Experimental protocol for activation-induced manganese-enhanced MRI (AIM-MRI) based on quantitative determination of Mn content in rat brain by fast T1 mapping.

In activation-induced manganese-enhanced MRI (AIM-MRI) experiments, differential accumulation of Mn in activated and silent brain areas is generally assessed using T(1)-weighted images and quantified by the enhancement of signal intensity (SI), calculated with reference to SI before Mn administration or to SI of brain regions unaffected by the specific stimulus. However, SI enhancement can be unreliable when animals are removed from and reinserted into the magnet. We have developed an experimental protocol based on repeated intraperitoneal (i.p.) injections of Mn, quantitative determination of T(1), and coregistration of images to a rat brain atlas that allows absolute quantification of Mn concentration in selected brain areas. Results showed that interanimal variability of postcontrast T(1) values was very low (compared to the experimental error in T(1) determinations) allowing detection of differential regional Mn uptake in stimulated and unstimulated animals. In addition we have determined in vivo relaxivity of Mn in brain tissue and its frequency dependence.

Synthesis and characterization of polyethylenimine-based iron oxide composites as novel contrast agents for MRI.

OBJECT: Use of polyethylenimines (PEIs) of different molecular weight and selected carboxylated-PEI derivatives (PEI-COOH) in the synthesis and stabilization of iron oxide nanoparticles, to obtain possible multifunctional contrast agents. MATERIALS AND METHODS: Oxidation of Fe(II) at slightly elevated pH and temperature resulted in the formation of highly soluble and stable nanocomposites of iron oxides and polymer. Composites were characterized and studied by atomic force microscopy (AFM), transmission electron microscopy (TEM), X-ray diffractometry, AC and DC magnetometry, NMR relaxometry and magnetic resonance imaging (MRI). RESULTS: From AFM the dimensions of the aggregates were found to be in the ~150-250 nm size region; the mean diameter of the magnetic core of the compounds named PEI-25, PEI-500 and PEI-COOH60 resulted d approximately 20 +/- 5 nm for PEI-25, d approximately 9.5 +/- 1.0 nm for PEI-500 and d approximately 6.8 +/- 1.0 nm for PEI-COOH60. In PEI-COOH60 TEM and X-ray diffractometry revealed small assemblies of mineral magnetic cores with clear indications that the main constituents are maghemite and/or magnetite as confirmed by AC and DC SQUID magnetometry. For PEI-COOH60, the study of NMR-dispersion profiles revealed r (1) and r (2) relaxivities comparable to superparamagnetic iron-oxide commercial compounds in the whole investigated frequency range 7 < or = nu < or = 212 MHz. CONCLUSION: PEI-25 was studied as possible MRI contrast agent (CA) to map the cerebral blood volume (CBV) and cerebral blood flow (CBF) in an animal model obtaining promising results. The reported compounds may be further functionalized to afford novel multifunctional systems for biomedical applications.

Predictive value of time-intensity curves obtained with contrast-enhanced ultrasonography (CEUS) in the follow-up of 30 patients with Crohn's disease.

