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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 127 records · Page 7Linked to original sources
PubMed2000

Changes in CD4 lymphocyte counts after interruption of therapy in patients with viral failure on protease inhibitor-containing regimens. Royal Free Centre for HIV Medicine.

OBJECTIVE: To describe the short-term changes in CD4 lymphocyte counts after the interruption of antiretroviral HIV therapy in order to increase the understanding of CD4 lymphocyte dynamics, and so that appropriate monitoring strategies can be designed. METHODS: We studied 35 HIV-infected patients with late-stage disease who had therapy interruptions leading to high viral load levels, median greater than 750 000 RNA log10 copies/ml, and in whom two CD4 cell counts (median 28 days apart) were available before beginning a salvage regimen. RESULTS: Overall, there was a substantial decline in CD4 cell counts from a median of 125 to 83 cells/mm3 in the average 28 day period, with median proportionate and absolute losses of 26% and 24 cells/mm3 per month, respectively (P < 0.008). This tended to be greater in individuals studied sooner after interrupting therapy (P = 0.03) and in those with CD4 cell counts above the pre-therapy baseline (P = 0.06). There was a strong negative correlation between the proportionate increase in viral load and the absolute change in CD4 cell count (-0.66, P = 0.0002). CONCLUSION: Patients with relatively advanced HIV infection interrupting antiretroviral therapy after failing a protease inhibitor-containing regimen require frequent monitoring because CD4 cell counts appear to fall quite rapidly, at least in the first few weeks after interruption.

Adult↗
PubMed2000

Substantial correlation between HIV type 1 drug-associated resistance mutations in plasma and peripheral blood mononuclear cells in treatment-experienced patients.

The correlation of detectable HIV-1 drug resistance mutations in plasma and PBMCs in patients extensively treated with all antiretroviral drug classes has not been fully elucidated. The detection of mutations in PBMCs may reveal resistant HIV-1 associated with past therapies. In addition, these measures in PBMCs may have a practical value when plasma virus is at low levels that are difficult to detect with current assays. The reverse transcriptase (RT) and protease (P) genes were analyzed for drug resistance, using an in-house method carried out on 36 paired samples of plasma and PBMCs from 12 treatment-experienced patients in order to investigate resistance in the two compartments. When viruses in plasma and PBMCs were analyzed by patient, the mean of the Cohen kappa values was 0.728 (substantial agreement). When viruses were analyzed by codon the mean of the Cohen kappa values was 0.715 (substantial agreement). Baseline samples were concordant at 280 of 288 (97%) codons analyzed. This study shows that a minority of mutations associated with previous therapy can be detected in PBMCs and not in plasma. Overall, mutations in plasma and PBMCs showed a substantial correlation in extensively treated patients, suggesting that either compartment is suitable for the detection of mutations as a virological guide for clinical care.

Anti-HIV Agents↗
PubMed2000

A new power law for determination of total (125)I seed activity for ultrasound-guided prostate implants: clinical evaluations.

PURPOSE: The intraoperative planning with peripheral loading approach is an important technique for ultrasound-guided transperineal prostate implant. In this paper a sphero-cylindrical dose model is described to generate a new power law or a look-up table for determination of the total (125)I activity required to deliver a prescription dose to a given prostate volume. METHODS AND MATERIALS: Dose calculations were based on the new standards for (125)I seeds (model 6711) implemented by the National Institute of Standards and Technology (NIST) in 1999. Using the sphero-cylindrical dose model with peripheral loading approach, a new power law for calculating total activity of radioactive iodine required to deliver a prescribed dose for the target volume was developed. Accounting for random variation of the seed positioning in the prostate and the current air-kerma strength standard of (125)I seeds, this new power law is formulated as follows: A (mCi) = 2.15 d (cm)(2.00) where A is apparent activity in mCi, or A (U) = 1. 69 d (cm)(2.00) where A is air-kerma strength in U, required to deliver a cumulative dose of 145 Gy to a prostate gland with an average dimension, d, in centimeters. RESULTS: The efficacy of using the new power law in prostate implants was demonstrated. For clinical evaluations of this new power law, 40 patients were chosen in 1998. The average D(90) of these 40 patients was 172.0 Gy (SD +/- 29 Gy). This means that on the average, 90% of the target volume received was 172.0 Gy. The average coverage index (CI) in this study was 94.7 (SD +/- 4.7). As a result, 94.7% of the target volume received the prescription dose. The dose homogeneity index (HI) which measured the degree of the dose inhomogeneity was 0.38 (SD +/- 0.21). CONCLUSION: This new and simple power law or a new mCi-volume look-up table for (125)I seed prostate implantation has been developed and formulated for clinical use. Clinical evaluations expressed in quantitative parameters such as D(90), CI, and HI in prostate implants have been thoroughly analyzed and clearly demonstrated the efficacy of this approach.

