Clavulanic acid sensitization seems more involved in cutaneous than systemic reactions in amoxicilline-clavulanate drug reactions.

Summary: BLs allergy is considered a major health issue, as BLs are the most frequently involved in drug allergic reactions. Amoxicillin (AX) is the most frequently involved drug in sensitization among all BLs. AX is commercialized alone or combined to clavulanic acid (CLA) in order to increase the antibiotic spectrum. The growing prescriptions of AX-CLA formulations contributed to increase the role of CLA as an allergy inducer. At present, little is known about the clinical characteristics of hypersensitivity reactions to clavulanate. The aim of this study was to assess the difference in the prevalence of cutaneous vs systemic reactions in patients who had a documented history of allergic reactions to amoxicillin-clavulanate and tested positive for clavulanate or penicillin/amoxicillin. Our study suggests that patients who presented only muco-cutaneous reactions were more often sensitized to CLA rather than AX.

Fibrinogen and factor VIIag in healthy adolescents: the Floren-teen (Florence teenager) Study.

At least five studies based on more than twenty thousand healthy subjects indicated that fibrinogen is an independent risk factor for cardiovascular events; less clear-cut is the relation between factor VII and risk for arterial thrombotic disorders, which was demonstrated in two of the three studies investigating this association. However, no study has investigated the behaviour of fibrinogen and factor VII in an adolescent population. In a study of Preventive Medicine and Education Program, fibrinogen (clotting method) and factor VIIag (ELISA), in addition to other metabolic parameters, life-style and familial history, were investigated in 451 students (313 females and 138 males, age 15-17 years) from two high schools of Florence. Fibrinogen levels were significantly higher in women than in men, whereas factor VIIag levels did not significantly differ. Both fibrinogen and factor VIIag significantly correlated with total cholesterol (p < 0.05) while only fibrinogen correlated with body mass index (p < 0.01). Factor VIIag was significantly correlated with systolic blood pressure (p < 0.001). This study provides information on coagulation risk factors in a population of adolescents which may be of importance in planning coronary heart disease prevention programs.

Fosinopril in the treatment of hypertension: effects on 24h ambulatory blood pressure and on blood pressure response to exercise.

This study evaluated the effects of medium-term once daily administration of fosinopril (20 mg) on BP profile and on BP response to exercise in patients with mild to moderate hypertension. Twenty patients (14 males and 6 females; 25-57 years of age), after a six week drug wash-out phase, underwent 24h ambulatory BP monitoring (ABPM) (Spacelabs 90207) and, the day after, maximal bicycle exercise testing. Patients then received a once daily treatment with fosinopril and ABPM and exercise testing were repeated 45-60 days later. Fosinopril decreased average 24h SBP and DBP (-13.5 mmHg and -9.7 mmHg, respectively, P < 0.002); a significant BP reduction was observed both in day and in nighttime, without alteration in diurnal BP profile. The antihypertensive effect was still evident 24h after dosing. Trough to peak ratio was 0.58 +/- 0.16. Fosinopril induced a reduction of SBP and DBP during exercise testing (-20 and -11 mmHg at baseline; -17 and -8 mmHg at peak exercise; -24 and -14 mmHg at the sixth minute of recovery; P < 0.002), with a slight prolongation of exercise time (+46 seconds, P = 0.041). These results indicate that fosinopril at a once daily dose of 20 mg provides a sustained 24h BP reduction associated with BP reduction during physical exercise. These effects have been obtained without altering diurnal BP profile, without excessive hypotension at the time of maximal antihypertensive effect and with a slight improvement of exercise tolerance.

Long-survival in responding patients with metastatic breast cancer treated with doxorubicin-docetaxel combination. A multicentre phase II trial.

