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PubMed1997

Tumour necrosis factor c2 microsatellite allele is associated with the rate of HIV disease progression.

BACKGROUND: The rate of immunological deterioration and progression to AIDS differs markedly between HIV-positive individuals, and may be influenced by cofactors, HIV phenotype and host T-cell response. Tumour necrosis factor (TNF)-alpha and lymphotoxin stimulate HIV replication and may induce apoptosis of HIV-infected and uninfected lymphocytes in vitro, thus accelerating disease progression and CD4 depletion. Variability in TNF production between individuals is to a degree genetically determined and may be predicted from polymorphisms of microsatellite regions surrounding the human TNF gene locus. METHODS: We examined TNf microsatellite polymorphisms in 24 HIV-positive patients with slower disease progression (CD4 count > 400 x 10(6)/l at > or = 6 years), 20 HIV-positive patients with faster progression (CD4 count < 200 x 10(6)/l within 5 years) and 109 healthy controls resident in north-west England. Typing was performed by polymerase chain reaction amplification of TNF a, b, c and d microsatellites and alleles were defined using fluorescence-based semi-automated microsatellite mapping techniques. RESULTS: No significant differences in TNF a, b and d allele frequencies were observed between faster and slower progressors, or with healthy controls. The frequency of the TNF c2 allele was significantly different between HIV-positive slower (60.9%) and faster (15%) progressors (P = 0.002) with an odds ratio of 0.1 (95% confidence interval, 0-0.6). TNF c2 was also less frequent in faster progressors than in healthy controls (45.9%, P = 0.006) with an odds ratio of 0.2 (95% confidence interval 0-0.8). CONCLUSIONS: This is the first report demonstrating a strong association between the TNF c2 allele and the rate of HIV progression. Although it is possible that this finding may have arisen as a result of linkage disequilibrium with other alleles within the major histocompatibility complex that exert a more powerful effect upon progression, evidence is mounting to suggest that both TNF-alpha and lymphotoxin are closely involved in HIV disease progression and CD4 depletion. Our results serve to highlight the potential importance of genetic polymorphism, particularly of the TNF locus, in influencing the progression of HIV infection.

Adult↗

PubMed1997

Reductions in HIV-1 disease progression for zidovudine/lamivudine relative to control treatments: a meta-analysis of controlled trials.

OBJECTIVES: Four randomized double-blind trials have demonstrated that zidovudine/lamivudine (ZDV/3TC) reduces HIV RNA and raises CD4 counts relative to control treatments (ZDV or ZDV/zalcitabine (ddC)]. A meta-analysis of the clinical events in these trails was conducted to determine whether treatment with ZDV/3TC was also associated with a clinical benefit. DESIGN: The four trials, ZDV/3TC versus ZDV (NUCA3001, NUCB3001, NUCB3002) or versus ZDV/ddC (NUCA3002), were run concurrently, using the same doses of ZDV and 3TC. SETTING: Investigational sites in Europe and North America. PATIENTS: The trials recruited 972 HIV-1-positive, male and female patients aged > or = 18 years, with CD4 counts of 100-500 cells x 10(6)I. Two trials were for ZDV-naive patients and two were for ZDV pre-treated patients. MAIN OUTCOME MEASURES: Progression to first new Centers for Disease Control and Prevention (CDC) B or C event was compared between all ZDV/3TC arms and all control (ZDV, ZDV/ddC) arms. RESULTS: A total of 118 patients progressed to a first new CDC B/C event during the four trials, while 28 progressed to a new CDC event. Meta-analysis of the trials showed a 49% reduction in progression to new CDC B/C events (relative risk, 0.509; 95% confidence interval, 0.365-0.710; P < 0.0001) and a 66% reduction in progression to new CDC C events (relative risk, 0.344; 95% confidence interval, 0.169-0.700; P = 0.003) for the ZDV/3TC patients relative to the control patients. Reductions in progression to CDC B/C disease were seen in subgroups of naive and pre-treated patients, those with high and low CD4 counts and symptomatic and asymptomatic patients. CONCLUSIONS: ZDV/3TC combination treatment delays the progression of CDC B/C disease compared with control treatments. In view of the low incidence of CDC C events, the results for progression to CDC C disease should be interpreted with caution.

