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Biomedical subjects

G R Williams

Publications and source records attributed to G R Williams.

At least 55 records · Page 3Linked to original sources
PubMed1999

Hormone regulation of chondrocyte differentiation and endochondral bone formation.

Endochondral bone formation, the formation of calcified bone on a cartilage scaffold, occurs during skeletal development, post natal growth and during bone remodelling and fracture repair. The epiphyseal growth plates represent classical tissues in which to study the ossification process, which requires two co-ordinated components; progressive chondrocyte differentiation and cartilage neovascularisation. Many gene knockout studies have produced new insights regarding how chondrocyte differentiation and angiogenesis are controlled at the molecular level. Additional genetic studies have produced new information regarding the role of hormones in the regulation of endochondral bone formation. The new challenge for the future is to determine how bone formation and turnover is physiologically regulated and co-ordinated to ensure that skeletal development and growth progresses correctly. This study reviews the emerging data in this quickly growing field which should ultimately provide fundamental insights into the normal control of endochondral ossification.

Animals↗
PubMed1999

Novel DAX1 mutations in X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism.

OBJECTIVE: Mutations of the DAX1 gene (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita critical region on the X chromosome gene 1), which encodes a novel orphan nuclear receptor, have been identified in patients with X-linked adrenal hypoplasia congenita (AHC) and hypogonadotrophic hypogonadism (HHG). We have investigated two kindreds with AHC and HHG for DAX1 mutations. METHODS: Two kindreds with five affected males, four carrier females and four unaffected males were investigated. The gonadotrophin deficiency in three of the boys was observed to be partial until mid-puberty. DAX1 mutations in the entire 1413 bp coding region were sought by DNA sequence analysis. RESULTS: Two DAX1 mutations, situated within exon 1, were detected. These consisted of an insertional mutation at codon 183 that led to a frameshift and a premature Stop at codon 184, and a missense mutation Leu278Pro that involved a highly conserved leucine residue within the proposed ligand binding domain. Co-segregation of these mutations with the disease in each family, and their absence from 107 alleles in 73 (39 males and 34 females) unrelated control individuals, was demonstrated by allele specific oligonucleotide hybridization (ASO) analysis for the insertional mutation, and by Ban I restriction endonuclease analysis for the missense mutation. CONCLUSIONS: Two novel DAX1 mutations have been detected in two families with adrenal hypoplasia and hypogonadotrophic hypogonadism. The finding of partial gonadotrophin deficiency in the affected males from these families is notable and an early recognition of such a possibility in a patient, which may be facilitated by DAX1 mutational analysis, may help to prevent the sequelae of delayed androgen replacement therapy.

Adolescent↗
PubMed1999

A comparison of three health status measures in primary care outpatients.

Our objective was to compare a brief, relatively new global health status measure, the Health Utilities Index Mark II (HUI), to two commonly applied health status measures (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36] and the Sickness Jgipact Profile [SIP] in a general medical outpatient population. Using a cross-sectional survey, we surveyed 160 patients in the General Medical Clinic of the Durham Veterans Affairs Medical Center. Each subject answered demographic questions and then completed the three health status measures. The mean tJgie taken to complete the measures was 3, 10, and 20 minutes for the HUI, SF-36, and SIP, respectively (p <.0001). The HUI exhibited a modest "floor" effect; that is, scores were concentrated near the sicker of the scale. In contrast, responses to the SIP were heavily concentrated near the healthier end of the scale. Spearman correlation coefficients between the HUI and scales within the other two measures ranged from. 54 (SF-36 mental health) to 0.69 (SF-36 physical functioning). Subjects accepted all measures well. These three health service measures varied in their distribution of responses and ttime required to complete. Users should consider the degree of sickness of the population to be assessed when choosing a measure.

Adult↗
PubMed1999

Anatomy of the scapulothoracic articulation.

