OBJECTIVE

To investigate the effect of cataract extraction on the results of automated perimetry in persons with glaucomatous visual field loss.

METHODS

Subjects from a retrospective study of visual field progression who underwent cataract extraction during follow-up were identified. Subjects came from the glaucoma service of a hospital-based tertiary referral center.

METHODS

Subjects had at least 7 Humphrey 24-2 or 30-2 visual fields over 5 years or more, with an abnormal glaucoma hemifield test result on the first 2 examinations. Visual field data were transferred to a microcomputer and comparison of the visual fields immediately before and after cataract extraction was performed.

RESULTS

Sixty-five eyes of 50 subjects (mean age, 71.8 years) were included in the analysis. A mean improvement in mean deviation (MD) of 1.68 dB (P<.001), and a mean worsening in corrected pattern SD (CPSD) of 0.54 dB (P=.09) was observed. The mean unweighted change in threshold in the 52 points of program 24-2 was 1.58 dB, corresponding to a 43.9% increase in sensitivity. A significant correlation between improvement in visual acuity and improvement in MD was also found. A mean increase in CPSD of 1.61 dB (P=.005) occurred in subjects with dense scotomas (minimum threshold value < or = 5 dB) and preoperative CPSD of 8 dB or less.

CONCLUSIONS

In persons with glaucomatous visual field defects, cataract extraction produces only a modest improvement in MD. After cataract surgery, the CPSD index worsened in many subjects with dense scotomas. This suggests that the development of cataract can mask progressive glaucomatous visual field loss in such persons.

Analysis of the sequence data obtained from the 5' portion of the Streptococcus pneumoniae type 19A capsular polysaccharide biosynthesis locus (cps19a) revealed that the first seven genes are homologous to the first seven genes in the type 19F (cps19f) locus. The former genes were designated cps19aA to -G and were 70 to 90% identical to their cps19f counterparts. Southern hybridization analysis of the cps loci from various S. pneumoniae serotypes with probes specific for the cps19aC, cps19aD, and cps19aE genes indicated a hybridization pattern complementary to that previously reported for cps19fC, cps19fD, and cps19fE. That is, all serotypes tested contained high-stringency homologues of either the cps19aC to -E genes or the cps19fC to -E genes, but not both. On this basis S. pneumoniae cps loci can be divided into two distinct classes. Long-range PCR was used to amplify the cps regions between cpsB and aliA from a variety of pneumococcal serotypes. Direct sequencing of the 5' end of these PCR products, and phylogenetic analysis of the sequence data, confirmed the presence of the two distinct classes of cpsC. Whereas members within one class are greater than 95% identical to each other, the DNA sequence identity between the two classes is only approximately 70%.

Surface capsular polysaccharides play a critical role in protecting several pathogenic microbes against innate host defenses during infection. Little is known about virulence mechanisms of the fish pathogen Streptococcus iniae, though indirect evidence suggests that capsule could represent an important factor. The putative S. iniae capsule operon contains a homologue of the cpsD gene, which is required for capsule polymerization and export in group B Streptococcus and Streptococcus pneumoniae. To elucidate the role of capsule in the S. iniae infectious process, we deleted cpsD from the genomes of two virulent S. iniae strains by allelic exchange mutagenesis to generate the isogenic capsule-deficient DeltacpsD strains. Compared to wild-type S. iniae, the DeltacpsD mutants had a predicted reduction in buoyancy and cell surface negative charge. Transmission electron microscopy confirmed a decrease in the abundance of extracellular capsular polysaccharide. Gas-liquid chromatography-mass spectrometry analysis of the S. iniae extracellular polysaccharides showed the presence of l-fucose, d-mannose, d-galactose, d-glucose, d-glucuronic acid, N-acetyl-d-galactosamine, and N-acetyl-d-glucosamine, and all except mannose were reduced in concentration in the isogenic mutant. The DeltacpsD mutants were highly attenuated in vivo in a hybrid striped bass infection challenge despite being more adherent and invasive to fish epithelial cells and more resistant to cationic antimicrobial peptides than wild-type S. iniae. Increased susceptibility of the S. iniae DeltacpsD mutants to phagocytic killing in whole fish blood and by a fish macrophage cell line confirmed the role of capsule in virulence and highlighted its antiphagocytic function. In summary, we report a genetically defined study on the role of capsule in S. iniae virulence and provide preliminary analysis of S. iniae capsular polysaccharide sugar components.

