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Progress in the implementation of Quality Management in Dutch health care: 1995-2000.

OBJECTIVES: Policymakers and researchers in all countries like to know whether the implementation of Quality Management (QM) in health care is proceeding satisfactorily. Longitudinal surveys can reveal whether sufficient progress is being made. The main objective of the study was to investigate the progress in QM in Dutch health care organizations during the period 1995-2000. A second objective was to explore whether the progress in QM was related to subsectors of care and/or to cultural characteristics of health care organizations. DESIGN AND PARTICIPANTS: The study has a descriptive longitudinal design, based on repeat measurements in 1995 and 2000. Empirical data about QM activities in health care organizations were gathered using a questionnaire. The analyses are based on data from the 474 health care organizations that participated in the study in 1995 and 2000. SETTING: Participants in the study were organizations from all subsectors of health care, including providers of home care, nursing homes, hospitals, and other care sectors. MAIN OUTCOME MEASURES: Outcome measures are 46 distinct QM activities, which were listed in the questionnaire. RESULTS: Two-thirds of the organizations had made progress in the implementation of QM activities. A mean of 25 QM activities per organization was found in 2000 compared with 20 in 1995. More care providers had set up a client council and had carried out patient satisfaction surveys. Home care organizations had made twice as much progress as many other health care organizations. However, nearly one-third of the health care organizations showed a decline in QM activities. Patient organizations were less often involved in the development of quality criteria and protocols. Progress in QM was weakly related to the dedicated and flexible attitude of employees and a non-hierarchical decision-making structure. CONCLUSION: The study demonstrates that the implementation of QM activities can be monitored at the national level and that differences between subsectors of care can be assessed. The decline in QM activities in one-third of the organizations needs to be researched further.

Delivery of Health Care↗

Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression.

BACKGROUND: Approximately one third of the patients with superficially infiltrative transitional cell (T1-TNM pathological staging system) bladder carcinoma who are treated with transurethral resection alone have disease progression. Despite precise pathologic staging and grading, clinical outcome in these patients is not predictable. Recent reports reveal that mutations of the p53 tumor suppressor gene (also known as TP53) occur commonly in bladder cancers. PURPOSE: The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein product(s) of the mutated p53 tumor suppressor gene are associated with tumor progression in patients with T1 bladder cancer. METHODS: We examined deparaffinized tumor tissue specimens from transurethral resection in 43 patients with T1 bladder cancer who had not received adjuvant therapy. Nuclear overexpression of p53 protein was detected by immunohistochemical analysis using the mouse monoclonal antibody PAb1801, which stains both wild-type and mutant p53 proteins. The data were then correlated with the following conventional prognostic variables: age, sex, histologic presence of associated carcinoma in situ, and vascular invasion of tumor. Disease progression rates per 100 person-years were calculated. RESULTS: Median follow-up was 119 months. None of the urothelial and stromal cells from normal bladder specimens showed nuclear overexpression of p53 protein, but patients with T1 bladder tumors could be stratified into two groups with different patterns of staining for p53 protein. Eighteen patients (42%) had no more than 20% tumor cells with positive nuclear staining (group A), while the remaining 25 patients (58%) had 20% or more tumor cells with nuclear immunoreactivity (group B). Patients in group B had a significantly lower progression-free interval (P < .001). Disease progression rates were 20.5% per year for group B and 2.5% for group A. CONCLUSION: These results suggest that T1 bladder cancers exhibiting nuclear overexpression of p53 protein have a higher probability of disease progression. This study also suggests that p53 overexpression is an important prognostic factor in these patients and may be useful in selecting appropriate therapy. IMPLICATIONS: Large prospective studies are needed to confirm these results and to evaluate nuclear overexpression of p53 protein as a prognostic marker in bladder cancer.

Adult↗

Brief report: social risk factors predict cigarette smoking progression among adolescents with asthma.

