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PubMed1999

The Cancer Genome Anatomy Project: EST sequencing and the genetics of cancer progression.

As the process of tumor progression proceeds from the normal cellular state to a preneoplastic condition and finally to the fully invasive form, the molecular characteristics of the cell change as well. These characteristics can be considered a molecular fingerprint of the cell at each stage of progression and, analogous to fingerprinting a criminal, can be used as markers of the progression process. Based on this premise, the Cancer Genome Anatomy Project was initiated with the broad goal of determining the comprehensive molecular characterization of normal, premalignant, and malignant tumor cells, thus making a reality the identification of all major cellular mechanisms leading to tumor initiation and progression ([Strausberg, R.L., Dahl, C.A., and Klausner, R.D. (1997). "New opportunities for uncovering the molecular basis of cancer." Nat. Genet., 16: 415-516.], www.ncbi.nlm.nih.gov/ncicgap/). The expectation of determining the genetic fingerprints of cancer progression will allow for 1) correlation of disease progression with therapeutic outcome; 2) improved evaluation of disease treatment; 3) stimulation of novel approaches to prevention, detection, and therapy; and 4) enhanced diagnostic tools for clinical applications. Whereas acquiring the comprehensive molecular analysis of cancer progression may take years, results from initial, short-term goals are currently being realized and are proving very fruitful.

Databases, Factual↗
PubMed2003

Is there a progression from abuse disorders to dependence disorders?

BACKGROUND: Recent studies suggest that a progression occurs from alcohol abuse to alcohol dependence. Although DSM-IV criteria for all substance use-related diagnoses are based largely on the alcohol dependence syndrome, progression from abuse to dependence might not generalize to other substances. AIMS: This study tested whether a progression from DSM-IV abuse to dependence occurs related to the use of cannabis, cocaine and opiates. DESIGN: Retrospective data from the DSM-IV Substance Use Disorders Work Group (n = 1226) were reanalysed using McNemar's chi2, configural frequency analyses and survival analyses. Participants were men and women who were primarily African-Americans or Caucasians. SETTINGS: Participants were recruited from community and clinical settings. The measure was the Composite International Diagnostic Interview-Substance Abuse Module. FINDINGS: For all substances, life-time dependence in the absence of life-time abuse was rare. Results were consistent with a progression occurring for alcohol and cannabis, but not for cocaine and opiates. Abuse and dependence occurred in the same year for 66% of the cocaine users who experienced both disorders (57% of users with any cocaine disorder) and 65% of the opiate users who experienced both disorders (46% of users with any opiate disorder). Because cocaine and opiate dependence in the absence of abuse were rare, it is possible that progressions in cocaine and opiate disorders occur more rapidly than cannabis and alcohol. CONCLUSIONS: Research is needed to clarify the mechanisms that influence progressions of substance use disorders. Potential factors leading to between-drug variation in rate of progression of disorders are discussed.

Alcoholism↗
PubMed2003

Metallothionein-overexpression as a prognostic factor for progression and survival in melanoma. A prospective study on 520 patients.

