Visceral artery aneurysms.

Visceral artery aneurysms are rare with an incidence of only 0.01-0.1% of the population. Open surgical or endovascular elimination should be performed for aneurysms greater than 2 cm in size. The risk of aneurysm rupture is then approximately 25-40%. If the aneurysm ruptures the mortality can be as high as 76%. For mycotic aneurysms or spurious aneurysms there is no lower limit to the diameter size for the need of treatment. Sudden abdominal pain during pregnancy can be caused by visceral artery aneurysms and must be further clarified. The indications for surgery during pregnancy should be made generously. The clinical symptoms (abdominal complaints) of visceral artery aneurysms are manifold. The treatment can be either an open surgical approach or endovascular treatment. In the emergency setting, if endovascular treatment is no longer possible, an open surgical treatment needs to be performed. There are so far no randomized studies which could identify one of the procedures (open surgery vs. endovascular surgery) as clearly being superior. The prognosis after treatment is satisfactory with a 5-10 year survival rate of approximately 90%.

[Management of lymphatic fistulas in the groin from a surgeon's perspective]. / Management von Lymphfisteln in der Leistenregion aus chirurgischer Sicht.

BACKGROUND: The postoperative occurrence of lymph fistulas in the groin is a complication that should be taken seriously. These fistulas cause an increase in morbidity and can support local and ascending infections. The treatment of this complication ranges from conservative procedures, such as compression dressings and bed rest to operative treatment with detection of the fistulas and ligation, negative pressure wound therapy (NPWT) or even muscle flaps. This review provides an overview of current therapeutic modalities. MATERIAL AND METHODS: On the basis of a current literature search via PubMed, we identified possible treatment options, which are described in this article. RESULTS: The conservative treatment options presented still have an importance in treating groin fistulas. A selection of safe and effective interventional and operative treatments is presented. CONCLUSION: If there are indications for an interventional or operative treatment a variety of safe and effective therapies are available, which can significantly reduce the length of hospital stay. The option of treatment using a muscle flap is of value as a last resort in the treatment of infected vascular prosthesis in the groin of Szilagyi type III and should be used when necessary.

Pereira's attack on legalizing euthanasia or assisted suicide: smoke and mirrors.

OBJECTIVE: To review the empirical claims made in: Pereira J. Legalizing euthanasia or assisted suicide: the illusion of safeguards and controls. Curr Oncol 2011;18:e38-45. DESIGN: We collected all of the empirical claims made by Jose Pereira in "Legalizing euthanasia or assisted suicide: the illusion of safeguards and controls." We then collected all reference sources provided for those claims. We compared the claims with the sources (where sources were provided) and evaluated the level of support, if any, the sources provide for the claims. We also reviewed other available literature to assess the veracity of the empirical claims made in the paper. We then wrote the present paper using examples from the review. RESULTS: Pereira makes a number of factual statements without providing any sources. Pereira also makes a number of factual statements with sources, where the sources do not, in fact, provide support for the statements he made. Pereira also makes a number of false statements about the law and practice in jurisdictions that have legalized euthanasia or assisted suicide. CONCLUSIONS: Pereira's conclusions are not supported by the evidence he provided. His paper should not be given any credence in the public policy debate about the legal status of assisted suicide and euthanasia in Canada and around the world.

Vitamin D receptor activation in a diabetic-like environment: potential role in the activity of the endothelial pro-inflammatory and thioredoxin pathways.

