Circulating and local bone marrow renin-angiotensin system in leukemic hematopoiesis: preliminary evidences

Until last the decade, the renin-angiotensin system (RAS) was considered as a circulating endocrine system. It is now known that there are local RASs in many tissues. It has also recently been hypothesized that there exists a local bone marrow (BM) RAS with paracrine/autocrine pathobiological functions. The aim of this study was to detect BM and peripheral blood levels of the essential RAS components in normal and leukemic hematopoiesis. Concentrations of renin and angiotensin-converting enzyme (ACE) were assayed in BM aspirates and in simultaneously drawn peripheral blood samples of 16 pre-chemotherapy leukemic and 10 post-treatment megaloblastic anemia patients with normal blood counts, as controls. In the leukemia group, the ACE concentration was found to be significantly higher in the BM (38+/-6.2 U/l) than in the peripheral blood (29.5+/-5.3 U/l), (p=0.029). In the leukemia group, although the BM renin concentration was higher than the peripheral blood levels (21.3+/-8.3 vs. 18.6+/-6.2 U/l), this difference was not statistically significant (p=0.196). In the control group, mean BM renin levels were insignificantly lower than in the peripheral blood (8.6+/-3 vs. 12.1+/-4.6 pg/ml) (p=0.059). In the leukemia group, serum ACE levels positively correlated with BM and peripheral blood blast percentages (p<0.05). Serum LDH level (p<0.01), BM blast (p<0.05) and peripheral blast percentages (p<0.01) were inversely correlated with serum potassium in the leukemia group.The results of this study can be considered as the preliminary evidence supporting the hypothesis of the presence of a local BM RAS. Further, molecular biologic and immunohistochemical studies are needed to shed light on this important subject. A better understanding of the interrelationships of RAS and hematopoiesis will bring new insights into the pathobiology and even novel therapies for such neoplastic diseases.     

Computed tomography features in malignant pleural mesothelioma and other commonly seen pleural diseases.

OBJECTIVE: To investigate the computed tomography (CT) features of malignant pleural mesothelioma (MPM) cases, comparing them to those in other malignant and benign pleural diseases. MATERIALS AND METHODS: We reviewed the CT findings of 215 patients; 99 with MPM, 39 with metastatic pleural disease (MPD), and 77 with benign pleural disease. The findings were evaluated in univariate and multivariate analysis for differentiation of pleural diseases. RESULTS: In patients with MPM, the most common CT features were circumferential lung encasement by multiple nodules (28%); pleural thickening with irregular pleuropulmonary margins (26%); and pleural thickening with superimposed nodules (20%). In the majority (70%) of cases, there was rind-like extension of tumor on the pleural surfaces. In multivariate analysis, the CT findings of "rind-like pleural involvement", "mediastinal pleural involvement", and "pleural thickness more than 1 cm" were independent findings in differentiating MPM from MPD with the sensitivity/specificity values of 70/85, 85/67, and 59/82, respectively. "Rind-like pleural involvement", "mediastinal pleural involvement", "pleural nodularity" and "pleural thickness more than 1 cm" were independent findings for differentiation of malignant pleural diseases (MPM+MPD) from benign pleural disease with the sensitivity/specificity values of 54/95, 70/83, 38/96, and 47/64, respectively. Invasion of thoracic structures such as pericardium, chest wall, diaphragm, mediastinum, with pleural disease and nodular involvement of fissures, was detected infrequently; however, since these invasions were not seen in benign pleural diseases, it was concluded these invasions, if detected on a CT scan, directly suggested malignancy. CONCLUSION: A patient has extremely high probability of malignant pleural disease if one or more of these CT findings are found and the possibility of MPM is high. These findings may be important for patients in bad state or patients who do not want any invasive biopsy procedures. It is also possible to identify cases with a low probability of malignant disease.     

