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Atypical immature cervical metaplasia: immunoprofiling and longitudinal outcome.

Atypical proliferations of immature cervical squamous metaplasia were reviewed and correlated with p16 and Ki-67 expression to determine whether immunoprofiling could enable more conventional classification. The longitudinal outcome of atypical immature metaplasia (AIM) and predictive role of biomarker expression were also investigated. All atypias of immature squamous metaplasia in the year 2000 were reviewed and stained with p16 and Ki-67. Biomarker features were evaluated and the Ki-67 index calculated. Diagnoses were correlated with the immunoprofile of each antibody, both separately and combined. The progression to squamous intraepithelial lesion (SIL) of lesions reclassified as AIM was determined, and biomarker immunoprofiles were correlated with outcome. The 172 atypias were reviewed as 3 (1.7%) negative, 54 (31.4%) benign, 60 (34.9%) AIM, 43 (25%) low-grade SIL (LSIL), and 12 (6.9%) high-grade SIL (HSIL). HSIL correlated significantly with a combined high index (>15%) and p16 diffusely positive profile (P = .01). Benign diagnoses correlated significantly with a low index (1%-15%) and p16 negative or focal profile (P = .01). AIM and LSIL correlations were not significant, but their profiles were very variable and nearly identical. AIM was the only pathology in 43 cases, and follow-up was available for 32 (74.4%). SIL developed in 66% (50% LSIL and 16% HSIL) and p16 positivity correlated (P = .02). p16 and Ki-67 immunoprofiling are reliable in reclassifying some atypical proliferations of immature squamous metaplasia as HSIL and some as benign. The similarity between AIM and LSIL in regard to their immunoprofile as well as outcome suggests AIM is a morphological type of LSIL.

Biomarkers, Tumor↗

The role of biomarkers in the assessment of lupus.

Although considered a prototypic autoimmune disease, the hallmark of systemic lupus erythematosus (SLE) is its heterogeneity. Accordingly, manifestations can vary widely from person to person, with the potential involvement of virtually any bodily organ. Furthermore, the genetic abnormalities underlying this condition are complicated, with diverse genetic polymorphisms described in different ethnic groups, strongly suggesting that the actual pathology underlying the immunologic disarray might not be the same for each patient. Evolving concepts of genetics and immunity have clarified that patients can carry unique arrays of exacerbating and protective factors. These factors, in conjunction with variable environmental triggers for SLE, probably determine the sequelae that an individual experiences. Therefore, it is not surprising that the clinical manifestations are diverse, the temporal sequence of organ involvement often unpredictable, and that the flares of inflammatory activity that characterize SLE can either remit without consequence or leave permanent damage in their wake. It is widely accepted that the current standard of care for SLE patients is inadequate. Programs to develop and test new drug and/or device therapies have been ongoing since the mid-1990s but have encountered formidable obstacles. With the current burst of drug discovery and the advent of several large international trials of promising new agents, the challenge to overcome these obstacles has never been greater. A burgeoning literature in the past decades nevertheless suggests that despite the complexities of the many immunologic pathways that impact on SLE, characteristic biologic markers are emerging as potential signposts that can characterize patient subgroups, predict prognosis, mark the exacerbations and remissions of SLE flares, and serve as endpoints in the determination of the dosing and timing of immune-modulating treatments. Several of the promising biomarkers are addressed in this chapter.

Biomarkers↗

Profiling alternatively spliced mRNA isoforms for prostate cancer classification.