OBJECTIVE

To test the hypothesis that cataract extraction in glaucomatous eyes improves overall sensitivity of visual function without affecting the size or depth of glaucomatous scotomas.

METHODS

Experimental study with no control group.

METHODS

One hundred fifty-eight eyes (of 140 patients) from the Advanced Glaucoma Intervention Study with at least two reliable visual fields within a year both before and after cataract surgery were included. Average mean deviation (MD), pattern standard deviation (PSD), and corrected pattern standard deviation (CPSD) were compared before and after cataract extraction. To evaluate changes in scotoma size, the number of abnormal points (P < .05) on the pattern deviation plot was compared before and after surgery. We described an index ("scotoma depth index") to investigate changes of scotoma depth after surgery.

RESULTS

Mean values for MD, PSD, and CPSD were -13.2, 6.4, and 5.9 dB before and -11.9, 6.8, and 6.2 dB after cataract surgery (P < or = .001 for all comparisons). Mean (+/- SD) number of abnormal points on pattern deviation plot was 26.7 +/- 9.4 and 27.5 +/- 9.0 before and after cataract surgery, respectively (P = .02). Scotoma depth index did not change after cataract extraction (-19.3 vs -19.2 dB, P = .90).

CONCLUSIONS

Cataract extraction caused generalized improvement of the visual field, which was most marked in eyes with less advanced glaucomatous damage. Although the enlargement of scotomas was statistically significant, it was not clinically meaningful. No improvement of sensitivity was observed in the deepest part of the scotomas.

OBJECTIVE

Normal pressure glaucoma (NPG) patients exhibit prolonged retinal arteriovenous passage times in fluorescein angiography and colour Doppler imaging suggests increased resistance downstream from the central retinal and posterior ciliary arteries. The aim of the study was to elucidate the morphological source of decreased perfusion and increased resistance of the ocular circulation in NPG.

METHODS

Retinal arteriovenous passage time (AVP) and peripapillary arterial and venous diameters were measured in digital scanning laser fluorescein angiograms. For estimation of retinal capillary density the area of the foveal avascular zone (FAZ) and the perifoveal intercapillary area (PIA) was quantified. 36 patients with NPG (mean age 57 (SD 13) years) and 21 healthy subjects (mean age 51 (13) years) were enrolled in the comparative study.

RESULTS

In NPG patients the AVP (2.55 (1.1) seconds) was significantly prolonged (p<0.001) when compared with healthy subject data (AVP: 1.70 (0.39) seconds). No differences for arterial or venous diameter, FAZ, and PIA were observed in NPG patients compared with healthy subjects. FAZ, PIA, arterial and venous diameter were not correlated with visual field indices (except venous diameter with PSD, r=0.35 (p<0.05)) or cup to disc ratios. AVP was significantly correlated (p<0.05) with the size of the optic nerve head (r=-0.28), visual field indices (MD: r=-0.3; PSD: r=0.3; CPSD: r=0.3), and contrast sensitivity (r=-0.34).

CONCLUSIONS

AVP times are significantly prolonged in NPG. The slowing of the retinal transit does not result from capillary dropout, or changes of peripapillary arterial or venous diameters with increased vascular resistance.

In non-Western countries, efficient and contextually valid methods of community screening are scarce. The present study describes the validation of a new, brief, 7-item multi-informant screener for conflict-affected children (Child Psychosocial Distress Screener; CPDS). To determine concurrent validity, the CPSD was administered to 65 children and their teachers. CPDS scores were compared with indication for psychosocial treatment based on an in-depth clinical assessment by a psychiatrist and psychologist. Construct validity was assessed by testing the measurement equivalence of the CPDS in a community sample (N = 2,240) in Burundi. The CPDS identifies indication for treatment with an accurateness of .81(sensitivity of .84; specificity of .60). Test?retest reliability of the instrument is good (.83). A robust and invariant factor structure provides evidence for the construct validity of the CPSD. The CPDS appears to be a useful multidimensional tool that measures nonspecific child psychosocial distress, detecting children with an indication for treatment. Because of brevity and the ability to be administered by nonspecialists, the CPDS can be an appropriate instrument to screen large populations of conflict-affected children.

