Background. In view of the lack of evidence on the possibility of an economically viable, easy, and readily available biomarker to substitute the traditional role of CD4 counts in HIV disease progression, this study seeks to investigate the potential use of body mass index (BMI), haemoglobin (Hb), and total lymphocyte count (TLC) as surrogate biomarkers for monitoring the disease. Methods. This cross-sectional study was undertaken at the antiretroviral clinic (ART) of the Bomso Hospital, Kumasi, Ghana. We recruited 384 individuals who were 18 years or older and confirmed HIV seropositive patients. Blood samples were assayed for TLC and Hb. Weight and height were determined and BMI was calculated. Result. At a cut-off point of 12.15 g/dL, Hb had sensitivity and specificity of 73.9% and 56.8%, respectively, whereas BMI had 69.6% and 80.1% sensitivity and specificity, respectively. The sensitivity and specificity were also 100% among the studied participants at a cut-off point of 1200 mm−3 for TLC. There was a significant positive correlation between CD4 count and Hb (rho 0.262, p = 0.0001), BMI (rho 0.301, p = 0.0001), and TLC (rho 0.834, p = 0.0001). Conclusion. The study demonstrates that TLC, Hb, and BMI may provide some useful prognostic information independent of that provided by CD4 count.
Preeclampsia is a devastating pregnancy-associated disorder characterized by the onset of hypertension, proteinuria, and edema with limited plausible pathophysiology known. Cystatin-C, a novel marker for the detection of renal impairment, is increased in preeclampsia at an early stage. This study was aimed to evaluate the diagnostic efficiency of Cystatin-C as an early marker of renal function in preeclampsia comparing it to the traditional renal markers. A hospital based comparative cross-sectional study was performed on 104 women (52 diagnosed cases of preeclampsia and 52 healthy pregnant women). Concentrations of Cystatin-C, creatinine, urea, and uric acid were measured in both the study groups. Mean serum Cystatin-C and uric acid levels were elevated in preeclampsia cases compared to controls (1.15 ± 0.37 versus 0.55 ± 0.12; 5.40 ± 1.44 versus 3.97 ± 0.68, resp.). ROC curve depicted that Cystatin-C had the highest diagnostic efficiency (sensitivity, 88.24%; specificity, 98.04%) compared to creatinine and uric acid. Serum Cystatin-C consequently seemed to closely reflect the renal functional changes, which are believed to lead to increased blood pressure levels and urinary excretion of albumin and may thus function as a marker for the stage of the transition between normal adaptive renal changes at term and preeclampsia.
Background Several studies have investigated copeptin as a prognostic marker of different acute diseases and as a diagnostic marker in disorders of water and salt homeostasis. However, no data of the normal circadian rhythm of copeptin in healthy subjects are available. Aim To investigate the circadian rhythm of copeptin in healthy subjects under standardized conditions. Methods 19 healthy volunteers aged 18 to 53 years, male and female, were studied in a prospective observational study. In all 19 participants, blood samples for copeptin were taken in regular intervals of 30 minutes for 24 hours after a fasting period of minimum 8 hours. Results The mean values of copeptin showed a circadian rhythm, similar to that described for AVP release, with a trend towards higher levels (5.9 ± 1 pmol/L) at night and early morning between 4 am and 6 am and lowest levels (2.3 ± 0.2 pmol/L) in the late afternoon between 5 pm and 7 pm. This finding was only observed in individuals with initial higher copeptin levels, whereas in individuals with lower basal copeptin levels no circadian rhythm was observed. Conclusion There is evidence for a circadian rhythm in copeptin release during 24 hours, however, of minor extent. These findings suggest that copeptin levels can be determined irrespectively of the time of the day.
