Dynamic magnetic resonance imaging in acute pyelonephritis.

PURPOSE: This study was conducted to evaluate the role and clinical impact of dynamic magnetic resonance imaging (MRI) in the diagnosis and follow-up of acute pyelonephritis (APN). MATERIALS AND METHODS: We retrospectively reviewed 442 consecutive renal MRI examinations (279 diagnostic and 163 follow-up) performed in 285 patients (mean age 42.17 years), 35 of whom were kidney transplant recipients with a clinical suspicion of APN. RESULTS: MRI showed signal abnormalities suggestive of APN in 125/244 (51.2%) patients with native kidneys. Except for two examinations performed without paramagnetic contrast material, the inflammatory foci appeared as areas of nonenhancement: single in 39/123 cases, multiple in 84/123, unilateral in 60/84 and bilateral in 24/84. Abscesses were present in 40/123 (32.5%) positive cases. During follow-up, we observed complete normalisation of MRI signs in 86/103 patients; 17/103 (16.5%) cases evolved into fibrosis and scarring. In 15/35 (42.8%) patients with transplanted kidney, MRI was positive for APN. CONCLUSIONS: Renal MRI is an effective tool for the diagnosis and follow-up of APN both in patients not at risk and those at higher risk, such as those with a transplanted kidney. The high costs of the examination are offset by better treatment planning and early complication detection.

Improvement in relative survival of patients with vasculitis: study of 101 cases compared to the general population.

Immunosuppressive treatment has changed the prognosis of renal vasculitis over time, but improvement in prognosis is difficult to analyze in different historical periods, and can be better demonstrated by comparison with life expectancy of sex- and age-matched people. Long-term survival of 101 patients diagnosed with systemic vasculitis at our center from 1975 to 2002 was retrospectively evaluated in comparison with that of the Region's age- and sex-matched population. Patient and kidney survival significantly increased over time. Multivariate analyses showed that risks of patient and renal death decreased by 10% and 7%, respectively, at each year of follow-up, and increased by 6.3% and 5.2% for each year of age. Relative survival significantly improved over time, approaching that of the general population for cases diagnosed after 1993, mainly in women < 60 years (from 0.671 at 5-years in the first period to 0.916 in the last period), while 5-year-relative-survival was still 0.530 and 0.682 in men and women greater than 60 years, respectively. Poisson-based multinomial analyses confirmed the significant risk of the first periods of diagnosis and of dialysis in worsening of the relative survival of patients compared to that of the general population. Life expectancy in patients with renal vasculitis has improved over time, paralleling a significant increase in steroid pulse/cyclophosphamide association therapy and an earlier diagnosis due to the introduction of the ANCA test. Relative survival has considerably improved, and now approaches that expected in the general population for women, but not for men.

Human polyomavirus BK in patients with lupus nephritis: clinical and histological correlations.

Polyomavirus BK (BKV) reactivation can occur in immunodeficient patients. Few studies on BKV infection in patients with systemic lupus erytematosus (SLE) nephritis are available. Aim of this study was to analyse the prevalence of BKV infection by quantifying viral load and to investigate the association with clinical and histological parameters indicating duration, type and activity of SLE.BKV-DNA was evaluated by polymerase chain reaction in serum (sBKV) and urine (uBKV) specimens from 40 patients with SLE nephritis and 29 healthy controls. Renal function, urinary activity, clinical index of SLE activity [SLE Disease Activity Index (SLEDAI) score], CD4+/CD8+ ratio, histological classes and duration of SLE nephritis were compared according to the BKV-DNA-positivity.sBKV was present in 15% of SLE patients and in 13.8% of controls; uBKV in 32% of SLE patients and in 17.2% of controls. There was no significant difference in terms of kidney function, urinary activity, SLEDAI score, presence of anti-dsDNA antibodies, CD4+/CD8+ ratio and BKV viremia and/viruria, as well as there was no significant correlation between SLEDAI score, anti-dsDNA antibodies titers and median viral load. Duration of nephropathy tended to be shorter in patients with BKV viremia and/or viruria; proteinuria/creatininuria ratio tended to be higher in patients with positive sBKV and uBKV. BKV-DNA-positivity tended to be more frequent in patients treated with an immunosuppressive agent versus those on steroid treatment. Reactivation of BKV infection can occur in patients with SLE, although prevalence data do not significantly differ from those obtained in the control group. The trend toward an association between BKV infection and degree of proteinuria and less duration of SLE nephritis could indicate a major susceptibility to develop BKV infection in more active phases of the disease. The role of BKV reactivation in terms of clinical parameters and histological pattern, as well as the role of therapeutic protocols in the onset of BKV reactivation and, conversely, the therapeutic implication of BKV reactivation in SLE patients remain to be defined and should be addressed in further studies on a larger number of patients.