OBJECTIVE: To compare smoking progression in adolescents with and without asthma and to compare their psychosocial risk factors. METHODS: Participants were 1,507 adolescents with asthma and 1,507 healthy matched controls from Waves I and II of the Add Health Project assessed at baseline and again 1 to 2 years later at follow-up. Three levels of smoking progression (defined as smoking more frequently and/or intensely over time) were identified: (a) Late Experimenters (never smokers at baseline, ever smokers at follow-up), (b) Early Experimenters (ever smokers at baseline, current/current frequent smokers at follow-up), and (c) Early Smokers (current smokers at baseline, current frequent smokers at follow-up). RESULTS: Twenty percent of adolescents experienced progression in their smoking behavior; those with and without asthma were equally likely to progress. Among adolescents who progressed, 37% were Late Experimenters, 42% were Early Experimenters, and 21% were Early Smokers. Exposure to friends who smoked was a consistent and powerful social risk factor for smoking progression among adolescents with asthma-more so than among adolescents without asthma. This effect was intensified among Late Experimenters by the presence of a positive history of parent smoking. CONCLUSIONS: Findings underscore the importance of addressing cigarette smoking behavior and its social risk factors among adolescents with asthma in both clinical and public health contexts, during early adolescence, and through research on this topic.

Adolescent↗

Plasma levels of lipoprotein (a) do not predict progression of human chronic renal failure.

Chronic renal failure is frequently accompanied by elevated plasma levels of lipoprotein (a) [Lp(a)]. Elevated Lp(a) levels have been proposed to contribute not only to increased risk of atherosclerotic and thrombotic complications but also to the progression of renal insufficiency. To investigate whether higher Lp(a) plasma concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of Lp(a) with the progressive decline of renal function in an observational study of human chronic renal disease. Forty-nine non-diabetic patients (40 men, nine women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.1 years, and the mean rate of decline in glomerular filtration rate (51Cr-EDTA clearance) was -2.8 (SD 4.1) ml/min/1.73 m2. The mean plasma concentration of Lp(a) at the beginning of the study was 19.2 (SD 18.6) mg/100 ml with a median value of 12.2 mg/100 ml. There was no association between the initial plasma concentration of Lp(a) and the rate of progression as assessed by linear regression analysis. Furthermore, the progression rate in patients within the highest quartile of the Lp(a) distribution (> or = 30 mg/100 ml) did not differ from that in patients with lower levels of Lp(a). In contrast, increased levels of apolipoprotein (apo) B, low-density lipoprotein (LDL)-cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. Based on these results, it was concluded that elevated plasma levels of Lp(a) are not associated with an increased rate of progression of renal insufficiency in human chronic renal disease. However, the results of this study suggest that other apoB-containing lipoproteins may play a significant role in this process.

Adult↗

Reduction of blood pressure retards the progression of chronic renal failure in man.

The effect of blood pressure reduction on the progression rate of chronic renal failure (CRF) was studied in 28 patients with CRF of diverse aetiology entering a prospective study (observation time 7-24 months, mean 16 months). Endogenous creatinine clearance was 12-66 ml/min (mean 30 +/- 3 ml/min). We aimed to keep the blood pressure below 160/90 mmHg. Dietary protein was not restricted. The progression rate of CRF was assessed from the regression coefficients of the regressions of creatinine clearance and the inverse of s-creatinine, respectively, on time. Progression rate and the means of all recordings of mean arterial blood pressure (MAP) and urinary protein excretion, respectively, in each patient during the prospective phase were compared with retrospective data from the proceeding period (observation time 4-25 months, mean 19 months). The patients received various combinations of antihypertensive drugs including diuretics, beta-blockers and vasodilatory drugs. In 19 patients MAP decreased from 109 +/- 2 to 102 +/- 2 mmHg (group I), whereas MAP increased from 105 +/- 2 to 108 +/- 2 mmHg in nine patients (group II). In group I proteinuria was significantly lower (P less than 0.05) and the progression of CRF was approximately 50% slower (P less than 0.01) in the prospective phase than in the retrospective phase; no changes were observed in group II. Calculated for all patients, significant correlations were observed between the change in MAP and the change in progression rate and protein excretion, respectively. These results indicate that lowering of blood pressure results in decreased proteinuria and retardation of the progression of CRF irrespective of the aetiology.

Adult↗

Induction and enhancement of progressive motility in hamster caput epididymal spermatozoa.

