Diffusion-weighted imaging in hyperacute haemorrhagic stroke patients presenting within thrombolysis window.

INTRODUCTION: Diffusion-weighted imaging (DWI) in magnetic resonance imaging (MRI) has been proposed as the first line of neuroimaging for acute ischaemic stroke. The reliability of DWI in detecting intracranial haemorrhage, however, is still unproven, compared with susceptibility-weighted imaging (SWI) and CT scan which being considered the gold standard. This study seeks to establish the reliability of DWI as a first-line imaging modality to detect the intracranial haemorrhage in the patients present within the thrombolysis window. MATERIALS AND METHODS: A retrospective cross-sectional analysis was performed on patients who presented to our institution from April 2020 until July 2021 for acute stroke and had MRI brain as first-line neuroimaging. A total of 31 subjects were included in this study. Two radiologists assessed the signal patterns in DWI sequence and compared them with SWI and CT Brain, whenever available, as the gold standard for observing the presence of intracranial haemorrhage. RESULTS: The majority of patients with hyperacute bleed proven to be revealed on SWI or CT, thus showed characteristics of central hyperintensity and peripheral hypointense rim, on DWI. Slightly more than half (51.6%) presented with mild to moderate NIHSS scores (1-15). The sensitivity, specificity, positive predictive value and negative predictive value of DWI in detecting intracranial intra-axial haemorrhages were exceptionally high. There is strong interobserver level of agreement in identifying central haemorrhagic signal intensity [kappa = 0.94 (0.06), p < 0.05]. CONCLUSION: This study supported the DWI sequence as a reliable sequence in MRI, to detect intracranial haemorrhage in hyperacute stroke.

A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: lights and shadows on the relationship with COVID-19 infection.

BACKGROUND: Acral chilblain-like lesions are being increasingly reported during COVID-19 pandemic. However, only few patients proved positivity for SARS-CoV-2 infection. The relationship between this skin manifestation and COVID-19 infection has not been clarified yet. OBJECTIVE: To thoroughly characterize a prospective group of patients with chilblain-like lesions and to investigate the possible relationship with SARS-CoV-2 infection. METHODS: Following informed consent, patients underwent (i) clinical evaluation, (ii) RT-PCR and serology testing for SARS-CoV-2, (iii) digital videocapillaroscopy of finger and toe nailfolds, (iv) blood testing to screen for autoimmune diseases and coagulation anomalies, and (v) skin biopsy for histopathology, direct immunofluorescence and, in selected cases, electron microscopy. RESULTS: Nineteen patients, all adolescents (mean age: 14 years), were recruited. 11/19 (58%) of them and/or their cohabitants reported flu-like symptoms one to two months prior to skin manifestation onset. Lesions were localized to toes and also heels and soles. Videocapillaroscopy showed pericapillary oedema, dilated and abnormal capillaries, and microhaemorrhages both in finger and toe in the majority of patients. Major pathological findings included epidermal basal layer vacuolation, papillary dermis oedema and erythrocyte extravasation, perivascular and perieccrine dermal lymphocytic infiltrate, and mucin deposition in the dermis and hypodermis; dermal vessel thrombi were observed in two cases. Blood examinations were normal. Nasopharyngeal swab for SARS-CoV-2 and IgG serology for SARS-CoV-2 nucleocapsid protein were negative. Importantly, IgA serology for S1 domain of SARS-CoV-2 spike protein was positive in 6 patients and borderline in 3. CONCLUSIONS: Chilblain-like lesions during COVID-19 pandemic have specific epidemiologic, clinical, capillaroscopic and histopathological characteristics, which distinguish them from idiopathic perniosis. Though we could not formally prove SARS-CoV-2 infection in our patients, history data and the detection of anti-SARS-COV-2 IgA strongly suggest a relationship between skin lesions and COVID-19. Further investigations on the mechanisms of SARS-CoV-2 infection in children and pathogenesis of chilblain-like lesions are warranted.

