Increased risk of malignancy in patients with systemic lupus erythematosus

BACKGROUND: Systemic lupus erythematosus is a chronic, multisystem, autoimmune disorder that primarily affects women. Morbidity and mortality have improved for lupus patients during the last 15 years. An increased risk of malignancy in patients with lupus has been shown in some, but not all studies. The purpose of this study was to ascertain cancer risk in lupus patients by linking two disease registries. METHODS: Participants in the Chicago Lupus Cohort included 616 women with lupus who were residents of Cook County, Illinois. They were seen during 1985-1995 at 4 University, inner city, and suburban inpatient and outpatient clinics in Chicago. Malignancies occurring in these subjects during the study interval, 1985-1995, were identified from the Illinois State Cancer Registry by matching name, birthdate, and social security number. Standardized incidence ratios (SIRs) were estimated for all malignancies in this cohort of lupus patients using age, gender, and all race or race-stratified specific cancer incidence data from Cook County, Illinois. RESULTS: The registry linkage study with the Illinois State Cancer Registry documented that 30 women with lupus had a malignancy. The expected number of malignancies for women in the lupus cohort was 15.0. There were 8 cases of breast cancer and 4 each of lung and cervical cancer. In the remaining 14 women, 12 different types of cancers were noted. The SIR and 95% confidence interval (CI) for malignancy for all women with lupus in the study were 2.0 (1.4, 2.9) and lung cancer was the only individual cancer increased in all women--SIR and 95% CI were 3.1 (1.3, 7.9). In the analysis stratified by race, the risk of malignancy (SIR and 95% CI) was increased in Caucasian women, 2.3 (1.4, 3.9). Breast cancer was the only individual cancer increased in Caucasian women with lupus with an SIR and 95% CI of 2.9 (1.4, 6.4). CONCLUSIONS: Lupus patients have an increased risk of malignancy. Breast, lung, and gynecological malignancies were the most common malignancies observed in the cohort and breast cancer was significantly increased in Caucasian women.     

Adenoviral-mediated suicide gene therapy for hepatic metastases of breast cancer

Metastases of breast cancer are a major cause of treatment failure. To evaluate the therapeutic efficacy of suicide gene therapy in metastatic breast cancer, we used the herpes simplex virus thymidine kinase (HSV-tk) gene followed by ganciclovir (GCV) administration to treat breast cancer, generated by an adenocarcinoma cell line MOD in syngeneic mice. The bystander effect of HSV-tk + GCV on tumor cell killing was illustrated by demonstrating complete regression of subcutaneous tumors consisting of 90% parental tumor cells and 10% HSV-tk transformed tumor cells. To establish a model of breast cancer metastases in the liver, tumors were generated by intra-hepatic implantation of MOD cells in syngeneic animals. Two weeks after tumor cell implantation, replication defective adenoviral vectors expressing HSV-tk (ADV.tk), or beta-galactosidease (ADV. beta-Gal) were injected intratumorally, followed by buffer or GCV administration. Treatment with ADV.tk + GCV resulted in significant regression of tumor (P < .001), as assessed by computerized morphometric analysis of residual tumor. This was reflected as a significant prolongation of survival in treated animals (P < .001). These results demonstrate that ADV-mediated suicide gene therapy in vivo can be incorporated in a comprehensive treatment strategy for liver metastases of breast cancer.     

Electron microscopic study of the permeability of terminal blood vessels of the M. triceps brachii to horseradish peroxidase in fetal, juvenile and adult rats

At the basis of some ultrastructural differences in fetal, juvenile and adult rat triceps muscle capillaries as described in preliminary papers the permeability of these capillaries to horse radish peroxidase was investigated. Capillaries of fetal and juvenile rats up to the 3rd week after birth were impermeable to horse radish peroxidase (HRP) for 2 and 10 minutes after injection, which can be explained with the low pinocytotic activity and the more complex structure of the junctions. Capillaries of the triceps brachii muscle in adult rats aged 2 month and more show a low permeability to HRP 2 and 5 minutes and a high permeability 15 minutes after the injection of the tracer. In the capillary segment of the terminal bed the tracer was traversed especially by the means of vesicles and some transendothelial channels built by linked vesicles. The interendothelial junctions seemed to be tight. In the venular segment of th capillaries and in small postcapillary venules additional to the vesicular transport a high permeability of some junctions was stated. The significance of the different permeability of distinct segments of the terminal vascular bed to small macromolecules is discussed with respect to the theories of th physiologists and compared with the results of recent investigators.     