Brachytherapy↗
PubMed2000

Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations.

Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced receptor oligomerization, was found to stem from ligand- independent interaction of wild-type and mutant Fas receptors through a specific region in the extracellular domain. Preassociated Fas complexes were found in living cells by means of fluorescence resonance energy transfer between variants of green fluorescent protein. These results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.

Animals↗
PubMed2000

Viral genetic heterogeneity in HIV-1-infected individuals is associated with increasing use of HAART and higher viremia.

OBJECTIVE: To assess the correlation between the outgrowth of mutant viruses (viral genetic heterogeneity), highly active antiretroviral therapy (HAART), and plasma HIV-1 RNA in a population-based observational cohort study. DESIGN: The study population consisted of 42 HIV-1-infected individuals receiving at least two nucleotide reverse transcriptase (RT) inhibitors and one or more protease inhibitors at study entry. There were no restrictions on antiretroviral therapy after enrollment. METHODS: Plasma samples were obtained from subjects at baseline, at therapy changes, and at quarterly intervals for quantitation of HIV-1 RNA levels and for sequence determination of the entire protease coding region and the first 235 codons of the reverse transcriptase coding region. Data were analyzed using the generalized estimating equation method for longitudinal data and using linear regression analysis. RESULTS: With increased time on HAART there were significant increases in the number of total HIV-1 mutations in the regions sequenced (P = 0.010). There were significant correlations between the increases in the plasma HIV-1 RNA levels and the numbers of total mutations and reverse transcriptase mutations (P = 0.007 and 0.021, respectively). CONCLUSIONS: The number of HIV-1 mutations increased over time. Failure of HAART in this study population was correlated with outgrowth of virus with numerous mutations in the reverse transcriptase and protease coding regions. Phenotypic results correlated with genotypic results, showing decreased susceptibility to antiretrovirals over time in the majority of this population during HAART. Both synonymous and non-synonymous mutations were observed, with a higher incidence of non-synonymous mutations occurring at codons associated with drug resistance.

Adult↗
PubMed2000

Urinary morbidity with a modified peripheral loading technique of transperineal (125)i prostate implantation.

