[Prudent use of computed tomography for the improvement of patient safety].

Computed tomography (CT) is one of the most useful imaging modalities, and has an important role in guided biopsies and therapeutic procedures. The expansion of CT practice is sometimes accompanied with disregard of the fact that it is an invasive methodology, with deviations from patient safety principles. The major risk is associated with ionizing irradiation which may damage the DNA, leading to malignant transformation. There are no direct data yet as to the actual cancer risk and the current assessments are based on theoretical modeLs and extrapolations from historical records. However, it is widely accepted that although the danger for an individual patient is small, a significant number of malignant disorders would be diagnosed many years later and the threat is particularly pertinent for children. Some CT scans are performed nowadays without proper indications. The reasons include: (a) physicians working burden, and the expectations from them to attain diagnoses rapidly; (b) patients demand CT scans unaware of its hazards; (c) private imaging facilities offer "sale prices" for CT scans, even when there are no definite indications, and perform them without physicians referrals. Other issues are incidental findings in screening CTs of healthy people, which may represent a genuine medical problem, but, more often, are insignificant. Undoubtedly, CT usage will increase with the development of new technologies. This process must be accompanied by patient safety measurements, including: (a) performing a CT only according to the clinical presentation and indications; (b) towering irradiation doses and monitoring the instruments and protocols; (c) instructing physicians and informing patients about the benefits and disadvantages of CT.

Tumor necrosis factor receptors support murine hematopoietic progenitor function in the early stages of engraftment.

Tumor necrosis factor (TNF) family receptors/ligands are important participants in hematopoietic homeostasis, in particular as essential negative expansion regulators of differentiated clones. As a prominent injury cytokine, TNF-alpha has been traditionally considered to suppress donor hematopoietic stem and progenitor cell function after transplantation. We monitored the involvement of TNF receptors (TNF-R) 1 and 2 in murine hematopoietic cell engraftment and their inter-relationship with Fas. Transplantation of lineage-negative (lin(-)) bone marrow cells (BMC) from TNF receptor-deficient mice into wild-type recipients showed defective early engraftment and loss of durable hematopoietic contribution upon recovery of host hematopoiesis. Consistently, cells deficient in TNF receptors had reduced competitive capacity as compared to wild-type progenitors. The TNF receptors were acutely upregulated in bone marrow (BM)-homed donor cells (wild-type) early after transplantation, being expressed in 60%-75% of the donor cells after 6 days. Both TNF receptors were detected in fast cycling, early differentiating progenitors, and were ubiquitously expressed in the most primitive progenitors with long-term reconstituting potential (lin(-)c-kit(+) stem cell antigen (SCA)-1(+)). BM-homed donor cells were insensitive to apoptosis induced by TNF-alpha and Fas-ligand and their combination, despite reciprocal inductive cross talk between the TNF and Fas receptors. The engraftment supporting effect of TNF-alpha is attributed to stimulation of progenitors through TNF-R1, which involves activation of the caspase cascade. This stimulatory effect was not observed for TNF-R2, and this receptor did not assume redundant stimulatory function in TNFR1-deficient cells. It is concluded that TNF-alpha plays a tropic role early after transplantation, which is essential to successful progenitor engraftment.

Expression of Fas and Fas-ligand in donor hematopoietic stem and progenitor cells is dissociated from the sensitivity to apoptosis.

OBJECTIVE: The interaction between the Fas receptor and its cognate ligand (FasL) has been implicated in the mutual suppression of donor and host hematopoietic cells after transplantation. Following the observation of deficient early engraftment of Fas and FasL-defective donor cells and recipients, we determined the role of the Fas-FasL interaction. METHODS: Donor cells were recovered after syngeneic (CD45.1-->CD45.2) transplants from various organs and assessed for expression of Fas/FasL in reference to lineage markers, carboxyfluorescein succinimidyl ester dilution, Sca-1 and c-kit expression. Naïve and bone marrow-homed cells were challenged for apoptosis ex vivo. RESULTS: The Fas receptor and ligand were markedly upregulated to 40% to 60% (p < 0.001 vs 5-10% in naïve cells) within 2 days after syngeneic transplantation, while residual host cells displayed modest and delayed upregulation of these molecules ( approximately 10%). All lin(-)Sca(+)c-kit(+) cells were Fas(+)FasL(+), including 95% of Sca-1(+) and 30% of c-kit(+) cells. Fas and FasL expression varied in donor cells that homed to bone marrow, spleen, liver and lung, and was induced by interaction with the stroma, irradiation, cell cycling, and differentiation. Bone marrow-homed donor cells challenged with supralethal doses of FasL were insensitive to apoptosis (3.2% +/- 1% vs 38% +/- 5% in naïve bone marrow cells), and engraftment was not affected by pretransplantation exposure of donor cells to an apoptotic challenge with FasL. CONCLUSION: There was no evidence of Fas-mediated suppression of donor and host cell activity after transplantation. Resistance to Fas-mediated apoptosis evolves as a functional characteristic of hematopoietic reconstituting stem and progenitor cells, providing them competitive engraftment advantage over committed progenitors.

