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PubMed1993

Comparison of the natural history of irregular and smooth coronary lesions: insights into the pathogenesis, progression, and prognosis of coronary atherosclerosis.

The coronary arteriograms of 255 patients who had two to four arteriograms within 2.6 +/- 1.7 years were reviewed. Two hundred three patients had lesions on at least one arteriogram; among the 167 patients without coronary surgery, there were 48 complex irregular lesions (suggesting a ruptured plaque and/or thrombosis) and 141 smooth lesions with follow-up, and 73 irregular and 164 smooth lesions with preceding arteriograms available. Severe irregular lesions (> or = 90% diameter occlusion) progressed to total occlusion (46%) more often than did severe smooth lesions (11.5%) (p < 0.01). Less severe lesions usually did not progress, with no difference in incidence of progression between irregular and smooth lesions (27.8% vs 23.9%). Irregular lesions > or = 80% usually occurred as a result of progression in less severe smooth lesion or occurred in areas that were minimally diseased or appeared normal, whereas smooth lesions > or = 80% had usually not changed since the previous arteriogram. Irregular lesions very rarely became smooth. A study of lesions in 36 patients with surgery was confirmatory. We conclude that plaque rupture is a common mechanism for progression of coronary disease but is not a common pathway for the growth of smooth lesions; irregular lesions remain irregular for years. There is no relationship between the severity of smooth plaques and their likelihood to rupture. Progression of coronary disease can occur by either of two modes: (1) gradual growth of a smooth-walled plaque or (2) plaque rupture with marked progression to a severe irregular lesion. Because most smooth and most irregular lesions remain stable for years, except possibly for > or = 90% irregular lesions, there is no anatomic finding that justifies urgent revascularization. Instability is a clinical diagnosis.

Aged↗
PubMed1990

Factors influencing progression of mitral regurgitation after transarterial balloon valvuloplasty for mitral stenosis.

This study analyzes the clinical, echocardiographic and hemodynamic factors affecting progression of mitral regurgitation (MR) after transarterial balloon valvuloplasty in 200 consecutive patients with rheumatic mitral stenosis. After valvuloplasty, the mitral valve area increased in all patients, from 1.03 +/- 0.36 to 2.06 +/- 0.71 cm2 (p less than 0.0001). With regard to the basal stage, the mitral valve was competent in 139 patients and there was mild MR in 61 (grade I in 53, and grade II in 8). Three patients had progression of MR induced by a technical deficiency and they were excluded from analysis. Patients were classified into 2 groups on the basis of the degree of MR before and after valvuloplasty: group A--no progression of MR (n = 167; 85%) when the degree of MR did not change, disappeared after valvuloplasty, or increased from grade 0 to I; group B--progression of MR (n = 30; 15%) when the degree of MR increased to greater than or equal to grade II. Progression of MR was observed more frequently in older patients with presence of chronic atrial fibrillation, larger left atrial size and left ventricular volumes, baseline MR, more severe stenosis and a lower ejection fraction. Multivariate analysis selected age, left ventricular volumes and ejection fraction as independent predictors of progression of MR. All these factors suggest that progression of MR after balloon valvuloplasty could be related to a more advanced degree of disease.

Age Factors↗
PubMed1996

Progressive tactile hypersensitivity: an inflammation-induced incremental increase in the excitability of the spinal cord.

