Hepatic manifestations in Still's disease

In children, as in adults, Still's disease usually presents with a hectic fever, a characteristic rash and arthralgia or arthritis. Visceral involvement is however classical; the hepatic manifestations were studied with respect to two cases. Biochemical changes are common, often mild: the commonest abnormality is cytolysis. Jaundice is less frequent and hepatic involvement may in exceptional cases be life threatening, usually in cases of serious polyvisceral disease often with disseminated intravascular coagulation. These manifestations may be spontaneous or secondary to salicylate therapy; the anatomical changes are the same; the salicylate would therefore seem rather to unmask and aggravate an underlying hepatic abnormality.     

Edematous syndromes caused by capillary hyperpermeability. Diffuse angioedema

Edema due to increased capillary permeability (ICP) may be diffuse or localized. Local edemas (Quincke edema, angioneurotic edema) are most often allergic or very rarely due to a defect in C1-inhibitor. Generalized edemas due to ICP share the following clinical features: Fluid retention (subcutaneous edema and diffused swelling) is predominant in lower limbs; it is worsened by orthostatism and warmth and alleviated by decubitus and cold, with important weight variations between morning and evening. It is associated with enhanced thirst, hypotension, oliguria, headaches and blood volume reduction; secondary hyperaldosteronism is the main mechanism. These troubles are due to ICP, associated with lymphatic drainage abnormalities; ICP is measured by the isotopic Landis Test. This abnormality is present in several diseases. Idiopathic orthostatic edema (IOE) is frequent and often unrecognized, occurring mainly in women, often associated with luteal insufficiency. Iatrogenic complications (diuretic and laxative abuses) are frequently superimposed. ICP may be corrected by vitamins P (rutin, anthocyanosides, diosmin, Ginkgo biloba extracts...) Cyclic shock due to ICP is rare. It is characterized by cyclic edema and shock with hypovolemia, hypoproteinemia; the mechanism of shock is a severe loss of fluid and protein from the vascular bed. It is often associated with monoclonal gammapathy and complement activation. In our personal case, the trouble in CP was present all along the disease with permanent edema and low blood pressure (especially in orthostatism). Vit "P" and Ginkgo biloba extracts were able to partially improve CP and the clinical troubles. However, in spite of this treatment a fatal shock occurred after ten years follow-up. Episodic angioedema associated with eosinophilia was first described by Gleich.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of a 32-kDa ligand for the CD40 antigen on activated human T lymphocytes

To identify the ligand(s) of the human CD40 antigen, a cDNA encoding the extracellular domain of the CD40 antigen was fused to a cDNA encoding the constant region (Fc) of human IgGl. The CD40-Fc fusion protein was able to specifically bind to CD4⁺ and various CD8⁺ T cell clones activated with immobilized anti-CD3. The ¹²⁵I-labeled CD40-Fc fusion protein bound anti-CD3 activated CD4⁺ T cell clone (MT9) with an equilibrium dissociation constant (Ka) of 10-20 nM. The human CD40-binding protein expressed on the cell surface of activated T lymphocytes is a monomeric protein of ≈ 32 kDa. Minor components of 29 kDa and 17 kDa were also detected. A small proportion of CD4+ and CD8⁺ blood mononuclear T cells activated by anti-CD3 expressed the CD40 ligand but its detection was best observed following depletion of B cells. Addition of B cells to purified T cells abolished the binding of CD40-Fc obtained after anti-CD3 activation.     

Primary Hepatic Lymphoma After Lung Transplantation: A Report of 2 Cases

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of non–Hodgkin lymphoma in the posttransplant setting. Treatment is based on chemotherapy; surgery is still debated and should be performed in very select cases.MethodsWe observed 2 patients out of 300 who underwent lung transplantation in the Nouvel Hopital Civil between 2013 and 2019 with primary hepatic lymphoma. Chemotherapy with a rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone protocol was performed in all patients. Mycophenolate mofetil was interrupted before treatment, and everolimus was introduced after chemotherapy by associating tacrolimus withdrawal.ResultsOne patient showed complete remission; after 7 years, no recurrence has been noticed. The second is still undergoing chemotherapy with no signs of disease progression.ConclusionsDLBCL risk is higher in solid organ transplant recipients than in the general population. Primary hepatic lymphoma diagnosis is often difficult and based on histologic findings after initial clinical and radiological suspicion of primary or secondary liver neoplasia. Diagnosis is challenging because no clinical, radiological, or biological features exist. Biopsy is always indicated for histologic confirmation. Chemotherapy is the mainstay of therapy, but surgery may be indicated in very select patients.     

