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Background: There are few recent studies evaluating trends in the epidemiology of candidemia including changes in species or utilization of antifungal agents in children., Methods: We performed a retrospective case series of candidemia at our children's hospital from 2002 to 2006. Our objectives were to study trends in the rates of candidemia, demographic characteristics, Candida species, antifungal susceptibility, and antifungal utilization. These data were obtained from the electronic medical records., Results: There were 203 episodes of candidemia in 154 subjects. During the study period, the average rate of candidemia was 5.52 per 1000 patient-discharges and did not change throughout the study. The mean and median ages of subjects were 3 years versus 9 months, respectively, and 38% were less than 3 months of age. Gastrointestinal disorders were a common comorbid condition (33%), especially for subjects with multiple episodes of candidemia. Overall, Candida parapsilosis and Candida albicans caused 43% and 26% of episodes, respectively, and candidemia caused by Candida glabrata (5.3%-23%) and Candida krusei (0%-8.5%) increased during the study. Ninety-eight percent of C. albicans and C. parapsilosis isolates remained susceptible to all antifungal drugs. From 2003-2006, the use of antifungal agents increased from 79 days to 150 days per 1000 hospital-days., Conclusions: While antifungal use at our hospital increased, candidemia rates remained stable. C. parapsilosis was the most common species but other non-C. albicans species increased during the study period. Local epidemiology should be monitored in pediatric populations for potential impact on management strategies.

Background: In 2003, the American Cystic Fibrosis (CF) Foundation published revised, evidence-based guidelines for infection control. We sought to assess potential barriers to adherence to these guidelines experienced by health care professionals (HCPs) caring for CF patients., Methods: From April 2004 to December 2005, a knowledge, attitude, and practice survey was administered to HCPs at randomly selected CF centers in the United States to explore potential barriers to adherence to selected guidelines: (1) obtaining quarterly cultures from CF patients, (2) discouraging socialization among CF patients during hospitalization, (3) educating patients and families about hand hygiene, (4) educating patients and families to clean and disinfect home nebulizers, and (5) cleaning the clinic exam rooms between CF patients., Results: The survey was completed by 528 HCPs from 25 sites (5-50 respondents per site). Only 60% of respondents were aware of the guidelines, but despite awareness, 31-47% were unfamiliar with the specific guidelines. Self-reported adherence was low; only 23-63% of respondents reported practicing the selected guidelines >75% of the time/opportunities. Lack of self-efficacy, that is, confidence in adequately performing the guidelines, was commonly experienced by respondents. Access to a copy of the guidelines was associated with increased agreement with the recommendations and increased self-efficacy., Conclusions: Strategies to reduce barriers to adherence to CF infection control guidelines are needed. Strategies could include quality improvement initiatives with enhanced education and skills workshops, sharing successful interventions among CF centers, and linking adherence to improved patient outcomes., ((c) 2008 Wiley-Liss, Inc.)

Complete androgen insensitivity syndrome (CAIS) is a genetic disease caused by mutations in the androgen receptor gene. CAIS patients are individuals with a 46, XY karyotype. The phenotype consists in female external genitalia, short vagina, absent mullerian structures, and abdominal, inguinal or intralabial testes. Our aim is to describe a group of CAIS patients in our centre and identify the difficulties in the diagnosis. The amount of patients with inguinal hernia in childhood was remarkable (83%). Interestingly, the diagnosis was suspected later when patients presented primary amenorrhea. CAIS must be suspected every time a female child shows inguinal hernia. Early diagnosis is very important for a correct genetic counseling.

We describe a technical modification of the apical repositioning flap in the conservative surgical treatment of the impacted canine in buccal position. This amendment improves the tooth's eventual visualization, thus permitting a better evolutive follow-up of its eruption process and, most importantly, providing the tooth with buccal attached gingiva that will accompany it in its downward progression, procuring a cervical contour without retraction, a satisfactory esthetic outcome and a physiologically correct periodontal ridge. The traditional apical repositioning flap also bestows the canine with attached gingiva; however, since the flap is sutured apically and its width is significantly smaller than the remaining surgical defect, the wound's closure is compromised at one of its edges and often requires healing by second intention at an undesired location next to the buccal sulcus. We believe the introduction of the meridian incision is a simple, expedient technical modification with efficient results.