BACKGROUND: The doxorubicin-docetaxel combination is active in breast cancer; the aim of the present study was to evaluate the complete response rate and safety profile of the doxorubicin and docetaxel regimen as first-line chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: Forty-three patients entered the study. Treatment plan was: doxorubicin (50 mg/m2, i.v. bolus) followed 1 hour later by docetaxel (75 mg/m2 i.v. infusion over 1 hour), q 3 weeks, for up to six courses. The patients achieving a response or a stabilisation of disease after 6 courses were allowed to intensify the treatment with docetaxel (100 mg/m2, q 3 weeks) for up to 2 courses. G-CSF (or GM-CSF) was administered if clinically indicated. RESULTS: Patients' median age was 57years (range 32-75) and 72% of them had visceral disease. A total of 217 doxorubicin-docetaxel courses were delivered, with 70% of patients receiving all the 6 planned cycles. Among the 40 patients assessable for response (WHO criteria), 7 (16%) achieved a complete remission and 22 (51%) a partial remission, for an overall response rate (intent-to-treat) of 67% (95% C.I. =53% to 81%). In 19 patients, the treatment was intensified with two more single-agent docetaxel cycles, without ameliorating the response. Twenty-seven patients with oestrogen receptor-positive received hormonal therapy as 'maintenance' after completing chemotherapy treatment. NCIC G3-G4 neutropenia was recorded in 58% of patients, with G/GM-CSF used in 23 (53%) patients and 91 (38%) cycles. No patients experienced severe cardiac or neurological toxicity. No toxic death occurred. With a median follow-up of 41 months among alive patients, we observed in responder patients an overall median time to progression and survival of 18 and 33 months respectively, with ten long-survivors still alive. CONCLUSION: This study confirmed the combination doxorubicin-docetaxel as a very active regimen for metastatic breast cancer. Remarkably long survival times were observed not only in complete responders, but also in those patients who responded partially. This might be equally attributed to first-line treatment and sequential maintenance hormonal therapy.

[The use of ambulatory pressure monitoring for evaluating antihypertensive treatment in clinical practice]. / Impiego del monitoraggio pressorio ambulatoriale per la valutazione del trattamento antipertensivo nella pratica clinica.

OBJECTIVE: To describe the clinical experience of our Centre in the assessment of antihypertensive therapy with 24-hour ambulatory blood pressure monitoring (ABPM). DESIGN AND PATIENTS: We retrospectively studied all the 241 out-patients on antihypertensive therapy submitted to ABPM (SpaceLabs 90207, USA) between March 1992 and March 1993 for clinical purposes. We evaluated: 1) the clinical indications for the test; 2) the modifications of drug treatment suggested by the ABPM results; 3) the referring physicians' acceptance of these suggestions; 4) the changes of office BP measured before and 3-6 months after ABPM. RESULTS: 1) The indications for ABPM were: resistant or poorly controlled hypertension (n = 170-71%); suspected "white coat effect" (n = 51-21%); assessment of symptoms (n = 20-8%). 2) The analysis of ABPM suggested to modify drug treatment in 51% of the patients; a "white-coat effect" was found in 18% of the patients. 3) The ABPM suggestions about treatment were accepted by the referring physicians in 89% of the patients. 4) Office BP decreased from 163 +/- 18/99 +/- 9 mm Hg (before ABPM) to 151 +/- 13/91 +/- 7 (3-6 months after ABPM), (p < 0.001). CONCLUSIONS: The use of ABPM in our Centre, which is based on specific clinical indications, provided indications to modify the drug treatment in a high percentage of patients.

Sublethal maternal pre-exposure of fish to cadmium. Effect on the survival of the newly hatched alevins.

The aim of this study was to determine the effects of the exposure of pregnant females of a viviparous teleost Cnesterodon decemmaculatus to sublethal Cd solutions on the survival of their offspring. Ovigerous females were acclimated and accomodated in aquaria containing the following solutions: artificial freshwater medium (AFW) and AFW with 25, 50 and 100 microg Cd(2+) /L (as chloride). Part of the offspring born from control females was transferred to media contain-ing 25, 50 and 100 microg/L of cadmium; the rest of the fry stayed in AFW solutions without cadmium. The offspring born from the females maintained in solutions of cadmium were transferred to aquaria with AFW, and to solutions containing metal at the same concentration as their mother. In all cases mortality was recorded daily for 168 h. The results demonstrated that the survival of newborn offspring was always related to the concentration of Cd(2+) to which they were exposed at birth, regardless of the concentration of the metal to which the mother was exposed during its pregnancy. When exposed to Cd(2+), alevins from non-exposed females showed a constant linear death rate while in those from Cd-exposed it resulted exponential.

