From transformation to chronification of migraine: pathophysiological and clinical aspects.

Chronic migraine is a neurological disorder characterized by 15 or more headache days per month of which at least 8 days show typical migraine features. The process that describes the development from episodic migraine into chronic migraine is commonly referred to as migraine transformation or chronification. Ample studies have attempted to identify factors associated with migraine transformation from different perspectives. Understanding CM as a pathological brain state with trigeminovascular participation where biological changes occur, we have completed a comprehensive review on the clinical, epidemiological, genetic, molecular, structural, functional, physiological and preclinical evidence available.

Assessment of liver fibrosis in the clinical setting: something is changing?

Clinical management of compensated chronic liver diseases (CLD) requires precise definition of the stage of liver fibrosis which is the key histologic predictor of progression to cirrhosis. Several methods are used to assess liver fibrosis. Among those, percutaneous liver biopsy is still the gold standard. However, the recent introduction of liver imaging techniques, the rising of statistical tests able to classify CLD noninvasively, and a reconsideration of its potential complications, have contributed to an audit of the evolving role of liver biopsy. At present, there is an increasing interest for noninvasive approaches to evaluate the stage of liver fibrosis in the clinical work-up of patients with CLD. Transient elastography (FibroScan) is a new, noninvasive method to assess liver stiffness and, consequently, the degree of liver fibrosis. Since its use in the clinical setting is of great interest, further studies should define the exact role of this procedure.

Survival of patients with early hepatocellular carcinoma treated by percutaneous alcohol injection.

BACKGROUND: Once small (<10 mm) nodules, suspicious for hepatocellular carcinoma, are detected in cirrhotics, the European Association for the Study of the Liver guidelines recommend to delay histological confirmation and treatment until they increase in size. AIM: To validate this policy by evaluating survival of 450 cirrhotics in Child-Pugh class A or B with unifocal 'early' hepatocellular carcinoma treated by percutaneous alcohol injection. METHODS: Patients were sorted by nodular size into three groups: < or =10 mm (n = 36, group A), >10 to < or = 20 mm (n = 142, group B) and >20 to < or = 30 mm (n = 272, group C). Overall and tumour-free survivals were estimated by Kaplan-Meier method. RESULTS: In groups A, B and C, mean follow-up was 33 +/- 26, 34 +/- 22 and 35 +/- 25 months (P = 0.89), mean survival time was 63 +/- 54, 57 +/- 48 and 62 +/- 66 months (P = 0.69) and mean tumour-free survival was 44 +/- 47, 46 +/- 58 and 41 +/- 68 months (P = 0.51), respectively. When patients were sorted by Child status, mean survival time was 76 +/- 82 and 38 +/- 29 months in Child A and B (P < 0.0001). CONCLUSIONS: The comparable survival of percutaneous alcohol injection-treated patients with single, early hepatocellular carcinoma sorted by nodular size supports the European Association for the Study of the Liver 'wait-and-see' policy for patients with lesions <10 mm, and suggests that allowing the nodules to grow prior to taking further diagnostic or therapeutic actions would not harm these patients.

Hepatic involvement in larva migrans of Toxocara canis: report of a case with pathological and radiological findings.

Patients with the clinical syndrome of visceral larva migrans as a result of Toxocara species, have typical lesions in the liver consisting of granulomas that contain numerous eosinophils and often Charcot-Leyden crystals. This syndrome is rarely taken into account in patients with cholestatic syndrome, especially when hypereosinophilic reaction is absent. We report the case of a 47-year-old immunocompetent woman who presented with abdominal pain, in whom multiple focal liver lesions were discovered. She had come in contact with dogs. Diagnosis of toxocariasi was done. A good clinical response has been obtained by treating with thiabendazole. We present the findings of various imaging studies of the patient. This report shows that visceral larva migrans may be the cause of a chronic liver disease and should be suspected also in patients without fever and hypereosinophilia with cryptogenic cholestatic and focal liver lesions.

Surgery for carcinoma of the gallbladder. Our experience.

BACKGROUND: Carcinoma of the gallbladder is a gastrointestinal malignancy with a very poor prognosis. The 5-year survival rate amounts to less than 5% in most series. In this study we reviewed the results of surgical treatment for gallbladder carcinoma with special reference to extended radical procedures. METHODS: Between 1995 and 2000 we enrolled 36 patients (17 males and 19 females), 24 of whom were treated with simple cholecystectomy and 12 with radical resection (partial hepatectomy, regional lymphadenectomy, and common bile duct resection). The tumours were classified by stage using the criteria of the American Joint Committee on Cancer (AJCC). Stages, operative procedures, results of pathologic examinations and the outcome of the resected cases were reviewed. RESULTS: There were 2 postoperative deaths (0.55%). The mean follow-up period was 19.1 months (range 1-60). For stage I and II disease extended cholecystectomy had a better result than simple cholecystectomy: the 5-year survival rates were 38.4 versus 19%, respectively. For the patients with advanced stage III or IV gallbladder carcinoma, a significant advantage of survival resulted in case of liver resection as compared to surgical treatment without liver resection: the 5-year survival rates were 20 and 0%, respectively. CONCLUSIONS: The survival of stage I-II patients was good. For the patients in higher stages the prognosis was significantly worse. In these cases more aggressive surgery may be needed.