PURPOSE: Analysis of urinary morbidity within the first 12 months following a modified peripheral loading technique for permanent transperineal transrectal ultrasound (TRUS) guided (125)I prostate implantation and comparison of urinary morbidity with various clinical and implant parameters. MATERIALS AND METHODS: Between October 1, 1996, and March 11, 1998, 87 patients with favorable, early stage prostate cancer were treated with permanent transperineal TRUS guided (125)I prostate implantation. A peripheral loading technique was utilized for source placement with 75-80% source distribution in the periphery and 20-25% source distribution centrally. A mean total activity of 38 mCi of (125)I was implanted (range, 19-66 mCi). The mean source activity was 0.43 mCi/source (range, 0.26-0.61 mCi/source) and the mean number of sources implanted was 88 (range, 56-134). The minimum prescribed dose to the prostate was 145 Gy. The median D(90), V(100), and V(150) were 152 Gy (range, 104-211 Gy), 92% (range, 71-99%), and 61% (range, 11-89%), respectively. The median follow-up time was 19 months (range, 12-29 months). Urinary morbidity was scored at 3 weeks and then at 3-month intervals for the first 2 years using a modified Radiation Therapy Oncology Group (RTOG) grading system (scale 0-5). RESULTS: Most patients developed at least minor urinary symptoms with frequency or nocturia being the most common. Overall, 79% (69/87) of patients experienced urinary morbidity with 21% (18/87) reporting no symptoms. The incidence of overall Grade 1 urinary morbidity was 37% (32/87); Grade 2 morbidity was 37% (32/87); and Grade 3 morbidity was 6% (5/87). There was no Grade 4 or 5 morbidity. The incidence of Grade 0 frequency/nocturia was 36% (31/87); Grade 1 was 33% (29/87); Grade 2 was 30% (26/87); and Grade 3 was 1% (1/87). Grade 0 dysuria was seen in 56% (49/87) of patients; 32% (28/87) had Grade 1; 10% (9/87) Grade 2; and 1% (1/87) Grade 3 dysuria. Most urinary symptoms started a few weeks after implantation and began to subside by 6 months. At 12 months, 22% (19/87) of patients had persistent urinary symptoms (78% Grade 0, 15% Grade 1, 3% Grade 2, and 3% Grade 3). The mean urethral point dose was 174 Gy (range, 99-315 Gy). The mean number of sources implanted correlated significantly with the likelihood of developing acute urinary morbidity (p = 0.03). The total activity implanted also correlated with the morbidity outcome dysuria (p = 0.01) with a threshold seen at 37 mCi. Urethral point dose, source activity, intraoperative TRUS prostate volume, D(90), V(100), V(150), patient age, pretreatment PSA, Gleason score, and T stage did not correlate with morbidity. CONCLUSIONS: Permanent transperineal TRUS guided (125)I prostate implantation using a modified peripheral loading technique is associated with mild urinary morbidity that resolves in 78% of patients by 12 months. Grade 3 urinary morbidity was encountered in only 6% (5/87) of patients. Urinary morbidity may be related to the total number of sources implanted and/or the total activity implanted. Overall urinary morbidity was not correlated with urethral point dose, source activity, intraoperative TRUS prostate volume, D(90), V(100), V(150), patient age, pretreatment PSA, Gleason score, and T stage. The low incidence of urinary morbidity may be a consequence of our modified peripheral loading technique and/or the selection of patients with good-to-excellent preimplant urological parameters. Longer follow-up is necessary to assess biochemical control rates and long-term morbidity.

Aged↗
PubMed2000

Time- and space-resolved dynamic studies on ceramic and cementitious materials.

A review is given of the results and lessons arising from a sustained in situ diffraction study of the structure and performance of functional ceramic/cementitious materials in which synchrotron-based energy-dispersive diffraction has been the central under-pinning technique. Five particular points of discussion emerge: the demands on time resolution; the use of penetrating radiation for the in situ mode; the need for complementary techniques; re-analysing of data; spatially resolved diffraction: a new tomography. These aspects are discussed in turn using illustrative examples taken from the fields of cement hydration, clay intercalation, cation-exchanged zeolites, and particulate/fluid invasion into building and archaeological objects.

Journal Article↗
PubMed2000

Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase.

Human fibroblasts expressing the catalytic component of human telomerase (hTERT) have been followed for 250-400 population doublings. As expected, telomerase activity declined in long term culture of stable transfectants. Surprisingly, however, clones with average telomere lengths several kilobases shorter than those of senescent parental cells continued to proliferate. Although the longest telomeres shortened, the size of the shortest telomeres was maintained. Cells with subsenescent telomere lengths proliferated for an additional 20 doublings after inhibiting telomerase activity with a dominant-negative hTERT mutant. These results indicate that, under conditions of limiting telomerase activity, cis-acting signals may recruit telomerase to act on the shortest telomeres, argue against the hypothesis that the mortality stage 1 mechanism of cellular senescence is regulated by telomere positional effects (in which subtelomeric loci silenced by long telomeres are expressed when telomeres become short), and suggest that catalytically active telomerase is not required to provide a protein-capping role at the end of very short telomeres.

Cell Line, Transformed↗
PubMed2000

Repeat HIV testing: high-risk behaviour or risk reduction strategy?

