intraobserver reliability was 0.64 when the fractures were assessed with radiographs alone, 0.72 when they were assessed with radiographs and computerized tomographic scans, 0.68 when they were classified according to the modified system in which displacement and angulation were not considered, and 0.84 for treatment recommendations; the mean kappa coefficients for interobserver reproducibility were 0.52, 0.50, 0.56, and 0.65, respectively. The interobserver reproducibility of the responses of the attending surgeons regarding diagnosis and treatment did not change when the fractures were classified with use of computerized tomographic scans in addition to radiographs or with use of the modified system in which displacement and angulation were not considered; the mean kappa coefficient was 0.64 for all such comparisons. Over-all, the addition of computerized tomographic scans was associated with a slight increase in intraobserver reliability but no increase in interobserver reproducibility. The classification of fractures of the shoulder remains difficult because even experts cannot uniformly agree about which fragments are fractured. Because of this underlying difficulty, optimum patient care might require the development of new imaging modalities and not necessarily new classification systems.

Decision Making↗