Cyclosporin A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes

In previous papers we demonstrated that cyclosporin A (CsA) was specifically oxidized in rabbit and human liver by cytochrome P-450IIIA. We therefore anticipated that any drug that is an inducer or an inhibitor of this cytochrome should lead to interaction with CsA when given in association with it. In order to confirm this hypothesis, primary cultures of human hepatocytes and human liver microsomes were used to "reproduce" in vitro clinically significant interactions observed between CsA and drugs known either as specific inducers (i.e., rifampicin) or as specific inhibitors (i.e., erythromycin) of P-450IIIA. Our results were in close agreement with the clinical reports. Human hepatocytes maintained in primary cultures for 72 hr in the presence of 50 microM rifampicin exhibited increased levels of P-450IIIA, determined by Western blot using specific antibodies, and concomitant increase in CsA oxidase activity, determined by HPLC analysis of extra and intracellular media. Conversely, these cultures exhibited erythromycin concentration-dependent decreases in CsA oxidase activity when incubated in the presence of 5, 20, and 100 microM erythromycin. In addition, a Lineweaver-Burk analysis of the erythromycin-mediated inhibition of CsA oxidase activity in human liver microsomes revealed competitive inhibition (with Ki of 75 microM) as expected, this macrolide being a specific substrate of P-450IIIA. Using this experimental approach, 59 molecules representative of 17 different therapeutic classes were screened for inducers and inhibitors of CsA oxidase activity. Our results allowed us to elucidate the molecular mechanism of previously observed, but unexplained, drug interactions involving CsA, and to detect drugs that should interfere with CsA metabolism as inducers or inhibitors. Drugs detected as potential inducers of CsA oxidase included: rifampicin, sulfadimidine, phenobarbital, phenytoin, phenylbutazone, dexamethasone, sulfinpyrazone, and carbamazepine. Drugs detected as potential competitive inhibitors included: triacetyloleandomycin, erythromycin, josamycin, midecamycin, ketoconazole, miconazole, midazolam, nifedipin, diltiazem, verapamil, nicardipine, ergotamine, dihydroergotamine, glibenclamide, bromocriptine, ethynylestradiol, progesterone, cortisol, prednisone, prednisolone, and methylprednisolone. Finally, cefoperazone, cefotaxime, ceftazidime, isoniazide, doxycycline, spiramycin, sulfamethoxazole, norfloxacin, pefloxacin, vancocin, trimethoprim, amphotericin B, valproic acid, quinidine, cimetidine, ranitidine, omeprazole, diclofenac, aspirin, paracetamol, debrisoquine, guanoxan, captopril, furosemide, acetazolamide, sparteine, gliclazide, and imipramine were found not to interfere with the hepatic metabolism of CsA.     

Results and indications of lateral ileostomy functionally terminated in colorectal surgery

Loop ileostomy (LI) ensures fecal diversion to protect an anastomosis or anatomic colorectal or ano-perineal damage. The aim of this retrospective study was to evaluate loop ileostomy morbidity in emergency and planned colorectal surgery. PATIENTS AND METHODS: From 1991 to 1996, 145 loop ileostomies were performed in 139 patients, 77 men and 62 women with a mean age of 48.7 years (15-82). The etiology was a rectal tumor (cancer or large villous tumor n = 47), inflammatory bowel disease (n = 47, ulcerative colitis = 37 and Crohn's disease = 10) Familial Adenomatous Polyposis (n = 13) and other diseases (n = 32). 80% LI (n = 116) protected ileo-anal anastomoses (n = 46) colo-anal anastomoses (n = 45, 26 with colonic pouch), ileo-rectal anastomoses (n = 11) and other anastomoses (n = 15). 20% LI (n = 29) dysfunctional ano-perineal lesions (n = 8), anastomosis leak (n = 4) or distal bowel without intestinal resection (n = 17). RESULTS: 7 deaths were not stoma-related. 91% LI were closed after a mean diversion time of 3.6 months. LI closure was performed by a parastomal (n = 128) or laparotomy procedure (n = 4). Morbidity during LI diversion was observed in 24 patients (16.5%) 12 of whom (8.3%) were operated for small bowel obstruction (n = 6; 4.2%) stoma revision (n = 5; 3.5%) and prolapse (n = 1; 0.7%). 2 patients had peristomal skin excoriations, and 5 patients required readmission for dehydration due to high LI output. Morbidity after LI closure was observed in 12 patients (8.6%) 5 of whom were operated for anastomotic leak (n = 4) or small bowel obstruction (n = 1). Low morbidity and defunctioning efficiency confirm the indications for LI. LI is our first-line stoma in planned or emergency colorectal surgery.     