Four fresh frozen human cadavers (eight extremities) consisting of the head, neck, thorax, and entire upper extremities were used for dissection of the scapulothoracic articulation. In each specimen, the spinal accessory nerve, all relevant muscle insertions, and bursae were identified and measured. The structures of the scapulothoracic articulation can be divided into superficial, intermediate, and deep layers. The superficial layer consists of the trapezius, latissimus dorsi, and an inconsistent bursa between the inferior angle of the scapula and the latissimus dorsi. The intermediate layer consists of the levator scapulae, rhomboid minor and major, spinal accessory nerve, and scapulotrapezial bursa located between the superomedial scapula and the overlying trapezius. In all specimens, the spinal accessory nerve traveled intimately along the wall of the scapulotrapezial bursa, an average of 2.7 cm lateral to the superomedial angle of the scapula. The deep layer consists of the serratus anterior, subscapularis, and two bursae: one between the serratus and the thorax, the scapulothoracic bursa; and one between the subscapularis and the serratus, the subscapularis bursa.

Accessory Nerve↗
PubMed1999

Incidence and occurrence of total (first-ever and recurrent) stroke.

BACKGROUND AND PURPOSE: It has recently been hypothesized that the figure of approximately half a million strokes substantially underestimates the actual annual stroke burden for the United States. The majority of previously reported studies on the epidemiology of stroke used relatively small and homogeneous population-based stroke registries. This study was designed to estimate the occurrence, incidence, and characteristics of total (first-ever and recurrent) stroke by using a large administrative claims database representative of all 1995 US inpatient discharges. METHODS: We used the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, release 4, which contains approximately 20% of all 1995 US inpatient discharges. Because the accuracy of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) coding is suboptimal, we performed a literature review of ICD-9-CM 430 to 438 validation studies. The pooled results from the literature review were used to make appropriate adjustments in the analysis to correct for some of the inaccuracies of the diagnostic codes. RESULTS: There were 682 000 occurrences of stroke with hospitalization (95% CI 660 000 to 704 000) and an estimated 68 000 occurrences of stroke without hospitalization. The overall incidence rate for occurrence of total stroke (first-ever and recurrent) was 259 per 100 000 population (age- and sex-adjusted to 1995 US population). Incidence rates increased exponentially with age and were consistently higher for males than for females. CONCLUSIONS: We conservatively estimate that there were 750 000 first-ever or recurrent strokes in the United States during 1995. This new figure emphasizes the importance of preventive measures for a disease that has identifiable and modifiable risk factors and for the development of new and improved treatment strategies and infrastructures that can reduce the consequences of stroke.

Adult↗
PubMed1999

Determining clinically important differences in health status measures: a general approach with illustration to the Health Utilities Index Mark II.

The objective of this article was to describe and illustrate a comprehensive approach for estimating clinically important differences (CIDs) in health-related quality-of-life (HR-QOL). A literature review and pilot study were conducted to determine whether effect size-based benchmarks are consistent with CIDs obtained from other approaches. CIDs may be estimated based primarily upon effect sizes, supplemented by more traditional anchor-based methods of benchmarking (i.e. direct, cross-sectional or longitudinal approaches). A literature review of articles discussing CIDs provided comparative data on effect sizes for various chronic conditions. A pilot study was then conducted to estimate the minimum CID of the Health Utilities Index (HUI) Mark II, and to compare the observed between-group differences observed in a recent randomised trial of an acute stroke intervention with this benchmark. The use of standardised effect size benchmarks has a number of advantages-for example, effect sizes are efficient, widely accepted outside HR-QOL, and have well accepted benchmarks based upon external anchors. In addition, our literature review and pilot study suggest that effect size-based CID benchmarks are similar to those which would be obtained using more traditional methods. For most HR-QOL instruments, we do not know the changes in score which constitute CIDs of various magnitudes. This makes interpretation of HR-QOL results from clinical trials difficult, and having a benchmarking process which is relatively straightforward would be highly desirable.

Clinical Trials as Topic↗
PubMed1998

A new in vivo technique for three-dimensional shoulder kinematics analysis.