[After the 2001 European Society of Cardiology Guidelines: is it possible to reduce the number of patients with syncope to be hospitalized?]. / Dopo le Linee Guida 2001 della Società Europea di Cardiologia: è possibile ridurre il numero di pazienti con sincope da ospedalizzare?

AIM: The aim of this paper was to evaluate how many patients with syncope should be hospitalized according to the 2001 European Society of Cardiology (ESC) Guidelines on the management of syncope. METHODS: Starting from August 2002 we prompted a Syncope Unit (SU), as a multi-disciplinary functional structure including the Emergency Department. One of the main objectives of the SU was the implementation of the 2001 ESC Guidelines on Syncope and of the relevant criteria for hospitalization. All the clinical data concerning the patients presenting with syncope were prospectively collected and stored in a dedicated database. RESULTS: Between September 1, 2002 and April 30, 2003, 402 patients were observed for a syncope. Out of these, 19 had a cardiogenic syncope, 3 focal neurologic disorders, 25 a severe trauma, 4 severe orthostatic hypotension and 5 carotid syncope. Therefore, 56 patients out of 402 were found to have indication to therapeutical hospitalization. Among the remaining 346 patients, 83 patients were found to have a structural heart disease and/or an abnormal ECG, 1 had syncope during exercise, 3 presented a familial history of sudden death. Thirty-three were found to have severe comorbidities and further 14 had occasional indication to hospitalization. Thus, 190 out of the 402 patients with syncope (47.3%) presented at least 1 criterion for hospitalization according to the ESC Guidelines. CONCLUSION: The implementation of the ESC Guidelines on Syncope is technically feasible. Nevertheless, even when the Guidelines are strictly observed, a high percentage of patients with syncope has still to be hospitalized. Our data suggest that new criteria should be established for a safe Emergency Department discharge of the patients with syncope, particularly of those with structural heart disease or abnormal ECG.

[Chlamydia pneumoniae and atherosclerosis]. / Chlamydia pneumoniae ed aterosclerosi.

There is widespread consensus that atherosclerosis is an inflammatory disease. Between possible pathogenetic mechanisms, infective hypothesis has received increasing attention. Researches have recently focused their attention on the role of Chlamydia pneumoniae, a gram-negative intracellular organism, as infection by this bacterium has been demonstrated frequently associated with atherosclerosis. This review attempts to analyze and critically evaluate available data of the literature about the association between Chlamydia pneumoniae and atherosclerosis in order to provide updated elements of judgement concerning a possible future revolutionary scenario: the consideration of atherosclerosis as an infective disease, susceptible to prevention and treatment by means of antimicrobial therapy. More than twenty sero-epidemiological studies have found a two-fold or greater risk of cardiovascular events in subjects with serological evidence of Chlamydia pneumoniae infection. The organism has been identified in over 50% of atherosclerotic plaques examined by various histopathological techniques, while it has been only rarely found in normal artery tissues; moreover, viable Chlamydia pneumoniae has recently been isolated from coronary and carotid atherosclerotic plaques. Several experimental studies have shown that the biological properties of Chlamydia pneumoniae can explain its potential role in initiating and/or modulating plaque formation. The most relevant issue, i.e. the possibility of preventing or slowing progression of the disease with antimicrobial treatment, is still unsolved: only data from experimental studies on animals and four small intervention trials on humans are available, and their encouraging results require confirmation in larger prospective studies. In conclusion, while the association between Chlamydia pneumoniae and atherosclerosis seems to be established, it is still uncertain whether or not the organism plays a causal role in atherosclerosis and its complications. It is hoped that the results of wide scale clinical intervention trials with antibiotics for the secondary prevention of atherosclerotic diseases now in progress will clarify this problem.

[Thrombosis of the superior sagittal sinus and ulcerative colitis. A case report]. / Trombosi del seno sagittale superiore e colite ulcerosa. Descrizione di un caso.

We describe a rare case of superior sagittal sinus thrombosis in a young man (26 years) with undiagnosed ulcerative colitis. The patient was hospitalized with headache and paresis of the right arm and leg. he had had rectal bleeding and diarrhea for the previous 4 weeks. Despite the fact that heparin therapy is still considered controversial, we successfully treated our patient with low doses of sub-cutaneous heparin. He did not suffer any side-effect.

