Factors associated with sepsis development in 606 Spanish adult patients with cellulitis.

BACKGROUND: Cellulitis, a frequent cause of admission of adult patients to medical wards, occasionally evolves to sepsis. In this study we analyze the factors related to sepsis development. METHODS: Prospective and observational study of 606 adult patients with cellulitis admitted to several Spanish hospitals. Comorbidities, microbiological, clinical, lab, diagnostic, and treatment data were analyzed. Sepsis was diagnosed according to the criteria of the 2016 International Sepsis Definitions Conference. Multiple logistic regression modelling was performed to determine the variables independently associated with sepsis development. RESULTS: Mean age was 63.4 years and 51.8% were men. Overall 65 (10.7%) patients developed sepsis, 7 (10.8%) of whom died, but only 4 (6.2%) due to cellulitis. Drawing of blood (P < 0.0001) or any (P < 0.0001) culture, and identification of the agent (P = 0.005) were more likely among patients with sepsis. These patients had also a longer duration of symptoms (P = 0.04), higher temperature (P = 0.03), more extensive cellulitis (P = 0.02), higher leukocyte (P < 0.0001) and neutrophil (P < 0.0001) counts, serum creatinine (P = 0.001), and CRP (P = 0.008) than patients without sepsis. Regarding therapy, patients with sepsis were more likely to undergo changes in the initial antimicrobial regimen (P < 0.0001), received more antimicrobials (P < 0.0001), received longer intravenous treatment (P = 0.03), and underwent surgery more commonly (P = 0.01) than patients without sepsis. Leukocyte counts (P = 0.002), serum creatinine (P = 0.003), drawing of blood cultures (P = 0.004), change of the initial antimicrobial regimen (P = 0.007) and length of cellulitis (P = 0.009) were independently associated with sepsis development in the multivariate analysis. CONCLUSIONS: Increased blood leukocytes and serum creatinine, blood culture drawn, modification of the initial antimicrobial regimen, and maximum length of cellulitis were associated with sepsis in these patients.

Factors predictive of relapse in adult bacterial osteomyelitis of long bones.

BACKGROUND: Osteomyelitis is a difficult-to-cure infection with a high relapse rate despite combined medical and surgical therapies. Some severity factors, duration of antimicrobial therapy and type of surgical procedure might influence osteomyelitis relapse. METHODS: 116 patients with osteomyelitis were followed for ≥1 year after hospital discharge. Demographic, microbiological and clinical data, eight severity factors and treatment (surgical and antibiotic) were analyzed. RESULTS: Mean age was 53 years and 74.1% were men. Tibia (62.1%) and S. aureus (58.5%) were the most commonly involved bone and bacteria, respectively. Mean follow-up was 67.1 months. Forty-six patients underwent bone debridement, 61 debridement plus flap coverage and 9 antimicrobial therapy only. Twenty-six patients (22.4%) relapsed, at a mean of 11.2 months since hospital discharge. Duration > 3 months (p = 0.025), number of severity factors (P = 0.02) and absence of surgery (P = 0.004) were associated with osteomyelitis relapse in the univariate analysis. In the Cox regression analysis, osteomyelitis duration > 3 months (P = 0.012), bone exposure (P = 0.0003) and type of surgery (P < 0.0001) were associated with relapse. Regarding the surgical modalities, bone debridement with muscle flap was associated with better osteomyelitis outcomes, as compared with no surgery (P < 0.0001) and debridement only (P = 0.004). CONCLUSIONS: Osteomyelitis extending for > 3 months, bone exposure and treatment other than surgical debridement with muscular flap are risk factors for osteomyelitis relapse.

Factors associated with long-term CD4 cell recovery in HIV-infected patients on successful antiretroviral therapy.