OBJECTIVES: CEUS can provide accurate quantitative estimates of intestinal wall microvascularization in Crohn's disease. We hypothesized that inflammation of the intestinal wall is correlated not with the amount of wall vascularization (study of vascularization patterns, SVP) but with the degree of wall flow during a period of time (time-intensity study, TIS). Our objective was to discover whether CEUS SPV and/or CEUS-TIS reflect(s) vascular inflammation of the intestinal wall and display(s) correlation with clinical activity of the disease at the time of the examination (T0) or at the 3- and 6-month follow-up (T3, T6). MATERIALS AND METHODS: 30 patients with Crohn's disease (12 men, 18 women, mean age: 41.96 years; treatment: 5-ASA (n = 8), steroids (n = 13), anti-TNF (n = 7), azathioprine (n = 2) were studied with CEUS SPV and CEUS-TIS and followed for at least 6 months. The sonographic examinations were performed with SonoVue (BR1, Bracco) and a dedicated scanner (TECHNOS MPX, Esaote) equipped with software for calculation of time-intensity curves. Four vascular patterns (1: vascularization of the entire wall; 2: vascularization of >50% of the wall; 3: flow exclusively within the submucosal layer; 4: no signal). The semiquantitative analysis consisted in measurement of the area under the curve (AUC) (cut-off between active and inactive disease, 15), mean intesnity (IMA) (cut-off = 10). Each examination (180 s) was digitally recorded and analyzed. RESULTS: T0: cDAI <150 in 22 pts; cDAI > 150 in 8; T3: 22 pts. with cDAI<150, 8 with cDAI >150. At T0 CEUS SPV and CEUS-TIS both displayed low specificity, diagnostic accuracy, and negative predictive values (p = ns). At T0, CEUS SPV produced 8 true positives (TP), 15 true negatives (TN), 8 false positives (FP), 0 false negative (FN) (sensitivity: 100%; specificity: 68.2%; diagnostic accuracy: 69.5%; Positive predictive value (PPV): 100%; negative predictive value (NPV: 53.3%), and CEUS-TIS produced 6 TP, 18 TN, 4 FP, 2 FN (sensitivity 75%; specificity: 81.8%; diagnostic accuracy: 75%; PPV: 60%; NPV: 90%). At T3, CEUS SPV produced 8 TP, 12 TN, 7 FP, 3 FN (sensitivity: 72.7%; specificity: 63.2%; diagnostic accuracy: 50%; PPV: 53.3%; NPV: 80%), and CEUS SIT produced the following results: 10 TP, 19 TN, 0 FP, 1 FN (sensitivity: 90,9%; specificity: 100%; diagnostic accuracy: 96,5%; PPV: 100%; NPV: 95%). At T3 CEUS-SVP displayed low sensitivity and low diagnostic accuracy, whereas SIT was able to predict clinical activity during follow-up in all but one case (which showed reactivation after 6 months) (p = 0.001) CONCLUSION: CEUS-TIS alone was found to reflect vascular inflammation of the intestinal wall in Crohn's disease and predicted clinical activity during follow-up.

Imaging detection of new HCCs in cirrhotic patients treated with different techniques: Comparison of conventional US, spiral CT, and 3-dimensional contrast-enhanced US with the Navigator technique (Nav 3D CEUS)().

INTRODUCTION: The commercially available Navigator system(©) (Esaote, Italy) allows easy 3D reconstruction of a single 2D acquisition of contrast-enhanced US (CEUS) imaging of the whole liver (with volumetric correction provided by the electromagnetic device of the Navigator(©)). The aim of our study was to compare the efficacy of this panoramic technique (Nav 3D CEUS) with that of conventional US and spiral CT in the detection of new hepatic lesions in patients treated for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From November 2006 to May 2007, we performed conventional US, Nav 3D CEUS, and spiral CT on 72 cirrhotic patients previously treated for 1 or more HCCs (M/F: 38/34; all HCV-positive; Child: A/B 58/14) (1 examination: 48 patients; 2 examinations: 20 patients; 3 examinations: 4 patients). Nav 3D CEUS was performed with SonoVue(©) (Bracco, Milan, Italy) as a contrast agent and Technos MPX(©) scanner (Esaote, Genoa, Italy). Sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values (PPV and NPV, respectively) were evaluated. Differences between the techniques were assessed with the chi-square test (SPSS release-15). RESULTS: Definitive diagnoses (based on spiral CT and additional follow-up) were: 6 cases of local recurrence (LocRecs) in 4 patients, 49 new nodules >2 cm from a treated nodule (NewNods) in 34 patients, and 10 cases of multinodular recurrence consisting of 4 or more nodules (NewMulti). The remaining 24 patients (22 treated for 1-3 nodules, 2 treated for >3 nodules) remained recurrence-free. Conventional US correctly detected 29/49 NewNods, 9/10 NewMultis, and 3/6 LocRecs (sensitivity: 59.2%; specificity: 100%; diagnostic accuracy: 73.6%; PPV: 100%; NPV: 70.1%). Spiral CT detected 42/49 NewNods plus 1 that was a false positive, 9/10 NewMultis, and all 6 LocRecs (sensitivity: 85.7%; specificity: 95.7%; diagnostic accuracy: 90.9%; PPV: 97.7%; NPV: 75.9%). 3D NAV results were: 46N (+9 multinodularN and 6 LR), 3 false-negatives, and one false-positive (sensitivity: 93.9; specificity: 97.9%; diagnostic accuracy: 95.6; PPV: 97.9; NPV: 93.9). CONCLUSIONS: 3D Nav CEUS is significantly better than US and very similar to spiral CT for detection of new HCCs. This technique revealed the presence of lesions that could not be visualized with spiral CT.