BACKGROUND: Prostate cancer is one of the leading causes of cancer illness and death among men in the United States and world wide. There is an urgent need to discover good biomarkers for early clinical diagnosis and treatment. Previously, we developed an exon-junction microarray-based assay and profiled 1532 mRNA splice isoforms from 364 potential prostate cancer related genes in 38 prostate tissues. Here, we investigate the advantage of using splice isoforms, which couple transcriptional and splicing regulation, for cancer classification. RESULTS: As many as 464 splice isoforms from more than 200 genes are differentially regulated in tumors at a false discovery rate (FDR) of 0.05. Remarkably, about 30% of genes have isoforms that are called significant but do not exhibit differential expression at the overall mRNA level. A support vector machine (SVM) classifier trained on 128 signature isoforms can correctly predict 92% of the cases, which outperforms the classifier using overall mRNA abundance by about 5%. It is also observed that the classification performance can be improved using multivariate variable selection methods, which take correlation among variables into account. CONCLUSION: These results demonstrate that profiling of splice isoforms is able to provide unique and important information which cannot be detected by conventional microarrays.

Algorithms↗

Computerized quantitative pathology for the grading of dysplasia in surveillance biopsies of Barrett's oesophagus.

Decision models for surveillance of Barrett's oesophagus (BO) are governed by the grade of dysplasia on endoscopic biopsy, but subjective grading is prone to observer variation. Computerized morphometry and immunoquantitation can objectively discriminate between different grades of dysplasia in oesophagectomy specimens with BO. The present study evaluated the feasibility of such quantitative analysis on surveillance biopsies of BO. Biopsy criteria for quantitative analysis were defined, excluding 101 (21%) of 472 archival BO surveillance biopsies. In the remaining haematoxylin and eosin (H&E) sections, 105 areas that distinctively displayed no dysplasia (ND), low-grade dysplasia (LGD) or high-grade dysplasia (HGD) were demarcated. Agreement on double-blind examination by two experienced pathologists was reached in 66 areas (63%; kappa: 0.44). For 21 ND/LGD and 11 LGD/HGD disagreement areas, corresponding sections for p53 and Ki67 immunohistochemistry were available. The best combination of two discriminating features was stratification index (SI) with p53 area % for ND versus LGD (89% correct classification), and SI with Ki67 area % for LGD versus HGD (91% correct classification). Fifteen of the 21 ND/LGD disagreement areas could be classified uniquely as either ND or LGD by SI and p53, and eight of the 11 LGD/HGD disagreement areas as either LGD or HGD by SI and Ki67. Correlation coefficients for repeated measurements of SI, Ki67, and p53 by the same observer were 0.94, 0.92, and 0.86, and by two independent observers 0.86, 0.93, and 0.92, respectively. Computerized quantitative pathology on BO surveillance biopsies is feasible provided that well-defined biopsy criteria are used. Using a combination of features associated with cellular differentiation and proliferation, such as SI, p53, and Ki67, quantitative pathological analysis assists in reducing diagnostic variability in the grading of dysplasia during surveillance of BO.

Barrett Esophagus↗

Sucrase-isomaltase is an independent prognostic marker for colorectal carcinoma.

PURPOSE: Expression of disaccharidase sucrase-isomaltase (SI) is significantly enhanced during neoplastic transformation of colonic epithelium. Our study was designed to determine whether expression of SI within primary tumors was significantly associated with survival in patients with colorectal carcinoma (CRC). METHODS: SI expression was analyzed by immunohistochemistry in paraffin sections from 182 Stage I to III CRC that had been resected for cure at the New England Deaconess Hospital between 1965 and 1977. Expression was scored as absent or present in 1 to 50 percent or more than 50 percent of tumor cells. Associations were explored among SI expression, other clinical or pathologic variables, and overall survival. The data set is mature, with 91 (56 percent) patients who had died of CRC at a median follow-up of 96 months. RESULTS: Fifty-five percent of primary CRC expressed SI. When the multivariate Cox analysis was performed, nodal status, T stage, primary site, grade, and SI expression were independent covariates. SI expression was not associated with the expression of other clinicopathologic variables but increased the risk of death from colorectal carcinoma by 1.83-fold. DISCUSSION: These results indicate that SI is a prognostic marker for CRC that is independent of stage-related variables in patients who have undergone potentially curative resections.

