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Results for “Disease progression”

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At least 19 recordsLinked to original sources

PubMed2001

HLA and interleukin 1 gene polymorphisms in primary biliary cirrhosis: associations with disease progression and disease susceptibility.

BACKGROUND AND AIMS: Twin and family studies suggest that there is a genetic component to primary biliary cirrhosis (PBC) but the genetic associations which have been described are weak with marked variations between centres. PBC is heterogeneous and genetic associations with disease progression may be obscured when the PBC population is analysed only as a whole and not subdivided. METHODS: We have investigated two candidate gene loci in 164 well characterised patients, 88 (54%) of whom had advanced disease. RESULTS: There was an increased frequency of the HLA DRB1*0801-DQA1*0401-DQB1*0402 haplotype in patients who had progressed to late stage disease (23% v 2% of controls; p=0000044; odds ratio (OR) 15.5, 95% confidence interval (CI) 3.52-68.4) but not in those with early stage disease (4% v 2%). Patients had a higher frequency of the IL-1B*1,1 genotype and lower frequencies of the IL-1B*1,2 and *2,2 genotypes (p=0.00078; OR 2.37, 95% CI 1.38-4.06), and higher frequency of the IL-1RN*1,1 genotype and lower frequency of the IL-1RN*1,2 genotype (p=0.0011; OR 2.28, 95% CI 1.34-3.89). The difference in the IL-1B*1,1 genotype distribution was most marked in patients with early stage disease (77% v 43% of controls; p=0.000003; OR 4.8, 95% CI 2.31-10) but the IL-1RN genotype distribution was similar in patients with early and late stage disease. CONCLUSIONS: These data indicate a complex relationship between immunoregulatory genes and PBC. While the IL-1 genes are markers of both disease susceptibility and progression, HLA genes appear to be principally associated with disease progression.

Case-Control Studies↗

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↗

PubMed1995

Karyotypic evolution in CLL: identification of a new sub-group of patients with deletions of 11q and advanced or progressive disease.

Chronic lymphatic leukaemia (CLL) is the most common leukaemia and is characterized by long-term survival. Previous studies have shown that karyotypic abnormalities are relatively stable and that certain abnormalities may be associated with a poor prognosis. In a prospective 5-year study of 45 patients with typical CLL, sequential karyotypic studies were undertaken every 6-12 months. Clonal karyotypic abnormalities were identified in 62% of patients, either at diagnosis or during the study period with 38% (17/45) exhibiting clonal evolution. In patients with no clinical disease progression, 13q abnormalities were most commonly detected compared with 11q deletions in patients with progressive disease. Karyotypic evolution was significantly associated with progressive disease (12/16, 75% vs 5/29, 17%; P < 0.001, chi2). Thus, karyotypic evolution is not uncommon in CLL, is usually associated with disease progression and deletions of 11q are the commonest detected abnormalities.

Adult↗

PubMed2004

"Late" regressions of metastases from renal cancer after a period of disease progression continuing the same intermittent low dose immunotherapy regimen.

We here describe two patients with metastatic renal cell cancer (mRCC) treated with immunotherapy in whom the metastases completely regressed after a period of progressive disease. The treatment schedule was based on repeated cycles of low-dose recombinant interleukin-2 and recombinant interferon-alpha, and was never changed during the course of the disease. The first patient received immunotherapy because of multiple bilateral lung metastases. Progressive disease, with mediastinal lymph node involvement and an increased number of lung metastases, was observed after 30 months of regularly repeated therapy; complete regression was achieved after 60 months of immunotherapy (after 16 immunotherapy cycles). The second patient began immunotherapy because of three small lung metastases. Disease progression was observed after three cycles, but complete regression was obtained about 16 months after the start of immunotherapy (after 5 immunotherapy cycles). Long-term low-dose immunotherapy may bring about an effective anti-tumour response even late in the course of the disease and after an initial disease progression.

Adenocarcinoma, Clear Cell↗

PubMed2005

Association of disease progression and poor overall survival with detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer.

