Gut T cell-independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells.

The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through nonredundant T cell-dependent (TD) and T cell-independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria, and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here, we show that the intestinal TI pathway required CD40-independent B cell-activating signals from TACI, a receptor for the innate CD40 ligand-like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria-specific SIgA responses through an intestinal TI program.

¹³¹I treatment of toxic nodular goiter under combined thyrostatic-thyromimetic medication is at low risk of late hypothyroidism.

AIM: Treatment of toxic nodular goiter with ¹³¹I is a first-line therapy for hyperthyroidism. To avoid a thyrotoxic storm, ¹³¹I is usually administered after pretreatment with antithyroid drugs, with thyroid-stimulating hormone (TSH) increase and functional recruitment of inhibited normal tissue. Therefore, both autonomous nodule(s) and normal tissue are irradiated. This may be a reason for late hypothyroidism occurring in 15-25% of patients. This study aimed at assessing different pretreatment modalities with combined methymazole and triiodothyronine, achieving euthyroidism with suppressed TSH. METHODS: After diagnosis of autonomously functioning toxic nodule, patients were subjected to thyrostatic medication. Two months later, TSH was checked; if >0.5 mU/L triiodothyronine treatment was associated. After 2 more months, if the TSH level was suppressed, patients received ¹³¹I-therapy. A total of 149 patients were consecutively enrolled, 41 of whom with uninodular and 108 with multinodular goiter. They were evaluated at diagnosis, pretreatment, 3 and 6 months after therapy and at late follow-up (6.8+/-4.2 years; range: 1-22 years). RESULTS: Administered activity was calculated according to ¹³¹I uptake and gland weight. Methymazole was discontinued 6 days before treatment and T3 was maintained until administration of ¹³¹I-therapy. Euthyroidism was achieved in 88% of patients. At late follow-up, subclinical hypothyroidism was observed in 10 patients (6.7%) and overt hypothyroidism in 5 patients (3.3%). No pathological consequences or side effects of ¹³¹I-therapy were found during the 6.8+/-4.2 year follow-up period. CONCLUSION: Treatment of toxic nodular goiter with ¹³¹I-therapy, under combined thyrostatic-thyromimetic treatment is a simple, safe, well-tolerated, and effective procedure.

Gated blood pool tomography for the evaluation of global and regional left ventricular function in comparison to planar techniques and echocardiography.

BACKGROUND: Multigated radionuclide ventriculography (MUGA) is a simple and reliable tool for the assessment of global systolic and diastolic function and in several studies it is still considered a standard for the assessment of left ventricular ejection fraction. However the evaluation of regional wall motion by MUGA is critical due to two-dimensional imaging and its clinical use is progressively declining in favor of echocardiography. Tomographic MUGA (T-MUGA) is not widely adopted in clinical practice. The aim of this study was to compare T-MUGA to planar MUGA (P-MUGA) for the assessment of global ejection fraction and to transthoracic echocardiography for the evaluation of regional wall motion. METHODS: A 16-segment model was adopted for the comparison with echo regional wall motion. For each one of the 16 segments the normal range of T-MUGA ejection fraction was quantified and a normal data file was defined; the average value -2.5 SD was used as the lower threshold to identify abnormal segments. In addition, amplitude images from Fourier analysis were quantified and considered abnormal according to three different thresholds (25, 50 and 75% of the maximum). RESULTS: In a study group of 33 consecutive patients the ejection fraction values of T-MUGA highly correlated with those of P-MUGA (r = 0.93). The regional ejection fraction (according to the normal database) and the amplitude analysis (50% threshold) allowed for the correct identification of 203/226 and 167/226 asynergic segments by echocardiography, and of 269/302 and 244/302 normal segments, respectively. Therefore sensitivity, specificity and overall accuracy to detect regional wall motion abnormalities were 90, 89, 89% and 74, 81, 79% for regional ejection fraction and amplitude analysis, respectively. CONCLUSIONS: T-MUGA is a reliable tool for regional wall motion evaluation, well correlated with echocardiography, less subjective and able to provide quantitative data.

Sentinel node biopsy in melanoma: the experience of Brescia Civic Hospital.

The accuracy of the sentinel node (SN) technique in the evaluation of lymph node involvement in melanoma was evaluated in 71 consecutive patients with localized disease and Breslow index >1 mm. Lymphoscintigraphy identified at least one SN in 70 of the 71 patients (98.5%). The following day 69 patients underwent selective SN excision. The SN was identified by portable probe. One hundred and twenty-two lymph nodes were removed, 14 (11.4%) of which were metastatic in 9 patients (13%). No metastases were found in 40 patients with Breslow <2 mm. Eight of the 9 patients with positive SNs underwent lymphadenectomy of the whole basin and in two patients new metastatic nodes were found. At 4-26 months' follow-up 1 of the 60 patients with negative SN (scalp melanoma with Breslow 6.2 mm) developed bilateral cervical metastatic nodes. Two more patients with Breslow 3.7 and 5 mm, respectively, developed liver and lung metastases. The remaining 57 patients are still disease free. Among the 9 patients with tumor-positive SNs, 1 was lost to follow-up, 3 died and 5 are still alive. Our data confirm the clinical reliability of the SN technique in melanoma; we feel the technique should be considered a standard tool in the evaluation of melanoma patients.