Induction of human beta defensin-2 (HBD-2) by mycobacteria has been reported. However, the molecular mechanism(s) by which mycobacteria up-regulates HBD-2 gene expression in epithelial cells remains poorly understood. In this work, we provide evidence that the induction of HBD-2 mRNA in response to Mycobacterium bovis bacillus Calmette-Guerin (BCG) was inhibited in a dose-dependent manner by pretreatment with a cell-permeable BAPTA-AM, which chelates intracellular calcium. Our data also demonstrate that HBD-2 mRNA induction by M. bovis in A549 lung epithelial cells requires activation of calmodulin. Interestingly, HBD-2 mRNA expression in response to M. bovis BCG was attenuated by pretreatment with SB203580 (an inhibitor of p38 mitogen-activated protein kinase [MAPK]), but not by an inhibitor of extracellular signal-regulated kinase (ERK): PD98059. Furthermore, we found that a second p38 MAPK inhibitor (SB202190) significantly blocked M. bovis BCG-mediated HBD-2 induction in A549 lung epithelial cells. Together, these data suggest that M. bovis BCG induces HBD-2 mRNA expression in A549 lung epithelial cells at least in part mediated through intracellular calcium flux as well as activation of signaling protein of p38MAPK, but not ERK.

Objective: Characterising legal action taken for protecting health rights in Manizales during 2003 and 2004., Methods: This was a descriptive kind of study, based on a sample of 375 legal actions filed in the city of Manizales' legal offices during 2003 and 2004. The study was carried out in two steps; the files kept in the legal offices were reviewed and semi-structured interviews were held with personnel from the General Social Health Security System (GSHSS), monitoring and control centres, the legal offices and the academic sector. Their concept regarding legal action and its subsequent impact on the health services was also consulted., Results: 54.2% of the 375 legal actions were brought by women. Information regarding age was only registered in 53.8% of the files consulted; 81% of these corresponded to the population group aged older than 25 and 3% were presented by the population group less than 5 years of age. 74.7% of the people were in the regime making contributions and 14% in the subsidized regime. Most reasons for making a claim were made on at least two grounds, including complaints about integral treatment including drug prescriptions, exams, surgery, specialist appointments, carrying out procedures, etc., Conclusions: Taking legal action has become the most effective tool for gaining access to health services in Manizales.

Susceptibility (18 antimicrobial agents including high-dose tobramycin) and checkerboard synergy (23 combinations) studies were performed for 2,621 strains of Burkholderia cepacia complex isolated from 1,257 cystic fibrosis patients. Minocycline, meropenem, and ceftazidime were the most active, inhibiting 38%, 26%, and 23% of strains, respectively. Synergy was rarely noted (range, 1% to 15% of strains per antibiotic combination).

Upon contact with airway epithelial cells, mycobacteria activate several signal transduction events that are required for induction of NF-kappaB-dependent chemokine gene expression. However, downstream signaling pathways, especially that of Ca(2+)-dependent protein kinase C alpha (PKCalpha), and in particular, the identity of the IKKalphabeta signal pathway for CXCL8 secretion in Mycobacterium bovis BCG-induced epithelial cells are still unknown. In this study, we demonstrated that the phosphoinositide-phospholipase C (PI-PLC) downstream signaling pathway is involved in M. bovis BCG-induced CXCL8 release, since A549 cells pretreated with U73122, a PI-PLC inhibitor, inhibited CXCL8 release, whereas U73343 the inactive analog had no effect. In addition, our results demonstrated that M. bovis BCG-induced CXCL8 production by A549 cells was significantly blocked by using neomycin (another well-described inhibitor of PI-PLC with a different mechanism of action), Ro-32-0432 and Ro-31-8220 (two PKCalpha inhibitors), PP1 and PP2 (two potent and selective inhibitors of the Src-family tyrosine kinases), and Bay 11-7082 (an IkappaB phosphorylation inhibitor). We also demonstrated that M. bovis BCG can rapidly induce translocation of PKCalpha from the cytosol to the membrane, and that treatment of cells with M. bovis BCG caused time-dependent increases in phosphorylation of c-Src at tyrosine 416. Finally, our studies revealed that M. bovis BCG induced the association of c-Src and IKKalphabeta during the interaction of PKCalpha and IKKalphabeta. Altogether, these results represent the first evidence to date suggesting that M. bovis BCG activates the PI-PLC/PKCalpha/c-Src/IKKalphabeta signaling pathway to induce CXCL8 release in human epithelial cells.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder which can adopt three clinical expressions: two classical forms -salt-wasting (SW), with residual enzymatic activity (EA) < or = 1% and simple virilizing (SV), with EA 1-2%- and a mild late onset or nonclassical (NC) form, with EA 10-60%. Our objective is to describe clinical characteristics, growth, and bone mass in a group of patients affected by 21-hydroxylase deficiency. Besides, molecular genetics studies were performed in patients, and also when available in their parents and siblings. Nine patients with neonatal diagnosis and 8 with pre or postpubertal diagnosis were studied. Analyses of 10-point mutations in the CYP21A2 gene were performed. We found that all the patients with the classical expression, except one with a de novo mutation R356W in one allele, were fully genotyped with predictive < 2% EA mutations. Signs of hyperandrogenism were present in 5/6 NC patients; one was diagnosed by searching for mutations in asymptomatic siblings. All the NC patients were compound heterozygotes carrying V281L mutation in one allele and a predictive low EA in the other, except for one not yet determined. In patients with neonatal diagnosis, mean height was low at one year of age, though it showed a significant increase before the onset of puberty. We conclude that neonatal diagnosis of classical CAH allows an adequate follow up enhancing growth. Molecular analyses of all members of an affected family may disclose asymptomatic patients. The presence of de novo mutations, as well as, the presence of mutations with low predicted EA in NC patients reinforces the importance of genotyping for appropriate genetic counseling. In fully genotyped NC patients, the lowest value of ACTH-stimulated 17OHP was 14 ng/ml. Lower cut-off values might overestimate the diagnosis of the NC form.

