A novel frame-shift deletion causing analbuminaemia in an Italian paediatric patient.

BACKGROUND: Analbuminaemia (OMIM #103600) is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. The trait is caused by a variety of mutations within the albumin gene. DESIGN: We report here the clinical and molecular characterization of a new case of congenital analbuminaemia in a 4-year-old Italian girl diagnosed on the basis of the low level of circulating albumin (= 10.0 g L(-1)). The albumin gene was screened by single-strand conformation polymorphism and heteroduplex analysis and the mutated region submitted to DNA sequencing. RESULTS: The proband was found to be homozygous, and both parents heterozygous, for a novel deletion in exon 8 (c.920delT). The subsequent frame-shift should have given rise to a putative polypeptide chain of 304 amino acid residues, which we could not identify in the proband's serum. CONCLUSIONS: A novel analbuminaemia causing mutation was identified and characterized at the clinical level in a child. The molecular diagnosis of the trait is based on the rapid localization of the mutation within the albumin gene by single-strand conformation polymorphism and heteroduplex analysis, followed by DNA sequencing of the mutated region.

Cardiovascular risk factors and ultrasound evaluation of carotid atherosclerosis in patients with HIV-1 infection.

A cross-sectional study was performed to evaluate classical risk factors for cardiovascular diseases and subclinical atherosclerosis by carotid ultrasonography in HIV-positive subjects, naïve or treated with antiretroviral agents. A total of 66 patients were enrolled into the study: 21 subjects were naïve to all antiretroviral agents (group A) and 45 patients were treated with antiretroviral therapy for >or=36 months (group B). The prevalence of carotid plaques was significantly higher in group B than in group A (44.7% versus 0%; P = 0.014). In group B, patients with high 10-year risk of coronary heart disease showed a significantly higher intima-media thickness and prevalence of carotid lesions than those with low risk. Moreover, carotid lesions were structurally comparable to classical atherosclerotique plaques observed in the general population, with iso-hyperechonegic aspects and irregular surfaces. The prevalence of carotid atherosclerosis in experienced patients is higher than in those naïve to highly active antiretroviral therapy and seems mostly associated with a longer duration of HIV infection, more severe lipid metabolism alterations, presence of lipodystrophy syndrome and a more elevated 10-year risk of cardiovascular diseases.

Measles outbreak in the city of Bologna, December 2007 to May 2008.

Several outbreaks of measles were reported after the year 2006 in various Italian regions, including Piemonte, Lombardy, Tuscany, Veneto and Emilia Romagna. Most reported cases occurred in the Piemonte region where a major outbreak began in September 2007 among a group of unvaccinated adolescents. This report is a preliminary description of the main epidemiological, clinical and laboratory features of 26 confirmed cases of measles diagnosed at the Institute of Infectious Diseases of the S. Orsola Hospital in Bologna in the northern Italian region of Emilia Romagna between December 2007 and May 2008.

Efficacy and tolerability of a fosamprenavir-ritonavir-based versus a lopinavir-ritonavir-based antiretroviral treatment in 82 therapy-naïve patients with HIV-1 infection.

Recent data indicate that fosamprenavir/ritonavir as part of an initial antiretroviral regimen in HIV-1-infected patients is associated with favourable efficacy and tolerability and in the KLEAN study (kaletra versus lexiva with epivir and abacavir in antiretroviral-naive patients) it was found to be non-inferior to lopinavir/ritonavir in association with abacavir/lamivudine. In our open-label, observational study conducted in 82 therapy-nasmall yi, Ukrainianve HIV-1-infected patients followed-up for 18 months, virological and immunological efficacy was comparable in subjects receiving a fosamprenavir/ritonavir-based and a lopinavir/ritonavir-based treatment (proportions of patients with HIV RNA <50 copies/mL at month 18 were 76.9% and 74.4%, respectively, when discontinuations were counted as failures). At the same time, frequency of treatment discontinuations and adverse events were similar in both groups, whereas incidence of diarrhoea and hypertriglyceridaemia was significantly higher in lopinavir-treated patients than in fosamprenavir-treated ones (53.5% vs. 25.6% and 69.8% vs. 43.6%, respectively; P < 0.01). In subjects with virological failure, no viral protease resistance mutations were detected by genotype analysis.

[Hyperlactacidemia during antiretroviral therapy: frequency and clinical-therapeutic correlations]. / Iperlattacidemia in corso di terapia antiretrovirale: frequenza e correlazioni clinico-terapeutiche.

