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.     

Epididymal sparing bilateral simple orchiectomy with epididymoplasty: preservation of esthetics and body image

PURPOSE: We report the surgical technique and results of epididymal sparing bilateral simple orchiectomy as an esthetic alternative to standard bilateral simple orchiectomy and luteinizing hormone releasing hormone (LH-RH) agonist injection therapy in patients with prostate cancer. MATERIALS AND METHODS: The study included 91 consecutive epididymal sparing bilateral simple orchiectomy (BSO) procedures that were performed at the Atlanta Veterans Affairs Medical Center during a 25-month period. All patients had pathologically confirmed prostate cancer. A total of 52 patients (57.1%) were receiving LH-RH agonist therapy prior to the procedure and the remaining 39 (42.9%) were not. All procedures were performed in an outpatient clinic setting using spermatic cord anesthesia block as the only method of anesthesia. In the 52 patients who were on LH-RH agonist therapy prior to the procedure the overall impression/satisfaction with the procedure was evaluated using a questionnaire. RESULTS: All 91 procedures were performed at the urology outpatient clinic using local anesthesia. Mean patient age was 74.2 years (range 44 to 86). Mean serum prostate specific antigen was 58.9 ng/ml. The mean time required to perform the spermatic cord anesthesia block was 3.9 minutes (range 2 to 6) and the volume of anesthetic solution was 18.9 ml per case (range 10 to 32). Despite significant difference in testicular size between patients receiving and not receiving LH/RH agonists there were no differences in anesthesia time or anesthetic volume (3.9 and 3.9 minutes, p = 0.97, and 18.6 and 19.4 ml, respectively, p = 0.47). Mean operative time for BSO excluding anesthesia time was 36.9 minutes (range 18 to 70). Mean operative time was similar in patients receiving and not receiving LH-RH agonists (36.2 and 37.8 minutes, respectively, p = 0.39). The procedure was well tolerated, as judged by the mean intraoperative pain score during BSO of 0.2 (range 0 to 3). The majority of patients (76 or 83.5%) were pain-free during the procedure. Pain scores were similar in patients who were and were not receiving LH-RH agonists during BSO (p = 0.97). There were no adverse events. Followup data were available on 26 of the 52 patients who were receiving LH-RH agonist therapy prior to the procedure. Of them 96.2% were satisfied with the results and 84.6% preferred the procedure over medical castration therapy with LH-RH agonist therapy. CONCLUSIONS: Epididymal sparing bilateral simple orchiectomy is a simple and safe procedure that can be conveniently performed in an outpatient clinic setting using pure local anesthesia. Preservation of the epididymis and subsequent epididymoplasty is effective for maintaining the esthetic appearance of the scrotum and patient satisfaction. The procedure offers patients the convenience of 1-time surgical therapy over lifelong medical injection therapy at a significantly lower cost and without significantly compromising the esthetic appearance of the scrotum.     

Handwashing in the intensive care unit: a big measure with modest effects

Handwashing is widely accepted as the cornerstone of infection control in the intensive care unit. Nosocomial infections are frequently viewed as an indicator of poor compliance of handwashing. The aim of this review is to evaluate the effectiveness of handwashing on infection rates in the intensive care unit, and to analyse the failure of handwashing. A literature search identified nine studies that evaluated the impact of handwashing or hand hygiene on infection rates, and demonstrated a low level of evidence for the efforts to control infection with handwashing. Poor compliance cannot be blamed as the only reason for the failure of handwashing to control infection. Handwashing on its own does not abolish, but only reduces transmission, as it is dependent on the bacterial load on the hand of healthcare workers. Finally, recent studies, using surveillance cultures of throat and rectum, have shown that, under ideal circumstances, handwashing can only influence 40% of all intensive care unit infections. A randomised clinical trial with the intensive care as randomisation unit is required to support handwashing as the cornerstone of infection control.