Aged↗

Geographic variation in hematological variables in adult and prefledgling herring gulls (Larus argentatus) and possible associations with organochlorine exposure.

The objectives of this study were (1) to describe variation in hematological values found in adult and prefledgling herring gulls (Larus argentatus) over a large geographic area, (2) to investigate relationships between hematological variables and other physiological indices, and (3) to examine potential associations between exposure to organochlorines and hematological variables. During 1991-93, we sampled 160 breeding adult gulls from 13 colonies and 101 4-week-old gulls from 11 colonies. All colonies were in the Great Lakes ecosystem, except for two colonies on Lake Winnipeg and the Atlantic coast. The hematological values measured in this study were similar to published values for herring gulls and related species. Significant intersite differences were found in hematological variables. Sex had little or no influence on leukocyte variables. Adults had lower total leukocyte counts and higher heterophil to lymphocyte ratios than chicks. PCV was lower in adult females than males. In adults, total leukocyte and total heterophil numbers were negatively associated with liver activity of ethoxyresorufin-O-deethylase (EROD) and concentrations of highly carboxylated porphyrins (HCPs), two biomarkers of organochlorine exposure. Total leukocyte and total heterophil numbers were positively associated with liver concentrations of DDE (1, 1-dichloro-2,2-bis(p-chlorophenyl)ethylene), and total lymphocytes were associated positively with PCB (polychlorinated biphenyl) and HCP concentrations. The heterophil to lymphocyte ratio was negatively associated with liver EROD activity and HCPs. In chicks, there was a positive association between the heterophil to lymphocyte ratio and HG-TEQs (dioxin toxicity equivalents calculated using herring gull-specific equivalency factors). PCV was associated with some measures of contaminant exposure in adults and chicks. Additional research is needed to elucidate causal relationships between hematological indices and such factors as contaminants, disease, and nutrition.

Age Factors↗

Identification of lymphatic endothelium in pediatric vascular tumors and malformations.

The distinction between lymphatic and other vascular vessels on microscopic sections is a challenging task. D2-40, a novel antibody, has been reported to be selective for lymphatic endothelium. We studied the specificity and sensitivity of D2-40 in pediatric vascular tumors and malformations. Fourteen lymphatic and 11 vascular lesions were randomly selected and stained with D2-40 and CD31 antibodies. The lymphatic lesions included 6 lymphatic malformations, 5 cystic hygromas (macrocystic lymphatic malformation), 2 lymphovenous malformations, and 1 lymphangioma, and the vascular lesions comprised 3 infantile hemangiomas, 3 Kaposiform hemangioendotheliomas, 2 tufted angiomas, 1 pyogenic granuloma, 1 arteriovenous, and 1 venulocapillary malformations. The staining patterns of the vascular channels were compared. In all lesions D2-40 labeled only the endothelium of thin-walled vascular channels morphologically consistent with lymphatic vessels (25 of 25). No staining of the vascular lesions (0 of 11) or of arteries and veins (0 of 25) was observed. All lymphatic lesions had D2-40-positive vessels; however, the percentage of vessels that stained varied. Five lymphatic lesions showed more than 75% D2-40-positive channels, 5 lesions had approximately 50%, and 4 cases showed fewer than 25% D2-40-positive channels. There was a tendency of more consistent D2-40 staining of small versus large lymphatic channels. CD31 constantly labeled arteries, veins, capillaries, and lymphatics in all lesions and all endothelial cells in the vascular lesions. D2-40 is a very specific antibody for lymphatic endothelium, with variable sensitivity. CD31 more reliably identifies lymphatic endothelium. Currently, D2-40 appears to be a good marker to identify lymphatic vessels in pediatric vascular tumors and malformations.

Adolescent↗

Screening for Down syndrome during the first and second trimesters: impact of risk estimation parameters.