Antithrombin III prevents deleterious effects of remote ischemia-reperfusion injury on healing of colonic anastomoses

BACKGROUND: Antithrombin III is known as the most important natural inhibitor of thrombin activity and has been shown to attenuate local harmful effects of ischemia-reperfusion injury in many organs. In recent animal studies, delaying effect of remote organ ischemia-reperfusion injury on healing of intestinal anastomoses has been demonstrated. In this study, we investigated whether antithrombin III reduces deleterious systemic effects of ischemia-reperfusion injury on healing of colonic anastomoses in rats. METHODS: Anastomosis of the left colon was performed in 24 rats that were divided into three groups: sham operated control (group I, n = 8), 30 minutes of intestinal ischemia-reperfusion by superior mesenteric artery occlusion (group II, n = 8), antithrombin III treated group (250 U/kg before and after the ischemia-reperfusion, group III, n = 8). On postoperative day 6, all animals were sacrificed, and bursting pressure and tissue hydroxyproline content of the anastomoses were assessed and compared. RESULTS: On postoperative day 6 the mean bursting pressures were 149.6 +/- 4.8, 69.8 +/- 13.5, and 121.8 +/- 8.7 mm Hg for groups I, II, and III, respectively (P = 0.000). Mean tissue hydroxyproline concentration values were 389.5 +/- 29.6, 263.1 +/- 10.0, and 376.0 +/- 33.8 microg/mg for groups I, II, III respectively (P = 0.005). CONCLUSIONS: This study showed that, antithrombin III treatment significantly prevented the delaying effect of remote organ ischemia-reperfusion injury on anastomotic healing in the colon. Further clinical studies are needed to clarify whether antithrombin may be a useful therapeutic agent to increase the safety of the anastomosis during particular operations where remote organ ischemia-reperfusion injury takes place.     

Diurnal variation of intraocular pressure and its correlation with retinal nerve fiber analysis in Turkish patients with exfoliation syndrome

Purpose The purpose was to evaluate the diurnal variation (DV) of intraocular pressure (IOP) in patients with exfoliation syndrome (XS), to measure retinal nerve fiber layer (RNFL) thickness by using scanning laser polarimetry, and to compare these measurements with those of normal subjects. Methods Forty-five subjects with XS and 40 healthy, age/sex matched subjects were recruited into the study. A detailed ophthalmologic examination was performed. IOP measurements were obtained at 08:00 am, 12:00 pm, 03:00 pm, and 06:00 pm. The XS group was further divided into DV ≥5 mmHg and DV<5 mmHg groups and also according to the existence of IOP fluctuation. The IOP measurements and RNFL thickness measurements were compared between the groups. Results The mean IOP value was found to be highest in the morning both in the XS and control groups. IOP showed a gradual decrease from 8.00 am to 6.00 pm in the control group, whereas a second peak at 03:00 pm was observed in the XS group. There was a fluctuation in 53.3% of the XS group, while none of the healthy subjects showed fluctuation. Superior and inferior ratios were statistically lower in XS patients than those in control subjects (p<0.05). Moreover, in patients with XS showing a DV ≥5 mmHg and/or a fluctuation, the superior ratio, inferior ratio, the number, superior average and superior integral were significantly different (all p values <0.05) from those of control subjects. Conclusions As the XS patients with high diurnal IOP variation and fluctuating pattern of IOP had lower RNFL thickness measurements, it is crucial to follow up these patients by performing scanning laser polarimetry in order to discover any possible glaucomatous damage at an earlier stage than with the use of conventional visual field analysis.     

Using two ipsilateral double j ureteral stents for extrinsic ureteral obstruction due to colon carcinoma

Although double J (DJ) ureteral stents are widely used in extrinsic ureteral obstruction, there are few studies using ipsilateral two DJ stents in the same ureter. We report using ipsilateral two ureteral DJ stents in the same ureter in a patient with extrinsic ureteral obstruction due to colon carcinoma.     

Reliability of free-flap coverage in diabetic foot ulcers

As microsurgery advances, microsurgical free-tissue transfers have become the reconstructive method of choice over staged or primary amputation, and enabling independent ambulation in difficult lower-extremity wounds. In this report, we present our experiences with free-tissue transfer for the reconstruction of soft-tissue defects in 13 diabetic foot ulcers. Following radical debridement, soft-tissue reconstruction was achieved in the following ways: anterolateral thigh fasciocutaneous flap in 5 patients, radial forearm fasciocutaneous flap in 3 patients, lateral arm fasciocutaneous flap in 1 patient, gracilis musculocutaneous flap in 1 patient, tensor fascia latae flap in 1 patient, deep inferior epigastric perforator flap in 1 patient, and a parascapular flap in the remaining patient. In 8 cases, diabetic wounds were in the foot, while wounds were at the level of the lower leg in the remaining patients. In all patients, vascular patency was confirmed by the Doppler technique. In suspicious cases, arteriography was then performed. While all flaps survived well in the postoperative period, one patient died from cardiopulmonary problems on postoperative day 16 in an intensive care unit. Amputation was necessary in the early postoperative period because of healing problems. In the remaining 10 cases, all flaps survived intact. In one case, arterial revision was performed successfully. The ultimate limb salvage rate was 83% for the 12 patients. Independent ambulation was achieved in these cases. During the follow-up period of 8 months to 2 years, no ulcer recurrence was noted, and no revascularization or vascular bypass surgery was needed before or after the free-tissue transfers. The authors conclude that free-tissue transfer for diabetic foot ulcers is a reliable procedure, despite pessimistic opinions regarding the flap survival and low limb salvage rates. It should be considered a useful reconstructive option for serious defects in well-selected cases.     