Onyx in Brain Arteriovenous Malformation Embolisation.

INTRODUCTION: Embolisation has long been used as an adjunct to surgical resection in the treatment of brain arteriovenous malformation (bAVM). The most commonly used embolic material, n-butylcyanoacrylate glue, requires experience and skill to handle its quick and unpredictable flow and polymerisation. A new liquid embolic agent, ethylene vinyl alcohol copolymer (Onyx), is less adhesive and polymerises slowly, which provides better control for radiologists performing embolisation. OBJECTIVE: To report our experience in embolisation using Onyx alone or in combination with histoacryl for bAVM embolisation in our tertiary referral centre. METHODS: We retrospectively reviewed the anatomy, technical conditions, complications and clinical outcome of all bAVM patients embolised at our centre using Onyx alone or in combination with n-butylcyanoacrylate glue. RESULTS: Between 2010 and 2013, 13 patients [6 (46.2%) male; 7 (53.8%) female; aged, 14-57 years] were included, and a total of 31 embolisations were performed. Clinical presentation included hemorrhage [9 (69.2%)], seizures [2 (15.4%)], and headache [2 (15.4%)]. Most AVMs were located in the brain hemispheres [12 (92.3%)] and measured <3 cm [7 (53.8%]. Complete occlusion of the AVM was obtained in 2 (15.4%) patients; 11 (84.6%) patients had partial occlusion [6 (54.5%) had <50% nidus occlusion]. Complications occurred in four procedures involving 3 patients (morbidity, 23.1%). This resulted in the death of 1 patient (mortality, 7.7%) and complete recovery with no disability in 2 patients. CONCLUSION: The total nidal occlusion achieved herein is comparable to other similar studies. Our morbidity and mortality were higher compared to other studies which may be attributed to the small number of patients. More data is being collected which may better reflect on our experience.

hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.

BACKGROUND: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. METHODS: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras(G12D/+),LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb. RESULTS: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo. CONCLUSIONS: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.

Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers.

BRAF(V600E) is the most frequent genetic mutation in papillary thyroid cancer (PTC) and has been reported as an independent predictor of poor prognosis of these patients. Current guidelines do not recommend the use of BRAF(V600E) mutational analysis on cytologic specimens from fine needle aspiration due to several reasons. Recently, immunohistochemistry using VE1, a mouse anti-human BRAF(V600E) antibody, has been reported as a highly reliable technique in detecting BRAF-mutated thyroid and nonthyroid cancers. The aim of this study was to test the reliability of VE1 immunohistochemistry on microhistologic samples from core needle biopsy (CNB) in identifying BRAF-mutated PTC. A series of 30 nodules (size ranging from 7 to 22 mm) from 30 patients who underwent surgery following CNB were included in the study. All these lesions had had inconclusive cytology. In all cases, both VE1 and BRAF(V600E) genotypes were evaluated. After surgery, final histology demonstrated 21 cancers and 9 benign lesions. CNB correctly diagnosed 20/20 PTC and 5/5 adenomatous nodules. One follicular thyroid cancer and 4 benign lesions were assessed at CNB as uncertain follicular neoplasm. VE1 immunohistochemistry revealed 8 mutated PTC and 22 negative cases. A 100% agreement was found when positive and negative VE1 results were compared with BRAF mutational status. These data are the first demonstration that VE1 immunohistochemistry performed on thyroid CNB samples perfectly matches with genetic analysis of BRAF status. Thus, VE1 antibody can be used on thyroid microhistologic specimens to detect BRAF(V600E)-mutated PTC before surgery.

Early onset absence epilepsy of childhood: Epidemiologic data, treatment and outcome in a sample of 56 patients born between 2000 and 2018.

