Rate Of Progression In Patients Research Articles

The Management of T1G3 Bladder Cancer

Introduction: The treatment of T1G3 bladder cancer is still a controversial issue. Nowadays, intravesical bacillus Calmette-Guérin (BCG) instillation is considered to be the treatment of choice for patients with high-grade superficial bladder tumour after transurethral resection of all visible tumour. The aim of this retrospective study was to determine the effects and results of this approach, recurrence and progression rates in patients with T1G3 superficial bladder tumours. Material and Methods: 43 patients (28 male, 15 female; mean age 65.5 years, range 21–82) with T1G3 TCC (transitional cell carcinoma) bladder tumour underwent transurethral resection and subsequent intravesical BCG according to Morales protocol, in the period 1993–1998 at our institution. The mean follow-up period was 52.5 (range 30–96) months. Results: After one or more initial courses of therapy, 33 patients were disease-free. Twelve patients (27.90%) had recurrent tumour after a median of 7 (range 3–46) months. After a second course of BCG treatment, 6 patients had no evidence of disease, 3 patients had progression and 3 had recurrence. Progression occurred in 7 (16.27%) patients after a median of 19 (range 3–43) months. Five patients underwent radical cystectomy and the remaining 2 underwent bladder-preserving therapies. Two patients died of TCC and 3 due to disease-unrelated conditions. Conclusion: Intravesical BCG instillation can be recommended as treatment modality for responders with T1G3 TCC bladder tumour. The benefit of the second course of intravesical BCG therapy has to be confirmed in further investigations.

Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette-Guérin (Danish 1331 strain).

To report recurrence and progression rates in patients with T1G3 superficial bladder carcinoma treated with intravesical bacille Calmette-Guérin (BCG, Danish 1331 strain) after complete transurethral resection. Data from the records of 111 patients with T1G3 bladder carcinoma treated between January 1991 and December 1999 were analysed for recurrence, progression, salvage therapy and survival. Of the 111 patients with T1G3 bladder tumours, 69 had intravesical BCG therapy, 20 radical cystectomy and 22 only transurethral resection (TUR). Of the 69 patients receiving BCG therapy 37 (54%) had no recurrence, and 24 (35%) had a recurrence that was not muscle-invasive (Ta/T1) and were treated with TUR only. The remaining eight (12%) progressed to muscle invasion and had salvage cystectomy. During the follow-up six patients died, four from disease and three from other causes, while the remaining 63 are alive and well. Of the other 42 patients, 15 are alive after radical cystectomy and 18 after TUR. This series further confirms the benefits of intravesical BCG (Danish 1331) in an adjuvant setting; furthermore, this treatment facilitates bladder preservation by reducing recurrences and delaying the progression in many patients.

Early Onset Alzheimer Type Dementia More Rapidly Deteriorates than Late Onset Type: A Follow‐up Study on MMSE Scores in Japanese Patients

Background:Cognitive function in patients with Alzheimer type dementia (ATD) changes over time, and the rate of progression varies according to reports. An aim of the study is to examine the rate of progression in patients with ATD by the onset of the disease. Methods:Forty patients with early onset dementia at the age of 65 or less and 99 patients with late onset dementia at the age of more than 65 years in whom Mini‐Mental State Examination (MMSE) scores could be followed up for at least 12 months were enrolled and examined retrospectively for changes in MMSE scores over time. Results:It was demonstrated that the rate of decrease in MMSE scores was significantly higher in Alzheimer disease (AD) than in senile dementia of Alzheimer type (SDAT) and that the decrease in MMSE scores was significantly slower in patients with higher initial scores. Conclusion:ATD patients are likely to be classified into AD or SDAT for evaluation of decreased cognitive function. Initial MMSE score and the subtype according to age at onset are important predictors for the progression of intellectual impairment in ATD patients.

SPECT and PET imaging of the dopaminergic system in Parkinson's disease.

