Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

The genotoxic effects in lymphocyte cultures of children treated with radiosynovectomy by using yttrium-90 citrate colloid

The aim of this study was to investigate the genotoxic effect on the peripheral blood lymphocytes potentially induced by yttrium-90 citrate colloid (Y-90) in children who were undergoing radiosynovectomy for hemophilic synovitis, using chromosomal aberration analysis (CA) and the micronuclei (MN) assay for detecting chromosomal aberrations, as well as the sister chromatid exchanges (SCE) technique for assessed DNA damage. MATERIALS AND METHODS: Cytogenetic analyses were undertaken in 18 boys (mean age, 14.5 +/- 2.1 years) with hemophilic synovitis who underwent radiosynovectomy with Y-90. CA, MN, and SCE were evaluated just prior to, then at 2 and 90 days following radiosynovectomy from the peripheral lymphocytes of the children. An activity of 185 MBq of Y-90 was injected into the 18 knee joints under aseptic conditions. To check the possibility of leakage from the joint and its migration within the body, the patients underwent scanning under a dual-headed gamma camera at the hours 2 and 48 following the procedure. RESULTS: The procedure was well tolerated in all the children, and there was no extra-articular activity owing to extra-articular leakage of radioactive material in whole-body imaging. The mean frequency of CA in lymphocytes determined prior to the onset of therapy (0.31 +/- 0.48/900 cells) was not significantly increased, in comparison to the control values obtained 2 (0.30 +/- 0.48/900 cells) and 90 days (0.15 +/- 0.37/900 cells) after radiosynovectomy (p = 1.0 and 0.625, respectively). We observed that MN frequency was mildly increased in lymphocytes 2 days after therapy (8.30 +/- 1.89 MN/1000 binucleated cells vs. 9.23 +/- 1.79 MN/1000 binucleated cells; p = 0.013). But there was no significant difference between the baseline and the day 90 control levels of MN (p = 0.196). In the analysis of SCE frequency, there were no significant differences between the baseline (8.11 +/- 0.77) and the control analysis performed 2 and 90 days following radiosynovectomy (8.18 +/- 0.77 and 8.07 +/- 0.74; p = 0.710 and 0.662, respectively). CONCLUSIONS: The results of this study indicated that high radiation doses are not obtained by peripheral lymphocytes of children who undergo Y-90 radiosynovectomy and, therefore, they contradict a high cancer risk.     

Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines.

We studied the effect of arsenic trioxide (As2O3) on prostate and ovarian carcinoma cell lines. As2O3 has been shown to be effective in leukemia, and acute promyelocytic leukemia in particular, both in vitro and in vivo. As model cell lines, we used DU145 and PC-3 for prostate cancer and MDAH 2774 for ovarian cancer. New modalities of treatment are essential in these kinds of cancers, which produce a high death toll. The 3-(4,5-dimethyl-thiazoyl-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to evaluate cytotoxicity. Flow cytometric analysis and mono-oligo nucleosome detection-based ELISA were used to determine the apoptosis. Isobologram analysis was used to evaluate synergism and/or the additive effects of As2O3 and conventional chemotherapeutic agents. We clearly demonstrated that As2O3 has significant cytotoxic effect on both prostate and ovarian carcinoma cell lines. The dose range of As2O3 in all three cell lines was approximately 10(-6) M. The mechanism underlying cytotoxicity of As2O3 was shown to be apoptosis. The experiments by butylated hydroxyanisole showed that the cytotoxic effect of As2O3 was not through superoxide generation. There was no synergism, but the additive effects of As2O3 were demonstrated with cisplatin, adriamycin, and etoposide. We strongly suggest that As2O3 alone or in combination with conventional chemotherapeutic agents be evaluated further as a new agent for the treatment of prostate and ovarian cancers.     

Efficacy and safety of bevacizumab plus capecitabine and irinotecan regimen for metastatic colorectal cancer

Recent phase III trials have proven the fact that adding bevacizumab to irinotecan plus infusional 5-fluorouracil (5-FU)/leucovorin (LV) should be preferred as a first-line treatment for metastatic colorectal cancer (mCRC). But, since the data regarding bevacizumab administered together with capecitabin, an oral fluoropyrimidine, and irinotecan in patients with mCRC is limited, we aimed to analyse the efficacy and safety of bevacizumab with capecitabine plus irinotecan (BEV-CAPIRI) regimen in mCRC patients. Records of patients treated with BEV-CAPIRI regimen between January 2005 and March 2008 were reviewed. Efficacy data regarding response rates (RR) as well as safety data were collected. Progression free survival (PFS) and overall survival (OS) analyses were done by using the Kaplan–Meier method. A total number of 53 metastatic colorectal cancer patients were treated with BEV-CAPIRI regimen. The median age of this population was 57.3 ± 11.5 (range 29–78). The treatment was well tolerated. The RR was 43.3%, while 30.1% of the patients achieved stable disease (SD). Median PFS and OS were 12.6 ± 1.4 and 20.6 ± 1.7 months, respectively. However, median OS was 21.3 months for male and 14.6 months for female patients. In addition, median OS and PFS was 25.3 months and 16.2 months for the patients who received BEV-CAPIRI as first-line treatment, respectively, and for the other patients it was 15.2 months and 10.2 months, respectively. In conclusion, BEV-CAPIRI is an effective and well-tolerated alternative regimen for mCRC, leading to disease control in a vast majority of patients with mCRC.     