While asymptomatic hyperlactacidemia is quite a frequent phenomenon among HIV-infected patients treated with highly active antiretroviral therapy (HAART), lactic acidosis is a rare, but potentially life-threatening occurrence. Epidemiology, clinical and laboratory presentation, evolution, and outcome of this phenomenon are currently under intensive investigation, and the most likely pathogenetic pathways seem to involve mitochondrial toxicity prompted by the administration of nucleoside reverse transcriptase inhibitors. Our case-control study on an extensive, single centre population treated for HIV infection provides novel insights on these emerging issues, reported and discussed on the basis of the most recently published findings.

Primary cytomegalovirus infection in otherwise healthy adults with Fever of unknown origin: a 3-year prospective survey.

BACKGROUND: Primary cytomegalovirus disease is probably still underestimated or missed in common clinical practice, and further prevalence studies should be performed, in particular in the setting of fever of under-determined origin (FUO) in adults. PATIENTS AND METHODS: In a 3-year prospective survey of 123 consecutive adult patients referred for FUO often associated with a broad spectrum of constitutional signs and symptoms, 18 patients (14.6%) were found to have a primary cytomegalovirus infection, after a clinical, instrumental and laboratory workup. RESULTS: In the majority of cases, this syndrome was consistently associated with altered white blood cell count, abnormal T-lymphocyte subsets and ultrasonography-confirmed hepatosplenomegaly. On the other hand, altered white blood cell differential and serum hepatic enzymes, and constitutional signs and symptoms were absent in 11.1-27.8% of cases, and an initial laboratory cross-reaction with anti-Epstein-Barr IgM antibodies was detected in 44.4% of episodes. Non-specific signs and symptoms were the only features in 27.8% of patients with adult cytomegalovirus disease, thus, confirming that this disorder may be still clinically underestimated, until virologic assays are performed. A prolonged and varied spectrum of subjective disturbances (similar to those encountered in infectious mononucleosis), which often limited daily activities, involved nearly 30% of subjects, and lasted for 3-15 months after recovery of acute cytomegalovirus disease. CONCLUSION: In the clinical, laboratory, and instrumental workup for FUO, rapid recognition of a primary cytomegalovirus disease is useful to exclude alternative diagnoses, avoid non-necessary exposure to antibiotics, and reassure patients of their self-limiting, benign disorder.

Key questions in antiretroviral therapy: Italian Consensus Workshop (2005).

A panel of leading Italian specialists in infectious diseases, virologists and immunologists met in Rome in 2005 to review critical data and discuss recommendations for each of the key questions in antiretroviral therapy today: When to start treatment? How to start? When to switch? What to switch to? Whether to stop or not to stop treatment, and how? The method of a nominal group meeting was used and recommendations were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed in this consensus statement, as well as some of the most recent data supporting these recommendations are provided.

Changing epidemiology of hepatitis A in the Bologna metropolitan area, northern Italy: importance of counselling and prophylactic measures for the male homo/bisexual population.

During a 6-year observational study, 122 cases of hepatitis A virus (HAV) infection were detected in Bologna, Italy, with a c. 300% increase in cases between 1999 and 2004. There were 104 cases (85.2%) in male adults, of whom nearly 70% had unprotected sexual contact as the probable risk-factor. There were increasing numbers of cases in immigrants between 1999 and 2004 (p 0.036), and concurrent cases of infection with human immunodeficiency virus, hepatitis B and C viruses and syphilis were also noted in adult males (p 0.0032). There is a need to re-emphasise targeted educational programmes and anti-HAV vaccination for at-risk subjects.

Human herpesvirus-8-related Kaposi's sarcoma after liver transplantation successfully treated with cidofovir and liposomal daunorubicin.

The iatrogenic form of Kaposi's sarcoma (KS) is typically observed among transplant recipients, and the most appropriate therapeutic approach (usually including reduction of immunosuppression, specific chemotherapy, and/or administration of antiviral agents against human herpes virus-8) is still controversial. Available experiences on the effect of the anti-herpes viruses drug cidofovir provide conflicting results. Herein, we report the clinical, histological, and virological features of a liver transplant recipient successfully treated with a combined therapy of cidofovir and liposomal daunorubicin, associated with a reduction of the immunosuppressive regimen, for an advanced cutaneous and visceral KS.

Bartonellosis: light and shadows in diagnostic and therapeutic issues.

Cat-scratch disease involves a prolonged and/or complicated course, and lymph node drainage is usually required. Culture and molecular techniques often yield negative results, but immunofluorescence assays may give early information, and elevated antibodies may persist for months. Cat-scratch disease should be suspected in patients with prominent swelling of lymph nodes draining from the upper limbs, limited systemic involvement, and typical epidemiological-clinical features. The temporal antibody response during the sub-acute course remains unknown. Although biomolecular assays are available, the time between onset and investigation is an obstacle to positive results. The role of surgical debridement and the unpredictable activity of antimicrobial agents warrant further investigation.

Limited access to hospitalization in an Italian infectious disease ward.