Fas ligand enhances hematopoietic cell engraftment through abrogation of alloimmune responses and nonimmunogenic interactions.

Early after transplantation, donor lineage-negative bone marrow cells (lin(-) BMC) constitutively upregulated their expression of Fas ligand (FasL), suggesting an involvement of the Fas/FasL axis in engraftment. Following the observation of impaired engraftment in the presence of a dysfunctional Fas/FasL axis in FasL-defective (gld) donors or Fas-defective (lpr) recipients, we expressed a noncleavable FasL chimeric protein on the surface of donor lin(-) BMC. Despite a short life span of the protein in vivo, expression of FasL on the surface of all the donor lin(-) BMC improved the efficiency of engraftment twofold. The FasL-coated donor cells efficiently blunted the host alloimmune responses in primary recipients and retained their hematopoietic reconstituting potential in secondary transplants. Surprisingly, FasL protein improved the efficiency of engraftment in syngeneic transplants. The deficient engraftment in lpr recipients was not reversed in chimeric mice with Fas(-) stroma and Fas(+) BMC, demonstrating that the host marrow stroma was also a target of donor cell FasL. Hematopoietic stem and progenitor cells are insensitive to Fas-mediated apoptosis and thus can exploit the constitutive expression of FasL to exert potent veto activities in the early stages of engraftment. Manipulation of the donor cells using ectopic FasL protein accentuated the immunogenic and nonimmunogenic interactions between the donor cells and the host, alleviating the requirement for a megadose of transplanted cells to achieve a potent veto effect. Disclosure of potential conflicts of interest is found at the end of this article.

[Sportsman's hernia--a plea for conservative therapeutical approach].

Sportsmen often suffer prolonged inguinal pain which can become a serious debilitating condition. In most cases the pain originates from a musculoskeletal problem. However, for some patients it has been suggested that the etiology is a weakness of the inguinal canal. This syndrome was termed "sportsman's hernia" although a hernia can not be found on physical examination. Imaging findings were found to be inconclusive regarding the alleged hidden hernia. Various types of operations, based on the variable theories regarding the pathophysiological process, have been developed for the treatment of this syndrome. Some surgeons focus on the external elements of the inguinal canal, and repair the external oblique fascia or enforce the groin with the rectus abdominis. Other surgeons perform an inguinal hernia repair procedure, either with sutures, synthetic mesh, or laparoscopically. Some researchers believe that the problem is in the lower abdominal muscles, or is caused by nerve entrapment, and treat it accordingly. There are no controlled comparative data on the results of the various surgical approaches, and there is no evidence that surgical treatment is more beneficial than conservative treatment. We recommend to operate only if conservative therapy, with prolonged rest, fails. During the operation the inguinal canal should be thoroughly explored, and will be enforced only if a hernia, or a definite weakness of the canal's floor, are found. Similarly, the release of a nerve should be performed only when the exploration reveals clear evidence of entrapment.

[Waiver of medical confidentiality].

The duty to maintain medical confidentiality is one of the fundamental and well-known obligations imposed on physicians, and is incorporated in the Law of Patient's Rights 1996 (the Law). Medical confidentiality applies to information conveyed to a physician for medical purposes trusting that the physician will not disclose it. The patient's identity and financial arrangements are not confidential. Any physician who breaches this duty may face civil, disciplinary or criminal lawsuits. The Law, as well as specific provisions in other rulings, defines the exceptions to the duty of upholding medical confidentiality. According to these provisions there are special circumstances in which a physician may, and even should, transfer medical data relating to his/her patients. One of these exclusions is the patient's consent to reveal the information. This article presents the legal infrastructure of medical confidentiality, and the means and circumstances in which medical confidentiality can be waived. Waiver of medical confidentiality does not constitute permission to convey all the information to one and all, and the Law determines that only the data required for specific purposes should be transferred. The way by which the patient waives his right for confidentiality is not defined by the Law or by regulations. A patient's consent to waive his right for confidentiality can be allegedly obtained in writing, orally or by behavior. It seems that the appropriate manner of waiving medical confidentiality is in writing. The waiver form should specify the nature and extent of information that can be conveyed, and it must be signed by the patient. The doctor is also responsible to ensure privacy during the transmission of the data. Specific subjects which are associated with the duty to maintain medical confidentiality are also discussed in this paper. In cases when a man's life or safety is at stake, the duty of a physician to protect life overweighs his duty to entrusted confidentiality. In such cases, the physician should transfer the information even if the patient did not waive his right for secrecy. This obligation also applies to patients who suffer from specific diseases, for example HIV. The duty to maintain medical confidentiality is relevant to the patient's relatives. Obtaining written consent to convey the information to family members is not practical. However, it is recommended that a physician should provide the information only to relatives he knows, and only when he can reasonably assume that the patient will agree.