Ochlerotatus albifasciatus in rain pools of Buenos Aires: seasonal dynamics and relation to environmental variables.

The immature stages of Ochlerotatus albifasciatus develop in temporary pools. The present study aims at evaluating the seasonal dynamics of the aquatic stages of this mosquito, also analyzing the relationship among their presence and breeding success to some relevant climatic and environmental variables in the ephemeral rain pools of an urban park. Nineteen cohorts of O. albifasciatus that developed synchronously after rain events were recorded in all seasons. The proportions of mosquito-positive pools were significantly higher during the fall-winter period than in the spring-summer months (p < 0.001). The presence of this mosquito species was positively related to the amount of rain (p < 0.001), whereas negatively correlated to air temperature (p < 0.05) within a 5.2 to 29.7 degrees C range. The distribution of the number of cohorts per pool throughout the year was grouped (variance/mean: 3.96), indicating that these habitats were not equally suitable as breeding sites. The immature stages of O. albifasciatus were detected in pools belonging to all of the categories of surface area, depth, duration, vegetation cover, and insolation. However, the proportion of pools where immature mosquitoes were detected was positively and significantly related to surface, depth, duration, and vegetation cover. On the other hand, the proportion of mosquito-positive pools was higher at an intermediate insolation degree. Our results suggest that although preimaginal stages were present in all seasons, high temperatures may be unfavorable to larval development, and substrate vegetation may regulate water temperature. The positive relationship between the proportion of mosquito-positive pools and pool size and duration might reflect a strategy of O. albifasciatus to accomplish immature development.

Ochlerotatus albifasciatus in rain pools of Buenos Aires: seasonal dynamics and relation to environmental variables

The immature stages of Ochlerotatus albifasciatus develop in temporary pools. The present study aims at evaluating the seasonal dynamics of the aquatic stages of this mosquito, also analyzing the relationship among their presence and breeding success to some relevant climatic and environmental variables in the ephemeral rain pools of an urban park. Nineteen cohorts of O. albifasciatus that developed synchronously after rain events were recorded in all seasons. The proportions of mosquito-positive pools were significantly higher during the fall-winter period than in the spring-summer months (p < 0.001). The presence of this mosquito species was positively related to the amount of rain (p < 0.001), whereas negatively correlated to air temperature (p < 0.05) within a 5.2 to 29.7ºC range. The distribution of the number of cohorts per pool throughout the year was grouped (variance/mean: 3.96), indicating that these habitats were not equally suitable as breeding sites. The immature stages of O. albifasciatus were detected in pools belonging to all of the categories of surface area, depth, duration, vegetation cover, and insolation. However, the proportion of pools where immature mosquitoes were detected was positively and significantly related to surface, depth, duration, and vegetation cover. On the other hand, the proportion of mosquito-positive pools was higher at an intermediate insolation degree. Our results suggest that although preimaginal stages were present in all seasons, high temperatures may be unfavorable to larval development, and substrate vegetation may regulate water temperature. The positive relationship between the proportion of mosquito-positive pools and pool size and duration might reflect a strategy of O. albifasciatus to accomplish immature development

Temporo-mandibular joint kinetics and chewing cycles in children. A 3-year follow-up.