OBJECTIVE AND METHODS: A four-year retrospective survey was carried out in our Infectious Disease ward, to point out discrepancies between immediately hospitalized patients, and those referred to us for admission, but needing transferal elsewhere, due to lack of a suitable hospital room. RESULTS: Since the year 2000, 439 patients out of 1,979 needing hospitalization (28.5%), could not be admitted to our ward. After increasing the number of rooms in our Ward (June 2002, 16 to 35 beds), the described phenomenon decreased sharply, but a subsequent stabilization followed until July 2003, with around 13% of Infectious Disease patients sent elsewhere for hospitalization. Patients with severe, transmissible diseases were of particular concern, when the accepting Infectious Disease unit is located 40-120 Km far from our city. This was the case for nearly 25% of patients refused by our Hospital, since the year 2000. CONCLUSIONS: Infectious Disease wards need a continuous fitting to economic, technical, human, and professional health care resources, on the ground of ever-changing predominant diseases and/or problems. A strict monitoring of hospital admission needs in the Infectious Disease setting is strongly needed, to improve care of managed patients in the Bologna metropolitan area in the future.

Capnocytophaga spp. brain abscess in an immunocompetent host: problems in antimicrobial chemotherapy and literature review.

The fourth case report of a brain abscess due to the fastidious Gram-negative organism Capnocytophaga spp. is described and discussed on the grounds of clinical, microbiological, and therapeutic evidence. A probable origin from a cat bite and/or an underlying severe mandibulary granuloma is suspected. Due to lack of clinical and neuroradiological response to neurosurgery and a combination of imipenem-amikacin-clindamycin-fluconazole, second-line empiric llnezolid treatment proved rapidly successful, in the absence of further microbial isolations. In vitro antimicrobial susceptibility testing is often unpredictable for Capnocytophaga spp., and agents usually active on Gram-positive organisms may also be effective, both in vitro and in vivo. Due to its favorable brain penetration and its dual mode of administration, linezolid may be an alternative option for patients with multiple risk factors, brain abscess of suspected polymicrobial origin, and lack of response to empiric or culture-driven therapeutic attempts.

Voriconazole proves effective in long-term treatment of a cerebral cryptococcoma in a chronic nephropathic HIV-negative patient, after fluconazole failure.

Although being a rare occurrence, brain cryptococcoma may represent an emerging issue, because of its relationship with a broadening range of risk factors, including malignancies, neutropenia, end-organ failure, bone marrow and solid-organ transplantation, and multiple underlying causes of primary-secondary immunodeficiency. A cerebral cryptococcoma in a chronic nephropathic HIV-negative subject with homocystinuria, completely cured with neurosurgery and voriconazole after fluconazole failure, is described.

A new syndrome of long-term idiopathic, severe CD4+ lymphocytopenia: isolated paraparesis and conjunctival ischemic microangiopathy.

An extraordinary case report of an adult patient followed-up for a decade with an extremely severe idiopathic CD4+ T-lymphocytopenia (as expressed by an absolute CD4+ count of 8-25 cells/microL), associated with an isolated paraparesis and a conjunctival ischemic microangiopathy is described, and discussed on the grounds of the available literature. Despite such a severe and prolonged immunodeficiency, no opportunistic disease occurred, in a observation period longer than ever reported to date. The neurological disorder was diagnosed concurrently with idiopathic CD4+ lymphocyte depletion, while the ocular complication occurred two years later, but remained stable thereafter. Both disorders remained stable during the subsequent eight years. Despite extensive and repeated instrumental and laboratory workout, only very limited immunological abnormalities were detected (besides the extremely low CD4+ lymphocyte count), and no apparent explaination was found for the disabling paraparesis syndrome. Idiopathic CD4+ lymphocytopenia, whose pathogenesis deserves careful investigation, has been associated with a very broad spectrum of signs and symptoms, ranging from negligible or no disturbances, to severe lymphoproliferative disorders, different opportunistic infections, and other focal diseases, including neurological pathologies. However, the association of a long-lasting profound peripheral CD4+ lymphocyte depletion in absence of any opportunistic infection or neoplasm, and isolated paraparesis and conjunctival microangiopathy, represents an absolutely unique finding, especially due to the apparently stable course of the above-mentioned syndrome.

Another emerging event occurring during HIV infection treated with any antiretroviral therapy: frequency and role of gynecomastia.

