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The aim of the study: This article presents the incidence of prostate cancer, isolated high grade prostatic intraepithelial neoplasia (PIN) and atypical lesions suspicious for prostate cancer (LSPC) during subsequent screening rounds in the centres of five of the countries participating in the European Randomized Study of Screening for Prostate Cancer (ERSPC). The incidence and predictive value of high grade PIN and LSPC for prostate cancer in subsequent biopsy following these diagnoses were evaluated. Patients and methods: Study group consisted of 56,653 screened men in the ERSPC centres of Finland, Italy, Netherlands, Sweden and Switzerland, who underwent 3-7 screening rounds at 2-4 year interval. Data for prostate cancer were obtained from the ERSPC central database. Data for high grade PIN and LSPC were gathered from each ERSPC centre. Detection rates of subsequent prostate cancer in the first re-biopsy after these diagnoses were determined. Results: The average cancer detection rate was 3.5%, 3.2% and 3.5% for the completed rounds 1, 2 and 3, respectively, in all five centres. Incidence of high grade PIN increased from 1.5% in the first round to 5.0% in the third round, varying among centres in the first round between 0.8% and 7.6%. The cancer detection rate in the first re-biopsy after the diagnosis of high grade PIN was 12.9%. Incidence of LSPC was 2.4%, 2.7%, 2.2% and 2.6% in the first, second, third and fourth round, respectively. The cancer detection rate at the first re-biopsy after the diagnosis of LSPC was in average 33.8%. Conclusions: Cancer detection rate was stable during the three screening rounds. The wide variation in frequency in particular of high grade PIN among the ERSPC centres suggests a considerable inter-observer variation. The average comparatively low detection rate of isolated high grade PIN in the first screening round may be screening-related, while its consistent increase during three screening rounds could be the consequence of a.o. previous screening and ageing of the population. The observed low risk of prostate cancer after isolated high grade PIN in this screening setting is in line with the current recommendation to abstain from early repeat biopsies after this diagnosis. The association of LSPC with high incidence of prostate cancer in re-biopsies confirms the need for early repeat biopsies and follow-up of these men. The low percentage of LSPC (

A panel of previously characterized monoclonal antibodies: B67.6, OKT3, OKT4, B53.4, Leu3a, OKT8, Leu2a, OKM1, M12 and B52.1 were used as a probe to assess mononuclear cells in peripheral blood (PB), lymph nodes (LN) and spleens of untreated patients with Hodgkin's disease (HD). The mean % and absolute number of T lymphocytes were significantly decreased in PB of HD patients when compared with control values. Reduction of circulating T lymphocytes reflected the selective loss of cells showing the ‘helper/inducer’ (‘H/I’) phenotype. In fact, a lower number of these cells was demonstrated in HD patients with advanced disease and, even though to a lesser extent, in those with localized disease. In contrast, decreased values of T cells with the ‘cytotoxic/syppressor’ (‘C/S’) phenotype were only found in patients with advanced disease, showing pan-lymphocytopenia. Unlike PB, LN and spleens involved by HD usually showed increased %s of T lymphocytes, especially of those possessing the ‘H/I’ phenotype. The displacement of T lymphocytes with ‘H/I’ phenotype from PB to lymphoid organs further supports the possibility of a chronic immune response against abnormal cells or unknown antigens in the affected organs of patients with HD.

Objective:Pregnant women with systemic sclerosis (SSc; scleroderma) have an increased risk of premature delivery and small full-term infants. During placental development, angiogenesis and vascular remodelling are essential for a successful pregnancy outcome. An analysis was made of the pathological changes and expression of angiogenic factors in SSc placentas.Methods:Placenta biopsies were obtained from three patients with SSc and four healthy uncomplicated pregnancies after delivery at 34–38 weeks of gestation. The sections were stained with Masson’s trichrome and phosphotungstic-acid-haematoxylin and immunostained for connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and receptors VEGFR-1 and VEGFR-2.Results:The pathological findings were signs of decidual vasculopathy, increased syncytiotrophoblast knotting, placental infarcts and villous hypoplasia. Severe and diffuse perivascular and stromal fibrosis of decidua and chorionic villi, and extensive deposition of fibrinoid material around decidual vessels and in intervillous spaces were observed. Strong CTGF expression in the vessel wall, decidual cells and fibroblasts and α-SMA+ myofibroblasts were found. VEGF and VEGFR-2 expression was stronger in SSc than in healthy placentas, while VEGFR-1 expression was similar to controls. PlGF immunopositivity was weaker in SSc.Conclusion:In SSc placentas, severe fibrosis and abnormal vascular remodelling were detected. This may result in reduced blood flow leading to deep sufferance of maternal placenta and possible premature delivery.

