Analysis of prognostic factors in 106 cases of carcinoma of the rhinopharynx treated with cobalt teletherapy

A series of 106 patients affected with nasopharyngeal carcinomas and treated by definitive external irradiation from January 1975 to December 1986 was retrospectively reviewed. The median follow-up, from the end of the treatment, was 43 months (range 24-90). The nasopharynx received not less than 60 Gy to the midplane: the clinically negative neck (N0) was treated with a total dose of 50 Gy and the patients who had N1-3 disease received not less than 60 Gy. Thirty-eight patients had a recurrence in the irradiated areas (31 in the nasopharynx, and 7 in the neck); 17 patients developed distant metastases. Disease-free survival at 60 months was 42%. The most significant prognostic factor (p less than 0.05) was the presence of advanced neck involvement (N2-3), since most of the lymphatic and distant recurrences were observed in this group of patients. The overall results did not reveal but slight differences in the survival according to histology, even though patients with undifferentiated carcinomas had a local recurrence rate significantly lower than those with squamous cell carcinomas. Our findings suggest that patients with N2-3 neck diseases or with locally advanced involvement (T3-4) be treated by adjuvant chemotherapy in order to decrease the risk of local and distant relapses.     

Expression and modulation of a mononuclear phagocyte differentiation antigen (PAM-1) during in vitro maturation of peripheral blood monocytes

Summary Human macrophages obtained by in vitro maturation of peripheral blood monocytes express a surface antigen, PAM-1, recognized by a monoclonal antibody and typical of pulmonary alveolar and tissue macrophages. PAM-1, undetectable in freshly isolated peripheral blood monocytes, was expressed in monocyte-derived macrophages after 3 days of in vitro adherent culture and was maximal after 14–15 days (50%–60% of positive cells). Similar levels of PAM-1 positivity were observed in non-adherent monocyte-derived macrophages suggesting that cell adhesion was not a critical requisite for the expression of this antigen. Bacterial lipolysaccharide and a monocyte chemotactic protein preparation respectively suppressed and upregulated PAM-1 expression in monocyte-derived macrophages. In contrast interferon-γ, although enhancing the levels of class II HLA-DR antigen in monocyte-derived macrophages, did not influence the kinetics of appearance and the levels of PAM-1 in these cells. Thus, expression of PAM-1, which is restricted to certain stages of the monocyte-macrophage differentiation pathway, is also differentially modulated by activation signals, which can be present in the microenvironment of inflammed tissues.     

Management of bacterial skin and skin structure infections with polymicrobial etiology

Introduction: Skin and Soft Tissue Infections (SSTIs) are some of the most commonly occurring bacterial infections, with a wide range of possible etiological pathogens and a considerable variety of clinical presentations and severity; from mild to severe life-threatening infections. Several classifications have been proposed based on a specific variable, such as anatomical localization, skin extension, progression rate, clinical presentation, severity, and etiological agent.

Areas covered: The last criteria allows the differentiation of SSTIs as monomicrobial and polymicrobial. Among them, especially those infections with a long lasting or chronic course can be sustained by multiple microbial etiology. Most polymicrobial SSTIs can be included in the following: diabetes foot infections (DFIs), pressure ulcers infection, burn infection, and infected chronic ulcers.

Expert commentary: The medical management of these infections comprises the administration of wide a spectrum antibiotic, taking into consideration the frequent occurrence of multidrug resistant microorganisms as responsible agents. An appropriate deep tissue specimen for microbiological examination is a very important issue, especially for polymicrobial infections, sometimes permitting the distinction between real pathogens and contaminants avoiding more complex antibiotic treatments. This aspect must be strongly emphasized, as frequently superficial swabs remain the specimen of choice because they are easy to obtain.     

