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Biomedical subjects

G Luzi

Publications and source records attributed to G Luzi.

At least 19 recordsLinked to original sources

Inflammatory cytokines and HIV-1-associated neurodegeneration: oncostatin-M produced by mononuclear cells from HIV-1-infected individuals induces apoptosis of primary neurons.

Neurologic abnormalities are common in HIV-1-infected patients and often represent the dominant clinical manifestation of pediatric AIDS. The neurological dysfunction has been directly related to CNS invasion by HIV-1 that is principally, if not exclusively, supported by blood-derived monocytes/macrophages and lymphocytes. By using primary long term cultures of human fetal sensory neurons as well as sympathetic precursors-like neuronal cells, we determined that blood-derived mononuclear cells from HIV-1-infected individuals spontaneously release soluble mediators that can potently inhibit the growth and survival of developing neurons as well as the viability of postmitotic neuronal cells by inducing apoptotic cell death. Analysis of the cytokines produced by lymphomonocytic cells, HIV-1 infected or activated, indicated that oncostatin M (oncM) is a major mediator of these effects. Since low TGF-beta1 concentrations were capable of enhancing oncM-mediated neuronal alterations, our data indicate that by acting in concert with other cytokines, oncM may induce neuronal demise in both the developing and the mature brain. Thus, this cytokine may contribute to the setting of the neuronal cell damage observed in HIV-1-infected individuals.

Apoptosis

Gastric pathology in patients with common variable immunodeficiency.

BACKGROUND/AIMS: Common variable immunodeficiency (CVID) is an immunological disorder characterised by defective antibody production. Patients with CVID have a high risk of gastric cancer. It has been suggested that gastric cancer results from an interaction between environmental factors and a genetic predisposition. The role of Helicobacter pylori as an environmental factor in gastric carcinogenesis is of current interest. Moreover, p53 gene mutations have been reported in gastric cancer. This study focuses on the gastric pathology of patients with CVID and correlation with H pylori infection. METHODS: Thirty four consecutive dyspeptic patients with CVID (mean age 49.6 years, range 14-72; 17 men) were included in the study. An upper gastrointestinal endoscopy was performed and biopsy specimens were taken from the antrum, incisura angularis, and gastric body. Biopsies were used for histological assessment, to identify the presence of H pylori, and to evaluate p53 overexpression. RESULTS: H pylori infection was detected in 14/34 (41%) patients. Chronic active gastritis involving both antrum and body was observed more frequently in H pylori positive (79%) than H pylori negative (20%) patients (p = 0.001). Similarly, a histological feature of multifocal atrophic gastritis was found more frequently in infected (50%) than uninfected patients (10%) (p = 0.012). In addition, one case of gastric adenocarcinoma and another of notable dysplasia were observed in the H pylori positive group. Overexpression of p53 was found in six (18%) patients, including one with normal gastric mucosa. CONCLUSIONS: It can be hypothesised that both H pylori and p53 alterations play a role in the gastric carcinogenesis of patients with CVID.

Adolescent

Immune-derived cytokines in the nervous system: epigenetic instructive signals or neuropathogenic mediators?

The investigation of the effects of inflammatory cytokines (IC) on the growth and differentiation of neural cells has provided new insights on the role of such soluble mediators in nervous system development and/or plastic remodeling as well as in the pathogenesis of inflammatory neurodegenerative disorders, which are characterized by chronic IC dysregulation in the central nervous system (CNS). Thus, the study of the interaction between CNS and immune-derived soluble signals in physiological or pathological conditions is of increasing interest. This review first discusses experimental evidence supporting the instructive/permissive role of immune-derived cytokines on CNS development and plasticity. Next, we focus on human neurological disease states such as multiple sclerosis and the neurodegeneration associated to the acquired immune deficiency syndrome in which different inflammatory cytokines have been proposed as potential neuropathogenic mediators.

Animals

Use of voriconazole in treatment of Scedosporium apiospermum infection: case report.

We report a case of disseminated Scedosporium apiospermum infection in a neutropenic patient with acute myeloid leukemia. Due to progression of the mycosis after 7 days of amphotericin B lipid complex therapy and to high susceptibility of the mold to voriconazole in vitro, the patient was treated with intravenous voriconazole. After a few days of therapy, fever disappeared and skin lesions improved. However, the patient died after 1 month due to intestinal bleeding. Despite a negative outcome, this case seems to indicate a promising role for voriconazole in the treatment of S. apiospermum infections.