Aim To assess the validity of PSA doubling time (PSADT) as a predictor of prostate sextant biopsy outcome in patients with PSA levels in the 4–10 ng/mL range. Material and methods A consecutive series of 355 sextant biopsies performed during 2001–2007 in subjects with negative digital rectal examination and transrectal ultrasonography was considered. Variables tested as possible predictors were age, total and free/total PSA value, PSA velocity and PSA doubling time. While PSA at time of biopsy and free/total PSA were determined with a standardized method undergoing strict quality control, previous PSA values used to assess velocity/doubling time came from other labs using different assays over widely varying intervals of time. The association with biopsy outcome (cancer vs non-cancer) was investigated by univariate and multivariate analysis. Results Apart from free/total PSA ratio, no other studied variable showed a statistically significant and independent association with biopsy outcome, either at univariate or multivariate analysis. No studied variable had a good performance as a biopsy indicator. Depending on the variable considered, 1.17 to 1.97 cancers would be missed to spare 10 benign biopsies. Conclusion When based on PSA data determined with different assays over widely varying intervals and in the absence of an underlying protocol for PSA surveillance, PSA velocity and doubling time should never discount a biopsy prompted by total PSA elevation.

WEB-2086 -- an antagonist of platelet-activating factor receptor (PAFR) with known anti-inflammatory, antiangiogenic and antileukaemic properties -- also proved to inhibit the proliferation in human solid tumour cell lines of different histology, and with much higher efficacy than in normal fibroblasts. A detailed analysis of WEB-2086 anticancer activity was then performed focusing on breast adenocarcinoma MCF-7 and MDA-MB-231 cells. WEB-2086-treated cells, either expressing (MCF-7) or unexpressing (MDA-MB-231) the oestrogen receptor (ER)alpha, underwent a dose-dependent growth arrest (IC(50)=0.65+/-0.09 and 0.41+/-0.07 mM, respectively) and accumulation in G(0)-G(1) phase. WEB-2086 also induced morphological and functional changes typical of mature mammary phenotype including (i) cell enlargement and massive neutral lipid deposition (best accomplished in MCF-7 cells); (ii) decrease in motility and active cathepsin D levels (mainly observed in highly invasive MDA-MB-231 cells). The expression of ERalpha was neither increased nor reactivated in treated MCF-7 or MDA-MB-231 cells, respectively. WEB-2086-induced differentiation in breast cancer cells involved the upregulation of PTEN, a key tumour suppressor protein opposing tumorigenesis, and was apparently independent of p53, PAFR, peripheral benzodiazepine receptor and ERalpha status. Overall, WEB-2086 can be proposed as an effective antiproliferative and differentiative agent with interesting translational opportunities to treat breast cancers in support to conventional chemotherapy.

The reported detection rate of prostate cancer, lesions suspicious for cancer, and prostatic intraepithelial neoplasia (PIN) in needle biopsies is highly variable. In part, technical factors, including the quality of the biopsies, the tissue processing, and histopathological reporting, may account for these differences. It has been thought that standardisation of tissue processing might reduce the observed variations in detection rate. Consensus among the members of the pathology committee of the European Randomised study of Screening for Prostate Cancer (ERSPC) concerning the optimal methodology of tissue embedding resulting in guidelines for prostatic needle biopsy processing was reached. The adoption of an unequivocal and uniform way of reporting lesions encountered in prostatic needle biopsies is considered helpful for decision taking by the clinician. The definition of parameters for quality control of prostatic needle biopsy diagnostics will further facilitate clinical epidemiological multicentre studies of prostate cancer.

In order to improve the diagnosis of amyloidosis and allow a standardized therapeutic approach, 20 years ago we created a specific Centre in Florence with a Register dedicated to the dise...

