Clinical utility of procalcitonin as a marker of sepsis: a potential predictor of causative pathogens.

OBJECTIVE: Sepsis is one of the leading causes of mortality in critically ill patients, and providing a timely diagnosis and early intervention is necessary for successful treatment. Procalcitonin (PCT) may be a better marker of sepsis than conventional inflammatory markers. The aim of this study was to evaluate the clinical utility of the PCT level as a marker of sepsis. METHODS: Forty-five patients with sepsis, 24 patients with pneumonia who did not meet the SIRS criteria (PN) and 56 controls were enrolled in this study. The levels of PCT and other serum markers were measured, and their utility as markers of sepsis was assessed. RESULTS: The serum PCT levels exhibited statistically significant differences between the three groups (p<0.0001). The PCT levels in the sepsis group (29.3 ± 85.3 ng/mL) were significantly higher (p<0.001) than those observed in the PN group (0.34 ± 8.6 ng/mL) and the control group (0.74 ± 2.1 ng/mL), according to a post hoc analysis. There were no differences in the white blood cell (WBC) counts or C-reactive protein (CRP) levels between the three groups. Fourteen of the 45 patients with sepsis had positive microbiological blood cultures (Gram-positive cocci [GPC] in seven patients, Gram-negative rods [GNR] in six patients, other types of bacteria in one patient). The 13 patients with GNR or GPC were categorized into the GNR group or GPC group according to the identified pathogens. The serum PCT levels were significantly higher in the GNR group (149.8 ± 199.7 ng/mL) than in the GPC group (19.1 ± 41.8 ng/mL) (p<0.05), although there were no differences in the WBC counts or CRP levels between these groups. When the cut-off value for the PCT level was set at 16.9 ng/mL, the sensitivity and specificity for the detection of GNR infection were 85.7% and 83.3%, respectively. CONCLUSION: The PCT level is a potentially useful marker of the type of causative pathogen in patients with sepsis whose measurement may facilitate the selection of appropriate empiric antibiotic treatment.

Serum level of soluble CD26/dipeptidyl peptidase-4 (DPP-4) predicts the response to sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea.

Dipeptidyl peptidase 4 (DPP-4) inhibitors is a new class of antihyperglycemic agents that is now available for the treatment of type 2 diabetes. We investigated the relationship between the baseline serum level of soluble CD 26/DPP-4 and the response to treatment with sitagliptin, a DPP-4 inhibitor, over 24 weeks in patients who had type 2 diabetes inadequately controlled by metformin and/or sulfonylurea therapy. We studied 52 consecutive patients with type 2 diabetes who had poor glycemic control despite treatment with metformin and/or sulfonylurea. All patients were given 50 mg/day of sitagliptin and were followed at monthly intervals for 24 weeks. Treatment with sitagliptin decreased significantly hemoglobin A1c (HbA1c) from 7.91 ± 1.08% at baseline to 6.96 ± 1.18% at 8 weeks, 7.04 ± 0.77% at 16 weeks, and 7.08 ± 0.80% at 24 weeks. The baseline serum level of sCD26 was correlated positively with HbA1c at both 16 weeks and 24 weeks. Furthermore, the serum sCD26 level at baseline was also correlated positively with the changes from baseline of HbA1c at 16 and 24 weeks (r = 0.318, P = 0.0296 and r = 0.516, P = 0.0003, respectively). In a multivariate logistic regression model that explained 56.1% (R(2) = 0.561) of the variation of the changes from baseline of HbA1c at 24 weeks, the baseline HbA1c (ß = -0.638, P < 0.001) and serum sCD26 (ß = 0.357, P = 0.041) were independent determinants of the change of HbA1c at 24 weeks. In conclusions, a higher serum level of sCD26 is associated with a worse response to sitagliptin in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea therapy.

[Effects of Calorie Mate Jelly eating before abdominal ultrasonography on the diagnosis--an evaluation in healthy adults].