Adolescent↗

PubMed2004

Infection with concurrent multiple hepatitis C virus genotypes is associated with faster HIV disease progression.

OBJECTIVE: To elucidate the importance of hepatitis C Virus (HCV) genotype in HIV disease progression. DESIGN: This study was conducted among 126 HIV/HCV co-infected drug users with a known interval of HIV seroconversion whose HCV genotype was known early in HIV infection. Both clinical progression (to AIDS) and immunological progression (to a CD4+ T-cell count of 200 x 10(6) cells/l) by HCV genotype were studied using Cox proportional hazards analysis. RESULTS: The median duration of follow-up was 7.3 years [interquartile range (IQR), 4.6-10.1 years]. The majority of the HCV infections concerned genotype 1 and genotype 3; The distribution was: HCV type 1: 48%, HCV type 3: 34%, HCV type 4: 13%, multiple HCV types: 5%. Concurrent multiple infections consisted of HCV genotypes 1b+3a, 1b+4 and 3a+4. HCV genotype 1 and multiple HCV genotype infections were associated with faster immunological progression [hazard ratio (HR), 2.02; 95% confidence interval (CI), 1.04-3.92 and HR, 2.74; 95% CI, 0.95-7.90, respectively]. Multiple HCV genotype infection was also associated with faster clinical progression (HR, 3.36; 95% CI, 0.82-13.79). These hazard ratios increased further and were all significant when analyses were limited to data in the pre-HAART era (HR, 3.92; 95% CI, 1.51-10.20; HR, 4.38; 95% CI, 1.04-18.40 and HR, 6.54; 95% CI, 1.39-30.76, respectively). CONCLUSION: HIV disease progression differs by HCV genotype and is especially faster in individuals whose HCV infection involves more than one HCV genotype. The effect of HCV genotype on HIV progression was greater in the pre-highly active antiretroviral therapy (HAART) era, suggesting that the effectiveness of HAART may diminish the effect of HCV genotype on HIV disease progression.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Transient radiographic progression during initial treatment of pulmonary tuberculosis: CT findings.

PURPOSE: A study was undertaken to describe the thin-section CT features of transient radiographic progression during initial treatment of active pulmonary tuberculosis. METHOD: The CT scans of 13 patients who developed transient radiographic progression during initial treatment of pulmonary tuberculosis were evaluated and compared with those of 10 patients with true progression of pulmonary tuberculosis. Two patients underwent transbronchial lung biopsy for pathologic evaluation of new lesion. RESULTS: Eight patients had increased opacity at the site of their original lesion, whereas five had new opacities elsewhere: ipsilateral (n = 3) or contralateral (n = 1) to the original lesion or both (n = 1). Relatively extensive areas of ground-glass attenuation were concomitantly depicted in three of the eight patients with progression in the area of the original lesion. In those with progression ipsilateral or contralateral to the lesion, the character of the new lesions was ground-glass opacity and/or consolidation mainly in the subpleural region. Transbronchial lung biopsy specimens obtained from two patients showed intraluminal organizing exudates and thickened alveolar septa with lymphocyte infiltration, whereas the dominant CT findings of true progression of pulmonary tuberculosis were nodules (n = 8) or centrilobular nodules (n = 7). CONCLUSION: Thin-section CT may be useful to differentiate transient radiographic progression from true progression of pulmonary tuberculosis.

Adult↗

PubMed2001

Malignant cytological washings from prostate specimens: an independent predictor of biochemical progression after radical prostatectomy.