AIM: To investigate morphological changes in Enterocytozoon bieneusi and the duration of symptomatic relief after combination treatment with furazolidone and albendazole in AIDS patients. METHODS: Four severely immunocompromised AIDS patients with symptomatic E bieneusi infection of the gut received an 18 day course of combined furazolidone and albendazole (500 + 800 mg daily). All patients were monitored for parasite shedding in stool by light microscopy at the end of treatment and monthly during follow up. At the end of treatment, duodenal biopsy specimens obtained from three patients were studied by transmission electron microscopy by two pathologists blind to the patients' treatment or clinical outcome. Duodenal biopsy specimens obtained from one of the patients two months after completion of treatment were also studied electronmicroscopically. RESULTS: All patients had long lasting symptomatic relief, with a major decrease--or transient absence--of spore shedding in stools from completion of treatment. After treatment, changes in faecal spores were persistently found by light microscopy in all cases, and there was evidence of both a substantial decrease in the parasite load and ultrastructural damage in the parasite in all biopsy specimens. The treatment was well tolerated, and no patient had clinical or parasitological relapse during follow up (up to 15 months). CONCLUSIONS: The long lasting symptomatic relief observed in all four treated patients correlated with the persistent decrease in parasite load both in tissue and in stool, and with the morphological changes observed in the life cycle of the protozoan. These data suggest that combined treatment with furazolidone and albendazole is active against E bieneusi and may result in lasting remission even in severely immunocompromised patients.

AIMS: To investigate the effectiveness of long term, low dose azithromycin treatment for chronic cryptosporidiosis in patients with AIDS. METHODS: Azithromycin was administered as initial daily treatment to 13 patients with AIDS: 6 patients received 500 mg for 30 to 40 days (mean 35); 3 patients received 1000 mg for 21 to 50 days (mean 37); and 4 patients received 1500 mg for 20 days. Nine of the 13 patients were also given low dose maintenance treatment with different schedules of azithromycin for 30 to 360 days (mean 129). Patients were monitored, during and after treatment, for parasite shedding in stool and for daily stool frequency and body weight. All but one patient had severe immunodeficiency. RESULTS: Long term, low dose maintenance treatment was associated with major clinical and parasitological benefits: there was probable eradication of infection in 2 patients, and 7 patients showed a complete response with persistent high decrease (5 patients) or clearance (2 patients) of parasite in stool. The drug was well tolerated, and there was no relapse either during treatment or during follow up (up to 21 months). These results were more impressive than those observed after the short term initial course of azithromycin, which was unable at any tested dose to achieve parasite clearance in stool (except in the patient with less advanced immunodeficiency) or to prevent relapse in 3 patients who discontinued treatment. Reversible side effects occurred with the 1500 mg daily dose. CONCLUSIONS: Long term, low dose azithromycin is well tolerated and may induce stable remission of chronic cryptosporidiosis in patients with AIDS. It may lead to probable eradication of the infection in some patients, even those with severe immunodeficiency.

The composition of the prostatic capsule is important from a clinical point of view, since it is considered to be a barrier against the spread of prostatic tumours. Clinical follow-up demonstrates that apparently intracapsular tumours, particularly in the posterosuperior region of the gland, are frequently understaged at clinical diagnosis. The morphology of the prostatic capsule was studied in 6 cadavers. In each case the prostate was obtained in one block together with the basal portion of the bladder, the seminal vesicles, the anterior wall of the rectum and the periprostatic connective tissue. Part of the material was plastinated, while the remainder was studied using histological and immunohistochemical methods. The prostate was found to be surrounded by connective tissue abundant with smooth muscle cells, and continuous with the stromal septa which subdivide the glandular tissue. A rich network of blood vessels was identifiable. In some regions, particularly in the posterosuperior region, a real capsule was not identifiable. The connective tissue seemed to constitute a continuum between the prostate gland and neighbouring organs, in particular, a connective tissue barrier between the prostate and the seminal vesicles was completely absent. Therefore, due to the absence of a capsular barrier and to the presence of a rich vascular network, a prostatic tumour which begins in the posterior region of the gland should be considered as potentially extracapsular.

Authors report the case of a newborn who died just a few hours after the birth as a result of intrauterine Parvovirus B19 infection. Diagnosis of fetal hydrops was made by ultrasound examination at the 25th week of pregnancy. Etiology was established on the basis of specific antibody findings in the serum of the mother, the fetus (by cordocentesis), and the neonate; B19 virus was then observed in the fetus and the neonate tissues after death using the dot-blot hybridization assay and the polymerase chain reaction technique for viral DNA. The severe fetal anemia was treated with intrauterine transfusions, but achieved poor results. The pathogenesis of fetal hydrops and advisability of intrauterine treatment in such cases are discussed.