The aim of this study was to define the frequency and clinical relevance of cytokeratin positive metastatic tumor cells in the peripheral circulation of patients with stage IV breast cancer. Peripheral blood was collected from 32 consecutive patients with metastatic breast cancer and 23 healthy donors. Tumor cells were enriched using positive selection with anti-HEA125-microbeads and cytospins were prepared of the positive selection eluate. Slides were incubated with a Fab2 fragment of the pancytokeratin antibody A45-B/B3 conjugated with alkaline phosphatase (AKP) and a CAM5.2-AKP monoclonal antibody and developed with an alkaline phosphatase anti-alkaline phosphate reaction (APAAP). All samples were evaluated using light microscopy and an automated image analysis system. In 8/32 (25%) patients cytokeratin positive (CK+) cells could be detected after anti-HEA125 enrichment in the peripheral blood whereas in none out of 23 healthy donors. One to 1000 (median 5) positive cells per patient sample were observed and cluster of tumor cells in one patient. Automated image analysis was as powerful in detecting micrometastases as conventional light microscopy. All patients with CK+ cells in the peripheral circulation (8/8, 100%) showed progressive disease at the time-point of blood draw whilst only 9/24 (37.5%) showed disease progression without detection of positive cells. The median overall survival of CK+ patients was 4+/-2 months compared to 13+/-7 months of CK- patients (p<0.001). CK+ cells are detectable in the peripheral circulation of 25% of patients with metastatic breast cancer after positive selection with anti-HEA125. Detection of tumor cells in the peripheral circulation might be correlated with progression of disease and shorter overall survival.

Adult↗

PubMed2003

Progressive disease following autologous transplantation in patients with chemosensitive relapsed or primary refractory Hodgkin's disease or aggressive non-Hodgkin's lymphoma.

To determine the outcome of patients with chemosensitive relapsed or primary refractory Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL) whose disease progresses after autologous stem cell transplantation (ASCT), we reviewed the records of 82 patients with HD and 139 patients with NHL transplanted between 1993 and 2000. Disease progression occurred in 25 patients with HD and 66 patients with NHL, with median times to progression (TTP) of 3.8 and 5.1 months, respectively. Median survival times following ASCT failure were 26 and 7.7 months for patients with HD and NHL, respectively. The second-line international prognostic index (sIPI) and the TTP (before or after 3 months from ASCT) independently were predictive of survival for NHL patients. In addition, treatment with rituximab for patients with B cell NHL was associated with improved survival (median 28.6 vs 4.1 months, P=0.003), independent of the sIPI and TTP. Prognostic factors for patients with HD were not identified. Only two patients, one of whom was among six patients who received second autologous transplants, remain disease-free. The uniformly poor outcome associated with disease progression after ASCT should prompt efforts to assess the feasibility and utility of detecting and treating post transplant residual disease during a minimal disease state, before overt progression.

Adolescent↗

PubMed2006

Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients.

BACKGROUND: Vpr (viral protein R) is a 96 amino acids soluble protein that is expressed late during viral replication. Recent studies have focused on the role of a mutation at position 77 that might be associated with the condition of long-term non-progression, but data are still controversial. PATIENTS AND METHODS: Fifteen long-term non-progressors (LTNP), 19 therapy-naive HIV-1-infected patients with progressive disease (Pr), 23 HIV-1-infected patients receiving sub-optimal therapy with dual nucleoside [nucleoside reverse transcriptase inhibitor (NRTI)] therapy but efficiently controlling viral replication (STP) and 19 antiretroviral therapy multi-experienced patients with actively replicating virus (MEP) were analysed. HIV-RNA was extracted from plasma samples, the Vpr region was amplified, cloned and sequenced. The Pol gene was amplified, directly sequenced and analysed using Sequence Navigator software. RESULTS: A significantly higher prevalence of the R77Q mutation was evidenced both in LTNP (86.7%) and STP (73.9%) in comparison with Pr (42.1%) and MEP (42.1%), (P = 0.007). Comparing groups of patients with progressive disease (Pr + MEP) and groups with non-progressive disease (LTNP + STP) the probability of harbouring the R77Q mutation was significantly higher in non-progressors (odds ratio, 5.16; P = 0.001). CONCLUSIONS: Our results support the hypothesis of the association of R77Q mutation in the Vpr gene with delayed progression of HIV-1 disease. R77Q does not seem to be linked to a particular viral strain but might be associated to immunologic selection. The R77Q mutation might reduce CD4+ T-cell depletion possibly affecting T-cell survival in vivo by altering the pro-apoptotic activity of Vpr.