OBJECTIVE: The field of shoulder kinematics research has long relied upon the use of cadaveric models or invasive techniques in human volunteers. In this paper, a novel method is presented that utilizes magnetic resonance imaging (MRI) and a software system called 3DVEWNIX. This method permits non-invasive, repetitive evaluation of living patients for glenohumeral kinematics analysis. The objectives of this study were twofold: to validate the quantitative accuracy of this technique; and to demonstrate glenohumeral relationships in asymptomatic volunteers during internal and external rotation of the arm. DESIGN: The translational accuracy was first assessed by comparing known cadaveric glenohumeral translations with calculations from MR images of the cadaver. Nine asymptomatic volunteers were subsequently placed in an external shoulder positioning device in the scanner and imaged in 10 degrees increments of actively achieved internal and external rotation. Three-dimensional reconstructions of the glenoid and humerus were used to evaluate the glenohumeral relationships in the tested positions of rotation. RESULTS: The quantitative analysis revealed an error of 0.61 mm (SEM 0.11 mm). Examination of the volunteers demonstrated normal relationships about the glenohumeral joint in internal and external rotation. In addition, this method provided detailed images of the bony surface architecture from any perspective. These images can be transformed into a cinematic three-dimensional depiction of active shoulder rotation. CONCLUSION: This new technique offers an accurate, non-invasive method for assessing the normal glenohumeral relationships in shoulder kinematics. We now possess the capability to investigate the kinematics of normal and abnormal shoulder conditions non-invasively in a large patient population.

Adult↗
PubMed1998

Total shoulder arthroplasty. Factors influencing prosthetic design.

There are many anatomic and biomechanical factors that define the structure and function of the normal glenohumeral joint. These factors influence the design and function of the prosthetic shoulder. Our best efforts in shoulder design should reflect an attempt to reproduce the normal structure-function relationships of the natural glenohumeral joint. Prosthetic design must also take into account the variable anatomic abnormalities associated with the pathologic condition. Prosthetic designs should attempt to facilitate the surgical correction of this pathology, with the goal of reproducing normal anatomy. Optimal prosthetic reconstruction of the shoulder is dependent on prosthetic design, prosthetic soft tissues, postoperative healing and rehabilitation, and the long-term biologic response to the implant. The success of any prosthetic reconstruction is dependant on many factors, and in some cases, normal anatomy and function cannot be achieved entirely by prosthetic design.

Arthroplasty, Replacement↗
PubMed1998

Impingement syndrome following total shoulder arthroplasty and humeral hemiarthroplasty: treatment with arthroscopic acromioplasty.

Pain following total shoulder arthroplasty or humeral hemiarthroplasty is uncommon. Impingement syndrome can be an infrequent source of pain following shoulder arthroplasty. We retrospectively reviewed six patients with refractory impingement syndrome treated with arthroscopic acromioplasty following either total shoulder arthroplasty (four patients) or humeral hemiarthroplasty (two patients). Chronic impingement syndrome requiring acromioplasty affected 3% of all patients who underwent total shoulder arthroplasty or humeral hemiarthroplasty during the study period. A thorough history, physical examination, and radiographic findings made the clinical diagnosis of impingement syndrome. All six patients had positive impingement signs and a positive impingement test with subacromial lidocaine injection. Preoperative radiographs revealed a type II or III acromion and subacromial outlet narrowing in five of six patients. Other sources of shoulder pain including prosthesis loosening, infection, and rotator cuff tear were ruled out preoperatively by physical examination and radiographic findings, and were confirmed by arthroscopic examination. The results of arthroscopic acromioplasty were a reduction in pain from 7.5 preoperatively to 1.6 postoperatively, on a scale from 0 to 10. Five of six patients were completely satisfied with the results of their arthroscopic surgery. Overall, according to the University of California at Los Angeles end-result score, the results were rated as excellent or good in five patients, and unsatisfactory in one patient. Arthroscopic acromioplasty can be a successful technique for the treatment of chronic impingement syndrome following total shoulder arthroplasty or hemiarthroplasty in appropriate patients.

Acromion↗
PubMed1998

Management of perioperative pain in hospitalized patients: a national survey.

A survey was carried out to provide "benchmark" data on current practices of in-hospital perioperative pain management. The 59-item survey questionnaire incorporated all key points contained in the Agency for Health Care Policy and Research and the American Society of Anesthesiologists published guidelines concerning institutional policies as well as practice patterns. The questionnaire was mailed to designated pain specialists in a sample of 400 hospitals that were systematically stratified by bed size and geographic region. Of the 400 questionnaires mailed, 223 (56%) were returned. Of the 223 respondents, 85% were board-certified anesthesiologists. There was good to excellent overall adherence to most of the guideline recommendations; significant exceptions were the infrequent use of nonpharmacologic techniques for pain control and the relatively high frequency of intramuscular opioid use. In general, large hospitals have a greater adherence to the recommendations of the guidelines than do smaller hospitals. No noteworthy variations in institutional policies or practice patterns were evident. These results provide comprehensive baseline data against which future developments in the field of perioperative pain management can be assessed.

