Correlates of HIV transmission risk factors and considerations for interventions in homeless,chemically addicted and mentally ill patients

A study was conducted to ascertain correlates of HIV high risk behaviors and attitudes toward HIV. A questionnaire was administered to 103 men living in a modified therapeutic community (TC) for homeless, chemically addicted and mentally ill men. The psychiatric diagnoses of the sample population included psychotic disorders (48%), depressive disorders (36%), and bipolar disorders (16%). Forty-two percent reported that their primary substance of abuse was cocaine and another 40% named alcohol as the substance to which they were most addicted. Two logistic regression analyses were conducted, one with needle sharing as the outcome measure and one with endorsement of the need for lifestyle changes to reduce risk of HIV transmission. Cocaine users were 3.4 times more likely to have shared needles than the rest of the sample. Patients who had a history of sexually transmitted diseases (STDs) were 17 times more likely to endorse the need for lifestyle changes. The level of HIV transmission knowledge was unrelated to HIV risk behaviors or attitudes.     

Expansion of CD8+ T cells that express low levels of the B cell-specific molecule CD20 in patients with multiple myeloma

An expanded cytotoxic/memory T-cell subpopulation expressing low levels of the B-cell-specific CD20 molecule was found in peripheral blood and bone marrow of patients with multiple myeloma at the time of diagnosis, but returned to normal levels following treatment. CD3+CD20dim cells were also increased in monoclonal gammopathy of unknown significance albeit at lower levels. Lower CD3+CD20dim cell numbers at baseline may be associated with lack of response to treatment and a poor outcome. Because expansion of these T cells may be related to disease status, further studies should investigate their potentially unique function in plasma cell dyscrasias.     

Bonding indirect resin composites to metal: Part 1. Comparison of shear bond strengths between different metal-resin bonding systems and a metal-ceramic system

PURPOSE: This laboratory study compared the shear bond strength between three indirect resin composites and a noble alloy using their respective bonding systems. MATERIALS AND METHODS: One hundred twenty disks cast in a medium-gold, high-noble metal-ceramic alloy (V-Deltaloy) were divided equally into four groups and received different treatments for veneering: Conventional feldspathic porcelain (Omega) was applied on one set of specimens to be used as a control, and three indirect resin composites (Artglass, Sculpture, Targis) with their respective bonding systems were used for the other groups. The specimens were tested in a parallel shear test, half of them after 24-hour dry storage at room temperature and the rest after 10-day storage in normal saline solution at 37 degrees C and thermocycling. The fractured specimens were evaluated to determine the nature of the failure. RESULTS: The mean shear bond strength values (in MPa), before and after wet storage and thermocycling, were 30 and 23 for the metal-ceramic group, 29 and 23 for the Artglass group, 20 and 19 for the Sculpture group, and 17 and 14 for the Targis group, respectively. The metal-ceramic and Artglass groups exhibited significantly higher bond strengths than the other two groups. All specimens, with the exception of the Sculpture group, showed a significant decrease in bond strength after wet storage and thermocycling. CONCLUSION: No group exceeded the shear bond strength of the metal-ceramic group, but the Artglass group with its respective metal-resin bonding system exhibited similar bond strengths. The Sculpture group showed a stable bond after water storage and thermocycling.     

Tumor necrosis factor biology in experimental and clinical arthritis

The successful introduction of antitumor necrosis factor treatments in clinical practice confirmed the biologic relevance of tumor necrosis factor function in chronic inflammatory conditions in humans, mainly in the pathogenesis of rheumatoid arthritis and inflammatory bowel disease. Studies on patients receiving antitumor necrosis factor treatments offered deeper insights into the mechanisms of antitumor necrosis factor action in arthritis and revealed a master regulatory role for tumor necrosis factor in a multitude of biologic processes underlying pathogenesis. However, within such pleiotropism of key functions, blockade of tumor necrosis factor has also led to a significant incidence of unwanted clinical complications. Experimental work in animal models is providing additional clues on the specific function of tumor necrosis factor and its receptors in disease, especially on the molecular and cellular pathways through which tumor necrosis factor orchestrates beneficial and deleterious responses.     

Primary aortojejunal fistula due to foreign body: a rare cause of gastrointestinal bleeding

Primary and secondary aortoenteric fistulae are infrequent causes of gastrointestinal bleeding. We report a rare case of a 49-year-old man with bleeding due to an aortojejunal fistula caused by a foreign body. This is the fifth case in the literature in which a foreign body was found to be associated with the development of an aortoenteric fistula. Our patient presented with two herald bleeds with an interval time of 1 week; in previous cases, only one herald bleed has been reported. In addition to the usual resuscitation measures, the patient was treated with primary repair of the small-intestine defect and replacement of the aneurysm with a prosthetic aortic graft. He remains in excellent health thereafter.     