Introduction: American cutaneous leishmaniasis is endemic in Colombia, where approximately 6.000 new cases are reported every year. Current prevention and control measures are restricted to the diagnosis and treatment of cases., Objective: To evaluate the efficacy of a multifaceted intervention to prevent the transmission of Leishmania in the endemic focus of Tumaco, on the Pacific Coast of Colombia., Materials and Methods: A group-randomized trial was conducted. Twenty villages were matched according to prevalence of Leishmania infection, number of inhabitants and level of community participation, and then randomly assigned to intervention or control. The intervention included deltamethrin-impregnated bednets, repellent (20% diethyltoluamide and 0.5% permethrin), modification of sand fly resting sites, and health education. Villages were under surveillance for one year and the use of the intervention measures monitored. The incidence of American cutaneous leishmaniasis and Leishmania infection in the two groups were compared, adherence to the intervention and adverse events were monitored, and the results were adjusted for village intraclass correlation., Results: Ten cases of American cutaneous leishmaniasis were confirmed in the intervention and 23 in the control group, OR = 0.42, 95% CI 0.14-1.26. The intervention had a greater effect in children < 10 years old, in people living on the periphery of the village and in villages with a prevalence of infection in small children > 1%. Adverse events associated with the use of the bednets and the repellent were reported in 2% of the participants and were always mild., Conclusion: Incident cases of American cutaneous leishmaniasis were reduced by 58% in the intervention group. However, the small number of cases renders the effect estimate imprecise and precludes us to claim a protective effect for the intervention. Specific populations could be the targets of simpler and more cost-effective interventions in the future.

Background: In patients with colorectal cancer, a preoperative colonoscopy is recommended to exclude synchronous lesions. Unfortunately, between 7% and 29% of patients with colorectal cancer present with acute colonic obstruction, making complete colonoscopy impossible., Objective: The aim of our study was to evaluate the feasibility of a preoperative colonoscopy after effective stent placement in patients with acute neoplastic obstruction., Design: Single-center prospective study., Setting: All examinations were carried out at a tertiary referral center with 24-hour emergency endoscopy service., Patients: Fifty-seven patients with acute neoplastic colon obstruction., Interventions: Patients who recovered from an acute colon obstruction by an effective stent placement and who had a resectable cancer underwent a preoperative colonoscopy., Main Outcome Measurements: Patients with a resectable cancer, complete preoperative colonoscopies, and synchronous lesions rates., Results: Self-expandable metallic stents (SEMS) were placed in 50 of 57 patients (87.8%). Thirty-one of 50 patients had a resectable cancer (62%), and a complete preoperative colonoscopy was possible in 29 of 31 patients (93.4%). A synchronous cancer was detected in 3 patients (9.6%), changing the surgical plan., Limitations: Seven patients in whom the SEMS placement (12.2%) was unsuccessful underwent an urgent surgical intervention. Nineteen of 50 patients who had stent placement were not eligible for our study because of unresectable cancer., Conclusions: Our study indicates that it is feasible in a majority of patients to perform full preoperative colonoscopy after relief of acute colonic obstruction with SEMS before surgical resection.