Systemic meningococcal infections in patients with acquired complement deficiency

Congenital deficiency of the late components of the complement may predispose the individual to systemic meningococcal infection. Assuming that patients with acquired complement deficiencies may also have an increased risk of contracting meningococcal infections, a retrospective and prospective study to assess this association was conducted. Over 20 years (1970-1989), 30 patients with meningococcemia or meningococcal meningitis, proven by blood or CSF culture, were treated at the Beilinson Medical Center. Only one patient died of the infection. Risk factors were found in three patients (10%). One had a congenital deficiency of C7, and two had acquired complement deficiency due to systemic lupus erythematosus (SLE) and membranoproliferative glomerulonephritis (MPGN). These latter two patients had low serum concentration of C3 and C4 and reduced complement hemolytic activity before onset of the infection. Since the incidence of culture-proven systemic meningococcal infection in the Jewish population in central Israel is 1/100,000, and the prevalence of SLE and MPGN is, at most, 250/100,000, the finding of two patients with meningococcal infection and these rare disorders is over 100 times the expected incidence. We conclude that patients with acquired complement deficiency are at significant risk of meningococcal infection.     

Traumatic tricuspid regurgitation complicating endocarditis and right-to-left intracardiac shunt. A case report of successful operation

OBJECTIVE: To assess the prevalence of cystinuria and cystine stone disease among families of patients with cystine stones, and to determine their distribution by age, sex and associated morbidity. SUBJECTS AND METHODS: The study comprised 180 relatives (87 males and 93 females, mean age 43 years) descended from two brothers over four generations who live in two areas in northern Jordan. Data were collected using a questionnaire and home visits, by urinary cystine testing and radiology to detect stone, and assessing hypertension and renal impairment. RESULTS: Of the 180 subjects, 104 (58%) had a positive reaction for cystine in urine; 33 (32%) of these were younger than 15 years. Twenty members (11%) of the families had evidence of renal cystine stone disease. Hypertension and renal impairment were detected in a significant proportion of individuals with cystine stone disease. CONCLUSION: Cystinuria is a major risk factor for cystine stone formation. Family screening is valuable in detecting the cystinuric population and in assessing individuals with stones. Early recognition, treatment and counselling result in better management and prevention. The establishment of a cystine study group in our region is essential.     

Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the Th1-biasing cytokines IL-12 and IFN-alpha

DNA-based immunization strategies designed to elicit cellular antitumor immunity offer an attractive alternative to protein- or peptide-based approaches. In the present study we have evaluated the feasibility of DNA vaccination for the induction of CTL reactivity to five different melanoma Ags in vitro. Cultured, monocyte-derived dendritic cells (DC) were transiently transfected with plasmid DNA encoding human MART-1/Melan-A, pMel-17/gp100, tyrosinase, MAGE-1, or MAGE-3 by particle bombardment and used to stimulate autologous PBMC responder T cells. CTL reactivity to these previously identified melanoma Ags was reproducibly generated after two or three stimulations with genetically modified DC. Co-ordinate transfection of two melanoma Ag cDNAs into DC promoted CTL responders capable of recognizing epitopes from both gene products. Coinsertion of genes encoding the Th1-biasing cytokines IL-12 or IFN-alpha consistently enhanced the magnitude of the resulting Ag-specific CTL reactivity. Importantly, DC transfected with a single melanoma Ag cDNA were capable of stimulating Ag-specific CTL reactivity restricted by multiple host MHC alleles, some of which had not been previously identified. These results support the inherent strengths of gene-based vaccine approaches that do not require prior knowledge of responder MHC haplotypes or of relevant MHC-restricted peptide epitopes. Given previous observations of in situ tumor HLA allele-loss variants, DC gene vaccine strategies may elicit a greater diversity of host therapeutic immunity, thereby enhancing the clinical utility and success of such approaches.     

