National audit of the outcome of primary surgery for rhegmatogenous retinal detachment. II. Clinical outcomes

PURPOSE: This national study was designed to audit anatomical outcome and complications relating to primary surgery for rhegmatogenous retinal detachments. This paper presents success and complication rates, and examines variations in outcome. METHODS: Sampling and recruitment details of this nationwide cross-sectional survey of 768 patients of 167 consultant ophthalmologists having their first operation for rhegmatogenous retinal detachment have been described. The main clinical outcomes detailed here are anatomical reattachment at 3 months after surgery and complications related to surgery. Consultants with a declared special interest in retinal surgery and able to perform pars plana vitrectomy were designated specialists for the analyses. RESULTS: Overall reattachment rate with a single procedure was 77% (95% CI 73.9-80.2). There were significant differences in reattachment rates between specialists and non-specialists. Without allowing for case-mix, specialists had a reattachment rate of 82% (95% CI 77.9-85.7) with a single procedure and non-specialists 71% (95% CI 65.9-76.0). Allowing for case-mix, there was a significant difference between specialists and non-specialists for grade 2 detachments of 87% and 70% respectively (P < 0.0001). Analysing detachments by break type, the largest difference between specialists and non-specialists was observed for retinal detachments secondary to horseshoe tears, 80% and 68% respectively (P < 0.003). Specialists met the standards set for primary reattachment rates, while non-specialists did not. Over a third of patients had at least one complication reported at some point during the audit period. CONCLUSIONS: Significant differences were seen in reattachment rates between specialists and non-specialists, overall and for specific subgroups of patients. This study provides relevant, robust and valid standards to enable all surgeons to audit their own surgical outcomes for primary retinal detachment repair in rhegmatogenous retinal detachments, identify common categories of failure and aim to improve results.     

Kinetics of fluoride release from zinc oxide-based cements

Considerable attention has been given to the release of the cariostatic fluoride ion from glass-based dental cements (dental silicate and glass ionomer). In these, the total available fluoride content is not precisely known since fluorine is distributed between the cross-linked aqueous salt matrix, partially dissolved glass, and undissolved glass. In analogous cements based on zinc oxide the fluoride is added as highly soluble SnF2. The object of this study is to compare the F- ion release profiles of commercial zinc polycarboxylate and zinc phosphate containing 4.4 and 3.6% SnF2, respectively. Mixed cements were clamped in split ring moulds to produce discs of 10 mm x 1 mm after storage at 37 degrees C for 1 h. Each was weighed and immersed in 10 ml of deionised water. When this changed, at 13 time intervals up to 98 days, the fluoride content was measured using an ion selective electrode. The mean (N = 3) values obtained were expressed cumulatively [F] in micromol F ion/g cement. The total [F] released was 111 for the zinc polycarboxylate and 286 for zinc phosphate compared with total F in the cements of 561 and 464, respectively. When the cumulative [F] was plotted versus t(1/2) close associations were found for both cements. For the polycarboxylate the regression line [F] = 10.6t(1/2) + 9.9 fitted well over the whole 98 days (R = 0.997). For the phosphate a better fit regression line was obtained using results up to 32 days only; [F] = 36.8t(1/2) - 8.4 (R = 0.999). For t > 32 days results increasingly deviated from this line. These results fitted a regression line of the form [F] = 81.7log(e) t - 87.3 (R = 0.9997). Comparisons are made with data from previous authors both for zinc phosphate cement and glass-based cements and with diffusion theory of F ion release. It is concluded that zinc-based cements provide some indications of how glass-based cements may behave over long periods of release and that zinc phosphate is the material of clinical choice for orthodontic cementation if maximal fluoride release is the prime criterion.     

Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso-prostaglandin F(2 alpha) in smoking and nonsmoking men and women

F(2)-isoprostanes are recently described prostaglandin F isomers produced by cyclooxygenase-independent free radical peroxidation of arachidonic acid. Their quantification in plasma and urine is a sensitive and specific indicator of lipid peroxidation and, hence, of oxidative stress in vivo. Some components of garlic are known to possess antioxidant properties. Thus, we have investigated the effect of dietary supplementation with aged garlic extract (AGE; Kyolic; Wakunaga of America, Mission Viejo, CA) on the plasma and urine concentrations of the F(2)-isoprostane 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2 alpha)). Because smokers are exposed to increased oxidative stress, this study was performed in both smoking and nonsmoking subjects. Plasma and urine concentrations of 8-iso-PGF(2 alpha) in nonsmoking individuals were 1.25 +/- 0.19 nmol/L and 272 +/- 53 pmol/mmol of creatinine, respectively. In age- and sex-matched smokers, plasma and urine concentrations of 8-iso-PGF(2 alpha) were 58% and 85% higher, respectively. Dietary supplementation with AGE for 14 d reduced plasma and urine concentrations of 8-iso-PGF(2 alpha) by 29% and 37% in nonsmokers and by 35% and 48% in smokers. Fourteen days after cessation of dietary supplementation, plasma and urine concentrations of 8-iso-PGF(2 alpha) returned to values not different from those before ingestion of AGE in both groups. Thus, dietary supplementation with AGE may be useful in reducing oxidative stress in humans.     

