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Biomedical subjects

R Ling

Publications and source records attributed to R Ling.

At least 19 recordsLinked to original sources

Presumed infectious endophthalmitis following cataract surgery in the UK: a case-control study of risk factors.

AIMS: To study risk factors for presumed infectious endophthalmitis complicating cataract surgery in the United Kingdom. METHODS: Two hundred and fourteen clinically diagnosed patients with presumed infectious endophthalmitis were compared with 445 control patients throughout the United Kingdom in a prospective case-control study. The cases were identified through the British Ophthalmological Surveillance Unit reporting card system. Control patients undergoing cataract surgery from 13 'control centres' throughout the United Kingdom were selected randomly. Risk factors were identified by univariate and multivariate logistic regression analyses. Pertinent variables relating to the cataract extraction procedure, antimicrobial prophylaxis, ophthalmic and medical history were analysed with regard to postoperative infection. RESULTS: Statistically significant risk factors in the multivariate model included inpatient cataract surgery (P=0.001), surgery in dedicated eye theatres (P<0.001), consultant grade surgeon (compared to registrar) (P=0.001), posterior capsule tear during cataract surgery (P=0.001). The use of face masks by the scrub nurse and surgeon during cataract surgery (P<0.001) and the administration of subconjunctival antibiotics at the end of surgery (P<0.001) were protective against postoperative infection. CONCLUSIONS: In order to minimise the risk of postoperative endophthalmitis we would recommend the wearing of face masks by the surgeon and scrub nurse during cataract surgery and subconjunctival antibiotics at the end of surgery.

Acute Disease↗

Effect of small-sized liposomal Adriamycin administered by various routes on a metastatic breast cancer model.

The antitumor effects of small-sized liposomal Adriamycin (LADR) administered by various routes were investigated in rabbits bearing well-developed VX2 tumors in the mammary gland. Rabbits received s.c. or i.v., or s.c. combined with i.v., injections of LADR 6 weeks after tumor implantation. The i.v. route showed a significant inhibitory effect on breast tumors and distant metastases. In comparison, metastases in axillary and mediastinal lymph nodes were more efficiently inhibited after s.c. injection. LADR administered concurrently by both the i.v. and s.c. routes produced satisfactory therapeutic activities on both primary breast tumors and metastases in local-regional lymph nodes, lungs and liver, as shown by slowed growth rates, decreased mRNA expression of proliferating cell nuclear antigen, and extensive necrosis and apoptosis of tumor cells. It is concluded that small-sized LADR administered s.c. provides reliable efficacy on lymphatic metastases of breast cancer and that the addition of treatment by the s.c. route to that by the conventional i.v. route can be recommended as a promising procedure to enhance chemotherapeutic effects in patients with metastatic breast cancer.

Animals↗

Surveillance of endophthalmitis following cataract surgery in the UK.

AIMS: To estimate the incidence of acute-onset presumed infectious endophthalmitis (PIE) following cataract surgery in the UK and provide epidemiological data on the presentation, management, microbiology, and outcome of cases of endophthalmitis. METHODS: Cases were identified prospectively by active surveillance through the British Ophthalmological Surveillance Unit reporting card system, for the 12-month period October 1999 to September 2000 inclusive. Questionnaire data were obtained from ophthalmologists throughout the UK at baseline and 6 months after diagnosis. Under-reporting was estimated by independently contacting units with infection databases. RESULTS: Data were available on 213 patients at baseline and 201 patients at follow-up. The minimum estimated incidence of PIE was 0.086 per 100 cataract extractions and the corrected incidence was 0.14 per 100 cataract extractions. For the management of PIE, 96% of patients received intravitreal, 30% subconjunctival, 65% oral, and 17% intravenous antibiotics. In all, 17% of patients received intravitreal steroid. From the intraocular samples taken for microbiological analysis, 56% were culture positive. At follow-up, 48% of patients achieved visual acuity of 6/12 or better and 66% achieved better than 6/60. 13% of patients were unable to perceive light or had evisceration of the globe. CONCLUSIONS: The incidence of PIE after cataract surgery in the UK is comparable to that of other studies. Approximately 50% of patients achieved a visual acuity close to the driving standard.