OBJECTIVE: To examine the characteristics of repeat and first-time HIV testers and consider their implications for HIV test counselling. METHODS: An anonymous questionnaire was completed by nearly 1500 people seeking an HIV test between September 1997 and July 1998 at a same-day HIV testing clinic in London, United Kingdom. Repeat testers were those people who had previously tested HIV negative and were returning for another test. Information was collected on self-reported unprotected penetrative sex (UPS) in the previous 3 months and reasons for seeking the present test. RESULTS: Overall, 50.6% (721/1446) of all clinic attenders were repeat testers: gay men 71.7% (337/470), heterosexual men 42.1% (208/494) and heterosexual women 38.6% (186/482). No significant differences were found between repeat and first time testers in the frequency of UPS (P > or = 0.06). However, gay men (but not heterosexual men and women) reporting three or more previous HIV tests were significantly more likely to report higher-risk UPS (i.e. with a partner whose HIV status was either positive or unknown) (42.2%) than those who had had one-two or no previous tests (25.3 and 25.4%, respectively; P = 0.002). Over half the heterosexual men and women, and one third of gay men said they were seeking the current HIV test in preparation for a new relationship; these proportions did not differ significantly between repeat and first-time testers (P > 0.1). CONCLUSION: In this London HIV testing clinic, no significant differences were found in the frequency of UPS between repeat and first-time testers with the exception of gay men with a history of three or more previous HIV tests, who reported elevated levels of high-risk sexual behaviour. For many people, repeat HIV testing has become part of a risk reduction strategy to establish seroconcordance with a regular partner. HIV test counselling provides the opportunity both to address high-risk behaviour and to reinforce personal risk-reduction strategies.

Female↗
PubMed2000

Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases.

Human brain ageing is associated with reductions in a variety of nicotinic receptors subtypes, whereas changes in age-related disorders including Alzheimer's disease or Parkinson's disease are more selective. In Alzheimer's disease, in the cortex there is a selective loss of the alpha4 (but not alpha3 or 7) subunit immunoreactivity and of nicotine or epibatidine binding but not alpha-bungarotoxin binding. Epibatidine binding is inversely correlated with clinical dementia ratings and with the level of Abeta1-42, but not related to plaque or tangle densities. In contrast, alpha-bungarotoxin binding is positively correlated with plaque densities in the entorhinal cortex. In human temporal cortex loss of acetylcholinesterase catalytic activity is positively correlated with decreased epibatidine binding and in a transgenic mouse model over expressing acetylcholinesterase, epibatidine binding is elevated. In Parkinson's disease, loss of striatal nicotine binding appears to occur early but is not associated with a loss of alpha4 subunit immunoreactivity. Tobacco use in normal elderly individuals is associated with increased alpha4 immunoreactivity in the cortex and lower densities of amyloid-beta plaques, and with greater numbers of dopaminergic neurons in the substantia nigra pars compacta. These findings indicate an early involvement of the alpha4 subunit in beta-amyloidosis but not in nigro-striatal dopaminergic degeneration.

Acetylcholinesterase↗
PubMed2000

Cell cycle basis for the onset and progression of c-Myc-induced, TGFalpha-enhanced mouse mammary gland carcinogenesis.

Using single and double transgenic mouse models, we investigated how c-Myc modulates the mammary epithelial cell cycle to induce cancer and how TGFalpha enhanced the process. In c-myc transgenic mice, c-myc expression was high in the hyperplastic mammary epithelium and in the majority of tumor areas. However, the tumors displayed focal areas of low expression of c-myc but high rates of proliferation. In contrast to E2F1 and cyclin A2, which were induced and co-localized with c-myc expression, induction of cyclins D1 and E occurred only in these tumor foci. Overexpression of cyclin D1 also occurred in the hyperplastic epithelium of tgfalpha-single and tgfalpha/c-myc-double transgenic mice. In tgfalpha/c-myc tumors, cells positive for cyclins D1 and E were randomly spread, without showing a reciprocal relationship to c-myc expression. In contrast to c-myc tumors, most tgfalpha/c-myc tumors showed undetectable levels of retinoblastoma protein (pRB), and the loss of pRB occurred in some cases at the mRNA level. These results suggest that E2F1 and cyclin A2 may be induced by c-Myc to mediate the onset of mammary cancer, whereas overexpression of cyclins D1 and E may occur later to facilitate tumor progression. TGFalpha may play its synergistic role, at least in part, by inducing cyclin D1 and facilitating the loss of pRB.

Animals↗
PubMed2000

Understanding factors that limit the productivity of suspension-based perfusion cultures operated at high medium renewal rates.