Hidradenitis suppurativa: Clinical characteristics and determinants of treatment efficacy

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that causes a significant decline in quality of life. There are numerous treatment options; however, real‐life data on the efficacy of these treatments is limited. This study was performed in two centers to describe clinical characteristics and assess treatment outcome in a cohort of 139 patients with HS. Data on demographic and clinical characteristics, Hurley stage and comorbidities were collected from patient charts and evaluated retrospectively. Treatment response was measured with HS clinical response index (HISCR). Mean body mass index was 27.8±4.88 . Inflammatory comorbidities were present in 23%. Among first‐line drugs systemic doxycycline resulted in 60% HISCR followed by rifampicin–clindamycin combination (46.4%). Isotretinoin had the lowest HISCR (30.7%) in this group. For second‐line therapies, all acitretin treated patients achieved response and patients treated with tumor necrosis factor alpha (TNF‐α) inhibitors had the highest HISCR. Currently recommended first‐line therapies have moderate efficacy in HS. Acitretin appears to be a reasonable alternative for the highly effective TNF‐α inhibitors in patients with severe and resistant HS. Overall, these results support that excessive inflammatory response play an important role in pathogenesis of HS.     

Prevention of pleural adhesions using a membrane containing polyethylene glycol in rats

Background: Recurrent thoracotomies regardless of the cause are not a rare occurrence. However, each thoracotomy results in adhesion to some extent. This adhesions increase morbidity and mortality presents a significant inconvenience for surgeons and prolongs the length of operations.Objective: We investigated the efficacy of Prevadh®, an anti-adhesion agent to prevent intrapleural adesions following thoracotomy in a rat model.Methods: Twenty male adult Wistar Albino rats were divided into a sham group (Group A, n = 4), a control group (Group B, n = 8), and a study group (Group C, n = 8). Only left thoracotomy was performed in Group A. Group B underwent left thoracotomy, induction of adhesion, and 1 ml saline solution was administered to the thoracic cavity. However, in Group C underwent left thoracotomy, induction of adhesion, and Prevadh® was placed between the pleura and the lung. The rats were sacrificed on day 21, and adhesions were analyzed using both macroscopic and histopathological methods. The results were statistically analyzed. A value of P<0.05 was considered statistically significant.Results: Mean lengths of adhesion differed statistically significantly among all three groups, while mean intensity of adhesion differed between Group A and Group B, and between Group B and Group C (P>0.05). There was also a statistically significant difference between Group A and Group C in mesothelium proliferation score (P>0.05). No statistically significant differences were found among the groups in terms of pleural thickness, macrophage and mononuclear cell infiltration (P>0.05).Conclusions: Prevadh® was shown in a rat model to effectively prevent post-thoracotomy adhesions.     

Neurological complications after liver transplantation

This was a single-centre, prospective study to assess the frequency of neurological complications and their impact on prolonged hospitalization in 137 liver transplant patients presenting between September 1997 and June 2010. Neurological complications were seen in 22 (16%) patients during their postoperative stay in the intensive care unit. Complications included new-onset, recurrent headache (five patients), generalized seizures (four patients), dysarthria (two patients), delirium with agitation (three patients), persistent flapping tremor (two patients), alteration in level of consciousness (three patients), central pontine myelinolysis (one patient), myopathy (one patient) and visual hallucinations (one patient). Seizures were associated with immunosuppressive drug toxicity (tacrolimus). Myopathy presenting as quadriplegia was diagnosed by muscle biopsy. The patient with central pontine myelinolysis lived in a persistent vegetative state for 2 years and died of pneumonia. In conclusion, neurological complications are frequently encountered after liver transplantation, and are an important cause of severe morbidity and prolonged intensive care unit and hospital stay.     

Intracerebral hematoma following lumboperitoneal shunt insertion: a rare case report

Lumboperitoneal shunting is widely used for the surgical management of pseudotumor cerebri and other pathologies such as communicating hydrocephalus. Although it is a safe method, it could be associated with complications including subarachnoid hemorrhage, subdural and rarely intracerebral hematoma. A 44-year-old female applied to our clinic with complaints of severe headache, retroorbital pain and blurred vision. Lumbar puncture demonstrated cerebrospinal fluid opening pressure of cmH2O. A non-programmable lumboperitoneal shunt with two distal slit valves was inserted due to pseudotumor cerebri. She deteriorated shortly after surgery. Immediate cranial computed tomography scan revealed a right parietal intracerebral hematoma. Development of intracerebral hematoma following lumboperitoneal shunt is a rare complication. We discuss this rare event accompanied by the literature.