Acute Disease↗

Suprachoroidal haemorrhage complicating cataract surgery in the UK: epidemiology, clinical features, management, and outcomes.

AIMS: To study the incidence, management, and outcomes of suprachoroidal haemorrhage (SCH) complicating cataract surgery in the United Kingdom. METHODS: Cases were prospectively collected by active surveillance through the British Ophthalmological Surveillance Unit. Details were obtained using an incident questionnaire with follow up at 6 months. RESULTS: 118 cases were reported in 1 year. The estimated incidence of SCH was 0.04% (95% confidence interval 0.034% to 0.050%). Cataract extractions were by phacoemulsification in 76.2%, extracapsular cataract extraction (ECCE) in 11.0%, and phacoemulsification conversion in 12.8%. SCH was "limited" (1 to 2 quadrants) in 48.7%, "full blown" (3 to 4 quadrants) in 43.1%. SCH in phacoemulsification was more likely to be limited (63.2%), compared with ECCE (11.1%) and phacoemulsification conversion (23.1%) (p<0.001, chi(2) test). Visual acuity (VA) was better than 6/60 in 57 of 95 (60%) cases after a median follow up interval of 185 days. 33 of 34 cases (97.1%) with secondary anterior segment revision had VA better than 6/60. VA was worse than 6/60 in 7 of 8 (87.5%) cases that had intraoperative sclerostomy, and in all 6 (100%) cases that had secondary posterior segment intervention. CONCLUSION: SCH is a rare but serious complication of cataract surgery. Poor prognostic factors included full blown SCH, ECCE, phacoemulsification conversion, retinal apposition, and retinal detachment.

Aged↗

Suprachoroidal haemorrhage complicating cataract surgery in the UK: a case control study of risk factors.

AIMS: To study the risk factors for suprachoroidal haemorrhage (SCH) complicating cataract surgery in the United Kingdom. METHODS: 109 cases of SCH complicating cataract surgery prospectively collected through the British Ophthalmological Surveillance Unit were compared with 449 controls that underwent cataract extraction from 13 "control centres" throughout UK in a case control study. 40 systemic, ophthalmic, and operative variables were examined. RESULTS: Statistically significant risk factors for SCH in univariate analysis included: older age (p<0.001), taking at least one cardiovascular medication (p<0.001), peripheral vascular disease (p = 0.014), hyperlipidaemia (p = 0.005), glaucoma (p<0.001), elevated preoperative intraocular pressure (p<0.001), sub-Tenon's local anaesthesia (LA) (p<0.001), topical LA (p<0.001), the lack of orbital compression following LA (p<0.001), posterior capsule (PC) rupture before SCH (p<0.001), elective extracapsular cataract extraction (ECCE) (p = 0.038), and phacoemulsification conversion (p<0.001). Logistic regression analysis identified the following significant independent risk factors: older age, taking at least one cardiovascular medication, glaucoma, elevated preoperative intraocular pressure, the lack of orbital compression, PC rupture before SCH, elective ECCE, and phacoemulsification conversion. CONCLUSION: The results allow identification of patients at risk of SCH. Attention to the various modifiable preoperative and intraoperative risk factors is recommended in order to minimise the risk of SCH.

Aged↗

Presbyopic phacovitrectomy.

AIM: To review the results and complications of combined phacoemulsification and vitrectomy in presbyopic patients. METHODS: Retrospective review of 90 consecutive presbyopic patients who underwent phacoemulsification and vitrectomy for primary rhegmatogenous retinal detachment (RRD) (21), redo-RRD (seven), stages 2 and 3 full thickness macular holes (FTMH) (38), stage 4 FTMH (six), idiopathic epiretinal membrane (ERM) (11), proliferative diabetic retinopathy (PDR) (three) and vitreous haemorrhage secondary to branch retinal vein occlusion (BVO) (four). RESULTS: Lens opacity was absent or mild in 84.5% of patients. Reattachment rates for primary RRD and redo-RRD after one procedure were 90.5% and 71.4% and final reattachment rates were 95.2% and 100%, respectively. Macular hole closure rate was 89.5% for stage 2 and 3 FTMH and 83.3% for stage 4 FTMH. There was significant improvement in the median logMAR visual acuity from 1.00 preoperatively to 0.48 postoperatively for the whole cohort (p<0.001, Wilcoxon test). Postoperative complications included fibrinous uveitis (13.3%), iris bombe (2.2%), IOL/iris capture secondary to gas overfill (1.1%), and posterior capsule opacification (51.1%). CONCLUSION: Combined phacoemulsification and vitrectomy is a safe and desirable option in the management of phakic, presbyopic patients with vitreoretinal pathologies that warrant vitreous surgery, even in the absence of significant lens opacity.