High blood and tissue concentrations of glucose and advanced glycation end products (AGEs) are thought to play an important role in the development of diabetic vascular complications. Thioredoxin interacting protein (TXNIP) is up-regulated in response to high levels of glucose and is an endogenous inhibitor of thioredoxin (TRX), and may play a contributory role in the occurrence of diabetic-related vascular diseases. Vitamin D inhibits endothelial proliferation and is a cardiovascular protective agent. The present study evaluated the impact of paricalcitol and calcitriol on the endothelial inflammatory and TXNIP pathways in cultured endothelial cells exposed to a diabetic-like environment. Fresh human umbilical vein cord endothelial cells (HUVEC) were treated for 24h with 200 µg/ml AGE-HSA and 250 mg/dl glucose concentrations, with paricalcitol or calcitriol. IL6, IL8, NFκB (p50/p65), receptor of AGE (RAGE), TXNIP, and TRX expressions were evaluated at the levels of mRNA, protein, and TRX activity. Calcitriol and paricalcitol significantly down-regulated the markers involved in the inflammatory responses. Only paricalcitol induced a significant decrease in TXNIP mRNA and protein expressions. Neither paricalcitol nor calcitriol affected TRX reductase activity or TRX mRNA and protein expressions. Our findings indicate that in an endothelial diabetic-like environment, paricalcitol and calcitriol significantly decreased the expression of genes involved in the inflammatory pathway. In this in vitro study, it seems that the TRX antioxidant system was not involved. The different effects found between paricalcitol and calcitriol might reflect the selectivity of vitamin D receptor (VDR) activation.

Changing preferences for information and participation in the last phase of life: a longitudinal study among newly diagnosed advanced lung cancer patients.

PURPOSE: The objective is to explore changes over time in the information and participation preferences of newly diagnosed stage IIIb/IV non-small-cell lung cancer patients. METHODS: Patients were recruited by physicians in 13 hospitals and interviewed every 2 months until the fourth and every 4 months until the sixth interview. RESULTS: Sixty-seven patients were interviewed three times. Over a period of 4 months from diagnosis, half of patients changed their information preferences for palliative care and end-of-life decisions with a possible or certain life-shortening effect (ELDs, e.g., non-treatment decisions) in both directions, from not wanting to wanting the information, but also--and as much--from wanting to no longer wanting it. The latter were more likely to be in a better physical condition. Preferences for participation in medical decision making also changed: 50% to 78%, depending on the type of decision (general, treatment, transfer or ELD), changed their preference towards wanting more or less participation. Pain seemed to be a trigger for patients wanting more involvement, which contrasts with studies suggesting that patients who are more ill tend to give up more control. CONCLUSIONS: Doctors should regularly ask their advanced lung cancer patients how much information and participation they want because preferences do change in unexpected ways.

Calcitriol counteracts endothelial cell pro-inflammatory processes in a chronic kidney disease-like environment.

In advanced chronic kidney disease (CKD), hypocalcemia, high levels of advanced glycation end products (AGEs), and parathyroid hormone (PTH) coexist and are considered to play a role in the development of chronic vasculopathies. The aim of the present study was to evaluate the impact of a CKD-like environment on cultured endothelial cell (EC) functions and to assess the impact of calcitriol on the expression of parameters such as endothelial nitric oxide synthase (eNOS), receptor of AGEs (RAGE), interleukin 6 (IL-6) and nuclear factor kappa B (NFκB). Human umbilical vein cord endothelial cells (HUVEC) were grown in medium containing low Ca(2+) concentration stimulated with AGE-HSA and PTH and treated with calcitriol for additional incubation. mRNA expression was established by reverse transcriptase-PCR, protein expression by Western blot analysis, IL-6 secretion by ELISA, NOS activity by conversion of [(14)C]arginine to [(14)C]citrulline and DNA-binding activity of NFκB-p65 assayed colorimetrically in nuclear extracts. The CKD-like environment characterized by the association of low Ca(2+) and high levels of AGEs and PTH, depressed eNOS system activity and enhanced RAGE and IL-6 expression/secretion. DNA-binding activity of nuclear NFκB-p65 was increased and the expression of IκBα decreased. Addition of calcitriol normalized the expression, secretion and activity of eNOS, RAGE and IL-6. The enhanced NFκB activity was also counteracted probably due to the increased IκBα expression. The effect of CKD-like environment on EC may partly explain the increased vasculopathies in CKD patients, in contrast to calcitriol, which suggests a vascular protective action.

Young-age onset of colorectal cancer in Israel.