Data Collection↗
PubMed1998

Validation of a quality assurance program for autologous cultured chondrocyte implantation.

The use of living human cells to facilitate repair of defects in structural tissues is a rapidly emerging treatment option. A quality assurance program based on U.S. Food and Drug Administration good manufacturing practice regulations and other guidance was established and implemented in a program to use autologous cultured chondrocytes for repair of articular defects of the knee. The development of ex vivo cell therapies presents novel issues of quality assurance. The implementation and evaluation of this quality program was based on the implantation of 303 patients with autologous cultured chondrocytes, in which we analyzed a number of quantifiable parameters and which meets the unique challenges of autologous cell therapy within a rigorous regulatory framework. Application of well-accepted principles of quality assurance and quality control coupled with a thorough understanding of the cell culturing processes will result in a safe and efficacious cell therapy product.

Cartilage, Articular↗
PubMed1998

Total shoulder arthroplasty biomechanics: a study of the forces and strains at the glenoid component.

The objective of this study was to examine how changes in glenohumeral joint conformity and loading patterns affected the forces and strains developed at the glenoid. After removal of soft tissue (muscles, ligaments, and labrum), force-displacement data were collected for both natural and prosthetically reconstructed joints. Joints were shown to develop higher forces for a given translation as joint conformity increased. A rigid body model of joint contact forces was used to determined the so-called effective radial mismatch of each joint. For the purposes of this study, the effective radial mismatch is defined as the mismatch required for a rigid body joint to have the same force-displacement relationship as the joint in question. This parameter is an indication of the deformation at the articular surface. The effective radial mismatch dramatically increased with increasing medial loads, indicating that under physiological loads, the effective radial mismatch of a joint is much greater than its measured mismatch at no load. This increase in effective mismatch as medial loads were increased was found to be threefold greater in cartilaginous joints than in reconstructed joints. Rosette strain gages positioned at the midlevel of the glenoid keel in the reconstructed joints revealed that anterior/posterior component loading leads to fully reversible cyclic keel strains. The highest compressive strains occurred with the head centered in the glenoid, and were larger for nonconforming joints (epsilon = 0.23 percent). These strains became tensile just before rim loading and were greater for conforming joints (epsilon = 0.15 percent). Although recorded peak strains are below the yield point for polyethylene, the fully reversed cyclic loading of the component in this fashion may ultimately lead to component toggling and implant failure.

Aged↗
PubMed1998

Hormone-induced changes in nuclear receptor stoichiometry in HL60 cells correlate with induction of monocyte or neutrophil differentiation.

HL60 cells differentiate to monocytes or neutrophils in response to 1 alpha,25(OH)2-vitamin D3 (D3) and retinoids respectively. D3 and retinoid actions converge since their receptors (VDR, RAR) heterodimerise with a common partner, RXR, which also interacts with thyroid hormone (T3) receptors (T3R). HL60 cells were treated with combinations of D3 and retinoids to induce differentiation and to investigate whether increased VDR or RAR expression correlated with monocyte or neutrophil differentiation and whether altered receptor concentrations affected DNA-binding specificity. As assessed by Western blotting, VDR and RXR expression was unchanged in monocytes relative to controls but levels of RAR and T3R were reduced. In contrast, only VDR expression was reduced in neutrophils. T3 did not promote differentiation or influence its induction by D3 or retinoids and did not affect expression of any receptor. Gel mobility-shift analysis revealed that nuclear extracts from undifferentiated cells, monocytes and neutrophils interacted differently with VDRE-, RARE- and RXRE-binding sites. Monocyte nuclear protein/DNA complexes contain readily detectable VDR and RXR whereas neutrophil complexes contain RAR and RXR. Thus hormone-induced changes in receptor stoichiometry favour either VDR/RXR or RAR/RXR heterodimerisation and correlate with hormone-induced differentiation of HL60 cells to monocytes or neutrophils respectively.