To identify HIV-associated episodes of gynecomastia occurred during antiretroviral therapy in a cohort of around 1,000 patients, and to investigate potential correlations with demographic and epidemiological variables, clinical-laboratory markers of HIV disease, metabolic disturbances, and antiretroviral treatment, a cross-sectional survey of 1.007 patients treated for at least 12 months (669 males: 66.4%), identified all subjects with true (ultrasonography-confirmed) gynecomastia, after exclusion of all other predisposing conditions. Special attention was paid to eventual metabolic alterations, including lipodystrophy syndrome, dyslipidemia, and hyperglycemia, and administered antiretrovirals. Fifteen of the 516 evaluable male subjects (2.9%), developed gynecomastia when aged 12-58 years. A concurrent lipodystrophy was present in all cases, while hypertriglyceridemia, hypercholesterolemia, and hyperglycemia were found in 11, 6, and 3 patients, respectively. Duration of seropositivity and time from start of antiretroviral therapy varied significantly, and no correlation was found with HIV disease progression, but 5 patients never received protease inhibitors, while an efavirenz-based treatment apparently prompted gynecomastia in 4 protease inhibitor-naive patients, and worsened this sign in other 4 patients switching from a protease inhibitor-based HAART. One patient developed gynecomastia while on isolated nucleoside analogue therapy. In the whole patient group, stavudine proved the nucleoside analogue administered more frequently and for a more prolonged time. During the follow-up, no significant ameliorament of gynecomastia was observed despite eventual therapeutic changes. Gynecomastia, as an emerging untoward event of treated HIV infection, deserves further investigation, from an epidemiological, clinical, and especially pathogenetic point of view. The frequent association with metabolic abnormalities suggests some common ethiologic pathway with other HAART-related disturbances.

True gynecomastia in congenitally HIV-infected children treated with antiretroviral agents.

Gynecomastia is an emerging untoward effect of HIV-infected patients treated with antiretroviral agents, but frequency, pathogenesis, relationship to single anti-HIV compounds, evolution, and outcome are still under investigation. We report the first two cases of true gynecomastia observed in prepubertal congenitally-infected boys, and clinical, antiretroviral, metabolic, hormonal, virological, and immunological aspects.

Type 1 autoimmune hepatitis: patterns of clinical presentation and differential diagnosis of the 'acute' type.

BACKGROUND: Autoimmune hepatitis (AIH) has three different presentations: chronic, acute and asymptomatic. AIM: To evaluate AIH presentation in Italian patients and investigate criteria that differentiate between acute-type AIH and acute viral hepatitis. DESIGN: Prospective observational study. METHODS: Eighty-six consecutive patients with type 1 AIH and 41 with acute viral hepatitis (controls) were studied. 'Acute' AIH was defined as recent-onset (<30 days) symptoms (jaundice and/or fatigue and/or fever) with marked alterations in serum liver tests; the 'asymptomatic' pattern as the occasional detection of liver abnormalities, and the 'chronic' pattern as the presence of signs and/or symptoms of long-lasting liver disease. RESULTS: Of 86 AIH patients, 59 (68%) presented with the chronic pattern, 22 (26%) with the acute pattern, and 5 (6%) were asymptomatic. 'Acute' patients had higher AST, ALT and bilirubin serum levels (p < 0.0001). No differences were detected with respect to age and serum levels of alkaline phosphatase, gamma-GT, albumin or gamma-globulin. All three groups had similar prevalences of moderate/severe (vs. mild) histological findings and liver cirrhosis. When compared with controls with acute viral hepatitis, 'acute' AIH patients were more often female (82% vs. 24%, p < 0.0001) and had higher serum gamma-globulin levels (26.9 vs. 13.4 g/l, p < 0.0001) and AST/ALT ratio (1.20 vs. 0.61, p < 0.0001). DISCUSSION: Although in Italy type 1 AIH patients usually present with a chronic pattern, some 25% have an acute presentation resembling that of viral hepatitis. 'Acute' AIH and viral hepatitis can be reliably differentiated by simple parameters such as gender, gamma-globulin serum levels and AST/ALT ratio.

Transient reversal of HIV-associated motor neuron disease following the introduction of highly active antiretroviral therapy.

Neurological diseases occur frequently in patients with human immunodeficiency virus (HIV) infection, and include a variety of neuromuscular disorders. On the other hand, only a few cases of motor neuron disease (MND) have been reported to date in HIV-positive patients, even though this neurological complication occurs with a 27-fold greater frequency in these subjects compared with the general population. A retroviral etiology for MND has long been hypothesized, and epidemiological and experimental data suggest a pathogenetic link between HIV infection and MND, because retroviral infections may cause motor neuron damage in both laboratory animals and humans, as a result of various pathways. Furthermore, the introduction of potent, protease inhibitor-based antiretroviral combinations has had a great impact on the natural history of HIV disease and produced a dramatic improvement in some patients with HIV-associated MND, but optimal treatment for this progressive neurological complication has not been well defined. A case of MND in a male HIV-infected patient with significant but transient reversal of neurological symptoms after the use of protease inhibitor-containing antiretroviral regimen is described.