Diffuse large b cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Gene-expression profiling in DLCBL has brought insight into the biological heterogeneity of the disease. two major subgroups have been identified: germinal center B (GCB) cell and non-germinal center (non-GCB). The aim of this study was to define retrospectively by immunohistochemistry the B-cell origin of 69 patients treated with R-CHOP14 and to evaluate if dose-dense therapy could improve their clinical outcome. According to immunohistochemistry analysis 28 patients were derived from germinal center and 41 from non-germinal center. After a median period of observation of 46 months (range 3-101 months) the overall survival (OS) was 75% and progression-free survival (PFS) was 53% and no differences were observed according to cell origin. In conclusion, we can point out that intensification could enhance the efficacy of the R-CHOP regimen and improve overall survival in patients with non germinal lymphoma.

A 64 year old woman died at the third attack of MFS. Histological examination demonstrated segmental demyelination and axonal swelling of the peripheral nerves studied, oculomotor included. In the C.N.S. only mild chromatolytic changes and rare pyknosis of the nerve cells in the midbrain were found without signs of primary inflammation. We reviewed the findings in all the 4 anatomoclinical cases of MFS and in 2 cases of GBS with ophthalmoplegia or ataxia. With one exception, they appear to be concordant with those of our case. As the histological examination showed CNS involvement consequent upon peripheral nerve impairment, we are bound to change our opinion on the nosological position of MFS. Any small CT enhancements in the brain in MFS may be due, as in some cases of demyelinating polyneuropathy, to focal rupture of the blood-brain barrier.

OBJECTIVE To assess the consistency of grading outcome among seven of eight participating centres of the European Randomised Screening Program of Prostate Cancer (ERSPC), a multicentre randomized trial intended to detect a difference in prostate cancer-related mortality between screened participants and a control group. Currently, tumour stage and grade in prostatectomy specimens represent the most predictive variables for biological behaviour. In prostate needle biopsies the tumour grade is a strong factor for deciding therapy. PATIENTS AND METHODS Within the ERSPC all prostate cancers detected in needle biopsies were graded according to the Gleason score system. Gleason scores were compressed in three categories of ≤ 6, 7 and 8–10. Data for grading outcome were obtained from the databases from seven individual centres; in one centre the slide sets with cancer were separately reviewed. RESULTS Combining the data of seven ERSPC centres 66% of cancers detected in the screening arm were Gleason score ≤ 6 and 92% were ≤7. Gleason score 8–10 cancers varied from 2 to 11%. This variation in Gleason scores may be attributed to differences in the population characteristics and biopsy indications. CONCLUSION These data indicate that in the seven ERSPC centres most screen-detected cancers have favourable characteristics on biopsy. Men with these cancers are amenable for treatment with curative intent. The observed differences in Gleason score distribution in different centres may partly be attributed to geographical differences and differences in the age range of the screened populations.

To assess the predictive value for a positive biopsy of different indicators (rectal examination, transrectal ultrasonography, total PSA, PSA density).Positive predictive value was assessed on 1107 consecutive US-guided transperineal biopsies performed from 1991 to 2001 (cancer=344, dysplasia (PIN)=64, atypical hyperplasia=4, benign hyperplasia=686, inadequate=9) with univariate and multivariate analysis.Increasing age (chi square for trend 52.2, p0.001), positive rectal examination (chi square 233, df=1, p0.001) or ultrasonography (chi square 191, df=1, p0.001), total PSA (chi square for trend 68.9, p0.001) and PSA density (cutoff 0.15, chi square 104, df=1, p0.001; cutoff 0.20, chi square 104, df=1, p0,001) were all significantly associated to the likelihood of a positive biopsy outcome. Multivariate analysis stresses the independent role of Psa density over total PSA. If the parameters studied had determined the biopsy, spared benign biopsies [positive rectal examination=505 (66%), positive ultrasonography=467 (61%), PSA4=124 (16%), PSA10=159 (74%), PSA density0,15=426 (62%), PSA density0.20=517 (75%)] would not have justified the amount of delayed cancer biopsies [positive rectal examination=103 (29%), positive ultrasonography=55 (15%), PSA4=42 (12%), PSA10=569 (46%), PSA density0,15=73 (25%), PSA density0,20=107 (37%)].The parameters currently available prior to biopsy, if used alone, allow no reliable prediction of biopsy outcome. Positive predictive value, particularly for PSA density, allows a better evaluation of biopsy indication, particularly for random sextant biopsies in the 4-10 ng/ml PSA range, which are frequently negative.