Acute Disease

Screening patients affected by common variable immunodeficiency.

Chronic immunoglobulin administration decreases the incidence of bronchial and pulmonary infections in patients affected by chronic variable immunodeficiency (CVI). In this study, an ENT screening was carried out in 22 patients affected by chronic variable immunodeficiency and treated with chronic immunoglobulin administration. All the patients underwent ENT physical examination, nasal endoscopy by fiberoptics, mucociliary transport test (MTT), anterior rhinorheomanometry (RRM), nasal provocation test with cold water (ANPT), audiometry and impedentiometry, olfactory evaluation, and paranasal sinus X rays. Dysphagia was present in 91% of the patients, nasal secretion and obstruction in 77%, and hypoacusia, tinnitus, and otodinia in 57%. Rhinitis and pharyngitis were observed in 86% of the patients, and serous middle ear effusion in 50%. Confirmed maxillary sinusitis was observed in five patients. Hyposmia was observed in 50% of the patients. MTT was significantly longer in the patients than in the controls (18.0 +/- 10.5 vs. 11.2 +/- 2.4 min; p < .05). Nasal resistance was lower in patients than in controls (0.46 +/- 0.32 vs. 1.11 +/- 0.22 Pa/L.s-1; p < .001). ANPT was positive in 9 patients out of 25 versus 1 control out of 15 (p < .05). Finally, seven patients were affected by transmissive hypoacusia, and one patient by neurosensorial hypoacusia. Our results suggest that chronic immunoglobulin administration in CVI patients is not effective against ENT disorders, probably because of the important role played by nasal hyperreactivity. Frequent ENT examination and early treatment of ENT disorders are therefore suggested in order to prevent chronic disease.

Adolescent

Left ventricular aneurysmectomy; comparison between two techniques; early and late results.

OBJECTIVE: The aim of the present study was to evaluate early and late results of two different surgical techniques for left ventricular aneurysms repair. The conventional aneurysmectomy and direct closure of the ventricular wall and the endoventricular patch plasty. METHODS: We retrospectively reviewed 118 patients operated on for postinfarction left ventricular aneurysm from 1981 to 1994. Eighty-seven patients (Group A) were operated upon between 1981 and 1991 with the conventional technique and 31 patients (Group B) between 1992 and 1994 with the endoventricular patch plasty technique. Preoperative clinical, hemodynamic and echocardiographic evaluation with operative procedures and early postoperative results of all patients are reported. We also analyzed results of late clinical and echocardiographic controls of 34 patients of Group A and all patients of Group B after a mean follow-up of 42 and 28 months, respectively. RESULTS: Mean number of by-pass grafts was 1.9 in Group A and 2.6 in Group B (P = 0.01). The left anterior descending coronary artery was revascularized in 27 patients of Group A (34.6%) and 26 of Group B (89.7%) (P < 0.001); the left internal mammary artery was used in seven patients of Group A (8.9%) and 24 of Group B (82.8%) (P < 0.001). Hospital mortality in Group A was 10.3% (9/87), in Group B there was no hospital mortality (P > 0.05). Thirty-two patients of Group A (36.8%) and 3 of Group B (9.7%) suffered of low cardiac output syndrome (P = 0.01). At late control, improvements observed in NYHA and CCS classes, left ventricular ejection fraction (all P < 0.001 in both groups versus preoperative values) and left ventricular end-diastolic diameter (P > 0.05 in Group A and P < 0.001 in Group B) proved to be statistically higher in patients of Group B. CONCLUSIONS: Endoventricular patch plasty associated with a complete myocardial revascularization, in particular of the anterior descending coronary, and a larger use of the internal mammary artery, permits, by means of reconstruction of the left ventricular geometry, a better outcome for patients undergoing left ventricular aneurysmectomy.

Adult

HIV-1 infection and the developing nervous system: lineage-specific regulation of viral gene expression and replication in distinct neuronal precursors.

