Analysis of the effectiveness of psychologic interventions in oncology regarding the quality of life and survival of cancer patients

Psychotherapy and psycho-social interventions in oncological rehabilitation, based on confirmed results of several controlled studies designed and conducted in a bio-psycho-social research framework, have been proved to reduce the psycho-social vulnerability of cancer patients and to enhance health related quality of life in this patient population. It is also supposed that psychological intervention increases survival outcomes of cancer patients through immune-modulation. Findings of psycho-neuro-immunological research have underlined that the human neurological and immunological system, mainly the NK, CD4 and CD8 cell activity and cytotoxicity, are mediators and modulators in the progress of malignant tumors. Positive outcomes of psycho-social rehabilitation in oncology reinforce not only its effectiveness in reducing stress and anxiety, strengthening active coping mechanisms and immune functions, and improving quality of life but also its cost-effectiveness in view of relatively low investment and the high, multiplied health related benefits.     

Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells

The 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are widely used and well tolerated cholesterol-lowering drugs. In rare cases, side effects occur in skeletal muscle, including myositis or even rhabdomyolysis. However, the molecular mechanisms are not well understood that lead to these muscle-specific side effects. Here, we show that statins cause apoptosis in differentiated human skeletal muscle cells. The prototypical representative of statins, simvastatin, triggered sustained intracellular Ca(2+) transients, leading to calpain activation. Intracellular chelation of Ca(2+) completely abrogated cell death. Moreover, ryanodine also completely prevented the simvastatin-induced calpain activation. Nevertheless, an activation of the ryanodine receptor by simvastatin could not be observed. Downstream of the calpain activation simvastatin led to a translocation of Bax to mitochondria in a caspase 8-independent manner. Consecutive activation of caspase 9 and 3 execute apoptotic cell death that was in part reversed by the coadministration of mevalonic acid. Conversely, the simvastatin-induced activation of calpain was not prevented by mevalonic acid. These data delineate the signaling cascade that leads to muscle injury caused by statins. Our observations also have implications for improving the safety of this important medication and explain to some extent why physical exercise aggravates skeletal muscle side effects.     

Prenatal diagnosis, phenotypic and obstetric characteristics of holoprosencephaly

The diagnosis of fetal malformations, especially those of the central nervous system, is strikingly important in the practice of genetic counseling. Early diagnosis is very significant, not only because of the prognosis, but also because of the emotional effects caused by the accompanying craniofacial malformations. The summary of the obstetrical and diagnostical characteristics should be useful in the management of holoprosencephaly. The analysis of the 50 cases we encountered between 1981 and 2000, including the anatomical, diagnostic and clinical aspects, as well as the associated craniofacial malformations, forms the essence of our publication. In one of the examined cases a familiar recurrence was verified.     

Aldose reductase inhibition counteracts oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation in tissue sites for diabetes complications

This study evaluated the effects of aldose reductase inhibition on diabetes-induced oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation. In animal experiments, control and streptozotocin-induced diabetic rats were treated with or without the aldose reductase inhibitor (ARI) fidarestat (16 mg . kg(-1) . day(-1)) for 6 weeks starting from induction of diabetes. Sorbitol pathway intermediate, but not glucose, accumulation in sciatic nerve and retina was completely prevented in diabetic rats treated with fidarestat. Sciatic motor nerve conduction velocity, hindlimb digital sensory nerve conduction velocity, and sciatic nerve concentrations of two major nonenzymatic antioxidants, glutathione and ascorbate, were reduced in diabetic versus control rats, and these changes were prevented in diabetic rats treated with fidarestat. Fidarestat prevented the diabetes-induced increase in nitrotyrosine (a marker of peroxynitrite-induced injury) and poly(ADP-ribose) immunoreactivities in sciatic nerve and retina. Fidarestat counteracted increased superoxide formation in aorta and epineurial vessels and in in vitro studies using hyperglycemia-exposed endothelial cells, and the DCF test/flow cytometry confirmed the endothelial origin of this phenomenon. Fidarestat did not cause direct inhibition of PARP activity in a cell-free system containing PARP and NAD(+) but did counteract high-glucose-induced PARP activation in Schwann cells. In conclusion, aldose reductase inhibition counteracts diabetes-induced nitrosative stress and PARP activation in sciatic nerve and retina. These findings reveal the new beneficial properties of fidarestat, thus further justifying the ongoing clinical trials of this specific, potent, and low-toxic ARI.     

