Effect of internal biliary drainage on plasma levels of endotoxin,cytokines, and C-reactive protein in patients with obstructive jaundice

Preoperative biliary drainage may improve the cytokine and acute-phase response derangements observed in patients with obstructive jaundice. We conducted a prospective longitudinal, before-after trial in our 600-bed teaching hospital. Twenty-four patients with obstructive jaundice were investigated, 11 with benign obstruction and 13 with malignant disease. Endoscopic internal biliary drainage was performed in all patients (7 by papillotomy and 17 by endoprostheses). Endotoxin, tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), nitric oxide production, and C-reactive protein (CRP) were determined at admission and on days 2 and 7 after internal biliary drainage was accomplished. Bile cultures were obtained before and at the time of drainage. Endotoxin, IL-6, TNF-a, and CRP were significantly higher in patients with cancer. After internal drainage, endotoxin (11.4 vs. 2 EU/L; p <0.05), TNF-a (87.5 vs. 48 pg/ml; p = 0.03), and IL-6 (324 vs. 232 pg/ml; p <0.05) plasma levels decreased significantly in the early postdrainage period in patients with cancer. Endotoxin, cytokines, as well as the CRP plasma values, however, increased again on day 7 after drainage. This trend was less marked in patients with benign obstruction. Patients with positive bile cultures after drainage displayed higher levels of CRP (115 vs. 62 mg/L; p = 0.03), IL-6 (598 vs. 330 pg/ml; p = 0.04), and endotoxin (10.6 vs. 4.8 EU/L; p = 0.02) than those with negative bile cultures. Biliary tract obstruction is associated with an increase in endotoxin levels, a positive acute-phase response, and plasma cytokine elevation. After biliary drainage a transitory improvement of these alterations was observed, although values remained high 1 week postdrainage. These findings were associated with positive bile cultures.     

Nonocclusive intestinal ischemia in patients with acute aortic dissection

BACKGROUND: In aortic dissection, visceral complications that result from aortic branch compromise have been described extensively, whereas intestinal ischemia not associated with the false lumen anatomy has rarely been discussed. The aim of this report is to identify clinical factors that may contribute to the development of this form of acute mesenteric ischemia, to profile the patients at greatest risk, and to review diagnostic and treatment methods that emerged from our experience. METHODS: With a computerized database, we identified 371 patients who underwent treatment in our institution with a diagnosis of aortic dissection between July 15, 1985, and January 10, 2001. Mesenteric ischemia was present in 73 patients (19%). In 36 patients (9%), bowel ischemia was not associated with a false lumen anatomy or an extension of the dissection process. From a general analysis of the determinants of mesenteric ischemia in aortic dissection, we investigated, with univariate and multivariate analysis, the specific characteristics of these patients with nonocclusive ischemia. A retrospective analysis of the oxygen metabolic profile of patients who underwent operation also was performed. RESULTS: The mortality rate in patients with nonocclusive mesenteric ischemia was 86%; sepsis and multiple organ failure were the causes of death in all nonsurvivors. Surgical treatment was beneficial only in the early phases of the disease. The results of the multivariate analysis showed the multifactorial origin of nonocclusive mesenteric ischemia; cerebral ischemia, thrombosis of the false lumen, severe coagulation disorders, chronic obstructive pulmonary disease, aortic calcinosis, prolonged hypotension, chronic renal insufficiency, and low cardiac output were independent predictors of the condition. In patients who underwent operation, the significant risk factors were severe coagulation disorders, postoperative cerebral ischemia, maximal oxygen extraction rate of more than 0.40, aortic calcinosis, chronic obstructive pulmonary disease, thrombosis of the false lumen, inotropic support, and chronic renal insufficiency. An oxygen extraction rate of more than 0.4 at 6 hours after operation was found to be an index of intestinal damage sufficient to initiate an evaluation for visceral ischemia. Significant differences with occlusive ischemia also were evidenced with this study. CONCLUSION: In aortic dissection, nonocclusive mesenteric ischemia shows some unique clinical and individual predisposing factors. Most instrumental investigations are of poor diagnostic value, and prognosis is poor, especially when mesenteric gangrene had already taken place. Prevention can be exercised only with a heightening of our awareness of this condition and with timely correction of metabolic disturbances. In suspected cases, an aggressive surgical attitude may represent the only means for reducing mortality.     