Two established phenomena contribute to the generation of post-injury pain hypersensitivity: peripheral sensitization, an increase in transduction sensitivity of high threshold A delta and C-fibre nociceptors, and central sensitization, an increase in excitability of neurones in the spinal cord triggered exclusively by C-fibre inputs. We now describe a novel phenomenon: progressive tactile hypersensitivity, which contributes to a cumulative allodynia during inflammation. Behavioural measurements in conscious intact animals showed that repeated light touch stimuli delivered at 5-min intervals to an inflamed paw, established 48 h earlier by an intra-plantar injection of complete Freund's adjuvant (CFA), resulted in a progressive reduction in the mechanical withdrawal threshold by more than 75%, from its already hypersensitive basal level. This hypersensitive state persisted for several hours after discontinuing the touch stimuli and did not occur in non-inflamed animals. To monitor nociceptive processing and the afferent fibres responsible, we also measured activity in posterior biceps femoris/semitendinosus flexor motor neurones. In non-inflamed decerebrate-spinal rats, the cutaneous mechanical threshold and pinch-evoked activity of these neurones are stable when tested repeatedly at 5-min intervals and are characterised by absent or small responses to low intensity mechanical stimuli or electrical activation of A beta-fibres. In inflamed animals, the spontaneous activity, touch-, pinch- and A beta-afferent-evoked responses of hamstring flexor motor neurones are significantly increased. The flexor reflex becomes, moreover, progressively more sensitized by repetition every 5 min, of standard mechanical stimuli (touch and pinch), that do not modify excitability in control non-inflamed animals. A cumulative increase in A beta-afferent-evoked responses also occurs when the test stimulus only comprises stimulation of the sural nerve at A beta strength (10 Hz, 10 sec), showing that A beta-afferents have the capacity to produce progressive hypersensitivity. Progressive hypersensitivity, measured here as a progressive tactile allodynia after inflammation in either intact or decerebrate-spinal rats, with its gradual build-up and contribution from A beta fibres, is very different from the central sensitization induced by C-fibre stimulation which is characterised by a peak increase in excitability soon after the conditioning input followed by a steady decrement to baseline levels. Progressive hypersensitivity is likely to be the consequence of an alteration in the function and phenotype of afferents innervating inflamed tissue and the pattern of excitation they produce in spinal neurones. The phenomenon may have an important role in the development of inflammatory pain and hypersensitivity.

Animals↗
PubMed1990

Ischemia-induced slowly progressive neuronal damage in the rat brain.

Ischemic neuronal damage has been believed to make rapid progress in the course of a few days even in delayed selective neuronal death, to say nothing of acute brain necrosis. In the present study, however, we demonstrate for the first time a new type of ischemia-induced neuronal damage which progresses in the course of several weeks or a few months and we tentatively call this process "slowly progressive neuronal damage". We have focused on the chronological changes of neuronal damage in the dorsolateral striatum and neocortex following various durations of transient middle cerebral artery occlusion, which does not cause cerebral infarction and is clinically designated "transient ischemic attack". In the rats subjected to 15 min middle cerebral artery occlusion, the neocortex and lateral striatum were rarely damaged, whereas the small to medium-sized neurons only in the narrow area restricted to the dorsal striatum showed slowly progressive neuronal damage. Prolongation of ischemic duration to 30 min accelerated the evolution of neuronal damage in the dorsolateral striatum and also extended the distribution of neuronal damage to the neocortex, especially to layer III and more superficial layers. Further prolongation of ischemic duration to 45 min resulted in more rapid progress of selective neuronal death in those areas described above, whereas no animal escaped 60 min ischemia, without acute total tissue necrosis in the middle cerebral artery territory. Ischemia-induced slowly progressive neuronal damage may be implicated in the pathogenesis of such slowly progressive neurologic deterioration as dementia or Parkinsonism in patients with cerebral arteriosclerosis.

Animals↗
PubMed1995

Differential progression of complex and smooth stenoses within the same coronary tree in men with stable coronary artery disease.