OBJECTIVES: The aim of the study was to study the factors associated with immunological recovery in HIV-infected patients with suppressed viral load. METHODS: Nadir and current CD4 cell counts were recorded in 821 patients, as well as many demographic, epidemiological, lifestyle, clinical, therapeutic, genetic, laboratory, liver fibrosis and viral hepatitis parameters. RESULTS: The median age of the patients was 44.4 years [interquartile range (IQR) 40.3-48.0 years], the median time since HIV diagnosis was 15.3 years (IQR 10.5-18.9 years), the median time of suppressed viral load was 7.0 years (IQR 4.0-10.0 years) and the median time on the current antiretroviral regimen was 2.8 years (IQR 1.4-4.7 years). The median nadir and current CD4 counts were 193.0 (IQR 84.0-301.0) and 522.0 (IQR 361.0-760) cells/µL, respectively, separated by a median period of 10.2 years (IQR 5.9-12.9 years). The median CD4 count gain during follow-up was 317.0 (IQR 173.0-508.0) cells/µL. Many variables were associated with CD4 cell gains in univariate analyses, including age, gender, epidemiology, prior clinical conditions, fibrosis stage, transient elastometry, aspartate aminotransferase (AST), nadir CD4 count and hepatitis B and C virus infections and genotypes, as well as the durations of follow-up since nadir CD4 count, overall antiretroviral treatment, current antiretroviral regimen, protease inhibitor therapy and suppression of viral load. Multivariate analysis revealed that longer duration of HIV suppression (P < 0.0001), more advanced clinical Centers for Disease Control and Prevention (CDC) stages (P < 0.0001), younger age (P = 0.0003), hepatitis C virus genotypes 1 and 4 (P = 0.003), sexual acquisition of HIV (P = 0.004), and lower transient elastometry values (P = 0.03) were independent predictors of CD4 cell gains. Overall, the model accounted for 14.2% of the variability in CD4 count. CONCLUSIONS: In addition to the duration of HIV suppression, HIV-related diseases, HIV epidemiology, age, hepatitis C virus genotypes, and liver fibrosis were independently associated with long-term immunological recovery.

The effect of gender and genetic polymorphisms on matrix metalloprotease (MMP) and tissue inhibitor (TIMP) plasma levels in different infectious and non-infectious conditions.

Matrix metalloproteases (MMPs) are increased in different infections due to their role in controlling immune responses and are regulated by tissue inhibitors (TIMPs). Different MMP promoter single nucleotide polymorphisms (SNPs) induce changes in MMP genes, mRNA and protein expression. Gender might also modify MMP plasma levels. In order to determine the weight of these variables on MMP secretion we studied MMP-1, -2, -3, -8, -9, -10, -13 and TIMP-1, -2, -4 plasma levels in 90 patients with severe bacterial sepsis, 102 with anti-retroviral (ARV)-treated HIV monoinfection, 111 with ARV-treated HIV-hepatitis C virus (HCV) co-infection and 86 non-infected controls (45 stroke and 41 trauma patients). MMP-1(-1607 1G/2G), MMP-3(-1612 5A/6A), MMP-8(-799C/T), MMP-9(-1562 C/T) and MMP-13(-77A/G) SNPs were genotyped. MMP-3 plasma levels were significantly higher in men than in women in each diagnostic group, and MMP-3 SNP allele 6A carriers also had higher levels than allele 5A carriers, an effect that was magnified by sepsis. Independent predictors of higher MMP-3 levels were male gender (P = 0.0001), MMP-3(-1612 5A/6A) SNP (P = 0.001), higher levels of TIMP-4 (P = 0.004) and MMP-8 (P = 0.006) and lower levels of MMP-1 (P = 0.03) by multivariate analysis. No strong associations with gender or SNPs were observed for other MMPs or TIMPs. In conclusion, male gender and MMP-3(-1612 5A/6A) 6A allele carriage increased MMP-3 plasma levels significantly, especially in patients with severe bacterial sepsis. This confounding gender effect needs to be addressed when evaluating MMP-3 plasma levels in any infectious or non-infectious condition.