OBJECTIVE

To investigate the ability of three diagnostic tests: frequency-doubling technology (FDT), scanning laser polarimetry (GDx), and nerve fiber layer (NFL) photographs to distinguish normal from glaucomatous eyes.

METHODS

Data were obtained in a cross-sectional, hospital clinic-based study, including one eye from each of 253 persons older than 40 years (68 normal, 94 glaucoma suspects and 91 glaucoma patients). We performed a comprehensive ocular examination, as well as static automated perimetry (Humphrey 24-2), screening FDT, GDx, optic nerve stereoscopic photographs and high-contrast NFL photographs.

RESULTS

The following were significantly different for glaucomatous patients compared with suspects and normals: mean values of mean deviation (MD, Humphrey 24-2) and corrected pattern standard deviation (CPSD), 11 GDx indices, mean FDT testing time and missed points, and NFL graded defects (ANOVA, Mantel-Haenszel test; p = 0.0001). Using Humphrey 24-2 test results and clinical assessment as the defining features of glaucoma, we found that the optimal mix of sensitivity and specificity values were 84% and 100% for FDT (presence of any defect); 62% and 96% for GDx (The Number, cut-off value of 27); and, 95% and 82% for NFL photographs (presence of any abnormality). FDT testing took the least time to be administered.

CONCLUSIONS

The FDT had the best diagnostic performance. Neural network analysis of GDx data outperformed other elements of its software.

OBJECTIVE

This study describes an investigation of the relation between the change of intraocular circulatory dynamics and visual field defect between primary open angle glaucoma (POAG) and normal tension glaucoma (NTG).

METHODS

The method was to determine the blood flow velocity of the ophthalmic artery using colour Doppler imaging and quantitative peak systolic flow velocity, mean envelope velocity, end diastolic velocity, and Pourcelot resistivity index (RI) were determined. The visual field was examined using program 30-2 of the Humphrey field analyser: the mean deviation (MD) and corrected pattern standard deviation (CPSD) were calculated as indices for visual field defects. There were 25 patients with POAG and 25 patients with NTG.

RESULTS

There were no significant differences in all the four indices of the ophthalmic arterial flow and in both of visual field indices between patients with POAG and those with NTG. However, NTG patients alone showed a statistically significant correlation between RI and MD.

CONCLUSIONS

The results suggest the vascular resistance of the ophthalmic artery may be associated with the development of visual field defect in NTG patients.

OBJECTIVE

To explore the relationship between asymmetric baseline intraocular pressure (IOP) and asymmetric visual field (VF) loss in the Low-Pressure Glaucoma Treatment Study.

METHODS

Randomized, multicenter, controlled clinical trial.

METHODS

Low-pressure glaucoma (LPG) patients 30 years or older were identified. Exclusion criteria included an untreated pressure>> 21 mmHg, advanced VF loss, and contraindications to study medications.

METHODS

A baseline VF was created using the average of 2 reliable Humphrey full-threshold examinations. A baseline diurnal IOP curve was performed without IOP-lowering medication.

METHODS

Mean diurnal, peak, trough, IOP range (peak - trough), and standard deviation (SD) of IOP measurements, and mean deviation (MD) and corrected pattern SD (CPSD) of VF examinations.

RESULTS

One hundred ninety patients were enrolled (mean age, 64.9+/-10.7 years). Mean deviation and CPSD were not correlated with mean, peak, trough, or peak minus trough (P - T) IOP (Ps = 0.2-0.9). Among patients with unilateral VF loss (n = 53 [27.9%]), there were no differences (Ps = 0.3-0.9) in any IOP parameter between the normal VF eye and fellow glaucomatous eyes. Among patients with bilateral VF loss (n = 137 [72.1%]), mean, peak, trough, and P - T IOPs were similar in eyes with a better VF MD compared with eyes with a worse VF MD (Ps = 0.2-0.7). Cross-classified contingency tables demonstrated no relationship (Ps = 0.1-0.3) between IOP and VF MD or CPSD using chi-square analysis.

