Expression of cell-matrix molecules and integrin receptors in human liver grafts during chronic rejection

Abstract The inflammatory response of immune cells to target cells and cell-matrix molecules is regulated by several receptor-ligand molecules. As fibrosis develops in ongoing chronic rejection after liver transplantation, it is of interest to analyze patterns of integrin receptors and cell-matrix molecules in order to study the relation between immune cells and the stromal and parenchymal cells. In the present study, we demonstrated the expression of these molecules in chronic rejected human liver grafts using immunohistochemical techniques. The results showed a differential expression and induction of integrin receptors and cell-matrix molecules on resident liver cells, especially on sinusoids, reflecting a state of chronic inflammation and a specific interaction between integrin receptors and cell-matrix molecules. The patterns of induced integrin receptors on graft-infiltrating cells was closely related to the local production of cell-matrix molecules and reflected the final sequence of a stepwise progress of the inflammatory reaction.     

Comparative clinical trial of fenticonazole ovule (600 mg) versus clotrimazole vaginal tablet (500 mg) in the treatment of symptomatic vaginal candidiasis

A multi-centre, randomized, single-blind, parallel-group clinical trial was undertaken in 50 patients (26 fenticonazole, 24 clotrimazole) with symptomatic vaginal candidiasis to compare the antifungal efficacy and tolerability of single-dose intra-vaginal treatment with a fenticonazole ovule (600 mg) or a clotrimazole vaginal tablet (500 mg). Assessment was by laboratory mycological investigation and symptomatic assessments for a period of 3 weeks from the day of treatment. Of the 50 patients, 43 (23 fenticonazole, 20 clotrimazole) returned for assessment 1 week after drug administration and 32 (17 fenticonazole, 15 clotrimazole) were re-assessed 3 weeks after drug administration. Both treatments resulted in very similar and highly significant improvements in symptoms, associated with disappearance of detectable Candida in approximately 70% of patients. There were no significant differences between treatments and no appreciable incidence of relapse during the 3-week period of observation. At the end of this period, 10 (59%) of 17 fenticonazole patients were totally disease-free, as compared with 10 (67%) of 15 patients after clotrimazole treatment. The cure rate observed was somewhat less than that previously seen when intra-vaginal cream formulations of the same two drugs were given on a multiple-dose basis. Both drugs were very well tolerated, with no reports of appreciable local or systemic adverse reactions to either drug.     

Acetabular preparation in cementless revision total hip arthroplasty

The rationale for and experience with the use of a hemispherical, cementless, microporous socket (Harris-Galante prosthesis) are presented as an approach to acetabular revision arthroplasty. Advantages are noted in preservation of existing bone, ease of rigid fixation, and bone grafting with either lyophylized particle allograft or autograft. The early results of a series of 75 sockets show no loss of fixation, mild to major resorption of non-contained bone graft, and favorable roentgenographic appearance of contained bone graft. In bone-grafted regions, a high percentage of lucencies at the graft-porous interface implies a lack of bone ingrowth. The authors were unable to characterize any roentgenographic behavioral differences between allograft or autograft. The approach is successful in severely deficient acetabulae, especially of the Type III combined cavitary and segmental medial wall deficiency.     

Prognostic value of blood glucose in patients with cardiogenic shock.

BACKGROUND: Although an elevated blood glucose has prognostic value in cardiovascular disease, few data are available regarding its prognostic value for patients across the spectrum of cardiogenic shock. METHOD AND RESULTS: A total of 81 patients with cardiogenic shock whose blood glucose and adrenaline were measured on arrival at the emergency room (ER) were enrolled in this prospective study. The primary endpoint was death from any cause in hospital. The rate of death was 12.3% (10/81), and the glucose level was lower among patients who were discharged alive than among those who died (8.7+/-3.7 mmol/L vs 13.8+/-6.7 mmol/L, p<0.001). The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of glucose level (p<0.05). The blood glucose level of 9.2 mmol/L had the highest combined sensitivity and specificity for the identification of death. In the multiple logistic-regression analysis for the primary outcome, the adjusted odd ratio for a glucose level of 9.2 mmol/L or more was 5.8 (95% confidence interval, 1.0-32.8, p=0.047). There was a significant positive correlation between the glucose and adrenaline levels (R=0.726, p<0.0001). CONCLUSION: The measurement of blood glucose level on ER arrival provides predictive information for use in risk stratification across the spectrum of cardiac emergencies complicated by cardiogenic shock.     