Neurologic abnormalities are common in HIV-1 infected patients and often represent the dominant clinical manifestation of pediatric AIDS. Although the neurological dysfunction has been directly related to CNS invasion by HIV-1, the pathogenesis of neurologic disorders remains unclear. Microglia and macrophages are major HIV-1 targets in the brain, whereas HIV-1 infected neurons or glial cells have been rarely reported. This suggests that indirect mechanisms may account for the severe neuronal damage observed in these patients. Nevertheless, immature, mitotically active neuronal and glial cells, which are present during fetal development, are susceptible to HIV-1 infection and replication in vitro, suggesting that HIV-1 infection during organ development may present unique features. To better characterize virus-host cells interactions in the developing CNS, we have examined the susceptibility of embryologically and biochemically distinct neuronal cell lines to HIV-1 infection. Here we show that mitotically active, immature neurons of distinct lineages, have different susceptibilities to HIV-1 infection and replication and different abilities to support viral gene expression. Mutational analysis of HIV-1 LTR reveals that a region of the viral promoter between nucleotide -255 to -166 is responsible for most quantitative and qualitative differences in viral transactivation among different neuroblasts. This suggests that specific regions of the viral promoter and cellular factors, either lineage- or differentiation-dependent, which bind to those regions, may contribute to control the levels of virus replication and possibly restrict the viral tropism in the developing brain. This may contribute to the establishment of a virus reservoir in the immature CNS and participate by either direct or indirect mechanisms to the severity of the AIDS-related pediatric neurological dysfunction.

Cell Line

Arteriomegaly and inflammatory abdominal aortic aneurysm. Case report.

In this case report inflammatory abdominal aortic aneurysm (IAAA) was superimposed on an arteriomegaly condition complicated by bilateral aneurysm of the common iliac arteries. Obstruction of the right ureter, mild hydronephrosis of the left system and a slight impairment of renal function were also present. Preoperative cellular and humoral immunological parameters were within normal limits while the erythrocyte sedimentation rate (ESR) was elevated (74 mm). Histological analysis showed numerous scattered lymphoid cells or organized in follicles with germinal centers within the adventitial thickening of the IAAA wall. Immunohistochemical analysis on frozen sections demonstrated that dispersed and perivascular lymphoid cells were mainly composed of similar amounts of CD3+/CD4+ and CD3+/CD8+ T lymphocytes. Histological analysis of the common iliac artery aneurysm showed a mild intimal thickening will small aggregates of macrophages. After aneurysm repair all peripheral blood analysis normalized within one month after surgery. The IAAA observed in our patient with arteriomegaly as underlying arterial disease cannot be interpreted as an inflammatory variation of an atherosclerotic aneurysm. The histological pattern of the inflammatory reaction and its resolution after surgery give, in our opinion, more credit to the etiopathogenetic hypothesis of a reaction elicited by an antigen within the arterial wall of the infrarenal aorta which might be enhanced by the lymphatic stasis subsequent to aneurysm compression.

Aged

Doppler velocimetry of different sections of the fetal middle cerebral artery in relation to perinatal outcome.

To assess the standard curves of pulsatility index (PI) in different segments of middle cerebral artery (MCA): initial segment (MI) and subcortical segment (M2); to determine the variation of the flow velocity waveforms (FVW) of the M1 and M2 segments of MCA in presence of fetal distress and to establish the possible correlation between the two segments of MCA. 50 normal pregnancies from 25 weeks of gestation to term and 20 pregnancy with alteration of fetal growth rate were investigated with serial records of the FVW of the M1 and M2 segments of the MCA and of the umbilical artery (UA) with a colour Doppler system. Severe fetal distress was associated to cerebral-placental ratio below 1 (C/P < 1). The perinatal outcome was established on the basis: 1) abnormal intrapartum CTG, 2) emergency cesarean section, 3) Apgar score at 1st and 5th minute after birth and 4) birth eight centiles. In normal pregnancy P1 of M2 was always higher than that of M1: therefore M2/M2 resulted below 1, with a maximum peak near 32 weeks of gestation. In presence of moderate fetal distress only P1 of M2 was reduced (M1/M2 > 1). It exists a significant difference of PI in M1 and M2 segments of fetal MCA during gestation: thus MCA so it is important to identify the tract of fetal MCA when recording its FVW. Moreover we suppose that an initial "cerebral sparing" effect exists in order to protect the cortex by the initial hypoxic injury: this is shown by a M1/M2 > 1. The progression of fetal distress results in a greater haemodynamic modification, the so called "brain sparing" which is usually present when C/P < 1.

