Extensive genital bowenoid papulosis responding to imiquimod.
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Biomedical subjects
Publications and source records attributed to J Cordoba.
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UNLABELLED: Cytomegalovirus infection is a common complication of renal transplantation. Antigen pp65 levels serve as indicators of viral load, although the technique is difficult to perform and interpret. We sought to determine whether quantitative PCR had a higher sensitivity and predictive value in CMV infection. METHODS: The study included 100 renal transplant recipients who were screened for IgM and IgG at the time of admission. On days 7, 15, 30, 45, 60, 75, 90, 120, 180, and 360, antigenemia tests were performed on blood (pp65) and urine, and a quantitative PCR on blood. Among 59 patients recruited between November 2003 and August 2004 the mean age was 54.5 +/- 12.9 years. Two patients did not reach 90 days follow-up (3%); four patients have not surpassed 90 days (7%); 22, 120 days (37%); and 31, 180 days (53%). Ninety-three percent of patients showed anti-IgG CMV-positive titers with all being IgM CMV-negative at baseline. The patients at risk for infection were given valgancyclovir as prophylaxis throughout the study. RESULTS: At 474 visits, 8 samples (2.4%) were positive with urine; 5 (1.4%) with pp65, and 15 (4.7%) with PCR. Among the 15 positive samples, two (>100,000 and 3250 copies) revealed agreement of positive IgM and shellvial test on urine; two (15,100 and 5670 copies), antigen pp65 1+; one (17,400 copies) with pp65 2+ and shellvial urine; two (99,400 and 28,300 copies) with pp65 1+ and shellvial urine; and eight remaining determinations, 749, 2250, 686, 928, 2250, 26600, 777, and 2790 copies. The rest of the tests were negative. CONCLUSION: The preliminary results of this study demonstrated that quantitative PCR was a useful rapid tool for diagnosing and monitoring CMV infections.
Resistance of HIV to antiretroviral drugs was studied in 210 samples taken in the last two years from patients at the Molecular Biology Unit of the Microbiology Department of the Hospital La Fe in Valencia, Spain. Once the viral load in plasma was determined, resistance was detected using complete gene sequencing for protease until position 3464 of the HIV-1 inverse transcriptase gene. The results were analyzed using the programs Omiga 1.2 (Oxford Molecular Group) and HR-ASAP 1.0 (Stanford University). The protease inhibitors the least affected by the presence of mutations leading to resistance were amprenavir (68.96% activity), and lopinavir (70.69% activity), and of the inverse transcriptase inhibitors, tenofovir (94.02% activity), D4T (74.62% activity) and 3TC (76.12% activity). The treatment combination with the greatest activity, based on the different mutations, was D4T + 3TC + NNRTI. To justify the persistence of viremia with relatively low genotypic resistance to antiretroviral drugs other variables must be considered, such as treatment compliance and the pharmacokinetics of the drugs.
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Magnetic resonance spectroscopy allows the assessment of several metabolites in brain tissue. In patients with hepatic encephalopathy, this technique shows a rise in glutamine and a decrease in myoinositol in brain tissue. However, the role of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy is not known. We report the case of a patient with a relapsing confusional syndrome who underwent magnetic resonance spectroscopy. Previously, hepatic encephalopathy was ruled out because of the negative results of a transjugular liver biopsy and normal hepatic venous pressure gradient. The results of magnetic resonance were characteristic of hepatic encephalopathy. Abdominal computed tomography demonstrated large portosystemic shunts associated with cirrhosis of the liver. This case shows that magnetic resonance spectroscopy is an useful technique for the diagnosis of hepatic encephalopathy in selected cases, such as those without clinical signs of cirrhosis and/or large portosystemic shunts.