Antibiotic treatment for acute 'uncomplicated' or 'primary' pyelonephritis: a systematic, 'semantic revision'.

The definition of acute pyelonephritis is controversial. There are two contrasting approaches: (1) acute pyelonephritis is a severe infectious disease involving the kidney parenchyma, and specific imaging techniques are required for diagnosis; (2) acute pyelonephritis is a urinary tract infection, and diagnosis and therapy follow simplified clinical and laboratory pathways. In this study, recent randomized controlled trials (RCTs) were systematically reviewed and the diagnostic and therapeutic approaches to acute 'uncomplicated' pyelonephritis were analysed. Medline, Embase, Cochrane Central Register of Controlled Trials (CCTR) and Chinal were searched employing Mesh, Emtree and free terms on 'pyelonephritis'. Limits included human, period (1995-2004), and trials-reviews (where available). In total, 904 references and 175 full-text were retrieved; 29 were pertinent RCTs. Seven RCTs were added from reference lists (indexed on urinary tract infections). Imaging examinations were performed in 11 of 14 studies on children (diagnostic requisite in two) and in two studies on adults; scarring was not analysed in adults. Clinical definitions varied widely (fever >37.8 to >39 degrees C, culture titres 10(4) >10(5)). Studies on adults were limited to short-term end-points (microbiological sterilization, clinical improvement). Duration of therapy was 4-20 days. The trend was towards shorter periods of therapy, mainly on an outpatient basis; intravenous therapy, if performed, was usually limited to the first 1-3 days. For acute uncomplicated pyelonephritis, the tendency is towards 2 weeks of mainly oral antibiotic therapy. However, the recent literature on adults does not discriminate among different upper urinary tract infections nor does it provide data on renal scarring. While cost constraints point towards short-term therapies, further studies are needed to assess the prevalence and long-term effect of kidney scars.

Development of kidney scars after acute uncomplicated pyelonephritis: relationship with clinical, laboratory and imaging data at diagnosis.

BACKGROUND: Acute pyelonephritis is a potential cause of kidney scars. AIM: To evaluate the relationship between clinical, laboratory and imaging data and the development of kidney scars in acute pyelonephritis. METHODS: All consecutive patients hospitalized for acute uncomplicated pyelonephritis in our nephrology unit from June 1996 to June 2004 were considered: 58 females, median age 25.6 years (16-52). Diagnosis of pyelonephritis required parenchymal lesions shown by CT or NMR scan. RESULTS: The lesions were bilateral in 17.2% (10/58) patients, unilateral, but multifocal in 81.0% (47/58); at CT or NMR, 65.5% of the lesions were classified as simple, 19% with tendency to colliquation and 15.5% abscessual. The median interval between first symptoms and diagnosis was 5 days (1-25); at referral, only 20.7% had a positive urine culture and 94.8% (55/58) had undergone previous antibiotic treatment. The therapeutic protocol required intravenous therapy for > or = 2 weeks, followed by 2-4 weeks of oral therapy. At 6-8 months, the prevalence of kidney scars was 29.3%. Their development was highly correlated with the type of lesions at diagnosis (highest risk with abscessual lesions; uni- and multivariate analysis). No other clinical or laboratory marker (age, fever, positive cultures, levels of acute phase reactants, interval between onset and diagnosis) was correlated with the outcome (scars). CONCLUSIONS: The type of lesion at diagnosis of acute uncomplicated pyelonephritis is highly correlated with the development of kidney scars. Further studies are needed to test the therapeutic schedules tailored according to the imaging data.

Antibodies to Chlamydia pneumoniae in healthy children from Bari, south Italy.

Specific IgG and IgM antibodies to Chlamydia pneumoniae were evaluated by microimmunofluorescence test in a group of healthy subjects (age 0-18 years). Antibody titers (IgG) > or = 1:16 were found in 9.7% of the age group 0-1 years, in 5.3% of the group of 2-3 years and rose to 19% in children of the group 4-6 years. The seroprevalence was 11% and 17.1% in the group 7-12 years and 13-15 years, respectively. In the last group of 16-18 years the seroprevalence was 9.1%. The overall seroprevalence was 11.8% and C. pneumoniae infection is acquired before school age. In addition, in our pediatric patients it seems that C. pneumoniae does not play an important pathogenic role, being responsible for only 1.6% of the acute lower respiratory infections. The factors that may account for these findings are discussed.

Polarizing response of human polymorphonuclear cells to Vibrio cholerae.