Apgar Score

[The use of radiotherapy in the prevention of heterotopic ossification in patients with total hip replacement].

In order to prevent heterotopic ossification (HO) after total hip replacement, 21 high risk hips were irradiated pre- and postoperatively to prevent heterotopic bone formation in the St. Paul Department of Radiation Oncology from 1993 to September, 1995. Eighteen hips in 15 patients were eligible for analysis with a minimum follow-up of 3 months. All the hips in our series were at high risk of heterotopic bone formation. All assessable patients had radiographic findings of ipsilateral or contralateral previous ectopic bone formation, 8 following total hip arthroplasty, 4 following trauma and 3 had heterotopic osteoarthritis. Four hips were treated 46 hours preoperatively, while all the others were treated on the first postoperative day. The irradiation field was limited to the hip region and radiation exposure to a rectangular field, ranging in size from 8 x 12 to 10 x 15 cm, to include the lateral aspect of the greater trochanter. We used a cobalt-60 unit. Opposed anterior-posterior fields were irradiated at midplan, with a source-to-axis distance of 80 cm; the dose was 6-8 Gy in one fraction. Preoperative irradiation appeared as effective as postoperative treatment, and more comfortable for the patients. There were neither side-effects nor failure of ossification. The treatment appeared effective in the prophylaxis of HO in 88% of patients, with clinical advantages in 67% of them.

Follow-Up Studies

[Functional aspects of the fetal urinary apparatus in relation to growth].

The normal and regular development of the fetal renal function is related to fetal growth and to the correct development of the fetal lung. Besides, the fetal kidneys plays an important role in the regulation of the hydro-electrolytic balance and in the modulation of the fetal arterial pressure. The postnatal renal failure is one of the most dangerous factors which may occur in the very small preterm babies (birth weight below 1000 g) and their therapeutical answer depends on the degree of kidney maturation. The knowledge of the kidney maturation process is one of the actual controversies in perinatal medicine. The development of the renal nephron and of the excretory system continues until 32-36 weeks of gestation, their maturation process ends only some months after birth. At 9 weeks of gestation the embryonic kidney may be seen in a transvaginal ultrasonographic scanning; the calico-pelvic system is visible from the 11th week of gestation and the bladder may be seen by ultrasound from the 12 weeks' gestation. The fetal glomerular ultrafiltration process starts at the 10-11 week of gestation and the most important factors that improve the volume of glomerular ultrafiltrate is the total renal mass which is related to the number of functional nephron units. The Doppler velocimetry performed on the fetal renal artery has shown that the fetal renal blood flow increases with the increase of the renal volume and gestational age and it depends on the cardiac output. In the renal artery the resistance to blood flow decreases with gestational age. During fetal hypoxia there is a reduction of the amniotic fluid production; this phenomenon is related to the redistribution of the fetal blood flow with a decrease of the perfusion of peripheric organs (as the kidney) and an increase of the perfusion of brain, heart, liver and adrenals. The hypoxic fetal kidney is ischemic; moreover, the urine production rate is diminished and the humoral response of the kidney increase the fetal arterial pressure which maintains the haemodynamic compensation to hypoxia. When this situation is prolonged, there is possibly renal failure. The fetal renal ultrasonographic examination can give important information about the maturity degree of the fetal kidney and the evaluation of Doppler velocimetry on renal artery and the evaluation of the amniotic fluid allow the monitoring of fetal hypoxia. In future the Doppler velocimetry of intrarenal arteries and the biochemical evaluation of the amniotic fluid may a real evaluation of the fetal renal function.

Adult

Risk factors of incomplete distribution of cardioplegic solution during coronary artery grafting.

