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Biomedical subjects

K Oliver

Publications and source records attributed to K Oliver.

At least 37 records · Page 2Linked to original sources

Current practice in primary total hip replacement: results from the National Hip Replacement Outcome Project.

As part of the National Study of Primary Hip Replacement Outcome, 402 consultant orthopaedic surgeons from three regions were contacted by postal questionnaire which covered all aspects of total hip replacement (THR). There was a 70% response rate of which 71 did not perform hip surgery, a further 33 refused to take part, leaving 181 valid responses. Preoperative assessment clinics were used by 89% of surgeons, but anaesthetists and rehabilitation services were rarely involved at this stage. Of respondents, 99% used routine thromboprophylaxis, with 79% using a combination of mechanical and chemical methods. Of surgeons, 84% routinely used stockings, whereas 95.5% used chemical prophylaxis, 63% employed low molecular weight heparins. Theatre facilities were shared with other surgical specialties by 6% of surgeons and 18% regularly used body exhaust suits for THR. Antibiotic loaded cement was used by 69% of surgeons, the majority (65%) used a single brand of normal viscosity cement with 9% using reduced viscosity formulations. Modern cementing techniques were commonly used at least in part, 87% used a cement gun and 94% a cement restrictor for femoral cementing. On the acetabulum, 47% pressurised the cement. In all, 36 different femoral stems and 35 acetabular cups were in routine use, but the majority of surgeons (55%) used Charnley type prostheses. Of the surgeons, 57% performed only cemented THR, while 3% exclusively used uncemented THR. Of consultants, 21% followed up their patients to 5 years, the majority discharge patients within the first year. Of concern is a large proportion of surgeons using low molecular weight heparins despite a lack of evidence with regard to reducing fatal pulmonary embolism, and also the small number of surgeons using prostheses of unproven value. Third generation cementing techniques have yet to be fully adopted. The introduction of a national hip register could help to resolve some of these issues.

Arthroplasty, Replacement, Hip↗

Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease.

We prospectively evaluated the clinical and biochemical responses to enzyme-replacement therapy (ERT) with macrophage-targeted glucocerebrosidase (Ceredase) infusions in 5 patients (age, 3.5-8.5 years) with type 3 Gaucher's disease. The patients were followed for up to 5 years. Enzyme dosage ranged from 120 to 480 U/kg of body weight/month. Systemic manifestations of the disease regressed in all patients. Neurological deficits remained stable in 3 patients and slightly improved in 1. One patient developed myoclonic encephalopathy. Cognitive deterioration occurred in 1 patient and electroencephalographic deterioration in 2. Sequential cerebrospinal fluid (CSF) samples were obtained during the first 3 years of treatment in 3 patients and were analyzed for biochemical markers of disease burden. Glucocerebroside and psychosine levels were not elevated in these specimens, whereas chitotriosidase and quinolinic acid were elevated in 2 patients. Progressive decrease in the CSF levels of these latter macrophage markers during 3 years of treatment implies a decreased number of Gaucher cells in the cerebral perivascular space. Similar changes were not observed in the patient who had a poor neurological outcome. In conclusion, ERT reverses systemic manifestations of type 3 Gaucher's disease and appears to reduce the burden of Gaucher cells in the brain-CSF compartment in some patients.

Antibodies↗

Excimer laser photorefractive keratectomy for the correction of hyperopia using an erodible mask and axicon system.

PURPOSE: The purpose of the study is to evaluate photorefractive keratectomy for the correction of hyperopia using the erodible mask and Axicon system. METHODS: Forty-three patients (43 eyes) with a mean refraction (spherical equivalent) of +4.54 diopter (D) (range, +1.75 to +7.50 D) were treated using a Summit Technology "Apex Plus" excimer laser. This system uses an erodible mask to create a 6.50-mm diameter hyperopic correction over the axial cornea. An Axicon then is used to fashion a 1.50-mm "blend zone" around the correction. On the basis of preoperative refractions, patients were assigned to 3 groups: 2 groups of 14 patients underwent either "+2.00 D" or "+3.00 D" corrections and 15 patients had "+4.00 D" corrections. RESULTS: All patients had a reduction in their hyperopia with an overcorrection, especially in the first month after surgery and some stability in the refractive change at 3 to 6 months. The mean manifest refraction (n = 43) at 6 months was -0.17 D (range, +4.50 D to -3.125 D). Patient satisfaction was high. At 6 months, all eyes had an improvement in unaided near visual acuity. Unaided distance acuity was improved in 37 eyes (86%). A ring of haze 6.5 mm in diameter appeared in all eyes 1 month after surgery. Night halo measurements at 6 months showed no differences from preoperative levels. Flicker contrast sensitivity and forward light scatter (glare) measurements showed no differences after surgery. CONCLUSIONS: In this short-term study, photorefractive keratectomy for hyperopia using the erodible mask and Axicon system appeared to be a promising procedure. Visual performance, in terms of flicker contrast sensitivity, forward light scatter, and night halos, was not compromised. There was an overcorrection based on the manufacturer's algorithms. Manipulation of the treatment algorithms should improve future predictability.