Arteriovenous malformation mimicking a renal-cell carcinoma

We describe a renal arteriovenous malformation in a patient with a 1-month history of flank pain. Imaging studies were interpreted as being consistent with renal-cell carcinoma. However, Doppler ultrasonography demonstrated turbulent blood flow, and selective renal angiography confirmed the diagnosis of an arteriovenous malformation. Embolization relieved the pain. This case calls attention to the need to consider arteriovenous malformations in the differential diagnosis of central homogenously enhancing renal lesions.     

Alternative sources of neurons and glia from somatic stem cells

Stem cell populations have been shown to be extremely versatile: they can generate differentiated cells specific to the tissue in which they reside and descendents that are of different germ layer origin. This raises the possibility of obtaining neuronal cells from new biological source of the same adult human subjects. In this study, we found that epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) cooperated to induce the proliferation, self-renewal, and expansion of neural stem cell-like population isolated from several newborn and adult mouse tissues: muscle and hematopoietic tissues. This population, in both primary culture and secondary expanded clones, formed spheres of undifferentiated cells that were induced to differentiate into neurons, astrocytes, and oligodendrocytes. Brain engraftment of the somatic-derived neural stem cells generated neuronal phenotypes, demonstrating the great plasticity of these cells with potential clinical application.     

Sequential multifocal electroretinogram findings in a case of Purtscher-like retinopathy

PURPOSE: To report the multifocal electroretinographic findings of a patient with pancreatitis-associated Purtscher-like retinopathy. DESIGN: Observational case report. METHODS: A 20-year-old man with a history of alcohol abuse and acute pancreatitis underwent multifocal electroretinography (mfERG; 103-scaled hexagons, 8-minute recording time) at 1 week, 4 weeks, and 6 months after the onset of the retinopathy. RESULTS: At 1 week, the patient had extensive cotton- wool spots in the posterior pole bilaterally, and visual acuity was significantly reduced. Both the A-waves and B-waves of the mfERG were depressed in the corresponding areas. At 4 weeks, neither visual acuity nor mfERG showed improvement, although the cotton-wool spots had resolved. Interestingly, at 6 months, visual acuity had improved significantly in the left eye, consistent with increased ratios of mfERG responses for the central area. CONCLUSION: There was no selective reduction of b-waves of the mfERG as anticipated in isolated inner retinal pathology. In this case, both the A-waves and B-waves were reduced, suggesting damage to both outer and inner retinal layers.     

The European glaucoma prevention study design and baseline description of the participants

OBJECTIVES: The European Glaucoma Prevention Study seeks to evaluate the efficacy of reducing intraocular pressure (IOP), with dorzolamide to prevent or delay patients affected by ocular hypertension from developing primary open-angle glaucoma. DESIGN: Randomized, double-blinded, controlled clinical trial. PARTICIPANTS: Patients (age > or =30 years) were enrolled from 18 European centers. The patients fulfilled a series of inclusion criteria including the measurements of IOP (22-29 mmHg), two normal and reliable visual fields (VFs) (on the basis of mean defect and corrected pattern standard deviation/corrected loss of variance of standard 30/II Humphrey or Octopus perimetry), and normal optic disc as determined by the Optic Disc Reading Center (vertical and horizontal cup-to-disc ratios; asymmetry between the two eyes < or =0.4). INTERVENTION: Patients were randomized to the treatment with dorzolamide or a placebo. MAIN OUTCOME MEASURES: End points are VF and/or optic disc changes. A VF change during the follow-up must be confirmed by two further positive tests. Optic disc change is defined by the agreement of two out of three independent observers evaluating optic disc stereo-slides. RESULTS: One thousand seventy-seven subjects were randomized between January 1, 1997 and May 31, 1999. The mean age was 57.03 +/- 10.3 years; 54.41% were women and 99.9% were Caucasian. Mean IOP was 23.6 +/- 1.6 mmHg in both eyes. Mean visual acuity was 0.97 +/- 0.11 in both eyes; mean refraction was 0.23 +/- 1.76 diopters in the right eye and 0.18 +/- 1.79 diopters in the left eye. Previous use of medication for ocular hypertension was reported by 38.4% of the patients, systemic hypertension by 28.1%, cardiovascular diseases by 12.9%, and diabetes mellitus by 4.7%. The qualifying VFs were normal and reliable according to protocol criteria. CONCLUSIONS: The mean IOP of the patients enrolled in the European Glaucoma Prevention Study is consistent with the estimated mean IOP (within the range of 22-29 mmHg) found in a large sample of the European population. The European Glaucoma Prevention Study should be able to better address the clinical question of whether pharmacological reduction of IOP (by means of dorzolamide) in ocular hypertension patients at moderate risk for developing primary open-angle glaucoma effectively lowers the incidence of primary open-angle glaucoma.     