BACKGROUND: Metallothioneins (MTs) are ubiquitous proteins with high affinity for heavy metal ions, e.g. zinc, copper and cadmium. In the last decade it has been shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and radiotherapy, and with a poor prognosis. OBJECTIVES: To examine the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. METHODS: In a prospective cohort study 760 patients with primary cutaneous melanoma were investigated over 5 years (1993-98) by using a monoclonal antibody (E9) against MT on routinely fixed and paraffin-embedded tissues. In total, 520 patients were able to be followed up for progression of their disease or death due to melanoma and were included for statistical analysis (Fisher's exact test, Mantel-Haenszel chi2 test, Kaplan-Meier curves). MT data, progress-free interval and overall survival were compared univariately and multivariately with other prognostic factors, e.g. Breslow thickness, Clark level, ulceration, localization, age and gender (Cox regression analysis). RESULTS: The immunohistochemical overexpression of MT in tumour cells (cut-off level > 10% of all tumour cells) in patients with primary melanoma (156 of 520; 30%) was associated with a higher risk for progression of the disease (33 of 45; 73%) and reduced survival (24 of 30; 80%) than MT-negative lesions [364 of 520 (70%), 12 of 45 (27%) and six of 30 (20%), respectively (P < 0.0001)]. Similarly, Kaplan-Meier tumour-free survival and overall survival curves for the comparison of MT-positive and MT-negative tumours gave highly significant advantages for the MT-negative group. In a univariate analysis (comparison with Breslow thickness: relative risk 2.9, 95% confidence interval, CI 1.46-5.76, P = 0.0023 for progression; relative risk 4.19, 95% CI 1.73-10.19, P = 0.0015 for survival), as well as in a multivariate analysis with other prognostic markers, MT overexpression turned out to be a highly significant and independent factor for prognosis in primary melanoma. CONCLUSIONS: MT overexpression in primary melanoma is associated with an increased risk for disease progression. This marker is independent from Breslow thickness and helps to identify those thin melanomas (< 1.5 mm) that are at increased risk of progression. Moreover, the immunohistochemical staining of paraffin material is a cheap, easy and widely available technique to gain these results.

Adolescent↗
PubMed2001

Pathology of lymphoma progression.

Reflecting the stepwise process of oncogenesis, lymphomas may cumulatively develop a more aggressive phenotype during the course of disease, a process referred to as lymphoma progression. Although morphological, clinical and biological aspects of lymphoma progression do not always overlap, changes in lymphoma morphology frequently indicate alterations in the clinical and biological behaviour of the disease. Indolent and aggressive lymphomas in disease progression can either be clonally related or represent clonally unrelated neoplasms. We propose to use the term 'lymphoma progression' in a biological sense denoting only clonal development of and within a lymphoma entity. The term 'composite lymphoma' should be used as a merely descriptive morphological designation for different lymphoma entities in one individual irrespective of clonal relationship. Many types of aggressive B-cell non-Hodgkin's lymphomas and Hodgkin's lymphomas are reported to secondarily develop in lymphoma progression. Genetic changes associated with lymphoma progression frequently abrogate the differentiating effects of alterations occurring in indolent lymphomas, leading to increased cell proliferation. Within different lymphoma entities, high-risk disease variants mimicking lymphoma progression exist.

Apoptosis↗
PubMed2000

Non-linear effects of blood pressure and glycosylated haemoglobin on progression of diabetic nephropathy.

OBJECTIVE: To describe the long-term simultaneous impacts of blood pressure and glycosylated haemoglobin values on the risk of progression of diabetic nephropathy. DESIGN: Prospective, multicentre, 6-year follow-up study. SETTING: One reference centre (university department of internal medicine) and nine general hospitals. SUBJECTS: A total of 601 type 1 diabetic patients on intensive insulin therapy with and without diabetic nephropathy. MAIN OUTCOME MEASURES: Progression of nephropathy was defined as change for the worse within five stages of nephropathy by at least one of these stages during the study period. By the use of logistic regression, the relationship between metabolic and blood pressure control and the risk of nephropathy progression was quantified. RESULTS: The main determinants of nephropathy progression were glycosylated haemoglobin and blood pressure, which were both non-linearly associated with the risk of progression. No significant threshold levels for any of the predictors of progression were identified. CONCLUSIONS: The results of this study underline the importance of optimizing metabolic and blood pressure control to arrest the progression of diabetic nephropathy without the evidence for a clinically relevant threshold effect.

Adult↗
PubMed2002

Quantification of fibrosis progression in patients with chronic hepatitis C using a Markov model.