AIM: The study was conducted to investigate the differences in clinical-pathological, ethnic, and demographic presentations and the expression of mismatch repair proteins in a cohort of young-onset (50 years) with colorectal cancer. MATERIALS AND METHODS: Clinical, demographic, and histopathological data of patients with colorectal cancer were collected retrospectively from medical records and pathology reports. RESULTS: Ninety patients, 50 years of age or younger with a mean age of 42 years were compared with a group of 190 patients above 50 years of 50 (see Table 1). Sixty percent of the young-onset patients were females, compared to 40% in the older age group (P = 0.02). Twenty-one percent of the young-onset patients were Arabs as compared to 2% of older-onset patients (P = 0.001). Younger patients displayed a higher percentage of mucinous cancers and a higher percentage of diagnosis at an advanced stage of disease; 40% of young-onset versus 31% of older-onset patients presented Duke's stages C and D (P = 0.02). CONCLUSIONS: Younger age of onset colorectal cancer in our cohort of Israeli patients is associated with higher percentage of Arab patients, mucinous cancers, female gender, and advanced stage at diagnosis.

Placental findings contributing to fetal death, a study of 120 stillbirths between 23 and 40 weeks gestation.

BACKGROUND: Intrauterine fetal death is an agonizing, often unpredictable event. Autopsies of stillborn fetuses, including placentas, are performed to clarify the cause of death. Autopsy results are not always easily understood by the patients or their healthcare providers. OBJECTIVE: To evaluate placental causes of death in stillbirths based on autopsy and placental findings that are related to maternal underperfusion, fetal underperfusion, or inflammatory etiologies in hierarchical order. METHODS: Retrospective review of 120 autopsy reports of singleton stillborn fetuses and placentas from 23 to 40 weeks of gestation. RESULTS: Among the placental causes of death there were 54(51%) cases with direct cause or major contributor to death in the etiology of maternal vascular supply abnormalities, 28(26%) cases in the etiology of fetal vascular supply abnormalities and 13(12%) in the etiology of inflammatory lesions. Maternal vascular supply abnormalities were more common in preterm stillbirths and fetal vascular supply abnormalities were more common among term stillbirths. In 88% of stillbirths, the direct cause or a major contributor to death was found in the placentas. The incidence of unexplained death was 8%. CONCLUSIONS: Pathological analysis of the placenta is essential for clarifying causes of stillbirths. Using specific simplified categories for abnormal placental findings may increase the benefits of the autopsy report.

Parathyroid hormone stimulates the endothelial expression of vascular endothelial growth factor.

BACKGROUND: We showed previously that parathyroid hormone (PTH) may stimulate the endothelial expression of pro-atherosclerotic and pro-inflammatory markers. Considering the impact of PTH on vasculature, we decided to evaluate its effect on mRNA and intra-cellular protein expressions of endothelial vascular endothelial growth factor (VEGF) taking into account that VEGF may play a role in the pathogenesis of endothelial dysfunctions. MATERIALS AND METHODS: Human umbilical vein cords endothelial cells (HUVEC) were stimulated for 24 h with 10(-12)-10(-10) mol L(-1) PTH. The VEGF-165 mRNA expression (critical in stimulating endothelial cell proliferation) was evaluated by RT/PCR and the intra-cellular VEGF protein expression by flow cytometry. The pathways by which PTH may have an effect on VEGF expression were also evaluated. RESULTS: PTH (10(-10) mol L(-1)) significantly increased VEGF-165 mRNA expression (P < 0.05). The addition of 50 nmol L(-1) protein kinase C (PKC) and 10 micromol L(-1) protein kinase A (PKA) inhibitors significantly reduced the VEGF-165 mRNA expression (P = 0.01). We also examined whether nitric oxide (NO) may be involved in the PTH-induced stimulation of VEGF-165 expression. Pre-treatment of the cells with 200 micromol L-nitro arginine methyl ester (L-NAME, NO synthase inhibitor) was found to inhibit VEGF-165 mRNA expression (P = 0.006). VEGF protein could not be detected in the medium of HUVEC but it was present in the cell cytoplasm. PTH had no significant effect on cytoplasmatic VEGF protein expression. CONCLUSION: The stimulatory effect of PTH on endothelial VEGF-165 mRNA expression is partly through PKC and PKA pathways and is also NO dependent.