Aged↗

Longitudinal study of a cohort of people with diabetes screened by the Exeter Diabetic Retinopathy Screening Programme.

PURPOSE: To evaluate the long-term outcome of a cohort of people with diabetes screened by the Exeter Diabetic Retinopathy Screening Programme. METHOD: The cohort comprised of diabetic patients from nine market town General Practices around Exeter who first attended the diabetic retinopathy screening programme in 1992. Screening was carried out by a combination of dilated fundoscopy by a screening technician and a single 45 degrees Polaroid photograph of each eye. The prevalence of diabetic retinopathy at the baseline, the incidence of sight threatening diabetic retinopathy (STDR) in the next two rounds of screenings, and the long-term visual outcome are described. RESULTS: The cohort consisted of 775 patients (104 Type I, 517 Type II non-insulin-requiring and 154 Type II insulin-requiring). The mean age was 72.1 years (15-100), with mean disease duration of 13.0 years (1-79). Baseline prevalence was as follows: background retinopathy: 21.4%, proliferative: 2.8%, clinically significant macular oedema: 6.1%. The incidence of proliferative disease was 2.20% and 2.25% respectively in the next two rounds of screening (P > 0.05, chi2 test). The incidence of clinically significant macular oedema was also constant over next two rounds of screening, at 4.79% and 5.18% respectively (P > 0.05, chi2 test). Ninety-five (12.3%) patients were deceased and a further 179 (23%) patients were lost to follow-up by the third round. Only two patients with newly diagnosed STDR suffered deterioration of visual acuity to 6/60 or worse as a result of diabetic retinopathy. CONCLUSION: The incidence of STDR remained constant throughout the period of screening, reflecting the chronic progressive nature of the disease. Significant numbers of patients were lost to follow-up. Screening seemed effective in preserving vision in those patients with newly diagnosed STDR.

Adolescent↗

Involvement of transporter recruitment as well as gene expression in the substrate-induced adaptive regulation of amino acid transport system A.

We investigated the molecular mechanism involved in the adaptive regulation of the amino acid transport system A, a process in which amino acid starvation induces the transport activity. These studies were done with rat C6 glioma cells. System A activity in these cells is mediated exclusively by the system A subtype, amino acid transporter A2 (ATA2). The other two known system A subtypes, ATA1 and ATA3, are not expressed in these cells. Exposure of these cells to an amino acid-free medium induces system A activity. This process consists of an acute phase and a chronic phase. Laser-scanning confocal microscopic immunolocalization of ATA2 reveals that the acute phase is associated with recruitment of preformed ATA2 from an intracellular pool to the plasma membrane. In contrast, the chronic phase is associated with an induction of ata2 gene expression as evidenced from the increase in the steady-state levels of ATA2 mRNA, restoration of the intracellular pool of ATA2 protein, and blockade of the induction by cycloheximide and actinomycin D. The increase in system A activity induced by amino acid starvation is blocked specifically by system A substrates, including the non-metabolizable alpha-(methylamino)isobutyric acid.

Adaptation, Physiological↗

Evidence for the transport of neutral as well as cationic amino acids by ATA3, a novel and liver-specific subtype of amino acid transport system A.