The knowledge of fibrosis progression in chronic hepatitis C and the impact of new treatments on progression is limited by the number of available liver biopsies per patient. Moreover, liver biopsies identify a patient's stage of fibrosis at a given point in time, but cannot quantify the time spent in that stage nor the date of transition to that stage. This paper assesses the potential of Markov modelling to overcome these difficulties. The data from interferon-treated (n=185) and untreated patients (n=102) are analysed to illustrate the power of this technique. The model accurately reproduced the distributions of patients in the different fibrosis stages at two subsequent biopsies. A quantification of the role of cofactors in the progression of the disease, and the impact of interferon treatment are given. In subjects who are 40 years old and have been infected for 10 years, the model predicted that 274 of 1000 untreated patients, but only 42 of 1000 treated patients, would progress from F0 or F1 to F3 or F4 fibrosis over the next 5 years. The model also confirms that as age and duration of infection increase, the risk of fibrosis progression increases, while the impact of treatment with interferon decreases. Hence Markov modelling is an accurate tool in the analysis of fibrosis progression in chronic hepatitis C. It will be valuable for the quantification of the effect of new treatments on fibrosis progression in hepatitis C.

Adolescent↗
PubMed1997

Clinical characteristics of progressive vitiligo.

BACKGROUND: Vitiligo is an acquired hypopigmentary disorder with a progressive clinical course. Various clinical characteristics and their significance in the progression of vitiligo were evaluated. METHODS: A clinical study was carried out on 400 patients who had visited the Vitiligo Special Clinic of Severance Hospital, Yonsei University College of Medicine. Questionnaires were completed regarding progression, sex, family history, clinical type, onset age, duration of disease, Koebner's phenomenon, leukotrichia, and mucosal involvement, and the results were recorded. RESULTS: Progression of vitiligo was seen in 355 patients (88.8%); 45 patients (11.2%) did not show progression. No difference in sex, onset age, or leukotrichia was noted between the two groups; however, patients with positive family histories, nonsegmental clinical type, longer duration, Koebner's phenomenon, and mucous membrane involvement showed more progression of vitiligo. CONCLUSIONS: Clinical characteristics such as family history, clinical type, duration of disease, Koebner's phenomenon, and mucous membrane involvement, may be relevant in predicting the progression or prognosis of vitiligo.

Adolescent↗
PubMed1999

Progression of congenital heart disease in the prenatal period.

BACKGROUND: Prenatal echocardiography has shown evidence of prenatal development of congenital heart disease. Prenatal cardiac anatomy, chamber size and function change during gestation, so that the appearance of cardiac structure in abnormal hearts may be different from that which is usually seen postnatally. METHODS: Published prenatal echocardiographic studies were reviewed and in utero development of congenital heart disease from midtrimester to the early postnatal period is discussed. RESULTS: The growth of the great vessels and ventricles is reduced in fetuses with ventricular outflow obstruction. Valve regurgitation may progress. The foramen ovale and ductus arteriosus have been reported to become restrictive in utero in several settings. Pulmonary vascular obstructive changes may progress prenatally. Fetal arrhythmia (both bradycardia and tachycardia) may develop in utero. Development of congestive heart failure is a very important issue during follow up of fetuses with significant cardiac or extracardiac problems. Some may progress to fetal hydrops and prognosis of the affected fetuses is usually very poor. CONCLUSIONS: Correct knowledge of possible development is important for accurate prenatal diagnosis. Information on prenatal progression of the cardiac anomaly is also important to make plans for follow up and perinatal management, to predict outcomes and to counsel family. Furthermore, the benefits of prenatal treatment instead of postnatal treatment should be assessed by the accurate prediction of the progression of the cardiac problem in utero. Further extensive studies using a large number of cases is required to predict progression accurately. In addition, further studies for elucidating the mechanisms of progression is important to provide better outcomes for fetuses with various congenital heart diseases.

Arrhythmias, Cardiac↗
PubMed2002

Prevention of autoimmune attack and disease progression in multiple sclerosis: current therapies and future prospects.