Background . The clinical diagnosis of pneumonia is sometimes difficult since chest radiographs are often indeterminate. In this study, we aimed to assess whether serum C-reactive protein (CRP) could assist in identifying patients with pneumonia. Methods . For one winter, all consecutive patients with acute respiratory symptoms admitted to the emergency ward of a single center were prospectively enrolled. In addition to chest radiographs, basic laboratory tests, and microbiology, serum levels of CRP were measured at entry. Results . A total of 923 (62.3%) of 1473 patients hospitalized for acute respiratory symptoms were included. Subjects with a final diagnosis of pneumonia had higher serum CRP levels (median 187 mg/L) than those with exacerbations of chronic obstructive pulmonary disease (63 mg/L) or acute bronchitis (54 mg/L, p<0.01). CRP was accurate in identifying pneumonia (area under the curve 0.84, 95% CI 0.82–0.87). The multilevel likelihood ratio (LR) for intervals of CRP provided useful information on the posttest probability of having pneumonia. CRP intervals above 200 mg/L were associated with LR+ > 5, for which pneumonia is likely, whereas CRP intervals below 75 mg/L were associated with LR < 0.2, for which pneumonia is unlikely. Conclusion . Serum CRP may be a useful addition for diagnosing pneumonia in hospitalized patients with acute respiratory symptoms.
Background. Biomarkers to distinguish latent from active Mycobacterium (M.) tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. Results. We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed). The median age was 15 years (range 4.5 to 49). Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3), in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1), and in controls it was 146.0 (40.3 to 200.0), with significantly higher levels in patients with active tuberculosis (p < 0.01). The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97) (p < 0.01). Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection.
Atrial fibrillation (AF) is the most common arrhythmia and is responsible for significant disease burden worldwide. Current evidence has suggested that systemic inflammatory response plays a crucial role in the initiation, maintenance, and progression of AF. So, recent efforts have been directed in search of measurable inflammatory biomarkers as additional tools in severity and prognosis assessment of AF. A simple, and easily obtainable, inflammatory marker is the neutrophil-lymphocyte ratio (NLR), which has shown good performance in preliminary studies as a potential prognostic biomarker in patients with AF. In this work, we performed a thorough review of clinical studies that evaluated the role of C-reactive protein (CRP), interleukin-6 (IL-6), and NLR as predictors of outcomes in AF. We gave a particular emphasis on the NLR because it is a simpler, widely available, and inexpensive biomarker.
The concept of disease-modifier genes as an element of genetic heterogeneity has been widely accepted and reported. The aim of the current study is to investigate the association between the promoter polymorphism TPH1 (rs10488682) and progression of idiopathic scoliosis (IS) in Eastern European population sample. A total of 105 patients and 210 healthy gender-matched controls were enrolled in this study. The TPH1 promoter polymorphism was genotyped by amplification followed by restriction. The statistical analysis was performed by Fisher's Exact Test. The results indicated that the genotypes and alleles of TPH1 (rs10488682) are not correlated with curve severity, curve pattern, or bracing. Therefore, the examined polymorphic variant could not be considered as a genetic factor with modifying effect of IS. In conclusion, this case-control study revealed no statistically significant association between TPH1 (rs10488682) and progression of IS in Eastern European population sample. These preliminary results should be replicated in extended population studies including larger sample sizes. The identification of molecular markers for IS could be useful for a more accurate prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures.
Objective. Use of tyramide signal amplification (TSA) to detect autophagy biomarkers in formalin fixed and paraffin embedded (FFPE) xenograft tissue. Materials and Methods. Autophagy marker regulation was studied in xenograft tissues using Amp HQ IHC and standard IHC methods. Results. The data demonstrate the feasibility of using high sensitivity TSA IHC assays to measure low abundant autophagy markers in FFPE xenograft tissue.