Seroprevalence for measles among healthcare workers in Madrid, Spain.

BACKGROUND: Immunity of healthcare workers (HCWs) against measles is a particular concern. They are more likely to contract it than the general population due to their occupational exposure which may cause a nosocomial outbreak. AIM: To assess the measles immune status of HCWs at five Spanish university hospitals. PATIENTS AND METHODS: Serologic testing (IgG) for measles by chemiluminescence indirect immunoassay (CLIA) was carried out prospectively and consecutively in HCWs from five university hospitals. All HCWs were classified into four epidemiological groups: vaccinated individuals, those with a history of measles disease, subjects with no history of measles or vaccination, and those who did not know whether they had measles or were vaccinated, and into five professional categories: physicians, nurses, nursing assistants, other clinical workers and non-clinical workers. A logistic regression model was constructed to identify the factors independently associated with immunity to measles. RESULTS: The study group was composed of 2157 HCWs. 89% had protective antibodies against measles. Of the 238 non-immune HCWs, 199 (83.6%) had been vaccinated, compared with 1084 of the 1919 (56.5%) immune individuals (P<0.0001). The parameters significantly predictive of having protective antibodies against measles were: older age (P<0.0001), epidemiological status (P=0.0002, mainly past measles disease), and professional category (P=0.02, in particular nurses). CONCLUSION: This study shows that HCWs, including those previously vaccinated, are currently at risk of measles and suggests that those with a natural history of infection are better protected. Therefore, knowledge and maintenance of immunity to measles are an essential part of infection control among HCWs.

Didanosine (ddI) associates with increased liver fibrosis in adult HIV-HCV coinfected patients.

The role of exposure to antiretrovirals (ARV) and serum matrix metalloproteases (MMPs) on liver fibrosis (LF) progression in human immunodeficiency virus (HIV) mono or HIV- hepatitis C virus (HCV) coinfection is unclear. Thus, 213 Caucasian adult HIV-infected patients were studied, 111 of whom had HCV-coinfection and 68 were HCV-monoinfected. Patients with ethanol consumption >50 g/day, hepatitis B coinfection, non-infective liver diseases or HAART adherence <75% were excluded. LF was assessed by transient elastometry (TE, Fibroscan). Serum levels of MMPs (MMP -1,-2,-3,-8,-9,-10 and -13) and their tissue inhibitors (TIMP-1,-2 and -4) were measured by ELISA microarrays. Associations with LF were statistically analysed. Protease inhibitors, usually administered to patients with advanced LF were excluded from the analysis. Increased LF was significantly associated with d4T (P = 0.006) and didanosine (ddI) use (P = 0.007), months on d4T (P = 0.001) and on ARV (P = 0.025), duration of HIV (P < 0.0001) and HCV infections (P < 0.0001), higher HIV (P = 0.03) and HCV loads (P < 0.0001), presence of lipodystrophy (P = 0.02), male gender (P = 0.02), older age (P = 0.04), low nadir (P = 0.02) and current CD4(+) T-cells (P < 0.0001), low gain of CD4(+) T-cells after HAART (P = 0.01) and higher MMP-2 (P = 0.02) and TIMP-2 serum levels (P = 0.02). By logistic regression the only variables significantly associated with increased LF were: use of ddI (OR 8.77, 95% CI: 2.36-32.26; P = 0.005), male gender (OR 7.75, 95% CI: 2.33-25.64, P = 0.0008), HCV viral load (in log) (OR 3.53, 95% CI: 2.16-5.77; P < 0.0001) and age (in years) (OR 1.21, 95% CI: 1.09-1.34, P = 0.0003). We conclude that only higher HCV viral load, older age, male gender, and use of ddI associated independently with increased LF in our study.

Evaluation of the possible influence of hepatitis C virus and liver fibrosis on HIV type 1 immunological and virological outcomes.