Multiple sclerosis (MS) is an important cause of progressive neurological disability, typically commencing in early adulthood. There is a need for safe and effective therapy to prevent the progressive central nervous system (CNS) damage and resultant disability that characterize the disease course. Increasing evidence supports a chronic autoimmune basis for CNS damage in MS. In the present study, we review current concepts of autoimmune pathogenesis in MS, assess current therapies aimed at countering autoimmune attack and discuss potential therapeutic strategies. Among currently available therapies, beta-interferon and glatiramer acetate have a modest effect on reducing relapses and slowing the accumulation of disability in relapsing-remitting MS. Beta-interferon is of doubtful efficacy in secondary progressive MS and appears to aggravate primary progressive MS, possibly by increasing antibody-mediated CNS damage through inhibition of B-cell apoptosis. Mitoxantrone may reduce relapses and slow disability progression in relapsing-remitting and secondary progressive MS, but its use is limited by the risk of cardiomyopathy. There are currently no effective treatments for primary progressive MS. Many therapies that are effective in the animal model, experimental autoimmune encephalomyelitis (EAE), are either ineffective in MS or--in the case of gamma-interferon, lenercept and altered peptide ligands--actually make MS worse. This discrepancy may be explained by the occurrence in MS of defects in immunoregulatory mechanisms, the integrity of which is essential for the efficacy of these treatments in EAE. It is likely that the development of safe, effective therapy for MS will depend on a better understanding of immunoregulatory defects in MS.

Adjuvants, Immunologic↗
PubMed2001

Progression of spontaneous seizures after status epilepticus is associated with mossy fibre sprouting and extensive bilateral loss of hilar parvalbumin and somatostatin-immunoreactive neurons.

The development of spontaneous limbic seizures was investigated in a rat model in which electrical tetanic stimulation of the angular bundle was applied for up to 90 min. This stimulation produced behavioural and electrographic seizures that led to a status epilepticus (SE) in most rats (71%). Long-term EEG monitoring showed that the majority of the rats (67%) that underwent SE, displayed a progressive increase of seizure activity once the first seizure was recorded after a latent period of about 1 week. The other SE rats (33%) did not show this progression of seizure activity. We investigated whether these different patterns of evolution of spontaneous seizures could be related to differences in cellular or structural changes in the hippocampus. This was the case regarding the following changes. (i) Cell loss in the hilar region: in progressive SE rats this was extensive and bilateral whereas in nonprogressive SE rats it was mainly unilateral. (ii) Parvalbumin and somatostatin-immunoreactive neurons: in the hilar region these were almost completely eliminated in progressive SE rats but were still largely present unilaterally in nonprogressive SE rats. (iii) Mossy fibre sprouting: in progressive SE rats, extensive mossy fibre sprouting was prominent in the inner molecular layer. In nonprogressive SE rats, mossy fibre sprouting was also present but less prominent than in progressive SE rats. Although mossy fibre sprouting has been proposed to be a prerequisite for chronic seizure activity in experimental temporal lobe epilepsy, the extent of hilar cell death also appears to be an important factor that differentiates between whether or not seizure progression will occur.

Animals↗
PubMed1996

The significance of tumour grade in predicting disease progression in stage Ta transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To determine the significance of tumour grade in predicting disease progression in stage Ta transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: From August 1975 to January 1991, 140 patients (121 men and 19 women, mean age 64.2 years, range 30-83) with stage Ta TCC of the urinary bladder were treated at the Veterans General Hospital-Taipei by transurethral resection and post-operative adjuvant intravesical chemotherapy. There were 48 patients (34%) with grade 1, 78 patients (56%) with grade 2 and 14 patients (10%) with grade 3 tumours. Disease progression and muscle invasion were assessed during a mean follow-up of 74.3 months and related to grade, urine cytology and the number and location of tumours. RESULTS: A total of 10 patients (7%) had tumour recurrence which invaded the muscle, of whom one had grade 1, six had grade 2 and three had grade 3 tumours. The patient with a grade 1 tumour developed muscle invasion within 16 months of surgery. The mean interval to the development of muscle invasion was 49.2 months in patients with grade 2 and 39.4 months with grade 3 tumour. In patients with stage Ta TCC, a grade 3 tumour was more likely to progress to muscle invasion (21%) than was a grade 1 (2.1%; P < 0.05) or grade 2 (7.7%; P < 0.05) tumour. One patient with a grade 2 and one patient with grade 3 tumour developed distant metastases without muscle invasion. Overall, the disease progression rate was 8.6% (12/140) in stage Ta TCC. Disease progression was more common with grade 3 (28.5%) than with grade 2 (9.0%; P < 0.05) and grade 1 (2.1%; P < 0.05) tumours. CONCLUSION: Tumour grade may be used to predict disease progression after resection of stage Ta urinary bladder cancer. A higher grade of tumour was associated with a higher incidence of disease progression.