Background: Ileoscopy is the criterion standard for mucosal lesions of terminal ileum but is performed in 5% of colonoscopy activity, and the need for training is undefined., Objective: To assess the learning curve and skill-keeping line of ileoscopy., Design: Prospective randomized study., Setting: Single GI endoscopy unit., Patients: Adult outpatients referred for colonoscopy., Interventions: Patient randomization to ileocolonoscopy by trainees and seniors., Main Outcome Measurements: Ileoscopy skill was divided into the following: ileocecal valve (ICV) intubation (success rate, time) and ileal exploration (length, time). Consecutive blocks of 10 procedures were used to calculate the learning curve and the skill-keeping line. Variables considered to influence ICV intubation were the following: endoscopist experience, ICV morphology, patient age, gender, body mass index, diverticular disease, and preceding abdominal/pelvic surgery., Results: Learning curve showed that competency in ICV intubation (80% success rate) and ileal exploration (16 cm) was achieved after 50 procedures. The skill-keeping line showed that ileoscopy was easy (97% success rate), fast (1 minute), and well accepted up to 45 cm of the ileum. Thin-lipped and volcanic ICV are the most difficult and easiest to intubate, respectively. Crohn's disease and adenomas of the proximal edge of ICV were diagnosed in 2.2%., Conclusions: Training in ileoscopy is recommended to achieve competency, and endoscopists should consider practicing ICV intubation to maintain and increase their skill. Ileoscopy can be difficult when the ICV is thin lipped or single bulged, and easy when it has a volcanic morphology.

After careful review of evidence-based literature, clinical and laboratory criteria for diagnosis of bacterial and fungal endocarditis are examined. The choice criteria for therapy of bacterial endocarditis, both empiric and directed against a specific pathogen, are reviewed, on the basis of the clinical and epidemiological context (prosthetic or native valve, left or right heart, drug addiction). Different treatment options are proposed, based on results of antibiotic resistance testing. Indications and contraindications for a parenteral home treatment and those for surgical treatment are examined, also according to the results of ultrasonography.

The present study investigates the effects of functional sensorial denervation, induced by administering capsaicin to hemiovariectomized adult female rats in each day of the estrus cycle, on ovulation and serum concentrations of estrogen and progesterone. The results indicate that the establishment of compensatory ovarian hypertrophy (COH) and compensatory ovulation (CO) depends on both the day of the estrous cycle when sensorial denervation was performed and on which ovary was extirpated. These results support the now accepted notion that the response of the ovaries to denervation is asymmetrical. The results seem to suggest that this asymmetric response is mediated by some specific neu-ral information that is registered in the ovary and sent to the CNS, that such information plays a role modulating the reactivity of the ovarian compartments to gonadotropins, and that the frequency of this signal varies along the estrus cycle.

Background: Acitretin is an aromatic retinoid analog of vitamin A. Drugs of this group are well-known teratogenic agents. Nevertheless, acitretin embryopathy has been described only in fetuses., Case: An infant was exposed to 10 mg/day of acitretin from the beginning of pregnancy until the 10th gestational week. At term, the newborn showed the following abnormalities: microcephaly, epicanthal folds, low nasal bridge, high palate, cup-shaped ears, anteverted nostrils, atrial septal defect, and bilateral sensorineural deafness. At 18 months of age, the patient showed microcephaly and neurodevelopmental delay., Conclusions: Our patient shows a pattern of anomalies resembling that observed in isotretinoin- and etretinate-exposed children. After ingestion, acitretin is partially converted into etretinate, and etretinate is partially metabolized into acitretin. A similar phenotype would therefore be expected after prenatal exposure to either drug. Moreover, in the present case, teratogenic effects were observed even though the dose was lower than in the previously reported acitretin embryopathy cases. Therefore, we propose that different retinoids, acitretin included, produce only one malformation pattern with variable phenotypic expression., ((c) 2004 Wiley-Liss, Inc.)

The first case of septicemia due to Yersinia pseudotuberculosis in an HIV-infected person was reported. The 42-year-old woman was severely immunosuppressed despite a prolonged exposure to HAART. Specific amplicons for inv, yadA, and lcrF genes showed the pathogenetic potential of the Y. pseudotuberculosis serotype O1 isolate. A favorable clinical response to ceftriaxone and levofloxacin was observed.