This paper gives an overview of the clinical importance of SPECT and PET imaging of the dopaminergic system in the differential diagnosis and for the determination of the progression rate of Parkinson's disease (PD). D2 receptor imaging can help to differentiate multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) from PD. In patients treated with neuroleptics it is possible to determine the rate of striatal D2 receptor blockade using this technique. This occupancy rate parallels the occurrence of parkinsonian side effects. Its measurement helps in the selection of newer atypical neuroleptics, which can be used to treat drug-induced psychosis in PD because they do not aggravate parkinsonian symptoms. Imaging of dopaminergic neurons with [123I]beta-CIT SPECT or [18F]DOPA PET is a way to visualize and quantify the nigrostriatal dopaminergic lesion in PD. Findings correlate with clinical rating scales and demonstrate the feasibility of detecting the preclinical lesion in patients with hemiparkinson or familial PD. [123I]beta-CIT SPECT can easily distinguish patients with essential tremor and patients with "lower body parkinsonism" due to a subcortical vascular encephalopathy. MSA and PSP cannot be separated from PD with this method alone. Longitudinal studies with [123I]beta-CIT SPECT and [18F]DOPA PET can quantify the progression rate in PD. SPECT results from our own group show a low rate of progression in patients with a long duration of disease and a more marked progression rate in patients with shorter disease duration. In the former group regions in the striatum with higher beta-CIT binding at the time of the first SPECT scan decline faster than regions with lower binding. These findings suggest a curvilinear course of progression which starts at different time points in different striatal regions and which levels off after several years of disease duration. These findings are in line with data from PET studies and underline the importance of an early start of neuroprotective strategies. Preliminary data from PET and SPECT studies in early PD suggest that dopamine agonists might have a slight neuroprotective effect and might slow down the rate of progression of the disease.

Association of a uteroglobin polymorphism with rate of progression in patients with IgA nephropathy

Uteroglobin gene–disrupted mice develop a nephritis very similar to immunoglobulin A (IgA) nephropathy. Megsin codes for a protein overexpressed in mesangium in patients with IgA nephropathy. Both are candidate genes that might have variants associated with an accelerated progression in patients with IgA nephropathy. We performed an association study of patients with IgA nephropathy and matching control subjects to test whether the G38A polymorphism in the uteroglobin gene, the C2093T polymorphism in the megsin gene, or the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism is associated with IgA nephropathy or rate of disease progression in patients with IgA nephropathy. Of 110 patients with IgA nephropathy, 87 patients were followed up for at least 3 years for the progression study. We also studied 104 healthy volunteers. The uteroglobin, megsin, and ACE polymorphisms were not distributed differently in the 110 patients with IgA nephropathy compared with healthy controls; Hardy-Weinberg equilibrium criteria were fulfilled. The GG genotype of the G38A uteroglobin polymorphism was more common in patients with progression (odds ratio [OR], 3.5; P < 0.006) than the AG+AA genotypes. The G allele was also more common (OR, 2.6; P < 0.009) in patients with versus without progression. The 1/serum creatinine over time plot (in deciliters per milligram per day) was sevenfold steeper in GG patients than the other two genotypes (P = 0.08). No significant associations with disease progression were found for the other gene polymorphisms, and a multivariate analysis showed no interactions. We suggest the hypothesis that the uteroglobin gene contains variant(s) with a bearing on progression rate in patients with IgA nephropathy.

Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1 disease progression: results from the EuroSIDA study.

The effect of previous CD4 cell count nadir on clinical progression in patients with increases in CD4 cell counts has not been investigated. To assess risk for progression of HIV disease in patients with CD4 counts of at least 200 cells/mm3 (stratified by the lowest previous CD4 count) and compare the rate of progression in patients with CD4 counts less than 50 cells/mm3 with that in patients whose CD4 counts rebounded from less than 50 cells/mm3 to at least 200 cells/mm3. Prospective, observational multicenter study. 52 HIV outpatient clinics in Europe. Two groups were identified: those with CD4 counts of at least 200 cells/mm3 (group A) and those with CD4 counts less than 50 cells/mm3 (group B). Group A was stratified according to the lowest previous CD4 count: at least 150 cells/mm3 (stratum 1), 100 to 149 cells/mm3 (stratum 2), 50 to 99 cells/mm3 (stratum 3), and 1 to 50 cells/mm3 (stratum 4). Patients were followed until a progression event occurred (first AIDS-defining event, new AIDS-defining event, or death) or until the CD4 count decreased to less than 200 cells/mm3 (group A) or increased to more than 50 cells/mm3 (group B). Incidence rates were based on a patient-years analysis and reported as events per 100 patient-years of follow-up; the relative hazards for progression were based on Cox proportional hazards models. The overall rate of disease progression in group A was 3.9 per 100 patient-years (95% CI, 3.5 to 4.3 per 100 patient-years), whereas in group B it was much higher (72.9 per 100 patient-years [CI, 69.0 to 76.8 per 100 patient-years]). In group A, the rate increased in patients with previous low CD4 cell count nadirs, resulting in a significant increase in the relative hazard for progression. The relative hazards for strata 2, 3, and 4 were 2.29 (CI, 1.30 to 4.03), 3.65 (CI, 1.94 to 6.85), and 2.94 (CI, 1.44 to 6.00), respectively. Increases in CD4 counts from very low levels to at least 200 cells/mm3 are associated with a much reduced rate of disease progression. However, a previously low CD4 cell count nadir remains associated with a moderately higher risk for disease progression among patients with CD4 counts of at least 200 cells/mm3.

