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Biomedical subjects

R Manfredi

Publications and source records attributed to R Manfredi.

At least 217 records · Page 12Linked to original sources

First-line nevirapine in combination with nucleoside analogues compared with nevirapine added to a salvage HAART.

BACKGROUND: Although non-nucleoside reverse transcriptase inhibitors are presently recommended as a part of an initial triple antiretroviral regimen, or as an adjunct to a rescue therapy in patients with poor response to highly active antiretroviral therapy (HAART), no controlled data are available comparing these two different strategies of administration of nevirapine. PATIENTS AND METHODS: Laboratorys data of 59 consecutive patients were prospectively followed up to compare the virologic and immunologic response to nevirapine in those starting a triple therapy combination (group A), versus subjects with prior HAART failure (group B). Laboratory data of 59 consecutive were prospectively followed up. RESULTS: In group A (33 cases), nevirapine was started with two nucleoside analogues in six subjects naïve to antiretrovirals, while in 27 cases it was added to a novel combination of nucleoside analogues. In group B (26 cases), highly experienced patients failing a protease inhibitor-containing HAART, were given nevirapine concurrently with nelfinavir in 19 cases, and with two protease inhibitors in seven patients. Compared with group B patients, subjects belonging to group A showed a more favorable 9-month virologic response (-2.2 Log10 after 9 months with two thirds of patients attaining viral suppression, versus -0.8 Log10 in group A, with only 34.6% of patients with undetectable viremia) (p < 0.001). A greater rise of mean absolute CD4+ lymphocyte count was also observed in group A as opposed to group B (p < 0.001). No significant difference was found comparing the laboratory response of antiretroviral-naïve versus -experienced patients, as well as of participants who changed one versus both nucleoside analogues at the time of nevirapine adjunct in group A, and between patients who switched to nelfinavir versus those treated with two protease inhibitors in group B. CONCLUSION: Nevirapine used as a component of an initial triple anti-HIV regimen seems to ensure a significantly more favorable virologic and immunologic outcome, compared with nevirapine adjunct to a salvage regimen carried out after HAART failure. Controlled data are needed, to better define the role of nevirapine in different therapeutic situations.

Adult↗

Typhoid fever and HIV infection: a rare disease association in industrialized countries.

Typhoid fever is still a global health problem, mainly in tropical and subtropical areas of the world and in developing countries, where relatively elevated morbidity and mortality rates still are present, mostly because of persisting poor hygienic conditions. In the majority of Mediterranean regions, including Italy, the disease is constantly present, though with a low prevalence rate, as a result of an endemic persistence of Salmonella typhi infection.1-4 On the other hand, in industrialized countries, most cases of S. typhi infection are related to foreign travel or prior residence in endemic countries.4-6 In the United States, 2445 cases of typhoid fever have been reported in the decade 1985 to 1994, and the annual number of cases remained relatively stable over time: over 70% of episodes were acquired in endemic countries (mostly Mexico and India).6 The persisting morbidity of S. typhi also may be supported by the increasing resistance rate of this pathogen against a number of commonly used antimicrobial compounds. For instance, 6% of 331 evaluable S. typhi strains were resistant to ampicillin, chloramphenicol, and cotrimoxazole, and 22% of isolates were resistant to at least one of these three agents in a recent survey performed in the United States.6 The spread of antibiotic resistance among S. typhi isolates is emerging in many countries, and multidrug-resistant strains have been isolated, as well as isolates with poor susceptibility to fluoroquinolones,3-5,7-9 so that in vitro susceptibility should be determined for all cultured strains, and antimicrobial treatment should be adjusted accordingly. Nevertheless, fluoroquinolones (e.g., ciprofloxacin and pefloxacin) or third-generation cephalosporins, still represent the best choice for empirical treatment,2,4,6-8,10 and mortality remains rare in Western countries (less than 1% of episodes), although it is expected to be greater in developing areas of the world. The aim of this report is to describe two cases of typhoid fever that occurred in patients with human immunodeficiency virus (HIV) infection, a rarely reported disease association in industrialized countries.