To evaluate the diagnostic value of thallium-201 single-photon emission computed tomography (201Tl SPECT) in the management of focal brain disorders in the era of highly active antiretroviral therapy (HAART), a validation study of diagnostic procedure was performed in a tertiary clinical care center in Italy. Thirty-eight consecutive HIV-infected patients with neurological impairment and focal brain lesions (FBL) were enrolled in a prospective evaluation and underwent diagnostic procedures according to a standardized protocol based on modified previously released guidelines. Six out of seven PCNSL presented high uptake at 201Tl SPECT [sensitivity 86% (95% CI 42-99); specificity 77% (95% CI 58-90); positive predictive value (PPV) 46% (95% CI 20-74); negative predictive value (NPV) 96% (95% CI 78-100)]. Among toxoplasmic encephalitis (TE) cases 14 showed no uptake and 5 showed an increased uptake [sensitivity 74% (95% CI 49-90); specificity 42% (95% CI 21-66); PPV 56% (95% CI 35-75); NPV 61% (95% CI 32-85)]. Patients taking HAART were more likely to display an increased uptake of 201Tl in the cerebral lesions than patients without HAART (OR 5.07; 95% CI 1.19-21.5). Considering only the patients with diagnosis of TE, 60% of patients who showed high radionuclide uptake were taking HAART, while 79% of patients without relevant uptake were not taking HAART. As a result of the impact of HAART, the diagnostic value of 201Tl SPECT in the management of HIV-associated FBL could be substantially reduced. This observation suggests that in HAART-treated patients, this diagnostic tool be used only when combined with other more specific diagnostic markers.

Recently, a 15-fold increased risk of T cell lymphomas has been estimated in HIV-infected populations. This increase has been observed for all T cell lymphoma subtypes. In the present report we describe clinical and pathological features of three consecutive cases of peripheral T cell lymphoma (PTCL) with cytotoxic phenotype in HIV-positive patients that came to our attention in May-September 2002. The diagnosis of PTCL was made in lymph node (two cases) and in needle biopsies from liver and bone marrow of the same patient. The patients were two females (31 and 45 years old) and one male (49 years old). The risk factor for each patient was heterosexual, injecting drug user, and homosexual, respectively. CD4 cell counts were low (79-81 cells/mm3). Two patients were naive for antiretroviral therapy. At histological examination, all the involved tissues were effaced by a neoplastic proliferation of CD3+/CD8+ medium to large pleomorphic cells containing TIA-1+ cytotoxic granules and a few granzyme B+ granules. Neoplastic cells were not infected by EBV or by HHV-8. They were negative for the B cell antigens CD20 and CD79a, for CD30 and for CD56. Clonal T cell receptor-g (TCR-g) rearrangements were demonstrated in the three cases.

Chemotherapy for cancer could have negative effects on HIV-1 dynamic in addition to the effects on immunological status. At the moment few data are available about the effects of chemotherapy on systemic HIV-1 replication, but the effects on the central nervous system, considered an independent compartment for viral replication, has never been investigated. We studied 19 HIV-1-infected patients with non-Hodgkin lymphoma (NHL) treated concomitantly with chemotherapy and highly active antiretroviral therapy (HAART) to evaluate HIV-1 replication and assess virological response to HAART in cerebrospinal fluid during chemotherapy. No patients were diagnosed with lymphoma involvement of the central nervous system. In 18 of 19 patients an HIV-1 load below 200 copies/ml was obtained in cerebrospinal fluid (CSF) during treatment. A correlation between plasma and CSF HIV-1 RNA levels was present at baseline, and was confirmed at the fourth cycle of chemotherapy. A significant decline in the mean difference between plasma and CSF HIV-1 RNA load was observed when comparing the value at the first cycle of chemotherapy with subsequent cycles. HAART even during chemotherapy allows us to obtain an effective control of HIV-1 infection in CSF in patients affected by NHL. In HIV-infected patients with NHL, the contemporaneous administration of HAART and chemotherapy is advisable to obtain a suppression of HIV-1 replication in CNS compartment during the potentially immunosuppressing effect of cancer treatment.

Background: Recent mortality profiles in Brazil show that circulatory diseases are the leading cause of death in Brazil. These disorders contribute to 34% of deaths, with 50% of those deaths occurring in people under 50 years of age, that is, in people who are still active in the workforce. We assume that the growing incidence of cardiovascular diseases has occurred as the globalization of Brazil continues and brings with it the associated health risk factors of modern lifestyles, including stress., Aim: This paper reports the evidence on the influence of stress in the development, onset and progress of cardiovascular diseases. We aim to define the concept of stress and to point systematically to the interrelationships between its emotional and bodily manifestations through a discussion of the history and study of stress. We then suggest that factors leading to the experience of stress in Brazil are no different than in any other modern nation. We further offer a perspective on nursing interventions currently undertaken in Brazil in both hospital and community settings, with their more recent emphasis on health promotion and prevention., Methods: An extensive literature review was undertaken. The data presented here were selected from reviews and clinical studies described in MEDLINE, LILACS, SciELO databases, as well as in the classical literature. We also refer to the current Brazilian literature on the prevalence of cardiovascular diseases and their associated risk factors., Conclusions: The incidence of cardiovascular diseases in Brazil is rising. Because of the globalization of Brazilian society, with its consequent competitiveness and accelerated modern lifestyles, Brazilians are no less immune to the usual health risk factors associated with cardiovascular diseases. Stresses associated with a modern lifestyle, however, are emerging as a new and major risk for developing cardiovascular diseases in Brazil.