Splenic cysts are rare in pediatric surgery. Congenital epidermoid cysts are exceptional representing only 2.5% of all splenic cysts in childhood. Nowadays, considering the short- and long-term complications of splenectomy in children, the management of epidermoid cyst consists of partial splenectomy or decapsulation of the cystic wall. To our knowledge, the case reported in this article describes the first successful laparoscopic decapsulation of an epidermoid splenic cyst in an 10-year-old child using the UltraCision LaparoSonic Coagulating Shears (LCS). Follow-up at six months confirms no recurrence. Laparoscopic splenic decapsulation provides minimal access and small surgical trauma for treating the cyst while preserving splenic function. The use of UltraCision LCS makes the laparoscopy safely, expeditiously, with minimal blood loss and short hospital stay.

Actinomycotic infections of the cervicofacial area are rare and frequently show a confusing clinical picture. We report a case of actinomycosis that mimicked a neoplasm of the tongue. The clinical and pathologic features and the differential diagnosis of this unusual oral infection are discussed.

We report our experience with large core biopsy (LCB: 14-Gauge needles) of questionable or suspicious breast lesions detected at mammography and/or US. All biopsies were performed under instrumental guidance. We also report on technique, costs, time, advantages and disadvantages of the method and, finally, give precise indications on when and why large core biopsy is needed.From january 1996 to may 2000 we performed 1000 microhistologic biopsies on breast lesions at the Unità Integrata di Senologia, Azienda Ospedaliera Careggi, Florence; 650 (65%) were non palpable lesions. Large core needles were used (14-Gauge caliber). In the majority of cases (70%) we used US guidance, in the others a stereotactic guidance was employed.Microhistologic biopsy allowed accurate characterization in most cases. Inadequate samples were obtained in 15 cases. The false negative rate was 6%. Surgery was needed to characterize the lesion unquestionably in 13 cases only.In agreement with literature reports, our results confirm large core biopsy as an adequate alternative to surgical biopsy and, to some extent, to FNAC, thanks to its moderate invasiveness, low costs, short execution time, little patient discomfort and high sensitivity (93.98%) and specificity (99.7%).

Any breast lesion/abnormality detected at mammography must be characterized as (non)-neoplastic before surgery. Fine needle aspiration cytology (FNAC) permits a precise diagnosis in over 70% of cases but exhibits many inadequate, false negatives or questionable findings. This makes surgical biopsy mandatory in many cases. An alternative is offered by fine needle biopsy (FNB: 16-18 G needles) or by large core biopsy (LCB: 14 G needles), which procedures can reduce the number of questionable diagnoses with no major discomfort or side-effects for the patient.January, 1996, to October, 1997, we performed 422 microhistologic biopsies on breast lesions at the Unità Integrata di Senologia, Azienda Ospedaliera Careggi, Florence, Italy. 383 of these lesions were nonpalpable. FNB was performed in 221 cases and LCB in 201. Most biopsies (65%) were carried out under US guidance and some others (25%) under stereotactic guidance.Microhistologic biopsy allowed accurate lesion characterization in most cases, even though LCB obviously performed much better. Samples were inadequate in 5.88% of cases with FNB and only in 2.98% of cases with LCB. The false negative rate was 1.92% for FNB and 0.99% for LCB. Surgical biopsy was needed for an unquestionable diagnosis only in 9.5% of FNB and 3.9% of LCB cases.Our results confirm the literature data on how LCB can be considered a valid alternative to surgical biopsy (and, to some extent, to FNAC); in particular, its advantages are: moderate invasiveness, little patient discomfort and high diagnostic accuracy. Moreover, the procedure is short (5-10 minutes) and costs much less than surgical biopsies (1/2 to 1/4).

To define the relationship between morphological injury of the intestinal mucosa and infections in AIDS patients.Forty-nine AIDS patients were examined by upper gastrointestinal (GI) endoscopy and 8 of them also by lower GI endoscopy. Biopsy specimens, taken from the lower duodenum, esophagus and rectum, were studied by light (L.M.) and transmission electron microscopy (T.E.M.). Stool examination for microorganisms was routinely performed in all patients.Microorganisms were detected in 37 of the 49 patients (75.5%) by combined tissue and stool examination. The histological study revealed villous atrophy, inter- and intra-enterocyte oedema and epithelial degenerative changes in most of the patients whether or not they had detectable microorganisms.Combined methods (endoscopy, L.M. and T.E.M., studies of tissue samples, microbiological study of stool samples) may be used to improve the documentation of infections and morphological injury of the intestinal mucosa in AIDS patients.