Calcitriol blunts pro-atherosclerotic parameters through NFkappaB and p38 in vitro.

BACKGROUND: Disturbances in vitamin D(3) metabolism are associated with an increased cardiovascular morbidity and mortality. The aim of this study was to assess the effects of calcitriol, the active metabolite of vitamin D3, on pro-atherosclerotic parameters in human umbilical vein cord endothelial cells (HUVEC). MATERIALS AND METHODS: Calcitriol at 10(-10) and/or 10(-9) mol L(-1) was given to cultured HUVEC which were either non-stimulated or lipopolysaccharide (LPS) stimulated. Inter cellular adhesion molecule-1 and platelet-endothelial cell adhesion molecule-1, were determined by flow cytometry analysis. The receptor of advanced glycation end product (RAGE) and interleukin-6 (IL-6) mRNA expressions by RT-PCR and IL-6 secretion by enzyme-linked immunosorbent assay (ELISA). Nuclear p65 DNA-binding activity was measured by transcription factor assay kit and the inhibitor-kappaBalpha (IkappaBalpha), phosphorylated-IkappaBalpha (P-IkappaBalpha) and phosphorylated-p38 mitogen-activated protein kinase (MAPK) protein levels were determined by Western blot. Results Calcitriol decreased the adhesion molecules expression, as well as the LPS-induced mRNA expressions of RAGE and IL-6 and LPS induced IL-6 secretion. Furthermore, the LPS induced nuclear factor kappaB (NFkappaB)-p65 DNA-binding activity was also decreased by calcitriol. IkappaBalpha levels were increased and p-IkappaBalpha levels decreased after calcitriol treatment. The increased levels of activated p38 MAPK after LPS treatment were also decreased due to pre-incubation with calcitriol. CONCLUSIONS: The decreased NFkappaB and p38 activities followed by calcitriol treatment may explain the anti-inflammatory/atherosclerotic properties of calcitriol that were observed previously and were emphasized in this study, demonstrating the inhibitory effect of calcitriol on the pro-inflammatory parameters: adhesion molecules, RAGE and IL-6.

[Life with Locked-In syndrome]. / Quelle vie après le Locked-In syndrome?

The Locked-In Syndrome (LIS) is classically caused by an anterior pontine vascular lesion and characterized by quadriplegia and anarthria with preserved consciousness and intellectual functioning. We here review the definition, etiologies, diagnosis and prognosis of LIS patients and briefly discuss the few studies on their quality of life and the challenging end-of-life decisions that can be encountered. Some clinicians may consider that LIS is worse than being in a vegetative or in a minimally conscious state. However, preliminary data from chronic LIS survivors show a surprisingly preserved self-scored quality of life and requests of treatment withdrawal or euthanasia, though not absent, are infrequent.

[Blink and you live: the locked-in syndrome]. / Le Locked-In Syndrome: la conscience emmurée.

INTRODUCTION: The Locked-In syndrome (LIS) is defined by: (i) the presence of sustained eye opening (bilateral ptosis should be ruled out as a complicating factor); (ii) preserved awareness; (iii) aphonia or hypophonia; (iv) quadriplegia or quadriparesis; and (v) a primary mode of communication that uses vertical or lateral eye movement or blinking. Acute ventral pontine lesions are its most common cause. Following such brainstem lesions patients may remain comatose for some time and then gradually awaken, remaining paralyzed and voiceless, superficially resembling the vegetative state. BACKGROUND: It has been shown that more than half of the time physicians fail to recognize early signs of awareness in LIS. Given appropriate medical care, life expectancy may be several decades but the chances of good motor recovery remain small. Eye-controlled computer technology now allows LIS patients to communicate and control their environment. Recent studies show that most LIS patients self-report meaningful quality of life and the demand for euthanasia is infrequent. CONCLUSION: Patients suffering from LIS should not be denied the right to die--and to die with dignity--but also they should not be denied the right to live--and to live with dignity and the best possible pain and symptom management and revalidation.