CONCLUSIONS

Intraocular pressure asymmetry is unrelated to VF asymmetry in the Low-Pressure Glaucoma Treatment Study, suggesting an unclear pathogenic relationship between IOP and glaucomatous damage in eyes with LPG.

A large ams gene cluster required for production of the acidic extracellular polysaccharide (EPS) amylovoran by the fire blight pathogen Erwinia amylovora was cloned. Tn5 mutagenesis and gene replacement were used to construct chromosomal ams mutants. Five complementation groups, essential for amylovoran synthesis and virulence in E. amylovora, were identified and designated ams A-E. The ams gene cluster is about 7 kb in size and functionally equivalent to the cps gene cluster involved in EPS synthesis by the related pathogen Erwinia stewartii. Mucoidy and virulence were restored to E. stewartii mutants in four cps complementation groups by the cloned E. amylovora ams genes. Conversely, the E. stewartii cps gene cluster was able to complement mutations in E. amylovora ams genes. Correspondence was found between the amsA-E complementation groups and the cpsB-D region, but the arrangement of the genes appears to be different. EPS production and virulence were also restored to E. amylovora amsE and E. stewartii cpsD mutants by clones containing the Rhizobium meliloti exo A gene.

OBJECTIVE

To prospectively study the effect of oral brovincamine, a relatively selective cerebral vasodilator, on further deterioration of visual field in patients with normal-tension glaucoma (NTG) with low-normal intraocular pressure (IOP).

METHODS

Fifty-two patients with NTG (average age 57.7 years) with an IOP that was consistently less than 15 mmHg were randomly assigned to receive oral brovincamine (20 mg three times daily) or to an untreated control group. The groups were prospectively followed for 2 years with visual field examinations every 4 months, using the 30-2 Humphrey perimeter program. Changes in mean deviation (MD), corrected pattern standard deviation (CPSD), and total deviation (TD) at 74 test points were analyzed using regression analysis with linear mixed model. Data from one eye without media opacity of each subject were analyzed.

RESULTS

There were no differences between groups in age; sex distribution; refraction; blood pressure; baseline IOP; MD, CPSD, or TD at each point. Changes in MD (standard error [SE]) during the study period were -0.778 (0.178) and -0.071 (0.195) dB/year in the control and brovincamine groups, respectively; change in the control group was significantly more negative than in the brovincamine group. Change in CPSD (SE) was 0.032 (0.015) and 0.004 (0.016) dB/year in the control and brovincamine groups, respectively. Change in the control group was significantly positive, but the intergroup difference was not significant. Change in TD was significantly negative at six test points in the control group, whereas no points showed a significant trend in the brovincamine group; the intergroup difference was significant. The average IOP was 13.2 mmHg and 13.1 mmHg in the control and brovincamine groups, respectively, and there was no significant intergroup difference.

CONCLUSIONS

Oral brovincamine may retard further visual field deterioration in patients with NTG who have low-normal IOP.

This new method, based on the use of MD and CPSD (or CLV) visual field indices, can instantly classify not only the stage of glaucomatous visual field damage, but also the type of defect (localized, generalized or mixed). This system was used to study glaucomatous visual field defects in 500 automated tests, performed with either Humphrey 30-2 or Octopus G1 threshold tests. The most common defects found were mixed, and purely local defects were very unusual, especially in advanced glaucoma.

OBJECTIVE

In this study, the capability of statistical analysis indices to characterize static automated visual fields (VFs) accurately in cases of far-advanced glaucoma was assessed.

METHODS

Retrospective observational case series.

METHODS

Sixteen eyes of 15 patients with end-stage glaucoma and evidence of collapse of VF statistical analysis indices were included in the study.

METHODS

End-stage glaucoma was defined as vertical cup-to-disc ratio of 0.9 or more, mean deviation less than -24 dB and with only a central or temporal island remaining in the VF gray scale. Collapse of statistical indices was defined as any of the following: pattern deviation probability plot without a single VF location showing P < 0.5%; corrected pattern standard deviation (CPSD) and pattern standard deviation (PSD) probability less than 5% or within normal limits (WNL); short-term fluctuation (SF) probability WNL; glaucoma hemifield test (GHT) not outside normal limits (ONL); or presence of a low patient reliability comment triggered by 40% or more false-negative (FN) responses.