One of the key parameters in perfusion culture is the rate of medium replacement (D). Intensifying D results in enhanced provision of nutrients, which can lead to an increase in the viable cell density (X(v)). The daily MAb production of hybridoma cells can thus be increased proportionally without modifying the bioreactor scale, provided that both viable cell yield per perfusion rate (Y(Xv/D)) and specific MAb productivity (q(MAb)) remain constant at higher D. To identify factors prone to limit productivity in perfusion, a detailed kinetic analysis was carried out on a series of cultures operated within a D range of 0.48/4.34 vvd (volumes of medium/reactor volume/day) in two different suspension-based systems. In the Celligen/vortex-flow filter system, significant reductions in Y(Xv/D) and q(MAb) resulting from the use of gas sparging were observed at D > 1.57 vvd (X(v) > 15 x 10(6) cells/mL). Through glucose supplementation, we have shown that the decrease in Y(Xv/D) encountered in presence of sparging was not resulting from increased cellular destruction or reduced cell growth, but rather from glucose limitation. Thus, increases in hydrodynamic shear stress imparted to the culture via intensification of gas sparging resulted in a gradual increase in specific glucose consumption (q(glc)) and lactate production rates (q(lac)), while no variations were observed in glutamine-consumption rates. As a result, while glutamine was the sole limiting-nutrient under non-sparging conditions, both glutamine and glucose became limiting under sparging conditions. Although a reduction in q(MAb) was observed at high-sparging rates, inhibition of MAb synthesis did not result from direct impact of bubbles, but was rather associated with elevated lactate levels (25-30 mM), resulting from shear stress-induced increases in q(lac), q(glc), and Y(lac/glc). Deleterious effects of sparging on Y(Xv/D) and q(MAb) encountered in the Celligen/vortex-flow filter system were eliminated in the sparging-free low-shear environment of the Chemap-HRI/ultrasonic filter system, allowing for the maintenance of up to 37 x 10(6) viable cells/mL. A strategy aimed at reducing requirements for sparging in large-scale perfusion cultures by way of a reduction in the oxygen demand using cellular engineering is discussed.

Animals↗
PubMed2000

Integrin alpha(2)I domain recognizes type I and type IV collagens by different mechanisms.

The collagens are recognized by the alphaI domains of the collagen receptor integrins. A common structural feature in the collagen-binding alphaI domains is the presence of an extra helix, named helix alphaC. However, its participation in collagen binding has not been shown. Here, we have deleted the helix alphaC in the alpha(2)I domain and tested the function of the resultant recombinant protein (DeltaalphaCalpha(2)I) by using a real-time biosensor. The DeltaalphaCalpha(2)I domain had reduced affinity for type I collagen (430 +/- 90 nM) when compared with wild-type alpha(2)I domain (90 +/- 30 nM), indicating both the importance of helix alphaC in type I collagen binding and that the collagen binding surface in alpha(2)I domain is located near the metal ion-dependent adhesion site. Previous studies have suggested that the charged amino acid residues, surrounding the metal ion-dependent adhesion site but not interacting with Mg(2+), may play an important role in the recognition of type I collagen. Direct evidence indicating the participation of these residues in collagen recognition has been missing. To test this idea, we produced a set of recombinant alpha(2)I domains with mutations, namely D219A, D219N, D219R, E256Q, D259N, D292N, and E299Q. Mutations in amino acids Asp(219), Asp(259), Asp(292), and Glu(299) resulted in weakened affinity for type I collagen. When alpha(2) D219N and D292N mutations were introduced separately into alpha(2)beta(1) integrin expressed on Chinese hamster ovary cells, no alterations in the cell spreading on type I collagen were detected. However, Chinese hamster ovary cells expressing double mutated alpha(2) D219N/D292N integrin showed remarkably slower spreading on type I collagen, while spreading on type IV collagen was not affected. The data indicate that alpha(2)I domain binds to type I collagen with a different mechanism than to type IV collagen.

Animals↗
PubMed2000

The SPICE study: 48-week activity of combinations of saquinavir soft gelatin and nelfinavir with and without nucleoside analogues. Study of Protease Inhibitor Combinations in Europe.

