In vitro changes in platelet function and metabolism following increasing doses of ultraviolet-B irradiation

Ultraviolet-B (UV-B) irradiation of platelet concentrates (PCs) may prevent the development of posttransfusion HLA alloimmunization. This study evaluated the effect of increasing doses of UV-B radiation on stored PCs. Pooled PCs were irradiated at UV-B doses of 600, 2400 or 10,000 mJ per cm2 and stored up to 96 hours under standard blood bank conditions. Compared to nonirradiated room-temperature and 37 degrees C controls, the irradiated units showed no significant changes in platelet count, white cell count, discharge of lactate dehydrogenase, release of beta-thromboglobulin, metabolism of ATP, ADP, ammonia, glutamine, glutamate, hypoxanthine, pCO2, or pO2 at any time of storage following any of the three UV-B doses. However, after a dose of 10,000 mJ per cm2, there were significant decreases in in vitro assays of platelet function-specifically, osmotic recovery and morphology score. Some metabolic systems were also affected by the 10,000 mJ per cm2 radiation dose, as shown by a decline in pH and bicarbonate and an increase in glucose consumption and lactate production (p < 0.05). The changes in these latter assays appeared only after 96 hours of postirradiation storage. Such changes were not seen in either the room- temperature or 37 degrees C control groups. Thus, heat generated during irradiation, per se, did not appear responsible for the observed in vitro changes in platelet function and metabolism. On the basis of the assays analyzed, it is concluded that UV-B irradiation of PCs at doses up to 10,000 mJ per cm2 does not induce significant metabolic or functional derangements following short-term storage (24-48 hours).(ABSTRACT TRUNCATED AT 250 WORDS)     

Obsessive Compulsive Disorder in a Patient with Twiddler's Syndrome

Twiddler's or twist syndrome is the twisting of pulse generators around themselves. It may result from mechanical manipulation that can induce the malfunction of the device. In this case, twiddler's syndrome resulted from compulsive checking of the device. The implantable cardioverter‐defibrillator (ICD) triggered the development of an obsessive compulsive disorder (OCD). Two invasive procedures were required to replace the ICD. Psychiatric intervention prevented the recurrence of twiddler's syndrome in this patient for more than 2 years. We believe that preimplant psychiatric assessment should be the rule.     

Mode of presentation and first line of management of non-recurrent urolithiasis in Kuwait

AIMS: To determine the incidence, mode of presentation, first line of management and composition of non-recurrent urolithiasis in Kuwait. METHODS: Consecutive patients admitted between January 1999 and December 2002 with non-recurrent urolithiasis were prospectively analyzed. RESULTS: The average annual incidence of hospital admission for non-recurrent urolithiasis in Kuwait was 43.44 per 100,000 population, representing men and women (ratio, 9:1) with a median age of 41.91 years. Of the hospital admissions for non-recurrent urolithiasis, 57.2% of cases were acute. Overall, the most predominant symptom was flank pain, while the least common symptom was acute urinary retention. Ureteroscopic stone manipulation was the most common initial treatment modality in the present series, as it was utilized in 43.3% and 37.09% for patients admitted on elective and emergency basis, respectively. Of the calculi available for chemical analysis, 91% contained calcium, 73% contained calcium oxalate, 17% contained mixed calcium and 1% contained calcium phosphate. The composition of the rest of the stones were urate in 7%, struvite in 1% and cystine in 1%. CONCLUSIONS: Urolithiasis is a common disease in the Kuwait region that mainly presents with flank pain. Ureteroscopic calculus removal is the most common modality of treatment. The majority of the calculi seen in Kuwait contained calcium.     

Analysis of apoptosis and a Th1/Th2 phenotype in HIV-infected patients

Lymphocytes from HIV patients, unlike those from normal HIV-negative subjects, underwent apoptosis upon in vitro culture. We found that the percentage of lymphocytes undergoing apoptosis was significantly higher (P = 0.005) in patients with low CD4 cell counts (< 200 CD4 cells/μl) (60%) than in patients at earlier stage (> 500 CD4 cells/μl) (35%). Serum IgE levels increased in two of six patients at last stage and in two of five patients at earlier stage. Spontaneous production of both IL-2 and IL-10, by peripheral blood mononuclear cells (PBMC) after 48 h in culture, was greater in HIV-infected subjects and increased with disease progression. IFN-γ production was greater in HIV-infected subjects but there was no evident change with disease progression. IL-4 production was barely detectable or not detected in both HIV-infected and HIV-negative individuals. These results indicate that spontaneous apoptosis is associated with advanced disease. However, there was no evidence of in vivo switch from the Th1 to Th2 phenotype in HIV-infected patients.     

Production of Chemotactic Factor and Lymphotoxin by Human Leukocytes Stimulated with Herpes Simplex Virus

Peripheral blood leukocytes (PBL) of 41 subjects were tested for their ability to be stimulated by herpes simplex virus antigens as measured by [(3)H]thymidine incorporation and lymphokine production (i.e., lymphocyte-derived chemotactic factor and lymphotoxin). The PBL of seronegative subjects failed to respond to viral antigens as measured by stimulation or lymphokine production. In contrast, PBL from seropositive subjects without clinical lesions of herpes labialis were stimulated by herpes simplex virus antigens and produced lymphokines. PBL from seropositive patients with clinical lesions of herpes labialis also produced lymphokines, but [(3)H]thymidine incorporation was slightly depressed. These findings suggest that lymphocytes from patients with a recent herpes simplex virus infection may respond less vigorously to in vitro stimulation by herpes antigens, but our study fails to show any basic defect in the responsiveness of the lymphocytes to account for recurrent herpetic episodes.     

