[What's the true value of a consensus conference?].
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Biomedical subjects
Publications and source records attributed to P Bernard.
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INTRODUCTION: Actinomycosis is a rare spreading suppurative and granulomatous disease. In 50 to 60 p. 100 of cases, cervico-facial area is involved. Involvement of other cutaneous areas is very uncommon. CASE-REPORTS: Two men (51 and 58 year-old, respectively) were admitted to the hospital because of erythematous and violaceous nodules with fistulization to the skin, localized on the perianal area and buttocks for several months. Bacterial cultures of the pus and of skin biopsy specimens yielded Actinomyces meyeri in case 1 and Actinomyces israelii in case 2. Patients did not have other infectious lesions. Treatment included systemic antibiotics and surgical iterative excisions in case 1. DISCUSSION: The main interest of those two cases is their similar clinical presentation and in one case the rarity of the micro-organism involved (Actinomyces meyeri). Since the lesions involved only the skin, we postulate that the organism may have extended from the oral mucosa through the gastrointestinal tract.
Ophthalmologic adverse effects of bisphosphonate therapy are infrequent and of unclear pathogenesis. The most common has been anterior uveitis, of which 18 cases have been reported. Onset was within 24 to 48 hours after infusion initiation, and both eyes were affected in most patients. The outcome was favorable within a few days after bisphosphonate discontinuation and topical glucocorticoid therapy, although rechallenge was frequently followed by a recurrence. Bisphosphonates are being used successfully in an increasingly broad range of disorders. We report a case of pamidronate-induced anterior uveitis and present a review of the relevant literature.
BACKGROUND: We report a case of typical exanthematous pustulosis rash that was particularly severe both clinically and biologically. Laboratory tests led to the diagnosis of acute parvovirus B19 infection. CASE REPORT: A 23-year-old man with no past medical history developed fever with an erythematous pustulosis rash predominantly involving the folds. Blood cell count revealed hyperleukocytosis. There was no previous drug intake. This skin reaction was associated with severe systemic manifestations including hypovolemic shock, and hematologic and metabolic disturbances. Virology tests revealed acute parvovirus B19 infection. The hospital physician caring for this patient also presented evidence of acute parvovirus B19 infection. DISCUSSION: The clinical features and the course of this skin eruption were typical of generalized exanthematous pustulosis. We discuss the rare viral causes of acute generalized exanthematous pustulosis and compare our case with a previously reported case of acute generalized exanthematous pustulosis with mononucleosic syndrome in a patient with no prior drug intake. The clinical and biological manifestations of this case were similar to drug hypersensitivity syndrome.
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BACKGROUND: Intravascular lymphoma is a proliferation of lymphoid cells, usually B cells, in small vessels, predominantly in the nervous system and skin. CASE REPORT: We report a case of a man with a 3-year history of lymphopenia with no detectable etiology (all viral causes were ruled out) who developed intravascular lymphoma in the cerebral vessels. DISCUSSION: This case was particular as the patient had idiopathic CD4+ lymphopenia. It points out the probable role of immunodepression in the development of lymphomas, particularly in endovascular localizations.
The ETV6 gene (also known as TEL) is the main target of chromosomal translocations affecting chromosome band 12p13. The rearrangements fuse ETV6 to a wide variety of partner genes in both myeloid and lymphoid malignancies. We report here 4 new cases of acute myeloid leukemia (AML) with very immature myeloblasts (French-American-British [FAB]-M0) and with a t(4;12)(q11-q12;p13). In all cases, ETV6 was found recombined to a new gene, homologous to the mouse Brx gene. The gene was named BTL (Brx-like Translocated in Leukemia). Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments indicate that the expression of the BTL-ETV6 transcript, but not of the reciprocal ETV6-BTL transcript, is a common finding in these leukemias. In contrast to the majority of other ETV6 fusions, both the complete helix-loop-helix (HLH) and ETS DNA binding domains of ETV6 are present in the predicted BTL-ETV6 fusion protein, and the chimeric gene is transcribed from the BTL promoter.