OBJECTIVES: To report the temporo-mandibular joint (TMJ) kinetics and masticatory function in healthy children. DESIGN: Temporo-mandibular joint palpation and electrognathographic registrations of chewing cycles were repeated for 3 years in order to evaluate changes. SETTING: Healthy children without systemic pathologies, decayed cavities and previous dental treatment. SAMPLE AND METHODS: Electrognathographic (EGN) registration of masticatory cycles and TMJ palpation were carried out on 52 patients (mean age: 5 years 8 months, range: 5 years 1 month, 6 years 8 months), by two university researchers, once a year for 3 consecutive years. TMJ palpation, differentiated TMJ synchronism (simultaneous bilateral opening movement) and TMJ asynchronism (not simultaneous bilateral opening movement), TMJ subluxation and click were observed. Electrognathographic registrations differentiated normal and abnormal jaw chewing cycles, and narrow and large cycles. RESULTS: Temporo-mandibular joint asynchronism was evident in 34 of 52 patients in the primary dentition, in 42 of 52 patients after the eruption of the first permanent molar, and in 31 of 52 patients after the eruption of the permanent incisors. TMJ subluxation increased during the full period of observation. Three temporomandibular clicks appeared after the eruption of the permanent incisors. Altered mastication was not always associated with TMJ disorders. CONCLUSIONS: In children, normal chewing cycles can coexist with occlusal discrepancies, cranio-facial growth and TMJ alterations.

Beta-blocking in heart failure patients. Balancing the evidence.

Evidence for the effectiveness of beta-blockers in the management of patients with heart failure is now compelling with a database of over 13000 patients enrolled in randomised prospective placebo-controlled clinical trials. However this therapy remains vastly underused in clinical practice. The different points challenging the widespread use beta blockade agents in the routine treatment in heart failure are presented and discussed. After a review of the potential mechanism hypothesised behind the benefits of beta-blockers in heart failure, the controversial effects on the haemodynamics, exercise tolerance, hospitalisation and mortality are underlined.

HCV-RNA occurrence in saliva of odontoiatric HCV seropositive patients.

BACKGROUND: HCV-RNA occurrence in saliva of patients suffering from C hepatitis induced to consider saliva as a possible diffusion mean of this disease. METHODS: Saliva and blood samples from 32 C hepatitis seropositive patients, followed for odontostomatologic problems in Odontoiatric Clinic of Brescia University were obtained. In every blood and saliva sample HCV-RNA concentration was evaluated following HCV-RNA 2.0 Assay (bDNA) Quantiplex test (Chiron), in Microbiology Institute of Brescia University. RESULTS: All patients showing HCV-RNA in serum presented virus in saliva also; two patients with negative HCV-RNA serum presented virus in saliva. In latter cases, we supposed that viral concentration in serum was under sensibility threshold of employed method. CONCLUSIONS: Saliva appears an easily and not invasively obtainable medium for epidemiological studies on HCV diffusion in humans. Its role in C hepatitis transmission, on the contrary, has not been cleared till now.

Effects of flooding and temperature on Aedes albifasciatus development time and larval density in two rain pools at Buenos Aires University City

Aedes albifasciatus is a floodwater mosquito that breeds in temporary waters. This semi-domestic species, widely distributed in Argentina, is a competent vector of the western equine encephalitis. The present study was carried out in two rain pools of the city of Buenos Aires, from April 1998 through March 1999. Samples were taken twice a week during the cold season and daily during the warmer months, starting from October. Immature mosquitoes were collected with a dipper, being the number of dippers proportional to the flooded area. The estimated rainfall thresholds to initiate cohorts of Ae. albifasciatus were: 16-17 mm in the fall-winter period, 25 mm in the spring, and 30 mm in the summer. The development time of the different cohorts and the mean air temperature of their respective periods were estimated in all seasons, ranging from six days (at 24o.C) to 32 days (at 13o.C). The equation that best expresses the relationship between development time and mean air temperature is dt =166,27.e-0,1435.T (R2=0,92). Significantly shorter development times were recorded for larvae of the first three stages as compared to the fourth larval stage and pupae

Chlorhexidine and taste. Influence of mouthwashes concentration and of rinsing time.