Acquired Immunodeficiency Syndrome↗

Recurrent 'migrainelike' episodes in patients with HIV disease.

Recurrent transient neurological deficits have been described in human immunodeficiency virus (HIV)-infected subjects, but their frequency, pathogenesis, and outcome are still unsettled. We describe 10 HIV-infected patients with transient neurological deficits (0.8% of all patients followed in our department during the last decade). All patients were in the advanced stage of immunological disease. None of the clinical or special investigations performed outside of the attacks indicated an underlying structural lesion of the central nervous system. In 80% of these patients, anticardiolipin antibodies were present. The final outcome was unrelated to these transient neurological deficits which, per se, had a benign course. We discuss the possible etiopathogenetic mechanisms of such episodes and suggest that they may be "migrainelike" events, possibly related to transient functional circulatory abnormalities secondary to an immunological antiphospholipid antibody-dependent mechanism.

Adolescent↗

Invasive mycotic and actinomycotic oropharyngeal and craniofacial infection in two patients with AIDS.

Two cases of invasive oropharyngeal and craniofacial infection caused by fungal and actinomycotic pathogens are described in HIV-infected patients. Two women with a previous diagnosis of AIDS, one with non-Hodgkin's lymphoma and one with Candida oesophagitis, developed a subacute, invasive inflammatory process characterized by ulcerative necrotizing lesions spreading from the oropharynx up to the soft and hard palate, maxillary sinuses and nasal cavity, with extensive soft-tissue necrosis. Although presenting with a very similar clinical picture, infection was due to Actinomyces spp. in the first case, while an apparent dual fungal aetiology (Aspergillus flavus and Candida spp.) was demonstrated in the second patient. Both cases were characterized by remarkable diagnostic difficulties leading to a late final recognition (confirmed by histological examination), and by a partial response to antimicrobial treatment.

AIDS-Related Opportunistic Infections↗

Role of fluconazole in the management of AIDS-related cryptococcosis, according to daily dosing.

No unanimous consent has been reached about treatment guidelines of cryptococcosis in the setting of AIDS, as well as about optimal fluconazole dosing in both initial and suppressive therapy. In order to evaluate the relationship between fluconazole dosing and clinical and microbiological outcome of AIDS-related cryptococcosis, a retrospective study was carried out on 30 consecutive patients. Among the 12 subjects treated with fluconazole doses < 400 mg/day, an unfavorable course was significantly more frequent (early mortality, poor clinical and microbiological response, appearance of early relapses) compared with the 18 patients who received daily doses > or = 400 mg, while no differences were observed between the two treatment groups according to known risk factors for a poor prognosis. When assessing maintenance treatment (22 evaluable cases), the 15 patients receiving oral fluconazole at doses < 200 mg/day showed earlier disease relapse and mortality as opposed to the 7 individuals treated with high-dose fluconazole (> or = 200 mg/day), in the absence of significantly different risk factors for disease recurrence. Our experience pointed out a significant difference in clinical activity of fluconazole in AIDS-related cryptococcosis according to its daily dosing, and suggested 400 and 200 mg as the threshold daily dose for an effective initial and suppressive therapy, respectively, since the probability of treatment failure seemed greater with low-dose drug administration, after controlling data for prognostic markers of disease severity. Controlled studies are warranted, comparing high-dose fluconazole with standard regimens containing amphotericin B in the treatment of AIDS-associated cryptococcosis, and identifying the best fluconazole dosing for both acute-phase and maintenance treatment.

AIDS-Related Opportunistic Infections↗

Acinetobacter infections in patients with human immunodeficiency virus infection: microbiological and clinical epidemiology.