Ophthalmic complications of slit-ventricle syndrome in children

OBJECTIVE: To present the ophthalmic features and visual prognosis of patients with slit-ventricle syndrome (SVS). DESIGN: Observational case series. PARTICIPANTS: Six patients diagnosed and treated with SVS at the Montreal Children's Hospital between 1985 and 1999. METHODS: Patients were included in this study if they had an appropriate ophthalmologic follow-up and if they fulfilled the criteria for the diagnosis of SVS based on intracranial pressure monitoring and neuroimaging studies. MAIN OUTCOME MEASURES: Features studied included patients' baseline ophthalmologic evaluation, visual outcome, and neurosurgical characteristics. RESULTS: The follow-up ranged from 1 to 14 years. The average number of shunting procedures was 3.7. Ocular examination performed on the initial visit revealed a normal visual acuity in four patients, esotropia in three of six patients, and nystagmus in two of six patients. Cycloplegic refraction was normal in all the subjects. Initial funduscopic evaluation revealed optic atrophy in a 4-month-old infant, whereas two children developed optic atrophy later in the course of the disease. One child developed severe visual field defects. The two children with optic atrophy had moderate to severe loss of visual acuity associated with SVS. CONCLUSIONS: A prompt recognition of patients with SVS is crucial, because these individuals are at an increased risk for significant visual loss.     

Expression of B7 molecules in the eye during experimental autoimmune anterior uveitis (EAAU)

PURPOSE: We have reported that CTLA4-Fc, a fusion protein that binds B7, prevents the induction of EAAU and reduces the severity of disease in Lewis rats. Since B7.1 and B7.2 have distinctive roles in other autoimmune diseases, we investigated their roles in the development of EAAU. METHODS: Lewis rats were immunized with melanin associated antigen (MAA). Eyes were collected at different stages of EAAU and the expression of B7 on iris and ciliary body (ICB) cell suspensions determined by flow cytometry analysis. The incidence of EAAU after treatment with anti B7, and the requirement of B7.1 and B7.2 for proliferation and cytokine production of lymphoid cells to MAA were also studied. RESULTS: B7.2 is up-regulated in resident ICB cells or bone-marrow derived cells which have infiltrated the ICB by day 10 and remains elevated during the acute phase of disease. B7.1 is expressed later during the acute phase. Both B7.1 and B7.2 are down-regulated during remission, with low levels of B7.2 and no detectable B7.1. The incidence of EAAU was reduced by anti-B7.2 treatment and completely inhibited by a combination of both B7.1 and B7.2 antibodies. Neither anti-B7.1 nor anti-B7.2 alone affected proliferation or cytokine production. However, administration of both anti-B7.1 and B7.2 completely inhibited proliferation as well as IL-2 and TNF-alpha production. CONCLUSIONS: B7.1 and B7.2 are expressed in the eye at different times during EAAU. Both B7 molecules are required for the induction of EAAU, although they probably have different roles.     

Molecular genetics of primary congenital glaucoma in Brazil

PURPOSE: To determine the distribution of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma (PCG). METHODS: PCG diagnosis was established by presence of buphthalmos in at least one affected eye and associated high intraocular pressures before the age of 3 years. CYP1B1 mutation screening of 52 patients with PCG was performed by SSCP and direct sequencing of PCR fragments. RESULTS: Eleven mutations, four of which are novel, were observed in 26 (50%) individuals. A new frameshift mutation (4340delG) was observed in 20.2% of all individuals screened. These individuals had early-onset, bilateral glaucoma that necessitated multiple surgical interventions. CYP1B1 mutations were twice as frequent in affected individuals of European descent as in individuals of African descent. Analysis of six intragenic single nucleotide polymorphisms (SNPs) established 5'-C-C-G-G-T-A-3' as the most common haplotype among the affected Brazilian individuals. A nonsense mutation (W57X) previously reported in an individual with Peters anomaly (compound heterozygote) was also observed in two individuals with PCG but combined with different mutations. A newly developed SSCP assay enabled us to detect all DNA mutations and polymorphisms previously detected by direct sequencing. CONCLUSIONS: Our results indicate that CYP1B1 mutations may be responsible for half of cases of PCG in the Brazilian population. The SNP haplotype 5'-C-C-G-G-T-A-3' was associated with the majority of CYP1B1 mutations. This haplotype harbors the high-activity V432 allele, which is emerging as a putative susceptibility factor in several cancers.