BACKGROUND: This study aims to define the influence of chlorhexidine on taste, considering either its concentration in mouthwashes or time of rinsing. METHODS: Suprathreshold taste acuity of 40 healthy subjects tasting variously concentrated solutions of sucrose, sodium chloride, citric acid and quinine hydrochloride was determined. Subjects were divided into four groups. Three groups rinsed their mouths during one minute, twice a day, for seven days, with a selected mouthwash (respectively 0.12%, 0.20%, and 0.30% chlorhexidine solutions). The fourth group rinsed in the same manner with a 0.30% chlorhexidine mouthwash, and time of rinsing was 15". RESULTS: All the mouthwashes reduced taste acuity for salt and bitter; the perception of sweet and sour was not significantly modified. Chlorhexidine acted on taste in different ways: salt perception reached the lowest value on the second day of treatment and the degree of hypogeusia changed no more till mouthrinses were interrupted. Bitter perception was progressively reduced and reached the lowest value on the seventh day. In both cases taste reduction lasted some days after the interruption of mouthrinses. Quality of all tastes was altered by mouthwashes, but incidence of dysgeusia was not related to chlorhexidine concentration. CONCLUSIONS: Hypogeusia induced by chlorhexidine concerns specifically salt and bitter. Chlorhexidine concentration in mouthwashes till 0.12% and mucosa exposure not exceeding 60" twice a day, seem the best procedure to protect tastes in clinical practice.

Effects of flooding and temperature on Aedes albifasciatus development time and larval density in two rain pools at Buenos Aires University City.

Aedes albifasciatus is a floodwater mosquito that breeds in temporary waters. This semi-domestic species, widely distributed in Argentina, is a competent vector of the western equine encephalitis. The present study was carried out in two rain pools of the city of Buenos Aires, from April 1998 through March 1999. Samples were taken twice a week during the cold season and daily during the warmer months, starting from October. Immature mosquitoes were collected with a dipper, being the number of dippers proportional to the flooded area. The estimated rainfall thresholds to initiate cohorts of Ae. albifasciatus were: 16-17 mm in the fall-winter period, 25 mm in the spring, and 30 mm in the summer. The development time of the different cohorts and the mean air temperature of their respective periods were estimated in all seasons, ranging from six days (at 24 degress C) to 32 days (at 13 degrees C). The equation that best expresses the relationship between development time and mean air temperature is dt =166,27.e(-0,1435.T) (R(2)=0,92). Significantly shorter development times were recorded for larvae of the first three stages as compared to the fourth larval stage and pupae.

Absence of Helicobacter pylori in dental plaque determined by immunoperoxidase.

BACKGROUND: Attempts to detect Helicobacter pylori in dental plaque have given contrasting results, and the possibility of an oral-oral transmission of the infection remains unclear. In this study, a sensitive and specific immunoperoxidase method has been employed to assess the presence of H. pylori in dental plaque. METHODS: Dental plaque smears from 80 patients undergoing gastroscopy were analyzed by an indirect immunoperoxidase test, employing a mixture of two monoclonal antibodies against H. pylori. RESULTS: No immunostained bacteria were shown in any of the examined dental plaque samples. CONCLUSIONS: H. pylori is not usually present in dental plaque, indicating that oral-oral transmission of the infection could be due to intermittent esophageal reflux only.

[Pathology of taste: knowledge and prospectives]. / La patologia del gusto: conoscenze e prospettive.

Taste anomalies have not been systematically investigated till recently in Italy. The influence of the taste on the choice of the foods, on the nutrition and on the same psycho-physic human mindedness has largely been demonstrated. In this study, taste anomalies associated with various pathologic conditions (nervous, endocrine, metabolic, infectious, immunological, carential or neoplastic disorders) are reported, as well as those produced by drugs, or surgical interventions. The type and the degree of taste anomalies associated to immunological diseases, allogeneic bone marrow transplantation and AL amyloidosis are particularly described.

Reduced taste perception in AL amyloidosis. A frequently unnoticed sensory impairment.

BACKGROUND: Sporadic observations suggest a possible taste impairment in AL amyloidosis, but the frequency and intensity of this sensory anomaly are not known. MATERIALS AND METHODS: We submitted 21 AL amyloidotic patients, drawn from subjects referred to the Amyloidosis Study Center of the Department of Internal Medicine and Medical Therapy, University of Pavia, to suprathreshold scaling analysis. RESULTS: Taste acuity was reduced in most of them. Every taste showed independent behavior, and 90% of these patients were hypogeusic. True ageusia for one or two tastes was observed in 35% of patients. No patient was aware of reduced taste acuity. Macroglossia did not seem to play a prominent role in dulling tastes. CONCLUSIONS: Impairment of taste perception suggests that gustative neuropathy is a frequently unnoticed expression of sensory involvement in AL amyloidosis.