Modeling the impact of interferon alfa treatment on liver fibrosis progression in chronic hepatitis C: A dynamic view

Background & Aims: Impact of hepatitis C treatment has never taken into account the dynamics of fibrosis progression. This study assessed the impact of interferon on liver fibrosis progression in patients with chronic hepatitis C according to 3-month aminotransferase activity response. Methods: We recruited 287 patients, 185 treated and 102 control, with paired biopsy specimens. Before follow-up, the fibrosis progression rate per year was estimated as the ratio between fibrosis stage in METAVIR units (1 U, 1 stage; 4 U, cirrhosis) and the duration of infection. During follow-up, fibrosis progression was assessed by the observed difference between stages divided by duration between biopsies. Results: The median fibrosis progression rate in treated patients decreased compared with the rate before treatment from 0.103 F METAVIR U/yr (95% confidence interval [CI], 0.087–0.120) to 0.000 (95% CI, 0.000–0.000; P ≤ 0.0001). Among 91 treated responders, fibrosis stage worsened in 19 (22%), compared with 21 (22%) of 94 treated nonresponders and 57 of 102 controls (56%; P ≤ 0.0001 compared with treated patients), and improved in 26 (29%), 17 (18%), and 8 (8%; P = 0.0002 compared with 29% and P = 0.03 compared with 18%), respectively. These observed differences persisted after genotype, viremia, sex, age at infection, duration of infection, and alcohol consumption were taken into account. Conclusions: Interferon treatment changes the natural fibrosis progression rate in patients with chronic hepatitis C independently of genotype and early response. GASTROENTEROLOGY 1999;116:378-386

Transitional cell carcinoma of the bladder in patients under 40 years of age.

A review of our records between 1993 and 1998 identified 25 patients with transitional cell carcinoma of the bladder who were less than 40 years old, 22 males and 3 females. The youngest patient was 19 years old. At the time of diagnosis 16 patients had superficial (Ta/T1) and 9 had invasive disease. Twenty-four patients were followed up for a period of 3-71 months (mean: 19.2 months). The recurrence rate for patients with superficial disease was 12.5%, and the progression rate for patients with invasive disease was 77.7%. We concluded that the patients under 30 years of age presented with lower grade and lower stage disease than those over 30. Transitional cell carcinoma of the bladder in young adults has a natural history similar to that seen in older patients. Accordingly, all patients, regardless of age, should be treated as aggressively as necessary on the basis of the stage and the grade of the tumour.

Prospective follow-up of Japanese women with cervical intraepithelial neoplasia and various human papillomavirus types

Objective: To evaluate the prevalence of genital human papillomavirus (HPV) types in cervical neoplasias and to evaluate the biological activity of individual HPV types in cervical carcinogenesis. Method: Cellular samples from 318 patients with cervical intraepithelial neoplasia (CIN) or invasive cervical carcinoma were examined for HPV DNA, using a polymerase chain reaction. Of these, 145 women with CIN grade I or II were prospectively followed to better understand the natural history of these precancerous lesions. Result: HPV DNA was detected in 88, 80 and 89%, of CIN grade I, II and III, respectively, and in 92% in invasive carcinomas. The CIN follow-up data showed a significantly higher progression rate in patients with CIN II than in cases of CIN I, and our classification of HPV types based on HPV prevalence data correlates well with the prospective follow-up data. A significantly higher progression rate was observed in HPV-negative CINs. Conclusion: Classification of HPV types according to risk to a malignant state seems to be possible. It seems that HPV negative lesions are likely to progress to a malignant state.