Adult↗

Regulated expression vectors demonstrate cell-type-specific sensitivity to human immunodeficiency virus type 1 Nef-induced cytostasis.

The nef gene product of both human and simian immunodeficiency viruses is critically important for virus replication and disease progression in vivo. However, the precise biological function of Nef remains poorly characterized in vitro, with previous reports suggesting that Nef might be either cytotoxic or cytostatic. As a result of difficulties encountered by several groups in establishing cell lines constitutively expressing Nef, we have developed two inducible systems resulting in stable Nef expression in various mammalian cell lines. Tetracycline-regulated Nef expression was achieved in HeLa cells but could not be established in human T cell lines. Jurkat E6-1 T cell and RAW264.7 murine macrophage cell lines expressing a regulated nef gene were generated using a system in which Nef expression was controlled by a mutated version of the heavy metal-inducible human metallothionein IIA promoter. Induction of high levels of Nef expression in HeLa-Nef and Jurkat-Nef cells resulted in a moderate (2-fold) and a dramatic (10-fold) retardation of cell growth respectively, supporting the contention that Nef may be a cytotoxic or cytostatic factor. This property was also observed at low basal levels of Nef expression in RAW264.7-Nef macrophage clones (5-fold reduction in growth) and was associated with an altered morphological phenotype suggesting that different cell types may be more susceptible to the cytostatic activity of Nef. The regulated Nef-expression systems provide tools for investigating the molecular basis of Nef function, including Nef-mediated cytopathogenicity, CD4 down-regulation and enhancement of virus infectivity.

Animals↗

Strain-specific enhancement or inhibition of coumarin hepatotoxicity in mice following pretreatment with two different liver enzyme-inducing agents.

Human exposure to coumarin continues despite controversy over its hepatotoxic potential. Greater understanding of human reactions to coumarin may be achieved by studying murine interstrain differences. The metabolic basis of coumarin hepatotoxicity and its modulation by liver enzyme inducers, beta-naphthoflavone (beta NF) and aroclor 1254 (ARO), were investigated in C3H/He and DBA/2 mice. Coumarin (200 mg/kg) was hepatotoxic to both strains, resulting in 2- to 15-fold plasma aminotransferase elevations, mild subcapsular linear hepatocyte necrosis after 24 hr, and, in some C3H/He mice, centrilobular necrosis. In this strain, beta NF pretreatment caused a 2- to 3-fold further increase in plasma aminotransferases and produced periportal necrosis. In contrast, ARO-pretreated C3H/He mice tended to exhibit lower plasma aminotransferases and occasional midzonal damage. Neither pretreatment significantly altered coumarin hepatotoxicity in DBA/2 mice. In C3H/He mice, hepatic microsomal metabolism of [3-14C]-coumarin via the 3-hydroxylation pathway doubled following both beta NF and ARO treatment. The contrasting nonresponsiveness of DBA/2 mice suggested that this pathway is linked to the Ah locus, which is defective in this strain. ARO treatment caused a maximal 5-fold increase in coumarin 7-hydroxylation in C3H/He mice, whereas DBA/2 mice were 30% less responsive. Potentiation of coumarin hepatotoxicity corresponded to an increase in the 3-:7-coumarin hydroxylation ratio. Pretreatment-dependent shifts in the location of hepatocyte damage may be related to changes in the translobular ratio of enzymes involved in activation and detoxication of coumarin. These data highlight how genetic background, individual variation, and xenobiotic-induced alterations in enzyme profiles, factors all relevant to human risk assessment, can influence the consequence of coumarin exposure.

Alanine Transaminase↗

Immunogenicity of full length and truncated forms of the human immunodeficiency virus type I envelope glycoprotein.

We have monitored the immunogenicity of a V1V2 sub-fragment of gp 120 in contrast to the full length protein and to a truncated form (PR12) where the V1, V2 and V3 regions were removed. In contrast to previously published work [1] these studies show that monomeric forms of envelope are capable of inducing antibodies specific for both linear and discontinuous epitopes. These antibodies are capable of neutralising HIV infectivity. The majority of neutralising antibodies were specific for epitopes within the V2 and V3 regions demonstrating the immunodominance of these regions in monomeric gp 120. Relatively few of the antibodies were specific for the CD4 binding site, suggesting that this region is poorly immunogenic. Immunisation of rats with the PR12 truncated protein did not significantly enhance the immunogenicity of the CD4 binding site. However, the immune response generated included antibodies capable of binding to diverse primary HIV-1 and HIV-2 envelope glycoproteins. We have shown that up to 30% of sera from HIV-1 infected individuals have antibodies that are capable of recognising conformation-dependent epitopes within the V1V2 region of the clone HXB10, suggesting the presence of conserved cross-reactive epitopes. Furthermore we have shown an association between the presence of V1V2 reactive antibodies and the neutralisation titre of the sera tested suggesting that antibodies to this region contribute to the cross-reactive neutralising response.

AIDS Vaccines↗

A cross sectional study of renal involvement in tuberous sclerosis.