Leucocytes have the capacity to respond to chemotactic factors by becoming morphologically and functionally polarized and this method has been found to be suitable for measurement of chemotaxis. This work evaluates the effect of whole Vibrio cholerae biotype El Tor polarization of human polymorphonuclear (PMN) cells in comparison with strains of V. cholerae NAG, Vibrio alginolyticus and Salmonella typhi. V. cholerae O1 induced, at different cell/bacteria ratios, a significant increase in the percentage of polarized cells compared with PMN cells stimulated with formylmethionyl-leucyl-phenylalanine (FMLP) and the other bacteria tested. The capacity of V. cholerae O1 to induce PMN cell polarization may play a role on the inflammatory response recently described in diarrhoea caused by V. cholerae.

Immunological responses in patients with tuberculosis and in vivo effects of acetyl-L-carnitine oral administration.

Tuberculosis (TBC) is characterized by a complex immune response which parallels the clinical course of the disease. In this respect, acquired resistance, delayed hypersensitivity reaction and anergy are the main types of immune reactivity to mycobacterial antigens. In view of the presence of nonspecific and specific immune deficits in TBC patients, a clinical trial was carried out in a group of 20 individuals with active pulmonary TBC by oral administration of acetyl-L-carnitine (ALC). This drug, which has been shown to possess immunomodulating activities, was able to upregulate the T-dependent antibacterial activity in TBC patients after 30 days' treatment, while the same activity decreased in patients receiving placebo only. On the other hand, ALC did not modify serum levels of tumour necrosis factor-alpha, in the same individuals. This cytokine plays a detrimental rather than beneficial role in TBC pathogenesis. In the light of these data, ALC seems to be a powerful immunomodulator in the course of Mycobacterium tuberculosis infection and other mycobacteriosis.

Neurological damage mediated by cytokines.

Our results suggest that CKs, in particular Interleukin-1 and Tumor Necrosis Factor (TNF)-alpha, are involved in the pathogenesis of some neurological disorders and HIV infection. Infact, we observed an exaggerated spontaneous release of TNF-alpha in patients with migraine without aura. Furthermore, in a broad spectrum of patients with HIV-infection we have also found increased amounts of serum TNF-alfa and IL-1. Interestingly, a strict correlation between plasma lipopolysaccharide (LPS) and IL-1 or TNF-alpha levels seems to exist in both group of patients, thus indicating that LPS could account for the production of CKs in the course of the above diseases.

Influence of ST 789 on interleukin-1, interleukin-2 and interferon-gamma production from normal human peripheral blood mononuclear cells.

ST 789, previously named PCF 39, is a synthetic hypoxanthine derivative endowed with immunomodulating properties. However, the mode of action of this compound on immunocompetent cells has not yet been elucidated and, in particular, no evidence has been provided on its ability to trigger monokine (MK) and lymphokine (LK) release. In this framework, here we have evaluated the influence of ST 789 on interleukin (IL)-1, IL-2 and interferon (IFN)-gamma production from normal human peripheral blood mononuclear cells (PBMC). Results will show that following stimulation of PBMC with lipopolysaccharides (LPS) or lectins [phytohemagglutinin (PHA) and concanavalin A (Con A)] in the presence of increasing concentrations of ST 789 no modification of cytokine release is obtained, in comparison with cultures activated with LPS or lectins. In addition, this hypoxanthine is not able per se to induce release of MKs and LKs. The overall results suggest that ST 789 acts on the immune system through mechanisms which are not dependent on the release of ILs and IFN-gamma.

Role of thymic hormones in neuroimmunomodulation. Their use in patients with phobic disorders.

Many evidences support the existence of a bilateral connection between the thymic gland and the hypothalamic-pituitary-adrenal axis (HPAA). In this respect, neurohormones such as the adrenal corticotropin hormone and glucocorticoids cause thymic involution, while the growth hormone and the prolactin upregulate thymic functions. On the other hand, a thymic hormone, the thymosin fraction 5, activates the HPAA, thus closing-up the regulatory loop between immune system and nervous system. In this review, a clinical trial with two thymic hormones (Timostimolina and Thymopentin) in agoraphobic patients with phagocytic dysfunctions is reported. Results obtained indicate that both substances lead to a partial and temporary immunological recovery, since a further depression of phagocytic activities occurs in coincidence with panic attack. The use of alternative immunomodulators in these patients is discussed.

Are TNF-alpha and IL-1 beta relevant in the pathogenesis of migraine without aura?