A rare and serious complication of the radial forearm flap donor site: osteomyelitis of the radius

Although the radial forearm flap has become a workhorse for the reconstructive surgeon, it has some known disadvantages, especially relating to donor area complications. The authors present a serious but rare complication of the radial forearm donor site. Osteomyelitis of the radius at the flap donor site was observed in a 48-year-old man 5 weeks after flap surgery. Although the flap was raised fasciocutaneously without a bony portion, infection of the radius was determined. The infection was successfully treated with surgical debridement and simultaneous administration of a proper antibiotic regimen. One should keep in mind that osteomyelitis of the radius may be encountered as one of the serious donor site complications of the radial forearm flap that may have detrimental effects on hand functions.     

Endoscopic and radiologic interventions as the leading causes of severe cholangitis in a tertiary referral center

BACKGROUND: Iatrogenic factors became the leading mechanisms of severe cholangitis in a referral center. PATIENTS AND METHODS: The records of the 58 patients treated for severe cholangitis between 1996 and May 2004 (inclusive) were evaluated. RESULTS: The most frequent underlying diseases were periampullary tumors and mid-bile duct carcinomas (22), followed by proximal cholangiocarcinomas (14). The triggering mechanism was an incomplete endoscopic retrograde cholangiopancreatography (ERCP) in 32 patients, incomplete or inappropriate percutaneous transhepatic biliary drainage (PTBD) in 6, apparently successful ERCP and stenting in 1, and percutaneous transhepatic cholangiography in 1. PTBD was the treatment of choice (38). Mortality was 29% (17/58); the major causes were refractory sepsis (8) and incomplete biliary drainage (advanced tumor, technical failure, or hemobilia) (8). CONCLUSIONS: In this series composed predominantly of patients referred after development of sepsis, ERCP and PTBD complications were the leading mechanisms of severe cholangitis. Nonoperative biliary manipulations are invasive procedures with potentially fatal complications. The decisions to perform such procedures and periprocedural management are responsibilities of an experienced multidisciplinary team.     

Antithrombin III attenuates pulmonary tissue injury caused by mesenteric ischemia-reperfusion

BACKGROUND: Mesenteric ischemia-reperfusion (I/R) is a well-known event causing both local and remote organ injuries, including the lungs. Recently, several studies indicated that activated leukocyte-endothelial cell interactions play an important role in the mechanisms of these injuries. As a natural inhibitor of serine proteases, antithrombin was shown previously to attenuate the tissue damage after local I/R in several organ systems. Here, we examined the effects of antithrombin on pulmonary injury after mesenteric I/R. METHODS: Wistar albino rats underwent median laparotomy and were randomized into 3 groups: (1) sham-operated control (n = 12), (2) 60 minutes of mesenteric ischemia and 3 hours of reperfusion (n = 12), and (3) antithrombin-pretreated (250 U/kg) group before the I/R (n = 12). At the end of reperfusion, animals were killed and neutrophil sequestration, myeloperoxidase (MPO) activity, and Evans blue dye extravasation in the lung parenchyma were assessed and compared. RESULTS: There was a statistically significant increase in the quantity of Evans blue dye concentration, leukocyte sequestration, and MPO activity in the I/R group when compared with the control group. The pretreatment of animals with antithrombin significantly decreased the pulmonary injury characterized by increased Evans blue dye extravasation, leukocyte sequestration, and MPO activity. CONCLUSION: The data of the present study suggest that mesenteric ischemia and reperfusion induces pulmonary injury characterized by activated neutrophil sequestration and increased microvascular leakage in the lungs. A significant attenuation of intestinal I/R-related lung injury with the use of antithrombin concentrate warrants further studies to elucidate the potential role of this natural serine protease inhibitor in clinical settings.