Triggering the ceramide pathway by exogenous treatment with neutral sphingomyelinase (Smase) inhibited human keratinocyte growth rate, while having no influence on cell apoptosis. Increasing the ceramide content of keratinocytes with Smase (100 U/ml) or C6-ceramide (1 microM) enhanced matrix metalloproteinase (MMP)-9 production. On the contrary, levels of MMP-2 secretion were unchanged. The inhibition of keratinocyte growth rate induced by ceramide could be annihilated by a peptide hydroxamate MMP inhibitor or an MMP-9 blocking antibody. In addition, inhibiting MMP-9 activity in control keratinocyte culture was found to stimulate keratinocyte proliferation. These data suggest a pivotal function of MMP-9 in the control of keratinocyte growth.
OBJECTIVE: To assess risk factors for erysipelas of the leg (cellulitis). DESIGN: Case-control study. SETTING: 7 hospital centres in France. SUBJECTS: 167 patients admitted to hospital for erysipelas of the leg and 294 controls. RESULTS: In multivariate analysis, a disruption of the cutaneous barrier (leg ulcer, wound, fissurated toe-web intertrigo, pressure ulcer, or leg dermatosis) (odds ratio 23.8, 95% confidence interval 10.7 to 52.5), lymphoedema (71.2, 5.6 to 908), venous insufficiency (2.9, 1.0 to 8.7), leg oedema (2.5, 1.2 to 5.1) and being overweight (2.0, 1.1 to 3.7) were independently associated with erysipelas of the leg. No association was observed with diabetes, alcohol, or smoking. Population attributable risk for toe-web intertrigo was 61%. CONCLUSION: This first case-control study highlights the major role of local risk factors (mainly lymphoedema and site of entry) in erysipelas of the leg. From a public health perspective, detecting and treating toe-web intertrigo should be evaluated in the secondary prevention of erysipelas of the leg.
BACKGROUND: Some forms of chemoresistance in leukemia may start from failure of tumour cells to successfully undergo apoptosis and Bcl-2 may play a role in this defect. Therefore, we evaluated the Bcl-2 content and synthesis in relation with the apoptotic potential in leukemic cell lines after anthracycline treatment. METHODS: U937, HL60, and K562 cells and their drug resistant (DR) variants were treated with varying concentrations of Idarubicin (IDA). Apoptosis was evaluated by fluorescence microscopy after acridine orange staining. Bcl-2 and Bax content were evaluated either by flow cytometry after indirect immunolabelling or by Western blot. RESULTS: High Bcl-2 contents were not related to a poor ability to undergo apoptosis in U937, HL60, K562 and their DR variants. IDA induced a concentration-dependent increase in Bcl-2 content in all cell lines as long as they do not perform apoptosis. Enhanced Bcl-2 expression was inhibited by cycloheximide, actinomycin D, or antisense oligonucleotide directed against bcl-2 mRNA. Bcl-2 expression was also increased in the resistant U937 variant after serum deprivation or C2-ceramide treatment. The synthesis of Bcl-2 led to an increased Bcl-2/Bax ratio solely in the cells with an apoptosis-resistance phenotype. CONCLUSIONS: These data suggest that exposure to IDA induces Bcl-2 expression in leukemic cell lines, and that this mechanism could contribute to apoptosis resistance and participate in the acquisition of chemoresistance. They also confirm that the evolution of the Bcl-2/Bax ratio reflects apoptotic ability better than the steady state level of Bcl-2 expression.