BACKGROUND: We evaluated the role of complications caused by Acinetobacter spp. in the setting of HIV infection. METHODS: Clinical records of 1,923 consecutive HIV-infected patients hospitalized in a 9-year period were retrospectively reviewed, in order to identify all cases of Acinetobacter spp. complications, and to assess their occurrence and outcome according to several epidemiological, clinical and laboratory parameters. RESULTS: Ten patients out of 1,923 (0.52%) developed Acinetobacter spp. infections: sepsis in four cases, urinary tract infection in three, pneumonia in two and septicaemic pneumonia in the remaining patient. All patients were severely immunocompromised, as shown by a mean CD4+ lymphocyte count of 122 cells/microl and a frequent prior diagnosis of AIDS. As opposed to other infections, septicaemia was associated with a significantly lower CD4+ cell count and a more frequent occurrence of neutropenia. Hospital-acquired Acinetobacter spp. infections were significantly more frequent than community-acquired ones, and prevailingly involved patients with AIDS and leucopenia, being responsible for frequent blood dissemination. Antimicrobial, corticosteroid and cotrimoxazole treatment were frequently carried out during the month preceding disease onset. Antibiotic susceptibility studies proved the complete resistance of microbial isolates to ampicillin and cephalothin and poor sensitivity to second-generation cephalosporins and gentamicin, while greater susceptibility was shown to ceftazidime, netilmicin and amikacin, followed by piperacillin, cotrimoxazole and quinolones. Appropriate antimicrobial treatment led to clinical and microbiological cure in all cases, with no related mortality or relapses. CONCLUSIONS: Since only 23 episodes of HIV-associated Acinetobacter spp. infections have been described to date in 11 different reports (nine cases of bacteraemia, eight of pneumonia, two of urinary tract involvement, one of intravenous access device infection, one of meningitis and two with unspecified localization), our series represents the largest one dealing with HIV-associated Acinetobacter spp. infections. According to our experience, Acinetobacter spp. may be responsible for appreciable morbidity among patients with HIV infection, above all when a low CD4+ cell count, neutropenia and hospitalization are present. Clinicians and microbiologists who work in the field of HIV infection should consider the potential pathogenic role of Acinetobacter spp. organisms even in the absence of some presumed risk factors, because of the relationship between these infections and immunodeficiency, hospitalization, other infectious complications, prior antibiotic and steroid treatment and extended antimicrobial resistance patterns.

Acinetobacter↗

The use of efavirenz as a part of late rescue antiretroviral treatment.

PURPOSE: Because rescue antiretroviral strategies are increasingly needed, patients' response to a late salvage treatment including efavirenz plus a novel protease inhibitor (PI), with or without at least one novel nucleoside analogue, was assessed. METHOD: 41 consecutive patients, who underwent four or more prior therapeutic failures and received nucleoside analogues alone for > or = 18 months and a PI-based HAART for > or = 15 months, had a 12- to 24-month prospective follow-up. 6 patients who interrupted treatment after 3-8 weeks because of side effects were excluded. In the remaining 35 evaluable participants, the efavirenz-containing rescue regimen included nelfinavir in 23 cases, indinavir in 7, ritonavir in 2, and ritonavir plus hard gel saquinavir in the remaining 3 cases. 17 of 35 patients concurrently introduced one or more novel nucleoside analogues. Initial mean viremia was 4.8 +/- 0.9 log(10) HIV RNA copies/mL, while mean baseline CD4+ lymphocyte count was around 100 cells/microL. Genotyping resistance testing was obtained at the time of treatment modification. RESULTS: The virologic response was both limited and transient. A significant drop of mean viremia was reached at the third month (-0.7 log(10)), but it was not maintained beyond the sixth month; only 4 patients reached viral suppression during the first 6 months. A more evident and sustained benefit on CD4+ cell count was observed throughout the study (p <.007, compared with baseline). The 31 patients who remained evaluable beyond 12 months did not show relevant modifications of laboratory parameters. The patient subgroup that received > or = 1 novel nucleoside analogue at the time of efavirenz adjunct had a significantly more favorable virologic outcome until the ninth month of follow-up and included all cases who reached viral suppression. Antiviral resistance pattern showed frequent mutations of the protease gene, and a cross-resistance with nonnucleoside reverse transcriptase inhibitors (NNRTIs; found in 19 cases of 41), although our patients were not previously exposed to these compounds. CONCLUSION: A late salvage therapy based on efavirenz plus a novel PI is not expected to achieve a complete and sustained virologic success in patients highly experienced with both nucleoside analogues and PIs and with a concurrent elevated viremia, probably due to extensive resistances acquired through time. Our rate of virologic failure proved even greater than that observed in previous studies of salvage therapy including NNRTIs. Prior long-term treatment with isolated nucleoside analogues and HAART, the use of highly sensitive techniques for monitoring of viremia, and a quite prolonged observation period may have played a role. However, the CD4+ response proved to be more evident and sustained than the virologic one, and the concurrent introduction of >/= 1 nucleoside analogue added significantly, especially during the first 9 months of salvage therapy.

