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Biomedical subjects

M Corti

Publications and source records attributed to M Corti.

At least 37 records · Page 2Linked to original sources

[Cavum lymphoma in a hemophilic patient with AIDS].

Intermediate and highly malignant non-Hodgkin and primary central nervous system lymphomas are marker diseases for AIDS. Cavum and oropharynx involvement by these tumors is uncommon. Although there are few cases reported in the literature, these may be primary localizations of the tumor. We present a hemophilic HIV+ patient with non-Hodgkin lymphoma of the cavum. The histologic diagnosis was high-grade, pleomorphic, centroblastic lymphoma. The patient was treated with chemotherapy plus intrathecal chemotherapy and highly active antiretroviral therapy (HAART). His evolution has been excellent. One year after diagnosis, the patient is asymptomatic with no evidence of residual tumor, and responding well to HAART.

Acquired Immunodeficiency Syndrome↗

Hypoxia induces selective SAPK/JNK-2-AP-1 pathway activation in the nucleus tractus solitarii of the conscious rat.

In the nucleus tractus solitarii, NMDA glutamate receptors are critical to the hypoxic ventilatory response. However, the signal transduction pathways underlying the hypoxic ventilatory response remain undefined. To assess the effect of a moderate hypoxic stimulus (10% O2) on tyrosine phosphorylation of proteins in the nucleus tractus solitarii, tissue lysates were harvested by repeated punch sampling at 0, 1, 10, and 60 min of hypoxia and examined for the presence of phosphorylated tyrosine residues by immunoblotting. Time-dependent phosphotyrosine increases occurred in proteins migrating at regions corresponding to molecular masses of 38-42, 50, 55, and 60 kDa, which were attenuated by pretreatment with the NMDA receptor channel blocker, MK-801. As extracellular signal-regulated kinase (Erk) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) phosphorylation may induce Fos and Jun gene transcription and activator protein-1 (AP-1) DNA binding, the activation of Erk1, Erk2, p38, and SAPK/JNK was examined in the nucleus tractus solitarii and neocortex during hypoxia and following administration of MK-801. Hypoxia enhanced Erk1, Erk2, and p38 activity in the cortex, but not in the nucleus tractus solitarii. Increased phosphorylation of SEK1 and SAPK/JNK-2 occurred in the nucleus tractus solitarii during hypoxia, whereas both SAPK/JNK-1 and SAPK/JNK-2 were recruited in cortex. MK-801 attenuated hypoxia-induced SEK1, SAPK/JNK-2, and AP-1 binding in the nucleus tractus solitarii, and the widespread activation of all MAP kinases in the cortex was also attenuated. We conclude that in conscious rats, a moderate hypoxic stimulus elicits NMDA-dependent widespread mitogen-activated protein kinase activation in cortex, but selective SAPK/JNK-2 and AP-1 activation in the nucleus tractus solitarii, thereby suggesting a functional role for the SAPK/JNK-2-AP-1 pathway.

Adaptor Protein Complex alpha Subunits↗

[Disseminated infection due to Mycobacterium fortuitum in an AIDS patient].

A patient with advanced HIV-1 disease bearing a rapidly growing, atypical mycobacterium is presented. Mycobacterium fortuitum was identified in sputum and purulent material obtained by aspirating subcutaneous abscesses. The treatment scheme is evaluated and the literature is reviewed.

AIDS-Related Opportunistic Infections↗

Gender- and age-specific cytotoxic susceptibility to benzene metabolites in vitro.

