Arsenic trioxide–loaded, microemulsion-enhanced cytotoxicity on MDAH 2774 ovarian carcinoma cell line

The antiproliferative effect of As(2)O(3)-loaded microemulsion (As(2)O(3)-M) on human MDAH 2774 ovarian cancer cells was compared with a regular solution of the As(2)O(3). We used MDAH 2774 as model cell lines for ovarian cancer. The (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) (XTT) and trypane blue dye exclusion tests were used to evaluate cytotoxicity. Apoptotic effect of solutions was evaluated using cell death detection kit. Standard microemulsion formulation used in this experiment contains 5 x 10(-6) M As(2)O(3). It was clearly demonstrated that As(2)O(3)-M had a significant cytotoxic effect on MDAH 2774 cell line, and the cytotoxic effect of As(2)O(3)-M was significantly higher than that of regular As(2)O(3) solutions. Even approximately 6000 times diluted microemulsion formulation loaded with 5 x 10(-6) M As(2)O(3) showed a cytotoxic effect. As a result, this diluted concentration (approximately 8 x 10(-10) M) was found to be approximately 6000 times more effective than regular As(2)O(3) solutions (5 x 10(-6) M). Moreover, this diluted concentration resulted in 1.5-fold enhancement of apoptosis. According to the in vitro cytotoxicity studies, we concluded that by incorporating As(2)O(3) into the microemulsion (As(2)O(3)-M), which is a new drug carrier system, it is possible to increase antiproliferative effect of regular As(2)O(3) on MDAH 2774 cells. Translating these results to in vivo conditions would open new windows in the treatment of ovarian cancer.     

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

Sequential study on the treatment of moderate-to-severe chronic plaque psoriasis with mycophenolate mofetil and cyclosporin

BACKGROUND: There are numerous studies that individually evaluate the efficacy/effectiveness and toxicity of drugs in the systemic treatment of psoriasis. On the contrary, we can hardly find studies that compare each other. OBJECTIVE: To evaluate and compare the effectiveness and toxicity of mycophenolate mofetil and cyclosporin in chronic plaque psoriasis through a prospective, sequential, cross-over, non-randomized, two-phase, open-label study. PATIENTS/METHODS: Eight patients (five women and three men; mean age 57, range 35-78) with moderate-to-severe chronic plaque psoriasis were included in the study. They were treated with oral mycophenolate mofetil (30 mg/kg/day) over a period of 16 weeks. Following a variable washout period and after a new outbreak of the disease, oral cyclosporin was introduced at a dose of 4 mg/kg/day. During both treatment regimens, follow-up visits were performed at 3, 8 and 16 weeks. RESULTS: In both groups, the PASI started to decrease once treatment was begun. Cyclosporin was faster and statistically a lot more effective than mycophenolate mofetil, reaching a higher number of complete remissions and better percentages of PASI improvement from baseline (45.7%, 60.2% and 60.5% at 3, 8 and 16 weeks respectively for mycophenolate mofetil, and 89.7%, 95.3% and 95.3% respectively at the same intervals for cyclosporin). Cyclosporin was also more predictable in its action as the percentage of improvement along the follow-up visits had a much wider range for mycophenolate mofetil. Overall, the tolerability of both drugs was good. None of the patients had to discontinue treatment because of an adverse event. Two patients treated with cyclosporin showed increased plasma levels of creatinine. CONCLUSIONS: Cyclosporin is more effective, fast, and predictable in its effect than mycophenolate mofetil to control moderate-to-severe chronic plaque psoriasis. Both drugs are well tolerated in short courses of treatment.     

Carotid endarterectomy with internal carotid artery segmental resection, temporary shunt and vein patch angioplasty: early and mid-term results.