PURPOSE: The aim of our work is to describe the characteristics of Early Onset Absence Epilepsy (EOAE) and to observe whether specific anamnestic, clinical or electroencephalographic characteristics can influence the drug sensitivity of this pathology. METHODS: We carried out a retrospective study of patients affected by absence epilepsy with onset under four years of age, born between January 1st 2000 and December 31st 2018, who were reffered to the Regional Epilepsy Center of Spedali Civili of Brescia. We then divided the sample into three groups based on the age of onset. RESULTS: Our sample is composed of 56 patients. Among the children with epilepsy onset under two years of age (11), all were still on therapy after three and six years of follow-up, and 64 % of them required polytherapy. Among patients with epilepsy onset between two and three years of age (24), 87 % were still on therapy after three years of follow-up and 68 % after six years of follow-up; 46 % of these subjects required polytherapy. Among patients with epilepsy onset between three and four years of age (21), 89 % were still on therapy after three years of follow-up and 38 % after six years of follow-up; 38 % of them required polytherapy. CONCLUSIONS: We observe that patients with an earlier epilepsy onset have a worse outcome and a lower drug sensitivity. This may allow to predict in which cases it would be appropriate to maintain antiseizure therapy for a prolonged period.

Multimodality imaging of intraosseous ganglia of the wrist and their differential diagnosis.

Intraosseous ganglion (IOG) is the most frequently occurring bone lesion within the carpus and is often an incidental finding on radiographs obtained for other reasons. Two types of IOG have been described: an "idiopathic" form (or type I), the pathogenesis of which has not been completely clarified, and a "penetrating" form (or type II), caused by the intrusion of juxtacortical material (often a ganglion cyst of the dorsal soft tissue) into the cancellous bone compartment. The differential diagnosis for IOG is wide-ranging and complex, including lesions of posttraumatic (posttraumatic cystlike defects), degenerative (subchondral degenerative cysts), inflammatory [cystic rheumatoid arthritis, chronic tophaceous gout (CTG)], neoplastic (benign primary bone tumours and synovial proliferative lesions), ischaemic (Kienböck's disease or avascular osteonecrosis of the lunate) and metabolic (amyloidosis) origin. Multimodality imaging of IOGs is a useful diagnostic tool that provides complete morphological characterisation and differentiation from other intraosseous cystic abnormalities of the carpus. Thin-slice multidetector computed tomography (MDCT) can provide high-spatial-resolution images of the cortical and cancellous bone compartments, allowing detection of morphological findings helpful in characterising bone lesions, whereas magnetic resonance (MR) imaging can simultaneously visualise bone, articular surfaces, hyaline cartilage, fibrocartilage, capsules and ligaments, along with intra- and periarticular soft tissues.

[Multimodal imaging in the differential diagnosis of soft tissue calcinosis]. / Imaging multimodale nella diagnosi differenziale della calcinosi dei tessuti molli.

Soft tissue calcinosis is a common radiographic finding, which may be related to different types of pathological processes. Multimodality imaging, combined with analysis of clinical and laboratory data, plays an important role for the differential diagnosis of these conditions. Conventional radiography is considered the first line approach to soft tissue calcinosis; CT and MRI may provide further information to better characterize calcified deposits. Imaging may help to distinguish metabolic calcification, such as primary tumoral calcinosis and the secondary one (associated with acquired disorders of calcium or phosphate regulation), from dystrophic calcification, which is associated to normal blood values of phosphate. The sedimentation sign typical of tumoral calcinosis has been demonstrated by plain film radiography, CT, MRI, and, more recently, by ultrasonography. Other types of soft tissue calcinosis may have a degenerative, metaplastic or neoplastic origin, and their characterization strongly relies on multimodality imaging.

Accidental Nasal Myiasis Caused by Megaselia rufipes (Diptera: Phoridae) in a Child.