Progressive motility was induced in hamster caput epididymal spermatozoa incubated in Tyrodes medium containing 50 mM theophylline, 1.0% Fraction V bovine serum albumin, and 15% (v/v) heat-treated human seminal plasma. Under these induction conditions, however, the maximum percent of caput spermatozoa exhibiting progressive motility (21%) and the time during which motility was sustained (120 min) were significantly less (p less than 0.05) than that of controls from the cauda epididymidis. Moreover, in contrast to caudal spermatozoa, the majority of the induced caput spermatozoa exhibited some degree of flagellar bending at the neck or midpiece. In subsequent experiments the procedure for motility induction was modified to achieve levels of motility in caput spermatozoa equivalent to those observed for caudal spermatozoa. The addition of 5 microM diamide, a sulfhydryl oxidant, to the induction medium prevented the flagellar angularity observed in induced caput sperm preparations. The percentage of caput spermatozoa induced to progressive motility was increased to levels characteristic of caudal spermatozoa (48%) by the addition of hamster caudal epididymal fluid (CEF) to the induction medium. Finally, the viability of the induced caput spermatozoa was significantly enhanced (p less than 0.05) by the removal of Fraction V albumin from the induction medium. In the presence of CEF and in the absence of albumin, 50% of the caput spermatozoa acquired progressive motility and sustained this motility for 4 h. Moreover, when fatty acid-free, charcoal-extracted albumin instead of Fraction V albumin was utilized in the induction procedure, a maximum of 43% of the caput spermatozoa acquired progressive motility and maintained this motility for 4 h, suggesting that the decreased sperm viability observed in the presence of Fraction V albumin was due to a contaminant of albumin, possibly fatty acids. The studies described herein demonstrate for the first time that immature quiescent caput epididymal spermatozoa can be induced to acquire progressive and sustained motility equivalent to that observed in mature caudal epididymal spermatozoa.

Animals↗

Progressive independence in clinical training: a tradition worth defending?

BACKGROUND: Progressive independence is a traditional premise of clinical training. Recently, issues such as managed care, work hours limitation, and patient safety have begun to impact the degree of autonomy afforded to clinical trainees. This article reviews empirical evidence and theory pertaining to the role of progressive autonomy in clinical learning. METHOD: A computerized literature search was performed using Medline, PsycINFO, Social Sciences Citation Index, and Educational Resources Information Center. This article presents a synthetic review of relevant empirical and theoretical concepts from the domains of medicine, psychology, education, kinesiology, and sociology. RESULTS: The clinical psychology and medical education literatures provide evidence that clinical trainees act more independently as their training progresses, but have not yet evaluated the educational efficacy of providing progressive independence, or the consequences of failing to do so. The expertise and motor learning literatures provide some theoretical evidence (as yet untested in complex clinical environments) that the provision of too much guidance or feedback to trainees could be educationally detrimental in the long term. The sociology literature provides insight into the cultural values underlying the behavior of clinical teachers and trainees relating to issues of supervision and independence. CONCLUSIONS: There is limited empirical support for the current model of progressive independence in clinical learning; however, diverse theoretical perspectives raise concern about the potential educational consequences of eroding progressive independence. These perspectives could inform future research programs that would create a creative and effective response to the social and economic forces impacting clinical education.

Counseling↗

Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017)

OBJECTIVE: To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Multicentre study in five European countries and Australia. PATIENTS: Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects with HIV p24 antigenaemia (> 10 pg/ml). INTERVENTION: Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250 mg four times daily dose regimen for the first 4 weeks. MAIN OUTCOME MEASURES: The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed. RESULTS: Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rank P = 0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a trend in a delay in progression to CDC stage IV disease was observed (P = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P = 0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed. CONCLUSIONS: Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.

AIDS-Related Complex↗

Use of immunological markers and continuous-time Markov models to estimate progression of HIV infection in homosexual men.