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BACKGROUND: Neuroblastoma is the most common extracranial solid tumor among pediatric patients, and orbital metastatic disease is not uncommon in these children. Physical signs as a consequence of orbital metastases, such as proptosis and periorbital ecchymosis, frequently are encountered. However, subsequent blindness is rare. METHODS: A retrospective study was conducted to determine the incidence, related physical findings, treatment, and outcome of children who developed visual loss during treatment for neuroblastoma. Medical records for a 24-year period (1971-1994) were reviewed to identify these patients. The charts, diagnostic imaging studies, and autopsy material of these patients were reviewed. RESULTS: Of the 450 patients treated for neuroblastoma at the study institution during this period, 47 presented with abnormalities in physical examination of the eye. Eight of these 47 patients and 7 others developed visual loss in at least 1 eye during the first week after diagnosis (n = 5), during primary therapy (n = 6), at recurrence (n 2), or after completion of therapy (n = 2). In ten patients the visual loss was a direct consequence of the primary disease process, whereas a direct relationship between loss of vision and neuroblastoma could not be identified in the remaining five patients. Proptosis and periorbital ecchymosis were the most common associated physical findings. Although ten patients received steroids and eight received radiation, visual loss could not be prevented or reversed in these patients. CONCLUSIONS: Early initiation of effective, multiagent chemotherapy remains the primary approach for the treatment of neuroblastoma and its ophthalmologic complications. Radiation therapy and steroids may have benefit but failed to show good effect in this series. The prevention and treatment of blindness is probably most relevant in infants and children age < 2 years because they have the best chance for cure.
OBJECTIVE: To elucidate the nature of the neuropsychological deficits associated with subclinical hepatic encephalopathy. DESIGN: Prospective study comparing the performance of patients with liver disease and carefully matched normal controls on a short but comprehensive neuropsychological test battery. SETTING: A university medical center. PARTICIPANTS: Twenty patients with cirrhosis (10 alcoholic and 10 nonalcoholic) and 20 controls carefully matched on the basis of age, sex, education, and alcohol history. RESULTS: The cirrhotic patients exhibited relatively selective deficits in complex attentional and fine motor skills, with preservation of general intellectual ability, memory, language and visuospatial perception. CONCLUSIONS: This pattern of neuropsychological deficits suggests a subcortical pathophysiology, possibly reflecting involvement of the basal ganglia. These neuropsychological findings are consistent with recent neuroradiological, electrophysiological, and neurophysiological research implicating basal ganglia involvement in cirrhosis.
Brain myo-inositol, an organic osmolyte, is decreased in cirrhotic patients with hepatic encephalopathy but appears unchanged in fulminant hepatic failure. An osmoregulatory response to the increase in brain glutamine may explain the decrease in brain myo-inositol; if this is the case, organic osmolytes may account for differences in the development of brain edema seen in acute or chronic liver failure. The response of myo-inositol and nine other organic osmolytes to the increase in brain glutamine at different time intervals after portacaval anastomosis (PCA) in the rat was studied. Organic osmolytes were measured in brain tissue and cerebrospinal fluid. Water in cerebral cortex was measured after ammonia infusion with the gravimetric method. Six weeks after PCA, despite an increase in brain glutamine (PCA, 16.4 +/- 2 mmol.kg wt-1.kg wt-1; sham, 5 +/- 1 mmol.L-1.kg wt-1), the content of total organic osmolytes did not increase (PCA, 44.1 +/- 3; sham, 43 +/- 4) because of a decrease of other osmolytes (myo-inositol, 54%; urea, 39%; taurine, 33%; and glutamate, 8%). Brain myo-inositol was lower at 3 weeks (3.4 +/- 0.5 kg wt-1) than at 1 day after PCA (4.7 +/- 0.5 kg wt-1). An ammonia infusion resulted in brain edema at both time points. In conclusion, the reduction in brain myo-inositol in PCA rats is accompanied by the decrease of other organic osmolytes, supporting the view that changes in myo-inositol reflect an osmoregulatory response. The decrease in brain myo-inositol is more marked as time elapses after PCA. In a model in which short-term and large doses of ammonia were infused, the decrease in brain myo-inositol did not prevent the development of brain swelling. Understanding brain osmoregulatory mechanisms may provide new insights into hepatic encephalopathy and brain edema in fulminant hepatic failure.
Nasopharyngeal carcinoma (NPC) paraffin samples, from Spanish patients, of distinct histological types, including squamous cell carcinoma (10 cases), nonkeratinising carcinoma (12 cases) and undifferentiated carcinoma (29 cases) were analysed for Epstein-Barr virus (EBV) detection and EBV-encoded latent membrane protein (LMP-1) expression using a sensitive nested-polymerase chain reaction with four oligonucleotide primers specific for EBV genome (EB-1, 2, 3, 4) and immunohistochemistry by means of CS1-4 pool monoclonal antibody. EBV genome was detected regardless of histological type in 100% of samples with sufficient DNA quality to permit viral diagnosis (50 out of 51 cases), supporting the previous view that all types of NPC are variants of an EBV-associated malignancy. However LMP-1, an EBV-encoded oncogenic protein, was detected in 40 out of 51 samples (78.4%) and LMP-1 immunohistochemical expression was not apparently influenced by histological type, primary or metastatic site, clinical stage, age or sex. This high percentage of detection of LMP-1 in our cases supports a role for EBV in the pathogenesis of different types of NPC, but the lack of constant expression of LMP-1 in NPC remains unclear and various reasons are postulated to explain the absence of this oncogenic protein in some EBV-associated NPCs.