A case of a nasal myiasis in a 3-yr-old Italian girl who was referred to Bambino Gesù Hospital in Rome, Italy, is reported. Larvae discharged with the nasal mucus were microscopically identified as Megaselia spp.; DNA barcoding analysis showed that they belonged to the 'scuttle fly' species Megaselia rufipes (Meigen). Based on the patient's history, she became infected when she played outside. This is the first report of myiasis in humans due to M. rufipes (Diptera: Phoridae).

[Multimodality imaging of chronic tophaceous gout]. / Imaging integrato nella gotta cronica tofacea.

The diagnosis of gout is usually based on clinical presentation and laboratory findings. Imaging plays a role in the assessment and grading of articular damage related to chronic, long-standing disease, which is characterized by granulomatous synovitis, tophi, and erosions. Multimodality imaging of chronic tophaceous gout may be useful in clinical practice for a variety of purposes, including assessment of disease-related anatomical changes and monitoring of articular and soft-tissue lesions over time, especially in response to urate-lowering therapy. Radiography remains the primary imaging technique. Ultrasonography may detect monosodium urate crystals on cartilage, is helpful to assess small joint effusion, to guide to joint aspiration, and to evaluate the volume of tophi. Computed tomography is considered to be more sensitive than plain radiography in the detection and evaluation of cortical bone erosions associated with tophi. MRI represents the only imaging modality which provides visualization of bone marrow oedema associated with erosions and may be useful to characterize and distinguish tophi from other soft tissue nodules.

Outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is considered an optimal indication for liver transplantation (LT) because it may eliminate both the tumor and the underlying liver disease. The present study sought to compare cumulative survival, rate of HCC recurrence, and causes of death among patients with cirrhosis and HCC before and after the adoption of more restrictive criteria (Milan selection criteria) at the time of patient listing. Among 226 adult patients who received an elective liver transplantation between 1999 and 2005, 58 (27%) had a diagnosis of HCC at the time. The 38 patients who underwent transplantation for HCC in the period 1989 to 1998 were considered the "historical group." After LT (mean follow-up, 34 + 28 months), the cumulative survival rate was better among HCC versus non-HCC recipients (93% vs 71% at 1 year and 81% vs 67% at 3 years, respectively; P < .046), although the difference tended to attenuate after 5 years (66% vs 67%, respectively). Tumor recurrence (evaluated in patients surviving at least 3 months after LT) was observed in 10/31 in the historical group versus 4/53 among those who underwent transplantation after 1999. Among the causes of death, recurrence represented 50% in the old series and 23% in patients who underwent transplantation after 1999. Cumulative survival significantly improved among HCC patients who underwent transplantation after 1999 (93% vs 66% at 1 year and 81% vs 50% at 3 years; P < .00001). The 58 patients who underwent transplantation with a diagnosis of cirrhosis and concomitant HCC after 1999 showed even better survival than patients who underwent transplantation for end-stage liver disease without malignancy.

Comparison of clinical, MRI and arthroscopic assessments of chronic ACL injuries, meniscal tears and cartilage defects.

PURPOSE: The aim of this study was to compare the accuracy of clinical examination to that of MRI evaluated by two independent radiologists for the diagnosis of meniscal tears and chronic anterior cruciate ligament injuries and to assess the MRI accuracy in the diagnosis of cartilage defects. METHODS: Seventy-six consecutive patients with suspected intra-articular knee pathology were prospectively evaluated by objective examination, 1.5 T MRI, re-examined by trained radiologist and arthroscopy. Accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated. Agreement analysis with kappa (К) coefficient values was performed for meniscal and ACL tears. RESULTS: No differences were found between diagnostic accuracy of clinical examination, the first and second MRI reports in diagnosis of medial meniscus (84 vs 96 vs 97 %) and anterior cruciate ligament injuries (93 vs 78 vs 89 %). For the lateral meniscal tears, the accuracy of the second radiologist was significantly higher than those of the first (96 vs 75 %; p < 0.01) and clinical examination (96 vs 86 %; p = 0.02). High diagnostic values were obtained for the diagnosis of full-thickness chondral defects with sensitivity of 100 %, specificity of 95 % and accuracy of 95 %. CONCLUSION: Clinical and MRI evaluations have no differences in the diagnosis of medial meniscus and anterior cruciate ligament injuries. A trained radiologist obtained better sensitivity, specificity and accuracy in the diagnosis of lateral meniscus. 1.5 T MRI does not represent the technique of choice in the evaluation of chondral defect but demonstrated high diagnostic accuracy for detection of full-thickness chondral defects. LEVEL OF EVIDENCE: Diagnostic prospective study, Level II.

Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation.

BACKGROUND: The alpha isotype of actin expressed by hepatic stellate cells reflects their activation to myofibroblast-like cell and has been directly related to experimental liver fibrogenesis, and indirectly to human fibrosis in chronic liver disease. AIMS: To evaluate the changes in distribution and percentage of alpha-smooth muscle actin-positive hepatic stellate cells and the correlation with the degree of the fibrosis in cirrhotic livers, as well as in patients with recurrent HCV chronic hepatitis after liver transplantation. METHODS: Human liver biopsies were divided in four groups: (1) normal livers obtained from cadaveric liver donors (n=35), (2) cirrhosis post-HBV hepatitis (n=11), (3) cirrhosis post-HCV hepatitis (n=10), and (4) post-transplant recurrent HCV chronic hepatitis (n=13). Samples were stained with anti-alpha-smooth muscle actin antibody by immunoperoxidase method and semi-quantitatively evaluated. Liver fibrosis was assessed from specimens stained with Masson's trichrome and quantified by computer image analysis. RESULTS: The percentage of alpha-smooth muscle actin-positive hepatic stellate cells was significantly higher in the HBV cirrhosis, HCV cirrhosis and post-transplant HCV recurrent hepatitis groups (36.1+/-15.2, 23.8+/-19.7 and 27.8+/-16.4%, respectively) compared to the liver donor group (2.9+/-4.0%). The alpha-smooth muscle actin-positive hepatic stellate cells to fibrous tissue ratio were significantly higher in the post-transplant recurrent HCV hepatitis group (2.36+/-1.12) compared to both the donor livers and the HCV cirrhosis groups (0.74+/-1.09 and 1.03+/-0.91, respectively). The alpha-smooth muscle actin-positive hepatic stellate cell percentage and fibrosis correlated positively in the post-transplant recurrent HCV hepatitis group and negatively in the HCV cirrhosis group. No difference in the immunohistochemical and morphometrical variables was found between the HCV cirrhosis and HBV cirrhosis groups. CONCLUSIONS: These results indirectly confirm that, in vivo, alpha-smooth muscle actin expression is a reliable marker of hepatic stellate cells activation which precedes fibrous tissue deposition even in the setting of recurrent HCV chronic hepatitis after liver transplantation, and it could be useful to identify the earliest stages of hepatic fibrosis and monitoring the efficacy of the therapy. In the presence of advanced cirrhosis other factors, rather than alpha-smooth muscle actin-positive hepatic stellate cells, may sustain fibrosis deposition.

Predictive factors of outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Studies to define the optimal upper limits of tumor size and number as predictors of outcome after orthotopic liver transplantation (OLT) have yielded conflicting results. We analyzed 72 patients with cirrhosis and hepatocellular carcinoma (HCC) who underwent OLT over a 12-year period in a single center. Predictive factors for survival and tumor recurrence, according to the Milan criteria, were also examined. Our cohort included 60 men and 12 women of mean age 54 +/- 8 years and mean follow-up of 40 +/- 39 months. Origin of cirrhosis was postviral in 70% and Child class B or C in two thirds of patients. HCC was multifocal in 61%; about one fifth of patients had micro- or macrovascular involvement or positive nodes upon histologic examination. The cumulative size of the lesions was <3 cm in 17 patients; >3 to < or =5 cm in 28 patients; >5 to < or =8 cm in 14 patients; and >8 cm in 13 patients. According to the number and size of tumor nodules, 49 patients met the Milan criteria. During follow-up 25 patients died, 13 due to tumor recurrence. The 1- and 2-year survivals were 90% and 85% for patients who met the Milan criteria versus 57% and 51% for patients exceeding those limits (P = .006). A cumulative tumor size >8 cm was predictive of survival and tumor recurrence upon multivariate analysis. The adoption of Milan criteria for selection of cirrhotic patients has improved survival and reduced the rate of tumor recurrence. The evaluation of cumulative tumor size might further improve patient selection.

