Ultrastructural analysis of the Fisher to Lewis rat model of chronic allograft nephropathy

Chronic allograft nephropathy (CAN) is the leading cause of graft loss following kidney transplantation. One factor contributing to CAN is chronic alloimmune injury. However, the involvement of alloantigen-dependent and -independent factors in CAN is unclear. The pathomechanism of CAN has been extensively studied by utilizing the Fischer-to-Lewis (F344-to-LEW) rat model. Transplant capillaropathy (circumferential multiplication of the peritubular capillary basement membrane) and transplant glomerulopathy (reduplication of the glomerular basement membrane) have recently been validated clinicopathologically as ultrastructural indicators of chronic alloimmune injury. To investigate the presence of these markers, F344-to-LEW kidneys were examined by electron and light microscopy 32, 40 and 52 weeks after implantation. F344 rats with or without 30-min ischemia of the left kidney following right nephrectomy served as controls. All transplanted rats displayed marked proteinuria. On electron microscopy, transplant capillaropathy, transplant glomerulopathy, and T-cell cytotoxicity (indicator of ongoing cellular rejection) were absent. On light microscopy, the arteries were devoid of intimal fibrosis. Focal-segmental glomerulopathy resembling hyperfiltration injury was encountered, with mild interstitial infiltration, fibrosis, and tubular atrophy. The proteinuria and kidney pathology were more severe in transplanted than in ischemic or uninephrectomized rats. Because chronic-active rejection could not be detected between weeks 32 and 52, we propose that the alloantigen-dependent initial graft injury subsides, but induces the late events: glomerular hyperfiltration, proteinuria, and glomerulosclerosis. Accordingly, the model - in the late phase - is suitable to investigate alloantigen-independent factors of CAN and lacks markers of alloantigen-dependent processes.     

Clinical experience with the hatchet-shaped gluteus maximus musculocutaneous flap

One of the most frequently used flaps for the coverage of sacral skin and soft-tissue defects (primarily decubiti) is the gluteus maximus musculocutaneous flap. The authors have developed a new, hatchet-shaped incision direction for the flap and have been using it for 6 years in the surgical treatment of various pelvic-area defects with good results. At the beginning, the gluteus maximus hatchet-shaped flap was used for treatment of pressure sores in the pelvic area: sacral decubitus on 31 patients, ischial pressure ulcer on 12 patients, and trochanteric ulcer on 1 patient. However, later the method was applied to nondecubitus defects, such as myelomeningocele on 4 patients, Crohn disease on 3 patients, pilonidal sinus on 2 patients, and traumatic defect on 1 patient, totaling 71 flaps on 54 patients. The seroma (4), hematoma (2), postoperative bleeding (1), and partial flap necrosis (1) healed following emptying and repeated surgery; recurrent ulcer was seen in 2 cases. Advantages of the method are the fewer incisions needed, the shorter operating time, and the smaller blood loss as compared with the methods known so far. The new incision direction improves the safety of circulation in the flap, the closure of the donor site is simpler, and no contour difference remains in the surgical area.     

Effects of Macroplastique® Implantation System for stress urinary incontinence and urethral hypermobility in women

A study was carried out to evaluate efficacy of Macroplastique® (MPQ) Implantation System (MIS) in women with urodynamic stress urinary incontinence (SUI) and urethral hypermobility after an unsuccessful conservative treatment. This is a prospective randomized controlled trial in women without previous incontinence surgery. Twenty-four women received MPQ. Twenty-one controls underwent a pelvic floor muscle exercises home program. Follow-up was at 3 months and the MPQ group also at 12 months. At 3 months, pad usage decreased significantly more in the MPQ group than in the control group (p?=?0.015). According to physician and patient self-assessment, respectively, 71% and 63% women in the MPQ group were considered cured or markedly improved. This was significantly higher compared to controls. There was a significant higher increase of Incontinence Quality-of-Life questionnaire score in the MPQ group compared to controls (p?=?0.017). Improvements in MPQ group at 3 months are sustained to 12 months. Adverse events were mild and transient. MIS is an acceptable option for women with SUI and urethral hypermobility.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (I)