Variations of baseline plasma concentrations of creatine kinase (CK), heat shock protein 70 (HSP70), and interleukin 6 (IL-6) have been reported. We report categorical associations which may influence these protein levels. Methods. Blood was harvested for DNA and plasma protein analysis from 567 adults. Mean protein levels of CK, HSP70, and IL-6 were compared by sex, ethnicity, genetic variants-CKMM Nco1 (rs1803285), HSPA1B +A1538G (rs1061581), and IL6 G-174C (rs1800795)-self-reported history of exercise, oral contraceptive use, and dietary supplement use. Results. SNP major allele frequencies for CKMM, HSPA1B, and IL6 were 70% A, 57% A, and 60%. Mean CK statistically differed by sex, ethnicity, oral contraceptives, and caffeine. Plasma HSP70 differed by caffeine and protein. Mean IL-6 concentration differed by sex, ethnicity, and genotype. Plasma IL-6 was significantly lower (29%) in males (1.92 ± 0.08 pg/mL) and higher (29%) among African Americans (2.85 ± 0.50 pg/mL) relative to the others. IL6 G-174C GG genotype (2.23 ± 0.14 pg/mL) was 19% greater than CG or CC genotypes. Conclusion. Differences in baseline CK and IL-6 plasma protein concentrations are associated with genetics, sex, ethnicity, and the use of oral contraceptives, caffeine, and protein supplements in this young and athletic population.
Melanoma is the most malignant type of skin cancer. Early detection of melanoma is thus critical for patient prognosis and survival. At present, examination by a skilled dermatologist followed by biopsy of suspicious lesions is the diagnostic gold standard. The aim of the present study was to examine an alternative and noninvasive method for the diagnosis of melanoma at an early stage. We identified and compared the volatile organic compounds (VOCs) in mouse urine and feces, before and after a subcutaneous injection of B16 melanoma cells. We identified a total of 16 VOCs in urine and 13 VOCs in feces that could serve as potential biomarkers. Statistical analysis significantly discriminated between the cancer and control groups. These results should be validated in a larger-scale animal study, after which a study could be designed in patients to develop a melanoma biomarker.
An early diagnosis and appropriate treatment are crucial in reducing mortality among people suffering from cancer. There is a lack of characteristic early clinical symptoms in most forms of cancer, which highlights the importance of investigating new methods for its early detection. One of the most promising methods is the analysis of volatile organic compounds (VOCs). VOCs are a diverse group of carbon-based chemicals that are present in exhaled breath and biofluids and may be collected from the headspace of these matrices. Different patterns of VOCs have been correlated with various diseases, cancer among them. Studies have also shown that cancer cells in vitro produce or consume specific VOCs that can serve as potential biomarkers that differentiate them from noncancerous cells. This review identifies the current challenges in the investigation of VOCs as potential cancer biomarkers, by the critical evaluation of available matrices for the in vivo and in vitro approaches in this field and by comparison of the main extraction and detection techniques that have been applied to date in this area of study. It also summarises complementary in vivo, ex vivo, and in vitro studies conducted to date in order to try to identify volatile biomarkers of cancer.
Acute pancreatitis is a potentially life threatening disease. The spectrum of severity of the illness ranges from mild self-limiting disease to a highly fatal severe necrotizing pancreatitis. Despite intensive research and improved patient care, overall mortality still remains high, reaching up to 30–40% in cases with infected pancreatic necrosis. Although little is known about the exact pathogenesis, it has been widely accepted that premature activation of digestive enzymes within the pancreatic acinar cell is the trigger that leads to autodigestion of pancreatic tissue which is followed by infiltration and activation of leukocytes. Extensive research has been done over the past few decades regarding their role in diagnosis and prognostic evaluation of severe acute pancreatitis. Although many standalone biochemical markers have been studied for early assessment of severity, C-reactive protein still remains the most frequently used along with Interleukin-6. In this review we have discussed briefly the pathogenesis and the role of different biochemical markers in the diagnosis and severity evaluation in acute pancreatitis.