Effects of adding sodium and fluoride ions to glass ionomer on its interactions with sodium fluoride solution

This investigates the effects of the addition of Na and F ions to a glass ionomer cement in which those ions are not inherently present on its interactions with dilute (0.2%) NaF solution. Both the effect of the solution on the cement's surface morphology and the effect of the cement on the solution in terms of take up of Na+ and F- and of change in pH are to be investigated. These results are to be compared to previous results obtained with glasses which contained both, one, or neither of the ions as components of their glasses. NaF (1.3% by weight in the mixed cement) was added to the powder components of a glass ionomer based on LG30 glass (which contains Al, Si, Ca, P, and O only). Discs of cement were set in moulds at 37 degrees C for 1 h then stored in water at 37 degrees C for 3 days. Each test disc was then immersed in 10 ml 0.2% NaF solution whereas controls remained immersed in water (N = 3 for test and control). Test and control disc surfaces were assessed both qualitatively by electron microscopy and quantitatively by linear profilometry (Ra values). Potentiometry was used to measure solution pH and Na and F concentrations using a pH electrode and suitable ion selective electrodes both before and after cement immersion. The surface of test specimens was subject considerable disruption with the polysalt cement matrix being removed and residual glass particles being disclosed. The controls showed no such disruption. This effect was reflected in a significant difference of Ra. Such an effect was not shown by test and control surfaces of LG30 but a similar effect was to that shown by LG26 (which contains F as a glass component). Solution pH changed by 1 unit which was much more than the change shown by LG30 or LG26 but is similar to that of AH2 and MP4 cements which both contain Na. The Na and F uptake was much lower than for LG30 whereas that of LG26 was higher than LG30. The Na:F ratio was 0.29:1 compared to 1.26:1 for LG30 (LG26 = 1.01:1, AH2 = 1.02:1, MP4 = 1.04:1). Fluoride addition to a F-free glass ionomer renders it vulnerable to surface disruption by NaF solution showing that fluoride complexes produced in glass dissolution are not necessarily involved in this process. Sodium addition to a Na-free glass ionomer confirms the role of this cement in enhancing pH change in NaF solution. The level of uptake of F- from a NaF solution in much lower than that for the F-free glass ionomer which shows there is no direct relationship between F- uptake and surface disruption. The ratio of Na:F uptake is below 0.3:1, but the pH change is similar to cements where the ratio is close to unity which indicates that F-/OH- interchange is not a significant mechanism even when anion/cation uptake is not balanced.     

Intravascular local gene transfer mediated by protein- coated metallic stent

Objective To assess the feasibility, efficiency and selectivity of adenovirus- mediated ge ne transfer to local arterial wall by protein- coated metallic stent. Methods A replication- defective recombinant adenovirus carrying the Lac Z reporter gene for nuclear- specific β- galactosidase (Ad- βgal) was used in this study. Th e coating for metallic stent was made by immersing it in a gelatin solution cont aining crosslinker. The coated stents were mounted on a 4. 0 or3. 0mmpe rcutaneous transluminal coronary angioplasty (PTCA) balloon and submersed into a high- titer Ad- βgal viral stock (2×10(10)pfu/ml) for 3 min, and then im planted into the carotid arteries in 4 mini- swines and into the left anterior d escending branch of the coronary artery in 2 mini- swines via 8F large lumen gui ding catheters. The animals were sacrificed7 (n=4), 14 (n=1) and 21 (n=1) days after implantation, respectively. The β- galactosidase expression was as sessed by X- gal staining. Results The results showed that the expression of transgene was detected in all animal. In 1 of carotid artery with an intact intima, the β- gal expression was l imited to endothelial cells. In vessels with denuded endothelium, gene expressi on was found in the sub- intima, media and adventitia. The transfection efficie ncy of medial smooth muscle cells was 38. 6%. In 2 animals sacrificed 7 days af ter transfection, a microscopic examination of X- gal- stained samples did not s how evidence oftransfection in remote organs and arterial segments adjacent to the treated arterial site.Conclusions Adenovirus- mediated arterial gene transfer to endothelial, smooth muscle cells and adventitia by protein- coated metallic stent is feasible. The transfection efficiency is higher. The coated stent may act as a good carrier of adenovirus - mediated gene transfer and have a potential to prevent restenosis following PT CA.     

Demonstration of homology between IS6110 of Mycobacterium tuberculosis and DNAs of other Mycobacterium spp.?

