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Biomedical subjects

C D Williams

Publications and source records attributed to C D Williams.

At least 37 records · Page 2Linked to original sources
PubMed1996

High-frequency cell surface expression of a foreign protein in murine hematopoietic stem cells using a new retroviral vector.

A retroviral vector (pSFF) derived from murine Friend spleen focus forming virus was used to transduce murine hematopoietic stem cells and express a cell surface marker protein, mutated murine prion protein, in vitro and in vivo after transplantation. To enhance retroviral vector integration in bone marrow cells, mice were treated with 5-fluorouracil (5-FU) to increase stem cell mitotic activity, which peaked on day 8 post-5-FU. The infectivity titer of the vector, pSFF-mPrP-3F4, was determined by a novel assay in which antigen-positive foci of infected cells were detected after replication and spread of the vector in cultures of mixed packaging cell lines. Infection of Sca-1+/Lineageneg-low cells with pSFF-mPrP-3F4 resulted in marker protein expression in 40% of the progeny cells after 7 days of culture. Transplantation of marrow cells or sorted Sca-1+/Lineageneg-low cells transduced with vector resulted in 3F4-positive mPrP expression in 11% to 37% of donor-derived peripheral blood leukocytes at 2 weeks. Though the percentage of 3F4-positive blood cells gradually declined, at 28 weeks 23% of recipient mice still maintained expression of the marker gene. Expression was observed in lymphoid, myeloid, and erythroid lineages and was detected in Sca-1+/Lineageneg-low marrow cells. The multilineage, high-frequency expression observed suggests that pSFF may be useful in gene therapy directed at hematopoietic stem cells and their differentiated progeny.

Animals↗
PubMed1996

Mechanical strength of scaphoid fixation.

We have investigated five devices suitable for scaphoid fixation (ASIF 2.7 mm and 3.5 mm cannulated screws, Herbert, Herbert-Whipple, and Howmedica Universal Compression Screw). The biomechanical properties tested were compression and resistance to cantilever bending. There was no statistically significant difference in compression between devices. There were significant differences in resistance to cantilever bending, with the Howmedica screw being strongest in both failure mode and in ultimate failure strength.

Bone Screws↗
PubMed1996

Purging of bone marrow in autologous bone marrow transplantation for non-Hodgkin's lymphoma: a case-matched comparison with unpurged cases by the European Blood and Marrow Transplant Lymphoma Registry.

PURPOSE: The use of in vitro purging of bone marrow in autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) has been a controversial issue; its benefit is as yet unproven. Its effect on the clinical outcome of ABMT in these patients is still unclear. We look at this issue using data from the European Blood and Marrow Transplant (EBMT) Lymphoma Registry. PATIENTS AND METHODS: Seventeen hundred twenty-six patients with NHL have been reported to the EBMT registry, of whom 270 had bone marrow purged at transplant. Two hundred twenty-four of these patients were compared with a case-matched group of 224 unpurged patients who had undergone the same procedure. The case matching was made following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis. Response, complications, and outcome in ABMT were analyzed. RESULTS: Time to hematologic engraftment, response to ABMT, and number of procedure-related deaths were similar in purged and unpurged patients. The overall survival (OS) rate was 54% at 5 years in purged patients and 48.3% in unpurged patients (P = .1813). The PFS rate was 44.3% and 44.6%, respectively (P = .1961). Patterns of relapse, including bone marrow relapse, were similar in both groups. Patients with low-grade lymphoma did not have a significantly improved PFS if the bone marrow was purged (P = .1757); however, they did have a significantly improved OS (P = .00184). This increased OS was found to be associated with non-totalbody irradiation (TBI) conditioning and also with the purged patients undergoing transplantation at large transplant centers (P = .0016). CONCLUSION: Purging of bone marrow in ABMT for NHL does not affect the rate of hematologic engraftment or risk of procedure-related death (PRD). There is no significant difference in PFS for patients whose bone marrow is purged as compared with unpurged.

Adolescent↗
PubMed1995

Biomechanical characteristics of suture techniques in extensor zone IV.

This study was designed to investigate several biomechanical parameters involved in repair of extensor tendons in Zone IV (over the proximal phalanx). Typical suture techniques over the proximal phalanx did not shorten the tendon significantly nor was there significant loss of flexion at the metacarpophalangeal or proximal interphalangeal joints. The Kleinert modification of the Bunnell technique and modified Kessler technique seemed to be the strongest and provided evidence that dynamic or active range of motion, under controlled conditions and in short arcs, might be physiologically tolerated by repaired tendons.

Biomechanical Phenomena↗
PubMed1994

Autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma and CNS involvement: those transplanted with active CNS disease have a poor outcome--a report by the European Bone Marrow Transplant Lymphoma Registry.