OBJECTIVES: We used continuous-time Markov models based on CD4 cell counts and anti-CD3 reactivity (i.e., measure for T-cell quality) to study the progression of HIV infection in a cohort study of homosexual men in Amsterdam. We also compared the effectiveness of anti-CD3 reactivity as a marker for disease progression with that of CD4 cell counts. METHODS: We used data from 467 men (6905 visits) with visits at 3-month intervals between October 1984 and March 1993. To account for measurement error and short time-scale variability, the immunological stage at each visit was determined using a kernel smoother on log-transformed data from each individual. The Markov model had six marker-defined stages and a seventh stage for clinical AIDS. The initial stage-occupation probabilities for seroconverters were used to estimate the incubation time from infection to AIDS. Confidence intervals were calculated using the bootstrap method to account for the effect of smoothing on the variability of our estimates. RESULTS: The CD4 staging scheme estimated the median time from seroconversion to AIDS at 8.3 years [95% confidence interval (CI), 8.1-8.6], and a similar estimate was obtained with the anti-CD3 staging model. The CD4 model predicts that 10.2% (95% CI, 9.9-13.1) will remain AIDS-free 15 years after seroconversion. The mean number of stages visited before AIDS is lower with the CD4 model (7.4; 95% CI, 7.2-7.7) than with the anti-CD3 model (11.3; 95% CI, 10.8-12.0), implying that anti-CD3 predicts progression less well than CD4 cell count. CONCLUSIONS: CD4 lymphocyte counts and anti-CD3 reactivity are each associated with an increased hazard for progression to AIDS. Therefore, men in different CD4-stages (anti-CD3 stages) follow different incubation period distributions to AIDS. However, anti-CD3 predicts progression less well than CD4 cell count. Staged time-continuous Markov models are useful to study immunological markers for HIV disease progression.

Adult↗

HIV-2 infection in 12 European residents: virus characteristics and disease progression.

OBJECTIVE: To assess the disease progression rate among 12 HIV-2-infected West European residents (nine of West African descent), compared with the disease progression rate among HIV-1-infected individuals of the same population, and the characteristics of the HIV-2 strains involved. METHODS: HIV-2-infected individuals were identified by commercially available serological assays, their clinical status and CD4+ cell counts were monitored, and HIV-2 was isolated from their peripheral blood mononuclear cells. T-cell-line tropism and syncytium-inducing capacities of the isolated viruses were determined and their phylogenetic relationships were analysed by comparing polymerase chain reaction-amplified nucleotide sequences of reverse transcriptase (RT) gene segments. RESULTS: Eight of the 12 HIV-2-infected individuals presented with progressive disease and one of them progressed from Centers for Disease Control and Prevention group A1 to A3 within 36 months after seroconversion. The ratios of asymptomatic versus symptomatic individuals among residents of the Rotterdam region of West African descent were 2:7 for HIV-2 and 8:9 for HIV-1-infected individuals. HIV-2 was isolated from six of the nine individuals with progressive disease. The time required for virus isolation correlated inversely with the individuals' CD4+ cell counts. Five of the HIV-2 isolates replicated in immortalized T-cell lines, and two isolates from patients with AIDS were syncytium-inducing. Five HIV-2 isolates from patients born in the Cape Verdian Isles grouped together within subtype A. The HIV-2 isolate from a patient of Ghanese origin belonged to subtype B. Mutations were identified in the RT genes from HIV-2 isolates of two zidovudine-treated patients, one of which has also been shown to be involved in zidovudine resistance in HIV-1. CONCLUSION: Disease progression in HIV-2 infection may be as rapid as in HIV-1. HIV-2 isolation and viral phenotype were related to disease status, and mutations identical to those observed in HIV-1 zidovudine resistance were observed in patients treated with zidovudine.

Adult↗

Association between serum vitamin A and E levels and HIV-1 disease progression.