Myocardial distribution of cardioplegic solution infused by combined antegrade/retrograde routes was assessed with myocardial contrast echocardiography in 18 patients with chronic stable angina and three-vessel disease undergoing elective coronary artery bypass grafting. Overall myocardial opacification was significantly greater in retrograde than in antegrade cardioplegia (77.7% +/- 13.4% versus 59.1% +/- 15.7%; p = 0.0009). The difference was affected by collateral circulation, as pointed out by the significant interaction between coronary collateral circulation and percent of myocardial opacification after antegrade and retrograde cardioplegia (p = 0.002). When we performed multiple comparisons, in patients with good collaterals the opacification difference between antegrade and retrograde cardioplegia was not statistically significant (66.4% +/- 10.2% versus 76.0% +/- 15.2%; p = not significant), whereas in patients with poor collaterals myocardial opacification during retrograde cardioplegia was significantly greater (44.3% +/- 15.0% versus 81.2% +/- 9.0%; p < 0.02). During antegrade cardioplegia, patients with poor collaterals showed a lower degree of myocardial opacification than patients with good collaterals (44.3% +/- 15.0% versus 66.4% +/- 10.2%; p < 0.01). Our results show that retrograde cardioplegia in patients undergoing elective coronary artery bypass grafting offers no advantage over antegrade cardioplegia when collateral circulation is well developed. On the other hand, conventional aortic root infusion may not provide adequate myocardial protection in the subset of patients with significantly narrowed or occluded coronary arteries and poor collaterals.

Angina Pectoris

Hepatitis C virus infection in hypogammaglobulinemic patients receiving long-term replacement therapy with intravenous immunoglobulin.

BACKGROUND: Hepatitis C virus (HCV) seroconversion and viremia have been reported in patients treated with intravenous immunoglobulin (IVIG). STUDY DESIGN AND METHODS: A prevalence study was conducted to evaluate the rate of HCV infection in patients undergoing long-term treatment with IVIG. Fifty-four patients with congenital or acquired hypogammaglobulinemia treated with IVIG at 300 to 400 mg per kg every 14 to 21 days for a mean of 6.6 years were enrolled for clinical and biochemical examination. The type of IVIG preparation (type 1 only, type 2 only, or other products) administered to each patient was recorded. Antibodies to HCV were measured by enzyme-linked immunosorbent assay and immunoblotting; HCV RNA was detected by nested polymerase chain reaction. RESULTS: Anti-HCV was detected in 31 patients (57.4%) and HCV RNA was found in 5 patients (9.2%), all of whom were anti-HCV-positive. Abnormal alanine aminotransferase (ALT) levels were found in 10 patients (18.5%). Circulating HCV RNA (p = 0.01) and elevated ALT (p = 0.01) correlated significantly with anti-HCV positivity. Moreover, the rates of anti-HCV positivity and of ALT elevation were significantly higher among patients treated with type 1 IVIG and other products than among those receiving type 2 IVIG (p < 0.001 and p = 0.05, respectively). CONCLUSION: Anti-HCV positivity and viremia were frequently observed. The significant correlation between the detection of HCV RNA, the elevation of ALT, and positivity for anti-HCV suggests HCV infection. Exclusion of anti-HCV-positive donors and of anti-HCV-positive IVIG lots should improve the safety of IVIG.

Adolescent

Frequency of provirus-bearing CD4+ cells in HIV type 1 infection correlates with extent of in vitro apoptosis of CD8+ but not of CD4+ cells.

Lymphocytes from HIV-1-infected subjects undergo massive apoptosis when cultured in vitro, and this phenomenon might reflect pathogenetic mechanisms leading to immune dysfunction in vivo. However, (1) lymphocyte death is not restricted to CD4+ cells but seems to involve predominantly CD8+ cells, and (2) the same phenomenon occurs in other viral infections. Furthermore, it is not known whether a relationship exists between the HIV-1 burden and this type of cell death. In this work we sought to determine whether the HIV-1 provirus load correlates with the propensity to apoptosis of CD4+ and CD8+ cells. We studied 10 HIV-1-infected patients with CD4+ cell counts above 500/mm3 and free of concomitant infections. We correlated the frequency of HIV-1-infected CD4+ cells with the extent of culture-induced apoptosis as well as with the phenotype of the apoptotic lymphocytes. We found that the magnitude of apoptosis correlated with the frequency of HIV-1-infected CD4+ cells (p = 0.0007), and that increasing viral load and apoptosis were associated with a shift to the selective death of CD8+ cells. Our data support the view that, in addition to CD4+ cell killing, another immunopathogenic effect of HIV might be that of priming CD8+ cells to apoptosis. In vivo, this could eventually lead to the exhaustion of the cytotoxic T cell compartment.