OBJECTIVES: To evaluate impact of risk estimation parameters for screening for Down Syndrome during the first and second trimesters. METHODS: We prospectively examined for their performance in the prenatal prediction of trisomy 21, alphafetoprotein (AFP), unconjugated estriol (uE3), total human chorionic gonadotropin (hCG), and its free subunits (free alpha-hCG, free beta-hCG) at both the first and second trimesters, and the impact of three sets of published risk estimation parameters. A total of 14,612 pregnancies were studied. All Down syndrome specimens (12 and 11 cases for first and second trimesters, respectively) and a sample of the unaffected pregnancies were analyzed. RESULTS: The median multiple of median (MoM) for total hCG was lower in the first trimester (1.83 vs. 2.01 in the second trimester) but no loss in discriminative power was observed if the lower variability of the results in the first trimester is taken into account (interquartile range of 0.251 vs. 0.338). The choice of distribution parameters did not alter significantly the detection rates for the various combinations of markers (p > 0.05). False positive rates were affected significantly however and for the combination AFP-uE3-free beta-hCG they varied from 14.6% to 22.6% (p < 0.001). CONCLUSIONS: Our results suggest that specific distribution parameters would be necessary to account for the lower variability of the markers in the first trimester and the peculiarity of the total hCG assay we used.

Adult↗

Sex-dependent variables in the modulation of postalimentary lipemia.

OBJECTIVE: To quantify in young adults the sex-dependent differences in lipemic responses to a fat meal, we measured the association of these responses with markers of atherosclerosis and determined their metabolic regulators. METHODS: Forty-nine normolipidemic volunteers, 25 women and 24 men, were matched according to age, body mass index, waist circumference, diet, physical activity, and apolipoprotein-E phenotyping. After receiving a standardized fat meal (40 g of fat/m2 of body surface area), serial blood samples were drawn for laboratory analysis. Common carotid intima-media thickness was measured. RESULTS: The lipemic responses were much greater in men than in women for plasma triacylglycerol (TAG), cholesterol, and TAG in TAG-rich lipoproteins, non-esterified fatty acids, phospholipids, and apolipoprotein-B100. Men presented with increased blood pressure, carotid intima-media thickness, TAG, hepatic lipase, and insulin and lower high-density lipoprotein cholesterol, apolipoprotein-AI, and non-esterified fatty acid concentrations. Only in men did carotid intima-media thickness correlate marginally with titers of autoantibodies to epitopes of oxidized low-density lipoprotein; in addition, phospholipids and cholesteryl esters were negatively related to autoantibodies. Multivariate analysis indicated that age (R2 = 45%), waist circumference (R2 = 19%), phospholipids (R2 = 39%), non-esterified fatty acids (R2 = 29%), insulin (R2 = 17%), lipoprotein lipase activity (R2 = 16%), and cholesteryl ester transfer protein (an exploratory variable; R2 = 6%) are strong determinants of postalimentary lipemia in women and that only insulin (R2 = 55%) and phospholipids (R2 = 37%) are determinants in men. CONCLUSIONS: We have provided data explaining that postalimentary lipemia is differently regulated by sex. Several risk factors for coronary heart disease and significant associations with atherosclerosis biomarkers were found only in men.

Adult↗

Variability of nitric oxide metabolites in exhaled breath condensate.

The collection of exhaled breath condensate (EBC) is simple and non-invasive, however, there are few data on the methodological aspects affecting concentrations of compounds in EBC. The aim of this study was to investigate methodological issues for measuring nitric oxide metabolites (NO(x)) in EBC. Twenty-five healthy adults (12 females, age range 23-55 years) and 22 children (11 females, age range 7-6 years) were recruited for studies investigating inter- and intra-day repeatability, repeatability with controlled expiratory flows and temperature, flow dependence, and analytical variability of EBC NO(x). Both intra- and inter-day repeatability was poor with a coefficient of repeatability of 103.4% of the mean difference between intra-day (15 min) measures and 118.6% of inter-day (24 h) differences. Repeatability was not improved when expiratory flow and temperature of the collection device were controlled. However, some of the variability (approximately 50%) may be accounted for by variability in the analytical technique (analytical variability) and this may result from difficulties in controlling for contamination. NO(x) levels were not affected by different expiratory flows in either adults or children but there was still significant variation within individuals. Levels of NO(x) in EBC seem to be highly variable and this needs to be considered if EBC NO(x) is to be used in clinical studies.