PURPOSE: Malignant cells have previously been identified in the cytological washings of prostate specimens obtained at radical prostatectomy for clinically localized prostate cancer. We investigated whether malignant cells in the cytological washings of radical prostatectomy specimens predict biochemical progression. The affect of total androgen blockade on cytological washings was also examined. MATERIALS AND METHODS: Cytological washings were obtained from radical prostatectomy specimens in 147 consecutive patients undergoing the procedure for clinically localized prostate cancer between November 1993 and April 1998. Of the 147 patients 54 were randomly selected to receive 1 month of total androgen blockade immediately before prostatectomy. To obtain the cytological specimen the extirpated prostate was subjected to a normal saline bath, as previously described. The cytology specimen was examined by a single cytopathologist blinded to preoperative and pathological findings. Biochemical progression, defined as prostate specific antigen 0.15 ng./ml. or greater, was determined using the Kaplan-Meier method. We also performed multivariate analysis of factors related to progression, including prostate specific antigen, pathological stage, margin status, Gleason grade and cytology status. Median followup was 37 months (range 13 to 66). RESULTS: Followup was available in 146 of 147 cases. Cytological washings were malignant in 14 of 92 patients (15%) who did not receive total androgen blockade preoperatively. In this group without androgen blockade the biochemical progression rate was significantly higher in those with positive cytology (p < 0.001). Positive cytology was an independent predictor of progression on multivariate analysis and a stronger predictor of progression than Gleason grade. No malignant cells were observed in cases of preoperative total androgen blockade (p < 0.001). However, biochemical progression was similar in the groups with and without androgen blockade (p = 0.355). CONCLUSIONS: Malignant cells may be identified in the cytological washings of radical prostatectomy specimens and they are an independent predictor of biochemical progression. One month of total androgen blockade preoperatively significantly decreases the rate of positive cytology but does not appear to change the rate of early biochemical failure.

Disease Progression↗

PubMed1997

Early detection of progression in adolescent idiopathic scoliosis by measurement of changes in back shape with the Integrated Shape Imaging System scanner.

STUDY DESIGN: A retrospective study of 78 patients with right thoracic idiopathic scoliosis was done. OBJECTIVES: To evaluate the reliability of the integrated Shape Imaging System scan (Oxford Metrics Ltd, Oxford, UK) in detecting progression of scoliosis and the use of back shape data in predicting scoliosis progression. SUMMARY OF BACKGROUND DATA: At first presentation and every 3-6 months during the follow-up period, all patients underwent integrated Shape Imaging System scans and radiographic examinations, from which the Cobb angle was measured. The follow-up period was 18-49 months (mean = 31.4 months). METHODS: Patients were divided into three groups according to the severity and progression of the Cobb angle. The spinal fusion, brace, and observation groups were compared using analysis of variance and the student's t test to detect significant differences among groups in the progression of deformity as measured by the integrated Shape Imaging System parameters and the Cobb angle. RESULTS: Three of the Integrated Shape Imaging System parameters detected significant progression in the spinal fusion group 1 year earlier than the Cobb angle. Only one of the Integrated Shape Imaging System parameters detected a significant difference in progression between the brace and observation groups. CONCLUSIONS: The Integrated Shape Imaging System technique demonstrated significant changes in this group of patients with progressive scoliosis. Serial measurements of back surface shape, particularly the size of the rib hump, may be predictive of progression. Serial Integrated Shape Imaging System scanning has advantages over serial radiography in the management of idiopathic scoliosis in addition to the avoidance of exposure to ionizing radiation.

Adolescent↗

PubMed2002

Acute progression of spondylolysis to isthmic spondylolisthesis in an adult.