Epidermal growth factor gene expression is regulated differently in mouse kidney and submandibular gland.

The concentration of the peptide mitogen epidermal growth factor (EGF) is hormonally and developmentally regulated in the granular convoluted tubule cells of the mouse submandibular gland. Using a labeled EGF nucleic acid probe, we have demonstrated that submandibular gland EGF mRNA concentrations increase during postnatal development of the gland and after the administration of testosterone or thyroid hormone. Recently, it was reported that EGF mRNA is present in kidney as well as a number of other mouse tissues. A comparison of EGF gene regulation in submandibular gland and kidney revealed that kidney EGF mRNA levels also increase during the postnatal period. Opposite sex differences were observed, with submandibular gland levels being about 16-fold higher in the male than in the female and kidney levels being 2- to 4-fold higher in the female than in the male. Renal EGF mRNA concentrations are less responsive to hormones than those in the submandibular gland. Renal EGF was localized immunocytochemically to the cells of distal convoluted tubules.

Effect of advanced age on the induction by androgen or thyroid hormone of epidermal growth factor and epidermal growth factor mRNA in the submandibular glands of C57BL/6 male mice.

We have compared the responsiveness of the submandibular glands of mature (12 month old) and senescent (26-28 month old) male C57BL/6 mice to dihydrotestosterone (DHT) or triiodothyronine (T3) in terms of steady state levels of epidermal growth factor (EGF) protein and EGF mRNA. Northern blot analyses did not disclose any differences with age in the apparent sizes of EGF mRNA species. In untreated animals, submandibular glands of 26-28-month-old mice contained approximately 50% less EGF, and 75% less EGF mRNA than those of 12-month-old males. With advanced age, there was a 20% reduction in the absolute volume of the granular convoluted tubule (GCT) compartment, which is the exclusive site of EGF and EGF mRNA in the gland. In general, GCTs of old mice were composed of smaller cells with fewer secretion granules, but there was considerable cell-to-cell variation. In addition, there was greater variation in the intensity of immunocytochemical staining for EGF in senescent GCT cells, which also gave a lower and more variable in situ hybridization signal for EGF mRNA. After hormonal stimulation for 1 week with either tri-iodothyronine (T3) or dihydrotestosterone (DHT), EGF protein concentration in the glands was induced to the same level at both ages. However, EGF mRNA was 50% less abundant in old hormonally stimulated glands, compared to similarly treated young ones. Although many GCT cells in treated glands of senescent males respond to hormonal stimulation by increases in size and in content of secretion granules, there was cell-to-cell variation in responsiveness, especially after treatment with T3. These findings indicate that the decreases seen in the entire gland in EGF and EGF mRNA are caused by a wide-spread deterioration of the GCT cells themselves, which apparently can be reversed in many but not all GCT cells by stimulation with supraphysiologic doses of either T3 or DHT.

Spatial arrangement of subepithelial deposits in lupus and nonlupus membranous nephropathy.