METHODS

Visual field statistical indices.

RESULTS

Of the 16 VFs showing misleading statistical calculations, 9 of 16 eyes had a normal pattern deviation probability plot. The PSD, SF, and CPSD parameters were normal or barely outside the normal range in 4 of 16, 10 of 16, and 5 of 16 eyes, respectively. The GHT was ONL in 7 of 13 eyes, borderline with generalized reduction of sensitivity (GRS) in three eyes, and only GRS in two additional eyes. Low patient reliability was triggered because of an FN score of 40% or more in 10 of 16 eyes.

CONCLUSIONS

Statistical indices are crucial for the interpretation of automated static VFs. However, in end-stage glaucomatous VF loss, both summary statistical indices and reliability indices may not detect abnormality, thus misleading the casual observer.

Trimeric autotransporter adhesins (TAAs) on the cell surface of Gram-negative pathogens mediate bacterial adhesion to host cells and extracellular matrix proteins. However, AtaA, a TAA in the nonpathogenic Acinetobacter sp. strain Tol 5, shows nonspecific high adhesiveness to abiotic material surfaces as well as to biotic surfaces. It consists of a passenger domain secreted by the C-terminal transmembrane anchor domain (TM), and the passenger domain contains an N-terminal head, N-terminal stalk, C-terminal head (Chead), and C-terminal stalk (Cstalk). The Chead-Cstalk-TM fragment, which is conserved in many Acinetobacter TAAs, has by itself the head-stalk-anchor architecture of a complete TAA. Here, we show the crystal structure of the Chead-Cstalk fragment, AtaA_C-terminal passenger domain (CPSD), providing the first view of several conserved TAA domains. The YadA-like head (Ylhead) of the fragment is capped by a unique structure (headCap), composed of three β-hairpins and a connector motif; it also contains a head insert motif (HIM1) before its last inner β-strand. The headCap, Ylhead, and HIM1 integrally form a stable Chead structure. Some of the major domains of the CPSD fragment are inherently flexible and provide bending sites for the fiber between segments whose toughness is ensured by topological chain exchange and hydrophobic core formation inside the trimer. Thus, although adherence assays using in-frame deletion mutants revealed that the characteristic adhesive sites of AtaA reside in its N-terminal part, the flexibility and toughness of the CPSD part provide the resilience that enables the adhesive properties of the full-length fiber across a wide range of conditions.

OBJECTIVE

To compare the clinical course and outcome of patients diagnosed with one of 4 neonatal-onset urea cycle disorders (UCDs): deficiency of carbamyl phosphate synthase 1 (CPSD), ornithine transcarbamylase (OTCD), argininosuccinate synthase (ASD), or argininosuccinate lyase (ALD).

METHODS

Clinical, biochemical, and neuropsychological data from 103 subjects with neonatal-onset UCDs were derived from the Longitudinal Study of Urea Cycle Disorders, an observational protocol of the Urea Cycle Disorders Consortium, one of the Rare Disease Clinical Research Networks.

RESULTS

Some 88% of the subjects presented clinically by age 7 days. Peak ammonia level was 963 μM in patients with proximal UCDs (CPSD or OTCD), compared with 589 μM in ASD and 573 μM in ALD. Roughly 25% of subjects with CPSD or OTCD, 18% of those with ASD, and 67% of those with ALD had a "honeymoon period," defined as the time interval from discharge from initial admission to subsequent admission for hyperammonemia, greater than 1 year. The proportion of patients with a poor outcome (IQ/Developmental Quotient <70) was greatest in ALD (68%), followed by ASD (54%) and CPSD/OTCD (47%). This trend was not significant, but was observed in both patients aged <4 years and those aged ≥ 4 years. Poor cognitive outcome was not correlated with peak ammonia level or duration of initial admission.

CONCLUSIONS

Neurocognitive outcomes do not differ between patients with proximal UCDs and those with distal UCDs. Factors other than hyperammonemia may contribute to poor neurocognitive outcome in the distal UCDs.

