Utilization of common inflammatory markers in new, symptomatic, primary care outpatients based on their cost-effectiveness.

Few studies have demonstrated the optimal usage of common inflammatory markers, alone or in combination, based on the cost-effectiveness. We analyzed the yield and cost of C-reactive protein (CRP), white blood cell count (WBC), erythrocyte sedimentation rate (ESR), sialic acid, and protein fractionation in 177 new primary care outpatients with inflammation-related symptoms. A useful result (UR) was assigned if tests contributed to a change in physician's diagnosis or decision-making. Costs of testing were calculated based on either single or simultaneous measurement. Five inflammatory markers generated 147 URs in 123 patients. CRP showed the best contribution to generation of UR, followed by sialic acid, protein fractionation, WBC, and ESR. CRP demonstrated poor correlation with WBC (r = 0.458), while sialic acid strongly correlated with total absolute amount of alpha1 and alpha2 fractions in protein fractionation (r = 0.855) and moderately with ESR (r = 0.651). The combination of CRP and WBC produced the best cost-effectiveness at a cost of Yen 1169 (US dollars 9.6 or Euro 9.7)/additional UR against CRP testing alone. Sialic acid, an automated multichannel analyzer-based test, demonstrated the favorable cost-effectiveness over ESR or protein fractionation when combined with CRP (and WBC). Our results indicate that the optimal usage of these inflammatory markers should involve careful cost-effectiveness considerations.     

Clinical parameters that predict histology of postchemotherapy retroperitoneal lymph node mass in testicular cancer

BACKGROUND: Since the advent of cisplatin-based chemotherapy, the majority of metastatic testicular cancers can be cured by chemotherapy followed by retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND confers no therapeutic benefit if the residual mass contains no viable cells. Therefore, to determine which parameters predict a patient's likelihood of having only necrosis in the residual mass, we retrospectively analyzed clinical parameters of patients who underwent postchemotherapy RPLND. METHODS: Data from 27 patients with metastatic testicular cancer were analyzed. The histology of the primary tumor was seminoma in 11 cases and non-seminoma in 16 cases. All of the patients with non-seminoma showed a normalization of tumor markers after chemotherapy. Analysis of clinical parameters included data for the initial histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal mass size, and the histology of the dissected RPLNs. RESULTS: Histological examination of dissected RPLNs showed residual tumor in 27% of seminoma patients and 38% of non-seminoma patients. In seminoma patients, no viable cells were found in all six patients with pretreatment lactate dehydrogenase (LDH) levels below 7.5 times the upper limit of normal, or in all five of the patients with postchemotherapy RPLNs less than 2.5 cm. In non-seminoma patients, no viable cells were found in nine of 10 patients with pretreatment alpha-fetoprotein (AFP) levels less than 2700 ng/mL, or in eight of nine patients with residual mass less than 2.5 cm. CONCLUSIONS: Both postchemotherapy RPLN mass size and pretreatment tumor marker levels are possible predictors for necrosis of the residual mass in testicular cancer patients.     

Immunohistochemical localization of cathepsin D, proliferating cell nuclear antigen and epidermal growth factor receptor in human breast carcinoma analysed by computer image analyser: correlation with histological grade and metastatic behaviour

 

Aims:

The purpose of this study is to examine the relationship between immunohistochemical localization of cathepsin D (CD), proliferating cell nuclear antigen (PCNA) and epidermal growth factor receptor (EGF-R) in 65 cases of breast carcinoma in Japanese women and traditional prognostic factors such as histological grade, lymph node status, mitotic rate and clinical stage, in order to possibly identify some indicator(s) that may be specifically associated with prognosis.  

Methods and results:

Serial sections of 5-μm thick were cut from the archival formalin-fixed, paraffin-embedded tissue blocks, and processed for CD, PCNA and EGF-R immunostaining. The results were analysed by computer-based image analysis system. All samples showed a positive immunoreaction for cathepsin D in both the parenchyma and stroma. However, the staining area and intensity varied from cell to cell in the parenchyma and stroma as well as among samples. Subsequently, the evaluation of immunostaining for CD was separately performed in both the parenchyma and stroma (CDpar and CDstr, respectively) and the combination of both components (CDtotal). PCNA and EGF-R showed positive immunostaining almost exclusively in the parenchymal component of the carcinoma tissue specimens. CDtotal significantly correlated with the histological grade, PCNA index (PI), mitotic rate (MR), EGF-R and lymph node metastasis. Significant correlation was also demonstrated between CDpar and the histological grade, EGF-R and lymph node metastasis, or between CDstr and MR, EGF-R and lymph node metastasis. EGF-R correlated highly with the histological grade, MR score, lymph node metastases and recurrence-free survival.  

Conclusions:

Both the CD parameters and EGF-R are valuable indicators for predicting the biological behaviour of human breast carcinoma.     

ALTERED HEPATIC METABOLISM OF FATTY ACIDS IN RATS FED A HYPOLIPIDAEMIC DRUG, FENOFIBRATE

The aim of this study was to examine the effects of dietary fenofibrate (0.05% in the diet) on ketone body production and lipid secretion in isolated perfused rat liver. Feeding with fenofibrate for 7–9 days caused an increased liver weight. Ketone body production was significantly greater in the livers perfused with oleic acid than in those perfused without fatty acid, with the elevation of the ratio ofβ-hydroxybutyrate:acetoacetate indicating an increased redox potential in mitochondrial compartments by exogenous fatty acid. On the other hand, fenofibrate feeding caused a further stimulation of ketone body production from both endogenous and exogenous fatty acid substrates, respectively, with a decreased ratio ofβ-hydroxybutyrate:acetoacetate as compared to respective control livers, indicating a decreased redox potential. Hepatic secretion of triglyceride, but not of cholesterol, was decreased markedly in the fenofibrate-fed rats, especially when oleate was provided, suggesting an inverse relationship between rates of ketogenesis and triglyceride secretion. These results suggest that the altered hepatic metabolism of long-chain fatty acids between oxidation and esterification caused by fenofibrate may thus be a factor responsible for the decreased secretion of triglyceride, hence leading to hypotriglyceridaemiain vivo.     