Age has proved to be an important prognostic factor in patients with advanced non-Hodgkin lymphoma (NHL) and these patients require intensive and extensive therapy. Dose-reduction and therapy attenuation have reduced treatment-related toxicity, but have also decreased therapeutic efficacy. Between January 1990 and December 1992, 41 previously untreated patients, 65 years with stage 2-4 intermediate- or high-grade NHL were treated with a new therapeutic scheme which included Mitoxantrone, Etoposide, Cyclophosphamide and Prednisone (MiCEP). Twenty-eight patients achieved a complete remission, ten patients partial remission (overall response rate of 93%) and two cases were resistant. The overall survival was 66% with a median follow-up of 24 months from diagnosis: three patients relapsed after a median period of 7 months. The relapse-free survival was 92% after a median follow-up of 18 months. Blood and other organ toxicity was acceptable and 12% of patients experienced a grade 4 (WHO) neutropenia. In conclusion, MiCEP was effective in inducing a good remission rate with moderate toxic effects in elderly patients with intermediate- or high-grade NHL and appears to be a useful combination to use in this group of patients.

La morphologie de la capsule prostatique a ete etudiee sur 4 cadavres par une methode de plastification et des examens histologiques. Dans plusieurs regions, en particulier dans celle des canaux ejaculateurs, de la vesicule seminale, de la base de la vessie et de la paroi anterieure du rectum, il n'est pas possible de definir une veritable capsule. La prostate est entouree d'un tissu vasculaire qui semble plus lier que separer les organes etudies. Nous considerons que cette organisation a des implications cliniques.

Two widespread human herpesviruses, the Epstein-Barr virus (EBV) and the Human Herpesvirus 6 (HHV-6), have been frequently associated with Hodgkin's Disease (HD) and, recently, it has been observed an HHV-6 transactivation effect on EBV replicative cycle. We studied the presence and the possible association between EBV and HHV-6 in childhood HD cases, nodular sclerosis subtype. We analyzed formalin-fixed and paraffin-embedded lymph nodes from 15 cases by PCR for HHV-6 genome, and by PCR and in situ hybridization (ISH) for EBV genome. One out 15 samples resulted positive for HHV-6 DNA PCR, while 5 resulted positive for EBV DNA PCR. Only one sample positive for HHV-6 resulted positive for both HHV-6 and EBV genome. All samples were negative in ISH. At the moment, it is not clear the exact role of EBV and HHV-6 in the lymphomagenesis, neither it is possible to establish the rate of their interaction; our data show that it does not exist in vivo an evidence of their association.

Considering the role proposed for myofibroblasts in inflammatory and hyperelastotic lung diseases, the possibility arises that these cells are involved in bronchial pathology, including asthma. To address this issue, we have analyzed by light microscopy, histochemistry and immunohistochemistry the structure of extra- and intra-pulmonary bronchi of patient died of asthma. We have demonstrated hyperplasia of connective tissue cells and fibers in the mucosa, all around the lumen of extra- and intra-pulmonary bronchi. The cells were thin and elongated, labeled by anti-actin and anti-vimentin antibodies and interspersed with many elastic and collagen fibers, therefore they were interpreted as myofibroblasts. These findings may explain the rigidity of the bronchial wall in patients with asthma, which causes the progressively more limited resolution of airway obstruction upon pharmacological treatment and the gross anatomical finding of bronchial stiffness at inspection of the lungs. The possibility should also be considered that myofibroblasts and elastic--not collagen--fibers have contributed to bronchial hyperreactivity at an early stage of the disease.

Authors report the case of a newborn who died just a few hours after the birth as a result of intrauterine Parvovirus B19 infection. Diagnosis of fetal hydrops was made by ultrasound examination at the 25th week of pregnancy. Etiology was established on the basis of specific antibody findings in the serum of the mother, the fetus (by cordocentesis), and the neonate; B19 virus was then observed in the fetus and the neonate tissues after death using the dot-blot hybridization assay and the polymerase chain reaction technique for viral DNA. The severe fetal anemia was treated with intrauterine transfusions, but achieved poor results. The pathogenesis of fetal hydrops and advisability of intrauterine treatment in such cases are discussed.

CT-guided fine-needle biopsy of the chest is nowadays a conventional diagnostic procedure, which can be furtherly improved so as to increase its diagnostic sensitivity and to reduce complications. We studied a series of possible improvements over a 2-year period (1990-1992). In our radiology department 164 CT-guided biopsies were performed in 130 men and 34 women. DBNH Haaga 20-G (15 cm) needles (Cook, Denmark) were used. This kind of needle is a coaxial cutting-edge needle used for simultaneous cytological and histological sampling. Exams were performed with a Philip Tomoscanner CX-S (scanning time: 2.8 seconds). Of 164 tissue samples, 153 (93.4%) were adequate for histological diagnosis. As for suspected neoplastic disease, our results demonstrated 108 true positives, 27 true negatives, 18 false negatives and no false positive. Sensitivity, specificity and diagnostic accuracy were 85.7%, 100% and 88.2%, respectively. In 24 cases there were minor complications--i.e., 5 cases of parenchymal hemorrhage and 19 cases of minor pneumothorax. In one case only there was major pneumothorax which required surgical drainage. On the basis of our experience, we suggest the use of such coaxial catheters as the DBNH Haaga type for the collection of both histological and cytological material because this needle reduces the need for repeated invasive and potentially dangerous maneuvers.