Irinotecan in combination with fluorouracil in a 48-hour continuous infusion as first-line chemotherapy for elderly patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors study.

PURPOSE: Elderly patients constitute a subpopulation with special characteristics that differ from those of the nonelderly and have been underrepresented in clinical trials. This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients. PATIENTS AND METHODS: Patients > or = 72 years old with metastatic colorectal cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, no geriatric syndromes, and no prior treatment were treated every 2 weeks with CPT-11 180 mg/m2 plus FU 3,000 mg/m2 in a 48-hour continuous infusion. RESULTS: By intent-to-treat analysis, in 85 assessable patients, the objective response rate was 35% (95% CI, 25% to 46%), and stable disease was 33% (95% CI, 23% to 44%). Median time to progression was 8.0 months (95% CI, 6.0 to 10.0 months), and median overall survival time was 15.3 months (95% CI, 13.8 to 16.9 months). Toxicity was moderate. Grade 3 and 4 neutropenia, diarrhea, and asthenia were observed in 21%, 17%, and 13% of patients, respectively. Only one case of neutropenic fever occurred. There were two toxic deaths, one was a result of grade 4 diarrhea and acute kidney failure, and the other was a result of massive intestinal hemorrhage in the first cycle. The study of prognostic factors did not reveal any predictive factor of response. Response to treatment and baseline lactate dehydrogenase were the main factors conditioning progression-free and overall survival. CONCLUSION: Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition.     

Post-voiding residual volume in 154 primiparae 3 days after vaginal delivery under epidural anesthesia

OBJECTIVES: To use 3-dimensional ultrasonography (3D-US) to determine the frequency of post-voiding residual volume (PVRV) > or =100 mL in primiparae 3 days after receiving epidural anesthesia for vaginal delivery. Potential relationships between day-3 PVRV > or =100 mL and obstetrical-pediatric parameters, especially those possibly implicated in post-obstetrical bladder dysfunction, were examined. STUDY DESIGN: We recruited 154 primiparae who vaginally delivered term singletons following uncomplicated pregnancies in the maternity unit of a French teaching hospital. All women had been systematically catheterized 2-h postpartum to measure precisely the volume of urine retained. On the morning of discharge (day 3), when the patient felt the urge to urinate, her 3D-US pre-voiding bladder volume was determined with BladderScan (BVI-3000), then her spontaneously voided urine was collected to accurately quantify its volume and 3D-US was repeated immediately to evaluate the PVRV. PVRV > or =100 mL on day 3 was considered pathological. RESULT: Among these 154 women, 88 (57%) felt the need to urinate and 97 (63%) had a retained volume > or =500 mL at 2-h postpartum. On day-3 postpartum, the median [range] volumes for the entire cohort were: 426.7 [158-999.7] mL 3D-US-measured pre-voiding, 350 [15-1000] mL collected by spontaneous urination, 82.2 [5.3-433.3] mL 3D-US-determined post-voiding; PVRV exceeded 100 mL for 55 (36%). According to our univariate analysis, no factor considered was able to predict PVRV > or =100 mL on day 3. CONCLUSION: Our observations confirmed the existence of PVRV > or =100 mL on day 3 in more than one-third of these primiparae who delivered vaginally under epidural anesthesia. No obstetrical-pediatric factor could be implicated in this bladder dysfunction. Therefore, we recommend frequent and systematic non-invasive 3D-US monitoring of all postpartum patients at least until day 3 to avoid excessive urine retention.