Occupational diseases Nos. 2108 and 2110 correspond to intervertebral disc-related diseases of the lumbar spine from many years of carrying or lifting heavy loads, occupations in extreme postures of full flexion or oscillation of the whole body when seated, and which compel the cessation of all activities which are or could be the cause for the origin, exacerbation or recurrence of the disease. These occupational diseases came into force at the start of 1993, but there have been considerable problems in their implementation. The present Part I of the contribution is the result of the work of an interdisciplinary study group and contains medical criteria for the assessment of possibly strain-related clinical characteristics and the evaluation of other possible causes. Part II is to be published in Volume 4/2005 and will deal with questions related to forced cessation and to the assessment of the loss of earning ability. Agreement was reached in many areas related to the assessment of occupational claims. This should allow for evidence-based decision making in the future for the occupational diseases Nos. 2108 and 2110.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (II)

The first part of this serial paper dealt with the medical criteria used in evaluation of the clinical picture caused by physical stress and the evaluation of other candidate causes and was published in issue no. 3/2005 (pp. 711–752) of Trauma and Berufskrankheit. This follow-up paper (II) presents criteria to be used in the evaluation of whether it is necessary to give up the occupations putting the spine at risk and in estimation of the degree of disability.     

Reproducibility and biological basis of in vivo T2* magnetic resonance imaging of liver metastasis of colorectal cancer

In this study, the reproducibility of MR imaging in colorectal liver metastases was assessed and values were correlated with the expression of the hypoxia‐related markers GLUT‐1 and CA‐IX as well as the relative vascular area, and the vessel density in resected tumors. The reproducibility of was analyzed in 18 patients with in total 22 colorectal liver metastases using the Bland and Altman method for the 16th, 50th, and 84th percentile values. Immunohistochemical staining was performed on 17 resected tumors obtained from 16 patients. The median of all liver metastases was 25.0 ± 5.6 ms vs. 23.0 ± 4.1 ms (median ± st.dev.) in normal liver. The coefficient of repeatability was 11.2 ms and the limits of agreement were ?13.2 ms and 9.1 ms for median values. On average, showed fair reproducibility. No correlations between values, hypoxia‐ and vascularity‐related markers were observed. Magn Reson Med, 70:1145–1152, 2013. © 2012 Wiley Periodicals, Inc.     

Impaired renal function is associated with markers of endothelial dysfunction and increased inflammatory activity.

BACKGROUND: Patients with end-stage renal disease (ESRD) as well as those with mild renal insufficiency are at increased risk for the development of cardiovascular disease, which cannot be attributed entirely to traditional risk factors. Endothelial dysfunction and chronic inflammatory activity, two important phenomena in atherogenesis, can be found in ESRD. At present, it is unclear whether endothelial dysfunction and chronic inflammatory activity are related to renal function in the pre-dialysis stage. METHODS: In a cross-sectional, single-centre study, four groups of 20 subjects with renal function ranging from a normal, calculated creatinine clearance (>90 ml/min) to a pre-dialysis situation (<31 ml/min) were investigated. We measured markers of endothelial function [von Willebrand factor (vWf), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and E-selectin (ES)], and markers of inflammatory activity [secretory phospholipase A(2) (sPLA(2)) and C-reactive protein (CRP)]. Using these markers, composite endothelial function and inflammatory activity scores were constructed. RESULTS: Creatinine clearance correlated with the endothelial function score (r=-0.43, P<0.001), the inflammatory activity score (r=-0.53, P<0.05), vWf (r=-0.54, P<0.001), sVCAM-1 (r=-0.50, P<0.001), sPLA(2) (r=-0.28, P<0.05), homocysteine (r=-0.61, P<0.001), age (r=-0.54, P<0.001) and blood pressure (r=-0.44, P<0.001). In multivariate analyses, creatinine clearance was an independent determinant of the endothelial function score (beta=-0.34, P=0.006), plasma vWf (beta=-0.37, P=0.022) and sICAM-1 (beta=-0.33, P=0.012). The relationship of creatinine clearance with sVCAM-1 and endothelial function score was not significant when plasma homocysteine was added to the model. Creatinine clearance was also a determinant of the inflammatory activity score (beta=-0.31, P=0.025) and sPLA(2) (beta=-0.32, P=0.024), although this was no longer significant after correction for systolic blood pressure. CONCLUSIONS: Renal dysfunction is associated with markers of endothelial dysfunction and inflammatory activity. Plasma homocysteine may be an intermediate factor in the relationship between endothelial dysfunction and renal function, while blood pressure may modulate the association between inflammatory activity and renal function.     

