Unrecognized HIV infection among patients attending sexually transmitted disease clinics

OBJECTIVES: This study examined voluntary HIV testing rates in sexually transmitted disease (STD) clinics. METHODS: Anonymous, unlinked surveys of HIV seroprevalence and medical chart abstractions were conducted in 28 STD clinics in 14 US cities in 1997. RESULTS: Among the 52 260 patients included in the anonymous HIV serosurveys, voluntary HIV testing rates by clinic ranged from 30% to 99% (median = 58%). Patients not tested were more likely to be HIV infected than were patients who were tested, even after those with documented HIV infection were excluded, regardless of demographic characteristics, risk group, or STD diagnosis. CONCLUSIONS: HIV infection is unrecognized in substantial numbers of patients with HIV infection visiting STD clinics. Efforts are needed to increase HIV testing and counseling of all patients visiting these clinics.     

The dimensional symptom structure of schizophrenia and its association with temperament and character

Recent studies suggest that personality may influence symptom expression and social functioning in schizophrenia. This study investigated the relationships between personality and symptom dimensions in schizophrenia patients. Fifty-two schizophrenia patients and 25 five healthy subjects were assessed using the Temperament and Character Inventory (TCI). The patients were also assessed for positive and negative symptoms using SAPS and SANS and scored according to Andreasen's (1995: Andreasen, N.C., Arndt, S., Alliger, R., Miller, D., Flaum, M. 1995. Symptoms of schizophrenia. Methods, meanings, and mechanisms. Arch. Gen. Psychiatry, 52, 341-351) classical three dimensional model and by the five dimensional model of Toomey et al. (1997: Toomey, R., Kremen, W.S., Simpson J.C., Samson, J.A., Seidman, L.J., Lyons, M.J., Faraone, S.V., Tsuang, M.T. 1997. Revisiting the factor structure for positive and negative symptoms: evidence from a large heterogeneous group of psychiatric patients. Am. J. Psychiatry, 154, 371-377). Comparisons between patients and controls revealed significant differences on various TCI scores consistent with a global disorganization of personality in schizophrenia involving both basic neurophysiological and potentially genetically determined traits (i.e. temperament) and developmental aspects of personality (i.e. character). Correlation analysis showed distinct associations between symptoms and personality dimensions. The results suggest that the negative and disorganized dimensions of schizophrenia are related temperamental factors, whereas the psychotic symptoms are more related to characterological abnormalities. The observed patterns of associations also underline the heterogeneity of the classical negative and positive dimensions of schizophrenia.     

Prevention and treatment of implanted central venous catheter (CVC) - related sepsis: a report after six years of home parenteral nutrition (HPN)

Catheter-related sepsis is a serious and common complication in patients receiving home parenteral nutrition (HPN). Prevention measures, prevalence of infections, types of agents and implanted central venous catheters (CVC), effectiveness of antibiotic therapy have been evaluated in 221 patients consecutively followed in our unit from January 1995 to December 2000. The clinical diagnosis of catheter-related infection was made using well-defined criteria. Patients were divided into two groups: A and B, receiving instructions with different modalities: standard (A) and detailed (B), respectively. Sixty CVC-related sepsis occurred in 32 (14%) patients. A multivariate analysis showed that the duration of HPN (P<0.001; OR=0.9), type of catheter (P=0.009; OR=0.12) and type of disease (P=0.033; OR=4.92) significantly influence catheter infection. The type of implanted CVC (159 port-a-cath in 153 patients and 71 tunnelled in 68) seems to affect the infection rate, this being lower in tunnelled (P=0.03). Infection rate was lower in B vs A group (P<0.001) with all types of catheters, suggesting the preventive role of very careful training. In particular, the incidence of CVC-related sepsis was 6/1000 days of HPN (i.e. 6/1000 days of catheterization) in Group A and 3/1000 in Group B. Systemic and antibiotic lock therapy was performed with an 83% successful rate. Gram-positive bacteria were the most frequent CVC infection agents, which are usually eradicated by antibiotic therapy lasting 7 days.     