Administration, Intravesical↗
PubMed2001

Impact of pregnancy on the progression of diabetic retinopathy in Type 1 diabetes.

AIMS: To evaluate the impact of pregnancy on the progression of diabetic retinopathy in women with Type 1 diabetes mellitus and to identify risk factors for the progression of retinopathy during pregnancy. METHODS: One hundred and seventy-nine pregnancies in 139 women with pregestational Type 1 diabetes were studied prospectively between January 1990 and December 1998. Dilated fundal examination was performed at booking, 24 weeks and 34 weeks or 4-6 weekly if retinopathy present at booking. Data were collected on glycaemic control (HbA(1c)) throughout pregnancy. RESULTS: Progression to proliferative retinopathy was seen in four (2.2%) pregnancies while moderate progression was seen in a further five (2.8%) pregnancies. Progression of retinopathy was significantly increased in women with duration of diabetes 10-19 years compared with duration < 10 years (10% vs. 0%; P = 0.007) and in women with moderate to severe background retinopathy at booking (30% vs. 3.7%; P = 0.01). Although HbA(1c) at booking was higher (7.5% vs. 6.6%; P = 0.08) and the fall in HbA(1c) between booking and 24 weeks was greater (1.6% vs. 1.2%; P = 0.2) in those women showing progression of retinopathy, these changes were not significant. CONCLUSIONS: Progression of retinopathy in pregnancy was uncommon (5.0% pregnancies) but was significantly more common in women with duration of diabetes > 10 years and in women with moderate to severe retinopathy at baseline. Laser therapy was needed in 2.2% pregnancies, which is much lower than that reported in earlier studies. Diabet. Med. 18, 573-577 (2001)

Age of Onset↗
PubMed2000

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.

Adult↗
PubMed2001

Role of iron in progressive renal disease.

The importance of iron in renal injury is derived from the ease with which iron is reversibly oxidized or reduced, enabling it to participate in the production of free radicals. Experimental evidence for the role of oxidants and iron in progressive renal disease falls into two broad categories. First, considerable data implicate oxidants in the proteinuria of glomerular disease. To the extent that proteinuria is an important determinant of progression, reduction of proteinuria would result in retardation of progression. Evidence also suggests a role of oxidants and iron in diabetic nephropathy, a major cause of end-stage kidney disease. Second, more direct studies have examined the role of oxidants and iron in models of progressive renal disease. These studies include the demonstration of increased iron in the kidney in models of progressive kidney disease; enhanced generation of oxidants, providing a mechanism by which iron can be mobilized; and more direct evidence of the beneficial effect of iron-deficient diets and iron chelators. Although the collective information on the role of oxidants and iron derived from in vitro studies and animal models of glomerular disease and progressive renal failure is impressive, control studies of patients are needed to show the efficacy of antioxidants and/or iron chelators in retarding the progression of renal failure and may offer an important therapeutic modality to patients with renal disease.

Animals↗
PubMed2002

Slowing the progression of chronic renal failure: economic benefits and patients' perspectives.