The insertion sequence IS6110 has an important role in diagnostic PCR and typing of Mycobacterium tuberculosis. We have evaluated a one-tube nested PCR which detects IS6110. Positive results were obtained with DNAs from four of four M. tuberculosis isolates, seven of eight M. fortuitum isolates, seven of seven M. avium-M. intracellulare complex isolates, four of five M. kansasii isolates, four of five M. xenopi isolates, two of four M. malmoense isolates, and one of two M. chelonei isolates. These results were confirmed by hybridization of genomic DNA from bp 505 to 685 of the IS6110 from M. tuberculosis H37Rv. Dot blot hybridization of genomic DNAs from these isolates with the same probe cinfirmed the presence of a homologous sequence in these mycobacterial species. These data suggest that false-positive results may be obtained for clinical samples when some methods based on IS6110 are used [corrected].     

Effect of monovalent ions in glass ionomer on their uptake and re-release

AIMS: The study aims to directly measure uptake of Na and F ions by glass ionomer cement from dilute NaF solution and compare this with the subsequent re-release of these ions into water. In addition, the effect of the presence or absence of Na and/or F as a component of the glass is evaluated. MATERIALS AND METHODS: The four glass ionomers used differed only in glass composition; AH2 contained both Na and F, LG26 contained F, MP4 contained Na and LG30 contained neither Na nor F. Discs of cement were set in moulds at 37 degrees C for 1 h and matured in water at 37 degrees C for 3 days. Test discs were immersed in 0.2% NaF solution for 24 h, control discs in water. Discs were subsequently immersed in water which was changed regularly. Ion-selective electrode measurements (F and Na) and atomic absorption spectrometry (Na) were used to determine uptake (change in immersion solution concentration) and re-release into water. RESULTS: All cements took up large quantities of Na and F ions (range 95-336 mumol g-1). This resulted in internal ion concentrations from 16 to 56 times higher than the immersing solution. All re-release was complete within 97 days. No cement re-released more ion than taken up. Glass ionomers containing fluoride took up more Na and F than fluoride-free ones and then re-released a lower percentage of these ions. The cements all took up Na and F ions in equimolar proportions, but initially re-released more F than Na with F-free cement results tending to unity by 97 days. CONCLUSIONS: Glass ionomer cements take up Na and F ions from NaF solution in large quantities and in equimolar proportion. This is re-released either wholly or in part in 97 days by which time the release does not differ from the controls. The presence or absence of F in the cement composition markedly influences both uptake and re-release. Fluoride/hydroxyl interchange does not appear to play an important role in uptake.     

Phenotypic and functional translation of IL33 genetics in asthma

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Interleukin-1beta and rhinovirus sensitize adenylyl cyclase in human airway smooth-muscle cells

Rhinovirus (RV) is a major cause of wheezing in asthmatics and has been reported to cause beta2 adrenergic receptor hyporesponsiveness in human airway smooth muscle (HASM) via cellular secretion of interleukin (IL)-1beta. We studied the effects of IL-1beta and RV on cyclic adenosine monophosphate (cAMP) production in HASM cells. Chronic incubation with IL-1beta or RV caused a significant increase (approximately 3- and approximately 2-fold, respectively) in forskolin (FSK)-stimulated cAMP production, suggesting a sensitization of adenylyl cyclase (AC). The observed augmentation of FSK-stimulated cAMP formation by IL-1beta was completely abrogated by pretreatment with an IL-1 receptor antagonist or cycloheximide, demonstrating that the effect is mediated via the IL-1 receptor 1 (IL-1R1) and that de novo protein synthesis is required. In contrast, RV-induced AC sensitization was not mediated via the IL-1R1 but was observed to be protein kinase C-dependent. We suggest that the sensitization of AC observed after exposure to IL-1beta or RV infection is a cellular defense mechanism to promote pathways that induce relaxation in the inflamed airway.     

Comparison of phenotypic and genotypic methods for pyrazinamide susceptibility testing with Mycobacterium tuberculosis

Mycobacterium tuberculosis converts pyrazinamide to its active form by using the enzyme pyrazinamidase. This enzyme is coded for on the pncA gene, and mutations in the pncA gene result in absence of active enzyme, conferring resistance to the drug pyrazinamide. We investigated 27 strains of Mycobacterium tuberculosis suspected of being multidrug resistant. Each isolate was tested for susceptibility to pyrazinamide by the BACTEC 460TB method, and 19 were pyrazinamide resistant. The presence of active pyrazinamidase enzyme was sought by using the Wayne assay, which was positive in all of the sensitive isolates and four of the resistant isolates. The pncA gene was amplified by PCR, and mutations were sought by single-strand conformation polymorphism (SSCP) analysis. We identified four isolates which were phenotypically resistant to pyrazinamide, but which had active pyrazinamide enzyme on the Wayne assay and normal pncA gene SSCP. MICs measured by BACTEC 460TB and susceptibility testing at a lower pH of 5.5 confirmed genuine resistance. The pncA gene was sequenced in these four isolates and found not to have any mutations. This implies that an alternative mechanism of resistance exists in these strains. We conclude that genotypic assessment of pyrazinamide resistance is unreliable, because it depends on the identification of a single resistance mechanism. Phenotypic methods such as the BACTEC 460TB technique remain the best methods for pyrazinamide susceptibility testing.