Adult↗

Prognostic impact of Cyfra21-1 and other serum markers in completely resected non-small cell lung cancer.

PURPOSE: The aim of this prospective study was to assess the prognostic impact of serum tumor markers (Cyfra21-1, carcinoembryonic antigen, neuron-specific enolase, squamous cell carcinoma-antigen and TPAcyk) in patients with non-small cell lung cancer (NSCLC) receiving complete resection. METHODS: Sixty-seven patients with histologically proven NSCLC and complete resection of stage I-IIIA disease were included. The serum levels of all markers were measured using commercially available immunoassays. RESULTS: With a median follow-up of 86 months for surviving patients, those with initial Cyfra21-1 serum levels higher than 3.57 ng/ml had a significantly worse prognosis (P=0.014). The remaining serum tumor markers showed no prognostic impact. In a Cox regression model, Cyfra21-1 proved to be an independent prognostic factor for both overall survival and disease-free interval. In addition, Cyfra21-1 sustained as an independent prognostic factor in completely resected stage I/II disease. CONCLUSIONS: With a cut-off value of 3.57 ng/ml, Cyfra 21-1 was an independent prognostic factor for survival in NSCLC-patients with complete resection. Further evaluation is needed, particularly in stage I/II disease. When the prognostic impact is confirmed with larger patient numbers this may contribute to the identification of stratification variables for future treatment approaches of NSCLC.

Antigens, Neoplasm↗

[Pulmonary activity in sarcoidosis: 67Ga uptake quantification and plasma determination of 1,25-dihydroxyvitamin D)].

AIM: The aim of our study was to produce a quantitative determination of Ga-67 pulmonary intake and correlate it with plasma levels of calcitriol. MATERIAL AND METHODS: A prospective study was conducted, and included 65 patients (29 female, 36 male) referred to our section due to suspected sarcoidosis or fibrosis of the lungs. Gammagraphic images were obtained after injecting Ga-67 citrate, and vitamin D was determined by IRMA method. The final diagnosis led to 4 groups of patients: 26 with active sarcoidosis; 5 with inactive sarcoidosis (4 with a previous gammagraphic study, included in the previous group); 8 with fibrosis of the lungs; and 30 patients with no demonstrable pathology following medical/instrumental examination. For the quantitative analysis, areas of interest were drawn around each lung, together with another region in soft tissue of the right shoulder (background). The geometric mean for each region was calculated, as well as the Ga intake rate (InGa = [lung activity-background]/background). RESULTS: Significant differences were found (p<0.01) when comparing each group's InGa, with the highest values occurring in the active sarcoidosis group. No significant differences were found when comparing plasma levels of calcitriol. No significant correlation was demonstrated between hormone and InGa rates. CONCLUSIONS: InGa would seem to be a useful parameter for assessing inflammatory activity in the parenchyma of the lungs. Perhaps as a result of their variability, plasma concentrations of the active vitamin D metabolite have a limited role in this assessment.

Biomarkers↗

Acinar phenotypes in salivary pleomorphic adenoma: unusual differentiation or disordered functional activity?

