Search PubMedSearch

Biomedical subjects

C J Sutherland

Publications and source records attributed to C J Sutherland.

At least 19 recordsLinked to original sources

The cytoadherence linked asexual gene family of Plasmodium falciparum: are there roles other than cytoadherence?

The binding of erythrocytes infected with Plasmodium falciparum to the endothelium lining the small blood vessels of the brain and other organs can mediate severe pathology. A region at the right end of chromosome 9 has been implicated in the binding of parasitised erythrocytes to the endothelial receptor CD36. A gene expressed in asexual erythrocytic stage parasites has been identified in this region and termed the cytoadherence linked asexual gene (clag). Antisense RNA production and targeted gene disruption of clag resulted in greatly reduced binding to CD36. Hybridisation to 3D7 chromosomes showed clag to be a part of a gene family of at least nine members. All members analysed so far have a conserved gene structure of at least nine exons, as well as putative transmembrane domains. The possible functions of the gene family are discussed.

Animals

A comparison of intramuscular tenoxicam with intramuscular morphine for pain relief following tonsillectomy in children.

A double blind trial was conducted to evaluate the analgesic efficacy of intramuscular tenoxicam for pain relief following tonsillectomy in children. Fifty children, aged 3-10 years, were randomly allocated to receive intramuscular tenoxicam 0.75 mg.kg-1 or intramuscular morphine sulphate 0.2 mg.kg-1 after induction of anaesthesia. Although the tenoxicam group required significantly more postoperative morphine.(mean 57.8 micrograms.kg-1 compared with 26.9 micrograms.kg-1, P = 0.025), the total morphine dose was significantly reduced after tenoxicam (57.8 micrograms.kg-1 compared with 226.9 micrograms.kg-1, P < 0.0001). There was no difference between the quality of analgesia after discharge from recovery. The incidence of postoperative vomiting was significantly reduced after tenoxicam (20%) compared with morphine (71%).

Analgesics, Opioid

Management of type III acetabular deficiencies in revision total hip arthroplasty without structural bone graft.

Seventeen patients with loose total hip acetabular components and type III osteolytic acetabular defects were prospectively identified and reconstructed with either spherical acetabular components or eccentric acetabular components without use of structural bone graft. A computed tomography (CT) scan and a three-dimensional (3-D) model were obtained in nine patients to determine whether a spherical component or eccentric component should be used. The clinical results were measured using the Harris Hip Score. Hip scores improved from 44 to 73 points for the entire group but were lower in the subgroup with eccentric components. Also, two of the eccentric cups developed loosening. The hip center was better restored in the eccentric implant group. The cost of the prosthesis was higher in the eccentric implant group due to the expenses of the CT scan and the 3-D model.

Acetabulum

Disruption of a novel open reading frame of Plasmodium falciparum chromosome 9 by subtelomeric and internal deletions can lead to loss or maintenance of cytoadherence.

Isolates of Plasmodium falciparum commonly undergo a large subtelomeric deletion of the right end of chromosome 9 during in vitro cultivation, accompanied by loss of ability to cytoadhere to melanoma cells and greatly lowered gametocyte production. ItG2, an isolate in which cytoadherence is stable, has undergone a subtelomeric deletion of intermediate length on chromosome 9. We show here that the deletions in all non-cytoadherent clones examined have breakpoints within or delete a novel open reading frame (the breakpoint open reading frame, BPORF) that is a unique sequence in the genome. Surprisingly, in ItG2 BPORF has been removed by an additional 15 kb internal deletion in chromosome 9. These results suggest mechanisms to account for the observed frequent deletion of the right arm of chromosome 9 and for the known stability of cytoadherence in ItG2. However, we were unable to detect var genes in this region of the ItG2 genome. We conclude that the product of a novel gene distinct from the var family is implicated in cytoadherence.

Animals

Excimer laser effects on human corneal endothelium. Modulation by serum factor(s).

OBJECTIVE: To determine the possibility of endothelial cell damage after excimer laser ablation. METHODS: Endothelial cell densities and morphology of human corneas after photoablations or mechanical keratectomy were compared with those of the untreated mates after 1 week of culture with or without serum. RESULTS: Corneas cultured in serum-free medium after ablation to a depth of 150 microns showed endothelial cell densities reduced to 60% of untreated, mate corneas; ultrastructural analysis showed endothelial cell damage not seen in untreated mates. Corneas ablated to the same depth and cultured in serum-enriched medium showed no endothelial cell density loss, nor did corneas cultured in serum-free medium after an ablation to a depth of 50 microns or mechanical keratectomies averaging 95 microns. CONCLUSIONS: Endothelial cell loss in deep laser resections may be prevented by factor(s) in fetal bovine serum. The apparent lack of cell loss in clinical studies may be related to the protective action of similar factors in aqueous humor.