STUDY DESIGN: Acute progression of spondylolysis to spondylolisthesis in an adult without degenerative disc disease at the slip level is reported. OBJECTIVE: To document a case of adult-onset progression of isthmic spondylolisthesis, in which the disc space height at the slip level was normal. There were no known risk factors for progression, and the olisthesis occurred acutely after minimal trauma. SUMMARY OF BACKGROUND DATA: Adult progression of spondylolysis to spondylolisthesis is reported infrequently because the highest risk for slip progression is before skeletal maturity. Previous reports documenting progressive slips in adults have uniformly related the olisthesis to progressive disc collapse and subluxation below the pars defect. METHODS: A 39-year-old woman was evaluated for a primary complaint of back and bilateral leg pain. Standing radiographs of her lumbar spine showed an L4-L5 and L5-S1 spondylolysis without spondylolisthesis. She had severe degenerative disc changes at L5-S1. The disc space height was normal at L4-L5. Two years later she was essentially immobilized by back pain after minimal trauma. Standing radiographs demonstrated a new Grade 2 L4-L5 isthmic spondylolisthesis. As demonstrated by magnetic resonance imaging, spontaneous reduction of the olisthesis has occurred with normal disc space height maintained. RESULTS: An L4-S1 anterior lumbar interbody fusion and posterior decompression and spinal fusion with instrumentation were performed without complication. At this writing, the patient has returned to work and is doing well 1 year after surgery. CONCLUSIONS: This case is important because it illustrates the potential for acute progression of spondylolisthesis with minimal trauma. A patient with known spondylolysis who sustains acute severe exacerbation of his or her back pain should have repeat standing radiographs.

Acute Disease↗

PubMed2002

Progressive supranuclear palsy: clinical and genetic aspects.

PURPOSE OF THE REVIEW: This review focuses on the recent additions to the literature in the clinical and genetic aspects of progressive supranuclear palsy. RECENT FINDINGS: Clinical features of progressive supranuclear palsy are reasonably well established and known to be quite characteristic. Recent epidemiological studies suggest that the disorder is more common than previously considered and that it is frequently misdiagnosed. New laboratory and novel imaging techniques are being tested and cerebrospinal fluid levels of tau protein have been found helpful in diagnosis. Pathological and biochemical studies in progressive supranuclear palsy brains have shown the predominance of hyperphosphorylated tau isoforms which contain the sequence encoded by exon 10 (4R) aggregated into filaments. Familial tauopathies linked to tau gene mutations showing clinical and neuropathological overlap with sporadic progressive supranuclear palsy have been described. Despite recent discoveries of the strong genetic association of sporadic progressive supranuclear palsy with tau gene polymorphisms, a specific risk allele for developing the palsy has not yet been identified yet. SUMMARY: Recent clinical studies and clinicopathological correlations are contributing significantly to the delineation of the clinical features of progressive supranuclear palsy. These features and the appropriate use of laboratory tests allow for an earlier identification of the disease and a more accurate premortem diagnosis. However, no specific biological markers for the disorder are available yet, and consequently diagnosis in the early stages or when some of the characteristic signs and symptoms are missing, remains a major challenge. Despite the recent advances in the understanding of genetic factors involved in progressive supranuclear palsy, the cause of the disease still remains unknown. Biochemical studies in brains from progressive supranuclear palsy patients provide a potential helpful instrument to improve the characterization of this disorder.

Humans↗

PubMed2004

New insights into progressive multifocal leukoencephalopathy.

PURPOSE OF REVIEW: Progressive multifocal leukoencephalopathy is a deadly demyelinating disease of the central nervous system, which occurs in immunosuppressed individuals. It is caused by a reactivation of the polyomavirus JC, which induces a lytic infection of oligodendrocytes. This review covers recent developments in the clinical and pathological presentations of progressive multifocal leukoencephalopathy, and advances in the understanding of JC virus biology. RECENT FINDINGS: The availability of highly active antiretroviral therapy has changed the clinical spectrum of progressive multifocal leukoencephalopathy in HIV-infected individuals; although the incidence has not diminished, mortality has decreased from 90% to approximately 50% during the first 3 months as a result of recovery of the immune system. More progressive multifocal leukoencephalopathy patients are now negative for JC virus in the cerebrospinal fluid by polymerase chain reaction, which calls for a new consensus terminology. Inflammatory forms of the disease are also becoming more frequent, and are associated with a strong cellular immune response mediated by JC virus-specific CD8 cytotoxic T lymphocytes, which are instrumental in preventing disease progression. SUMMARY: Advances in the understanding of JC virus biology have shed new light on the pathogenesis of progressive multifocal leukoencephalopathy, and on its possible role in cerebellar atrophy in HIV-infected individuals. Findings on the cellular immune response against the virus have direct implications for patient management, and may lead to new forms of immunotherapies for progressive multifocal leukoencephalopathy. An animal model of progressive multifocal leukoencephalopathy in non-human primates will facilitate the development of novel therapeutic strategies.