Incidence of positive surgical margins after biopsy-selected nerve-sparing radical prostatectomy

Objectives. The selection criteria for a nerve-sparing radical prostatectomy (NSRP) are not thoroughly investigated and are based mainly on preoperative digital rectal examinations and intraoperative findings. At our institution NSRP is performed only on patients whose preoperative systematic sextant biopsy of the prostate showed only unilateral cancer. To prove the safety of these criteria, we analyzed the incidence of positive surgical margins and tumor progression rate in patients who were selected for an NSRP only by the result of the biopsy. Methods. Preoperative systematic sextant biopsies revealed unilateral cancer in 69 preoperatively potent men of 289 consecutive prostatic cancer patients (23.9%); contralateral NSRP was performed on these 69 patients. The prostate specimens were investigated by using a 3-mm step-section technique to identify positive surgical margins. Tumor progression was defined as a prostate-specific antigen (PSA) level greater than 0.4 ng/mL in the native and greater than 0.025 ng/mL in the suprasensitive postoperative blood test. Mean follow-up was 15 months (range 6 to 24). Results. In 69 patients who underwent NSRP, 11 positive margins (15.9%) were found. Only 3 patients (4.3%) had a positive margin on the nerve-sparing side. In 220 patients who underwent non-NSRP 59 positive margins (26.8%) were detected. PSA recurrence rate after 12 months was similar in patients with NSRP and non-NSRP. Analysis of systematic sextant biopsies gives safe selection criteria because in approximately 95% the surgical margin on the nerve-sparing side will be negative. Conclusions. Basing the indication for an NSRP on the results of preoperative systematic biopsies was safe according to margin status and postoperative PSA, when all patients with tumor in one of the three biopsy cores of each side of the prostate were excluded from an NS technique on that side. Such a strict approach will exclude approximately 30% of patients from NSRP unnecessarily because of tumor findings on a prostate side where the cancer is still organ-confined. Less strict criteria, including patients with only well-differentiated cancer and a maximum of one positive biopsy on the evaluated side, seem to be as safe as the described selection. However, data on these patients need further evaluation.

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.

Radical prostatectomy for clinically localized prostate cancer: local tumor extension and prognosis.

This study was performed to evaluate the frequency of local tumor extension and its effect on disease progression after radical prostatectomy. The study consisted of 66 consecutive men who underwent radical prostatectomy for clinically localized prostate cancer without any prior hormonal therapy. Cases were stratified according to pathologic findings. Sites of capsular penetration were also evaluated. The overall incidences of lymph node metastases, seminal vesicle invasion, capsular penetration, and positive surgical margin were, respectively, 23%, 32%, 55% and 35%. The disease progression rate in patients with positive lymph nodes differed significantly from that in those without nodal metastases (P < 0.0001). Although seminal vesicle invasion, capsular penetration, or positive surgical margin had an adverse effect on prognosis, the difference in progression missed statistical significance, when patients with positive lymph node metastases were excluded. The most common site of capsular penetration was posterolateral, in the area of the neurovascular bundle. Extraglandular tumor extension and positive surgical margins are common features of radical prostatectomy specimens. A nerve-sparing operation should be performed selectively and with great caution. The markedly adverse effect of lymph node involvement on progression must be accounted for when evaluating other variables relating to progression.

Low dose corticosteroids in early rheumatoid arthritis. Can these drugs slow disease progression?

The role of corticosteroids in treating rheumatoid arthritis is controversial, but recourse to the available evidence of efficacy should guide patient management decisions. Earlier evidence suggested that symptomatic control could be improved for periods of 6 to 12 months, but not longer, without increasing doses to unacceptably high levels. The effect of corticosteroids on joint destruction has been unclear. Recent findings from a controlled clinical trial show that prednisolone 7.5 mg/day can significantly retard the rate of erosive progression in patients with relatively early disease (< 2 years' duration). These results have implications for both disease management and our understanding of the pathogenesis of joint destruction in rheumatoid arthritis.