Benzene, a widely used compound, is a known carcinogen and hematopoietic toxicant. Several studies have shown gender and age differences in the responses to benzene-induced hematotoxicity. It is not known if these differences in response are due to age- or gender-associated metabolic differences or to age- or gender-associated differences in the susceptibilities of the target cells. In order to address this issue, mouse colony-forming units-erythroid (CFU-e, an erythroid precursor cell particularly susceptible to benzene toxicity) were cultured in the presence of either individual benzene metabolites or binary mixtures of these metabolites. CFU-e were obtained from unexposed age-matched adult male and female (both virgin and pregnant) Swiss Webster (SW) mice and from SW male and female 16-day fetuses. The metabolites used were phenol, hydroquinone, catechol, benzoquinone, and trans, trans-muconic acid. The concentrations of the individual metabolites used were 10, 20, and 40 microM. Binary mixtures of metabolites were prepared using the lowest concentrations of the individual metabolites that caused cytotoxicity. These concentrations were 10 microM for hydroquinone, catechol, and benzoquinone, and 40 microM for phenol and muconic acid. In general, the CFU-e from adult females (both virgin and pregnant) were more resistant to the toxic effects of the individual metabolites than CFU-e from other subjects. CFU-e from adult males were more susceptible to the cytotoxic effects of hydroquinone and benzoquinone than CFU-e from other subjects and CFU-e from both male and female fetuses were highly sensitive to the toxic effects of catechol. On the other hand, CFU-e from adult males were less susceptible to the cytotoxic effects of catechol than CFU-e from other subjects. Similar results were observed with binary mixtures of metabolites. CFU-e from adult males were more susceptible to the binary mixtures than CFU-e from virgin females and CFU-e from fetal males were more susceptible than CFU-e from fetal females. In addition, CFU-e from fetuses were more 'resistant than CFU-e from adults to the cytotoxic effects of those binary mixtures that did not contain catechol. In contrast, binary mixtures containing catechol were more toxic to fetal cells than to adult cells. These results suggest that differences in benzene hematotoxicity associated with gender and age may be due, at least in part, to intrinsic factors at the level of the target cell rather than solely to age- or gender-related differences in the metabolism of benzene.

Age Factors↗

On-line assessment of delivered dialysis dose.

BACKGROUND: The adequacy of the delivered dialysis dose is essential to prevent patient morbidity and mortality. The determination of effective ionic dialysance (D) is easy, non-invasive and inexpensive, and its use instead of effective urea clearance (K) in kinetically determining apparent" urea distribution volume (Vt) is likely to lead to a correct Kt/V, even though the Vt value may be incorrect. The aim of this study was to test the possibility of using the measurement of D to monitor Kt/V on-line during each dialysis treatment. METHODS: Forty-four patients were dialyzed using a monitor equipped with specially designed "Diascan Module" (COT; Hospal) that measures effective D by means of a single conductivity probe. Vt was calculated according to the SPVV three BUN method urea kinetic model using D instead of K values. One month later, Kt/V was calculated as Dt/V, using actual D and T values and the predetermined Vt values updated for the current final body wt. Both the Dt/V and Kt/V determined according to the Smye and Daugirdas methods were compared with the Kt/V determined using the SPVV kinetic model (Kt/Veq) RESULTS: The Kt/V values calculated using ionic dialysance and predetermined Vt were approximately equivalent to those of Kt/Veq (1.14 +/- 0.16 vs. 1.14 +/- 0.17, mean difference 0.00 +/- 0.07), as were those determined according to the Smye and Daugirdas methods (1.10 +/- 0.18 and 1.13 +/- 0.17, mean difference -0.03 +/- 0.06 and 0.01 +/- 0.06, respectively). CONCLUSION: Once Vt has been determined, the evaluation of ionic dialysance in stable patients makes it possible to calculate the Kt/V accurately at each dialysis session without blood or dialysate sampling, and at no additional cost.

Blood Urea Nitrogen↗

Effect of on-line conductivity plasma ultrafiltrate kinetic modeling on cardiovascular stability of hemodialysis patients.