OBJECTIVES: We sought to compare the evolution of complex and smooth stenoses within the same coronary tree in patients with stable coronary artery disease. BACKGROUND: Progression of coronary stenosis has prognostic significance and may be influenced by local and systemic factors. Stenosis morphology is a determinant of disease progression, but no previous study has systematically assessed progression of complex and smooth stenoses within the same patient. METHODS: We studied 50 men with stable angina who 1) had one complex coronary stenosis and one smooth stenosis in different noninfarct-related coronary vessels at initial coronary angiography, and 2) had a second angiogram after a median interval of 9 months (range 3 to 24). Patients with lesions > or = 10 mm long, at a major branching point or with > 85% diameter reduction were not included. Coronary lesions were measured quantitatively from comparable end-diastolic frames. Stenosis morphology was determined qualitatively by two independent observers. RESULTS: All patients remained in stable condition during follow-up. Progression, defined as an increase in diameter stenosis by > or = 15% was seen in only eight complex stenosis (16%) but in no smooth lesions (p < 0.01). The severity of complex stenoses changed more than that of corresponding smooth stenoses (mean +/- 1 SD 5.8 +/- 13% vs. -0.06 +/- 6%, p < 0.01). On average, the annual rate of growth was 11.4 +/- 28% and 1.5 +/- 14% for complex and smooth lesions, respectively (p < 0.01). CONCLUSIONS: Few coronary stenoses progress rapidly in stable angina. Complex and smooth coronary stenoses progress at different rates within the same coronary tree. complex stenosis morphology itself is an important determinant of progression of stenosis in patients with apparently clinically stable coronary artery disease.

Aged↗
PubMed2005

Effect of intensive lipid lowering on progression of coronary atherosclerosis: evidence for an early benefit from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial.

Statins reduce both atherogenic lipoproteins and high-sensitivity C-reactive protein (hsCRP). The optimal strategy for administration of lipid-lowering agents has evolved considerably during the past 2 years. Several studies have compared the effects of intensive versus moderate lipid lowering in secondary prevention of coronary events. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study was a double-blind, randomized trial comparing the effect that 2 different statins, administered for 18 months, had on atherosclerotic burden measured by intravascular ultrasound (IVUS). At 34 centers in the United States, 654 patients were randomized to moderate lipid lowering using pravastatin 40 mg or intensive treatment with atorvastatin 80 mg. IVUS was performed during baseline catheterization and repeated after 18 months of treatment. Efficacy parameters included changes in atheroma burden determined by IVUS, lipoprotein levels, and CRP levels. Baseline low-density lipoprotein (LDL) cholesterol (mean, 3.9 mmol/L [150.2 mg/dL]) levels were reduced to 2.8 mmol/L (110 mg/dL) in the pravastatin 40-mg group compared with 2.0 mmol/L (79 mg/dL) in the atorvastatin 80-mg arm (p <0.0001). CRP decreased 5.2% with pravastatin and 36.4% with atorvastatin (p <0.0001). Changes in atheroma burden showed a significantly lower progression rate in the intensive arm for all 3 prespecified IVUS efficacy measures. For all IVUS end points, progression occurred in the moderate-treatment cohort. However, plaque volume was unchanged in the intensive arm, indicating absence of progression. Post hoc analyses demonstrated that greater reductions in both lipid levels and hsCRP were associated with slower disease progression. The slowest progression occurred in patients with above-median reductions in both LDL cholesterol and CRP. For patients with coronary artery disease, intensive treatment with atorvastatin 80 mg reduced progression of coronary atherosclerosis compared with a more moderate regimen consisting of pravastatin 40 mg. Compared with baseline, intensively treated patients had no change in atheroma burden, whereas moderately treated patients showed progression. These differences are related to the greater reduction in atherogenic lipoproteins and CRP in intensively treated patients.

Atorvastatin↗
PubMed2005

Soluble interleukin-2 receptor as a marker for progression of coronary artery calcification in type 1 diabetes.