PURPOSE: CNS involvement of non-Hodgkin's lymphoma (NHL) has always been considered a poor prognostic factor in relation to survival with conventional therapy. However, its effect on the outcome of autologous bone marrow transplantation (ABMT) has not been assessed. We examined this using data from the European Bone Marrow Transplant (EBMT) Lymphoma Registry. PATIENTS AND METHODS: One thousand four hundred sixty-four patients with NHL have been reported to the EBMT registry, of whom 62 had CNS involvement. Patients were divided into those who were clear of CNS disease at the time of ABMT and those who were not. Response, complications, and outcome to ABMT were analyzed, as were details of CNS diagnosis, treatment, and prophylaxis. RESULTS: Status at transplant was the only factor that significantly affected outcome of ABMT on univariate analysis (P = .03). The progression-free survival (PFS) rate of the group that had no CNS involvement at ABMT was 42% at 5 years, compared with 27% in a group of stage IV NHL patients without CNS disease (matched for status at transplant and histology). There were four of 45 (8.9%) toxic deaths. The PFS rate of the group that had CNS involvement at ABMT was 9% at a median follow-up time of 71 months, which was significantly different (P = .001) from that of the other group. There were five of 17 (29.4%) toxic deaths (P = .043). Patients who had CNS involvement at diagnosis, as compared with relapse, and those treated with both intrathecal chemotherapy and irradiation had a better outcome. CONCLUSION: The presence of CNS disease before ABMT but not present at transplant does not adversely affect the outcome of ABMT. In contrast, patients with CNS involvement at the time of ABMT have a poor prognosis, although a small number survive in complete remission (CR).

Adolescent↗
PubMed1994

Autologous bone marrow transplantation in multiple myeloma: a single centre experience of 23 patients.

We report the complications and outcome of high-dose melphalan and TBI combined with ABMT used in the treatment of multiple myeloma at a single centre. Twenty-three patients, aged 65 years or less, who underwent the procedure are reviewed. All had chemosensitive disease. Response to ABMT assessed at 3 months showed 75% of evaluable patients to have further tumour cytoreduction of at least 50%, with 24% of patients who entered ABMT with residual disease eventually achieving CR. There was one toxic death. The overall survival is 60% and the progression-free survival is 49.8% at a median follow-up time of 17 months. Relapse or disease progression has occurred in 27% of patients, of whom half have died. No significant prognostic factors affecting survival were found although those patients with IgG myeloma had a better outcome. Patients transplanted in first plateau appeared to do significantly better if they had been resistant to their first-line chemotherapy but had then responded to further conventional chemotherapy (p = 0.029).

Adult↗
PubMed1993

Autologous bone marrow transplantation for pediatric Hodgkin's disease: a case-matched comparison with adult patients by the European Bone Marrow Transplant Group Lymphoma Registry.

PURPOSE: We analyzed the outcome of autologous bone marrow transplantation (ABMT) in pediatric and adult patients with Hodgkin's disease (HD) by means of a case-controlled study. PATIENTS AND METHODS: Eighty-one pediatric HD patients who had undergone ABMT and who had been reported to the European Bone Marrow Transplant Group (EBMTG) Lymphoma Registry were compared with a case-matched group of 81 adult patients who had undergone the same procedure. The case-matching was performed following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis. RESULTS: The PFS rate was not significantly different between the groups (39% for the pediatric group v 48% for the adult group). The overall relapse/progression rates for the groups were 52% and 40%, respectively. This was not a statistically significant difference and the sites of relapse were similar. There was no significant difference in the incidence or causes of procedure-related morbidity or mortality of the two groups. CONCLUSION: This study suggests that patients with pediatric HD have the same outcome at ABMT as their adult counterparts; however, long-term complications will need to be carefully monitored.

Adolescent↗
PubMed1992

Biomechanical characteristics of extensor tendon suture techniques.

Despite their ease of exposure, extensor tendons can be difficult to handle and suture well. Compared with flexor repair, little is known about the various factors that affect the suturing of extensor tendons. The present study was designed to investigate several biomechanical parameters involved in extensor repair. All techniques studied shortened the tendon considerably and produced significant losses of flexion at the metacarpophalangeal and proximal interphalangeal joints. In addition, repairs achieved with all suture techniques were considerably weaker than those achieved when comparable techniques were used on flexor tendons. However, the Kleinert modification of the Bunnell technique provided the strongest sutures in extensor tendons, produced no gapping, caused the least worrisome loss of metacarpophalangeal and proximal interphalangeal flexion, and best approximated the results found in an idealized tendon-shortening model.

Biomechanical Phenomena↗
PubMed1991

Comparison of the real-time use of glycosylated haemoglobin and plasma fructosamine in the diabetic clinic.