Renal disease is a frequent manifestation of tuberous sclerosis (TSC) and yet little is known about its true prevalence or natural history. We reviewed the notes of 139 people with TSC, who had presented without renal symptoms, but who had been investigated by renal ultrasound. Information on the frequency, type, and symptomatology of renal involvement was retrieved. The prevalence of renal involvement was 61%. Angiomyolipomas were detected in 49%, renal cysts in 32%, and renal carcinoma in 2.2%. The prevalence of angiomyolipoma was positively correlated with age, compatible with a two hit aetiology. Renal cysts were the commoner lesion in young children, and their prevalence did not appear to be age related. Renal investigation in people with TSC had been inconsistent and limited. We suggest guidelines for renal investigation in those with TSC.

Adolescent↗

Optical consequences of asymmetries in normal corneas.

A survey of videokeratographs of normal corneas shows many with substantial peripheral asymmetries. For sufficiently large pupils (5.5 mm in this study) these asymmetries lead to coma-like axial aberrations large enough to produce measurable losses in vision in a number of cases. Starting from the output of a videokeratographic instrument, a method of estimating the optical effects of corneal asymmetries using Zernike circle polynomials is outlined. It is further shown that in a first approximation corneal asymmetries can be identified with the primary aberration coma and that this aberration is approximately due to a uniform gradient of refractive power across the cornea. Calculations for a representative case predict that a significant improvement in modulation transfer would follow from correction of this aberration.

Adolescent↗

Corneal optics from videokeratographs.

Recent developments in measuring corneal topography make possible an improved understanding of corneal optics. It is shown, using a wavefront analysis, that optical quantities of interest follow from knowledge of sagittal depths of a cornea, and that sagittal depths are provided by or readily found from the output of commercially available instruments. The errors for normal corneas are expected to be quite small based on measurements on calibration spheres and ellipsoids. As an example the optical consequences of a peripheral asymmetry are estimated for a particular normal cornea.

Anthropometry↗

The effects of cytokines and adherent cells on the interleukin 4-mediated induction of Ia antigens on resting B cells.

In this report we have extended our previous studies on interleukin 4 (IL-4) [previously termed B-cell stimulatory factor-1 (BSF-1)]. Our results demonstrate that 8 hr of exposure to IL-4 is sufficient to induce maximal expression of Ia antigens. This increase in expression of Ia antigens on resting B cells is due to the direct action of IL-4 on the B cells since adding or removing adherent cells or utilizing low density cultures of B cells at 50-100/culture had no effect on the IL-4-mediated increase in Ia. Monoclonal anti-IL-4 antibody completely abrogated the Ia-inducing activity of IL-4. A variety of other purified lymphokines including interleukin 2 (IL-2), interleukin 1 (IL-1), and a source of either B-cell differentiation factor for IgM (BCDF mu), or B-cell growth factor II (BCGF II), did not alter the expression of Ia antigens on resting B cells. However, interferon-gamma can partially inhibit the IL-4-mediated induction of Ia.

Animals↗

B-cell growth factor (B-cell growth factor I or B-cell-stimulating factor, provisional 1) is a differentiation factor for resting B cells and may not induce cell growth.

B-cell growth factor I [BCGF I or B-cell-stimulating factor, provisional 1 (BSFp1)] has been defined as a T-cell-derived lymphokine that acts as a co-stimulator of polyclonal B-cell growth in B cells cultured with anti-mu, anti-delta, or anti-Ig. Based on a number of studies it has been suggested that anti-Ig induces cell enlargement, entry into the G1 phase of the cell cycle, and expression of receptors for BSFp1. BSFp1 then induces entry of the cells into S phase. By adding BSFp1 prior to anti-Ig, we have found evidence that BSFp1 renders cells susceptible to anti-Ig-mediated entry of cells into G2/S phase. In contrast, if cells are first treated with anti-Ig, washed, and then cultured with BSFp1, they do not enter S phase. Taken together, these results suggest that BSFp1 acts on the resting B cells not as a growth factor but rather as a lymphokine that prepares cells for anti-Ig-mediated activation. Taken together with previous reports that BSFp1 induces increased expression of Ia antigens on resting B cells, these studies suggest that BSFp1 may be a differentiation factor rather than a growth factor and that it acts on resting B cells.

Animals↗

A Goldmann perimeter with high luminance chromatic targets.

We have modified the original Goldmann perimeter by replacing the source and shutter by a Xenon arc source with maximum target luminance of 3183 cdm-2, and a quartz iodine lamp yielding maximum background luminance of 150 cdm-2, both measured at the bowl. Colorimetric and spectrophotometric specifications of the new colour targets are comparable to the original, but give luminance intensities equivalent to 318 cdm-2: levels only realized for the white target in the original system. Chromatic profiles are comparable to previous profiles for achromatic targets and the close correspondence between the retinal threshold gradients produced by the two methods simplifies comparison of data obtained with out instrument with those obtained from routine static perimetry. Under high luminance conditions we do not find the relative foveal scotoma for blue targets observed by other researchers. The use of photometrically equated targets well withi; the photopic levels is an improvement on present methods of colour perimetry.

Color↗

The DNA sequence and comparative analysis of human chromosome 20.

The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.

Animals↗