Adult↗

PubMed1990

Patients with asymptomatic primary sclerosing cholangitis frequently have progressive disease.

We identified and analyzed 45 patients with asymptomatic primary sclerosing cholangitis to better understand the natural history of this disease. Disease progression was monitored at regular intervals for the development of symptoms and physical signs as well as changes in liver biochemistry, cholangiography, and liver histology. During a median follow-up of 75.2 mo, 34 patients (76%) had evidence of disease progression. Fourteen patients (31%) developed liver failure which resulted in death or referral for liver transplantation. For patients with primary sclerosing cholangitis, survival curves computed using the Kaplan-Meier method were significantly worse than expected when compared to age-, sex-, and race-specific survival rates for the United States north central population (p less than 0.001). These findings indicate that primary sclerosing cholangitis is generally a progressive disease with considerable morbidity and mortality even when detected before the onset of symptoms.

Adult↗

PubMed1992

Early detection of local disease progression from stage A1 prostate carcinoma by transrectal ultrasonography.

Fifty-two patients with Stage A1 prostate cancer diagnosed by transurethral resection performed between 1975 and 1989 were re-examined by transrectal ultrasonography and ultrasonographically guided biopsies. Follow-up after the initial diagnosis ranged from 1 to 15 years (mean, 5.8 years). For eight patients, results of digital rectal examination were abnormal. For 44 patients, results were normal or indicated a low probability of cancer. Serum prostate-specific antigen (PSA) levels (4.6 to 14.6 ng/ml) were elevated in ten patients. Ultrasonography showed from one to three hypoechoic areas in 29 patients. Locally progressive disease, defined as moderately to poorly differentiated cancer, was detected in five (10%) patients, three of whom underwent radical prostatectomy. Histopathologic examination of the specimens revealed localized disease (no capsular invasion). The remaining two patients had radiation therapy. In three patients, results of digital rectal examination and the serum PSA level were normal, but focal, well-differentiated cancer, identical to that initially diagnosed, was detected after a follow-up of 5 to 10 years. Because the clinical significance of this finding is unknown, these three patients were not considered to have progressive disease and did not have additional treatment. Our data suggest that transrectal ultrasonography is valuable in early detection of local disease progression and should be used in the follow-up program for patients with Stage A1 prostate cancer.

Adenocarcinoma↗

PubMed2002

Breast carcinoma: a report on the potential usage of the CC chemokine RANTES as a marker for a progressive disease.

BACKGROUND: High incidence and intensity of RANTES (CC chemokine) expression were noted in advanced breast carcinoma. OBJECTIVE: To present two cases of breast carcinoma patients in whom RANTES expression was analyzed in parallel to disease progression. RESULTS: Although no evidence of malignancy was detected in the axillary lymph nodes of the two patients, their disease progressed. The expression of RANTES in both patients was positive at diagnosis and predicted the clinical course. CONCLUSIONS: These results, combined with our previous findings on the correlation between RANTES expression and advanced breast carcinoma, suggest that the assessment of RANTES expression may be useful for the identification of patients with apparently poor prognosis who may benefit from aggressive treatment. The above results call for large-scale studies by numerous research groups to determine the prognostic value of RANTES expression.

Adult↗

PubMed2006

Response evaluation in gastrointestinal stromal tumours treated with imatinib: misdiagnosis of disease progression on CT due to cystic change in liver metastases.