Detection of hepatocyte growth factor/scatter factor receptor (c-Met) and MUC1 from the axillary fluid drainage in patients after breast cancer surgery.

BACKGROUND: Drains are inserted in the dissected axilla of most patients during surgery for breast cancer. OBJECTIVE: To evaluate the presence and prognostic value of MUC1 and Met-hepatocyte growth factor/scatter factor in the axillary drainage of these patients. METHODS: The study group included 40 consecutive patients with invasive ductal carcinoma of the breast who were suitable for breast-conserving treatment; 20 malignant melanoma patients found to have negative axillary sentinel lymph node served as the control group. The output of the drains, which had been placed in the axilla during operation, was collected, and the presence of MUC1, Met-HGF/SF and beta-actin were assessed in the lymphatic fluid by reverse transcription-polymerase chain reaction assays. The data were compared to the pathologic features of the tumor and the axillary lymph nodes, and to the estrogen and progesterone receptors status. RESULTS: RT-PCR assays of the axillary lymphatic drainage were positive for MUC1 and Met-HGF/SF in 15 (37.5%) and 26 (65%) of the patients, respectively. Patients in whom MUC1 and Met-HGF/SF were not found in the axillary fluid had smaller tumors and less capillary and lymphatic invasion, compared to patients with positive assays (P < 0.0 for all these comparisons). The lymph nodes were negative for metastases in all patients with negative assays (P < 0.001). The presence of MUC1 and Met-HGF/SF showed negative correlations with the estrogen and progesterone receptors (P < 0.05). CONCLUSION: MUC1 and Met-HGF/SF can be detected in the axillary fluids of patients with breast cancer. The expression of both tumor markers in the axillary drainage is strongly associated with unfavorable tumor features and can be used as a prognostic factor.

Detection of hepatocyte growth factor/scatter factor receptor (c-Met) in axillary drainage after operations for breast cancer using reverse transcriptase-polymerase chain reaction.

BACKGROUND: The diverse biological effects of hepatocyte growth factor/scatter factor (HGF/SF) are mediated by c-Met, which is preferentially expressed on epithelial cells. Met signaling has a role in normal cellular activities, and may be associated with the development and progression of malignant processes. In this study we examined whether Met can be detected in the axillary drainage from patients who underwent conservative operations for breast cancer, and its prognostic significance. METHODS: Thirty-one consecutive patients with invasive ductal carcinoma of the breast suitable for breast-conserving treatment were studied. The output of the drain that had been placed in the axilla during the operation was collected, and the presence of Met and beta-actin were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) assays. The data were compared with the pathological features of the tumor and the axillary lymph nodes, and with the estrogen receptor and progesterone receptor status. RESULTS: RT-PCR of the axillary lymphatic drainage was positive for Met in 23 (74.2%) of the patients. Positive assays were correlated with increasing tumor size and grade, with capillary and lymphatic invasion, and with lymph node metastasis (P < 0.02, for all comparisons). All 12 patients with axillary lymph node metastases had positive assays for Met, compared with 57.9% of patients without lymph node metastases. All five patients with tumor involvement in the margins of the resection had positive assays for Met in their lymphatic fluid, compared with 18 of 26 positive assays (69.2%) for patients without involved margins (P < 0.04). Finally, Met showed negative correlations with positivity for estrogen receptor and progesterone receptor (P < 0.02). CONCLUSION: Met can be detected in the axillary fluids of patients with breast cancer and its expression in the axillary drainage may have potential as a prognostic factor. This finding might be relevant to therapeutic considerations, because a positive assay for Met in histologically node-negative patients might point to the need to search for node microinvasion or involvement of the excision margins with tumor.

Breast carcinoma: a report on the potential usage of the CC chemokine RANTES as a marker for a progressive disease.