Due to technical difficulties in performing amniocentesis before the 12th week of pregnancy, very little is known about the components of human amniotic fluid before that time. Amniocentesis was performed between the 7th-11th week of gestation in 25 informed and consenting patients, who had to undergo therapeutic interruption of pregnancy. The cells from the amniotic fluid were stained, counted on a hemocytometer, and checked for vitality. The origin of these cells was determined from cellular cultures the intracellular content of the hemoglobin and the chloroacetate esterase content of the hemoglobin and the chloroacetate esterase contents were also studied. Taking advantage of the "in vitro" adhesive properties of these cells to the bone marrow stromal feeder layer, we obtained clonal growth of an erythroid nature from 18 out of 33 samples. At the 17th week of gestation, an increased number of cells and a decrease in their vitality was found. Between the 7th and 12th week, the cellular composition of the fluid was totally different from that found later in the pregnancy. Small nucleated, round cells were identified as hematopoietic progenitor cells. At the beginning of the 11th week, a cellular population, typically used to perform prenatal diagnosis of chromosomal abnormalities from the 14th week of pregnancy appeared. Since hematopoietic progenitor cells were found in the amniotic fluid before the 12th week of gestation, these cells most probably come from the hematopoietic cells of the yolk sac through the thin membrane of the yolk sac at this time.

A review on infections by Isospora belli and Sarcocystis spp. both in healthy and in AIDS patients is done on the basis of literature and personal data. In this view a special focus is made on isospora belli infection in AIDS because of its high recurrence after successful attack therapy. Consequently the most recent protocols for maintenance and attack therapy in these patients are reported. At the end, concerning ultrastructural pathology, the features of some Isospora belli developing stages are described by means of electron microscopy on duodenal biopsy specimens from a patient.

An imported case of intestinal schistosomiasis in AIDS is analysed by the relationships between immune response, diagnostic methods, pathogenetic mechanisms. The inconclusiveness of negative results from both serology and stool parasitology is remarked whereas the efficacy of associated histological, histochemical and immunohistochemical methods is emphasized in order to get better data on aetiological diagnosis and on cell types and size of reactive granulomas. In the case studied, negative serology, absent fecal egg excretion and uneffective granulomatous response with scarcity of T and B lymphocytes have been documented by means of the above methods.

Three italian siblings, two brothers and one sister, two of whom affected from MGUS and one from Waldenstrom Macroglobulinemia (WM), were found to have sytemic amyloidosis. Two patients showed the same HLA typing and the same light chain (k), but differed in presenting clinical symptoms. Caryotype studies however did not show any peculiar abnormalities shared by the three brothers. Family history and clinical investigations did not account for a typical heredofamilial form, either for re active or senile amyloidosis. Since evidence of familial occurrance has already been demonstrated for immunoglobulin-related (AL) amyloidosis, we suggest that our three patients may represent a new case of familial AL-Amyloidosis. Routine investigations for amyloidosis in patients with familial MGUS will better define in future the prevalence of such familial form and, eventually, the underlying genetic mechanisms.

Excessive consumption of alcoholic beverages may be associated with gastrointestinal symptoms, including dyspepsia and diarrhoea. It is not clear whether or not chronic alcohol ingestion damages the mucosa of the small intestine. We investigated the effect of chronic alcohol abuse on the duodenal mucosa, and particularly on its extracellular matrix (ECM) network. Duodenal biopsy specimens were obtained during upper gastrointestinal endoscopy from 50 chronic alcoholics without cirrhosis and 10 healthy subjects. Morphological studies were performed by routine histology, immunohistochemistry and electron microscopy. Morphometry of duodenal tissues was performed with a computerized image analyser. No significant duodenal epithelial changes were found in alcoholics, despite an evident reduction in the enterocyte turnover. Myofibroblast-like cells were significantly increased in the villus stroma of alcoholics in comparison to controls. These cells stained positively for desmin, alpha-smooth muscle actin and for several ECM components. In alcohol abusers the thickness of the mucosal basement membrane was greater and the staining for collagen I and III was enhanced both in the basement membrane and in the villus stroma. A higher expression of tenascin was also seen at the base of villi of alcoholics. Chronic alcohol abuse may induce fibrosis of duodenal villi which is associated with a transformation of villus juxta-parenchymal cells into active subepithelial myofibroblast-like cells able to produce different ECM components.