In transabdominal ultrasonography, the production of gas in the gastro-intestinal tract and contraction of the gallbladder have to be prevented to obtain clear observation images of any lesions. Therefore, patients avoid food and drink for many hours from the night before the examination. However, long-term fasting exacerbates energy homeostasis in patients with cirrhosis. Thus, it is necessary to develop a method of transabdominal ultrasonography allowing the shortening of the fasting time. In this study, subjects ingested Calorie Mate Jelly three hours before transabdominal ultrasonography. Then, we studied the effect of the Jelly on ultrasonographic images. Three hours after its consumption, imaging diagnosis involving the liver, in liver, gallbladder, pancreas, spleen, and kidney could be successfully carried out in all healthy adults. Thus, our observations indicated that the abdominal organs can be effectively observed by transabdominal ultrasonography if Calorie Mate Jelly is consumed up to three hours before the examination. Calorie Mate Jelly may help to prevent worsening energy homeostasis in patients who are required to fast for a prolonged period.

Effects of histologic type on levels of macrophage colony-stimulating factor in liquid contents of benign ovarian tumors.

BACKGROUND: Normal ovarian tissue is rich in cytokines. Cytokines are important in the physiology of ovarian function. Most of the same cytokines that are found in normal ovarian tissue are also found in association with benign and malignant tumors in contrast to their functions in normal tissues. Thus, we measured macrophage colony-stimulating factor (M-CSF) levels in the liquid contents of benign ovarian tumors--serous cystadenoma, mucinous cystadenoma, and mature cystic teratoma--and investigated whether M-CSF levels were associated with the histologic type of the ovarian tumors. METHODS: We enrolled 65 patients, 52 with benign ovarian tumor and 13 in the early postmenopausal period with symptoms of a menopausal disorder. Among the 52 patients with benign ovarian tumor, 16 had serous cystadenoma, 21 had mucinous cystadenoma, and 15 had mature cystic teratoma. Immediately after surgery, the liquid content was drawn from the ovarian tumor, then centrifuged, and the separated supernatant was stored at -30 degrees C. The M-CSF level was determined by the sandwich enzyme-linked immunosorbent assay method with use of three antibodies. RESULTS: The level of M-CSF was 12,513 U/mL (median) (range, 0-169,000 U/mL) in serous cystadenoma, 915 U/mL (0-82,500 U/mL) in mucinous cystadenoma, and 149 U/mL (0-6,230 U/mL) in mature cystic teratoma. The M-CSF levels increased significantly from mature cystic teratoma to mucinous cystadenoma to serous cystadenoma. The serum M-CSF levels were 308 to 499 U/mL in patients with benign ovarian tumor. The M-CSF levels did not differ significantly among the three groups. The serum M-CSF levels were 162 U/mL (0-473 U/mL) in menopausal patients. CONCLUSIONS: Elevation of levels of M-CSF varies according to histologic type in benign ovarian tumors. This implies that the antitumor activities of M-CSF for serous cystadenoma, mucinous cystadenoma, and mature cystic teratoma differ by histologic type.

Elevation of macrophage colony-stimulating factor in amniotic fluid at late stage of normal pregnancy.

PROBLEM: Macrophage colony-stimulating factor (M-CSF) promotes placental growth and maintenance, and regulates trophoblast invasion into the placental bed. We evaluated whether the amniotic fluid M-CSF levels at the late stage of normal pregnancy is altered compared with those at the middle stage. METHOD OF STUDY: This study enrolled 52 subjects experiencing normotensive pregnancies with single fetuses, of whom 26 were women at the late stage (term gravidas) and 26 were women at the middle stage (controls). The average gestational age at entry was 38 weeks of gestation and 17 weeks, respectively. Amniotic fluid was collected from these subjects. Amniotic fluid M-CSF levels were determined by the enzyme-linked immunosorbent assay method then compared between term gravidas and controls. RESULTS: Amniotic fluid M-CSF concentrations were 4815 pg/mL (median) in term gravidas and 3795 pg/mL in controls; the concentrations were significantly higher in term gravidas than in controls. CONCLUSIONS: We demonstrated a significant increase in amniotic fluid M-CSF levels in term gravidas. These results suggest that elevated levels of M-CSF in amniotic fluid have an important immunological function in the maintenance of pregnancy and fetal growth.