Idiopathic scoliosis (IS) is the most common spinal disorder in children and adolescents. The current consensus on IS maintains that it has a multifactorial etiology with genetic predisposition factors. In the present study the association of two functional polymorphisms ofleptin(rs7799039) andBMP4(rs4898820) with susceptibility to IS and curve severity was investigated in a Bulgarian population sample. The molecular detection of the genotypes was performed by amplification followed by restriction technology. The statistical analysis was performed by Pearson’s chi-squared test. This case-control study revealed no statistically significant association between the functional polymorphisms ofleptinandBMP4and susceptibility to IS or curve progression (p>0.05). On the basis of these results the examined polymorphic variants ofleptinandBMP4could not be considered as genetic variants with predisposition effect or as risk factors for the progression of the curve. In addition, these results do not exclude a synergistic effect of the promoter polymorphisms ofleptinandBMP4in the etiology and pathogenesis of IS. The identification of molecular markers for IS could be useful for early detection and prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures.
Granulomatosis with polyangiitis (GPA) is a small blood vessel vasculitic disorder with a high mortality rate if undiagnosed or treated inadequately. Disease relapse is a key feature of this disease and early identification of relapse episodes is very important in limiting end-organ damage. The advent of indirect immunofluorescence to detect antineutrophil cytoplasmic antibody (ANCA) with specific reactivity against the enzyme proteinase-3 (PR3) has been very useful in the diagnosis of GPA but is less helpful in predicting relapse. Indeed, up to date no satisfactory biomarker has been identified that can reliably predict relapse. This study assessed the probability of the occurrence of a relapse when a change was noted in a range of commonly used laboratory tests. These tests included levels of C-reactive protein (CRP), anti-PR3 antibodies, ANCA titre, and the neutrophil count. A group of 30 GPA patients with a total of 66 relapse episodes was investigated and a novel clinical yield score was devised. When a combined rise in CRP, anti-PR3 antibodies, and neutrophil count was observed in the 6-month period before a relapse event, 59% of patient relapses could be predicted. Monitoring changes in this set of parameters helps identify disease relapse.
Prostate cancer (PCA) is a major health concern in current times. Ever since prostate specific antigen (PSA) was introduced in clinical practice almost three decades ago, the diagnosis and management of PCA have been revolutionized. With time, concerns arose as to the inherent shortcomings of this biomarker and alternatives were actively sought. Over the past decade new PCA biomarkers have been identified in tissue, blood, urine, and other body fluids that offer improved specificity and supplement our knowledge of disease progression. This review focuses on superiority of circulating biomarkers over tissue biomarkers due to the advantages of being more readily accessible, minimally invasive (blood) or noninvasive (urine), accessible for sampling on regular intervals, and easily utilized for follow-up after surgery or other treatment modalities. Some of the circulating biomarkers like PCA3, IL-6, and TMPRSS2-ERG are now detectable by commercially available kits while others like microRNAs (miR-21, -221, -141) and exosomes hold potential to become available as multiplexed assays. In this paper, we will review some of these potential candidate circulating biomarkers that either individually or in combination, once validated with large-scale trials, may eventually get utilized clinically for improved diagnosis, risk stratification, and treatment.
Colorectal cancer (CRC) is the third common carcinoma with a high rate of mortality worldwide and several studies have investigated some molecular and clinicopathological markers for diagnosis and prognosis of its malignant phenotypes. The aim of this study is to evaluate expression frequency of PAGE4, SCP-1, and SPANXA/D cancer testis antigen (CTA) genes as well as some clinical risk markers to predict liver metastasis of colorectal cancer patients. The expression frequency of PAGE4, SCP-1, and SPANXA/D cancer/testis antigen (CTA) genes was obtained using reverse transcription polymerase chain reaction (RT-PCR) assay in 90 colorectal tumor samples including both negative and positive liver metastasis tumors. Statistical analysis was performed to assess the association of three studied genes and clinical risk factors with CRC liver metastasis. The frequency of PAGE4 and SCP-1 genes expression was significantly higher in the primary tumours with liver metastasis when statistically compared with primary tumors with no liver metastasis (P < 0.05). Among all clinical risk factors studied, the lymph node metastasis and the depth of invasion were statistically correlated with liver metastasis of CRC patients. In addition, using multiple logistic regression, we constructed a model based on PAGE4 and lymph node metastasis to predict liver metastasis of CRC.