Aged

Use of spontaneous electromyography during revision and complex total hip arthroplasty.

Intraoperative peripheral nerve injury is a serious potential complication of orthopaedic surgery and various intraoperative neurophysiologic monitoring techniques have been used to avoid this complication. Although somatosensory evoked potentials have been used effectively in spinal surgery, the efficacy of this technique has not been demonstrated in total hip arthroplasty. Spontaneous electromyography is a promising, alternative nerve monitoring technique. This technique was used in 44 consecutive revision and complex hip arthroplasty procedures. Five cases demonstrated sustained electromyography activity during surgery that subsided after retractors were removed and the limb brought into an anatomic position. In none of these five cases was there any evidence of clinical neurologic dysfunction after surgery. One patient developed causalgia without any motor deficit, but had no sustained electromyography activity during surgery. Spontaneous electromyography provides real-time monitoring of nerve function that allows immediate corrective action to be taken before nerve injury occurs.

Adolescent

Treatment of type III acetabular deficiencies in revision total hip arthroplasty without structural bone-graft.

The use of structural bone allografts has been advocated for the reconstruction of type III acetabular defects, but the results reported for this method have shown revision rates from 20 to 30% and failure rates averaging 50% at short-, to intermediate-term follow-up periods. A prospective study was undertaken to determine the results of reconstructing type III defects without structural allograft and to compare the results using spherical components with the results using eccentric components. Quantitative inclusion criteria were developed and applied to all hips undergoing revision arthroplasty between 1987 and 1991. Twenty-one hips (20 patients) were identified and included in this study. An evaluation protocol including radiographs, and for defects greater than 30 mm, computed tomography scans and three-dimensional models, was used. At an average follow-up period of 46 months, 19 hips (18 patients) were evaluated. Hip scores of these patients improved from 46 to 75. The location of the hip center was improved to a greater degree in those hips with revised to eccentric components, but implant stability was poor. Overall, the mechanical failure rate was 26%, the clinical failure rate was 16%, and the revision rate was 11%. These results compare favorably with the results of reconstruction using structural graft at the same length of follow-up time. Good results can be achieved by reconstructing type III defects without structural allograft if a cementless spherical component can be placed in stable position on host-bone.

Acetabulum

Positional cloning of a sequence from the breakpoint of chromosome 9 commonly associated with the loss of cytoadherence.

Isolates of Plasmodium falciparum commonly undergo a large, subtelomeric deletion of the right end of chromosome 9 during in-vitro cultivation. This deletion is usually accompanied by loss of ability to cytoadhere to melanoma cells, loss of a var-gene product from the red-cell surface and a reduction in gametocyte production. However, cytoadherence is stable in the isolate ItG2, remaining after many generations in culture. Deletions in all the non-cytoadherent clones examined have breakpoints within or delete a novel open-reading frame, called the breakpoint open-reading frame (BPORF), that is a unique sequence in the genome. In ItG2, surprisingly, BPORF has been removed by a 15-kb deletion, internal in chromosome 9. These results indicate mechanisms to explain why the deletion of chromosome 9 occurs so frequently and why cytoadherence is stable in ItG2.

Animals

Morphine consumption in patients receiving rectal paracetamol and diclofenac alone and in combination.

Paracetamol and diclofenac have different mechanisms of action, and the combination may be more effective than each drug used alone in treating postoperative pain. In a double-blind, controlled design, we studied 60 patients undergoing elective abdominal gynaecological surgery, who received suppositories of paracetamol 1.5 g, diclofenac 100 mg or a combination of the two before the start of surgery. Patients received morphine in the intraoperative period, and cumulative morphine use from a patient-controlled analgesia system was recorded to measure the analgesic effect of the suppositories. Morphine consumption was greatest in the group that received paracetamol alone and lowest in the group given the combination (P < 0.01). There was no difference in the incidence of morphine-related side effects between the groups. We conclude that a diclofenac-paracetamol combination reduced the amount of morphine used compared with paracetamol alone.

Acetaminophen

Infusions of subhypnotic doses of propofol for the prevention of postoperative nausea and vomiting.