Imatinib is a highly effective treatment for patients with metastatic gastrointestinal stromal tumours (GIST). In most instances, response to imatinib treatment is assessed with CT. We present two cases where CT demonstrated the appearance of new low density liver lesions after 8-12 weeks of imatinib treatment. While this finding is consistent with progressive disease due to new lesions appearing at a previously uninvolved site, we hypothesise that the appearance of new liver lesions is in fact due to cystic change within previously occult, solid metastases. These untreated solid metastases were not visible on conventional portal phase CT due to their small size and vascular nature. Our hypothesis is supported by the observation that extrahepatic sites of disease had reduced in size over the same period of imatinib treatment and by the subsequent disease outcomes of these two cases. One patient, who continued imatinib because of significant symptomatic improvement despite the CT findings, remained stable on the same dose of imatinib for 18 months. The other patient, whose disease progressed when imatinib was withdrawn, had a dramatic response to treatment when imatinib was restarted at the same dose 2 years later. It is important that radiologists and oncologists who are involved in the management of GIST recognize that the appearance of new, low-density liver lesions on CT may represent a response to treatment. This finding must be correlated with symptomatic response and with tumour sites outside the liver before erroneously withdrawing effective imatinib treatment.

Aged↗

PubMed2006

Serum immune responses predict rapid disease progression among children with Crohn's disease: immune responses predict disease progression.

BACKGROUND AND AIM: Crohn's disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients. METHODS: Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated. RESULTS: Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5-80.4); p = 0.03). Pediatric CD patients positive for > or =1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03). CONCLUSIONS: The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients.

Adolescent↗

PubMed1991

Expression of interleukin-1 alpha, interleukin-1 beta and interleukin-6 in chronic B lymphocytic leukaemia (B-CLL) cells from patients at different stages of disease progression.

We have previously found that isolated B-CLL cells from progressive disease produce less interleukin-1 beta (IL-1 beta) as compared with cells from patients with indolent disease. Here we extend that finding to include measurements of IL-1 beta mRNA and secretion of IL-1 alpha and interleukin-6 (IL-6). As before, a lower production of IL-1 beta was found in cells from progressive disease. IL-6 was produced by cells from patients at all stages, with a tendency to follow the IL-1 beta production. Low secretion of IL-1 alpha was noted. When viable cells were permeabilized and analysed at the single cell level with monoclonal antibodies, most B-CLL cells were found to contain IL-1 alpha. A minor fraction of non-permeabilized cells expressed IL-1 alpha at the cell membrane. However, only small fractions of cells were positive for intracellular IL-1 beta (less than 1%) and almost no IL-6-positive cells were found. We conclude that either IL-1 beta and IL-6 are produced by a minor population of undefined cells, or that a more sensitive in situ method is needed to detect production of these cytokines in B-CLL cells. The possible biological significance of secreted, and membrane-expressed helper factors in B-CLL is discussed.

Adult↗

PubMed1993

Is disease progression the major factor in morphine 'tolerance' in cancer pain treatment?

To assess the contribution of pharmacological tolerance to increasing doses of morphine, 29 cancer patients requiring oral morphine to treat pain were studied by two teams working independently. The first team assessed physical impairment, pain intensity and pain treatment. The second team assessed depressive disorders (DSM III criteria), emotional and behavioural depressive patterns (Retardation Depressive Scale, Polydimensional Mood Scale). All patients were seen at the initiation of morphine therapy and followed to the first morphine dose modification. Evaluations were carried out in out-patient clinics except staging investigations which were undertaken at the beginning and at the end of the study. Our results showed that (1) in 24 of the 25 patients for whom morphine doses were increased, progressive disease was recorded; (2) in 4 patients, morphine doses were not increased and in these patients their disease was stable or in remission; and (3) changes in depressed mood were not correlated with pain intensity. These data strongly suggest that, instead of pharmacological tolerance, the main factor resulting in increasing oral morphine requirement in cancer pain management is pain increase due to disease progression.

Adult↗

PubMed1993

Motor neurone disease: a progressive disease requiring a coordinated approach.

1. Such a variety of causes are implicated for MND that it is unlikely a single cause exists. 2. There is no actual treatment for the disease other than alleviating symptoms and improving function by the use of aids and appliances. 3. Care of people with MND is highly specialised, requiring multidisciplinary cooperation to ensure effective patient care. 4. Nurses owe it to their patients to acquaint themselves with the disease and support networks available.

Female↗

PubMed2000

Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease: power calculations and estimates of sample size to detect treatment effects.