Intranasal or oral immunization of inbred and outbred mice with murine or human rotavirus VP6 proteins protects against viral shedding after challenge with murine rotaviruses

Intranasal (i.n.) administration of an Escherichia coli-expressed chimeric VP6 protein from the EDIM strain of murine rotavirus to adult BALB/c (H-2(d)) mice along with LT(R192G), an attenuated mutant of the mucosal adjuvant E. coli heat-labile toxin, has been found to consistently stimulate ca. 99% reductions in rotavirus shedding after subsequent EDIM challenge. This study was designed to determine the robustness of this protection, i.e. can VP6 immunization consistently protect against shedding in this model, thus, providing an indication of its potential as a vaccine. Intranasal immunization with two 8.8 microg doses of EDIM VP6 and 10 microg of LT(R192G) was found to stimulate 99% reductions in EDIM shedding in four additional strains of inbred mice belonging to three haplotypes, i.e. DBA/2 (H-2(d)), C57BL/6 (H-2(b)), 129 (H-2(b)) and C3H (H-2(k)). Protection stimulated against EDIM antigen shedding following i.n. immunization with VP6 from the human CJN strain was less (P=0.02) than induced by EDIM VP6 (86% versus 99%), but no further loss of protection was observed when the dose of CJN VP6 was reduced 100-fold. Protection against EDIM shedding was also maintained after i.n. immunization of three strains of outbred mice (CF-1, CD-1 and Swiss Webster) with either EDIM or CJN VP6, i.e. EDIM VP6 immunization reduced EDIM shedding by 99% while CJN VP6 immunization produced reductions of 86-96%. Protection stimulated by oral immunization of BALB/c mice with two 8.8 microg doses of either VP6 chimera plus LT(R192G) was not significantly different from that induced by i.n. immunization. Finally, protection found after either oral or i.n. immunization with EDIM or CJN VP6 was no different when the mice were challenged with McN, another strain of murine rotavirus. These results support further evaluation of VP6 as a vaccine.     

Micellar-type complexes of tailor-made synthetic block copolymers containing the HIV-1 tat DNA for vaccine application

A novel class of cationic block copolymers constituted by a neutral hydrophilic poly(ethylene glycol) (PEG) block and a positively charged poly(dimethylamino)ethyl methacrylate block was prepared for delivery of DNA. These block copolymers spontaneously assemble with DNA to give in aqueous medium micellar-like structures. Five of these novel block copolymers (K1-5), differing in the length of both the PEG chain and the linear charge density of the poly(dimethylamino)ethyl methacrylate block, were prepared and analyzed for gene delivery, gene expression and safety. All five block copolymers protected DNA from DNAse I digestion and delivered the DNA into the cell. However, only three of them (K1, K2 and K5) released the DNA at level allowing efficient gene expression into cells. No toxic effects of both the copolymers alone or their DNA complexes were observed in vitro or in mice. In addition, copolymers were scarcely immunogenic. These results indicate that this novel class of cationic block copolymers is safe and possesses the biological characteristics required for DNA delivery, thus, representing promising vehicles for DNA vaccination.     

Hysteroscopic assessment of menopausal breast-cancer patients taking tamoxifen; there is a bias from the mode of endometrial sampling in estimating endometrial morbidity?

The aim of this study is to evaluate the accuracy of hysteroscopy in detecting tamoxifen-associated endometrial morbidity. Ninety-eight menopausal breast cancer patients taking tamoxifen underwent hysteroscopy because of an endometrial thickness above 4 mm measured by Transvaginal Ultrasonography. Thirty-one women recorded uterine bleeding while 67 were asymptomatic. Hysteroscopies with operative facilities were performed, mainly in out-patient setting. Hysteroscopic findings were matched with histopathology derived from various modalities of tissue collection as suction-curettage, oriented-streak curettage, hysteroscopically-targeted biopsies or polypectomies and hysterectomies. Accuracy of hysteroscopy to estimate a normal or abnormal endometrium was calculated. Abnormal endometrium was detected in 35 patients (64.5% in symptomatic and 22.3% in asymptomatic women, P < 0.001). We found six carcinomas, 18 polyps and 11 hyperplasias. Hysteroscopy showed sensitivity and specificity of 89.2 and 98.4%, respectively. By blind sampling, tissue collection was too scant to give a diagnosis in 29.1% of patients and in 80.5% of patients in whom hysteroscopy showed cystic atrophy the pathologist failed to confirm this condition. Moreover, eight endometrial polyps (36.3%) detected by hysteroscopy were missed. Conversely, by tissue sampling under vision no inadequate specimen was sent to the pathologist and all hysteroscopies showing cystic atrophy and polyps were pathologically confirmed. From literature data, the detection-rate of endometrial pathology in tamoxifen users varies from the lowest to the highest prevalences whether blind or hysteroscopically-targeted modalities of tissue sampling were used, respectively. Hysteroscopy with targeted sampling appears to be the most effective method to assess the endometrial lining. In our experience it is safe, well tolerated and it should be considered the reference test to assess a thickened endometrium in women under tamoxifen.     