Urinary mutagenic activity after different immunosuppressive protocols in renal transplant patients.

Cyclosporin (CsA) and azathioprine (AZA) are useful immunosuppressive drugs in the management of kidney and liver transplant recipients. We investigated urinary mutagenicity in three groups of kidney transplant recipients after different immunosuppressive protocols. Urinary mutagenicity was detected in a base-pair strain, E. coli WP2uvrA, in a liquid incubation assay. No mutagenic activity was detected in the urines of patients treated with CsA (4.5 mg/kg); 85% of the urines in the second group treated with AZA (1.26 mg/kg) showed high mutagenic activity, whereas mutagenic activity was found in 40% of the urines of subjects treated with CsA and AZA (3.89 mg/kg + 1.15 mg/kg). These data suggest that immunosuppressive therapy with AZA carriers a high risk of urinary mutagenicity, while immunosuppressive combined treatment with CsA and AZA significantly reduces this risk.

Mutagenic activity in wastewater concentrates from dye plants.

Wastewater concentrates from the wastewater treatment systems of three dye plants were tested for mutagenic activity in Salmonella typhimurium TA98 and Escherichia coli WP2uvrA using a fluctuation assay. Concentrates were prepared by passing samples of wastewater (5-6 or 30 litres) through two porous resins (XAD-2 and XAD-7) in series. S. typhimurium in the presence of microsomal activation proved to be the more sensitive marker of mutagenicity. Mutagenic responses were observed in concentrates from all three plants tested. The results show that mutagenic activity was particularly high in the incoming waters and increased after active, biological treatment. Physico-chemical treatment may be effective in decreasing mutagenic activity, but only if appropriately used.

Elevated serum chromogranin A in patients with hepatocellular carcinoma.

Chromogranin A is a cellular marker forneuroendocrine tumors. Elevated levels of chromogranin A are also found in patients with cancers of epithelial origin when neuroendocrine differentiation occurs, which is associated with a poor prognosis. We investigated the prevalence of serum levels of chromogranin A in patients with primary liver cancer. Seventy-nine patients (65 males, mean age 67.6 years, range 48-88 years) with liver cirrhosis and hepatocellular carcinoma were studied. The etiology of cirrhosis was identified as due to hepatitis C virus infection in 47 patients, to hepatitis C virus and alcohol in 7, to alcohol alone in 14, to hepatitis C and B virus in 2, and to hepatitis B virus alone in 4. Of the remaining patients, 2 suffered from hemochromatosis and 3 had cryptogenic cirrhosis. According to the Child-Pugh's score, 54 patients belonged to class A, 22 to class B, and 3 to class C. The concentration of chromogranin A was measured in serum with a commercial solid-phase two-site immunoradiometric assay. Elevated serum levels of chromogranin A were found in 32 of 79 patients (43%). Levels over 600 ng/ml were present in 7 of 76 patients (9.2%), all of whom had very high serum levels of alpha-fetoprotein. Hence, elevated serum levels of chromogranin A are present in over one third of patients with hepatocellular carcinoma. It is therefore possible that some hepatocellular carcinomas could acquire a neuroendocrine differentiation. We propose further studies to ascertain whether serum levels of chromogranin A are useful as a prognostic marker for hepatocellular carcinoma as in prostate cancer.

[Markers of type B viral hepatitis]. / I markers dell'epatite virale di tipo b.

The discovery of Australian antigen (HBsAg) has led to an increasing deal of knowledges about the virus of type B hepatitis (HBV); several markers of HBV have been detected and are becoming disposable for clinical and epidemiological purposes. The HBsAg is carried by 3 types of particulate structures discovered by electron microscopy as small spherical particles having diameter around 22 nm, long filaments and spherical particles having an overall diameter of the 42 nm (Dane-particle) with an electron-dense core. Dane-particle core contains circular double-stranded DNA molecules and an enzyme, the DNA polymerase. At present, Dane-particle is thought to represent the HBV, having properties consistent with those of a complete virus. Four antigen/antibody systems related to viral type B hepatitis have been discovered; they have been designated with the following nomenclature: HBsAg/anti-HBs, HBcAg/anti-HBc, HBeAg/anti-HBe, epilon antigen/anti epilson. The availability of the HBV markers for clinical purposes will permit a better understanding of the sequence of the biological reactions as well as of the clinical and epidemiological features concerning this viral infection: incubation period, acute disease, resolution, chronic carrier state, actively or passively immunized subject, persistent or subsided infectivity, prognosis.