[Effects of reperfusion and coronary reocclusion on the variability of heart rate in patients with acute myocardial infarction]. / Influenza della riperfusione e della riocclusione coronarica sulla variabilità della frequenza cardiaca in pazienti con infarto miocardico acuto.

The aim of this study was to analyze the very early (first 24 hours) effect of successful or failed thrombolytic therapy on the autonomic nervous system. Thirty consecutive patients with a first acute myocardial infarction were enrolled in the study, and admitted to the Coronary Care Unit within 6 hours of the onset of symptoms and treated with systemic thrombolytic therapy. All patients underwent 24-hour Holter monitoring in order to analyze ST segment variation. The autonomic nervous system was evaluated by frequency-domain heart rate variability: low frequency/high frequency ratio (LF/HF) was measured at the beginning of Holter monitoring (T1), 15 min after reperfusion or 1 hour from the start of thrombolytic therapy (T2) and after 24 hours (T3). Reperfusion status was assessed by a > or = 50% reduction in ST segment elevation within 90 min of thrombolytic therapy, and early CK-MB peak. Early coronary reocclusion was detected by early reduction in ST segment elevation followed by stable ST segment re-elevation. Twenty patients (66%) showed successful thrombolytic therapy (Group 1), 5 patients (17%) had no evidence of successful thrombolytic therapy (Group 2) and 5 patients (17%) showed an early reocclusion (Group 3). LF/HF ratio values at T1 were similar in the three groups (5.66 +/- 1.7 vs 5.65 +/- 1.2 vs 5.51 +/- 0.9, NS). At T2, LF/HF ratio was significantly higher in Group 1 and 3 than Group 2 patients (9.21 +/- 1.7 and 11.1 +/- 1.2 vs 5.58 +/- 1.4, respectively, p < 0.001). In Group 1 LF/HF ratio was significantly lower at T3 when compared with T1 and T2 (1.9 +/- 1 vs 5.66 +/- 1.7 and 9.21 +/- 1.7, respectively, p < 0.001). Conversely, in Group 3 LF/HF ratio at T3 was similar to values measured at T1 (5.59 +/- 1.7 vs 5.51 +/- 0.9, respectively, NS) and significantly higher than those detected in Group 1. In Group 2, LF/HF ratio resulted substantially unchanged at T3 (5.49 +/- 1.7, NS). In conclusion, 1) successful thrombolytic therapy induces early beneficial effects on the autonomic nervous system function, as shown by increased heart rate variability values, when compared with failed thrombolytic therapy; 2) however, during the early period following coronary reperfusion, a transient but dramatic increase in sympathetic activity is observed. This could trigger coronary flow instability, thus facilitating reocclusion, by activating different pathogenetic mechanisms (increased vascular tone, platelet activation, thrombogenic factor prevalence); 3) early coronary vessel reocclusion precludes favorable effects of reperfusion on sympatho-vagal balance observed after the first 24 hours.

[Primary carcinoma of the medium and distal third of the biliary tract. Personal experience in diagnosis and treatment]. / Carcinoma primitivo del terzo medio e distale della via biliare principale. Diagnosi e trattamento nella nostra esperienza.

A group of 36 patients, observed between 1985 and 1995, with primary carcinoma localized in the medium and distal third of biliary tract is presented. Sixteen patients (44.4%) have undergone radical surgical treatment and the other twenty (55.5%) received a palliative procedure with an average survival of 33.7 months and 8.8 months for the first and second group respectively. The actual location of the tumor was obtained by ERCP and its final stadiation occurred during operation mainly trough intraoperative ultrasonography. The preoperative biliary drainage led to a better postoperative outcome and to a better prognosis. In the case where the tumor was localized only in the third medium of the biliary tract, a limited resection of the biliary tract with Roux's reconstruction was carried out. Otherwise in the cases where the lesion was localized in the border between the medium and distal third and in the distal tract, a duodenocephalopancreasectomy was performed. Even if this is a group of lesions with a poor prognosis, when it is possible to have an early diagnosis it is necessary to carry out an aggressive surgical treatment considering the higher percentage of survival compared to any other palliative procedure.

[Evaluation of an immunoenzymatic method for determining the tumor marker CA 15-3)]. / Valutazione di una metodologia immunoenzimatica per la determinazione del marcatore tumorale CA 15-3.