Migraine without aura (MWA) is a clinical condition characterized by multiple immune deficits, which may play an important role in the pathogenesis of the disease. In this respect, previous studies have demonstrated that patients with MWA exhibit profound dysfunctions of phagocytosis and killing exerted by polymorphonuclear cells (PMN) and monocytes. This may correlate with the increased frequency of infectious processes observed in these patients. The overall results suggested to evaluate the presence of circulating cytokines (CKs) in subjects affected by MWA. In particular, the present data point out an exaggerated spontaneous release of tumor necrosis factor (TNF)-alpha in a group of MWA individuals, which correlates with detectable levels of bacterial lipopolysaccharides (LPS) in their plasma. In view of the different biological activities displayed by TNF-alpha in the host, such as effects on the nervous and vascular systems, hemodynamics modifications and demyelinating properties, the intervention of this CK in the pathogenesis of MWA will be discussed.

Lyme disease in Italy.

We present the first cases of Lyme disease found in Italy. The diagnosis was based on clinical and laboratory data. The antigen used for indirect immunofluorescence (I.I.F.) was kindly supplied to us by Prof. R. Ackermann (Köln). Reciprocal titer was 64 in five patients, 128 in six, 256 in three and 512 in one. The patients came either from the Eastern Ligurian Coast or the Trieste Karst: these are consequently the first two Italian areas where Lyme disease has been recognized up to the present.

Endotoxin-like activity associated with Lyme disease Borrelia.

The newly recognized spirochete, Borrelia burgdorferi, the causative agent of Lyme Disease, has been examined for endotoxin-like activities as measured by the standard Farmacopea Ufficiale della Republica Italiana rabbit fever test and the Limulus amoebocyte lysate assay. The suspension of heat-killed microorganism caused a febrile response at a dose of 1 X 10(8) bacteria pro kilo. Similar results were obtained in the Limulus assay where the heat-killed spirochetes stimulated formation of solid clot until the concentration of 1 X 10(5) per ml. Both in pyrogen test and in Limulus assay heat-killed Escherichia coli exhibited a higher degree of potency. These results show that LD-Borrelia possess endotoxin-like activities which could help in understanding the pathogenesis of the clinical symptomatology of the disease.

Endotoxicity associated with the Lyme disease Borrelia: recent findings.

The endotoxicity of Borrelia burgdorferi, the causative agent of Lyme Disease, a tick-borne spirochetosis, was studied using Limulus assay and pyrogen test in rabbit. Some suspensions of Ixodes ricinus and Ixodes dammini associated Borrelia were able to gelify Limulus lysate and demonstrated a febrile response in rabbit. These findings and other recent data demonstrating an endotoxin-like activity of the Lyme Disease agent are discussed in the context of the pathogenic mechanisms of the illness.

Lyme disease in Italy: first reported case.

The AA describe the first italian case of Lyme Disease in a middle aged woman: the patient developed after a tick bite the classical erythema chronicum migrans lesions and one month later an oligoarthritis. By indirect immunofluorescence assay it has been found a significant titre compatible with an infection by Borrelia burgdorferi, the causative agent of Lyme Disease.

In vitro generation of procoagulant activity by Corynebacterium parvum-stimulated mononuclear leukocytes.

Thromboembolic complications are known in cancer patients after i.v. administration of Corynebacterium parvum. We examined the ability of this organism to induce production of procoagulant activity by human blood mononuclear leukocytes in vitro. After 4 hours incubation Corynebacterium parvum was an effective stimulant for mononuclear leukocytes, behaving in the same way as the typical gram-negative bacterium Escherichia coli, whereas mononuclear cells incubated with Staphylococcus aureus were not affected. Corynebacterium parvum used was found devoid of endotoxin by the Limulus assay and was not affected by Polymyxin B, which, on the contrary, inhibited Escherichia coli-induced production of procoagulant activity. Intact Corynebacterium parvum may be required for the production of procoagulant activity and, although this specific aspect of the research will require further study, from the exposed data it is concluded that such a production could be a factor contributing to the pathogenesis of the coagulopathy following Corynebacterium parvum therapy.

In vitro effect of Leptospira icterohaemorrhagiae on human mononuclear leukocytes: comparison of virulent with non virulent strain.

The in vitro effect of a virulent and a non virulent strain of Leptospira interrogans serotype icterohaemorrhagiae on human peripheral mononuclear cells was investigated. After addition of bacteria to citrated whole blood the production of mononuclear cell procoagulant activity (tissue factor) was observed. Indeed mononuclear cells isolated from whole blood-bacteria mixtures after prolonged incubation shortened the recalcification time of normal plasma. The virulent strain induced a significantly higher procoagulant activity than non virulent and this effect was dependent on the number of bacteria. The production of tissue factor, a potent trigger of blood clotting, by Leptospira icterohaemorrhagiae could help to understand the mechanism(s) responsible for the activation of intravascular coagulation sometimes associated with leptospirosis.