OBJECTIVES: The aim of the study was to evaluate the possible effect of hepatitis C virus (HCV) coinfection on the viroimmunological outcomes of HIV-1 infection. METHODS: A cross-sectional study of 805 patients with active HCV infection receiving or not receiving antiretroviral therapy (ART) was carried out. RESULTS: A number of parameters were significantly associated with undetectable HIV-1 viral load in univariate analyses, such as age, toxic habits, CD4 cell count, liver test results, HCV viral load and ART. However, only current ART (P<0.0001), CD4 cell count (P<0.0001), age (P=0.004) and current injecting drug use (P=0.02) were independently associated with undetectable viral load in multivariate analysis. None of the many HCV- and liver fibrosis-related parameters analysed showed a significant association with HIV-1 viral load or CD4 cell count in multivariate analyses, with the exception of the annual fibrosis progression index which almost reached statistical significance in the subgroup of ART-untreated patients (P=0.06) and was inversely predictive of CD4 cell count in the whole group (P=0.007). However, its relative weight was modest, as it only explained 0.8% of the total variability in CD4 cell count. CONCLUSIONS: HCV-related parameters did not significantly affect virological and immunological outcomes of HIV-1 infection in ART-treated and untreated patients. In contrast, liver fibrosis, as measured using the annual fibrosis progression index, was inversely associated with CD4 cell count, although its weight was relatively small. Therefore, HCV- and liver fibrosis-related factors do not seem appreciably to influence these outcomes from a practical viewpoint in ART-naïve patients, nor impair CD4 and HIV-1 viral load responses to ART.

Association of HIV transmission categories with sociodemographic, viroimmunological and clinical parameters of HIV-infected patients.

To analyse sociodemographic, viroimmunological and clinical parameters in different HIV-transmission categories at baseline and during treatment, 3039 patients were followed up for 12 months after the initiation of a nelfinavir-based regimen. Multiple baseline parameters were significantly different in the diverse categories, including CD4 counts (P<0.0001) and viral load (P=0.02). There were differences in the groups regarding the CD4 response (P=0.01), but not the virological response (P=0.4), to therapy over time. Multivariate analyses revealed that transmission categories were significantly related to baseline CD4 counts (P=0.01), viral load at 12 months (P=0.0006), poorer adherence to therapy of injecting drug users (IDUs) vs. each of the other groups (P<0.001) and failure to complete the 12-month evaluation of IDU vs. heterosexual (P=0.003) and men who have sex with men (MSM) groups (P=0.02). We conclude that transmission categories had a significant influence on several baseline parameters and viroimmunological outcomes following highly active antiretroviral therapy (HAART), as well as on adherence to therapy and to medical appointments.

[Handgrip strength in children and teenagers aged from 6 to 18 years: reference values and relationship with size and body composition]. / Dinamometría en niños y jóvenes de entre 6 y 18años: valores de referencia, asociación con tamaño y composición corporal.

INTRODUCTION: Handgrip strength is an important test to evaluate physical fitness and nutritional status. The main objective of this research is to prepare a reference standard applicable to the Spanish population of both sexes between 6 and 18 years old. At the same time, to extend our knowledge of normal variation of this characteristic with age, gender, size and body composition. MATERIALS AND METHODS: The sample consisted of 2125 subjects between the 6 and 18 years (1176 boys and 949 girls). The handgrip strength of both hands was taken with a digital adjustable dynamometer. Weight, height, forearm circumference and skin fold thickness were measured mass index, fat free. Body mass, percentage of fat and total, muscle and fat forearm areas were estimated. Ontogenetic and sexual variability of dynamometric force was analysed and a table was produced with the mean, standard deviation and percentile distribution, by hand, age and gender. Multiple correlation analysis was applied to establish the relationship between handgrip dynamometric force, body mass index and body composition variables. RESULTS AND CONCLUSION: Handgrip strength increases with age and a significant sexual dimorphism from the age of 12 years is observed. Growth charts with normal values obtained in healthy Spanish children and teenagers could be used as a reference pattern. The correlation between hand static force and fat free mass or arm muscle area is stronger than with direct size variables or body mass index.