We report here on the cloning and functional characterization of the third subtype of amino acid transport system A, designated ATA3 (amino acid transporter A3), from a human liver cell line. This transporter consists of 547 amino acids and is structurally related to the members of the glutamine transporter family. The human ATA3 (hATA3) exhibits 88% identity in amino acid sequence with rat ATA3. The gene coding for hATA3 contains 16 exons and is located on human chromosome 12q13. It is expressed almost exclusively in the liver. hATA3 mediates the transport of neutral amino acids including alpha-(methylamino)isobutyric acid (MeAIB), the model substrate for system A, in a Na(+)-coupled manner and the transport of cationic amino acids in a Na(+)-independent manner. The affinity of hATA3 for cationic amino acids is higher than for neutral amino acids. The transport function of hATA3 is thus similar to that of system y(+)L. The ability of hATA3 to transport cationic amino acids with high affinity is unique among the members of the glutamine transporter family. hATA1 and hATA2, the other two known members of the system A subfamily, show little affinity toward cationic amino acids. hATA3 also differs from hATA1 and hATA2 in exhibiting low affinity for MeAIB. Since liver does not express any of the previously known high-affinity cationic amino acid transporters, ATA3 is likely to provide the major route for the uptake of arginine in this tissue.

Amino Acid Transport Systems↗

Traumatic rupture of the medial rectus muscle.

Traumatic rupture of an extraocular muscle, in the absence of significant injury to the globe and adnexa, is uncommon. We report the case of a patient with an isolated mid-belly rupture of the medial rectus muscle following ocular trauma and describe the technique of repairing the ruptured muscle by suturing the distal segment to the Tenon sleeve of the proximal segment. This was combined with postoperative botulinum toxin injection to the ipsilateral lateral rectus muscle. Good primary position alignment was achieved 7 months after surgery. The patient regained a useful horizontal field of binocular single vision totaling 27 degrees.

Adult↗

Detection of sporadic cases of hepatitis E virus (HEV) infection in China using immunoassays based on recombinant open reading frame 2 and 3 polypeptides from HEV genotype 4.

We reported previously on the complete sequence of hepatitis E virus (HEV) genotype 4, isolated from patients with sporadic cases of acute HEV infection in China. At least eight HEV genotypes have now been described worldwide, and further isolates await classification. Current immunoassays for the detection of anti-HEV antibodies are based on polypeptides from genotypes 1 and 2 only and may be inadequate for the reliable detection of other genotypes. Because genotypes 1 and 4 predominate in China, we wished to investigate the antigenic reactivities of HEV genotype 4 proteins. Four overlapping regions of open reading frame 2 (ORF2) (FB5, amino acids [aa] 1 to 130; E4, aa 67 to 308; F2-2, aa 288 to 461; E5, aa 414 to 672) and the entire ORF3 product were expressed in Escherichia coli as fusion proteins. Enzyme immunoassays based on each of the five purified polypeptides were evaluated with sera from patients with sporadic cases of acute HEV infection. Individual immunoassays derived from HEV genotype 4 detected more cases of acute hepatitis E than a commercial assay. Some serum samples, which were positive for anti-HEV immunoglobulin G only by assays based on HEV genotype 4, were positive for HEV RNA by reverse transcription-PCR. Polypeptide FB5, from the N terminus of ORF2, had the greatest immunoreactivity with sera from patients with acute hepatitis E. These data indicate that the N terminus of ORF2 may provide epitopes which are highly reactive with acute-phase sera and that assays based on genotypes 1 and 2 alone may be inadequate for the detection of HEV infection in China, where sporadic cases of HEV infection are caused predominantly by HEV genotypes 4 and 1.

Acute Disease↗

A mesoscale phytoplankton bloom in the polar Southern Ocean stimulated by iron fertilization.

Changes in iron supply to oceanic plankton are thought to have a significant effect on concentrations of atmospheric carbon dioxide by altering rates of carbon sequestration, a theory known as the 'iron hypothesis'. For this reason, it is important to understand the response of pelagic biota to increased iron supply. Here we report the results of a mesoscale iron fertilization experiment in the polar Southern Ocean, where the potential to sequester iron-elevated algal carbon is probably greatest. Increased iron supply led to elevated phytoplankton biomass and rates of photosynthesis in surface waters, causing a large drawdown of carbon dioxide and macronutrients, and elevated dimethyl sulphide levels after 13 days. This drawdown was mostly due to the proliferation of diatom stocks. But downward export of biogenic carbon was not increased. Moreover, satellite observations of this massive bloom 30 days later, suggest that a sufficient proportion of the added iron was retained in surface waters. Our findings demonstrate that iron supply controls phytoplankton growth and community composition during summer in these polar Southern Ocean waters, but the fate of algal carbon remains unknown and depends on the interplay between the processes controlling export, remineralisation and timescales of water mass subduction.