[Type B viral hepatitis. Recent findings]. / Epatite virale di tipo B. Recenti acquisizioni.

The discovery of hepatitis B surface antigen by Blumberg in 1965 offered a specific marker that could readily be employed in the clinical, epidemiological and experimental investigation of type B viral hepatitis. It has since been followed by the continuous gathering of further knowledge concerning this disease. The morphology and immunological and biochemical features of virus B, the epidemiology and prevention of hepatitis B, and marker determination techniques are examined in an overview of the present situation.

Reliability of the MB/BacT system for testing susceptibility of Mycobacterium tuberculosis complex isolates to antituberculous drugs.

The susceptibility of 115 Mycobacterium tuberculosis complex clinical isolates to isoniazid, streptomycin, ethambutol, and rifampin was assessed by the MB/BacT and BACTEC 460TB systems. The correlation between the two tests was 98.3% for isoniazid, 100% for streptomycin and rifampin, and 95.8% for ethambutol. Turnaround times for antimicrobial susceptibility testing ranged from 5 to 11 days (median, 8.5 days) for MB/BacT and from 4 to 8 days (median, 6 days) for BACTEC 460TB.

Enzyme immunoassay (ELISA) for the detection of specific IgG antibodies to Toxocara canis ES antigens.

This paper reports the development of an enzyme-immunosorbent assay for the detection in human serum of specific IgG against excretory/secretory antigens of second stage Toxocara canis larvae. Similar tests have been already used in several countries for clinical and epidemiological purposes on human Toxocariasis and currently represent the only specific means for the serological diagnosis of this parasitic disease. Specificity and sensitivity have been proved and original data on the epidemiological setting of Toxocara infection in Northern Italy are given.

Comparison of the MB/BacT and BACTEC 460 TB systems for recovery of mycobacteria from various clinical specimens.

A total of 1,830 specimens (75.7% respiratory and 24.3% nonrespiratory) were cultured in parallel with the MB/BacT and BACTEC 460 TB systems and on Lowenstein-Jensen (LJ) medium. Mycobacteria were identified from 173 (6.5%) specimens. The most common species recovered were Mycobacterium tuberculosis complex (65. 9%), Mycobacterium avium complex (22.5%), and Mycobacterium chelonae (9.2%). The recovery rates by individual systems were 96.5, 99.4, and 95.9% for MB/BacT, BACTEC 460 TB, and LJ medium, respectively, for all mycobacteria; the recovery rates were 99.1, 100, and 98.2%, respectively, for M. tuberculosis complex alone. The difference among the recovery rates for all mycobacteria and those for individual species was not significant. The BACTEC 460 TB system detected M. tuberculosis isolates more rapidly than the MB/BacT system (8 versus 11.8 days for smear-positive specimens [P < 0.01] and 18 versus 21 days for smear-negative specimens [P < 0.05]), whereas the MB/BacT system more rapidly detected the nontuberculous mycobacteria (17.1 versus 12.7 days [P < 0.01]). These results indicate that the nonradiometric MB/BacT system is a rapid, sensitive, and efficient method for the recovery of M. tuberculosis and nontuberculous mycobacteria from both pulmonary and extrapulmonary clinical specimens.

IgE and IgG antibodies in Toxocara canis infection. A clinical evaluation.

The relationship between IgE and IgG antibodies against the metabolic exoantigen of Toxocara canis (TEX antigen) in sera of selected patients with the ocular and visceral form of the disease have been investigated. The specificity and sensitivity of the TEX antigen employed in immunoenzymatic and radioimmunologic assays have been verified. Six hundred and forty-one sera from healthy donors were tested as controls. Our data emphasize the importance of IgE antibodies to ocular larva migrans syndrome and suggest that they play a significant role as a marker of infection. In the visceral form, IgG antibodies seem to mask the presence of IgE by a competitive mechanism toward the same epitopes of the parasite. In fact, IgE antibody titers increase after depletion of IgG from serum.

Inflammatory pseudotumour of the liver: diagnosis by fine needle biopsy in two cases and a review of the literature.

Inflammatory pseudotumours of the liver are rare: over 40 cases had been reported up to 1992, the majority of which are surgical or laparoscopic findings. In this paper we describe two additional cases in which diagnosis was acquired by fine needle biopsy under ultrasonographic guidance. This approach allowed sufficient sampling of tissue for diagnostic purposes.