Low prevalence of Listeria monocytogenes in cull sows and pork

The goal of this study was to determine the prevalence of Listeria monocytogenes in sows slaughtered at a single Midwestern plant on two occasions (trial 1, n = 179 sows; trial 2, n = 160 sows). Fecal samples collected antemortem (trial 1) as well as animal tissues, and carcass swabs collected at the abattoir (trials 1 and 2) were analyzed. Eight isolates of L. monocytogenes were recovered from five samples that represented 0.18% of the total samples (n = 2,775). In trial 1, L. monocytogenes was detected in a tonsil sample (0.6%; 1 positive of 181 tonsils), in a carcass (0.6%; 1 positive of 179 carcasses), which was sampled prior to the organic rinse, and in two chopped meat block samples (1.2%; 2 positive of 165 samples). In trial 2, L. monocytogenes was only detected in a single chopped meat block sample (0.15%; 1 positive of 688 total samples). These data indicate the low prevalence of L. monocytogenes in the cull sow.     

Vascular pathology of malignant cervical lymphadenopathy: qualitative and quantitative assessment with power Doppler ultrasound

BACKGROUND: Malignant vascular pathology has traditionally been studied with invasive angiography or in vitro immunohistochemistry. The objective of this study was to investigate the vascular patterns and vascular density of benign and malignant cervical lymphadenopathy using power Doppler ultrasound combined with a computed quantitative image processing system. METHODS: Investigations of 189 cervical lymph node lesions were undertaken prospectively using a 5-10 MHz linear array transducer in power mode. The types of vascular patterns displayed with power Doppler ultrasound, after sweep-scanning over the whole lymph node, were classified as hilar, spotted, peripheral, or mixed. Quantitative assessment of vascularity was made by sampling three parallel planes of each lymph node. A computed image processing system automatically calculated the density of vascular signals (called the "vascularity index" in this study) within the lymph node plane. RESULTS: Malignant lymph node lesions were shown to have higher vascularity indices (0.169+/-0.147, P < 0.01). The vascular patterns of benign lesions were mostly of avascular or hilar type (in 83% of cases). Malignant lesions were characterized by patterns of mixed (47%), spotted (20%), or peripheral type (11%). When vascular pattern (nonhilar type) and vascularity index (maximum > or = 0.09) were combined, the specificity for diagnosing malignant lymphadenopathy was as high as 97%. Variance in tumor vascularity was noted in both the benign and malignant groups. CONCLUSIONS: Power Doppler ultrasound combined with a computed image processing system provided an objective tool for assessing tumor vascularity quantitatively. Using this modality, the vascular pathology of malignant lymphadenopathy was found to be characterized by higher vascular density and aberrant vascular patterns.     

Passivity phenomena at the silicon/electrolyte interface

The current/potential behaviour of silicon in aqueous alkaline systems was investigated by potentiostatic techniques. In general, curves typical of metal passivity phenomena were obtained, although the effect of the semiconducting nature of silicon was evident. Corrosion and anodic dissolution rates correlated closely with the current/potential curves, but the decrease in corrosion rate after passivation was not as large as is observed with most passivated metal systems. The presence of the passivating oxide had a marked effect on the interfacial capacitance. The oxide itself is not a capacitive element in the interfacial circuit, but exerts an effect on the number of charge-trapping centres (surface states) at the termination of the silicon lattice.     

INFLUENCE OF EXTRUSION ON DAMPING CAMCITIES OF AS-SPRAY DEPOSITED HIGH SILICON ALLOY ZA27 MODIFIED BY CERIUM

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