CA 15-3 determination has graved to be of clinical utility for diagnosis, evaluation and monitoring patients suffering from tumor. The aim of our study was to compare Sorin (kit ETI CA 15-3 K) and BMI (Enzymun-test CA 15.3) screening between two methodologies' capability. The results obtained were evaluated by using a Passing and Bablok correlation, Spearman rank correlation coefficient. The results obtained shown an over-valuation of the Sorin method vs. BMI.

[Evaluation of an immunoenzymatic method to determine the tumor marker CA 125]. / Valutazione di una metodologia immunoenzimatica per la determinazione del marcatore tumorale CA 125.

CA 125 determination has proved to be of clinical utility for diagnosis, evaluation and monitoring patients suffering from tumor. The aim of our study was to compare Sorin (kit ETI CA 125 K) and BMI (Enzymun-Test CA 125) screening between two methodologies' capability. The result obtained was evaluated by using a Passing and Bablok correlation, Spearman rank correlation coefficient. The results obtained show a low correlation between the two methods.

[Congenital dilatation of the common bile duct in an adult]. / Dilatazione congenita della via biliare principale nell'adulto.

The Authors present a case of congenital dilatation of the common bile duct in adult life, selecting this lesion from the cystic dilatations of biliary tract group. The type I of biliary tract cystic dilatations is, in fact, considered a clinical-pathological situation apart, that, because of his frequence and his peculiar characteristics especially present in the adult, puts particular problems regarding his arrangement an treatment. The most recent aspects of etiophatogenetic and therapeutic problems of this lesion are treated. The increased risk of neoplastic degeneration in the adult, the recognition of an anomalous pancreaticobiliary duct junction as etiophatogenetic fondamental cause and the necessity of a radical exeretic treatment in in opposition to the old therapheutic orientations are especi-5ally considered.

Vulvo-vaginitis and reproduction.

The main micro-organisms able to interfere with the reproductive function have been considered. In particular, the problems concerning the vaginal environment and its interactions with spermatozoa, immunological aspects and contraception. Lastly, reference has been made to methods of prevention and study in the field of diagnostics and of clinical management.

[Determination of the cut-off for marker TPA in healthy children]. / Determinazione del cut-off in una popolazione pediatrica sana per il prolifigen TPA.

In the present study the authors investigated the normal range of the marker TPA in the sera of 100 children (apparently healthy) aged from 0 to 6 years. Well-defined criteria as guide-lines to the interpretation of laboratory results are a very urgent necessity for the expanding utilization of clinical laboratory data. To avoid possible mistakes on such an important area as new MT for the definition of a decisional standard for all the most relevant laboratory marker test. All patients have serum TPA values of less than 95 U/l and confirmed the distribution of TPA values in healthy individuals.

[The efficacy of the hysteroscopic treatment of menorrhagia associated with uterine fibromyomas]. / Efficacia del trattamento per via isteroscopica della menorragia associata con fibromiomi uterini.

Objective of our study was to determine the effectiveness of hysteroscopic surgery in the treatment of menorrhagia associated with uterine myomas. 25 women with clinical and ultrasonographic diagnosis of intramural or submucous myomas were treated for menorrhagia by hysteroscopic surgery: 9 by resection and 16 by resection and endometrial ablation. In both groups there was a significant decrease of dysmenorrhea. The mean number of pads used during the heaviest day of menses decreased significantly from 19.5 to 7.4 in women undergoing resection only, and from 20.8 to 2.9 in women treated by resection and endometrial ablation. 2 women of 9 became amenorrheic and no one underwent hysterectomy. 12 of 16 became amenorrheic and 2 underwent hysterectomy. Our study show that menorrhagia can be treated by hysteroscopic surgery of uterine myomas in some selected women.

A case of ovarian endometriosis in late post-menopause.

We describe a case of ovarian endometriosis in a 67 years old woman admitted to our hospital. After clinical examination and instrumental investigation, we opted for surgical operation including bilateral ovarosalpingolisis, bilateral hysteroannexectomy and appendectomy.

Cyto-histological aspects of chorionepithelioma in fluorescence.

The Author illustrates cytochemical and histochemical pictures of the chorion-epithelioma, which the fluorochromization with orange acridine, according to the Bertanlanffy's method, gives with extreme clearness. The intense colouring of both nucleic acids, DNA and RNA indicates a lively functional activity and elevated trophism of the trophoblastic cells.

Effect of CDP-choline treatment on mitochondrial and synaptosomal protein composition in different brain regions during aging.