A case of pachydermoperiostosis characterised by the presence of finger clubbing, periostosis, sweating of hands and feet is described. Modifications of capillaroscopic pattern and of arteriovenous anastomoses are reported. The periungual border and finger tip tissue showed diffuse endothelial hyperplasia, hyalinosis, and sclerosis with packing of collagen fibres. Electron microscopy showed hypertrophic and activated endothelia (numerous and hypertrophic Golgi complexes, several Weibel-Palade bodies, vesicles of micropinocytosis, and glycogen particles), the basal membrane thickened and reduplicated, perivasal infiltrate in superficial derma, reticulation and segmentary reduplication of basal membrane in arteriovenous shunt. In the perineural connective tissue numerous Luse bodies (long spacing collagen) were evident. The data indicate that in the early phase of pachydermoperiostosis morphological endothelial and collagen fibre abnormalities are present, though there is a normal peripheral blood flow.

Fifty-five consecutive patients with primary gastrointestinal intermediate or high grade non-Hodgkin's lymphoma were analysed to assess the efficacy of chemotherapy following surgical tumour resection. Histological subtypes were high grade (n = 18), intermediate grade (n = 36) and unclassified (n = 1). The majority of patients had gastric presentation (71%) and localised disease (84%). Surgery consisted of radical resection in 25 patients (45%) and partial or palliative excision in the remaining cases (22 and 8 respectively). Four subjects died within 3 months of surgery, two patients refused adjuvant chemotherapy and 49 completed the postoperative chemotherapeutic programme. Chemotherapy included either Fi2/74 (adriamycin + vincristine + bleomycin + cyclophosphamide + prednisone) or Fi3/74 (adriamycin + VM26 + bleomycin + cyclophosphamide + prednisone). Excluding the group who underwent radical tumour resection, postoperative chemotherapy induced complete remission in 81% of the remaining 30 patients. The 10-year cause-specific survival for the 53 treated patients was 76% (median follow-up 58 months) with a stable curve plateau after 80 months. Proportional-hazard multivariate statistics showed that survival was influenced by type of surgical resection (P less than 0.05) and stage (P less than 0.05), whereas age, sex and histological subtype were not influential. Our data indicate that chemotherapy following surgical resection of gastrointestinal lesion induces long-term remission in primary gastrointestinal lymphomas.

With the aid of CT acute hemorrhagic leukoencephalopathy (AHL) was diagnosed before death in a 65 year old woman. On the histopathological evidence, which is very similar to that for experimental allergic encephalomyelitis (EAE), AHL is considered to be a highly acute variant of parainfective encephalomyelitis.

Endogenous splenic colonies are increased in methylcellulose-treated irradiated mice, 10 days after sublethal irradiation (450 R). The spleen shows an enhancement of megakaryopoiesis, especially localized around foam-cell foci. This suggests that the macrophage system, activated through phagocytic activity against methylcellulose, affects megakaryopoiesis by a microenvironmental mechanism.

In order to verify differences between the fibrinolytic activity in normal and neoplastic pulmonary tissue, 16 subjects underwent infra-operatory biopsy.Samples from normal lung and neoplastic tissue areas were obtained from each subject and then examined using Todd's histoehemical method (Doni A. et al.: VII International Congress on Fibrinolysis, Venezia 1984)The results were evaluated using Wilcoxon’s test, and were expressed by an Index of the Potentiality of Fibrinolysis (I.P.F.) = % Lysis area/% tissue area and by the Ratio between I.P.F. at 30’ and I.P.F. at 45’ of incubation.A statistically significant difference between I.P.F. of normal tissue and the neoplastic one at 30’ and 45’ of incubation was found while no difference between the Ratio of normal and neoplastic tissue was noted.These data suggest that differences in fibrinolytic activity exist as regards normal and neoplastic pulmonary tissue and that these differences may be related to the different amounts of plasmonogen activators (perhaps tPA) present in normal and neoplastic tissue (Doni A. et al.: VIII International Congress on Fibrinolysis, Vienna 1986).Kinetics of fibrinolysis did not show statistically significant differences