BACKGROUND: High incidence and intensity of RANTES (CC chemokine) expression were noted in advanced breast carcinoma. OBJECTIVE: To present two cases of breast carcinoma patients in whom RANTES expression was analyzed in parallel to disease progression. RESULTS: Although no evidence of malignancy was detected in the axillary lymph nodes of the two patients, their disease progressed. The expression of RANTES in both patients was positive at diagnosis and predicted the clinical course. CONCLUSIONS: These results, combined with our previous findings on the correlation between RANTES expression and advanced breast carcinoma, suggest that the assessment of RANTES expression may be useful for the identification of patients with apparently poor prognosis who may benefit from aggressive treatment. The above results call for large-scale studies by numerous research groups to determine the prognostic value of RANTES expression.

[Repair of anorectal fistulas using fibrin glue tissue adhesive--preliminary experience in 15 patients].

PURPOSE: The goal of this study was to evaluate whether commercially produced fibrin sealant can be used for the treatment of complex anorectal fistulae. METHODS: Fibrin glue was used for patients with primary and recurrent ano-rectal fistulae, but patients with Crohn's disease or AIDS were excluded. The procedure was performed under anesthesia in the operating room. The primary and secondary openings were identified using blue dye. The secondary opening and the tract of the fistula were curetted, and 4 ml of fibrin sealant were injected through the secondary opening until fibrin sealant was seen coming from the primary opening. The patients were discharged on the next day following the procedure, and were followed-up closely in the outpatient clinic. RESULTS: Fifteen consecutive patients underwent one trial of fibrin glue injections. The average follow-up period was 4 months. Overall, eleven of the 15 patients (73.3%) had successful closure of their fistulae. The healing rates for intersphincteric, transsphincteric and suprasphincteric were 50%, 77.7% and 100% respectively. Fibrin glue treatment was effective in five out of the 6 patients (83.3%) who were operated on for recurrent fistulae. Of the 4 patients in whom the treatment failed, the mean time for recurrent symptoms was 4 weeks. No patient suffered from fecal or gas incontinence and all of the patients returned promptly to routine life. CONCLUSION: Sealing the tracts with fibrin glue is a unique mode for the treatment of ano-rectal fistulae, and our preliminary results with this technique are promising. The procedure is safe and easy to perform, and can be offered as an alternative to conventional surgery. Most importantly, this method minimizes the risk of fecal incontinence and the discomfort of prolonged wound healing.

A non-laser light source for photodynamic therapy: in vitro effects on normal and malignant cells.

AIM: Photodynamic therapy (PDT) involves the use of photosensitizing drugs combined with light to treat tumors. Laser systems, the current source of light for PDT, have several inherent drawbacks: the spectrum is essentially monochromatic which may be problematic for second generation photosensitizers, the systems are bulky and nearly impossible to move between hospital locations and require complicated electrical and cooling installations, the cost of a typical system is enormous, and its maintenance and operation require highly trained personnel. We now introduce a new non-laser light system, Versa-Light, which appears to work as effectively and has none of the above drawbacks. METHODS: A series of in vitro studies were performed using various murine and human normal and cancer cells which underwent PDT using aluminum phthalocyanine (AlPcS4) as a photosensitizer and Versa-Light as the light source. RESULTS: PDT of cancer cells at light energy levels of 50, 100 and 200 j/cm2 significantly decreased cell viability. PDT also decreased cell viability of normal murine splenocytes and normal human lymphocytes, but to a lesser extent. The observed significant hyperthermia was light dose-dependent. CONCLUSIONS: We believe that Versa-Light can replace laser systems as an enhanced light source for PDT. Further in vitro and pre-clinical studies are in progress.

Nuclear magnetic resonance spectroscopy in pancreatic disorders

Nuclear magnetic resonance spectroscopy (NMRS) is a powerful technique that enables continuous monitoring of biochemical processes in tissues and organs in a non-invasive manner. A model of isolated perfused rat pancreas, suitable for NMRS studies, was developed. Acute pancreatitis was induced by injections of either 0.5 me 5 per cent sodium taurocholate (TC) into the bile ducts, or 1.0 ml 10 per cent TC injection into the pancreatic parenchyma. Phosphorus (P) NMRS of experimental pancreatitis were characterized by a transient signal at -0.18ñ0.04 ppm which was assigned as solubilized lecithin, and cana be used as an indicator of the early also found during acute pancreatitis,and paralleled the extension of the pathological damage. The role of NMRS in pancreatic cancer diagnosis and its treatment were assessed in three moeels of pancreatic neoplasms. Perfused MIA PaCa-2 human pancreatic cancer cells, subcutaneously implanted pancreatic tumors in hamster, and pancreatic tumors induced in-situ in rats by direct application of the carcinogen 7,12-dimethil benzanthracene, were studied by phosphorus (P), sodium (Na) and proton (H) NMRS. P spectra of pancreatic cancer were similar in both the normal pancreas and the pancreatic tumors (39-40 mmol/g wet weight)...