Because of the predicted increase in end-stage renal disease (ESRD) incidence (projected increase from 1998 to 2010; 86,825 to 172,667), prevalence (projected increase from 1998 to 2010; 326,217 to 661,330), and cost (total cost based on 1998 ratio of Medicare versus non-Medicare cost; $16.74 billion in 1998 to $39.35 billion in 2010), a cohesive national effort is needed to develop strategies to slow the progression of chronic renal failure (CRF). The question arises to how much reduction in the progression of CRF would lead to a meaningful decrease in the prevalence and cost of ESRD. There are no objective data that show the economic impact of slowing the progression of CRF. We developed a mathematical model to assess the economic impact of decreasing the progression of CRF by 10%, 20%, and 30%. US Renal Data System (USRDS) projections were used to model the rate of increase in ESRD incidence and prevalence. Glomerular filtration rate (GFR) at the initiation of ESRD therapy and cost per patient-year were based on USRDS data. The average decline in GFR in subjects with CRF was estimated to be 7.56 mL/min/y. All dollar savings reflect 1998 costs, discounted for the future at 3% per annum. We also determined how much slowing of the progression of CRF is important from patients' perspectives by means of a written questionnaire (which inquired about willingness to go on a restricted diet, take six extra medications per day, and make six extra office visits per year) and calculation of the pre-ESRD time gained for different degrees of reduction in the progression of CRF. If the rate of decline in GFR decreased by 10%, 20%, and 30% after December 31, 1999, in all patients with GFRs of 60 mL/min or less, cumulative direct healthcare savings through 2010 would equal approximately $18.56, $39.02, and $60.61 billion, respectively. For a 10%, 20%, and 30% decrease in the rate of decline in GFR in all patients with a GFR of 30 mL/min or less, estimated cumulative savings through 2010 equal $9.06, $19.98, and $33.37 billion, respectively. Responses to the questionnaire showed that approximately 79% of subjects with CRF (n = 113) perceived a few weeks' dialysis-free period significant (P < or = 0.0001), a period corresponding to a 10% reduction in the rate of decline in GFR. Our data suggest that the cumulative economic impact of slowing the progression of CRF, even by as little as 10%, would be staggering. They provide strong support for the development and implementation of intensive reno-protective efforts beginning at the early stages of chronic renal disease and continued throughout its course.

Disease Progression↗
PubMed1998

Progression of coronary artery disease in young male post-infarction patients is linked to disturbances of carbohydrate and lipoprotein metabolism and to impaired fibrinolytic function.

AIMS: To assess determinants of coronary artery disease progression in men with previous myocardial infarction. METHODS AND RESULTS: A total of 102 unselected non-diabetic Swedish men (age 40.4 +/- 3.6, range 23-44 years) entered the study 3-6 months after a first myocardial infarction. The programme included metabolic and haemostatic investigations and routine coronary angiography at baseline, followed by re-angiography 5 years later. Of the original cohort, 76 patients underwent a second angiogram. Separate semiquantitative scoring systems were used for diffuse coronary atherosclerosis and distinct stenoses in 15 proximal coronary segments. Smoking, global severity of coronary atherosclerosis and presence of multi-vessel disease at baseline (P < 0.001) characterized patients with severe progression of both diffuse and focal lesions. Higher plasma levels of low density lipoprotein cholesterol (P < 0.01) and low density lipoprotein triglycerides (P < 0.05), a lower plasma high density lipoprotein2 cholesterol level (P < 0.05) and higher plasma plasminogen activator inhibitor-1 activity (P < 0.05), together with a high baseline stenosis score (P < 0.001) characterized patients with severe progression of coronary atherosclerosis. On the other hand, more pronounced fasting and post-prandial glycaemia (P < 0.05), together with higher plasma plasminogen activator inhibitor-1 activity (P < 0.01) characterized severe progressors with respect to coronary stenosis. Multivariate analysis identified the presence of multi-vessel disease as an independent predictor of progression of both coronary atherosclerosis (P = 0.008) and stenoses (P = 0.007), whereas a high low density lipoprotein triglyceride level (P < 0.01) was independently related to progression of coronary atherosclerosis and a high fasting glucose level (P = 0.02) to progression of coronary stenoses. CONCLUSION: Disturbances in carbohydrate and lipoprotein metabolism and impaired fibrinolytic function are associated with progression of coronary artery disease in young male post-infarction patients.

Adult↗
PubMedDate not supplied

Relapse pattern after complete resection and early progression after incomplete resection of childhood craniopharyngioma.