OBJECTIVE

To perform a preliminary assessment of the relation between optic nerve circulatory parameters and glaucomatous visual field progression.

METHODS

This study included 29 eyes of 23 patients with open angle glaucoma that had typical glaucomatous nerve fibre bundle visual field defects and increased cup to disc ratios. Laser Doppler flowmetry (Oculix) was used to measure relative optic nerve blood volume (Vol), velocity (Vel) and flow in the superior temporal (ST) and inferior temporal (IT) neuroretinal rim of the optic nerve. After blood flow measurements patients were followed for 6-62 months (mean 33 (SD 17) months) and 2-11 Humphrey visual fields (4.7 (2.6) fields) were obtained. Progression of glaucoma was assessed by the slope of the corrected pattern standard deviation (CPSD) values versus time, which was calculated manually for each eye using regression analysis.

RESULTS

A significant negative correlation was observed between Vol in the IT rim and the CPSD slope (r=-0.56, p=0.002); patients with lower Vol tended to show faster progression of glaucomatous field damage than those with higher Vol. When the eyes were arbitrarily divided into two groups according to lower Vol (0.32 (0.06) arbitrary units, AU, n=15) or higher Vol (0.49 (0.06) AU, n=14), those with lower Vol had significantly worse mean CPSD slopes (0.50 (0.48) dB/year) than those with higher Vol (-0.67 (1.38) dB/year; Student's t test, p=0.009).

CONCLUSIONS

In the IT rim, the area most prone to develop glaucomatous field damage, lower Vol is associated with subsequently faster CPSD progression. These measurements suggest that circulatory abnormalities may have a role in the development of glaucoma.

OBJECTIVE

To compare the correlation between visual field loss and the pretreatment intraocular pressure (IOP) in primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG).

METHODS

In a cross sectional observational study of 74 patients (43 PACG, 31 POAG), pretreatment IOP was measured at presentation, before treatment was initiated. The severity of visual field loss was assessed by AGIS score, mean deviation (MD), pattern standard deviation (PSD), and corrected pattern standard deviation (CPSD). Glaucomatous optic neuropathy was assessed from simultaneous stereo disc photographs.

RESULTS

There was a stronger correlation between pretreatment IOP and the extent of visual field loss in PACG subjects than in those with POAG for both MD (PACG: Pearson correlation coefficient (r) = 0.43, p = 0.002; r(2) = 0.19), (POAG: r = 0.21, p = 0.13; r(2) = 0.04) and AGIS score (PACG: r = 0.41, p = 0.003; r(2) = 0.17), (POAG: r = 0.23, p = 0.19; r(2) = 0.05 respectively). No such associations were seen for pattern standard deviation (PSD) or corrected pattern standard deviation (CPSD) in either group (p> 0.29). Both horizontal and vertical cup-disc ratio were well correlated with severity of field loss but not with presenting IOP for either diagnosis.

CONCLUSIONS

This is consistent with the hypothesis of a greater IOP dependence for optic nerve damage in PACG than POAG and, conversely, a greater importance of other, less pressure dependent mechanisms in POAG compared to PACG.

Streptococcus pneumoniae produces a protective capsular polysaccharide whose production must be modulated for bacterial survival within various host niches. Capsule production is affected in part by a phosphoregulatory system comprised of CpsB, CpsC, and CpsD. Here, we found that growth of serotype 2 strain D39 under conditions of increased oxygen availability resulted in decreased capsule levels concurrent with an ∼5-fold increase in Cps2B-mediated phosphatase activity. The change in Cps2B phosphatase activity did not result from alterations in the levels of either the cps2B transcript or the Cps2B protein. Recombinant Cps2B expressed in Escherichia coli similarly exhibited increased phosphatase activity under conditions of high-oxygen growth. S. pneumoniae D39 derivatives with defined deletion or point mutations in cps2B demonstrated reduced phosphatase activity with corresponding increases in levels of Cps2D tyrosine phosphorylation. There was, however, no correlation between these phenotypes and the level of capsule production. During growth under reduced-oxygen conditions, the Cps2B protein was essential for parental levels of capsule, but phosphatase activity alone could be eliminated without an effect on capsule. Under increased-oxygen conditions, deletion of cps2B did not affect capsule levels. These results indicate that neither Cps2B phosphatase activity nor Cps2D phosphorylation levels per se are determinants of capsule levels, whereas the Cps2B protein is important for capsule production during growth under conditions of reduced but not enhanced oxygen availability. Roles for factors outside the capsule locus, possible interactions between capsule regulatory proteins, and links to other cellular processes are also suggested by the results described in this study.