Is rationing the inevitable consequence of medical advance?

The past decades have seen an impressive advance in medical technology. However, there are concerns about the growing costs of medical technology and the need to ration health care services. Some economists argue that the use of technology might be expensive now but that it would be unwise to ration technological advances as they will save money in the long-term. The author argues that increased productivity in health care does not necessarily lead to reduction of costs. In fact, it has often resulted in increased costs because such innovations made possible a widening of the indications for the treatment. Rationing of medical technology is inevitable, as further advances of technology will lead to higher pressures on the financing of the public health care system and the increased removal from the basic package of long-term care services for chronic conditions, the provision of which is an important responsibility of our society.     

Neuronal nitric oxide synthase: its role and regulation in macula densa cells

Macula densa (MD) cells detect changes in distal tubular sodium chloride concentration ([NaCl](L)), at least in part, through an apical Na:2Cl:K co-transporter. This co-transporter may be a site for regulation of tubuloglomerular feedback (TGF), and recently angiotensin II (Ang II) was shown to regulate the MD Na:2Cl:K co-transporter. In addition, nitric oxide (NO) produced via neuronal NO synthase (nNOS) in MD cells attenuates MD-TGF signaling. This study investigated [NaCl](L)-dependent MD-NO production, the regulation of co-transporter activity by NO, and the possible interaction of NO with Ang II. MD cell Na(+) concentration ([Na(+)](i)) and NO production were measured using sodium-binding benzofuran isophthalate and 4-amino-5-methylamino-2',7'-difluorescein diacetate, respectively, using fluorescence microscopy. Na:2Cl:K co-transport activity was assessed as the initial rate of increase in [Na(+)](i) when [NaCl](L) was elevated from 25 to 150 mM. 10(-4) M 7-nitroindazole, a specific nNOS blocker, significantly increased by twofold the initial rate of rise in [Na(+)](i) when [NaCl](L) was increased from 25 to 150 mM, indicating co-transporter stimulation. There was no evidence for an interaction between the stimulatory effect of Ang II and the inhibitory effect of NO on co-transport activity, and, furthermore, Ang II failed to alter MD-NO production. NO production was sensitive to [NaCl](L) but increased only when [NaCl](L) was elevated from 60 to 150 mM. These studies indicate that MD-NO directly inhibits Na:2Cl:K co-transport and that NO and Ang II independently alter co-transporter activity. In addition, generation of MD-NO seems to occur only at markedly elevated [NaCl](L), suggesting that NO may serve as a buffer against high rates of MD cell transport and excessive TGF-mediated vasoconstriction.     

Neoadjuvant chemotherapy in advanced stomach cancer--a case of complete response

In the treatment of gastric cancer R0 surgical resection is the only hope for cure. Unfortunately most patients are first seen when they are in an advanced stage, when the possibility of R0 resection is very poor. In these cases administration of other therapies is justified. In the last decade neoadjuvant combination chemotherapy had been introduced with promising results. ECF neoadjuvant chemotherapy has 60% response rate in irresectable cases. We report about a patient with locally advanced gastric cancer treated with neoadjuvant ECF chemotherapy. The patient reacted with complete response, so following chemotherapy R0 resection could be carried out. We describe different therapies used for patients with locally advanced gastric cancer. Neoadjuvant chemotherapy is a recommended therapeutic modality in locally advanced gastric cancer, because it may have the effect of irresectable disease becoming resectable.