Diagnostic approach to and follow-up of difficult cases of AL amyloidosis.

BACKGROUND: Routine electrophoretic analysis fails to detect a monoclonal component (MC) in a considerable portion of AL amyloidosis patients. We investigated whether the combination of immunofixation (IF) on agarose gel electrophoresis and bone marrow plasma cell (BMPC) light chain kappa/lambda ratio analysis could contribute to diagnosis in these cases. The possible use of the BMPC kappa/lambda ratio in monitoring the clone was also investigated. METHODS: We performed BMPC kappa/lambda ratio analysis and IF of serum and urine in 16 selected patients with no detectable MC at routine analysis, despite clinical features suggestive of primary amyloidosis. An anti-idiotypic monoclonal antibody specific for the amyloidogenic immunoglobulin and the BMPC kappa/lambda ratio were used to monitor the clone in a patient who underwent autologous peripheral blood stem cell transplantation. RESULTS: Abnormal kappa/lambda ratios were found in 14 (sensitivity 87.5%), and a MC in 12 (sensitivity 75%). Combination of the two analyses confirmed diagnosis in all cases. In one patient changes in the size of the clone, monitored on serial bone marrow aspirates by an anti-idiotypic antibody, paralleled variations of the kappa/lambda ratio. CONCLUSIONS: This study demonstrates that the combined use of IF and the BMPC kappa/lambda ratio is extremely powerful in AL amyloidosis. In addition, the BMPC kappa/lambda ratio should be considered for monitoring the amyloidogenic clone when serum or urine MC is not quantifiable.

Interaction of the anthracycline 4'-iodo-4'-deoxydoxorubicin with amyloid fibrils: inhibition of amyloidogenesis.

All types of amyloidosis are structurally characterized by the cross beta-pleated sheet conformation of the fibrils, irrespective of their biochemical composition. The clinical observation that the anthracycline 4'-iodo-4'-deoxy-doxorubicin (IDOX) can induce amyloid resorption in patients with immunoglobulin light chain amyloidosis was the starting point for this investigation of its possible mechanism of action. IDOX binds strongly to all five types of natural amyloid fibrils tested: immunoglobulin light chains, amyloid A, transthyretin (methionine-30 variant), beta-protein (Alzheimer), and beta 2-microglobulin. Quantitative binding studies showed that IDOX, but not doxorubicin, binds strongly to amyloid fibrils. This binding is saturable and involves two apparently distinct binding sites with Kd values of 5.9 x 10(-11) M and 3.4 x 10(-9) M. IDOX inhibited in vitro insulin amyloid fibrillogenesis. In vivo studies using the experimental amyloid murine model confirmed the specific targeting of IDOX to amyloid deposits. Preincubation of amyloid enhancing factor with IDOX significantly reduced the formation of amyloid deposits. It is hypothesized that IDOX exerts its beneficial effects through the inhibition of fibril growth, thus increasing the solubility of existing amyloid deposits and facilitating their clearance. IDOX may represent the progenitor of a class of amyloid-binding agents that could have both diagnostic and therapeutic potential in all types of amyloidoses.

AL amyloidosis. Characterization of amyloidogenic cells by anti-idiotypic monoclonal antibodies.