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Human cytomegalovirus (HCMV) is the most common cause of viral intra-uterine infection. The experience with prenatal diagnosis remains limited and is based on few reports of small numbers of cases. It is thus difficult to compare the accuracy of the different tests because the groups studied were small and heterogeneous. We describe here our experience on a series of 98 pregnancies leading to HCMV congenital infection, among which 71 have been tested by amniotic fluid (AF) sampling followed by culture and/or polymerase chain reaction (PCR). Independently of the delay between AF sampling and the first HCMV IgM positive result, the mean sensitivity of both culture and PCR was around 70 per cent. The best sensitivity (95.5 per cent) was obtained after a delay > or = 6 weeks in late pregnancy (> or = 23 weeks). The present study demonstrated clearly that the delay between AF puncture and the presumed date of seroconversion is more important for sensitivity than the technique used for the diagnosis (PCR or culture). However, even in the best diagnostic conditions, negative results of HCMV culture or PCR in AF cannot formally exclude intra-uterine infection.
We have used chemo-immunotherapy with 5-fluorouracil (5-FU), thymosin alpha1 (T alpha1) and interleukin-2 (IL-2) to treat multiple liver metastases from colorectal cancer induced by DHD/K12 cells in syngeneic BDIX rats, comparing one and two cycles of treatment, and different treatment combinations. 5-FU was delivered loco-regionally as a continuous infusion via an intraperitoneal (i.p.) catheter from a subcutaneously implanted mini-pump, a method we developed for this study. We show here that two cycles of a triple chemo-immunotherapy regimen significantly increased the average survival time compared to one cycle, and compared to untreated controls or those treated with two cycles of 5-FU alone. At 150 days, two rats treated with two cycles of triple therapy were cured, showing no signs of cancer at autopsy; all the other rats died before this time. Triple chemo-immunotherapy resulted in significantly fewer extra-hepatic metastases than in the controls and in those treated with 5-FU only. Further, we found that two cycles of triple treatment significantly increased the absolute number of peripheral T cells expressing IL-2 receptor, CD4 and CD8 compared to controls. We conclude that two cycles of chemo-immunotherapy with 5-FU, T alpha1 and IL-2 were superior to one cycle of treatment and to other treatments tested. Our results suggest that the triple therapy acts by increasing numbers of effector T cells. This method shows promise for the use of multi-cycle chemo-immunotherapy in the treatment of unresectable metastases of colorectal cancer in humans.
AIM OF THE STUDY: The aim of this retrospective study was to report the results of the surgical treatment for large bowel cancer in patients over 75 years of age. PATIENTS AND METHOD: From 1985 to 1996, 240 patients. 114 men and 126 women, aged 75 years or over (mean age: 82, range: 75 to 95 years) underwent surgical treatment for large bowel carcinoma. Tumors were located in the right colon (n = 120), left colon (n = 100), transverse colon (n = 5), or were multiple (n = 15). Clinical presentation was failure of general condition (25%), intestinal obstruction (20%), rectal bleeding (20%), abdominal pain (17%). ASA score was I (n = 1), II (n = 69), III (n = 134), or IV (n = 36). Emergency surgery was mandatory in 110 cases (43 urgent and 67 delayed procedures) and 130 patients underwent elective surgery. Surgical resection was performed in 221 cases, including 177 cases with curative intent (67%). Surgical procedures included right colectomy (n = 119), left colectomy (n = 59), transverse colectomy (n = 9) or subtotal colectomy (n = 31). Histopathological staging was Astler--Coller A (n = 8), B (n = 116), C (n = 54) et D (n = 62). RESULTS: The postoperative course was uneventful in 157 cases (65.4%). Medical complications occurred in 46 patients with 34 deaths; and surgical complications in 39 patients with 20 subsequent reoperations and 15 deaths. The overall postoperative mortality rate was 20.4% (n = 49). Postoperative mortality rate was higher after emergency operations (32.7% vs 10%), higher with the level of ASA grading (class II: 8.6%, Class III: 17.1%, Class IV: 38.8%), higher in patients over 90 years (37.4% vs. 19.1%) and in patients without surgical resection (42% vs 18.5%). Disease specific 5-year survival rate was 45% and did not differ when compared to patients younger than 75 years (42%, data not reported). CONCLUSIONS: Patients older than 75 years remain a high risk group, specially if operated on emergency. Nevertheless, age is not a limiting factor in the surgical treatment of colon cancer. Prognosis is mostly depending on ASA grading. Colectomy with curative intent has to be performed when possible.