Bacterial osteomyelitis: microbiological, clinical, therapeutic, and evolutive characteristics of 344 episodes.

OBJECTIVE: Osteomyelitis is a difficult-to-cure infection, with high relapse rate despite adequate therapy. Large published osteomyelitis series in adults are rare. METHODS: A total of 344 adult osteomyelitis patients were studied and followed > 12 months after hospital discharge. Demographic, microbiological, clinical, therapeutic and outcome data were analyzed. RESULTS: Mean age was 52.5 ± 18.3 years and 233 (67.7%) were male. Main osteomyelitis types were post-surgical (31.1%), post-traumatic (26.2%) and hematogenous (23%). Tibia (24.1%) and femur (21.8%), and methicillin-susceptible S. aureus (29.6%) were the most commonly involved bone and bacteria, respectively. Median follow-up was 12.0 (IQR 0-48) months. Inflammatory markers were increased in 73.6%. Overall, patients were treated by IV and oral routes with one (IV: 44.5%, oral: 26.7%), two (IV: 30.1%, oral: 21.8%) or ≥ 2 (IV: 15.2%, oral: 6.1%) antibiotics. Median duration on IV/oral antimicrobials was 28.0 (IQR 24-28) and 19.5 (IQR 4-56) days, respectively. Anti-staphylococcal ß-lactams cloxacillin/cefazolin (19.2%) and ciprofloxacin (5.5%) were the most frequently used IV and orally, respectively. Overall 234 (68.0%) underwent surgery, 113 (32.8%) debridement, 97 (27.4%) debridement + muscle flap and 24 (7%) amputation. At the end of follow-up 208 patients (60.6%) did not have relapsed. Operated patients had significantly less relapses (p<0.0001). A total of 23 (6.7%) died, 11 (3.2%) by infectious complications and 48 (14%) were lost in the follow-up. CONCLUSIONS: Osteomyelitis is due to different causes complicating its therapy. Risk factors or causal microorganism could influence its treatment and outcome. Aggressive surgery along with adequate antimicrobial therapy are mandatory for cure.

Thrombin-induced changes of intracellular [Ca2+] and pH in human platelets. Cytoplasmic alkalinization is not a prerequisite for calcium mobilization.

We have studied the effects of thrombin (0.1 U/ml) on intracellular Ca2+ ([Ca2+]i) and pH (pHi) in human platelets loaded with fluorescent indicators. Thrombin produced a transient decrease of pHi which reached its maximum within 15-25 seconds (s) and was followed by a sustained alkalinization which brought pHi above the resting value. [Ca2+]i increased transiently peaking at 5-10 s. The late alkalinization induced by thrombin was antagonized by ethylisopropylamiloride, an inhibitor of Na+-H+ exchange, and by sphingosine, an inhibitor of protein kinase C, with little effect on the [Ca2+]i transient. The early acidification was not inhibited by these treatments. We conclude tha the thrombin-induced changes of [Ca2+]i and pHi are mediated by different mechanisms. The late alkalinization is due to activation of Na+/H+ exchange mediated by protein kinase C and, contrarily to previous proposals (Siffert, W. and Akkerman, J.W.N. (1987) Nature 325, 456-458), it is not necessary for calcium mobilization from intracellular stores.

Pneumococcal pyomyositis. Case report, review of the literature, and comparison with classic pyomyositis caused by other bacteria.