OBJECTIVE

To determine the long term efficacy of monotherapy with topically applied beta blocking agents and to determine whether selective beta blockers were able to preserve the visual field more effectively than non-selective agents.

METHODS

A prospective randomised, open, comparative study of three topically applied beta blockers-timolol, betaxolol, and carteolol-was carried out on 153 patients (280 eyes) with newly diagnosed open angle glaucoma. Those patients who were not withdrawn were followed by the same observers for a minimum of 2 years and a maximum of 7 years, with clinical observations, Goldmann tonometry and 24.2 Humphrey visual field analysis.

RESULTS

All three drugs lowered the IOP significantly from untreated levels but betaxolol took up to 12 months in some instances to reach the maximum pressure reduction. After 7 years only 43% of the eyes begun on timolol, 34% of those started on carteolol, and 29% of those on betaxolol were still being treated with these medications alone. Visual fields were analysed throughout the trial by CPSD and MD and at the end by linear regression analysis (PROGRESSOR). The visual fields remained the same without apparent improvement or deterioration throughout the period of follow up. Eight patients (11 eyes) were withdrawn because of continuing field loss in spite of reduction in IOP (six using carteolol and five using betaxolol).

CONCLUSIONS

Analysis shows that less than half the eyes initially treated with topical beta blockers might be expected to still be being treated with their original medication after 5 years. The rest required either additional medication or trabeculectomy. There was no statistically significant improvement or deterioration in the visual fields over a 7 year period. On the evidence of this trial there are no particular advantages in using selective beta blockers.

Quantitative PCR (qPCR), applied to complex environmental samples such as water, wastewater, and feces, is susceptible to methodological and sample related biases. In this study, we evaluated two exogenous DNA spike-and-recovery controls as proxies for recovery efficiency of Bacteroidales 16S rDNA gene sequences (AllBac and qHF183) that are used for microbial source tracking (MST) in river water. Two controls--(1) the plant pathogen Pantoea stewartii, carrying the chromosomal target gene cpsD, and (2) Escherichia coli, carrying the plasmid-borne target gene DsRed2--were added to raw water samples immediately prior to concentration and DNA extraction for qPCR. When applied to samples processed in replicate, recovery of each control was positively correlated with the observed concentration of each MST marker. Adjustment of MST marker concentrations according to recovery efficiency reduced variability in replicate analyses when consistent processing and extraction methodologies were applied. Although the effects of this procedure on accuracy could not be tested due to uncertainties in control DNA concentrations, the observed reduction in variability should improve the strength of statistical comparisons. These findings suggest that either of the tested spike-and-recovery controls can be useful to measure efficiency of extraction and recovery in routine laboratory processing.

Thirty two eyes of 19 patients with capillary non-perfusion from preproliferative and early proliferative diabetic retinopathy underwent visual field testing on the 30-2 program of the Humphrey visual field analyser. The mean defect (MD) p value was < 5% in 30 (94%) eyes and the corrected pattern standard deviation (CPSD) was < 10% in 31 (97%) eyes. Areas of capillary non-perfusion demonstrated by fundal fluorescein angiography were closely associated with areas of reduced retinal sensitivity in these 31 eyes. More severe visual field defects were present in non-insulin dependent diabetics and in older patients. MD and CPSD p values of less than 0.5% and 1% respectively were found to be associated with non-insulin dependent diabetes (p < 0.05 and p < 0.01 respectively) and with the older age group (p < 0.05). There was no correlation between severity of field defects with hypertension and degree of retinopathy.

OBJECTIVE

The current study is designed to determine the effect of light scattering (simulated cataract) on glaucomatous visual fields.