INTRODUCTION: Soluble interleukin-2 receptor (sIL2r), a marker of T cell activation, is elevated in inflammatory processes, such as rheumatoid arthritis, hepatitis and neoplasm. We explored a potential association between plasma sIL2r levels and progression of coronary artery calcification (CAC), a marker for subclinical atherosclerosis, in a prospectively followed cohort of type 1 diabetic and non-diabetic subjects, aged 20-59 years, with no history of coronary artery disease. MATERIALS AND METHODS: CAC progression was assessed by electron beam tomography over 2.6 years (range 1.6-3.2). Plasma sIL2r levels were measured in a nested case-control substudy of 98 subjects (67 diabetic, 31 non-diabetic) with and 173 subjects (84 diabetic, 89 non-diabetic) without significant CAC progression. Log-transformed sIL2r levels were analyzed by conditional logistic regression to compare subjects with and without significant CAC progression. RESULTS: SIL2r was a significant predictor for CAC progression after adjusting for presence of baseline CAC, age, gender, diabetes status, baseline calcium volume score and adiponectin (OR 1.99, 95% CI 1.09-3.61, p = 0.02 for a doubling of sIL2r level). Addition of BMI, LDL, HDL, hypertension, smoking status, HbA1c, CRP, fibrinogen, homocysteine and PAI-1 to regression models weakened but did not remove sIL2r as a predictor of CAC progression. There was no indication that this effect was different by diabetes status (p = 0.6 for diabetes-sIL2r interaction). DISCUSSION: Elevated plasma sIL2r is associated with CAC progression independent of traditional coronary artery disease risk factors in type 1 diabetic and non-diabetic young adults. SIL2r should be considered as a novel marker of inflammation leading to coronary artery disease.

Adiponectin↗
PubMed2005

Bone mineral density and vertebral fracture history are associated with incident and progressive radiographic knee osteoarthritis in elderly men and women: the Rotterdam Study.

OBJECTIVE: To study the association between baseline femoral neck and lumbar spine bone mineral density (BMD), prevalent fractures and incident and progressive radiographic osteoarthritis (ROA) of the knee in men and women. METHODS: A sample of 1403 subjects (829 women and 574 men) was drawn from the Rotterdam Study, a prospective population-based cohort study of the elderly. Incidence and progression of ROA in quartiles of femoral neck (FN) and lumbar spine (LS) BMD were determined using the Kellgren score, and separate analyses were made for men and women. Furthermore, incidence and progression of ROA were compared in subjects with and without a prevalent vertebral or non-vertebral fracture at baseline. RESULTS: The incidence of knee ROA of subject in the highest FN BMD (10.5%) and LS BMD (14.3%) was significantly higher than of those in the lowest quartiles (3.4% and 3.3% respectively), with corresponding adjusted odds ratios (95% confidence interval) of 2.8 (1.2-6.8) and 4.7 (2.1-10.7). The same trend was seen in the association between LS BMD and the progression of knee ROA, but no association was found between FN BMD and progression of ROA. Separate analyses for men and women both showed significant increased risks in the presence of high baseline BMD, with higher odds ratios in men than in women but larger confidence limits due to lower number of cases in men. Combined incidence and progression of knee ROA in subjects with a prevalent vertebral but not with a prevalent non-vertebral fracture at baseline was 8 times lower than subject without a fracture, independent of baseline BMD. CONCLUSIONS: High systemic BMD at baseline is associated with increased incidence and progression of knee ROA in both men and women, while a prevalent vertebral fracture has a protective effect.

Aged↗
PubMed2004

Improving documentation of patient acuity level using a progress note template.

BACKGROUND: Accurately documenting patient comorbidities and complications improves case-mix representation, coding accuracy, and risk-adjusted mortality estimates for benchmarking. We hypothesized that a progress note template containing comorbidities and complications would improve documentation and teach residents to correctly document comorbidities and complications. STUDY DESIGN: Surgical residents and patients on three inpatient services were followed for a 1-year prospective cohort study. After a 6-month baseline period, a progress note template was developed and implemented for 6 months, and administrative data were retrieved. Residents were given three case examinations assessing documentation knowledge pre- and postintervention, and a satisfaction survey. Demographics, Charlson comorbidity score, ICD-9 codes, template-specific ICD-9 codes, All Patient Refined (APR)-DRG patient severity, DRG relative weight, predicted mortality (University Healthcare Consortium), pre- and postexam scores, and resident satisfaction were collected. RESULTS: No difference in age, gender, race, or Charlson comorbidity score existed between pre- and postintervention patient groups. The length of stay decreased from 5.5 days to 4.8 days (p = 0.013). In the intervention group, total ICD-9 codes, template-specific ICD-9 codes, APR-DRG, DRG weight, and UHC predicted mortality had significant increases. Residents exposed to the progress note template improved their knowledge scores from 52% to 63% (p < 0.001), and 73% agreed that the progress note template was an improvement over handwritten notes. Residents not exposed to the progress note template did not improve their scores. CONCLUSIONS: A progress note template improves documentation of comorbidities and complications, APR-DRG patient severity for benchmarking, and case-mix index, and increases patient-specific predicted mortality. The progress note template also improves surgical residents' documentation knowledge and satisfaction.