Leukocyte-Endothelium Interaction in the Rat Mesenteric Microcirculation during Halothane or Sevoflurane Anesthesia

Background: The effects of inhalational anesthetics on the microcirculation, including leukocyte dynamics, remain to be clarified. The authors investigated halothane and sevoflurane anesthesia to determine if these agents evoked leukocyte adhesion through endothelial cell-dependent mechanisms involving such adhesion molecules.

Methods: Rats were anesthetized with halothane or sevoflurane in 100% oxygen and the lungs were mechanically ventilated. Leukocyte behavior in mesenteric venules was recorded through intravital video microscopy under monitoring microvascular hemodynamics. To examine the mechanisms for leukocyte rolling and adhesion, these studies were repeated after animals were pretreated with a monoclonal antibody against P-selectin (MAb PB1.3) or against intracellular adhesion molecule-1 (ICAM-1; MAb 1A29): P-selectin required for rolling of circulating leukocytes and ICAM-1 for firm adhesive interactions with leukocyte integrins.

Results: Under baseline anesthetic conditions (1 minimum alveolar concentration [MAC]), venular wall shear rates, an index of the disperse force on marginating leukocytes, in the sevoflurane-treated rats were about two times higher than those with halothane. At 2 MAC, halothane caused a marked arteriolar constriction and decreasing shear rates concurrent with an increasing density of venular leukocyte adhesion. Sevoflurane at 2 MAC induced leukocyte rolling and adhesion, which were attenuated by PB1.3 and 1A29, without alterations in the wall shear rates. Halothane-induced leukocyte adhesion was not prevented by PB1.3 but it was by 1A29.     

Improvement of Transdermal Delivery of Tetragastrin by Lipophilic Modification with Fatty Acids

The in-vitro permeability of chemically modified tetragastrin with fatty acids through the rat skin was studied. The permeability of these compounds through intact skin and stripped skin of rat was determined with a Franz-type diffusion cell. The permeation of tetragastrin across the intact skin was improved by chemical modification with acetic acid and butyric acid. However, tetragastrin and caproyl-tetragastrin did not permeate across the intact skin up to the end of experiment. The permeation of tetragastrin across the stripped skin was improved by chemical modification, the skin flux of these acyl derivatives being in the order: acetyl > butyroyl > caproyl. The stability of tetragastrin in skin homogenate was also significantly improved by chemical modification with fatty acids. These results suggest that chemical modification of tetragastrin with fatty acids increases its lipophilicity, which makes it permeable across the stratum corneum. Moreover, the chemical modification reduced the degradation of tetragastrin in the viable skin, resulting an increase in permeation of tetragastrin across the skin.     

Extracardiac Direct Total Cavopulmonary Connection

We report a successful extracardiac direct total cavopulmonary connection without prosthetic materials performed in a 3-year-old boy with tricuspid atresia, infundibular pulmonary stenosis, and normally positioned great arteries. The transected pulmonary trunk was bought down posterolaterally with respect to the right atrium and was anastomosed end-to-end with the inferior vena cava.     

Genomic analysis in Candida albicans]

With the recent advances in DNA sequencing technology, a succession of entire genome sequences have been published. A number of genome projects are underway in pathogenic fungi. From these, we present the history and current status of the genomic analysis of Candida albicans. The sequencing project for this organism has been undertaken at Stanford University, and is now nearing the end.     

Effects of obstructive jaundice on neutrophil production and acquisition of chemotactic activity in the bone marrow

Background and Aims:  Increased numbers and enhanced functions of peripheral neutrophils have been observed in obstructive jaundice. However, the effects of obstructive jaundice on the bone marrow, that is neutrophil production and acquisition of neutrophil chemotactic activity, have been poorly understood. In the present study, differentials of bone marrow cells and chemotactic activity of bone marrow neutrophils were evaluated in bile duct-obstructed rats.
Methods:  Male Wistar rats underwent either bile duct obstruction for 10 days or bile duct obstruction for 4 days followed by 6 days' internal biliary drainage. Differentials of peripheral blood and bone marrow cells were sequentially determined. Chemotactic activity of peripheral and bone marrow neutrophils was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-β) as a chemoattractant.
Results:  Numbers of peripheral neutrophils significantly increased after bile duct obstruction. Significant increases in the myeloid/erythroid (M/E) ratio of bone marrow cells were observed after bile duct obstruction. The neutrophil proliferative pool (promyelocytes and myelocytes) increased initially, followed by an increased neutrophil storage pool (metamyelocytes, bands, and segmented neutrophils). The M/E ratio as well as the neutrophil proliferative and storage pools normalized after internal biliary drainage. Chemotactic activity was enhanced in both peripheral and bone marrow neutrophils after bile duct obstruction, and enhanced chemotaxis was alleviated with internal biliary drainage.
Conclusion:  The present results strongly suggest the principal role of the bone marrow in increasing the number of neutrophils and their chemotactic activity during obstructive jaundice.