OBJECTIVE: To examine the associations between serum vitamin A and E levels and risk of progression to three key outcomes in HIV-1 infection: first AIDS diagnosis, CD4+ cell decline to < 200 cells x 10(6)/l, and mortality. DESIGN: Non-concurrent prospective study. METHODS: Serum levels of vitamins A and E were measured at the enrollment visit of 311 HIV-seroprevalent homo-/bisexual men participating in the Baltimore/ Washington DC site of the Multicenter AIDS Cohort Study. Cox proportional hazards models were used to estimate the relative hazard of progression to each outcome over the subsequent 9 years, adjusting for several independent covariates. RESULTS: Men in the highest quartile of serum vitamin E levels (> or = 23.5 mumol/l) showed a 34% decrease in risk of progression to AIDS compared with those in the lowest quartile [relative hazard (RH), 0.66; 95% confidence interval (CI), 0.41-1.06)]. This effect was statistically significant when comparing the highest quartile of serum vitamin E to the remainder of the cohort (RH, 0.67; 95% CI, 0.45-0.98). Associations between serum vitamin A levels and risk of progression to AIDS were less clear, but vitamin A levels were uniformly in the normal to high range (median = 2.44 mumol/l). Similar trends were observed for each vitamin with mortality as the outcome, but neither vitamin was associated with CD4+ cell decline to < 200 cells x 10(6)/l. Men who reported current use of multivitamin or single vitamin E supplements had significantly higher serum tocopherol levels than those who were not taking supplements (P = 0.0001). Serum retinol levels were unrelated to intake of multivitamin or single vitamin A supplements. CONCLUSIONS: These data suggest that high serum levels of vitamin E may be associated with slower HIV-1 disease progression, but no relationship was observed between retinol levels and disease progression in this vitamin A-replete population.

Acquired Immunodeficiency Syndrome↗

Progressive congenital scoliosis treatment using a transpedicular anterior and posterior convex hemiepiphysiodesis and hemiarthrodesis. A preliminary report.

STUDY DESIGN: Patients treated with a transpedicular anterior and posterior convex hemiepiphysiodesis and hemiarthrodesis for progressive congenital scoliosis were followed to evaluate this treatment. OBJECTIVE: To evaluate an alternative to a separate anterior approach for performing an anterior hemiepiphysiodesis for progressive congenital scoliosis. SUMMARY OF BACKGROUND DATA: Previous investigators have reported a transpedicular anterior fusion combined with a bilateral posterior fusion. The authors are unaware of a previous report on a transpedicular anterior convex hemiepiphysiodesis and fusion combined with a unilateral convex posterior spinal fusion to treat progressive congenital scoliosis. METHODS: Nineteen curves were fused in 16 patients who had a variety of congenital anomalies. The average age at surgery was 4.8 years (range, 11 months to 13 years) The average follow-up period was 4.8 years (range, 2 to 9.6 years). RESULTS: The average preoperative and postoperative fused curves measured 36 degrees and 38 degrees, respectively. Of the 19 fused curves, seven curves (37%) improved, eight curves (42%) were unchanged or progressed less than 7 degrees, three curves (16%) progressed 10 degrees to 15 degrees, and one curve (5%) progressed more than 15 degrees. CONCLUSIONS: This procedure appears to be most effective in arresting growth in the young patient who has an isolated hemivertebrae and no excessive kyphosis. The epiphysiodesis effect is less predictable.

Bone Transplantation↗

Progression of vertebral wedging in an asymmetrically loaded rat tail model.

STUDY DESIGN: A rat tail model was used to test the hypothesis that angulation and asymmetric axial compressive loading would lead to vertebral wedging because of asymmetric longitudinal growth in the physes. OBJECTIVES: To study the effect of angulation and asymmetric loading on the progression of spinal curvature in a rat tail model. SUMMARY OF BACKGROUND DATA: Large idiopathic scoliotic curves in children with significant growth remaining are the curves most likely to progress. The mechanism of progression of skeletal deformities is thought to be controlled by the Hueter-Volkmann law, whereby additional axial compression decelerates growth, and reduced axial compression accelerates growth. It has been hypothesized that spinal curvature leads to asymmetric loading transversely along the vertebral growth plate, causing progressive vertebral wedging by means of a vicious cycle. METHODS: Two 32-mm diameter external ring fixators were glued to 0.7-mm pins that had been inserted percutaneously through the eighth and 10th caudal vertebra of 10 6-week-old Sprague-Dawley rats. Calibrated springs and 15 degrees wedges, mounted on stainless steel threaded rods passing through holes distributed around the rings, imposed a 30 degrees Cobb angle and axially compressed the instrumented vertebrae. Fluorochrome labels and radiographs were used to document the progression of vertebral wedging. RESULTS: The wedging initially was entirely in the intervertebral discs, but by 6 weeks the wedging of the discs and vertebrae were approximately equal. Fluorochrome labeling confirmed that the vertebral wedging resulted from asymmetric growth in the physes. CONCLUSIONS: This study shows that vertebrae, when asymmetrically loaded, become wedged. This is consistent with the concept of mechanically provoked progression of scoliotic deformities according to the Hueter-Volkmann law.