Adjuvant chemotherapy in gastric cancer: a meta-analysis of randomized trials and a comparison with previous meta-analyses

AIMS AND BACKGROUND: Up to now adjuvant chemotherapy after curative resection for gastric cancer (GC) has been considered an experimental approach. The results of existing phase III randomized trials comparing chemotherapy with control after surgery are controversial. Three meta-analyses have been published in recent years. It is likely that each of them presents a theoretical bias, mainly as regards the inclusion criteria of the trials. In this article we re-examine this potential bias, highlighting the differences between the present and past meta-analyses on adjuvant chemotherapy for GC. METHODS: Only randomized controlled clinical trials comparing systemic adjuvant chemotherapy with control after radical resection of GC were eligible. Total mortality was assessed as outcome measure of the treatment effect and a pooled odds ratio was calculated using the Peto-Mantel-Haenszel method. RESULTS: After the selection process 17 papers (18 comparisons) proved eligible for inclusion in the meta-analysis with a total of 3118 patients, of whom 1546 randomized to the treatment arms and 1572 to the control arms; 762 and 871 deaths occurred in the treatment and control arms, respectively. Statistical analysis suggests an absence of significant heterogeneity between the trials and a significant advantage in survival for adjuvant chemotherapy (pooled odds ratio, 0.72, 95% Cl, 0.62-0.84). CONCLUSIONS: Our meta-analysis would seem to indicate that adjuvant chemotherapy results in a significant survival advantage in patients with GC. However, this observation undoubtedly requires confirmation in large randomized controlled trials including cisplatin before adjuvant chemotherapy after curative resection for GC can be proposed for use in clinical practice.     

Tumor microenvironment: what have we learned studying the immune response in this puzzling battlefield?

Recent developments hallmark the progress in the understanding of tumor immunology and related therapeutic strategies. The administration of interleukin-2 (IL-2) to patients with cancer has shown that immune manipulation can mediate the regression of established cancers. The identification of the genes encoding cancer antigens and the development of means for effectively immunizing against these antigens has opened new avenues for the development of active immunization of patients with cancer. However, an efficient immune response against tumor comprises an intricate molecular network still poorly understood. Only when the code governing immune responsiveness of cancer will be deciphered, new therapeutic strategies could be designed to fit biologically defined mechanisms of immune rejection of cancer. In this review, we propose that the mechanisms regulating tumor rejection in response to vaccination will be more efficiently identified by following the evolution of treatment induced events within the tumor microenvironment taking advantage of recently developed technological tools. As a model, we will discuss the observed immune response to tumor antigen -specific immunization and its relationship with the systemic administration of IL-2.     

Tumour cell uptake of the metastasis inhibitor ruthenium complex NAMI-A and its in vitro effects on KB cells

PURPOSE: The uptake of NAMI-A (imidazolium trans-imidazoledimethylsulphoxidetetrachlororuthenate) by KB cells in vitro was compared with the effects of this compound on the cell cycle phase distribution of the cells. METHODS: NAMI-A uptake was determined by flameless atomic absorption spectroscopy, and the cell cycle phase distribution was determined by flow cytometry. RESULTS: NAMI-A uptake was proportional to its concentration in the incubation medium. The use of a number of incubation conditions showed that NAMI-A uptake from MEM was independent of the presence of serum and dependent on the presence of amino acids in the incubation medium, and that NAMI-A uptake was markedly higher when the cells were incubated in PBS. The uptake increase observed in PBS did not occur when the cells were kept at 0-4 degrees C, suggesting the presence of active transportation of NAMI-A into cells. In addition, the presence of divalent cations such as Ca(2+) and Mg(2+), appeared to facilitate NAMI-A uptake. The anionic substance transport inhibitor probenecid significantly reduced the active transportation of NAMI-A into cells. The effects of NAMI-A on cell cycle distribution were strictly dependent on its uptake by tumour cells and not on its extracellular concentration. CONCLUSIONS: These findings suggest the interaction of NAMI-A with biological components resulting in possible consequences for the distribution of the compound itself. Furthermore, NAMI-A enters tumour cells both by passive diffusion and by active transportation.