To explain the occurrence in salivary pleomorphic adenoma of structures with an arrangement and appearance of tumour cells resembling acini, two tumours showing such structures and, for comparison, a tumour showing goblet cells were examined with the use of histochemistry and immunocytochemistry for constituents of the salivary secretory process. One tumour consisted mainly of slightly granular cells with an acinar arrangement, which contained neutral and carboxylated glycoproteins, -SH groups and cytoplasmic epithelial membrane antigen. The second tumour showed a minor component of structures resembling mucous acini, which contained neutral and carboxylated glycoproteins, -SS- groups and fucoglycoconjugates. The goblet cells of the third tumour contained sulphated glycoproteins and were associated with cystic lumina. Acinar phenotypes in salivary pleomorphic adenoma could reflect either an unusual line of differentiation or luminal cells with increased synthesis and/or retention of variably mature glycoproteins different from those of goblet cells. Disordered secretion and externalization of glycoproteins are possible factors influencing phenotypes in this tumour.

Adenoma, Pleomorphic↗

Radioimmunometric assay of natriuretic peptide type-B (BNP) in heart failure.

The aim of this study was to assess the value of the radioimmunometric determination of natriuretic peptide type-B (brain natriuretic peptide, BNP) in the diagnosis and prognosis of heart failure, and to study the association between BNP and the clinical, analytical and echocardiographic variables associated with the evolution of heart failure. The study group included 169 patients (74 women and 95 men; mean, 66 years) with heart failure of different causes, admitted consecutively to our hospital. BNP levels were measured with a radioimmunometric assay (Shionora BNP Cis ) after day 3 of admission. Patients were also studied by echocardiography. A significant association between the cause of heart failure and the BNP concentration was found (patients with ischaemic disease had the highest BNP values). Systolic function was worse in patients with ischaemic disease or dilated cardiomyopathy. High BNP values were also associated with advanced functional class and male sex. Plasma creatinine correlated positively with plasma BNP. However, we found no significant association with the other clinical variables evaluated. Of the echocardiographic variables analysed, BNP correlated positively with the ventricular diameter and pulmonary artery systolic pressure, and inversely with the shortening fraction; patients with severely impaired systolic function had the highest BNP values. It can be concluded that BNP levels (by radioimmunometric assay) are increased in patients with heart failure, and increase in relation to left ventricular dysfunction and the severity of heart failure. The strong independent association of plasma BNP with the left ventricular ejection fraction, its stability and the low cost of measurement suggest that plasma BNP assay could become a routine test. BNP assay could be included as an important factor in clinical and therapeutic decision making, as it complements the information provided by other variables used in the diagnosis of heart failure.

Atrial Natriuretic Factor↗

Esterified estrogen therapy in postmenopausal women. Relationships of bone marker changes and plasma estradiol to BMD changes: a two-year study.

OBJECTIVE: To determine the relationships among bone mineral density changes, bone marker changes, and plasma estrogens in postmenopausal women receiving estrogen replacement therapy. DESIGN: A total of 406 postmenopausal women received 1,000 mg calcium and continuous esterified estrogens (0.3 mg, 0.625 mg, or 1.25 mg) or placebo daily for up to 24 months. Bone mineral density and bone marker measurements were determined at 6-month intervals; plasma estrogens were measured in a subset after 12, 18, and 24 months. RESULTS: Esterified estrogens produced significant increases in bone mineral density (lumbar spine, hip) compared with baseline and placebo at 6, 12, 18, and 24 months. Bone markers decreased from baseline with all esterified estrogen doses relative to placebo. Bone marker changes at 6 months correlated negatively with bone mineral density changes at 24 months (correlation coefficient range = -0.122 to -0.439). The strongest correlation was noted for spine bone mineral density changes and serum osteocalcin. Mean plasma estrogen levels increased with esterified estrogen dose, and bone mineral density changes correlated positively with plasma estrogen levels. Positive bone mineral density changes were noted in treatment groups with plasma estradiol levels at and above 25 pg/mL. CONCLUSIONS: Esterified estrogens, at doses from 0.3 mg to 1.25 mg/day, unopposed by progestin, increase bone mineral density of the spine and hip in postmenopausal women. These bone mineral density changes correlated significantly with bone marker changes at 6 months and with plasma estrogens at 12, 18, or 24 months. Data variability minimizes the predictive value of the bone marker changes in monitoring individual therapy.