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Ammonia toxicity appears to contribute to the genesis of brain edema, a leading cause of death in fulminant hepatic failure. Because dialysis has been recommended for acute hyperammonemia in other conditions, we have conducted a study to analyze the determinants of ammonia clearance with the use of a single-pass dialyzer. We have used an ionic solution with a constant concentration of ammonia to estimate clearance at different blood flow rates, at dialysate flow rates, and with different dialyzer surfaces. Once hemodialysis had been optimized, we estimated ammonia, glutamine, and urea removal by using a single-compartment model. Our results show that the clearance of ammonia is blood flow dependent and is also influenced by dialysate flow rate and dialyzer surface. At clinically feasible conditions, ammonia can be extracted by more than 80% by setting the dialysate flow at a high rate. In addition to ammonia removal, hemodialysis allows the clearance of urea and glutamine, molecules that can be regarded as ammonia equivalents and that also undergo flow-dependent elimination.
Subclinical hepatic encephalopathy (SHE)--cognitive deficits in the absence of overt encephalopathy--is frequently present in patients with cirrhosis. In the absence of biological correlates, diagnosis of SHE relies on psychometric tests. Attentional and motor abnormalities are the most common neurocognitive deficits. Sleep disturbances--a frequent complaint in cirrhosis--may be part of the spectrum of SHE. The impact of SHE on daily activities is controversial as patients may adapt their lives to cognitive limitations. Demanding activities, such as driving motor vehicles, may be impaired, though a blanket restriction appears premature. The benefit of treating SHE is not established. Antiencephalopathic drugs may be effective and can be considered in certain individuals.
With the wide acceptance of liver transplantation as a therapeutic alternative in fulminant hepatic failure (FHF), the successful management of patients with this syndrome has acquired a new urgency. Topping the list of medical problems is the development of brain swelling. Two decades after the recognition of its importance, brain edema and intracranial hypertension still constitute a major cause of death in these patients. In a more recent classification of FHF, brain edema was especially prominent in those subjects with "hyperacute failure," in whom a period of 7 days or less elapsed between the development of jaundice and encephalopathy. The goal of this review is to discuss two aspects of this clinical problem. On one hand, elucidation of its pathogenesis should lead to a more rational therapeutic approach; such an information would also be valuable to understand the relationship between hepatic encephalopathy and brain edema, a source of controversy. Studies of pathogenic mechanisms are difficult to perform in humans and animal models of FHF have proven valuable, as brain swelling can be detected with some regularity. On the other hand, an increasing array of techniques is now available in the intensive care setting to monitor patients with FHF. Of these, intracranial pressure monitoring has received the most critical attention. However, concerns with the risks of craniotomy and the need to acquire more dynamic information has led several groups to explore non-invasive methods that evaluate the consequences of intracranial hypertension. Their role, though potentially exciting, is still uncertain.
Twenty-four-hour polysomnographic recordings were obtained during asymptomatic (ASP) and symptomatic (SP) periods in a patient with periodic hypersomnia. During both periods, an abnormal sleep architecture was detected, with a greater sleep fragmentation during the SP. An unexpected finding was a shortening of the latency of slow-wave sleep, with a difference of more than 5 hours between the ASP and the SP. The greater fragmentation of rapid eye movement sleep during the SP may suggest a disorganization of the ultradian rhythm of rapid eye movement sleep.
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PATIENT: A young boy with hyper-immunoglobulin M (IgM) syndrome had recurrent severe infections, failure to thrive, and chronic neutropenia for 2 years despite treatment with i.v. gammaglobulin (IVIG). METHODS AND RESULTS: With the addition of granulocyte colony-stimulating factor (G-CSF; Filgrastim, Amgen, Inc., Thousand Oaks, CA), increased doses of IVIG, and prophylactic trimethoprim-sulfamethoxazole, his absolute neutrophil count increased from 0.64 x 10(9)/L to 3.36 x 10(9)/L, and he has been free of significant infection for the past 22 months. CONCLUSIONS: The use of G-CSF merits consideration in patients with hyper-IgM syndrome and severe neutropenia.