STUDY AIM: In children, living donor liver transplantation has been shown to be efficient in treating end-stage liver diseases when the left lateral segment is harvested. In adults, more liver mass is needed to provide adequate hepatic function. The aim of this study is to report 2 successful cases of living donor liver transplantation using a right hepatic lobe from adult. PATIENTS AND METHODS: In 2 sons, the right hepatic lobe was harvested without the middle hepatic vein for transplantation in their fathers who were suffering from end-stage liver cirrhosis. Hepatectomy was done without vascular inflow occlusion after dissection of vascular and biliary structures, itself strictly restricted to the right side. In recipients, the graft was implanted orthotopically with preservation of the native inferior vena cava and after temporary porto-caval shunt. RESULTS: The duration of donors procedures was 7 h and 11 h 45 min; intra-operative transfusions comprised of 700 mL from cell-saver in the first case, and 1300 mL plus 1 autologous red blood cell unit in the second case. Graft weights were 770 g and 1100 g. None of the donors experienced liver failure and both were able to leave the hospital 9 days after the operation. In recipients, initial graft function was excellent in the first case and correct in the second case, despite the necessity to redo intra-operatively the hepatic vein anastomosis secondary to a twisting. Patients were discharged 20 and 40 days respectively following transplantation. CONCLUSION: Adult living donor liver transplantation using a right hepatic lobe is efficient and safe. This option could contribute to reducing the mortality of patients on the waiting list.
Tumour liberated particles (TLP) have been proposed as a potential new serum tumor marker. In particular, a high percentage of patients with early stages of lung cancer scored positive for serum TLP, suggesting its possible role as a marker for early diagnosis of disease. The aim of the present study was to analyze the expression of TLP in the colorectal adenoma-carcinoma sequence in order to determine whether its expression correlates with the various stages of cancer transformation. TLP distribution was assessed by immunohistochemistry in normal, premalignant, and malignant colorectal lesions. Normal colonic mucosa and hyperplastic polyps showed no positive staining, whereas adenomas and adenocarcinomas reacted to anti-TLP serum. The percentage of positive tumor cells increased from adenomas with mild dysplasia to adenomas with severe dysplasia. Moreover, a supranuclear staining pattern was observed mainly in adenomas with mild dysplasia, whereas adenomas with severe dysplasia as well as adenocarcinomas showed a characteristic diffuse staining pattern and a strong staining intensity. Only a few cases of adenocarcinoma were found to be TLP-negative and all were poorly differentiated. Our results suggest that TLP antigen expression may be considered as a marker of epithelial atypia in the colorectal tract and as a potential target for new diagnostic and/or therapeutic approaches to human colorectal cancer.
Supplementary doses of opioids are recommended to relieve dyspnea in terminally ill cancer patients. We conducted a randomized continuous sequential clinical trial to evaluate their efficacy. We recruited 33 terminally ill cancer patients from three palliative care centers, all of whom had persistent dyspnea after rest and treatment with oxygen. Patients formed 15 successive pairs matched on route of administration. Within each pair, the order of allocation was randomly assigned, one patient receiving 25%, the other 50% of his 4-hourly opioid dose. Five measurements of dyspnea intensity and respiratory frequency were made during 4 hours of follow-up. For each pair, a preference was attributed to the more effective regimen. The two regimens received an almost equal number of paired preferences (8 vs. 7). Overall, both mean dyspnea intensity and respiratory frequency decreased significantly relative to baseline. Dyspnea reduction was relatively greater in patients with initially low and moderate dyspnea intensity. In terminally ill cancer patients with persistent dyspnea, 25% of the equivalent 4-hourly dose of opioid may be sufficient to reduce both dyspnea intensity and tachypnea for 4 hours.