Value of diffusion weighted magnetic resonance imaging in grading of urinary bladder carcinoma

Aim of the study: to evaluate the role of diffusion weighted magnetic resonance imaging in urinary bladder cancer grading in comparison to histopathological grading.

Prognosis after local recurrence after conservative surgery and radiation for early-stage breast cancer

PURPOSE: To determine the long-term prognosis of patients who develop a local recurrence (LR) after conservative surgery (CS) and radiation therapy (RT) for early-stage invasive breast cancer. METHODS AND MATERIALS: Between 1970 and 1987, 2102 patients with clinical Stage I-II breast cancer were treated with CS+RT. LR was defined as any recurrence within the ipsilateral breast with or without simultaneous regional nodal or distant metastasis. Patients were at risk for a LR until the first of distant metastases, second nonbreast malignancy, or death (DF/S/D). The final study population comprised 341 patients with LR. The median time to LR was 72 months. The median follow-up time after LR was 85 months. A proportional hazards model of time from LR to DF/S/D was done to investigate the influence of factors at initial diagnosis and at LR on subsequent outcome. RESULTS: The actuarial freedom from DF/S/D 5 years after LR was 65% and the survival was 81%. Variables significantly associated with time to DF/S/D were: LR histology (invasive vs. ductal carcinoma in situ, hazard ratio [HR] = 4.1, p < 0.0001); local therapy for LR (none vs. mastectomy or unknown, HR = 3.2, p < 0.0001; and CS +/- RT vs. mastectomy or unknown, HR = 2.0, p = 0.02); time to LR (< or =2 years vs. >5 years, HR = 2.6, p < 0.0001; and 2-5 years vs. >5 years, HR = 1.8, p = 0.006); and age at initial diagnosis (> or =60 vs. <60, HR = 1.6, p = 0.01). CONCLUSIONS: Many patients with LR after CS+RT have prolonged distant disease-free survival, particularly those able to be treated with mastectomy. Patients with a noninvasive LR, longer interval to LR, or age <60 had a longer time to distant failure, second malignancy, or death than other patients.     

Thymoquinone Crosstalks with DR5 to Sensitize TRAIL Resistance and Stimulate ROS-Mediated Cancer Apoptosis

Objective: Cancer treatment using a targeted inducer of apoptosis like tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) faced the obstacle of resistance, thus providing a plus drug like Thymoquinone (TQ) could be of great interest to tackle breast cancer cells. The aim of the present work is to examine the genetic modulation impacts of the TRAIL receptors and apoptotic markers upon the combinatorial remedy of TRAIL plus TQ on human breast cancer cell lines. Methods: To achieve this rationale, the protein content-based cytotoxicity using SRB assay, as well as the genetic expressions of the TRAIL receptors (DR4 and DR5) and apoptotic markers (Bcl-2, Cas-8, and FADD) using real time qRT-PCR technique were preceded against breast cancer MCF-7 and MDA-MB-231 cancerous cell lines. Results: The current study showed that the combination therapy of TQ+TRAIL significantly inhibited the protein content-based proliferation of MDA-MB-231 cells more than MCF-7 cells. The synergistic effect of them significantly up-regulated the genetic expressions of DR4, DR5, Cas-8, and FADD genes and inhibited the genetic expression of the Bcl-2 gene in the proposed cell lines treated for 24 h. The induction of the apoptotic genes using the combined therapy was stimulated by the elevation of the reactive oxygen species (ROS); nitric oxide (NO) and malondialdehyde (MDA) levels. Conclusions: The synergistic influence between TQ which induced the DR5 and TRAIL, facilitating the connection between TRAIL and its receptors on the cancerous cell membrane. Hence, the proposed combination therapy induced the ROS-mediated apoptotic stimulus.     

Melanoma differentiation-associated gene 7/interleukin (IL)-24 is a novel ligand that regulates angiogenesis via the IL-22 receptor

The melanoma differentiation-associated gene 7 (mda-7), also called interleukin (IL)-24, suppresses the growth of some cancers in vitro and in vivo as a result of the ectopic expression of its protein. However, the function of the secreted form of the protein in cancer has not been previously studied. The purpose of this study was to determine the antiangiogenic function of a secreted form of the MDA-7/IL-24 protein (sMDA-7/IL-24). In vitro, sMDA-7/IL-24 inhibited both endothelial cell differentiation and migration of endothelial cells induced by vascular endothelial growth factor and basic fibroblast growth factor. The sMDA-7/IL-24-mediated inhibitory effect was 10-50 times more potent than endostatin, IFN-gamma, and IFN-inducible protein 10 in vitro. Furthermore, the inhibitory effect was not mediated by IFN or IFN-inducible protein 10. IL-22 receptor mediated the antiangiogenic activity of sMDA-7/IL-24. Administration of a blocking antibody to IL-22 receptor in conjunction with sMDA-7/IL-24 led to abrogation of inhibition of endothelial differentiation. sMDA-7/IL-24 inhibited vascular endothelial growth factor-induced angiogenesis as evidenced by reduced vascularization and hemoglobin content in in vivo Matrigel plug assays. In vivo, the growth of human lung tumor cells was significantly inhibited, and vascularization was reduced when the cells were mixed with 293 cells stably expressing sMDA-7/IL-24. Systemic administration of sMDA-7/IL-24 inhibited lung tumor growth in a mouse xenograft model. Associated with tumor growth inhibition was decreased tumor microvessel density and hemoglobin content, indicating the presence of antiangiogenic activity. These data demonstrate that sMDA-7/IL-24 is a novel and potent antiangiogenic effector and support the development of MDA-7/IL-24-based therapeutics.