Non-alcoholic fatty liver disease is a clinicopathological condition that comprises a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. Non-alcoholic steatohepatitis represents only a stage within the spectrum of non-alcoholic fatty liver disease and is defined pathologically by the presence of steatosis together with necro-inflammatory activity. The true prevalence of non-alcoholic fatty liver disease is unknown, but it is estimated that it affects 10-24% of the general population in different countries. The diagnosis of non-alcoholic fatty liver disease is based upon convincing evidence of absent or minimal alcohol consumption, compatible histological changes in liver biopsy and the exclusion of other liver diseases. The natural history of non-alcoholic fatty liver disease remains to be defined. Patients with pure steatosis on liver biopsy follow a relatively benign course, whereas patients with histological necro-inflammatory changes and/or fibrosis may progress to end-stage liver disease. An initial step in the treatment of non-alcoholic fatty liver disease is the management of associated conditions, such as obesity, diabetes mellitus and hyperlipidaemia. Non-alcoholic fatty liver disease patients with steatohepatitis and/or fibrosis on liver biopsy may benefit from investigational pharmacological therapy. Patients with decompensated cirrhosis from non-alcoholic fatty liver disease may be candidates for liver transplantation.

Objective: To determine the effectiveness of antiretroviral therapy in controlling cerebrospinal fluid (CSF) HIV-1 replication and to assess factors related to virological response in advanced patients., Design: A cross-sectional and longitudinal study., Methods: Consecutive paired CSF and plasma samples from HIV-1-infected patients were collected before starting or changing highly active antiretroviral therapy (HAART)., Results: In the cross-sectional analysis 75 patients were included, 55 (73%) with neurological disease, 28 (37%) naive for antiretroviral agents. A significant correlation between plasma and CSF levels at baseline was observed only in antiretroviral-experienced patients. The absence of neurological disease, lower plasma HIV-1 load and a previous exposure to indinavir were all associated with a baseline CSF HIV-1-RNA level less than 80 copies/ml at multivariate analysis. In 29 patients included in the longitudinal study a significant reduction in CSF HIV-1 RNA was observed. Plasma HIV-1-RNA change, CSF HIV-1-RNA level at baseline, overall months of antiretroviral treatment and the magnitude of difference between plasma and CSF HIV-1-RNA levels were all correlated to CSF HIV-1-RNA change during treatment. A significant difference in the magnitude of CSF HIV-1-RNA reduction was observed according to naive status and to the use of three or more drugs penetrating the blood-brain barrier., Conclusion: HAART effectively reduces HIV-1 replication in CSF. A variable response to antiretroviral therapy was observed in CSF, reflecting a different compartmentalization of infection during treatment. Naive status and the use of CNS-penetrating drugs substantially enhance antiviral response. A negative interaction between virological response and the duration of antiretroviral treatment suggests long-term selection of drug-resistant CSF HIV-1 strains.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome of unknown etiology frequently associated with inflammatory bowel disease and characterized by diffuse inflammation and fibrosis of the intra and/or extrahepatic bile ducts. Recent studies seem to favor autoimmunity in the context of a genetic predisposition as the most likely underlying mechanism for the development of the disease, however our knowledge on the pathogenesis of PSC is still incomplete and further work is needed. The most common manifestations are fatigue, pruritus, jaundice and abdominal pain; however, the increasing use of invasive cholangiography has led to diagnosing this condition in a high proportion of asymptomatic patients. PSC usually follows a progressive course leading to biliary cirrhosis with complications of portal hypertension and hepatic failure. Patients with PSC also may develop a number of other complications, including bacterial cholangitis, dominant biliary strictures, conditions of chronic cholestasis, colorectal cancer and cholangiocarcinoma. Currently, no medical therapy aimed at disrupting disease progression is available, although high-dose ursodeoxycholic acid and other medicines are being evaluated in clinical trials. A better understanding of the pathogenesis of the disease will serve as a guide for evaluating new medical approaches. Liver transplantation is the only therapeutic alternative that improves survival in patients with end-stage PSC. Prognostic models are useful in determining the timing of liver transplantation.