BACKGROUND: AL amyloidosis is characterized by systemic tissue deposition of monoclonal Ig light chains synthesized by a bone marrow plasma cell (PC) clone whose biologic characteristics remain undetermined. EXPERIMENTAL DESIGN: Anti-idiotypic (anti-Id) monoclonal antibodies (MoAbs) were used as specific probes to identify and study amyloidogenic cells in two patients by means of immunofluorescence methods. These MoAbs recognized populations of bone marrow pre-PC, PC, and peripheral blood lymphocytes. To test whether the circulating Id+ lymphocytes were capable of PC differentiation, peripheral blood lymphocytes were incubated with the differentiation-inducing agents, interleukin-3 and interleukin-6 in liquid culture. Preincubation with the anti-Id MoAb and complement was used to inhibit formation of Id+PC in vitro. RESULTS: The anti-Id MoAb identified three types of cells in the bone marrow with cytoplasmic Ig having the same isotype as the monoclonal component: a) lymphoid cells, that were slightly larger than common peripheral blood lymphocytes (47% CD45RA+, 28% CD45R0+, 97% CD38-, 100% CD10-, 100% mu-chain-); b) lymphoplasmacytoid cells with more abundant cytoplasm and Id+ Ig (CD45RA-, CD45RO-, CD10-, 53% CD38+); 3) mature PC that were very similar to normal PC in morphology and antigenic profile (CD38+, PCA1+, CD56-). A different picture was seen when anti-Id MoAb were used to detect peripheral blood Id+ elements: analysis revealed a population of mature resting surface Ig+ B lymphocytes. Circulating Id+ lymphocytes differentiated in vitro to PC and lymphoplasmacytoid cells that were very similar to those present in the bone marrow. A significant reduction in the number of Id+ PC was obtained after incubation with the anti-Id MoAb and complement. CONCLUSIONS: This study shows that the amyloidogenic cell clone is constituted by at least the following cell populations: a fraction of bone marrow cells (lymphoid, lymphoplasmacytoid cells and PC) and a subset of peripheral blood post-switched B lymphocytes. The results suggest a relationship among these cells, indicating that circulating Id+ lymphocytes may be the possible precursors of the more differentiated bone marrow population.

[Taste changes in patients with AL amyloidosis. Preliminary studies]. / Le alterazioni gustative dei pazienti affetti da amiloidosi AL. Ricerche preliminari.

Taste acuity in 20 subjects affected by AL amyloidosis without oral complications was investigated by threshold determination. Sixteen cases did not recognize one or more fundamental tastes. Sour was the most frequently lost taste, as it was not recognized by 10 out of 20 cases. So, sensorial neuropathy, altering taste generation and/or transmission, seems frequently associated to AL amyloidosis. Further researches will show if taste losses realize typical symptomatic features in this disease.

Reversal of nephrotic syndrome due to reactive amyloidosis (AA-type) after excision of localized Castleman's disease.

The patient (TAL), a chronic asymptomatic HBV carrier with HBsAg-anti-HBsAg circulating immune complexes, was admitted to our hospital because of a nephrotic syndrome due to renal amyloidosis. There was no family history of hereditary amyloidosis. Recurrent arthralgias, asthenia, and weight loss were the prominent clinical features. Laboratory test results showing that severe chronic inflammatory activity had been present for 6 years. Interleukin-6 (IL-6) serum concentration was 10 times normal and C-reactive protein was 1.9 mg/ml. A complex immunological picture was also present (immune complex formation, exuberant B-cell reactivity, and decrease in the number of CD4 T cells). A localized form of Castleman's disease (CD) (plasma-cell type) was diagnosed by surgical excision of a giant axillary lymph node. AA amyloid was present in the blood vessels. Within 60 days after excision of the mass, the systemic symptoms subsided, laboratory signs of inflammatory activity disappeared and IL-6 serum concentration returned to normal, thus establishing a causal relationship between the localized Castleman's disease, elevated IL-6 concentration and the chronic inflammation responsible for AA amyloidosis. At 10 months of follow-up, the nephrotic syndrome has reversed, kidney function has slowly ameliorated, and the patient has gained 12 kg. Abdominal fat aspirates drawn to search for amyloid, positive before surgery, were subsequently negative. The latter finding, and the remission of the nephrotic syndrome, provided strong evidence for regression of the amyloid deposits. However, the HBsAg-anti-HBsAg immune complexes and depression of T-helper cell activity persist. This immunological derangement is therefore not a consequence of CD. Chronic stimulation of the immune system due to the patient's inability to eliminate HBV, in the contest of perturbed immunity, may have favored the genesis of the lymphadenopathy.