Schedule dependency of the combination methotrexate-vinblastine against human urothelial cancer grown in nude mice

The combination of methotrexate (MTX) and vinblastine (VLB) was evaluated using different doses and treatment schedules in human transitional cell carcinoma line SW-1738, TCC-K1 and TR-49 grown in the nude mouse. Maximally tolerated weekly doses of MTX, 30 mg/kg, and VLB, 3 mg/kg, were given intraperitoneally for four consecutive weeks singly, concurrently, and separated by 24, 48 and 72 hour intervals. MTX-VLB drug sequence was not a factor in determining tumor regression or response rates when the second agent was administered 24 or 48 hours after the first agent. However, when VLB was administered 72 hours after MTX, a significant statistical difference (0.005 greater than p greater than 0.001) was observed for all tumor lines studied compared to either controls, simultaneous administration of both agents and/or VLB administered 24 or 48 hours after MTX. Additionally, dose reduction of either agent by 30% proved ineffective. Thus, tumor response to MTX-VLB combination was dependent both on schedule and dose. Application of this schedule dependency may be beneficial in management of urothelial tract tumors.     

Time Dependence of the Radiation-Modifying Effect of cis-Diamminedichloroplatinum II (cisplatin, DDP) on Human Urothelial Cancer Grown in Nude Mice

Previous reports have indicated that human urothelial cancer is more sensitive to combination radiation-cisplatin than to either treatment given alone and that the treatment schedule may be an important factor in determining the magnitude of tumor response. In the present study we have investigated the effect of timing and the sequence of combination “radiation-cisplatin” on human urothelial cancer grown in nude mice. Tumors were exposed to 1000 rod x-irradiation and received cisplatin treatment in the amount of 5 mg/kg once on each specified day before or after radiation. Best tumor responses, characterized by significant tumor growth delay and tumor regression, were observed when cisplatin was given on Day 3 and 6 postradiation. The present work has indicated that timing and sequence of treatments in the combination “radiation-cisplatin” are important factors in determining tumor response and may be of assistance in formulating the most effective clinical trials of urothelial cancer patients.     

Altered proximal aortic stiffness and endothelin plasma levels in diabetic patients with end-stage renal disease

Peripheral artery stiffness is altered in diabetic patients with end-stage renal disease (ESRD), whereas few data exist to confirm this trend for proximal aortic stiffness. The pulse wave velocity of the proximal aorta (PWVr) and of the carotid-to-femoral aortic segment (PWVcf) were determined by ultrasound imaging in 160 patients with ESRD (70 diabetic) and in 160 matched control subjects. Also, plasma levels of endothelin, homocysteine, and high-sensitivity C-reactive protein were determined in both groups. Patients with ESRD had increased pulse pressure, left ventricular (LV) end-diastolic diameter, LV mass index, PWVr, and PWVcf compared with control subjects (p < 0.05). Diabetic patients had increased LV mass index, PWVr, and PWVcf compared with nondiabetic patients with ESRD (p < 0.05). Endothelin levels exhibited a strong relation with PWVr (r = 0.32, p < 0.001) and PWVcf (r = 0.33, p < 0.001) measurements in ESRD patients. Multivariate linear regression analysis revealed that age, diabetes, and plasma levels of endothelin were major determinants of increased PWVr measurements in the total ESRD population. After adjustment for age, body surface area, time on dialysis, systolic blood pressure, history of hypertension, and plasma endothelin levels, diabetes was an independent factor associated with PWVr in ESRD subjects. Diabetic patients with ESRD had significantly increased proximal aortic stiffness and significantly altered plasma levels of endothelin as compared with the nondiabetic.     

Comparative study of serum and synovial fluid interleukin-11 levels in patients with various arthritides

Objective: To determine the levels of serum and synovial fluid (SF) interleukin (IL)-11 in patients with various arthritides and estimate the contribution of IL-11 to acute phase response (APR).

Design and methods: Serum and SF IL-11 were measured by ELISA in patients with rheumatoid arthritis (RA, n = 31), seronegative spondyloarthritis (SSA, n = 23), gout (GT, n = 14) and osteoarthritis (OA, n = 20) and were correlated with ESR and acute phase proteins as well as with cytokines IL-1, IL-1β, IL-6, and TNF.

Results: IL-11 was detected in both serum and SF in each group, with IL-11 being statistically higher in SF than serum in all groups, suggesting reduced catabolism or increased synthesis of IL-11 intra-articularly. Median SF IL-11 levels were higher in OA patients than in other groups and in the treated than in the untreated RA subgroup. Moreover, serum and SF IL-11 were correlated significantly with each other, and moderately with the other cytokines examined in RA, SSA, and GT, but not in OA patients, while a significant negative correlation was found with a few of the inflammatory markers examined in each group.

Conclusions: Our findings provide evidence of extensive intra-articular expression of IL-11 in arthritides, especially in OA and treated RA patients, suggesting a protective role for IL-11 in joints, probably through the induction of tissue inhibitor of metalloproteinases.     

BALF and BLOOD NK- cells in different stages of pulmonary sarcoidosis

Background and objective:Data on natural killer (NK)- and natural killer T (NKT)- like cells in the immunopathogenesis of sarcoidosis remain limited. The aim was to assess NK- and NKT-like cells across different stages in bronchoalveolar lavage (BALF) versus peripheral blood (PB) in comparison to controls.Methods:Forty four patients (32 women and 12 men, mean age 46.6±14.4 years) with biopsy-proven sarcoidosis and 10 healthy individuals (6 women, 4 men mean age 52.6±19.1 years) were submitted to BALF. Total cells and cell differentials were counted, while CD45+, CD3+, CD4+, CD8+, CD19+, CD3-CD16/56 (NK cells) and CD3+CD16/56+ (NKT-like cells) were determined by dual flow cytometry in BALF and PB.Results:A significantly lower percentage of both NK and NKT-like cells was observed in BALF of controls and sarcoid patients (SP) compared to PB. Both BALF NK and NKT-cell counts were significantly higher in SP than in controls (NK: p=0.046, NKT-like: p=0.012) In addition BALF NK cell percentage differed among sarcoidosis stages (p=0.005). In PB NK-cell count was lower in sarcoidosis patients but the difference did not reach statistical significance. Also, in sarcoid patients’ BALF NK-cell percentage negatively correlated with lymphocyte percentage (r=-0.962, p<0.001).Conclusions:The increased count of BALF NK and NKT-like cells in sarcoidosis compared to controls along with the increase of NK cells with stage progression are in line with a growing number of investigations suggesting the involvement of NK- and NKT-like cells in the pathogenesis of sarcoidosis.     

The management of acute gastric volvulus

Acute gastric volvulus occurs when the stomach or a part of it rotates more than 180 degrees which leads to obstruction (closed loop syndrome), that finally concludes to incarceration and ischemia of the organ. It can be observed as a result of diaphragmatic hernia, a gap of the diaphragm, pancreatic or gastric cancers, traumatic injuries and fixation anomalies. Par? first described acute gastric volvulus in 1579, in a patient with diaphragmatic injury after trauma. The first reports of successful surgical repair and anatomo-pathologic findings were published in 1866 and 1897.