Acute Disease↗
PubMed2005

Progressive specialization within general surgery: adding to the complexity of workforce planning.

BACKGROUND: Although most general surgeons receive comparable training leading to Board certification, the services they provide in practice may be highly variable. Progressive specialization is the voluntary narrowing of scope of practice from the breadth of skills acquired during training; it occurs in response to patient demand, rapid growth of medical knowledge, and personal factors. Progressive specialization is increasingly linked to fellowship training, which generally abruptly narrows a surgeon's scope of practice. This study examines progressive specialization by evaluating trends in fellowship training among general surgeons. STUDY DESIGN: Because no database exists that tracks trainees from medical school matriculation through entrance into the workforce, data from multiple sources were compiled to assess the impact of progressive specialization. Trends in overall number of trainees, match rates, and proportion of international medical graduates were analyzed. RESULTS: The proportion of general surgeons pursuing fellowship training has increased from > 55% to > 70% since 1992. The introduction of fellowship opportunities in newer content areas, such as breast surgery and minimally invasive surgery, accounts for some of the increase. Meanwhile, interest in more traditional subspecialties (ie, thoracic and vascular surgery) is declining. CONCLUSIONS: Progressive specialization confounds workforce projections. Available databases provide only an estimate of the extent of progressive specialization. When surgeons complete fellowships, they narrow the spectrum of services provided. Consequently, as the phenomenon of progressive specialization evolves, a larger surgical workforce will be needed to provide the breadth of services encompassed by the primary components of general surgery.

Adult↗
PubMed2006

Prediagnosis prostate specific antigen velocity is associated with risk of prostate cancer progression following brachytherapy and external beam radiation therapy.

PURPOSE: Prostate specific antigen velocity 2.0 ng/ml per year or greater in the year before prostate cancer diagnosis is associated with cancer specific survival following radical prostatectomy and radiation therapy. We evaluated the relationship between prediagnosis prostate specific antigen velocity and cancer progression following primary radiation therapy. MATERIALS AND METHODS: We analyzed the records of 24,893 men from a community based prostate cancer screening study and identified 237 with clinically localized prostate cancer who elected primary radiation therapy. Our final cohort consisted of 130 men, including 83 treated with external beam radiation and 47 treated with brachytherapy. Patient specific variables at diagnosis were analyzed for their value in predicting biochemical progression using American Society for Therapeutic and Radiation Oncology criteria. RESULTS: Mean followup +/- SD was 64 +/- 35 months. Prostate specific antigen at diagnosis, family history of prostate cancer and prediagnosis prostate specific antigen velocity 2.0 ng/ml per year or greater were associated with cancer progression following brachytherapy or external beam radiation. Of men with prostate specific antigen velocity 2.0 ng/ml per year or greater 38% had cancer progression compared to 12% with prostate specific antigen velocity less than 2.0 ng/ml per year (OR 4.3, p = 0.003). The 6-year progression-free survival estimate was 57% in men with prostate specific antigen velocity 2.0 ng/ml per year or greater and 82% in men with prostate specific antigen velocity less than 2.0 ng/ml per year (p < 0.001). On multivariate analysis absolute prostate specific antigen at diagnosis and prostate specific antigen velocity 2.0 ng/ml per year or greater were independently associated with cancer progression in men treated with external beam radiation therapy or brachytherapy. CONCLUSIONS: Men with a prediagnosis prostate specific antigen velocity of 2.0 ng/ml per year or greater are at increased risk for cancer progression following brachytherapy or external beam radiation compared to men with a prostate specific antigen velocity of less than 2.0 ng/ml per year.