AIDS-Related Opportunistic Infections↗

PubMed2004

Progression of renal disease: new insights into risk factors and pathomechanisms.

PURPOSE OF REVIEW: Progression of renal failure, irrespective of the primary cause, is characterized by modification of renal structure, which culminates in terminal renal insufficiency. Interfering with progression continues to be a major challenge and is at the forefront of renal research. This review focuses on recent progress in the understanding of the mechanisms of progression and efforts to interfere with this process. RECENT FINDINGS: In addition to the long-known risk factors (hypertension and inadequate activation of the renin-angiotensin system), several novel risk factors and pathomechanisms, such as obesity, hyperglycemia, smoking, and several hormones, have recently been identified and investigated. Furthermore, the specific and blood pressure-independent pathogenetic roles of the sympathetic nervous system and the endothelin system in progression have been further clarified. Finally, novel animal models and techniques for studying specific aspects of progression have been developed and introduced. SUMMARY: Recently, considerable progress has been made concerning novel risk factors, understanding the underlying pathomechanisms, and interfering with the course of progression of renal diseases. Such improved insights will undoubtedly lead to new strategies in the future.

Animals↗

PubMed1998

The impact of chronic hepatitis C virus infection on HIV disease and progression in intravenous drug users.

OBJECTIVE: It is unclear whether co-infection with hepatitis C virus (HCV) can influence HIV related morbidity or mortality, either by accelerating HIV-related disease progression, or by contributing to end stage liver disease. The aim of this study was to examine the effect of HCV infection on the severity and progression of HIV disease in a cohort of Edinburgh intravenous drug users (IDUs). METHODS: In 240 (47%) out of 508 patients in the Edinburgh IDU cohort both HIV seroconversion dates and anti-HCV serology were available. Demographic variables and HIV-related progression between anti-HCV positive and anti-HCV negative groups were compared. Parameters assessed included clinical endpoints (time of development of significant symptoms attributable to HIV (CDC stage IV), time of development of AIDS, and time of death) and immunological endpoints (time of CD4+ counts dropping below 200/mm3, 100/mm3 and 50/mm3). RESULTS: Two hundred and two out of 240 patients (84%) had positive anti-HCV serology. There was no significant difference in the frequency of clinical and immunological endpoints between the anti-HCV positive and negative groups. Progression analysis from HIV seroconversion to HIV related clinical endpoints indicated that anti-HCV serology was not a significant factor influencing the rate of HIV progression (relative risks (RR) for anti-HCV positive group: seroconversion to CDC IV, 1.01; seroconversion to AIDS, 1.05; seroconversion to death, 0.90). Likewise, HCV serostatus did not significantly affect progression to immunological endpoints (RR for anti-HCV positive group: seroconversion to CD4+ < 200/mm3, 1.04; seroconversion to CD4+ < 100/mm3, 1.13; seroconversion to CD4+ < 50/mm3, 0.97. Overall mortality from end stage liver failure was 4% in HCV-seropositive patients without AIDS. This suggests that HCV has had a clinically (though not statistically) significant impact on overall survival in this cohort. CONCLUSIONS: This study demonstrates that HCV co-infection does not influence the rate of progression to either clinical or immunological endpoints in our population of HIV-infected drug users. Further data are required to assess the effect of HIV on thge progression of HCV-related liver disease.