Characterization of fetal arrhythmias by means of fetal magnetocardiography in three cases of difficult ultrasonographic imaging

Characterization of ultrasound detected fetal arrhythmias is generally performed by means of M-mode and pulsed Doppler echocardiography (fECHO), sonographic techniques that allow only indirect and approximate reconstruction of the true electrophysiological events that occur in the fetal heart. Several studies demonstrated the ability of fetal magnetocardiography (fMCG) to identify fetal arrhythmias. We report on three women, studied after the 32nd gestational week, who were referred for fMCG because of unsatisfying fetal cardiac visualization with fECHO due to maternal obesity, fetus in constant dorsal position hiding the fetal heart, intrauterine growth retardation, and oligohydramnios. Minor pericardial effusion was present in the third patient and digoxin therapy was given. FMCG were recorded with a 77-channel MCG system working in a shielded room. Independent Component Analysis (FastICA algorithm) was used to reconstruct fetal signals. The good quality of the retrieved fetal signals allowed real-time detection of arrhythmias and their classification as supraventricular extrasystoles (SVE), with/without aberrant ventricular conduction and/or atrioventricular block. The time course of the fetal cardiac rhythm was reconstructed for the entire recording duration; hence, fetal heart rate variability could be studied in time and frequency. Since isolated extrasystoles may progress to more hazardous supraventricular tachycardias, the noninvasive antenatal characterization of, even transient, fetal arrhythmias and their monitoring during pregnancy can be of great clinical impact.     

Lack of rapid virological response predicts interferon-alpha2b/ribavirin therapy failure in HCV genotype 2 patients: a single-centre study

BACKGROUND: A minority of patients with HCV-2 chronic hepatitis does not attain a sustained virological response to interferon-based therapies. Registration trials have failed to identify the real proportion of HCV-2 non-responders, and predictors of non-response. The analysis of 'real-life' HCV-2 patients might help define the effectiveness of anti-HCV therapy and the role of response moderators. METHODS: A re-analysis of all treatment-naive HCV-2 patients who consecutively received weight-dosed ribavirin with either 3 MU three times a week standard interferon-alpha2b or 1.5 microg/kg/week pegylated interferon-alpha2b. RESULTS: The 94 interferon-treated patients and the 136 pegylated-interferon-treated patients were comparable for demography, prevalence of cirrhosis (25%) and adherence to therapy (74%). By intention-to-treat analysis, the overall sustained virological response rate was 80% (82% interferon versus 78% pegylated interferon). Overall, sustained virological rates were 83% for the 182 patients who cleared HCV RNA at week 4 (rapid virological response) and 52% for the 48 who did not (P < 0.001). The corresponding week 12 figures of HCV RNA clearance were 90% and 32%, respectively (P < 0.001). Sustained response was independent of gender, age, body mass index, modality of infection, duration and severity of liver disease, adherence to therapy and interferon type. After stratification for interferon type, the only treatment failure predictor was persistence of HCV RNA at week 4 and 12. CONCLUSIONS: Despite the prevalence of moderators of treatment outcome, HCV-2 patients showed as high sustained virological response rates as those reported in registration trials for HCV-2 and HCV-3 pooled patients; pegylated interferon therapy failure was predicted by lack of rapid virological response.     

Identification and characterization of an endogenous chemotactic ligand specific for FPRL2

Chemotaxis of dendritic cells (DCs) and monocytes is a key step in the initiation of an adequate immune response. Formyl peptide receptor (FPR) and FPR-like receptor (FPRL)1, two G protein-coupled receptors belonging to the FPR family, play an essential role in host defense mechanisms against bacterial infection and in the regulation of inflammatory reactions. FPRL2, the third member of this structural family of chemoattractant receptors, is characterized by its specific expression on monocytes and DCs. Here, we present the isolation from a spleen extract and the functional characterization of F2L, a novel chemoattractant peptide acting specifically through FPRL2. F2L is an acetylated amino-terminal peptide derived from the cleavage of the human heme-binding protein, an intracellular tetrapyrolle-binding protein. The peptide binds and activates FPRL2 in the low nanomolar range, which triggers intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases through the G(i) class of heterotrimeric G proteins. When tested on monocytes and monocyte-derived DCs, F2L promotes calcium mobilization and chemotaxis. Therefore, F2L appears as a new natural chemoattractant peptide for DCs and monocytes, and the first potent and specific agonist of FPRL2.     