Adult↗
PubMed2006

Role of anemia in progression of chronic kidney disease.

Anemia is a well-known consequence of chronic kidney disease (CKD), and its prevalence progressively increases when the estimated glomerular filtration rate decreases to less than 60 mL/min/1.73 m2. However, analyses of the consequences of anemia and of the mechanisms of progression of CKD suggest that anemia also could contribute to the deterioration of kidney function. This hypothesis is based mostly on experimental data that imply that hypoxia of tubular cells plays an important role in tubulointerstitial damage associated with CKD and, thus, in the progression of renal failure. It also is supported by the fact that red blood cells represent a major antioxidant component of blood and that oxidative stress appears to contribute to glomerulosclerosis and tubulointerstitial damage. In humans, post hoc analysis of the Reduction of End points in non insulin-dependent diabetes mellitus (NIDDM) with the Angiotensin II Antagonist Losartan study and analyses of smaller prospective cohorts of CKD patients have shown that anemia is an independent risk factor for progression of CKD. In addition, 3 small randomized studies have suggested that anemia correction could slow the progression of CKD. Thus, the existence of a relationship between anemia and progression of CKD is not only plausible biologically, but also is supported by observational studies and by small intervention studies. However, only a large, randomized, prospective trial will be able to establish if anemia correction can slow the progression of CKD effectively.

Anemia↗
PubMed1988

Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.

PURPOSE: Progressive disseminated histoplasmosis is now diagnosed frequently in patients with the acquired immunodeficiency syndrome (AIDS) living in the central United States. Previous review articles of AIDS have failed to mention this infection. Herein, we describe 48 AIDS patients with progressive disseminated histoplasmosis in an effort to better understand the clinical presentation and diagnosis of the condition in this setting and to assess the efficacy of antifungal chemotherapy. PATIENTS AND METHODS: In the Houston metropolitan area, there were 66 cases of progressive disseminated histoplasmosis among 1,300 confirmed cases of AIDS from January 1983 to July 1987. Of AIDS patients in East Texas with histoplasmosis, 16 patients were available for follow-up by one of us, and the histories of 32 were obtained by examination of hospital charts and physician records. RESULTS: Fever, weight loss, and splenomegaly were the most common presenting signs and symptoms, occurring in 81, 52, and 31 percent, respectively. One-third of the patients had hematologic abnormalities. Infiltrates on chest roentgenograms were observed in 52 percent. Progressive disseminated histoplasmosis was the initial manifestation of AIDS in almost three-fourths of our patients. Biopsy and culture of the bone marrow established the diagnosis of progressive disseminated histoplasmosis in 69 percent. Clinical or autopsy proof of relapse occurred in three patients despite an initial course of more than 2 g of amphotericin B chemotherapy followed by ketoconazole suppression. CONCLUSION: Progressive disseminated histoplasmosis is often the first sign of immunodeficiency in patients with AIDS, and the diagnosis of this condition is most often established by bone marrow biopsy and culture. Because of the permanence of the immunodeficient state in these patients, progressive disseminated histoplasmosis is resistant to treatment.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Characteristics of progressive renal disease.