METHODS

Twelve patients with relative scotomas caused by glaucoma underwent the 30-2 threshold test with the Humphrey Visual Field Analyzer twice: once with and once without having a light-diffusing piece of ground glass in front of the eye, which, in previous experiments, has been shown to decrease perimetric threshold by 4.4 decibels (dB) in normal eyes. As controls, 12 patients underwent the same examination with and without a piece of clear glass in front of the eye. In each pair of fields, five points were analyzed within the relative scotoma and compared with five points in a normal area of the opposite hemifield.

RESULTS

The diffusing ground glass produced a mean decrease of perimetric threshold of 5.7 dB (standard deviation [SD] = 3.3 dB) within the area of relative scotoma compared with 6.1 dB (SD = 2.4 dB) within the normal area and 4.4 dB (SD = 2.25 dB) at the fovea. The differences between means were not statistically significant. In addition, the diffusing glass did not affect the corrected pattern SD (CPSD) index (6.5 dB with the diffuser and 6.5 dB without).

CONCLUSIONS

Light scattering depresses the glaucomatous visual field diffusely. Relative glaucomatous scotomas and normal areas are depressed equally, expressed as change in decibel of sensitivity. Therefore, in following patients with cataracts and glaucoma, depression of threshold sensitivity in glaucomatous areas out of proportion to normal areas should not be attributed to the light-scattering effect of the cataract, but rather to possible worsening of glaucomatous damage.

A 4074-bp EcoRI fragment of Streptococcus salivarius ssp. thermophilus (S. thermophilus) chromosomal DNA containing genes involved in exocellular polysaccharide (EPS) was identified and cloned. The nucleotide sequence of this fragment was determined and found to contain one partial and four complete open reading frames. These were designated cpsA, cpsB, cpsC, cpsD and cpsE and encoded proteins of>> 130, 243, 230, 246 and 455 amino acids, respectively, that showed homology with the genes of the cps cluster, involved in polysaccharide biosynthesis, in Streptococcus pneumoniae Type 19F. The cpsA gene is predicted to encode a transcriptional regulator, while cpsC and cpsD are predicted to encode proteins involved in polysaccharide polymerization and export. The cpsE gene is likely to encode the phosphate-prenyl glycosyl-1-phosphate transferase catalyzing the first step in polysaccharide biosynthesis in S. thermophilus. Southern blot analysis revealed that cpsE is found only in polysaccharide producing strains of S. thermophilus.

Bacterial capsular polysaccharides (CPS) are produced by a multi-protein membrane complex, in which a particular type of tyrosine-autokinases named BY-kinases, regulate their polymerization and export. However, our understanding of the role of BY-kinases in these processes remains incomplete. In the human pathogen Streptococcus pneumoniae, the BY-kinase CpsD localizes at the division site and participates in the proper assembly of the capsule. In this study, we show that the cytoplasmic C-terminal end of the transmembrane protein CpsC is required for CpsD autophosphorylation and localization at mid-cell. Importantly, we demonstrate that the CpsC/CpsD complex captures the polysaccharide polymerase CpsH at the division site. Together with the finding that capsule is not produced at the division site in cpsD and cpsC mutants, these data show that CPS production occurs exclusively at mid-cell and is tightly dependent on CpsD interaction with CpsC. Next, we have analyzed the impact of CpsD phosphorylation on CPS production. We show that dephosphorylation of CpsD induces defective capsule production at the septum together with aberrant cell elongation and nucleoid defects. We observe that the cell division protein FtsZ assembles and localizes properly although cell constriction is impaired. DAPI staining together with localization of the histone-like protein HlpA further show that chromosome replication and/or segregation is defective suggesting that CpsD autophosphorylation interferes with these processes thus resulting in cell constriction defects and cell elongation. We show that CpsD shares structural homology with ParA-like ATPases and that it interacts with the chromosome partitioning protein ParB. Total internal reflection fluorescence microscopy imaging demonstrates that CpsD phosphorylation modulates the mobility of ParB. These data support a model in which phosphorylation of CpsD acts as a signaling system coordinating CPS synthesis with chromosome segregation to ensure that daughter cells are properly wrapped in CPS.