Adult↗

PubMed2006

Geometric and electromyographic assessments in the evaluation of curve progression in idiopathic scoliosis.

STUDY DESIGN: The natural history of patients with idiopathic scoliosis was analyzed radiographically and electromyographically in a prospective longitudinal study. OBJECTIVES: To identify changes in geometric variables and the sequence in which these changes occur during curve progression in the natural history of patients with idiopathic scoliosis. In addition, to study the relationship between several geometric variables and electromyographic (EMG) measurements to determine their predictive value as risk factors to curve progression of the scoliotic deformity. SUMMARY OF BACKGROUND DATA: The main area of concern in treating children with adolescent idiopathic scoliosis is the unpredictability of curve progression during the early development of the deformity. METHODS: The changes in radiographic geometric and EMG variables between the first presentation and consecutive 4-6-month follow-up periods were analyzed in 105 patients with idiopathic scoliosis. Statistical analyses were performed to elucidate in more detail how spinal geometry evolves during curve progression. RESULTS: Curve severity was associated with remaining growth potential expressed as an increasing spinal growth velocity (SGV). With increasing SGV, an enhanced EMG activity at the lower part on the convex side of the curve expressed as EMG ratio was found. High EMG ratio was associated with increased axial rotation and diminished kyphosis before the rapid increase in Cobb angle. Lateral deviation, wedge angle, and axial rotation all increased during periods of progression. Changes in tilt angle and lordosis were not associated with curve progression. CONCLUSIONS: In the natural history of idiopathic scoliosis, SGV and EMG ratio at the lower end vertebra are prominent risk factors of curve progression. The asymmetric muscle activity is associated with increased axial rotation, which in its turn is associated with increasing Cobb angle and diminishing kyphosis. The combination of these variables provides insight in the physiologic and 3-dimensional biomechanical evolution of the natural history of curve progression in idiopathic scoliosis.

Adolescent↗

PubMed2005

Revisiting drug progression: long-range effects of early tobacco use.

AIMS: Drug progression models have been a cornerstone of scientific and public policy discussions for decades. These models have been criticized for their lack of causal mechanisms leading to drug dependence. Future research should focus on identification of pathways and covariates. This study re-examines tobacco use onset and progression to drug dependence in a multi-ethnic sample followed longitudinally from early to late adolescence (1990 to 1998-2000). METHODS: Data were collected in schools (n = 1208) during early adolescence (mean age 11.07), and subsequently face-to-face interviews were conducted at late adolescence (mean age 20.01). FINDINGS: Results indicated ethnic differences in rates and progression of tobacco use, with African Americans and foreign-born Latinos having larger proportions of abstainers and lower rates of persistent use. Most early adolescent smokers progressed to regular use. The odds of progression to marijuana abuse or dependence by later adolescence were highest (O.R. = 4.9) among persistent smokers, but not significant for foreign-born Latinos. The odds of progression to drug abuse or dependence were also highest (O.R. = 6.4) for persistent smokers, but not significant for African Americans. CONCLUSIONS: Implications for research on pathways and mechanisms of progression are discussed. Prevention programs may interrupt drug progression if they delay onset of tobacco use until mid-adolescence. Preventing targeted marketing efforts by the tobacco industry, regulating and enforcing tobacco control laws and pricing cigarettes at cost levels that adolescents find prohibitive are effective supplements to traditional behavior change interventions.

Adolescent↗

PubMed1995

Progression of coronary artery disease in non-dilated sites in the months following balloon angioplasty: time-dependent relation with restenosis.