Virtually all renal diseases progress to terminal renal failure relatively independently of the initial disease. Arresting the rate of the deterioration of kidney failure has a great impact on reducing the number of patients reaching the stage of expensive renal replacement therapy. Understanding the mechanisms of the progression of kidney disease has greatly been improved during recent years. The nature of the progressive renal damage with various etiologies includes various well-known factors where hemodynamics, renin-angiotensin system (RAS) and progressive proteinuria play the central roles. Proteinuria has to be shown as an independent risk factor for renal disease progression. Also, disturbances in lipid metabolism as well as the later structural lesions contribute to the progression. Various modalities have been used for the prevention of progressive renal disease, e.g. low-protein diet, antihypertensive therapy, antifibrotic therapy. Many recent experimental and clinical studies have shown that besides the systemic blood pressure lowering effect, RAS blocking agents provide renal protective effects via direct, hemodynamic, and indirect, non-hemodynamic, pathways: (1) lowering intraglomerular capillary hydraulic pressure, and increasing the glomerular ultrafiltration coefficient; (2) lowering proteinuria; (3) lowering hyperlipidemia; (4) diminishing kidney growth; (5) diminishing infiltration of macrophages; (6) downregulation of proinflammatory cytokines. Therefore, RAS blocking agents are widely prescribed not only for antihypertensive but also for renoprotective purposes in diabetic and non-diabetic nephropathies.

Angiotensins↗
PubMed1999

Augmentation of kidney injury by basic fibroblast growth factor or platelet-derived growth factor does not induce progressive diabetic nephropathy in the Goto Kakizaki model of non-insulin-dependent diabetes.

Diabetes is now the most common cause of kidney failure. The pathogenesis of diabetic nephropathy in both type 1 and type 2 diabetes, however, is still incompletely understood. Two mechanisms postulated to contribute to the pathogenesis of progressive diabetic nephropathy are glomerular cell proliferation and glomerular visceral epithelial cell or podocyte injury. The aim of the current study was to determine whether the aggravation of mesangial cell injury or podocyte injury in isolation would induce progressive diabetic nephropathy. Specifically, we examined whether the administration of either platelet-derived growth factor (PDGF) or basic fibroblast growth factor (bFGF) in sub-nephritogenic doses might lead to an aggravation of kidney structural changes associated with hyperglycemia, resulting in progressive kidney damage in the Goto Kakizaki (GK) rat, which is a genetic model of non-obese non-insulin-dependent diabetes mellitus (NIDDM), in which progressive kidney disease does not develop spontaneously. The results demonstrate that the administration of PDGF to hyperglycemic GK rats led to acute mesangial cell proliferation and activation as assessed by 5-bromo-2'-deoxyuridine-positive nuclei and immunostaining for alpha-smooth muscle actin. Despite acute mesangial cell activation and proliferation, PDGF treatment had no long-term effect on either kidney structure or function. Similarly, treatment of GK rats with bFGF, despite the augmentation of podocyte injury as demonstrated by de novo expression of glomerular desmin expression, did not lead to the development of progressive diabetic nephropathy. In summary, the data in the current manuscript suggest that the additive effect of hyperglycemia and superimposed isolated mesangial cell or podocyte injury does not lead to progressive diabetic nephropathy. This further emphasises the multifactorial nature of the pathogenesis of progressive diabetic nephropathy.

Actins↗
PubMed1993

Predictability of recurrent and progressive disease in individual patients with primary superficial bladder cancer.