Factors influencing progression of renal failure in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) frequently leads to end-stage renal failure (ESRF) in the sixth decade of life, but considerable heterogeneity exists in the rate of progression of renal failure. The respective contribution of genetic factors and of potentially amendable factors, such as blood pressure control or protein intake limitation, on the rate of progression in ADPKD patients is still debated. To evaluate the role of factors influencing the rate of progression of renal failure in ADPKD, we retrospectively analyzed the annual rate of decline of creatinine clearance (Ccr) in 109 ADPKD patients followed from the time a Ccr value of 30 to 50 mL per min/1.73 m2 was measured until ESRD and need for hemodialysis (Study A), and in 48 undialyzed ADPKD patients followed for at least 4 yr from the time a Ccr value of 50 to 60 mL per min/1.73 m2 was measured (Study B). In Study A, the decline in Ccr (delta Ccr) (mean +/- SE) was 5.8 +/- 0.2 mL per min/1.73 m2 per year in the whole series, and was lower in females than in males (5.0 +/- 0.2 versus 6.4 +/- 0.2, P < 0.001). Accordingly, ESRF was reached at a later age in female patients (55.1 +/- 1.2 versus 50.6 +/- 1.2 yr, P < 0.01). The age at ESRF in male patients was lower when the disease was transmitted by mother than by father (46.3 +/- 1.9 versus 54.1 +/- 1.8 yr, P < 0.01), whereas no significant effect of the gender of the affected parent was apparent in female patients. By regression analysis, there was a positive but weak relationship between delta Ccr and mean arterial pressure (average value during follow-up, 107 +/- 1 mm Hg, r = 0.224, P < 0.05) but not with dietary protein intake (mean value in follow-up, 0.87 +/- 0.03 g/kg per day, r = 0.10, P = 0.33) nor with proteinuria at baseline, which was lower than 0.3 g/day in 104 cases (r = 0.10, P = 0.28). There was a negative relationship between age at ESRF and delta Ccr (r = 0.245, P < 0.05), with a later and slower progression in older subjects. In Study B, the mean decline in renal function during follow-up was 5.3 +/- 0.4 mL/min/1.73 m2 per year, a value close to that observed in Study A. By multiple regression analysis of the overall population (studies A and B combined), only MAP, age and gender were independent predictive factors of delta Ccr but all studied parameters taken together accounted for at best 20% of delta Ccr variation. We conclude that the rate of progression of renal failure in ADPKD patients is mainly determined by gene expression, with female gender and older age associated with a slower progression, whereas blood pressure control, but not protein intake, exerts a limited beneficial influence on the rate of progression in patients with advanced polycystic kidney disease who already have significant renal insufficiency.

Severe restrictive lung disease in systemic sclerosis.

We sought to identify risk factors for developing severe restrictive lung disease and to determine the time of onset and rate of progression in patients with systemic sclerosis (SSc). Using the University of Pittsburgh Scleroderma Databank, we grouped patients according to their lowest forced vital capacity (FVC) value: > 75% predicted, 50-75% predicted, and < 50% predicted. In patients with severe restrictive disease, we examined serial pulmonary function test (PFT) results to determine the rate of loss of lung volume over time. Of 890 SSc patients, 60% (n = 531) never had an FVC < or = 75% predicted; 27% (n = 243) had moderate restrictive disease, with an FVC value of 50-75% predicted; and only 13% (n = 116) of the patients had severe restrictive disease, with FVC < or = 50% predicted. Black race, male sex, early disease, and primary cardiac involvement due to SSc were the features most frequently associated with severe restrictive lung disease (by multiple logistic regression). Fifty-five patients with severe restrictive lung disease had their first of at least 2 PFTs during the first 5 years after onset of any SSc (not pulmonary) symptoms. In 30 patients, the FVC declined by 32% per year in the first 2 years of illness, in 16 patients the annual loss was 12% in years 2-4 after disease onset, and in 9 patients annual loss was 3% during years 4-6 of disease (P < 0.005 by 1-way analysis of variance). In SSc patients, black men with early disease who have cardiac involvement are the most likely to have factors associated with the development of severe restrictive lung disease (which is increasingly becoming a major cause of death). Disease subtype (diffuse versus limited cutaneous) and serum anti-topoisomerase I antibody do not differentiate between moderate and severe restrictive disease. Careful monitoring of pulmonary function early in the disease, when the greatest loss of lung function occurs, may help identify patients likely to respond to new therapy.

'How far' vs 'how fast' in Alzheimer's disease. The question revisited.

To expand on a recent study of 42 patients with probable Alzheimer's Disease that found that the only significant predictors of certain clinical end points were the degree of severity features at entry ("how far"). A case series study of a cohort of 81 patients with Alzheimer's disease that used survival analysis methods similar those of the previous study but included a new technique for calculating rate of progression ("how fast") as well as entry characteristics ("how far"). A university medical center and its affiliated Veterans Affairs Medical Center. All patients with probable and definite Alzheimer's disease studied at the Aging Clinical Research Center at Stanford University, Palo Alto, Calif, in the years 1981 and 1992 who met the following criteria: a mild to moderate level of severity of the disease (Mini-Mental State Examination score of 15 or above) at entry into the study and a minimum of three test points spaced approximately 6 months apart (to allow estimation of rate of progression). A total of 81 such patients were identified. These patients had been followed up for a mean of 4.53 +/- 2.3 years, with a range of 1.0 to 14.5 years. The outcome measure was the average rate of decline on the Mini-Mental State Examination. The results of our study replicated a previous finding that the degree of severity is a strong predictor of time course, but in addition we found that the rate of progression also appears to be a strong predictor of clinical course. There appears to be substantial heterogeneity in the rate of progression in patients with Alzheimer's disease, and, like initial degree of severity, rate of progression appears to be a strong predictor of clinical course.