Blotting, Western↗
PubMed1998

Operative treatment of malunion of a fracture of the proximal aspect of the humerus.

We retrospectively reviewed the medical records, operative reports, and preoperative and postoperative radiographs of thirty-nine patients who had been managed operatively for malunion of a fracture of the proximal aspect of the humerus. The malunions were categorized according to the presence of osseous abnormalities, including malposition of the greater or lesser tuberosity (type I; twenty-eight patients), incongruity of the articular surface (type II; twenty-six patients), and malalignment of the articular segment (type III; sixteen patients). Soft-tissue abnormalities, such as soft-tissue contracture, a tear of the rotator cuff, and impingement, were also recorded. At an average of forty-four months (range, twelve to fifty-three months) postoperatively, the patients were assessed for pain relief, the range of motion of the shoulder, and the ability to perform activities of daily living. The result was satisfactory for twenty-seven patients (69 per cent) and unsatisfactory for the remaining twelve (31 per cent) at the latest follow-up evaluation. Of the twenty-seven patients who had a satisfactory result, twenty-six (96 per cent) had had complete operative correction of all osseous and soft-tissue abnormalities. Of the twelve patients who had an unsatisfactory result, four had had complete operative correction of these abnormalities (p < 0.0001). Twenty-six patients (67 per cent) had incongruity of the glenohumeral joint at the time of presentation. Twenty-three of these patients had the incongruity corrected with prosthetic arthroplasty (twenty-two) or arthrodesis of the glenohumeral joint (one); the result was satisfactory for seventeen (74 per cent). In contrast, the result was unsatisfactory for all three patients in whom the incongruity had not been corrected at the time of the operation (p = 0.01). Eleven patients had malposition of the greater or lesser tuberosity but a congruent joint surface preoperatively. Ten patients in this group were managed with either osteotomy of the tuberosity or acromioplasty, and nine of them had a satisfactory result at the latest follow-up evaluation. The result was unsatisfactory for one patient who was managed with only correction of a soft-tissue contracture (that is, no treatment of the malposition) (p = 0.05). Both osseous and soft-tissue abnormalities were identified as the cause of pain and stiffness in patients who had malunion of a fracture of the proximal aspect of the humerus. We concluded that operative management of these patients is successful only if all osseous and soft-tissue abnormalities are corrected at the time of the operation.

Acromion↗
PubMed1998

Effect of domperidone on the health-related quality of life of patients with symptoms of diabetic gastroparesis.

OBJECTIVE: To describe the health-related quality of life (HRQOL) of patients with insulin-treated diabetes and symptoms of diabetic gastroparesis and to assess the impact of domperidone on HRQOL in these patients. RESEARCH DESIGN AND METHODS: This two-phase multicenter study was part of a safety and efficacy investigation. Phase I involved 4-week single-blind treatment with domperidone 20 mg q.i.d. (n=269). Patients demonstrating significant symptomatic improvement (n=208) continued to phase 11, a 4-week, double-blind, parallel-group study with patients receiving placebo (n=103) or domperidone (n=105). Patients completed the Medical Outcomes Study Short-Form-36 Health Survey at selection and at the end of each phase. Physical component summary (PCS) and mental component summary (MCS) scores served as primary parameters, and the eight subscales were secondary parameters. RESULTS: HRQOL scores of subjects enrolled in the trial were significantly lower than norms from the general population and people with diabetes (P < 0.001). Subjects experiencing symptomatic improvement after 4 weeks of single-blind treatment demonstrated significant improvement in all HRQOL parameters (P < 0.001); PCS, MCS, and six subscale scores of nonresponders did not change. Between-group change score differences were significant for PCS, MCS, and seven subscales (P < 0.05 to P < 0.001). During phase II, the domperidone group maintained their HRQOL; the placebo group showed a significant decline in PCS and four subscales (P < 0.05). The between-group difference in the PCS score change was statistically significant (-1.77 vs. 0.65, P=0.05). CONCLUSIONS: Results suggest that patients with symptoms of diabetic gastroparesis experience notable HRQOL impairment and that symptomatic relief with domperidone is accompanied by improvements in HRQOL that can be sustained over 4 weeks of treatment.

Adult↗