There is scant information on the progression of coronary artery disease in non-dilated sites in the months following percutaneous transluminal coronary angioplasty (PTCA) or on its relationship with restenosis. To assess the incidence of this progression and its relationship with restenosis at various times after PTCA, the authors selected 371 consecutive patients who had undergone a first successful PTCA for angina on native coronaries followed by a repeat angiographic study. The angiograms were analysed by a computer-assisted method; progression was defined as a 20% decrease in diameter and restenosis as a 30% decrease in diameter or a return to > 50% stenosis. The relationship between progression and restenosis was analysed in the whole population and then, using the Mantel-Haenszel chi-square test, in two subgroups: patients with a stable clinical state, who were restudied routinely and those whose worsened state had prompted repeat angiography. The relationship was assessed at different times between angioplasty and the repeat angiography. Progression was observed in 80 patients (22%) and restenosis in 155 patients (42%). There was a highly significant relationship between progression and restenosis in the total population (chi 2 = 26.4, odds ratio = 3.9 and P < 0.0003) and in the group of patients that were routinely restudied (chi 2 = 31.6, odds ratio = 5.3 and P < 0.0001), but not in the group of patients in whom restudy was performed because of clinical worsening (chi 2 = 0.13, odds ratio = 1.5 and P = NS). With respect to the length of follow-up, in the total population the relationship was significant only at 6 and 7 months (P < 0.0001), and in the group receiving a routine restudy only at 4-5 and 6-7 months (P < 0.001). Progression in non-dilated sites appeared to be strongly and transiently linked with restenosis, suggesting that PTCA may enhance both restenosis and progression over a short period.

Aged↗

PubMed2005

Chronic hepatitis B virus infection in the Asia-Pacific region and Africa: review of disease progression.

Countries in the the Asia-Pacific region and Africa tend to have the highest prevalence of hepatitis B infection worldwide. Hepatitis B infection progresses from an asymptomatic persistently infected status to chronic hepatitis B, cirrhosis, decompensated liver disease and/or hepatocellular carcinoma. The aim of this review was to summarize rates and risk factors for progression between disease states in the Asia-Pacific region and Africa. A literature search was conducted employing MEDLINE and EMBASE (1975-2003) using the following key words: hepatitis B, natural history, disease progression, cirrhosis, hepatocellular carcinoma, mortality, Africa and the Asia-Pacific region. Bibliographies of articles reviewed were also searched. Ranges for annual progression rates were: (i) asymptomatic persistent infection to chronic hepatitis B, 0.84-2.7%; (ii) chronic hepatitis B to cirrhosis, 1.0-2.4%; and (iii) cirrhosis to hepatocellular carcinoma, 3.0-6.6%. Patients with asymptomatic persistent infection and chronic hepatitis B had relatively low 5-year mortality rates (<4%); rates (>50%) were much higher in patients with decompensated liver disease and hepatocellular carcinoma. No data were found for progression rates in African populations. Hepatitis B e antigen was a risk factor for chronic hepatitis B, and bridging hepatic necrosis in chronic hepatitis B increased the risk of cirrhosis. Risk factors for hepatocellular carcinoma included cirrhosis, co-infection with hepatitis C virus, and genetic and environmental factors. In this review, wide ranges of disease progression estimates are documented, emphasizing the need for further studies, particularly in Africa, where progression rates are largely not available. Summarizing information on factors associated with disease progression should assist in focusing efforts to arrest the disease process in those at most risk.

Africa↗

PubMed1999

High-risk types of human papillomavirus associated with the progression of cervical dysplasia to carcinoma.