Pyomyositis is caused by staphylococci in 70% to 90% of patients. We report a case of pneumococcal pyomyositis (PP), review the 11 cases previously published, and compare the features of pneumococcal pyomyositis with those of classic (nonpneumococcal) pyomyositis. Several clinical characteristics have been identified that are notably different in both groups. Psoas muscle involvement was observed in two thirds of the patients with PP, and a source for the infection was identified in half of the patients. Patients with PP were older than those with classic pyomyositis. Men were affected less often than women with PP, but the opposite was the rule in classic pyomyositis. The systemic response to the infection was more prominent in patients infected with pneumococci than from other causes. Most patients with PP were successfully treated with antibiotics and drainage. Secondary meningitis was observed in 3 patients with psoas muscle abscess caused by pneumococci. Mortality is low in pyomyositis regardless of the causative pathogen.

Interleukin-6 concentrations in the vitreous body of patients with retinal detachment.

OBJECTIVE: To measure interleuquin-6 (IL-6) levels in the vitreous body of patients with retinal detachment (RD). PATIENTS AND METHODS: Undiluted vitreous samples were obtained from 40 patients with no history of prior vitreous or intraocular surgery. Patients were divided into two groups: A (n=20) patients with RD and B (n=20) patients with pre-retinal macular membranes and macular holes. IL-6 was determined using radioimmunoassay. RESULTS: IL-6 vitreous concentration in group A was 122.4+-16pg/mL (range 91.5-620) and in group B was 46+/-23pg/mL (range 3-150) (p <.001). CONCLUSIONS: These results show that the concentration of IL-6 in the vitreous body was significantly higher in patients with RD than in the control group.

cAMP reduces the affinity of Ca2+-triggered secretion in platelets.

Prostacyclin and other related compounds known to increase intracellular cAMP levels inhibit platelet responses. The mechanisms involved are only partially known, especially those concerning the complex relations between Ca2+ and cAMP as opposite intracellular mediators. Here, we have investigated aggregation and secretion in quin2-loaded platelets under conditions in which Ca2+ and cAMP are the only intracellular mediators. Our results show that cAMP inhibits aggregation and secretion in ionophore-treated cell without modifying their intracellular Ca2+ levels. This result suggests that the inhibition takes place on some intracellular target for Ca2+.

Hypersensitivity reactions to rifampin. Pathogenetic mechanisms, clinical manifestations, management strategies, and review of the anaphylactic-like reactions.

Many of the adverse events induced by rifampin have been considered allergic in origin. The flu-like syndrome and other hypersensitivity reactions seem to be caused by immune complexes, although their pathogenetic mechanisms are not fully elucidated. Many cases have been reported of the flu-like syndrome, thrombocytopenia, hemolytic anemia, and renal failure caused by rifampin. In almost all of the patients in whom they were sought, nonreaginic antirifampin antibodies were detected. On the other hand, anaphylactic reactions seem to be IgE-mediated. We have analyzed the 18 reported cases of anaphylactic reactions severe enough to cause marked hypotension. The interval between the onset of treatment and the anaphylactic reaction was highly variable. Most patients presented with prodromes, mainly rash, before the development of anaphylactic symptoms, and, in most cases, the reaction occurred after reexposure to rifampin. Clinical findings include a variety of symptoms, such as fever, exanthem, dyspnea, abdominal pain, and vomiting. Seven of the 9 patients in whom HIV status was known were seropositive, including the only 2 patients who died. We believe that, in case of a non-life-threatening adverse reaction caused by immune complexes, rifampin could be readministered, if necessary, at a more frequent and reduced dose, perhaps with the addition of corticosteroids. In case of anaphylactic reactions the drug should be avoided, although desensitization procedures may be useful. Certain laboratory findings may serve as a clue to predict anaphylactic reactions in patients who have experienced minor adverse events to rifampin. However, the diagnostic value of such findings is not well established and, therefore, patients with previous adverse reactions should be carefully monitored if reexposure to rifampin is essential.

Resolution of a brainstem abscess through antituberculous therapy.

We describe an immunocompetent patient with a solitary brainstem abscess that responded to antituberculous therapy. Although prompt surgical therapy has been advocated, the possibility of medical resolution of brainstem tuberculous abscesses should be considered.

Sequential evaluation of serum adenosine deaminase in patients treated for tuberculosis.