Intense lipid peroxidation in premature clinical coronary atherosclerosis is associated with metabolic abnormalities

Increased oxidative stress is associated with rapid progression of atherosclerosis. In this study we sought to determine whether premature onset of clinical coronary atherosclerosis is associated with increased levels of lipid peroxidation. We measured plasma levels of malondialdehyde (MDA), using high-pressure liquid chromatography, in 42 male patients with early- (<56 years) or late-onset (>64 years) unstable angina and in 2 age-matched control groups (n=20). Plasma MDA levels were higher in the patients with unstable angina than in the control groups (1.57 +/- 0.07 vs 1.14 +/- 0.03 nmol/mL; P<.001). Patients with early-onset angina showed higher MDA levels than those in late-onset patients (1.75 +/- 0.11 vs 1.44 +/- 0.097 nmol/mL; P<.05), despite a similar prevalence of risk factors for atherothrombosis. The inflammatory component, measured with the use of a high-sensitivity enzyme-linked immunosorbent assay for C-reactive protein, and platelet activity, measured as prothrombin fragment 1+2, failed to predict MDA level. Fasting glucose (P<.05) was the best predictor of MDA level in patients with early-onset unstable angina; uric acid (P=.09) and body-mass index (P=.15) showed trends toward significant correlation with MDA level in the same group of patients. Metabolic abnormalities related to insulin resistance in patients with premature coronary atherosclerosis appear to be important mediators of major plasma oxidative damage.     

Real-time automated polymerase chain reaction (PCR) to detect Candida albicans and Aspergillus fumigatus DNA in whole blood from high-risk patients

We report the development and evaluation of a real-time PCR assay using the LightCycler instrument for the detection of C. albicans and A. fumigatus DNA in whole blood. Recently published consensus criteria for the diagnosis of invasive fungal infection (IFI) were used for all patient samples. Unique and published primer pairs were developed and assessed for sensitivity, specificity, and reproducibility to detect C. albicans and A. fumigatus DNA in samples spiked with purified DNA, and whole blood samples from 8 high-risk patients and 45 negative controls. The real-time assay demonstrated an analytical sensitivity of 10 fg of purified C. albicans and A. fumigatus DNA and was found to be specific for each species. The standardized approach was highly reproducible and detected C. albicans and A. fumigatus DNA in two patients with proven IFI and in one patient with a possible IFI. In addition, we report for the first time the use of recently published international consensus criteria for the diagnosis of IFI in the evaluation of a mildly invasive fungal diagnostic assay. Standardized clinical criteria and a more standardized approach to detect fungal DNA in less invasive patient samples, may permit a more reliable comparison of future studies. A rapid real-time detection of fungal DNA in whole blood, combined with standard clinical markers of response, may be more useful for monitoring patients at risk of developing IFI than other diagnostic methods currently available.     

Prevention of bedside errors in transfusion medicine (PROBE-TM) study: a cluster-randomized, matched-paired clinical areas trial of a simple intervention to reduce errors in the pretransfusion bedside check

BACKGROUND: Transfusion of the incorrect blood component is a frequent serious incident associated with transfusion and often involves misidentification of the patient and/or the unit of blood. The objective of this study was to assess the effect of a simple intervention designed to improve performance of the bedside check and to observe the durability of any effect. The intervention was a tag on blood bags reminding staff to check the patient's wristband. The tag was positioned in such a way that the transfusionist was required to remove the tag to spike the unit. STUDY DESIGN AND METHODS: The intervention was tested in a multicenter cluster-randomized controlled trial incorporating short-term and long-term follow-up periods. The primary endpoint was the proportion of patients transfused with red cell units for whom the key elements of the bedside check were all correctly completed. RESULTS: Fifteen matched-paired clinical areas at 12 participating hospitals in six countries were included in the trial. Combining data from all participating hospitals, the bedside check was correctly performed in 37 percent of transfusions during the baseline audit period. There was no evidence of a favorable effect of the intervention immediately after its introduction (pooled odds ratio, 1.09; 95% confidence interval, 0.54-2.17). There was similarly no evidence of a favorable effect after continued use of the intervention for an additional 8 weeks. CONCLUSIONS: A simple intervention in the form of a barrier warning label on blood bags reminding staff to check the patient's wristband failed to improve bedside transfusion practice. The robust study design developed for this study could be applied to investigate other interventions to improve the safety of bedside transfusion practice.