Somatostatin treatment attenuates proteinuria and prevents weight loss in NZB/W F1 mice.

Somatostatin, a naturally occurring neuropeptide, is an immunomodulator which inhibits humoral and cell mediated immunity as well as secretion of proinflammatory cytokines. The objective of this study was to examine the effects of a somatostatin analogue on the severity of glomerulonephritis in the female NZB/W F1 murine model of systemic lupus erythematosus (SLE). Twenty female NZB/W F1 mice were treated at 23 weeks of age with 10 mg/kg of the somatostatin analogue Sandostatin- LAR, IM every four weeks. Ten control mice received IM injection of vehicle. Mice were assessed at four-week intervals for weight change, proteinuria, anti-DNA antibodies and splenocyte cytokine profile. The mice were sacrificed at age 34.5 weeks. Kidneys were collected and evaluated by light and immunofluorescence (IF) microscopy. Spleens were collected and splenocyte intracellular cytokines were measured by FACS analysis. In the treatment group significantly less proteinuria was observed four weeks after the second somatostatin analogue injection (dipstik scale: +2.07 +/- 0.95 versus. +3.5 +/- 1.08, P = 0.0002). The treated mice did not lose weight while the control group lost weight over time (P = 0.016). No differences were noted between the groups in anti-DNA antibody titres, cytokine profile or the severity of lupus nephritis as assessed by light and IF microscopy. Somatostatin analogue treatment attenuated proteinuria and prevented weight loss in NZB/W F1 mice, suggesting a possible beneficial effect on renal parameters and systemic manifestations of the disease. Further studies will be needed to assess the value of somatostatin analogue treatment in lupus nephritis, utilizing higher doses, at different stages of the disease, for longer periods.

High incidence of BRCA1-2 germline mutations, previous breast cancer and familial cancer history in Jewish patients with uterine serous papillary carcinoma.

OBJECTIVE: To test the carrier status of the three germline founder mutations in Jewish patients with uterine serous papillary carcinoma (USPC) and to evaluate its association to their personal and familial cancer records. METHODS: Retrospective analysis of histologically confirmed USPC Jewish patients diagnosed between April 1, 1997 and December 31, 2003. All cases were genetically tested for the three BRCA1-2 founder germline mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2). The analysis was performed on genomic DNA extracted from whole blood or paraffin embedded normal tissue of these patients, employing PCR amplification of target sequences and differential digestion with restriction enzymes. The carrier frequency was compared to the known population frequency of these mutations. RESULTS: The study group comprised 22 Jewish patients with USPC diagnosed within this timeframe. The mean age was 71.8 years (range 56-79). FIGO surgical stage distribution revealed 59% at stages III-IV. Seven USPC patients (32%) with a previous diagnosis of breast cancer were identified. Familial cancer history was recorded in 23% of the patients (four with breast cancer and one with ovarian cancer). DNA analysis revealed six BRCA1-2 germline mutation carriers (27%) as follows: three with BRCA2-6174delT, two with BRCA1-185delAG, and one with BRCA1-5382insC mutation. Three of the carriers had a previous diagnosis of breast cancer. Four carriers had familial cancer history in first-degree relative (three with breast cancer and one with ovarian cancer). CONCLUSIONS: The high rate of BRCA germline mutations in USPC patients observed in the present study, coupled with the strong personal and familial cancer history as well as the histological and clinical resemblance to the ovarian cancer, may indicate that USPC is a part or an expression of the hereditary breast-ovarian cancer syndrome. This option may have implications in our clinical recommendations for non-affected BRCA1-2 carriers.

Altered expression of the DNA mismatch repair proteins hMLH1 and hMSH2 in cutaneous dysplastic nevi and malignant melanoma.