Local release of C-reactive protein from vulnerable plaque or coronary arterial wall injured by stenting.

OBJECTIVES: The purpose of this study was to assess local release of C-reactive protein (CRP) from atherosclerotic plaques or the vessel wall injured by stenting. BACKGROUND: Recent research has focused on the local production of CRP, especially in inflammatory atherosclerotic plaques. METHODS: The study consisted of two separate protocols. In protocol 1, we measured serum high-sensitivity-CRP (hs-CRP) levels in coronary arterial blood sampled just distal and proximal to the culprit lesions in 36 patients with stable angina and 13 patients with unstable angina. In protocol 2, we measured serial serum hs-CRP levels and activated Mac-1 on the surface of neutrophils in both coronary sinus and peripheral blood in 20 patients undergoing coronary stenting. RESULTS: In protocol 1, CRP was higher in distal blood than proximal blood in both stable (p < 0.05) and unstable angina (p < 0.01). The translesional CRP gradient (distal CRP minus proximal CRP, p < 0.05) as well as the proximal CRP (p < 0.05) and distal CRP (p < 0.05) was higher in unstable angina than in stable angina. In protocol 2, the transcardiac CRP gradient (coronary sinus minus peripheral blood) and activated Mac-1 increased gradually after stenting, reaching a maximum at 48 h (p < 0.001 vs. baseline for both). There was a positive correlation between the transcardiac CRP gradient and activated Mac-1 at 48 h (r = 0.45, p < 0.01). CONCLUSIONS: C-reactive protein is an excellent marker for plaque instability or poststent inflammatory status, and its source might be the inflammation site of the plaque or the coronary arterial wall injured by stenting.

[The assessment of arteriolosclerosis by serum lipids data, and carotid ultrasonography and pulse wave velocity, and its evaluation as a tool for preventive medicine: II. Carotid ultrasonography and pulse wave velocity for hyperlipemia and diabetes mellitus].

We studied the test results of carotid ultrasonography and pulse wave velocity against a sample of hyperlipemia and diabetes mellitus. Sixty four hyperlipemia samples (HL), 85 diabetes mellitus samples (DS), and 27 complicated samples (CS) were compared with 56 healthy samples (HS). Hyperlipemia samples were selected from cholesterol under 300 mg/dl, and neutral fat under 300 mg/dl. Diabetes mellitus samples were selected from fasting plasma glucose (FBS) under 200 mg/dl. Samples from severe conditions with various disease were excluded. Ratio over 1.1 mm intima-media thickness (IMT) was 0% in HS, 48% in HL, 40% in DS and 33% in CS. PWV value was max 1896cm/s in CS. There was no significant correlation within IMT, serum lipid(Total Cholesterol, Neutral Fat, HDL-Cholesterol, LDL-Cholesterol) and FBS. For early treatment or accurate diagnosis of arteriosclerosis in hyperlipemia or diabetes mellitus patients, who are at high risk of developing arteriosclerosis, to vital function tests (carotid ultrasonography and pulse wave velocity) should be performed, in addition to normal blood tests.

Tumor necrosis factor-alpha in the placenta is not elevated in pre-eclamptic patients despite its elevation in peripheral blood.