Adult

Detection of IgM antibodies to human herpesvirus 6 in Romanian children with nonprogressive human immunodeficiency virus disease.

The prevalence of human herpesvirus 6 (HHV-6) infection and the course of human immunodeficiency virus (HIV) disease were investigated in 25 Romanian children with nosocomial HIV-1 infection. HHV-6 IgM and IgG antibodies were detected by enzyme immunoassay (EIA) and immunofluorescence assay (IFA) at the beginning of the study and after 18 months, concomitantly with collection of virologic, immunologic and clinical data. The initial HHV-6 seropositivity was 92% by EIA and 76% by IFA, whereas final testing showed 100% positivity by EIA and 84% by IFA. Positive HHV-6 IgM antibodies were detected in 10 children (40%) by EIA and IFA. Of these 9 children (36%) by EIA and 6 (24%) by IFA had both initial and final IgM antibodies. Children with HHV-6 IgM antibodies had a higher prevalence of pneumonitis than those without (100% vs. 53.3%; P < 0.01). In addition they more frequently showed positive p24 antigen detection (67% vs. 40%) and positive HIV-1 culture (80% vs. 69%). Nevertheless the patients with HHV-6 IgM antibodies showed a slight increase in the final mean CD4+ T cell count (from 1.140 to 1.185 x 10(6)/liter), whereas those with HHV-6 IgG alone showed a statistically significant (P = 0.01) decrease (from 1.395 to 968 CD4+ T-cells x 10(6)/liter). Therefore current or recent HHV-6 infection, as revealed by positive HHV-6 IgM antibodies, appeared to be associated with the development of pneumonitis but not with progression of HIV disease. A possible competitive inhibition of HIV-1 by HHV-6 or a stimulating effect of HHV-6 on CD4+ T-cell production may be suggested.

AIDS-Related Opportunistic Infections

Diagnosis of persistent left superior vena cava by multiplane transesophageal echocardiography.

Persistent left superior vena cava occurs in 2-4% of all congenital cardiac defects. The diagnosis is often missed if the lesion is not accurately looked for. Drainage to the coronary sinus is well tolerated, whereas drainage to the left atrium produces right to left shunt and may be associated with brain abscesses and/or embolization secondary to intravenous therapy administered through the left arm. This paper describes for the first time the diagnosis of persistent left superior vena cava by transesophageal contrast echocardiography. Echocardiography is the method of choice in the diagnosis of persistent left superior vena cava, because it can be used at the patient's bedside and allows easy detection of the drainage site.

Echocardiography, Transesophageal

The role of telemetry in perinatal monitoring.

In the field of transmission and exchange of clinical information particularly good results are foreseen with the development of data telemetry. In perinatal medicine the telemetric technologies are being employed in several situations. It is possible to subdivide the telemetric technologies into short and long distance systems. Short distance telemetry employs devices which utilize radiowaves or laser techniques to transmit data from the original source to centralized equipment; the main application is the transmission of the cardiotocographic signal to permit ambulation of the patient during recording. It may allow fetal heart rate testing to be performed in a setting more acceptable to patients telemetric not be physically confined to a bed or a chair. The telemetric transmission of the cardiotocogram (CTG) may solve problems of organization when the ratio of parturient to midwife exceeds 1:1. Long distance telemetry consists of the telephone transmission of data obtained from distant source to a consultation center where the data can be evaluated, stored and where hospital staff may suggest appropriate decision related to clinical course. In prenatal medicine, the system can offer the monitoring of maternal blood pressure, automatic urine and glucose analyses, surveillance of fetal heart rate and uterine contractions. CTG telemetry has been used with good results for the prevention of preterm labor while blood pressure control by telemetry may be useful for the prevention and management of gestational hypertension. Knowledge by the pregnant woman that it is possible to continuously monitor by telemetric technology her health and the health of her fetus provides reassurance during a delicate period.(ABSTRACT TRUNCATED AT 250 WORDS)

Female