Nematode infection may be a risk factor for pyogenic liver abscess in children and we hypothesized that the immunomodulation induced by those parasites would be a risk factor for any staphylococcal infection in children. The present study was designed to compare, within the same hospital, the frequency of intestinal nematodes and Toxocara infection in children with and without staphylococcal infections. From October 1997 to February 1998, 80 children with staphylococcal infection and 110 children with other diseases were submitted to fecal examination, serology for Toxocara sp., evaluation of plasma immunoglobulin levels, and eosinophil counts. Mean age, gender distribution, birthplace, and socioeconomic conditions did not differ significantly between the two groups. Frequency of intestinal nematodes and positive serology for Toxocara, were remarkably higher in children with staphylococcal infections than in the non-staphylococcal group. There was a significant correlation between intestinal nematodes or Toxocara infection and staphylococcal infection in children, reinforced by higher eosinophil counts and higher IgE levels in these children than in the control group. One possible explanation for this association would be the enhancement of bacterial infection by the immunomodulation induced by helminth infections, due to strong activation of the Th2 subset of lymphocytes by antigens from larvae and adult worms.

HIV encephalopathy has been in the past years the most typical CNS disorder in patients with AIDS. Histologic abnormalities consist in astrocytosis, myelin pallor, infiltration by infected macrophages, resident microglia and multinucleated giant cells, generally in absence of direct infection of neurons. Mononuclear phagocytes in the brain are the main target of HIV-1 infection and the site of productive viral replication, and viral stimulation leads to the release of neurotoxic products causing neurologic damage. Subclinical cardiac abnormalities are common in HIV+ patients and several studies suggested a role for cytokines and other inflammatory products as mediators of cardiac abnormalities. The common pathway for neurologic and cardiac manifestations supports the relationship between neurologic disease and cardiac dysfunction in HIV infection. Clinical observations suggest that cardiomyopathy could be associated with encephalopathy in HIV+ patients and that it may affect survival. Antiretroviral therapy may reduce impact of neurologic and cardiac abnormalities by suppressing plasma HIV-1 viral load.

Objectives: To evaluate the impact of response to highly active antiretroviral therapy (HAART) on the natural history of AIDS non-Hodgkin's lymphoma (NHL) and to analyse the feasibility, efficacy and toxicity of HAART in combination with chemotherapy., Design: Prospective observational study in two AIDS clinical centres in Italy., Methods: All consecutive HIV-infected patients with NHL were included (n = 44; 48% high-risk group) and prospectively followed for 27 months. HAART was administered concomitantly with chemotherapy. The association between response to HAART and clinical presentation, response to chemotherapy and toxicity was analysed by univariate and multivariate models. Survival analysis was performed by Kaplan-Meier estimates and the Cox proportional hazards regression model., Results: A complete response (CR) to chemotherapy was achieved in 71% of HAART responders and 30% of non-responders. Virological response to HAART was the only variable associated with tumour response on multivariate analysis. A higher relative dose intensity (RDI) of chemotherapy was administered in patients with virological response compared with those without. The probability of 1 year survival was higher in patients with virological or immunological response. At Cox regression analysis, immunological response, a higher RDI and a CR to chemotherapy were all associated with a reduced risk of death., Conclusion: In HIV-infected patients with NHL, response to HAART was strongly associated with a better response to chemotherapy and prolonged survival. Concurrent treatments were well tolerated, and HAART-responder patients could receive a higher RDI of chemotherapy. In patients with AIDS lymphomas, combining HAART with chemotherapy could be a feasible and effective approach.

To analyze the clinical efficacy of cidofovir combined with highly active anti-retroviral therapy (HAART) in AIDS-related progressive multifocal leukoencepalopathy (PML), a multicenter observational study was performed. Consecutive HIV-positive patients with histologically or virologically proven PML and at least 4 weeks of treatment after diagnosis were examined: 27 patients were treated with HAART, whereas 16 patients were treated with HAART plus cidofovir 5 mg/kg intravenously per week for the first 2 weeks and every other week thereafter. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR. Baseline virologic, immunologic, and clinical characteristics as well as HIV RNA and CD4 responses to HAART were homogeneous between the groups. The median follow-up was 132 weeks. In one case (6%), cidofovir was permanently discontinued because of severe proteinuria. One-year cumulative probability of survival was 0.61 with cidofovir and 0.29 without (log rank test P = 0.02). After adjusting for baseline CD4 counts, JC viral load in CSF, Karnofsky, and use of HAART prior to the onset of PML, the use of cidofovir was independently associated with a reduced risk of death (hazard ratio, 0.21, 95% confidence interval, 0.07-0.65; P = 0.005). A randomized study will definitively establish whether cidofovir confers significant advantage over HAART alone in AIDS-related PML.