OBJECTIVE: To evaluate the rate of brain atrophy calculated from serial magnetic resonance imaging (MRI) registration as a surrogate marker of disease progression for use in clinical trials in Alzheimer disease (AD). METHODS: Eighteen patients with mild to moderate AD and 18 age-matched normal controls underwent 2 MRI brain scans separated by a 12-month interval. Each individual's later scan was registered to their first scan, and the volume of cerebral tissue loss calculated directly from the registered and subtracted MRI scan pairs. The mean and SD of the rate of brain volume changes were used to estimate the sample sizes that would be needed in a clinical trial with a drug anticipated to modify disease progression by varying degrees. Comparable sample size estimates were performed with data for other methods of monitoring rates of brain atrophy, extracted from published papers. RESULTS: The mean (SD) rate of brain atrophy for the patients with AD was 2.37% (1.11%) per year, while in the control group it was 0.41% (0.47%) per year. Based on these figures, to have 90% power to detect a drug effect equivalent to a 20% reduction in the rate of atrophy, 207 patients would be needed in each treatment arm. This assumes a 1-year placebo-controlled trial with a 10% patient dropout rate, and that 10% of scan pairs are unusable. CONCLUSION: Registration of serial MRI volume images provides a powerful method of quantification of brain atrophy that can be used to monitor progression of AD in clinical trials.

Aged↗

PubMed2000

Sensory evoked potentials in SIV-infected monkeys with rapidly and slowly progressing disease.

Human immunodeficiency virus (HIV-1) infects the central nervous system (CNS) early in the course of disease progression and leads to some form of neurological disease in 40-60% of cases. Both symptomatic and asymptomatic HIV-infected subjects also show abnormalities in evoked potentials. As part of an effort to further validate an animal model of the neurological disease associated with lentiviral infection, we recorded multimodal sensory evoked potentials (EPs) from nine rhesus macaques infected with passaged strains of SIVmac (R71/E17), prior to and at 1 month intervals following inoculation. The latencies of forelimb and hindlimb somatosensory evoked potentials (SEP) and flash visual evoked potentials (VEP) were measured. Within 14 weeks of inoculation, all but two animals had progressed to end-stage disease (rapid progressors). The two animals with slowly progressing disease (AQ15 and AQ94) had postinoculation life spans of 109 and 87 weeks, respectively. No significant changes were observed in evoked potentials recorded during the control period or at any time in the animals with slowly progressing disease. However, all of the monkeys with rapidly progressing disease exhibited increases in latency for at least one evoked potential type. The overall mean increases in somatosensory and visual evoked potential peak latencies for the rapid progressors were 22.4 and 25.3%, respectively. For comparison, the changes in slow progressors were not significant (1.8 and -1.9%, respectively). These results, coupled with our previous finding of slowed motor evoked potentials in the same cohort of macaques (Raymond et al.: J Neurovirol 1999;5:217-231), demonstrate a broad and somewhat variable pattern of viral injury to both sensory and motor system structures, resembling the findings in HIV-infected humans. These results coupled with our earlier work demonstrating cognitive and motor behavioral impairments in the same monkeys support the use of the SIVmac-infected rhesus macaque as a model of AIDS-related neurological disease.

Animals↗

PubMed2005

Disease system analysis: basic disease progression models in degenerative disease.

PURPOSE: To describe the disease status of degenerative diseases (i.e., type 2 diabetes mellitus, Parkinson's disease) as function of disease process and treatment effects, a family of disease progression models is introduced. METHODS: Disease progression is described using a progression rate (Rdp) acting on the synthesis or elimination parameters of the indirect response model. Symptomatic effects act as disease-dependent or -independent effects on the synthesis or elimination parameters. Protective drug effects act as disease dependent or -independent effects on Rdp. RESULTS: Simulations with the ten disease models show distinctly different signature profiles of treatment effects on disease status. Symptomatic effects result in improvement of disease status with a subsequent deterioration. Treatment cessation results in a disease status equal to the situation where treatment had not been applied. Protective effects result in a lasting reduction, or even reversal, of the disease progression rate and the resulting disease status during the treatment period. After cessation of treatment the natural disease course will continue from the disease status at that point. CONCLUSION: Disease system analysis constitutes a scientific basis for the distinction between symptomatic versus protective drug effects in relation to specific disease processes as well as the identification of the exposure-response relationship during the time-course of disease.

Biomarkers↗