The aim of this multicenter, prospective, randomized cross-over study was to clarify whether on-line conductivity ultrafiltrate kinetic modeling (treatment B), as a substitute for sodium kinetic modeling, is capable of reducing intradialytic cardiovascular instability in comparison with standard treatment (treatment A), by reducing the sodium balance variability. Both treatments were performed by means of a modified hemodiafiltration technique. Treatment A was performed using fixed dialysate conductivity; treatment B made use of the dialysate conductivity derived from a conductivity kinetic model, in order to obtain an end-dialysis ultrafiltrate conductivity at each dialysis session that was equal to the mean value determined in the same patient during the four-week run-in period. Thus, during treatment B, the expected end-dialysis ultrafiltrate conductivity value of each patient should have been constant. The study was carried out according to a multicenter cross-over design of 16 weeks with two treatments (A or B), two sequences (1 = ABB and 2 = BAA), a run-in period of four weeks (period 1, treatment A), and three consecutive experimental periods of four weeks each. Analysis of variance for a cross-over design was used for the statistical analysis. Forty-nine hemodialysis patients prone to intradialytic hypotension (> 25% of sessions) were enrolled from 16 participating centers, and randomly assigned to either sequence 1 (26 patients) or sequence 2 (23 patients). Six patients dropped out and four were protocol violators, which left 39 patients selected for statistical analysis. There was no difference in the average dialysate conductivity, predialysis and end-dialysis plasma water ultrafiltrate conductivity or body weight between treatment A and treatment B. Thus, the observed mean sodium balance was not different and, as expected, only the intra-patient variability of end-dialysis ultrafiltrate conductivity (index of sodium balance variability) was reduced (21%). During treatment A, systolic blood pressure decreased by 23 mm Hg (95% confidence intervals 21 to 24 mm Hg) at the end of dialysis with respect to the pre-dialysis values. Treatment B reduced this intradialytic decrease (P = 0.001) with a maximum effect at the third hour of dialysis (4.4 mm Hg, 95% confidence intervals 1.9 to 6.9 mm Hg, 23% less than during treatment A, P 0.0005) without any period or carry-over effect (P = 0.53 and 0.08, respectively). There was no treatment effect on intradialytic diastolic blood pressure (P = 0.291). In conclusion, intradialytic cardiovascular stability was significantly improved by matching the interdialytic sodium load with intradialytic sodium removal using on-line conductivity ultrafiltrate kinetic modeling as an alternative to sodium kinetic modeling. Although highly significant, this effect was clinically not very large. By applying this conductivity kinetic model to patients with a more variable sodium intake from one session to another, a greater benefit can be expected.

Aged↗

Dexamethasone activates expression of the PDGF-alpha receptor and induces lung fibroblast proliferation.

Corticosteroids (CSs) are commonly used for anti-inflammatory therapy in asthma and in interstitial lung diseases. In attempting to understand the mechanisms through which CSs control cell proliferation, we have carried out experiments to test the effects of dexamethasone (Dex) on the growth of lung fibroblasts. Using mouse 3T3 fibroblasts as well as early-passage rat lung fibroblasts (RLFs), we show that the quiescent cells in 1% serum or in serum-free media proliferate significantly in response to the addition of 10(-7) to 10(-9) M Dex. Increases as high as fourfold in cell numbers were recorded for the RLFs after 48 h in culture. A polyclonal antibody to the AB isoform of human platelet-derived growth factor (PDGF) blocked the proliferative response. As expected, the fibroblasts produced primarily PDGF-A chain, and the RLFs exhibited few PDGF-alpha receptors (PDGF-R alpha), the receptor type necessary for binding the AA isoform. Accordingly, we determined that Dex upregulated PDGF-R alpha mRNA and protein. Therefore, we can postulate that Dex-induced fibroblast proliferation is mediated, at least in part, by PDGF-AA, which binds to the PDGF-R alpha.

3T3 Cells↗

Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis.

Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. The CTGF gene promotor contains a transforming growth factor-beta1 (TGF-beta1) response element. Because TGF-beta1 expression is upregulated in several models of fibroproliferative lung disease, we asked whether CTGF is also upregulated in a murine lung fibrosis model and whether CTGF could mediate some of the fibrogenic effects associated with TGF-beta1. A portion of the rat CTGF gene was cloned and used to show that primary isolates of both murine and human lung fibroblasts express CTGF mRNA in vitro. There was a greater than twofold increase in CTGF expression in both human and murine lung fibroblasts 2, 4, and 24 h after the addition of TGF-beta1 in vitro. A bleomycin-sensitive mouse strain (C57BL/6) and a bleomycin-resistant mouse strain (BALB/c) were given bleomycin, a known lung fibrogenic agent. CTGF mRNA expression was upregulated in the sensitive, but not in the resistant, mouse strain after administration of bleomycin. In vivo differences in the CTGF expression between the two mouse strains were not due to an inherent inability of BALB/c lung fibroblasts to respond to TGF-beta1 because fibroblasts from untreated BALB/c mouse lung upregulated their CTGF message when treated with TGF-beta1 in vitro. These data demonstrate that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.