PROBLEM: Tumor necrosis factor-alpha (TNF-alpha) is present in human placental and uterine cells at the early and late stages of gestation and promotes the regulation of trophoblast growth and invasion. We evaluated whether TNF-alpha levels in the placenta and blood of pre-eclamptic women differed from those with normal pregnancies. METHOD OF STUDY: The subjects were 39 pregnant women carrying single fetuses (21 normal-pregnant and 18 pre-eclamptic patients). Their average gestational age at entry was 38-39 weeks. Peripheral blood was collected before the onset of labor and separated serum was stored at -20 degrees C. A tissue segment of the placenta was cut and frozen in liquid nitrogen immediately after delivery at -80 degrees C. The frozen placental tissue was added to phosphate-buffered saline. The tissue was fully homogenized and centrifuged. Separated supernatant was stored at -80 degrees C. TNF-alpha levels in separated serum and TNF-alpha and total protein (TP) levels in separated supernatant were measured. The presence of TNF-alpha in the placenta was evaluated by immunohistochemistry in five pre-eclamptic and five normal-pregnant patients. RESULTS: Serum TNF-alpha levels were higher in pre-eclampsia than in normal pregnancies. However, TNF-alpha/TP levels in the placenta did not differ significantly between the two groups. As for TNF-alpha immunostaining of trophoblastic cells in the placenta, it was weak in three and moderate in two of the normal pregnancies, while it was absent in two, weak in one, and moderate in two in the pre-eclampsia group. CONCLUSIONS: We demonstrated no significant increase in TNF-alpha/TP levels in the placenta in pre-eclampsia despite a significant increase in serum TNF-alpha levels. There was no strong immunostaining for TNF-alpha detected by immunohistochemistry in the pre-eclampsia group. These findings suggest that TNF-alpha in the placenta is not a key cytokine to interfere with normal trophoblast invasion into the myometrium in pre-eclampsia, and that sources other than the placenta may contribute to the elevated levels of TNF-alpha found in the circulation of pre-eclamptic patients.

Serum levels of macrophage colony-stimulating factor after cesarean section, vaginal delivery, or laparotomy in normal pregnant women and gynecologic patients.

BACKGROUND: Macrophage colony-stimulating factor (M-CSF) is located in villous cells lining the vessels in the placenta in the third trimester and has been implicated in placental growth and development. Macrophage colony-stimulating factor levels in peripheral blood increased significantly with progression of pregnancy in uncomplicated pregnancies. The serum levels of M-CSF appear to be altered after laparotomy in normal pregnant women and nonpregnant gynecologic patients. Thus, the present study examined changes in serum levels of M-CSF before and after laparotomy and compared these findings between the two groups. Macrophage colony-stimulating factor levels before and after vaginal delivery were also examined. METHODS: Peripheral blood was collected before, 1 day, and 10 days after laparotomy or vaginal delivery from 38 subjects, of whom 14 were normal pregnant women who underwent cesarean section (group 1), 12 were gynecologic patients (group 2), and 12 were normal pregnant women who delivered vaginally (group 3). The M-CSF level was determined by the sandwich ELISA method using three antibodies. RESULTS: In all groups, the serum levels of M-CSF increased significantly 1 day after laparotomy or vaginal delivery, but then decreased significantly after 10 days. The net increase 1 day after laparotomy was significantly lower in group 1 than in group 2. Before and 1 day after laparotomy, the M-CSF levels were significantly higher in group 1 than in group 2, but not 10 days after laparotomy. Changes in M-CSF levels in group 3 were relatively similar to those in group 1. CONCLUSIONS: Serum levels of M-CSF were significantly higher in groups 1 and 3 than in group 2, before laparotomy or vaginal delivery. The M-CSF level increased moderately 1 day after cesarean or vaginal delivery, and it increased remarkably after gynecologic laparotomy. The increases in M-CSF levels postlaparotomy may occur via different mechanisms between groups 1 and 2. Placental removal and termination of pregnancy might contribute to the decrease in M-CSF levels, leading to only a moderate increase in M-CSF levels 1 day after laparotomy in group 1.

[Laboratory information and consultation service with a ordering system].

We built a laboratory information system that does not require resident medical technologists or medical doctors. The laboratory information system used the following two methods. In the first method, the receiver of questions/complaints/consultations about laboratory tests used e-mail carried by an ordering system. In the second method, the Web utilized a laboratory test information retrieval system by intranet. As for e-mail inquirers, doctors made up 76.7%(46/60), and other types of job were office workers 11.7% (7/60), nurses 8.3%(5/60), and pharmacists 3.3%(2/60). The question(consultation) contents were test methods 30.0%, demands/complaints 28.3% for ordering, specimen saving requests 13.3%, consultations 11.7%, and other 16.7%. Since introducing this system, compared to previously telephone inquiries have by about 60% decreased, and basic questions such as reference intervals or containers have decreased even more. The system operates 24 hours a day and dose not increase the current workload, thus allowing the accumulation of a laboratory information system.