Adult↗

Growth hormone (GH) and the immune system: impaired phagocytic function in children with idiopathic GH deficiency is corrected by treatment with biosynthetic GH.

Thirty-seven prepubertal children evaluated for severe growth retardation were studied by assessment of total granulocyte, monocyte and lymphocyte count, lymphocyte subsets CD3+, CD3+Dr+, CD3+Dr-, CD4+, CD8+, CD8+CD57+, CD8+CD57-, CD16+, CD20+ and CD23+, serum immunoglobulin concentrations, and phagocytic activity of circulating neutrophils and monocytes (by a flow cytometric assay). Idiopathic GH deficiency was diagnosed in 21 of 37 patients; the remaining 16 healthy subjects served as controls. Fourteen patients received biosynthetic GH (rhGH), and their immune parameters were assessed at baseline and after 6 months of therapy. Phagocytic function mediated by both polymorphonuclears and monocytes was significantly impaired in GH-deficient subjects compared to controls (p < 0.003 for neutrophils, p < 0.007 for monocytes), while a significant increase of phagocytic activity was obtained during long-term rhGH replacement therapy (p < 0.02 for neutrophils, p < 0.001 for monocytes), thus suggesting that GH may affect the functional activity of circulating phagocyte cells. No significant differences were found in total granulocyte, monocyte and lymphocyte counts, T- and B-lymphocyte subsets and immunoglobulin levels, between GH-deficient patients and controls, and between values observed before and during rhGH substitution treatment.

Adolescent↗

Magnetic resonance imaging of pelvic endometriosis.

Endometriosis is a multifocal disease involving multiple pelvic sites. Although laparoscopy is the elective exam in the study of patients with clinically suspected endometriosis, MR imaging represents a valid noninvasive procedure for the study of areas unapproachable with laparoscopy. On MR imaging, areas of endometriosis over 1 cm in size appear homogeneously hyperintense in T1-weighted images and hypointense in T2-weighted images, while areas of endometriosis less than 1 cm in size appear hyperintense in T1-weighted images and with variable signal in T2-weighted images. Endometriosis may also appear as small cystic lesions, hyperintense in T1-weighted images. While MR imaging has some limitations in the visualization of small endometriotic implants and adhesions, it has the ability to characterize the lesions, to study extraperitoneal locations and the contents of pelvic masses. The reliability of MR imaging findings of endometriosis and the assessment of pelvic organ involvement is important for guiding subsequent laparoscopy.

Adult↗

[Prion diseases. The association of bovine spongiform encephalopathy with new variant of Creutzfeldt-Jakob disease].

This review summarizes current knowledge of prion diseases and investigates connections between the bovine spongiform encephalopathy epidemic, observed in Great Britain since 1986, and the new variant of human Creutzfeldt-Jakob disease, reported for the first time in 1996. Information from the international literature and results of the most recent experimental studies on prion diseases and transmissible spongiform encephalopathies are evaluated, and particular attention is focused on the possible transmission of the etiological agents of spongiform encephalopathy, the prions, from animals to humans. Epidemiological, clinical, and histopathological data and experimental results seem to confirm the suspected link between bovine spongiform encephalopathy and the new variant of Creutzfeldt-Jakob disease. In this context, transmission of prions from infected cattle to humans by oral intake seems not only possible but also very probable.

Animals↗

An apparent idiopathic case of relapsing acute pancreatitis.