Whereas most AIDS-related neurologic disorders have reduced incidence since HAART therapy was introduced, we find that the incidence of progressive multifocal leukoencephalopathy (PML) did not significantly differ between the pre-HAART and the HAART period (OR 0.78; 95% CI 0.41-1.50). These findings were confirmed by the preliminary results of the Italian Register Investigative Neuro AIDS (IRINA) Study, a prospective multicenter study started in January 2000, which showed that PML was the second most frequently diagnosed neurologic disorder after TE. A similar proportion of cases were found in HAART-naïve and HAART-experienced patients in our experience. PML was more common in the presence of HIV RNA > 500 copies/ml. Most of the cases occurring in HAART-exposed patients developed within the first 6 months of therapy. As others have reported, we find a prolonged survival in PML subjects prescribed HAART (245 days in the group treated with HAART versus 66 days in the group not treated with HAART; P at log rank = 0.001). However despite the survival benefit, AIDS-associated PML still has a serious prognosis. In fact, PML had the lowest 1-year survival probability of any cerebral disorder in our study (P = 0.0005). Our findings also confirm that CSF JCV DNA burden at baseline is a useful prognostic indicator with a threshold of 4.7 log(10) JCV copies/ml (P at log rank = 0.01) in our experience. CSF JCV DNA load at 4 weeks of follow-up and clearance of JCV-DNA from CSF are associated with a better neurologic outcome and a longer survival.

Kyphomelic dysplasia (KD) is a rare autosomal recessive entity characterized by shortening and bowing of the limbs, skin dimples, abnormalities of methaphysis and ribs, a short trunk, a narrow thorax, neonatal respiratory distress, platyspondyly, and facial dysceptism with micrognathia, midfacial hypoplasia, and a broad nasal bridge. Some children die in early infancy. The survivors show normal hands, feet, cranium and psychomotor development. The condition varies in severity. The facial features and bowing improve during childhood, and stature remains short during adulthood. We report here a family with KD inherited as an autosomal dominant trait, which appears to be less severe than the autosomal recessive form, without facial and vertebral a favorable outcome and with involvement and final short stature.

Two experiments were carried out with dairy ewes to determine the effects of supplementation of calcium soaps of olive fatty acids at 10% of the basal diet on digestibility, roughage intake, milk production and composition, and response to early induced ovulation. The addition of calcium soaps of olive fatty acids to the diets of dairy ewes significantly decreased the digestibility of dietary dry matter but not the digestibility of other components. The digestibility of crude fat was enhanced. Voluntary intake of roughage, with fixed concentrate allowances, was slightly, but not significantly, reduced for ewes fed the supplemented diet. After weaning at 35 d postpartum and during the next 5-wk period of twice daily milking, ewes fed the supplemented diet produced more total solids in milk than did ewes fed the basal diet. Ewes fed the supplemented diet also tended to produce more milk protein, and milk energy and tended to have greater milk fat percentages. The composition of milk fatty acids was changed by the calcium soaps of olive fatty acids. Fewer short- and medium-chain fatty acids (C6:0, C8:0, C10:0, C12:0, C14:0, and C16:0), less C18:2, and more C18:1 and C18:0 were obtained in the milk of ewes fed the supplemented diet. Responses to ovulation induced at 60 d after lambing, while ewes were still lactating, were significantly higher for ewes fed the diet supplemented with calcium soaps of olive fatty acids than for ewes fed the basal diet. The calcium soaps of olive fatty acids appeared to be a useful source of energy for dairy ewes, and dairy ewes may be a good model for the study of the effects of nutrition during early lactation on reproductive performance of dairy ruminants.

Up to now many controversies exist regarding the value of different diagnostic techniques available in alkaline esophagitis. The Authors studied 92 patients with histologic diagnosis of esophagitis obtained by endoscopic biopsy, by radiological study of upper gastrointestinal tract, esophageal manometry, combined 24 hour esophago-gastric pH-metry and cholangio-scintigraphy, too. These last two techniques have the highest specificity and accuracy rates. These techniques should be considered complementary and their combined employment has to be considered essential to reach the highest rate of accuracy in the diagnosis of alkaline esophagitis.

A case of granulomatous peritonitis produced by starch is presented. This is a rare pathology caused by abdominal contamination with starch from surgical gloves during an operation. The symptoms can be very similar to acute abdomen, therefore, it is sometimes necessary to carry out a second operation in order to confirm the diagnosis. A peritoneal biopsy or cytology of the ascitic liquid usually provides the correct diagnosis as the typical starch granules show up. With non-steroid analgesics, or steroids in some cases, the process can controlled.