The ultimate goal of prognostic assessment is optimization of individual counseling. Often, however, studies on prognostic factors focus on discriminating between high risk and low risk subgroups without considering the relevance of 1 or more factors for predicting disease outcome in individual patients. We quantified the accuracy of prediction of future recurrences and disease progression in individual patients with primary superficial bladder cancer. The study cohort consisted of 1,674 patients who were followed prospectively between 1983 and 1991 in the Netherlands. By analyzing half of the patients with proportional hazards regression, we computed relative risks of recurrence and progression. A prognostic index score based on these relative risks was then applied to the other half of the patients to determine whether group outcome could be predicted accurately. To assess the accuracy of prediction in individuals we used a method similar to the construction of receiver operating characteristic curves in diagnostic test assessment. The 3-year risk of first recurrence was 55% (95% confidence interval 51 to 59%). The 3-year risk of first progressive disease was 10% (95% confidence interval 8 to 12%). For the risk of first recurrence, tumor stage, tumor extent and multicentricity had statistically significant prognostic ability. Prognostic factors for the risk of disease progression were tumor stage, grade, multicentricity and the result of random biopsies from cystoscopically normal-appearing urothelium. For patients with a prognostic index score that suggested a low risk for recurrent and progressive disease the predicted 3-year risk of first recurrence was still 44% but the predicted 3-year risk of progression was only 3%. For patients with a prognostic index score that suggested a high risk the predicted risks were 74% and 22%, respectively. These predicted risks appeared to be fairly accurate when applied to the other half of our case series. However, in any 2 patients chosen at random the chance that the patient with the worst predicted prognosis would have a shorter recurrence-free and progression-free followup was calculated to be only 58% and 67%, respectively. Although the available prognostic factors in superficial bladder cancer may be useful to identify high risk and low risk subgroups, predictability in individuals is highly inaccurate. More relevant prognostic factors are needed to decrease current overtreatment and undertreatment rates, and to improve the followup policy.

Adult↗
PubMed1993

Influence of capsular penetration on progression following radical prostatectomy: a study of 196 cases with long-term followup.

We studied 196 radical prostatectomy cases performed for clinical stage B prostate cancer with capsular penetration; in all cases seminal vesicles and lymph nodes were free of tumor. The mean followup in patients who showed no evidence of progression was 5 years. Focal capsular penetration was seen in 93 cases. There was no difference in progression in this group, irrespective of whether margins were negative or positive. High grade tumors (Gleason score 7 or more) had a significantly higher risk of progression compared to lower grade tumors (p = 0.0002). Established capsular penetration was seen in 103 tumors. Cancers with established capsular penetration had a higher risk of progression than those with focal capsular penetration. Established capsular penetration tumors were stratified into 3 groups with increasing risks of progression: 1) margins were negative and grade was low, 2) margins were positive or grade was high yet both adverse features were not present or 3) margins were positive and grade was high. The differences in progression among these 3 groups were statistically significant. Because of the negligible influence of positive margins in patients with focal capsular penetration the status of capsular margins should not influence the decision on whether to administer immediate postoperative adjuvant therapy. To evaluate the efficacy of adjuvant therapy following radical prostatectomy, tumors with capsular penetration should be stratified into groups having similar risks of progression according to the extent of capsular penetration, surgical margins of resection and grade.

Humans↗
PubMed2000

[Prognostic markers of progression to AIDS in infants vertically infected by human immunodeficiency virus type-1].

BACKGROUND: To study the prognostic AIDS progression value of the percentage of CD4+, CD8+, and plasma viral load (VL) (copies/ml) in HIV-1-vertically infected children. PATIENTS AND METHOD: We study a cohort of 115 HIV-1 infected children older than 12 months of age. The VL was quantified using standard molecular assay. CD4 and CD8 T lymphocytes were determined by flow cytometry. RESULTS: The children with a median of VL > 4.5 log10 (p < 0.001) and percentage of CD8+ < 25% (p = 0.05) during follow-up, progressed faster to AIDS than children with a median of VL < 4.5 log10 and CD8 > 25%. The relative risk (RR) of AIDS progression was 7-fold higher in children with median VL above 4.5 log10. When considering VL as a continuous variable, risk of progression to AIDS is 3.5-fold higher for each increase of one log10 of VL. The percentage of CD8+ T-cells had a RR of AIDS progression of 0.95/% CD8+ at entry to the study and of 0. 19/% CD8+ during follow-up, indicating protection against progression to AIDS. CONCLUSIONS: Our results indicate that each basal values at entry in the study and during the follow-up of the percentage of CD8+ and VL helps to determine the risk of AIDS progression in HIV-1-infected children. More interestingly, the use of the two predictive markers together had higher predictive value.

Acquired Immunodeficiency Syndrome↗