Animals↗

[Intestinal tuberculosis and AIDS. Case report and literature review].

We describe a patient with HIV-1 infection and disseminated tuberculosis complicated with intestinal localization. The authors describe the clinical and radiological findings and the histological and microbiological diagnosis corroboration of the intestinal biopsy. The incidence of tuberculosis has been increasing during the last decade. The resurgence of tuberculosis, secondary to AIDS pandemic, mandates that the clinician be aware of the wide spectrum of presentation of intestinal tuberculosis.

AIDS-Related Opportunistic Infections↗

[Malaria in Grosseto Maremma: a social disease].

Several kind of sources testify that, since XIVth century, people living in Grosseto during the summer moved to healthy towns located in neighbouring hills. Starting from the XVIth century malaria became a true scourge for people living in Maremma (especially day labourers and soldiers), and local "signorie" planned some attempts to improve their condition. However, only after the unification of Italy, and the discovery of the role of anopheles in transmitting the etiological agent, the fight against malaria acquired a scientific basis. At the end of the last century, the epidemiology of malaria in the Maremma Grossetana was studied by outstanding scientists (Koch, Grassi and Gosio among others). The present essay explores the archival sources concerning the history of malaria in the Maremma Grossetana from the beginning of "estataura" to antimalarial campaigns carried out during the first three decades of the XXth Century.

Archives↗

[Disseminated tuberculosis with cutaneous manifestations in AIDS patients. Presentation of 4 cases].

BACKGROUND: Acute cutaneous miliary tuberculosis is a rare form of Mycobacterium tuberculosis infection which has been described in only 25 published cases in the last 15 years. The appearance of serious disseminated forms of tuberculosis is enhanced by the severe immunodeficiency which characterizes AIDS. METHODS: Four cases are described of disseminated tuberculosis with cutaneous localization clinically described as the acute miliary form. Patients had AIDS and CD4 lymphocyte levels of < 100 cells/mm3. Diagnosis was established in all cases by scraping of cutaneous lesions and direct examination with Ziehl-Neelsen coloration. RESULTS: The 4 patients presented signs and symptoms of disseminated tuberculosis with cutaneous manifestations, without a definite pattern and with localization predominantly on the thorax. Three had BAAR-positive sputum. Multiresistant strains of Mycobacterium tuberculosis were confirmed by antibiogram. One patient infected by a strain sensitive to first-line drugs responded favorably to conventional treatment for disseminated tuberculosis. In the remaining three with multiresistant strains, the evolution of the disease was rapid and unfavorable. CONCLUSIONS: Abrupt appearance of cutaneous lesions in a patient with disseminated tuberculosis and advanced HIV-disease should raise the suspicion of its etiology. Scraping and direct examination using Ziehl-Neelsen coloration is practical, economical and non-invasive diagnostic method.

Acquired Immunodeficiency Syndrome↗

Chronic hemodialysis: Kt/V or solute removal index to evaluate the effective delivered dose?

A standard for quantifying the hemodialysis dose has not yet been defined. Many authors suggest the use of an alternative method to Kt/V: the solute removal index (SRI). We compared three methods based on blood-side urea determinations with the direct quantification method (DDQ) for estimating the delivered dialysis dose, expressed as SRI as well as Kt/V. Eight patients underwent three consecutive dialysis sessions, with the same dialytic efficiency. For each patient and each dialytic session the SRI and Kt/V were determined using the DDQ method and the single pool variable volume kinetic model, in its classical version (SPVV) as well by using the postdialysis urea value determined 30 min after the end of the session (eqSPVV). Double pool Kt/V was also estimated by the Daugirdas-Schneditz rate equation. Our results showed that the SPVV kinetic model significantly overestimated the delivered dialysis dose, the mean value of SRI and Kt/V were respectively 8.9% and 17% higher than those obtained by DDQ. The eqSPVV allowed the SRI to be estimated with a difference of -0.3% and Kt/V with a difference of -2% in comparison with DDQ. By using the Daugirdas-Schneditz rate of equation, which does not require blood samples to be drawn after the end of the session, the difference in Kt/V value was 3%. Therefore, both the eqSPVV kinetic model and the Daugirdas method allow quantification of the delivered dialysis dose with results similar to those determined by DDQ, which cannot be routinely applied. Kt/V seems the best marker for dialytic doses quantification.