The within-clinic use of glycosylated haemoglobin (HbA1) and plasma fructosamine results in assessing blood glucose control and clinical management was compared in 1030 diabetic patients. The physician initially reviewed the patient with one randomly allocated measure (HbA1 or fructosamine) and completed a questionnaire concerning perception of blood glucose control, alteration to diet, alteration to medication, referral for diabetes education, and follow-up interval. The patient was then re-assessed using the second measure and the questionnaire repeated. Discordance rates for the study end-points, judged as binary outcomes, were: blood glucose control 15%; alteration to diet 7%; alteration to medication 9%; referral for education 3%; follow-up interval 4%. A significantly greater number of patients were rated as poorly controlled with HbA1 than with fructosamine (p less than 0.001) and were, in consequence, more frequently recommended alteration to diet and medication, referral for education and shorter follow-up interval; the rate of discordance for at least one of the management decisions was 16%. Multifactorial analysis showed that discordant management was dependent on the reviewing physician (p less than 0.001) and a history of cardiovascular disease (p less than 0.01); but neither type of diabetes, nor presence of nephropathy or variant haemoglobins, nor plasma glucose concentration, significantly influenced the likelihood of a discordance. Replacing HbA1 with fructosamine in the diabetic clinic may result in significant differences in the physician's perception of blood glucose control and in the management of patients.

Adult↗
PubMed1991

Circulatory dissemination of 15-mu particles from the immature rat femur.

Venous drainage from the femur of adult animals is not interrupted by occlusion of the blood supply in the soft tissue surrounding the diaphysis of the bone. Previous studies have shown that the metaphyseal drainage system is capable of rapidly transporting particles up to 100 mu in diameter to the lungs. The present study was performed to determine if venous drainage from the femur of immature animals possesses similar characteristics. Three-week-old rats were given a 5-microliters intramedullary injection containing radioactively labeled 15-mu-diameter microspheres. In the intact animal, the particles moved from the injection site in the femur to the lungs within two minutes; however, obliteration of blood flow in the soft tissue surrounding the femoral diaphysis significantly reduced this movement in most animals. The ratio of particles moving through the lungs into the peripheral arterial circulation was slow and similar to that found in adult animals.

Aging↗
PubMed1990

Data management and expert systems for outpatient diabetes care--16 years experience with diabeta.

The continuing development and implementation of a computer-based diabetes register and management system are described. For 15 years the system has been used as a readily accessible source of clinical data, for letter generation, for prompting screening procedures and for clinical audit and research. Later developments include the incorporation of specialist "intelligence" for advising management of individual patients. This is intended for use by non-specialists to enable their greater participation in diabetes care. It is currently undergoing preliminary evaluation with a view to conducting clinical trials both in Hospital and in General Practice.

Data Collection↗
PubMed1989

The principles and prototyping of a knowledge-based diabetes management system.

This paper describes the principles and prototyping of a computer-based system being developed to assist in the management of diabetes mellitus. Unlike other approaches based upon mathematical modelling or the use of computer algorithms, this system adopts one derived from artificial intelligence, seeking to incorporate the dynamics of glucose and insulin in a manner which reflects their clinical importance. The resultant logical model (qualitative algebra) defines the relationships between changes in insulin dose and site and time of injection and glycaemic response. In this manner the computer-based system, implemented in Prolog, can be used to provide advice concerning insulin therapy by means of making qualitative predictions of patient outcome of blood glucose profile resulting from alternative insulin regimens.

Blood Glucose↗
PubMed1989

The effect of a high protein diet on leucine and alanine turnover in acid maltase deficiency.

Leucine and alanine production rate was measured in 5 patients with acid maltase deficiency in the postabsorptive state, following 6 months on a normal diet with placebo and 6 months on an isocaloric high protein diet (16-22% protein). Whole body leucine production rate, a measure of protein degradation, expressed in terms of lean body mass was significantly greater than in five control subjects. Following the high protein diet, leucine production rate was decreased in four of the five patients but this was not statistically significant. Alanine production rate expressed in terms of lean body mass was significantly greater than in control subjects. After the high protein diet, alanine production rate and concentration were significantly decreased (p less than 0.05). There were no significant improvements in any of the clinically relevant variables measured in these patients. It is possible that a larger increase in protein intake over a longer time period may have a clinical effect.

Adult↗
PubMed1989

Altering local soft-tissue circulation fails to halt venous drainage from the femur.

It has been suggested that tourniquet application proximal to bone biopsy in an extremity can reduce the number of tumor cells spread through circulation. This study investigates the anatomical pathway through which rapid cell spread could occur. Radioactively labeled 15-mu microspheres were injected into the medullary canal of rat femurs. The ratio of injected particles found in the femur was compared among groups that received application of a tourniquet prior to injection, no tourniquet, or transection of all soft tissue proximal to the injection site. Obliteration of circulation in the soft tissue surrounding the femur with a tourniquet or tissue transection did not alter the spread of particles from the femur. The pulmonary circulation trapped approximately 95% of particles reaching the lungs, limiting their access to peripheral arterial circulation. If the number of particles injected into the femur was increased, the number of particles leaving the femur increased at an even greater rate. These data suggest that (1) a particle can exit the femur without traveling through the soft tissue surrounding the femur; (2) most particles that reach the lung are retained; and (3) the injected bone acts as a sponge, retaining some particles and permitting the rest to enter the venous drainage.

Animals↗