Several age-dependent modifications of inner mitochondrial membrane and synaptosomal plasma membrane proteins from different brain regions of 4-, 12-, 18- and 24-month-old male Wistar rats, were observed. Some proteins, identified by immunoblotting assay as various subunits of mitochondrial respiratory chain complexes and calmodulin, were particularly impaired. Chronic treatment with CDP-choline at a dose of 20 mg/kg body weight per day for 28 days caused significant changes in the amounts of several of the above mentioned proteins. Most of the proteins, which decreased during aging, showed a significant increase after CDP-choline treatment compared with the corresponding control values at the same age. The effect of CDP-choline might be due to: the increased availability of cytidylic nucleotides, which in the brain are present in limited amounts compared to the other nucleotides; the increased content of total adenine nucleotides; the improvement of brain energy metabolism.

[DNA extraction from hard dental tissues]. / Estrazione di DNA dai tessuti duri del dente.

Two different standard ways of DNA extraction (salting out and phenol-chloroform methods) were assayed in order to recovery nucleic acids from dental tissues. The DNA extracted was tested for purity by means of transverse alternating field electrophoresis (TAFE) using Saccharomyces cerevisiae chromosomes as markers. Both extraction methods give similar qualitative and quantitative results being a DNA yield from hard dental tissues approximately 30% of those extracted from the whole tooth. Our results indicate salting out as a preferable method due to its rapidity and usefulness.

Modifications of synaptosomal plasma membrane protein composition in various brain regions during aging.

The age-dependent modifications of synaptosomal plasma membrane protein composition in three different rat brain regions (cerebral cortex, cerebellum and striatum) at various ages (4, 12 and 24 months) were studied. The proteins were separated by gel-electrophoresis and the quantity of the different polypeptides was determined densitometrically from the stained gels. In the three brain regions examined several age-related modifications in the amount of the synaptosomal plasma membrane proteins were observed. In particular a significant decrease in the content of some synaptosomal plasma membrane proteins at 24 months of age was found. The age-related modifications in the protein composition of synaptosomal plasma membrane may cause changes in many brain functions, such as neurotransmission, ionic transport and enzyme activities. Particularly interesting is the decrease of a protein with 18 kDa mol. wt. This protein has been identified as calmodulin by immunoblotting assay. The decrease in the amount of this protein may be correlated to the impairment of several Ca(2+)-requiring processes in the aging brain.

[Trials of the diagnostic potentials of TPA in tumorous and nontumorous lung pathologies in 303 cases]. / Sperimentazioni sulla potenzialità diagnostica del TPA nelle patologie tumorali e non del polmone in 303 casi.

Serum tissue polypeptide antigen (TPA) has been determined in 271 patients with pleural or pulmonary neoplastic diseases (131) or with benign lung diseases (140). Using a cut-off of 95 U/L, TPA has a sensitivity and specificity of 65%. Therefore, TPA serum determination can suggest a diagnosis of malignancy, but its evaluation, as a single test, is not useful to differentiate between malignant or benign disease. TPA can be useful as an ancillary test in the follow-up of lung cancer therapy.

A motion correction algorithm for an image realignment programme useful for sequential radionuclide renography.

The correction of organ movements in sequential radionuclide renography was done using an iterative algorithm that, by means of a set of rectangular regions of interest (ROIs), did not require any anatomical marker or manual elaboration of frames. The realignment programme here proposed is quite independent of the spatial and temporal distribution of activity and analyses the rotational movement in a simplified but reliable way. The position of the object inside a frame is evaluated by choosing the best ROI in a set of ROIs shifted 1 pixel around the central one. Statistical tests have to be ful-filled by the algorithm in order to activate the realignment procedure. Validation of the algorithm was done for different acquisition set-ups and organ movements. Results, summarized in Table 1, show that in about 90% of the simulated experiments the algorithm is able to correct the movements of the object with a maximum error less or equal to 1 pixel limit. The usefulness of the realignment programme was demonstrated with sequential radionuclide renography as a typical clinical application. The algorithm-corrected curves of a 1-year-old patient were completely different from those obtained without a motion correction procedure. The algorithm may be applicable also to other types of scintigraphic examinations, besides functional imaging in which the realignment of frames of the dynamic sequence was an intrinsic demand.

[Correlation between serum glutathione reductases and bone densitometry values]. / Correlazione tra glutatione-reduttasi serica e valori densitometrici ossei.

Free radicals, because of their marked chemical activity, have often been found to be involved in many human diseases. Enzymatic antioxidant systems, namely glutathione-reductase, present both in red blood cells and in serum, have been demonstrated to play a key role as free radicals scavengers. The present work has been carried out in order to evaluate the possible role played by free radicals in the demineralization process of the bone matrix. Glutathione-reductase activity, assayed by a slightly modified Horn's method, was related to bone density measurements. All the subjects with reduced densitometric values showed reduced glutathione-reductase levels. Our results seem to support the hypothesis of a strict relationship between low activity of antioxidant systems and demineralization process of the bone, in consequence of enhanced free radical levels.