Hemodialysis Solutions↗

Conductivity: on-line monitoring of dialysis adequacy.

Cardiovascular disease and the inadequacy of delivered dialysis are the main factors determining morbidity and mortality in dialysis patients. We have already demonstrated that a conductivity kinetic model makes it possible to match interdialytic sodium loading and intradialytic sodium removal (the main factor determining cardiovascular morbidity) without the need for blood samples and, thus, in routine clinical practice. The aim of the present study was to test the possibility of using the conductivity method also to determine Kt/v without blood or dialysate sampling. In 18 steady-state patients, the urea distribution volume (V) was kinetically determined once using ionic dialysance (D) values instead of those of effective urea clearance. One month later, the Kt/V was determined by using the current D and T values and the predetermined V (Dt/V), then compared with the equilibrated Kt/V computed by means of the SPVV kinetic model (eqKt/V). The mean value of Dt/V was 1.18+/-0.15; while of eqKt/V it was 1.18+/-0.16, with a mean difference of 0.00+/-0.07. The conductivity method therefore seems to be very promising not only for monitoring the sodium balance, but also for quantifying delivered dialysis. Since its simplicity and low-cost make it suitable for use at each dialysis session, the conductivity method could therefore lead to significant progress in dialytic practice by contributing to the elimination of the two main causes of morbidity and mortality in dialysis patients.

Anuria↗

Hepatitis E virus infection in haemodialysis patients: a seroepidemiological survey.

BACKGROUND: Hepatitis E virus (HEV) is the causative agent for enteric non-A, non-B hepatitis. Transmission is via the faecal route but the possibility of transmission by blood has been raised. Data concerning anti-HEV prevalence among chronic haemodialysis (HD) patients are few and give conflicting results. METHODS: We tested for anti-HEV antibody 204 chronic HD patients attending a single dialysis unit. A specific solid-phase enzyme-linked immunoassay (Abbott HEV EIA) was used. RESULTS: We found six anti-HEV-positive patients, the anti-HEV prevalence was 3% (95% CI 0-6%). The prevalence rates of HBV and HCV infections were 39% (31-45%) and 22% (16-28%) respectively. No anti-HEV-positive patient showed past or current biochemical signs of liver damage. One of six (17%) anti-HEV-positive patients was an immigrant; no risk factor for anti-HEV antibody was identified in the other anti-HEV-positive individuals. CONCLUSIONS: We observed a low anti-HEV prevalence: there was no association between HEV and blood-borne infections (HBV, HCV, and HIV) in our HD patients; most anti-HEV-positive patients we found were probably related to a local infection by HEV. This is one of the first reports concerning seroepidemiology of HEV infection in a large cohort of chronic HD individuals.

Adult↗

Serologic survey for control of hepatitis C in haemodialysis patients: third-generation assays and analysis of costs.

There is little information about the serologic survey for control of hepatitis C by using third-generation assays among chronic haemodialysis (HD) patients, and no analysis of costs has been made to this end. A serologic survey for control of hepatitis C was performed in 190 HD patients attending a single dialysis unit, using second- and third-generation assays. Costs of both serologic surveys were calculated. Anti-HCV prevalence tested by third-generation assays increased from 25% (48/190) to 28% (53/190) compared to second-generation testing; 56% (9/16) of patients showing uncertain findings by second-generation tests gave unequivocal results by third-generation assays; median duration of HD treatment and raised aminotransferase levels were positively associated (P = 0.004 and P = 0.012, respectively) with anti-HCV detected by third-generation assays. The serologic survey for control of hepatitis C in HD patients at our centre was slightly more expensive by third-generation assays compared to second-generation testing (US$18866 vs US$17200 per year). In summary, the use of third-generation tests largely clarified the uncertain results of second-generation tests; new additional positive patients were detected by third-generation assays compared to second-generation testing. Third-generation assays showed the association of duration of HD treatment and raised aminotransferase levels with anti-HCV antibody, as previously found by first- and second-generation assays. To date, third-generation screening and confirmatory assays seem extremely useful in the serologic survey for control of hepatitis C in HD centres without a considerable outlay.

Adult↗