We describe a case of relapsing acute pancreatitis apparently idiopathic in a 55-year-old man. The patient did not smoke and was a modest and irregular drinker of wine. Endoscopic retrograde cholangiopancreatography showed an initial dilatation of secondary ducts like a chronic pancreatitis of class I of Cremer. Ultrasound and computed tomography resulted negative for pancreatic lesions. In the follow-up however, magnetic resonance cholangiopancreatography detected the presence of an intraductal mucin-hypersecreting neoplasm, a duct-ectatic mucinous cystic tumor of the pancreas, in the uncinate process. This is a benign lesion clearly recognized nowadays by magnetic resonance cholangiopancreatography, because this radiological technique shows the grape-like clusters of cystic lesions in secondary ducts communicating with the main duct on the same plane. The radiological picture above excludes a malignant lesion and a biopsy specimen is not required. Furthermore, an intraductal mucin-hypersecreting neoplasm of the pancreas does not require an immediate surgical resection because of its slow evolution and can be followed-up. Conversely cystoadenocarcinoma spreads in peripheral ducts and does not communicate with the Wirsung duct. It requires both surgical resection and a biopsy specimen for histological diagnosis. In the last episode of acute pancreatitis, a sphincterotomy was performed at endoscopic retrograde cholangiopancreatography and our patient had no more pain for one year.

Acute Disease↗

[Malignant biliary hilar stenosis: MR cholangiography compared with direct cholangiography].

AIM: To assess the diagnostic value of three-dimensional (3D) magnetic resonance cholangiography (MRC) versus direct cholangiography such as endoscopic retrograde cholangiography (ERC) and percutaneous transhepatic cholangiography (PTC) in malignant biliary stenosis. MATERIAL AND METHODS: Twenty-nine patients (15 female and 14 male) (mean age 62 years) with malignant biliary strictures underwent MRC and ERC. Breath-hold 3D steady state free precession MR cholangiography was performed on a 1.5-T imager in the patients before ERC. In 25 patients findings at ERC/PTC were considered the standard of reference: 19 patients underwent ERC, 5 PCT and 1 both ERC and PTC due to unsuccessful papilla cannulation during the endoscopic examination. In the 4 remaining patients the surgical specimen was considered the standard of reference. In the 29 patients studied, histology performed during direct cholangiography and the examination of the surgical specimens demonstrated that the malignant hilar stenoses were caused by hilar cholangiocarcinoma (n=7), cholangiocarcinoma of the distal VBP (n=1), gallbladder cancers (n=6), endometrial metastasis (n=2), ovary metastasis (n=1), colon metastasis (n=1), breast metastasis (n=1). The correct identification of biliary stenosis and extension of the tumor (according to the Bismuth classification) by MR cholangiography and ERC were independently assessed by two readers blinded to each other's report. The results were compared. RESULTS: Identification of biliary stenosis and neoplastic extension were accurate in respectively 29/29 (100%) and 26/29 (89%) cases with MR cholangiography. The comparison of ERC/PTC and MRC images yielded the following results: Bismuth Type I (6 vs 6), Type II (5 vs 8), Type III (13 vs 10), Type IV (5 vs 5). Our results indicate that MR is less capable of identifying the extension of small lesions at the primary confluence of bile ducts than are ERC/PCT. DISCUSSION AND CONCLUSIONS: MR cholangiography is a non-invasive technique for biliary tract imaging. It does not require administration of contrast medium and allows complete visualisation of the biliary ducts. MR cholangiography allowed accurate diagnosis of malignant hilar stenosis providing equal information as direct cholangiography and may therefore obviate the need for ERC/PTC.

Aged↗

High resolution spiral computed tomography of the pancreas.

Computed tomography (CT) is a very useful tool in the assessment of pancreatic disease. Searching for subtle signs, as in chronic pancreatitis or staging of adenocarcinoma, high spatial and contrast resolution is needed. The high resolution computed tomography (HRCT) technique for pancreatic scans, and its evolution from dynamic CT to multislice spiral CT, is described. 2D and 3D dimensional reconstructions are depicted and their role in diagnosis is focused. Together with spatial resolution, contrast enhancement protocols are discussed, aimed to achieve optimal contrast between the lesion and normal parenchyma.