Animals↗

Progression of kidney disease in chronic renal transplant rejection.

The rate of progression of renal insufficiency was quantitated from reciprocal of serum creatinine versus time plots in patients with clinical and histologic evidence of chronic renal transplant rejection. The plots were evaluated by the breakpoint test. This method identifies breakpoints in a linear plot and compares the statistical significance of the fit provided by two intersecting lines with that of a single straight line. The breakpoint test when applied to the 22 patients with a significant linear correlation between the reciprocal of serum creatinine versus time detected a change in the slope in 20 cases (90.9%) indicating the presence of a breakpoint. The average diastolic, systolic, and mean arterial pressures before the breakpoint were significantly correlated with the value of the serum creatinine at the time of the change of the slope (r = 0.45, P less than 0.05; r = 0.58, P less than 0.01; r = 0.56, P less than 0.05, respectively) demonstrating more severe hypertension in those patients with the more severe renal dysfunction. The slope after the breakpoint was significantly correlated with the mean diastolic blood pressure values after the breakpoint (r = 0.48, P less than 0.05) with higher pressures being found in those patients with faster rates of decline in renal function. Both before and after the breakpoint occurred, the rate of progression of the renal disease, as estimated by the reciprocal of serum creatinine versus time plot, was greater when the mean diastolic blood pressure was higher than 90 mmHg. In conclusion, the vast majority of patients with proven chronic rejection progress linearly although a change in the rate of progression was frequent. Higher levels of blood pressure correlate with greater rates of progression of renal insufficiency, and a faster progression associates with a diastolic blood pressure greater than 90 mmHg.

Adolescent↗

Uteroglobin gene polymorphisms affect the progression of immunoglobulin A nephropathy by modulating the level of uteroglobin expression.

Uteroglobin (UG) is an anti-inflammatory/immunomodulatory protein. Targeted disruption of UG rendered mouse glomerulonephritis resembling immunoglobulin (Ig)A nephropathy (IgAN). Sequence analysis on exon 1 of UG showed several putative binding sites for transcription factors, and polymorphisms in this site might influence the expression level of UG as a competitive protein. We speculated that the single nucleotide polymorphism at the 38th nucleotide (A to G) from the transcription initiation site of UG exon 1 would impact the progression of IgA nephropathy (IgAN). Polymerase chain reaction-restriction fragment length polymorphism and single-strand conformation polymorphism were instituted to determine the genetic polymorphism. Luciferase assay was performed using the gene constructs containing a region 404-bp long located upstream of UG exon 1 initiation site to analyse whether this polymorphism would affect the expression level. UG polymorphism was distributed no differently in patients with IgAN (n = 111) compared to 60 healthy control subjects. An excess of A genotype was found in one patient having progressive disease (P = 0.03) and the risk for the disease progression increased as the number of A alleles increased (P for trend = 0.03) after follow-up for 116 months. The odds ratio for progression with the AA genotype was 4.9 (95% Cl = 1.0-23.9) compared to patients having the GG genotype. Significant interactive effects of hypertension and genetic polymorphisms of UG on the disease progression were observed (P for interaction = 0.001). In the luciferase assay, the gene construct with A at the 38th site showed a decreased activity of 74 +/- 8.4% compared to that showed by G gene construct. Our results suggest that polymorphism at the 5' UTR region of UG exon 1 is an important marker for the progression of IgAN and may modulate the level of protein expression.

5' Untranslated Regions↗

Lipoprotein lipase locus and progression of atherosclerosis in coronary-artery bypass grafts.