Subepithelial deposits are a common feature of idiopathic membranous glomerulonephritis (MGN) and lupus membranous glomerulopathy (LMGN). We investigated the spatial arrangement of immunoglobulin G (IgG) and C3c fraction of complement (C3c) in the immune deposits of MGN and LMGN with confocal laser scanning microscopy to correlate specific patterns of IgG-C3 interactions with different diseases. Ten patients with MGN and 8 patients with LMGN (World Health Organization class VB) were selected. A determination of the spatial arrangement of the two fluorochromes and the glomerular area occupied by each fluorochrome was performed for each case. Our results showed MGN specimens have an orderly distribution of IgG and C3c, with each deposit showing an outer ring of sole IgG. IgG was always more abundant than C3c (1,619 +/- 271 v 790 +/- 105 micrometer(2), P = 0.002). In LMGN, IgG and C3c were haphazardly arranged, with deposits made of C3c only and an outer ring of IgG only rarely present. Also, the relative amounts of the two antigens were variable, and two groups could be identified (group 1: IgG, 5,515 +/- 1,179 micrometer(2) v C3c, 4,810 +/- 1,174 micrometer(2); P = 0.02; group 2: IgG, 3,358 +/- 658 micrometer(2) v C3c, 4,047 +/- 740 micrometer(2); P = 0.03). Our data show that diffuse IgG capping of the subepithelial immune deposits is diagnostic of MGN. The absence of an orderly three-dimensional arrangement in LMGN deposits (ie, outer ring of IgG) is likely to render active complement components more readily available to inflammatory activities.

Ultrastructural investigation of circulating villous lymphoid cells: a tool in the differential diagnosis of splenic lymphoma with villous lymphocytes.

Ultrastructural examination of circulating lymphoid cells was performed in three cases of splenic lymphoma with circulating lymphocytes (SLVL) in order to define morphological features helpful to distinguish this lymphoma from hairy cell leukemia (HCL). The samples for ultrastructural investigation were obtained by Ficoll sedimentation from peripheral blood and routinely processed for electron microscopy. The ultrastructural features examined were: morphology of villi, morphology of nuclei, presence of nucleoli, distribution of heterochromatin, type of cytoplasmic organelles, presence of specific intracytoplasmic structures such as the ribosome-lamella complex, lysosome-like bodies and perinuclear microfibrils. Our results and a careful review of the literature seemed to confirm that SLVL has electron microscopic features typical enough to be relevant in the differential diagnosis with HCL.

Atypical renal onset and involvement in primary antiphospholipid syndrome in a child.

A case of primary antiphospholipid syndrome (APS) with renal involvement in a 10-year-old child is reported. The peculiarity of the case resided not only in the apparent "primary" occurrence of APS in the pediatric age, but also in the involvement of the kidney. The renal picture in the case described consisted of a focal proliferative glomerulonephritis, without any sign of glomerular thrombosis. We conclude that this should lead to a consideration of primary APS in the differential diagnosis of nephropathies, also in childhood.

Acute cholestatic hepatitis induced by bupropion prescribed as pharmacological support to stop smoking. A case report.

We report the first case of acute cholestatic hepatitis induced by bupropion. This antidepressant was taken by a 49-year-old female as adjuvant treatment to stop smoking. After 20 days of bupropion, the patient presented a symptomatology characterized by asthenia, nausea and scleral icterus and biochemical analyses showed a dramatic increase in direct bilirubin (up to 28 mg/dl) and transaminases (up to 68-fold normal limits). Antinuclear antibodies were positive (title = 1:80; speckled pattern). Biochemical analyses and antinuclear antibodies were normal two years earlier. The histology showed a pattern of acute hepatitis with involvement of bile ducts and with features of centrolobular cholestasis. Treatment with methylprednisolone was commenced and continued for 20 days. Liver enzymes and bilirubin returned to normal within two months of withdrawal of bupropion and remained normal during the 4-month follow-up. Antinuclear antibodies also became negative. Other causes of liver damage were excluded. Considering the clinical diagnostic scale for hepatotoxic adverse drug reaction, our patient showed a score compatible with the final diagnosis of bupropion-related cholestatic hepatitis.