Influence of Hemorrhagic Shock Followed by Crystalloid Resuscitation on Propofol: A Pharmacokinetic and Pharmacodynamic Analysis

Background: Previous work has demonstrated that ongoing hemorrhagic shock dramatically alters the distribution, clearance, and potency of propofol. Whether volume resuscitation after hemorrhagic shock restores drug behavior to baseline pharmacokinetics and pharmacodynamics remains unclear. This is particularly relevant because patients suffering from hemorrhagic shock are typically resuscitated before surgery. To investigate this, the authors studied the influence of an isobaric bleed followed by crystalloid resuscitation on the pharmacokinetics and pharmacodynamics of propofol in a swine model. The hypothesis was that hemorrhagic shock followed by resuscitation would not significantly alter the pharmacokinetics but would influence the pharmacodynamics of propofol.

Methods: After approval from the Animal Care Committee, 16 swine were randomly assigned to control and shock-resuscitation groups. Swine randomized to the shock-resuscitation group were bled to a mean arterial blood pressure of 40 mm Hg over a 20-min period and held there by further blood removal until 42 ml/kg of blood had been removed. Subsequently, animals were resuscitated with lactated Ringer's solution to maintain a mean arterial blood pressure of 70 mm Hg for 60 min. After resuscitation, propofol (750 [mu]g[middle dot]kg-1[middle dot]min-1) was infused for 10 min. The control group underwent a sham hemorrhage and resuscitation and received propofol at the same dose and approximate time as the shock-resuscitation group. Arterial samples (20 from each animal) were collected at frequent intervals until 180 min after the infusion began and were analyzed to determine drug concentrations. Pharmacokinetic parameters for each group were estimated using a three-compartment model. The electroencephalogram Bispectral Index Scale was used as a measure of drug effect. Pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model.

Results: The raw data demonstrated minimal differences in the mean plasma propofol concentrations between groups. The compartment analysis revealed some subtle differences between groups in the central and slow equilibrating volumes, but the differences were not significant. Hemorrhagic shock followed by resuscitation shifted the concentration effect relationship to the left, demonstrating a 1.5-fold decrease in the effect-site concentration required to achieve 50% of the maximal effect in the Bispectral Index Scale.     

Enzyme-linked Immunosorbent Assay of Pro-gastrin-releasing Peptide for Small Cell Lung Cancer Patients in Comparison with Neuron-specific Enolase Measurement

Our previous study demonstrated that pro-gastrin-releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.     

Cystic pancreatic tumors: CT and sonographic assessment

Thirty-five CT scans and 23 sonograms of 45 pathologically proved pancreatic cystic neoplasms (16 microcystic adenomas, 17 mucinous [macrocystic] cystadenomas, and 12 mucinous [macrocystic] cystadenocarcinomas) in 43 patients were retrospectively and blindly reviewed. Radiologic findings and their usefulness in differentiating microcystic from mucinous subtypes were assessed. The number of cysts within the tumors (more than six in microcystic adenomas and six or fewer in mucinous cystadenomas and cystadenocarcinomas) and the diameter of the majority of cysts within the tumor (less than or equal to 2 cm in microcystic adenomas and greater than 2 cm in mucinous tumors) were the most helpful radiologic findings in differentiating tumor types. Calcification was present in 38% of microcystic adenomas, 18% of mucinous cystadenomas, and 8% of mucinous cystadenocarcinomas by CT. Calcification was not definitely identified on any of the sonograms. A central scar was identified in only two (13%) of 16 microcystic adenomas. Blind retrospective review was often able to correctly classify tumors as either microcystic (CT, 93%; sonography, 78%) or mucinous (CT, 95%; sonography, 93%). All tumors with a typical appearance on either CT or sonography were categorized correctly. Cystic pancreatic tumors may be difficult to prospectively separate from other types of pancreatic cysts. Assuming a cystic neoplasm is present, it often can be classified correctly as microcystic or mucinous (macrocystic) by using the above criteria.     

Platelet alpha granule secretion in cerebral ischemia: effect of short and long term low dose aspirin treatment

The effect of short and long-term therapy with aspirin (50 mg/day) on platelet alpha granule secretion was studied in 11 healthy controls and 57 patients suffering from transient cerebral ischemic attacks (TIA) with and without accompanying diabetes and hypertension. Plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) were measured as indicators of platelet alpha granule secretion. beta-TG and PF 4 levels were increased following cerebral ischemia. Aspirin treatment failed to suppress plasma levels of both proteins when measured a month and then a year after initiation of treatment. Therefore, these proteins may be poor indicators of platelet inhibition by aspirin.