PURPOSE: Our aim was to test whether polymorphisms in the lipoprotein lipase (LPL) gene were associated with the progression of atherosclerosis in grafts examined in the Post-Coronary Artery Bypass Graft Trial (Post-CABG Trial). METHODS: 843 subjects in the post-CABG trial were genotyped for the LPL-D9N, N291S, PvuII, (TTTA)n, and HindIII polymorphisms. Associations between genotype and angiographically measured progression of atherosclerosis in grafts, medical history, and family history were examined. RESULTS: Greater progression of atherosclerosis was observed in subjects with LPL-HindIII 2/2 (56% versus 42% of those with other LPL HindIII genotypes, P = 0.025) and with LPL (TTTA)n 4/4 (63% versus 43% of those with other (TTTA)n genotypes, P = 0.020). Mantel-Haenszel analysis yielded an odds ratio of 1.84 for the effect of LPL HindIII 2/2 genotype on the progression of atherosclerosis in grafts (P = 0.015) and demonstrated that the effect of genotype on progression was of the same magnitude as, but independent of, the effect of drug treatment. CONCLUSION: The LPL-HindIII 2/2 genotype is a marker for genetic variation in the 3'-end of LPL that acts as an independent risk factor for the progression of atherosclerosis in grafts examined in the Post-CABG Trial.

Arteriosclerosis↗

Intermediate term biochemical progression rates after radical prostatectomy and radiotherapy in patients with screen detected prostate cancer.

PURPOSE: We compared biochemical progression rates measured by increasing prostate specific antigen (PSA) levels using a standard definition of biochemical recurrence among patients with screen detected prostate cancer treated with radical prostatectomy (RP) or radiotherapy (RT). MATERIALS AND METHODS: A total of 1,939 patients diagnosed with clinically localized prostate cancer in a community based screening study from 1989 to 1998, followed through 2001, were treated with RP or RT and agreed to enroll in a followup study. This prospective cohort study (median followup 62 months, range 0.2 to 141) used adjusted Cox proportional hazards models to examine time to progression. Selection bias was addressed with propensity scores. Biochemical evidence of cancer progression was defined as PSA greater than 0.2 ng/ml in patients who underwent RP and 3 consecutive PSA increases as recommended by the American Society for Therapeutic Radiology and Oncology criteria for radiotherapy. RESULTS: Of the patients 17% had evidence of cancer progression. The percentage with progression-free survival at 5 and 9 years for RP was 84% and 76%, respectively, and for RT 80% and 70%, respectively. Cox proportional hazards models produced a hazard ratio of 1.63 (95% CI, 1.12, 2.38) for RT compared with RP, adjusting for clinical stage, Gleason grade, preoperative PSA, biopsy age, treatment year and propensity for treatment type. CONCLUSIONS: With intermediate term followup, patients treated with RT were more likely to have cancer progression than with RP adjusting for demographics, clinical factors, selection bias and treatment year.

Adult↗

Progressive hippocampal and extrahippocampal atrophy in drug resistant epilepsy.

PURPOSE OF REVIEW: This article reviews recent experimental and clinical evidence for seizure-related progressive brain damage and discusses possible mechanisms of ongoing brain atrophy in epilepsy. RECENT FINDINGS: Experimental data indicate that seizures induce brain plasticity that may result in either damage or protection. Brief seizures or status epilepticus may promote resistance to additional damage but also induce cumulative neuronal loss and increase susceptibility to network synchronization. Some experimental studies indicated that, following the initial damage caused by status epilepticus, further brief seizures may not produce significant continuing neuronal loss and hippocampal atrophy, whereas other studies showed the contrary. There is recent evidence that progressive damage and atrophy may occur after an acute insult but are not directly associated with recurrent seizures. Clinical research data continue to show discrepancies regarding whether ongoing seizures cause progressive atrophy. Some cross-sectional and longitudinal magnetic resonance imaging studies in patients with partial epilepsies have shown progressive hippocampal and extrahippocampal atrophy, the severity of which correlated with the duration of epilepsy, seizure frequency, or lifetime seizure number, whereas others have failed to show a clear association. SUMMARY: Experimental data indicate that epileptogenesis in developing brain may not require significant neuronal loss, which is in keeping with clinical observations that progressive cognitive and behavioural impairment may occur in patients with no detectable brain atrophy. A better understanding of why, when and how progressive brain atrophy occurs will lead to better clinical management, earlier surgical intervention when necessary and, ultimately, prevention of epileptogenesis.

Anticonvulsants↗