STUDY OBJECTIVE: To delineate the course of serum adenosine deaminase (s-ADA) in patients with tuberculosis who are receiving effective therapy. SETTING: A medical ward and an outpatient clinic in a general hospital. PATIENTS: Twenty-five immunocompetent patients with pleural or pulmonary tuberculosis. INTERVENTIONS: All patients received standard chemotherapeutic regimens with isoniazid, rifampin, and pyrazinamide. MEASUREMENTS AND RESULTS: Six measurements of several variables, including s-ADA, were carried out at different periods of time during the 6 months of follow-up. There were no significant differences in s-ADA values between sexes and there was no significant correlation with age or with the other variables analyzed. There was a significant decline in the s-ADA values during the first 2 months in the patients as a whole (p=0.04), followed by a stabilization of the s-ADA activity. This decline was due to a marked decrease in the s-ADA in the 13 patients (52%) who had initial high levels of the enzyme (p=0.03), whereas there were no changes in those patients with normal initial levels (p=0.27). Patients with increased s-ADA activity at the time of the first measurement reported symptoms for a longer period than patients with normal s-ADA (median, 15 vs 10 days; p=0.02). CONCLUSIONS: s-ADA levels in patients with tuberculosis decrease during the initial months of effective treatment. Perhaps this decrease might reflect the normalization of the altered lymphocyte turnover induced by tuberculosis. The measurement of s-ADA could be of some help to evaluate the response to therapy, particularly in those patients with increased values of the enzyme.

Systemic lupus erythematosus associated with acute parvovirus B19 infection.

Acute parvovirus B19 infection has been implicated in the pathogenesis of several autoimmune conditions, including systemic lupus erythematosus. Viruses, including human parvovirus B19, may trigger bouts of systemic lupus erythematosus in genetically susceptible individuals. Herein, we report on two patients who developed systemic lupus erythematosus associated with acute parvovirus B19 infection and discuss the possible pathogenetic mechanisms implicated.

Role of the measurement of serum procollagen type III N-terminal peptide in the evaluation of liver diseases.

Serum N-terminal procollagen-III peptide (PIIIP) was measured in 151 patients with diverse liver diseases together with other clinical and laboratory data. Patients with cirrhosis had higher serum PIIIP than those without cirrhosis (P < 0.0001). Significant associations were found between PIIIP and many data characteristic of liver diseases, including alcohol markers. Serum PIIIP was also associated with portal hypertension (P = 0.0001), although such association was probably due to the fact that most patients with portal hypertension were cirrhotic patients. The predictive values of PIIIP in portal hypertension were too low to be clinically useful. No one single factor could be identified as responsible for the increase in PIIIP and the data suggest that the mechanism is multifactorial. Measurement of serum PIIIP has a limited clinical value in the evaluation of patients with diverse liver diseases.

CA 19-9 in non-neoplastic liver diseases. A clinical and laboratory study.

CA 19-9 is a tumor marker with frequent false-positive results in pancreatic and hepatobiliary diseases. This study was carried out to evaluate the behaviour of CA 19-9 in 159 patients with benign diffuse hepatic disease, 85 cirrhotics and 74 non-cirrhotics, who underwent a thorough clinical and laboratory evaluation. CA 19-9 was correlated with numerous clinical and biochemical features of liver diseases: bilirubin and alkaline phosphatase activity were the most reliable predictors of the CA 19-9 concentrations. There were abnormal concentrations of CA 19-9 in 34.6% of the 159 patients and in 47.1% of the 85 cirrhotics. Because of the large number of abnormal values and the high concentrations attained in some of them, the cut-off used in patients with diffuse hepatic disease needs to be set at more than twice the basal level, thus allows only 10% of false positives. Even higher values are required for cirrhotic or icteric patients. The results indicate that cholestasis plays an important role in causing the raised CA 19-9 in these patients, although there were also abnormal concentrations in normobilirubinemic patients.