AIM: The authors report an alternative procedure to carotid endarterectomy with internal carotid artery (ICA) segmental resection and end-to-end anastomosis associated with temporary shunt and venous patch angioplasty. Design: prospective cohort study. METHODS: Between May 1995 and December 2004, 192 patients underwent 200 primary CEAs for significant ICA stenosis. There were 131 men and 61 women with a mean age of 72.4+/-8.4 years. The indications for CEA were asymptomatic lesions in 51.5%, transient ischemic attack in 27.5% and stroke in 21%. RESULTS: The combined early morbidity and mortality rate was 2%. Two patients died, one due to fatal intracerebral hemorrhage and the second patient died of acute mesenteric ischemia. Neurological complications occurred in 2 patients, including 1 TIA and 1 nondisabling cerebrovascular accident. Non-neurological complications occurred in 26 patients (13.5%). Seventeen patients (8.8%) developed hypertension, 3 neck hematomas (1.5%) required surgical evacuation, 1 patient had reversible supraventricular arrhythmia (0.5%) and 1 patient had pneumonia (0.5%). Furthermore, 1 asymptomatic carotid occlusion was identified (0.5%) and 3 patients suffered permanent cranial nerve injury (1.5%). Mean follow-up was 45.7 months and there were 41 late deaths (21.8%). Survival rates at 1 and 5 years were 96.7+/-1.2% and 73.58+/-4.2%, respectively. CONCLUSIONS: CEA with ICA shortening and reanastomosis is a safe and reliable procedure without any increase in morbidity or mortality.     

On medical screening of civilian candidates for cosmonauts by exposure to the head-to-pelvis acceleration profiles]

The subject of analysis was the data on +3 and +5 Gz tolerance of 130 civilian non-pilot applicants for cosmonauts (men and women, aged 23 to 55) gathered over the past 30 years. Length of the centrifuge arm was 7.25 meters and the total number of primary centrifuge runs was 309. For nearly every second of the applicants (46.7%) acceleration at +5 Gz was an ordeal causing distinct vascular or coronary decompensation. Thus, 29.7% exhibited various combinations of brief visual disturbances, tachycardia, tachypnea, and systolic arterial pressure in the shoulders; in 17%, visual disturbances and/or their precursors were combined with exaggerated cardio-vascular functional parameters, arrhythmia, and serious vegetative disorders. Most of those who had failed to endure the first centrifugation were unable to improve G tolerance during next runs; indeed, they showed negative G-tolerance dynamics. G intolerance grew in significance or was exacerbated by new disorders and their combinations. These results testify against exposure of non-pilot applicants for cosmonauts to +5 G, during the primary medical screening.     

129A Summary of Scientific Studies and Clinical Results with a Glycerine Based Dressing

The importance of controlling the bioburden in wounds can not be over emphasized. Glycerine based gel sheets have been used extensively to show their bacteriostatic/fungistatic properties. Hoekstra studied animal wounds and compared glycerine dressings with water based dressings and the glycerine showed superior bioburden reduction. Vandeputte showed similar results when comparing hydrogel and hydrocolloid dressings and looked at the histology of the wounds to find differences in the quantities of the types of cells present. The reduced scar formation of wounds are thought to be attributed to the influence of the glycerine on the healing process. Hoestra has reported the dramatic reduction in the inflammation reaction soon after application of the glycerine gel dressing. Studies by Oliveria‐Gandia, Davis, and Mertz showed the glycerine dressings to be more effective than hydrogel or hydrocolloid dressings in reducing bioburden in animal wounds that were inoculated with microbes and also reducing biocounts in appropriate growth medium. Vandeputte conducted a diabetic study(no exclusions) that compared the glycerine dressing (n = 15) with standard protocol(n = 14) for diabetic foot wounds, that showed the test dressing to be far superior. He along with thousands of other nurses around the world have reported the use of glycerine dressings on superficial burns to reduce pain, reduce the chance for infection, reduce scar formation, and to protect the wound from friction and pressure. J. Baksa extensively used the glycerine gel sheets in his burn unit not only for the superficial wounds but also for 3^rd and 4^th degree burns on children as well as after surgical removal of hypertrophic and keloid scars to prevent reoccurrence. T.M. Baum and M.J. Busuito also reported the use of the glycerine dressing for scar prevention and treatment. The glycerine dressing has been used extensively for te treatment and prevention of pressure ulcers in hospitals, nursing homes, athletic fields, as well as, under casts, splints and braces. R. Horchner reported a >95% reduction in pressure ulcers in a direct comparison to the control and to hydrocolloids.