Chronic alcohol consumption is reported to be associated with increase in plasma homocysteine levels which is further influenced by the polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene. The present study aims to understand the extent of the MTHFR C677T polymorphism in alcohol dependent (AD) cases of Meiteis of Manipur, a Mendelian population of India. MTHFR C677T polymorphism was screened in 313 controls and 139 alcohol dependent (AD) cases who all met DSM-IV criteria for alcohol dependence. Both AD cases and controls were unrelated up to 1st cousin. Among the control group, different drinking patterns like abstainer/nondrinkers (NDs), occasional drinkers (ODs), and moderate drinkers (MDs) are included. Both the groups were found to be in Hardy-Weinberg equilibrium (P > 0.05). Genotypic and allelic frequency distribution of MTHFR C677T polymorphism did not differ significantly between AD cases and controls (P > 0.05). However, individuals carrying mutant (T) allele show more than 1-fold increased risk for AD though not significant (OR = 1.43; 95% CI 0.41–5.01, P > 0.05). In conclusion, MTHFR C677T polymorphism is not found to be risk marker for AD in present studied population. However, higher prevalence of the mutant T allele may exacerbate deleterious health risk in future especially among alcohol drinkers.
Granulomatosis with polyangiitis (GPA) is a small blood vessel vasculitic disorder with a high mortality rate if undiagnosed or treated inadequately. Disease relapse is a key feature of this disease and early identification of relapse episodes is very important in limiting end-organ damage. The advent of indirect immunofluorescence to detect antineutrophil cytoplasmic antibody (ANCA) with specific reactivity against the enzyme proteinase-3 (PR3) has been very useful in the diagnosis of GPA but is less helpful in predicting relapse. Indeed, up to date no satisfactory biomarker has been identified that can reliably predict relapse. This study assessed the probability of the occurrence of a relapse when a change was noted in a range of commonly used laboratory tests. These tests included levels of C-reactive protein (CRP), anti-PR3 antibodies, ANCA titre, and the neutrophil count. A group of 30 GPA patients with a total of 66 relapse episodes was investigated and a novel clinical yield score was devised. When a combined rise in CRP, anti-PR3 antibodies, and neutrophil count was observed in the 6-month period before a relapse event, 59% of patient relapses could be predicted. Monitoring changes in this set of parameters helps identify disease relapse.
The present study aimed to determine the day to day variability and reliability of several blood oxidative stress markers at rest in a healthy young cohort over a four-week period. Twelve apparently healthy resistance trained males (24.6 ± 3.0 yrs) were tested over 7 visits within 4 weeks with at least 72 hrs between visits at the same time of day. Subjects rested 30 minutes prior to blood being obtained by vacutainer. Results. The highest IntraClass correlations (ICC's) were obtained for protein carbonyls (PC) and oxygen radical absorbance capacity (ORAC) (PC = 0.785 and ORAC = 0.780). Cronbach's α reliability score for PC was 0.967 and for ORAC was 0.961. The ICC's for GSH, GSSG, and the GSSG/TGH ratio ICC were 0.600, 0.573, and 0.570, respectively, with Cronbach's α being 0.913, 0.904, and 0.903, respectively. Xanthine oxidase ICC was 0.163 and Cronbach's α was 0.538. Conclusions. PC and ORAC demonstrated good to excellent reliability while glutathione factors had poor to excellent reliability. Xanthine oxidase showed poor reliability and high variability. These results suggest that the PC and ORAC markers were the most stable and reliable oxidative stress markers in blood and that daily changes across visits should be considered when interpreting resting blood oxidative stress markers.