Absorptiometry, Photon↗

The relationship between bone mineral density and the number of remaining teeth in community-dwelling older adults.

Tooth loss and osteoporosis may share common aetiologic agents which influence the process of both diseases. The purpose of this study was to evaluate the relationship between bone mineral density (BMD) of the os calcis and the number of remaining teeth, controlling the known confounding factors. Among all 70-year-old inhabitants in Niigata City, Japan, 600 people were selected randomly in order to have approximately the same number of each gender. We analysed 460 subjects. We evaluated the BMD of the os calcis using an ultrasound bone densitometer, then we counted the number of remaining teeth excluding the third molars. Stiffness is a clinical index which is calculated by the spread speed of supersonic waves. To monitor the general health condition of the subjects, serum levels of disease markers and smoking habits were also investigated. The mean number of remaining teeth for the osteopenia group (OG) and the no-osteopenia group (NOG) was 15.97+/- 9.98 and 18.31+/- 8.06, respectively in females, and 16.32+/- 9.93 and 18.12+/- 9.33, respectively in males (OG versus NOG, P=0.047 by two-way anova). In addition, stiffness was significantly associated with the number of remaining teeth (CV=-0.157, P=0.005) using linear multiple regression analysis adjusted by four other variables. In this study, there was a significant relationship between the number of remaining teeth and BMD of the os calcis.

Adipose Tissue↗

Calprotectin as a marker of inflammation in cystic fibrosis.

Calprotectin is an abundant neutrophil cytosolic protein released during neutrophil activation or death. The use of plasma calprotectin concentration as a marker of pulmonary inflammation was tested in 31 children with cystic fibrosis, none of whom was acutely unwell or pyrexic. Twenty three were receiving antibiotics, 21 had positive sputum cultures, but none of the traditional tests clearly diagnosed ongoing infection. Plasma calprotectin was significantly higher in the cystic fibrosis group than in matched controls. Sixteen children with cystic fibrosis had values above the control range (320-1570 micrograms/l). Their chest radiograph Northern score, an index of accumulated pulmonary involvement, and their plasma copper, an index of acute phase response, both correlated with plasma calprotectin. Plasma gamma-glutamyltransferase also correlated weakly with plasma calprotectin: thus, hepatic pathology may be a confounding variable. However, the data still suggested that plasma calprotectin is a better index of inflammation than the traditional indices in general use.

Adolescent↗

Inflammatory response in the early prediction of severity in human acute pancreatitis.

The role of the inflammatory response in acute pancreatitis and its relation with the clinical course was examined. This study examined if the serial measurement of polymorphonuclear granulocyte (PMN) elastase/A1PI complex, phospholipase A catalytic activity, C reactive protein, and other acute phase proteins, and the protease inhibitor alpha 2-macroglobulin, provides meaningful information for prognosis. Eighty non-consecutive patients with acute pancreatitis, classified according to their clinical outcome into mild (n = 40) and severe pancreatitis (n = 40), were followed up daily. Between 48 hours, median values of PMN-elastase, C reactive protein--and most of the acute phase proteins--and phospholipase A activity, were significantly higher in the severe pancreatitis group. PMN elastase shows a dynamic course and it reaches an early peak value at days 1-2, followed by C reactive protein (days 2-4) phospholipase A (day 3), and a negative peak for alpha 2-macroglobulin (days 4-5). PMN elastase (day 1) and C reactive protein (day 2) were selected by discriminant analysis as the most useful variables studied to allow the early accurate prediction of severity (sensitivity 100%, specificity 95%). Little or no predictive additional value was found for all other variables studied. These results strongly suggest a close relation between inflammatory parameters and clinical course in acute pancreatitis, and discriminant analysis of these variables provides a useful method to classify severity.

Acute Disease↗