Contrast Media↗

Magnetic resonance pancreatography (MRP): morphology and function.

MRCP is able to non-invasively assess the pancreatic ducts, with moderate/high agreement with ERCP: There is however a high number of false negative results, mainly due to the small size of the main pancreatic duct, especially in the tail, and side branches. Secretin stimulates the exocrine pancreas with accumulation of fluid and bicarbonates in the ductal system, and subsequent enlargement. This increase in caliber improves the assessment of the morphology of pancreatic ducts and their abnormalities. MRCP accuracy in assessing ductal abnormalities, improves after secretin administration. Furthermore, dynamic MRCP during secretin administration is also able to afford the functional evaluation of the pancreatic flow dynamics. Papillary stenosis, either idiopathic or due to Santorinicele, is easily diagnosed by means of S-MRCP. Furthermore a noninvasive assessment of the pancreatic exocrine reserve can be performed with dynamic MRCP during secretin administration.

Cholangiography↗

Imaging of acute pancreatitis.

Pancreatitis is one of the most complex and clinically challenging of all abdominal disorders. It is classified according to clinical, morphologic and histologic criteria. The primary role of radiologic imaging in patients with suspected pancreatitis is to confirm or exclude the clinical diagnosis of pancreatitis. Second, if possible, the cause of the disease is established with the assessment of disease severity and detection of complications. Imaging can also provide guidance for percutaneous therapy. Sonography in acute pancreatitis is a good screening test in patients with suspected biliary pancreatitis and a mild clinical course. Contrast-enhanced CT is preferred for patients with acute pancreatitis because it can accurately diagnose and stage the disease and the necessary information for percutaneous management is provided. The diagnosis of acute pancreatitis on MRI relies on the presence of morphologic and peripancreatic changes. Pancreatic necrosis and complications of acute pancreatitis such as hemorrhage, pseudocysts or abscesses are well-examined by MRI.

Acute Disease↗

Imaging of chronic pancreatitis.

Chronic pancreatitis is characterized by progressive, irreversible morphologic changes whose most common cause is excessive alcohol intake. Radiologic imaging plays a major role in the diagnosis, staging of disease severity, detection of complications and selection of treatment options. The sensitivity of US ranges from 60% to 70% while its specificity is higher reaching 80%-90% in the detection of abnormalities of main pancreatic duct. As for CT, its sensitivity and specificity in the diagnosis of chronic pancreatitis, in recent studies is 74% and 85% respectively. The performance of Magnetic Resonance cholangiopancreatography was shown to be enhanced by secretin stimulation with better visualization of ductal and parenchymal changes. However, endoscopic retrograde cholangiopancreatography is the most sensitive indicator of the presence and extent of the disease. Ductal abnormalities can be used to classify chronic pancreatitis.

Cholangiopancreatography, Endoscopic Retrograde↗

Staging of pancreatic ductal adenocarcinoma with spiral CT and MRI.

Detection of pancreatic adenocarcinoma is crucial for accurate staging both with spiral CT and dynamic MRI; consequently an accurate technique is required and so-called pancreatic phase is recognized as the best one for tumor conspicuity. For vascular involvement optimal results have been achieved in assessing unresectability; vein involvement seems more difficult to be defined as it is sustained by a different spread compared to arterial involvement. Grading of vessel circumference contact represents the best tool in "venous" staging, but shape deformation and collateral veins dilation are also important signs. Lymph node staging is less accurate, lacking in specificity, but spiral CT demonstrated better results if compared with dynamic MRI. Assessment of liver metastases has been improved by the advent of spiral CT and dynamic contrast enhanced MRI, while peritoneal staging seems to be unaffected. In conclusion, both spiral CT and dynamic contrast enhanced MRI are accurate in pancreatic adenocarcinoma staging, mainly for vessels and liver involvement; no definite differences have been established, because only a few studies have compared them both with state-of-art techniques. Therefore standardized multicentric trials are desirable. Up to now, the choice of which technique to employ should be based on local expertise; moreover, the aggressive approach of surgical equipes should be kept in mind.

Carcinoma, Pancreatic Ductal↗