Molecular alterations in the mismatch repair system suggest that this mechanism may be important in the evolution of cutaneous melanoma. Our current study evaluated the expression of two mismatch repair proteins, hMLH1 and hMSH2, in dysplastic nevi (DN) and cutaneous melanoma (CM). Immunohistochemical staining of these proteins was performed on 55 CM and 30 DN specimens. The staining results were divided into three groups: negative, partially positive and strongly positive. Normal adjacent skin cells served as an internal control for positive immunostaining. Altered immunoreactivity of one of the proteins was found in four (13.4%) DN and seven (12.7%) CM. Lack of staining for hMLH1 was observed in two (6.7%) cases of DN and five (9.1%) cases of CM; staining for hMSH2 was absent in two (6.7%) of the DN and two (3.6%) of the CM specimens. Partially positive staining was found in 33.3% and 53.3% for hMLH1 and hMSH2, respectively, in DN, and in 54.5% and 69.1%, respectively, in CMM. Our study shows that complete or partial loss of MMR protein expression occurs in a subset of both DN and CM and may represent a distinct pathway in the development of some DN and CM.

Small bowel obstruction secondary to Crohn disease: CT findings.

We investigated the computed tomographic (CT) findings in patients with small bowel obstruction (SBO) and Crohn disease (CD). Fourteen patients, seven men and seven women (mean age, 41.3 years), were retrospectively reviewed. All presented with clinical symptoms and signs of SBO. Eleven had a history of CD, whereas three experienced the bowel obstruction as the first manifestation of the disease. On CT, features of complete SBO were seen in nine patients, whereas incomplete obstruction was found in the other five. One patient had CT findings of an adhesive obstruction. The other 13 were diagnosed as having CD-related SBO; a markedly stenotic bowel segment caused the obstruction in one patient, and a thickened-wall small bowel segment with luminal narrowing was evident at the transition zone in the other 12. The mural thickening had a target appearance in seven and homogeneous thickening in the other five. Additional thickened bowel segments were found in five patients and mesenteric involvement was found in 10. Five patients were treated conservatively, and the other nine underwent surgery (one with adhesiolysis only). Resection of the stenotic bowel was performed in six patients and stricturoplasty was done in the other two, with associated intestinal biopsy in one of these two patients. Histopathology revealed findings of active on chronic disease in all. CT is frequently performed for suspected SBO, so radiologists should be aware of the diagnosis of CD, because SBO may be its first manifestation. Alternatively, radiologists can accurately diagnose a CD-related obstruction in a patient with known CD and differentiate it from an obstruction due to adhesions. Patient management in these cases, however, is based most often on the clinical condition.

Drugs used for euthanasia in Flanders, Belgium.

PURPOSE: Our aim was to describe and assess the medicinal products and doses used for euthanasia in a series of cases, identified within an epidemiological death certificate study in Belgium, where euthanasia was until recently legally forbidden and where guidelines for euthanasia are not available. METHODS: In a random sample of the deaths in 1998 in Belgium, the physicians who signed the death certificates were identified and sent an anonymous mail questionnaire. The questionnaires of the deaths classified as euthanasia cases were reviewed by a multi-disciplinary panel. RESULTS: A total of 22 among 1925 questionnaires pertained to voluntary euthanasia. In 17 cases, detailed information on the euthanatics (medicinal substances used for euthanasia) used was provided. Opioids were used in 13 cases (in 7 as a single drug). Time between last dose and expiry ranged from 4 to 900 min. The panel judged that only in 4 cases effective euthanatics were used. CONCLUSIONS: In the end-of-life decision cases perceived by Belgian physicians as euthanasia, pharmacological practices were disparate, although dominated by the use of morphine, in the very late phase of dying, in doses which were unlikely to be lethal. Most physicians clandestinely engaging in euthanasia in Belgium seemed unaware of procedures for guaranteeing a quick, mild and certain death. Information on the pharmacological aspects of euthanasia should be included in the medical curriculum and continuing medical education, at least in countries with a legal framework permitting euthanasia under specified conditions.