OBJECTIVES: To compare the efficacy and safety of saquinavir soft gelatin capsules (SQV-SGC) and nelfinavir (NFV), with or without two concomitant nucleoside reverse transcriptase inhibitors (NRTIs), in an exploratory objective to identify populations most likely to benefit from quadruple therapy. DESIGN: Phase II/III, open-label, randomized, parallel-arm, multicenter trial. PARTICIPANTS: Enrollment included 157 protease inhibitor-naive adults (> or = 13 years) with HIV-1 RNA > or = 10,000 copies/ml; 132 participants completed 48 weeks of therapy. INTERVENTIONS: SQV-SGC 1200 mg, NFV 750 mg, SQV-SGC 800 mg plus NFV 750 mg, all with two NRTIs, and SQV-SGC 800 mg plus NFV 750 mg alone, all three times daily for 48 weeks. MAIN OUTCOME MEASURES: Proportion of participants with HIV-1 RNA <50 copies/ ml (16 and 48 weeks); time to virologic relapse (48 weeks). RESULTS: Proportions of patients with HIV RNA <50 copies/ml were not statistically significantly different between arms at 16 or 48 weeks, although trends favored the quadruple-therapy arm. In patients experiencing virologic relapse, time to relapse was statistically significantly longer in the quadruple-therapy arm than in the other three arms (p = .007). Quadruple therapy provided benefit in NRTI-experienced patients and those with viral loads above the median value at baseline. Adverse events were mainly mild gastrointestinal disorders in all treatment arms. CONCLUSIONS: Quadruple therapy, including SQV-SGC and NFV, gave a more durable response than triple therapy with either single protease inhibitor. Quadruple therapy might particularly benefit NRTI-experienced patients and those with high baseline viral loads.

Adult↗
PubMed2000

Loosening pattern in a cementless custom-made hip stem: X-ray analysis, finite-elements and photoelasticity measurements.

Thirty-three X-press cementless stems (Depuy) manufactured according to standardized X-rays were inserted from 1992 to 1994. The patients' mean age was 49 (range 15-79) years with a mean follow-up of 32 (+/-6) months. A characteristic radiographic pattern of aseptic loosening with erosion of the medial cortex by the tip of the stem occurred in 28 patients and a valgus shift of the implant in 14 cases. A radiolucent line with increased sclerosis below the tip (zone Gruen 4) was observed in 17 cases. Four stems were revised due to histologically confirmed aseptic loosening. Biomechanical investigation of one of the revised stems with the typical pattern of valgus angulation and medial cortex erosion included photoelasticity and finite-element analysis. The intertrochanteric fit and fill obviously resulted in an unfavorable distribution of contact areas, including peaks of high stress on the medial tip of the stem. These experimental findings are even evident for a postulated rotational stability. The clinical and radiographic results of the cementless X-press stems do not seem to support the fixation concept of intertrochanteric fit and fill of femoral components.

Adolescent↗
PubMed2000

Factors associated with long-term progression or stability in primary open-angle glaucoma.

PURPOSE: To evaluate long-term risk factors for progression or stability in patients with primary open-angle glaucoma. METHOD: We retrospectively included consecutively reviewed patients who had primary open-angle glaucoma for at least 5 years in this multicenter trial. Historical and clinical factors in these patients were evaluated for their association with stability or progression of the glaucoma. RESULTS: We included 218 patients in this study; of these, 34 progressed over an average length of follow-up of 45.5 +/- 30.0 months, and 184 were stable over an average of 72.8 +/- 18.3 months. The mean intraocular pressure over the follow-up period for the progressed group was 19.5 +/- 3.8 mm Hg and for the stable group 17. 2 +/- 3.1 mm Hg (P =.001). The average standard deviation of individual intraocular pressures was greater in the progressed group (5.1 mm Hg) than the stable group (3.9 mm Hg, P =.012). Baseline characteristics indicating a greater potential to progress were a larger cup-to-disk ratio (P <.001), a greater number of medications (P =.02), older age (P.007), and worse visual acuity (P =.003). However, no difference was observed in pressure levels that prevented progression in these subpopulations compared with the total sample size. CONCLUSIONS: This study suggests that lowering the intraocular pressure is important in the treatment of primary open-angle glaucoma to help prevent long-term progression. Lowering the pressure, however, is not uniformly effective in preventing progression. Additionally, risk factors for progression do not further help identify pressure levels that prevent worsening of glaucoma.

Aged↗