Embolic stroke after "cured" prosthetic aortic valve endocarditis

The authors report on the case of a patient with infective endocarditis of a prosthetic valve in the aortic position, after receiving percutaneous transluminal coronary angioplasty. Transesophageal echocardiography provided valuable information about the existence and size of vegetations at the time of initial diagnosis and during followup. Despite successful treatment resulting in good control of the infection and a significant reduction of vegetation size, the patient still suffered a major cerebral embolic event early after hospital discharge.     

Sequence specificity of aminoglycoside-induced stop condon readthrough: potential implications for treatment of Duchenne muscular dystrophy

As a result of their ability to induce translational readthrough of stop codons, the aminoglycoside antibiotics are currently being tested for efficacy in the treatment of Duchenne muscular dystrophy patients carrying a nonsense mutation in the dystrophin gene. We have undertaken a systematic analysis of aminoglycoside-induced readthrough of each stop codon in human tissue culture cells using a dual luciferase reporter system. Significant differences in the efficiency of aminoglycoside-induced readthrough were observed, with UGA showing greater translational readthrough than UAG or UAA. Additionally, the nucleotide in the position immediately downstream from the stop codon had a significant impact on the efficiency of aminoglycoside-induced readthrough in the order C > U > A > or = G. Our studies show that the efficiency of stop codon readthrough in the presence of aminoglycosides is inversely proportional to the efficiency of translational termination in the absence of these compounds. Using the same assay, we analyzed a 33-base pair fragment of the mouse dystrophin gene containing the mdx premature stop codon mutation UAA (A), which is also the most efficient translational terminator. The additional flanking sequences from the dystrophin gene do not significantly change the relatively low-level aminoglycoside-induced stop codon readthrough of this stop codon. The implications of these results for drug efficacy in the treatment of individual patients with Duchenne muscular dystrophy or other genetic diseases caused by nonsense mutations are discussed.     

Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release

The tumor drug concentrations, drug distributions, and therapeutic efficacies achieved by three fundamentally different liposomes, nonthermosensitive liposome (NTSL), traditional thermosensitive liposome (TTSL), and low temperature sensitive liposome (LTSL); free doxorubicin (DOX); and saline in combination with hyperthermia (HT) were directly compared in a human tumor xenograft model. NTSL is a nonthermosensitive liposome in the physiological temperature range, TTSL is a traditional thermosensitive liposome that triggers in the range of approximately 42-45 degrees C and releases drug over approximately 30 min, and LTSL is a new low temperature sensitive liposome that triggers in the range of approximately 39-40 degrees C and releases drug in a matter of seconds. Because of the different attributes of the liposomes, it was possible to delineate the relative importance of liposome drug encapsulation, HT cytotoxicity, HT-drug interaction, HT-induced liposomal delivery, and HT-triggered liposomal drug release in achieving antitumor activity. Athymic nude mice bearing the FaDu human tumor xenograft were given a single i.v. dose of 5 mg/kg of DOX (free drug or liposome encapsulated), and the tumors were then heated to either 34 degrees C or 42 degrees C for 1 h at 34 degrees C. All treatment groups were similar, achieving low concentrations of DOX (0-4.5 ng/mg). At 42 degrees C, the LTSL (25.6 ng/mg) achieved the highest DOX concentration (P < 0.04), but all three liposomal formulations (7.3-25.6 ng/mg) were higher than saline or DOX (0-0.7 ng/mg; P < 0.02). LTSL + HT was also the only group that resulted in significant amounts of DNA-bound DOX (silver nitrate-extractable fraction; P < 0.02). Tumor tissue sections were visualized for DOX fluorescence to investigate the local distribution of the drug in the tumor and confirm the relative drug concentrations based on fluorescence intensity. There was relatively little fluorescence seen with treatment groups at 34 degrees C. At 42 degrees C, the LTSL showed the most DOX fluorescence (P < 0.01), and the fluorescence, although not homogeneous, was pervasive throughout the tumor sections. Therapeutic efficacy of treatments was determined from tumor growth time. At 34 degrees C, the only treatment group significantly better than the saline group (9.8 days) was the NTSL group, with a growth time of 20.9 days (P < 0.02). At 42 degrees C, all three liposomal formulations were more efficacious than DOX. LTSL + HT had the longest growth time (51.4 days) and the most number of local controls at 60 days (six of nine tumors). With HT, the DOX concentrations and fluorescence were tightly correlated with tumor growth delay, indicating that adequate (increased) drug delivery can be predictive of therapeutic effect. Overall, the LTSL + HT group showed the largest DOX concentration, the highest and most pervasive DOX fluorescence, and the most antitumor effect. Thus, HT-triggered liposomal drug release may account for the largest differential therapeutic effect and demonstrates the importance of rapid drug release from the drug carriers at the tumor site.