Atmosphere↗

Histidine-tagged ubiquitin substitutes for wild-type ubiquitin in Saccharomyces cerevisiae and facilitates isolation and identification of in vivo substrates of the ubiquitin pathway.

A general method for purification of any substrate of the ubiquitin pathway, the major eukaryotic proteolytic pathway, should utilize the common characteristic of covalent linkage of ubiquitin to substrate lysyl residues. The utility of a N-terminal histidine-tagged ubiquitin (HisUb) for in vivo conjugation and isolation of ubiquitinated proteins by metal chelation chromatography is conditioned by the requirement that HisUb conjugate to the same set of proteins as wild-type ubiquitin. Stringent in vivo tests with Saccharomyces cerevisiae strains expressing ubiquitins only from plasmids were performed to show that HisUb could substitute for wild-type ubiquitin. The utility of HisUb as a method for purification of proteins ubiquitinated in vivo was demonstrated by metal chelation chromatography of yeast extracts expressing HisUb and immunoblotting for Rpb1, the largest subunit of RNA polymerase II. A fraction of Rpb1 was present in the ubiquitinated form in vivo. The ability to use HisUb expression in transgenic organisms that retain expression of their endogenous ubiquitin genes was demonstrated through transgenic Arabidopsis thaliana expressing HisUb or its variant HisUbK48R. UbK48R is a version of ubiquitin capable of conjugation to proteins, but cannot serve as an attachment site for ubiquitin via the major in vivo interubiquitin linkage. Whereas transgenic plants expressing HisUb showed insignificant enrichment of ubiquitinated proteins, transgenic Arabidopsis lines expressing HisUbK48R gave a much better yield.

Arabidopsis↗

Unusual hepatitis B surface antigen variation in a child immunised against hepatitis B.

Perinatal transmission of and infection with hepatitis B (HBV) in early childhood are observed in a small proportion of the offspring of hepatitis B surface antigen (HBsAg)-positive mothers who are vaccinated against HBV immediately after giving birth. The children may be infected by wild-type HBV or by variants with amino acid substitutions in the "a" determinant of HBsAg, particularly at position 145 and, rarely, at positions 120, 126, 129, 131, 141, and 144. Four hundred and forty-six newborn infants of HBsAg-positive mothers in the northeastern part of the Czech Republic received combined active and passive immunisation against HBV. Only one child became an HBsAg carrier. This followed a mild, acute HBV illness in the beginning of the second year of his life. HBV DNA encoding the "a" determinant and surrounding region of HBsAg was sequenced after amplification from the plasma of the child and his mother. The child was infected with variants of HBsAg with substitutions at residues 137 and 139. The virus of the mother had changes at residues 120 and 121. HBV from both child and mother had an unusual substitution at residue 118 and seemed to be of the ayw subdeterminant.

Amino Acid Sequence↗

The complete sequence of hepatitis E virus genotype 4 reveals an alternative strategy for translation of open reading frames 2 and 3.

Isolates of hepatitis E virus (HEV) have recently been described from China that are distinct from Burmese, Mexican and US viruses and constitute a novel genotype (genotype 4). Here, the complete genomic sequence of a representative isolate of genotype 4 HEV, amplified directly from the stool of an acutely infected patient, is presented. Analysis of the entire sequence confirms our previous conclusion, based upon partial sequence data, that these Chinese isolates belong to a novel genotype. Typical of genetic variation in HEV, most nucleotide substitutions occur in the third base of the codon and do not affect the amino acid sequence. The genotype 4 virus is unusual in that a single nucleotide insertion in the ORF 3 region changes the initiation of ORF 3, and perhaps also ORF 2. The consequences of these changes are discussed.

Adult↗