Tubular-derived cytokines and human renal disease progression

We still know remarkably little about why renal function in many chronically-diseased human kidneys continues to decline at a predictable rate over time. If patients whose renal function is likely to decline can be diagnosed early, effective measures to slow the rate of progression could be introduced before irreversible renal scarring occurs. Three such predictive factors have emerged. Firstly, the preservation of the tubulointerstitium rather than the glomerulus appears to be the major histological determinant of renal outcome in a wide variety of classical glomerulopathies [1]. Secondly, the extent of the interstitial infiltrate (which consists largely of T cells and macrophages) correlates well with the degree of functional impairment and is a good predictor of long-term prognosis [2]. Thirdly, the magnitude of proteinuria appears to correlate positively with the rate of progression in patients with impaired glomerular filtration rates according to preliminary results from the large multicentre 'Modification of Renal Disease by Diet' study [3]. No doubt, controversy will continue to rage over the pathogenic potential of filtered plasma proteins since direct in-vivo evidence of this, in the absence of other potentially relevant factors such as changes in glomerular function, has not yet been obtained [4], It seems possible though that, in addition to filtered albumin, larger non-albumin proteins such as lipoproteins [5] might prove to be 'tubulo-toxic' and thus provide a convenient link between primary glomerular injury and secondary tubular injury.

Early Orchiectomy for Patients With Stage D1 Prostatic Carcinoma

Staging lymphadenectomy revealed stage D1 disease in 30 of 94 patients with clinically localized prostatic carcinoma. Early orchiectomy resulted in a 46 per cent treatment failure rate after 45 months and established local disease control in almost all patients. The interval to treatment failure in this group compares favorably to the progression rate in patients treated with other modalities

Segmental analysis of the rate of progression in patients with progressive coronary atherosclerosis

Bruschke et al.’ have shown that the likelihood of finding progressive coronary atherosclerosis at second catheterization increases in relation to time and severity of the initial lesion. Defining a rate of progression, however, has been difficult. Sudden, unpredicted events intermittently punctuate the clinical course of patients with coronary atherosclerosis, suggesting that there may be more than one rate of progression (fast versus slow), or that there may be some events occurring independently of time as a function of other variables.

Unfair to Baboons

<h3>Objective.</h3> To describe the natural course of radiographic progression and to differentiate rates of progression in patients with ankylosing spondylitis (AS). <h3>Methods.</h3> Overall, 146 patients with AS who had never received anti-tumor necrosis factor therapy were analyzed in this retrospective cohort study. The main inclusion criterion was the availability of complete sets of cervical and lumbar radiographs from at least 2 timepoints within 6 years. Using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), we quantified the structural changes and assessed different rates of radiographic progression based on development of new syndesmophytes/year. <h3>Results.</h3> The mean followup time was 3.8 ± 1.7 years (range 1–6) and the mean number of consecutive radiographs was 2.7 (range 2–6) per patient. The mean mSASSS change/year was 1.3 ± 2.5 units. Radiographic progression showed much variability, since 43% of patients showed a 4-fold greater rate of progression than the mean, and 23% had no progression. The data-based definition for “fast progression” was calculated as a change &gt; 5 mSASSS units or &gt; 2 new syndesmophytes; for “moderate progression” as change of 2.0–5.0 mSASSS units or &lt; 2 new syndesmophytes; and for “slow progression” as change of &lt; 2 mSASSS units or no more than 1 new syndesmophyte within 2 years. The only factor to predict future radiographic progression was the number of syndesmophytes at baseline. <h3>Conclusion.</h3> Radiographic progression in AS is rather variable and many patients show high rates of progression. On the basis of this retrospective dataset we propose to differentiate patients on an individual level according to their progression rates: patients with fast, moderate, and slow radiographic progression, assessed by counting new syndesmophytes. Predicting radiographic progression remains difficult; only the prevalence of syndesmophytes at baseline is predictive of future damage.