Radiographic comparison of two glenoid preparation techniques in total shoulder arthroplasty

We compared the prevalence of periglenoid radiolucencies between two glenoid component preparation techniques used in total shoulder arthroplasties. Seventy-two consecutive patients with primary osteoarthritis had total shoulder arthroplasties using one prosthetic system with flat-back keeled polyethylene glenoid components. Thirty-seven shoulders had glenoid implants that were cemented after standard curettage preparation of the keel slot. Thirty-five shoulders had glenoid implants that were cemented after using bone compaction to prepare the keel slot. The immediate postoperative and 2-year postoperative radiographs were examined to evaluate the presence and progression of periglenoid radiolucencies. The curettage group had a higher rate (38%) of keel radiolucencies than the compaction group (11%) seen on the immediate postoperative radiographs. Both groups had progression of periglenoid radiolucencies with time. Progression of the radiolucent lines was worse in the curettage group 2 years after arthroplasty. Preparation of the glenoid component keel slot with the bone compaction technique seems to achieve better fixation of flat-back keeled polyethylene glenoid components in total shoulder arthroplasties.     

Expanding masses of the posterior orbit

The expanding masses of the posterior part of the orbit consist of the intraorbital space occupying processes, located posteriorly to the frontal plain, crossing the anatomic equator of the eyeball. Modern surgery of this part of the orbit is included ?n the larger field of the anterior skull base surgery. Successful orbital surgery is a multidisciplinary team work, based on precise preoperative diagnosis, adequate surgical technique and comprehensive anatomical knowledge of the operated region. This paper presents the experience of the authors on 73 cases of expanding masses of the posterior orbit, admitted and treated ?n the Neurosurgical Clinic from Cluj-Napoca.     

The adenosine A3 receptor agonist,N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide,is protective in two murine models of colitis

This study evaluated the effects of the adenosine A(3) receptor agonist, N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA), in two murine models of colitis, the dextran sodium sulphate-induced colitis and the spontaneous colitis found in interleukin-10 gene deficient mice. IB-MECA was given orally twice a day at a dose of either 1 or 3 mg/kg/day. Evaluation of colon damage and inflammation was determined grossly (body weight, rectal bleeding) and biochemically (colon levels of myeloperoxidase, malondialdehyde, chemokines and cytokines). There was significantly increased inflammatory cell infiltration into the colon associated with an increase in colon levels of cytokines and chemokines; with subsequent free radical related damage in both dextran sodium sulphate-induced colitis and 10-week-old interleukin-10(-/-) mice. IB-MECA protected in both models against the colitis induced inflammatory cell infiltration and damage and attenuated the increases in colon inflammatory cytokine and chemokine levels. Thus activation of the adenosine A(3) receptor is effective in protecting against colitis.     

Targeting the epidermal growth factor receptor in cancer: apoptosis takes center stage

Aberrant activation of the epidermal growth factor receptor (EGFR) is frequently observed in neoplasia,notably in tumors of epithelial origin. Attempts to treat such tumors with EGFR antagonists have met with remarkable initial successes, particularly when EGFR antagonists were used in combination with chemotherapy or ionizing radiation. Considering the almost ubiquitous expression of the EGFR in normal epithelial tissues, these clinical trials also revealed a surprisingly low rate of adverse side effects associated with EGFR blockade. This review highlights antiapoptotic effects of EGFR activation as they relate to therapeutic efficacy of EGFR blockade. We introduce the concept that control of cell survival through EGFR activation is conditional in the sense that it is rate limiting to tumor cell survival but not to survival of normal epithelial cells. Specifically, normal epithelial cells are provided with a full complement of physiological cell-cell contacts and cell-matrix interactions that lessen their dependence on survival signals provided by the EGFR. By contrast, malignant tumor cells faced with inadequate cell-matrix contacts critically depend on EGFR activation for survival, rendering them more susceptible to apoptosis induction by EGFR blockade. Redundant control of cell survival by the EGFR and extracellular matrix/cell adhesion receptors is enabled, in part, by shared signal transduction pathways that control expression and activation states of members of the Bcl-2 family of apoptosis regulators.