We studied the antiemetic effects of a low dose infusion of propofol for 24 h after major gynaecological surgery in a double-blind, randomised, controlled trial. Fifty women of ASA physical status 1 or 2 undergoing major gynaecological surgery received an infusion of 1% propofol or intralipid at 0.1 ml.kg-1.h-1 for 24 h after surgery. Pain was managed using morphine delivered by a patient-controlled analgesia pump. The degree of postoperative nausea and vomiting was assessed by the nurses using a four-point ordinal scale, by the patients using a visual analogue scale and by the amount of rescue antiemetic given by the nurses. There were no differences between the two groups in any of the measures of postoperative nausea and vomiting during the first 48 h after surgery. Postoperative nausea and vomiting in the control group was less on the second day compared with the first postoperative day, but not in the propofol group. There were no side effects from the propofol infusion.

Adult

Early experience with eccentric acetabular components in revision total hip arthroplasty.

Osteolysis associated with acetabular component loosening can produce significant acetabular defects. The combined (segmental and cavitary) or type III defect can present a very challenging reconstructive problem. Several methods of reconstruction for type III defects have been described, including the use of oblong or eccentric sockets. These implants are attractive, theoretically, because they allow restoration of the hip center without use of structural bone graft. The results of this method however have not been widely reported. From a series of type III defects reconstructed from 1987 to 1991, six hips were reconstructed with eccentric acetabular components, provided by three different manufacturers. Four of these six implants were custom and two were off-the-shelf. At 4-years minimum follow-up, three of the six sockets had failed and had been revised. All three failures had been custom implants produced by the same manufacturer. The other three sockets had produced good clinical results. The features common to the failed implants were: (1) custom manufacture; (2) small ingrowth pads not integral with the body of the implant; and (3) lack of specific instrumentation (reamers) for insertion of the implant. Eccentric sockets may have limited, although well-defined, indications for use, such as acetabular revision needed in the presence of a well-fixed or monolithic femoral stem. Early experience suggests that custom eccentric acetabular components are not well suited for such indications.

Acetabulum

An investigation of the effects of massage on quadriceps performance after exercise fatigue.

Thirteen males and 7 females completed their maximum number of leg extensions against a half maximum load. In a randomised, crossover study they were exercised to fatigue using an ergonometer, ski-squats and leg extensions followed either by a 6 min massage or rest after which they again completed their maximum number of leg extensions against half maximum load. The process was repeated a few days later with the alternative condition (rest or massage). The results showed that massage after exercise fatigue significantly improved quadriceps performance compared to rest (p = 0.001). The data was further analysed in relation to age and gender.

Adult

Identification of a program of contractile protein gene expression initiated upon skeletal muscle differentiation.

The functional diversity of skeletal muscle is largely determined by the combinations of contractile protein isoforms that are expressed in different fibers. Just how the developmental expression of this large array of genes is regulated to give functional phenotypes is thus of great interest. In the present study, we performed a comprehensive analysis of contractile protein isoform mRNA profiles in skeletal muscle systems representing each generation of fiber formed: primary, secondary, and regenerating fibers. We find that in each system examined there is a common pattern of isoform gene expression during early differentiation for 5 of the 6 gene families we have investigated: myosin light chain (MLC)1, MLC2, tropomyosin, troponin (Tn)C, and TnI. We suggest that the common isoform patterns observed together represent a genetic program of skeletal muscle differentiation that is independent of the mature fiber phenotype and is found in all newly formed myotubes. Within each of these contractile protein gene families the program is independent of the isoforms of myosin heavy chain (MHC) expressed. The maintenance of such a program may reflect a specific requirement of the initial differentiation process.

Animals

Complications of proximal femoral allografts in revision total hip arthroplasty.

Four revision hip arthroplasties using a well-described surgical construct involving a large frozen femoral allograft to replace a deficient proximal femur developed six major complications related to the use of the allograft or of the surgical construct. These cases represent three consecutive cases using this surgical construct performed by the senior author and one postoperative referral that used the same construct. The complications included three allograft fractures, two nonunions at the host-allograft junction, and one postoperative infection. All four of the patients previously had cemented revisions before the allograft procedure, and all had deficient proximal femurs at the time of the allograft procedure. All three of the fractures occurred at the tip of the femoral prosthesis within the allograft. The unacceptably high fracture rate, three of four, was associated with the allograft functioning as an unsupported load-bearing element in this study.

Bone Transplantation

Measurement of acetabular component migration using two-dimensional radiography.

The relationships between apparent acetabular component migration, choice of anatomic landmarks, and changes in rotation of the pelvis were determined by examining radiographs of a pelvic model in multiple projections. The minimum apparent migration associated with transverse and longitudinal rotation of 5 degrees from neutral was 2 mm. The least apparent migration was noted when the teardrop was used as the principal anatomic landmark. Determination of component migration in clinical studies from serial radiographs involves a minimum projection and magnification error of 2 mm.

Acetabulum