OBJECTIVES: In the past several years, much evidence has accumulated that strongly implicates human papillomavirus (HPV) as an etiological agent of cervical cancer. However, the natural history of HPV infection is not yet completely understood, and at present there is no good marker to predict progression to invasive cancer in individual patients with dysplasia. METHODS: Tissue specimens from 45 patients with cervical dysplasia were classified as showing progression to carcinoma (progression group; 26 women), spontaneous regression (regression group; 16 women), and persistence (persistence group; 3 women). The presence of HPV 16, 18, 33, and 52 DNA was examined in 90 formalin-fixed, paraffin-embedded surgical and biopsy specimens of dysplasia using the PCR method, and the relationship between the presence of HPV and cervical carcinogenesis was analyzed. The mean follow-up period was 25.8 months in the progressed group and 34.0 months in both the persistent and regressed groups. The mean ages were 46.4 in the progressed group and 46.8 in the persistent and regressed groups. RESULTS: HPV 16, 18, 33, and 52 DNA were detected in 19 of the 26 patients (73.1%) in the progressed group. All patients with HPV 16, 18, or 52 DNA showed progression to carcinoma. The HPV 33 DNA was detected in 5 of the 16 patients (31.3%) in the regressed group and in 2 of the 3 patients (66.7%) in the persistent group, while HPV 16, 18, and 52 DNA were not detected in the 19 patients that comprised the regressed and persistent groups. CONCLUSION: This retrospective study suggests that cervical dysplasia in patients with high-risk types of HPV possessed the potential to progress to carcinoma in situ and eventually to invasive carcinoma as well.

Adult↗

PubMed2005

Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in relation to the patient's risk profile for progression.

Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) is a slowly progressing disease, with some patients progressing more rapidly than others. In 80% of patients who progress this is caused by the worsening of symptoms. The physician can predict the risk of progression from the patient's clinical profile; increased symptom severity, a poor maximum urinary flow rate (Qmax), and a high postvoid residual urine volume (PVR), are major risk factors for overall clinical progression of LUTS/BPH. A large baseline prostate volume and a high serum prostate-specific antigen (PSA) level are the predominant risk factors for developing acute urinary retention. After predicting risk, the most appropriate treatment should be established by balancing the benefits of treatment against the possible risks and bother resulting from adverse events. From the Medical Therapy Of Prostatic Symptoms study it can be concluded that monotherapy with an alpha1-adrenoceptor (AR) antagonist is an appropriate treatment for many patients with LUTS/BPH. However, for those at high risk of progression (those with a large prostate volume and high PSA level), it appears more appropriate to add a 5alpha-reductase inhibitor to the alpha1-AR antagonist to obtain maximum relief of symptoms, and ideally to halt the progression of the disease. This was confirmed by the RAND Appropriateness Method study, in which 12 urologists determined the most appropriate treatment for patients with LUTS/BPH based on their clinical profile, combination of clinical variables and/or risk factors. This study also indicates that patients at very high risk of progression, with severe obstruction (poor Qmax and high PVR), are potential candidates for immediate surgery.

5-alpha Reductase Inhibitors↗

PubMed2005

Role of calcium-phosphorous disorders in the progression of renal failure.

Among factors related to disturbed calcium-phosphate metabolism in chronic kidney disease, the following must be mainly considered as potential culprits in the progression of renal dysfunction: hyperphosphatemia, hyperparathyroidism, lack of active vitamin D, and possibly excess of the phosphaturic hormone FGF 23. Early experimental work suggested a parathyroid hormone (PTH)-independent beneficial role of phosphate restriction on progression in rats (animals with physiologic hyperphosphatemia), so that the generalization of the data is uncertain. Recent observational studies also found a correlation between S-phosphate and progression, but it remains uncertain whether the relationship is causal. There is very little direct experimental or clinical evidence for a role of PTH in accelerating progression, although the PTH1 receptor is expressed in podocytes and PTH affects podocyte function (i.e., Kf). It is undoubtedly a candidate that requires more sophisticated investigation. Recently, it has been shown that progression is significantly attenuated by calcimimetics (and equally by parathyroidectomy), but it is currently impossible to exclude a confounding effect of lower blood pressure values. The most solid evidence for an impact on progression exists for active vitamin D. In the past, it was widely assumed that vitamin D was "nephrotoxic." In retrospect, nephrotoxicity was the result of hypercalcemia. Recent evidence is overwhelming that 1,25(OH)2D3 and its analogues attenuate progression in noninflammatory and inflammatory models of chronic kidney disease. The main target cells identified so far are podocytes and mesangial cells. It is currently unknown whether the novel phosphaturic hormones have an impact on progression.

Aniline Compounds↗