In HIT Endo data on therapy and prognosis of 306 patients with childhood craniopharyngioma (CP) were analyzed. The 5 years-overall survival rate was 94 +/- 4 % in irradiated patients and 93 +/- 5 % in non-irradiated patients. Aims of the prospective study KRANIOPHARYNGEOM 2000 were to collect data on the incidence and time course of relapses after complete surgery and tumour progressions after incomplete resection. Furthermore, the impact of irradiation therapy (XRT) on tumour relapse and recurrence rates was analyzed. Since 2001 ninety-eight patients with CP were recruited at a median age at diagnosis of 9.9 years ranging from 1.8 to 18.0 years. Complete resection was achieved in 44 %, incomplete resection in 54 %. XRT was performed in 24 of 98 CP patients; in 10 early after incomplete resection, in 14 of 24 after progression of residual tumour or relapse, in 3 of 14 after second surgery of relapse. XRT was performed at a median age of 12.0 years ranging from 5.0 to 18.9 years and in median after an interval of 9 months after first diagnosis. The analysis of event-free survival rates (EFS) in patients with CP showed a high rate of early events in terms of tumour progression after incomplete resection (3y-EFS: 0.22 +/- 0.09) and relapses after complete resection (3y-EFS: 0.60 +/- 0.10) during the first three years of follow-up. A high rate of early events (1y-EFS: 0.78 +/- 0.10; 2y-EFS: 0.57 +/- 0.15) was also found for patients after XRT (3 cystic progressions, 3 progressions of solid tumour; in 24 patients after XRT). We conclude that tumour progression and relapse are frequent and early events even in irradiated patients. Monitoring of cerebral imaging and clinical status is recommended in follow-up of patients with childhood CP. In order to analyze the appropriate time point of XRT after incomplete resection, QoL, EFS and overall survival in patients (age > or = 5 years) will be analyzed in KRANIOPHARYNGEOM 2007 after stratified randomization of the time point of irradiation after incomplete resection (early irradiation versus irradiation at progression of residual tumour).

Adolescent↗
PubMed1995

Race, sex, drug use, and progression of human immunodeficiency virus disease.

BACKGROUND: The rates of progression of human immunodeficiency virus (HIV) infection and survival have been reported to differ among sociodemographic groups. It is unclear whether these differences reflect biologic differences or differences in access to medical care. METHODS: We measured disease progression and survival in a cohort of 1372 patients seropositive for HIV who were treated at a single urban center (median follow-up, 1.6 years). We calculated the rates of survival for the entire cohort and the rates of progression to the acquired immunodeficiency syndrome (AIDS) or death among the 740 patients who presented without AIDS. We used Cox proportional-hazards analysis to examine factors associated with progression to AIDS and death. RESULTS: Progression to AIDS or death was associated with a CD4 cell count of 201 to 350 per cubic millimeter (relative risk, 2.0; P < 0.001), the presence of symptoms at base line (relative risk, 2.0; P < 0.001), prior antiretroviral therapy (relative risk, 1.7; P = 0.003), and older age (relative risk per year of age, 1.02; P = 0.03). However, there was no relation between disease progression and sex, race, injection-drug use, income, level of education, or insurance status. In the entire cohort, a lower CD4 cell count, a diagnosis of AIDS, older age, and the receipt of antiretroviral therapy before enrollment were associated with an increased risk of death, whereas the use of prophylaxis against pneumocystis pneumonia, zidovudine use after enrollment, and having a job at base line were associated with lower risks of death. There was no significant difference in survival between men and women, blacks and whites, injection-drug users and those who did not use drugs, or patients whose median annual incomes were $5,000 or less and those whose incomes were more than $5,000. CONCLUSIONS: Among patients with HIV infection who received medical care from a single urban center, there were no differences in disease progression or survival associated with sex, race, injection-drug use, or socioeconomic status. Differences found in other studies may reflect differences in the use of medical care.

Acquired Immunodeficiency Syndrome↗