[Hypersensitivity vasculitis after thrombolytic therapy with APSAC (anisoylated plasminogen streptokinase activator complex). Presentation of a clinical case and review of the literature]. / Vasculite da ipersensibilità post-terapia trombolitica con APSAC (anisoylated plasminogen streptokinase activator complex). Presentazione di un caso clinico e revisione della letteratura.

We describe a rare case of hypersensitivity vasculitis associated with APSAC administration in a 54-year-old man. Fifteen days after receiving thrombolytic therapy (APSAC 30 U) for acute myocardial infarction, the patient was admitted to our department for myalgia, livedo reticularis and erythema of the legs with an ulcerative necrotic lesion of the fifth toe of the right foot. The presence of circulating immune complexes at high titer supported the diagnosis of hypersensitivity vasculitis.

[Determination of genomic and replicative RNA of hepatitis C virus in patients treated with interferon]. / Determinación del RNA genómico y replicativo del virus de la hepatitis C en pacientes tratados con interferón.

We have investigated the presence of genomic and replicative RNA strands of hepatitis C virus in liver and serum. Eleven patients with proven chronic hepatitis C, received Interferon a2a 4,5 MU, three times a week during six months. RT-PCR was used with sense primer to detect the replicative strand and an antisense primer to identify genomic strand. Before treatment, genomic strands were present in liver and serum of all patients. Replicative strands were present in liver and serum in five and six cases, respectively. Seven out of eleven responded to treatment. In responders, genomic strands were absent in liver of 3 cases (43%) and replicative strands in liver of 4 (57%). In plasma genomic and replicative strands were absent in 5 (71%) and 7 (100%), respectively. In all non responders, genomic strands in liver and plasma remained present. Replicative strands in liver and plasma were present in 100% and 25%, respectively. Knodell score improved in 5 out of 7 responders and remained unchanged in 3 out of 4 non responders. In 2 out of 4 responders with genomic and replicative strands in liver, Knodell score remained unchanged or worse. In all non responders, genomic and replicative strands in liver were present and Knodell score remained unchanged or worse. Genomic and replicative strands in plasma tended to be negative after treatment in responders. Genomic strands in plasma remained present in non responders. Conversely, genomic and replicative strands in liver were present in all non responders. It seems to exist a relationship between genomic and replicative strands in liver and the same or worse Knodell score. After a follow up, it will be possible to determined whether responders who still present viral RNA in liver would be prone to a relapse.

Type I interferon and Toll-like receptor expression characterizes inflammatory myopathies.

OBJECTIVES: Juvenile dermatomyositis (JDM), adult dermatomyositis, and polymyositis (PM) are idiopathic inflammatory myopathies (IIMs) characterized by muscle infiltration and specific muscle fiber alterations. They are thought to have an autoimmune etiology, but triggering factors, and how immunologic attack induces muscle weakness, remain unknown. Recent evidence suggests a key role for type I interferon (IFN)-mediated innate immunity in dermatomyositis, which we explored in JDM, dermatomyositis, and PM by gene expression profiling, and other methods. METHODS: Ten IIM and 5 control muscle biopsies were assessed for expression of approximately 16,000 genes by microarray; 37 additional IIM, 10 dystrophinopathic, and 14 nonmyopathic control muscles were studied for type I IFN-dependent genes, and Toll-like receptor (TLR) expression by immunochemistry and PCR. RESULTS: Type I IFN-dependent transcripts were significantly upregulated in IIM muscles compared to controls; in JDM the most expressed were ISG15 (408-fold), IFIT3 (261-fold), MX1 (99-fold), and IRF7 (37-fold). IFN-ß (but not IFN-α) transcripts were upregulated in PM as well as dermatomyositis/JDM. TLR3 was upregulated particularly in JDM, being localized on vascular endothelial cells, muscle infiltrating cells (mainly myeloid dendritic cells), and regenerating myofibers; TLR7 and TLR9 proteins were present in IIM (prominently in PM), mainly on cell infiltrates, particularly plasma cells, and on some injured myofibers. CONCLUSIONS: IFN-ß and type I IFN-induced molecules are involved in PM as well as JDM/dermatomyositis. Endosomal TLRs (effectors of innate immunity) are also involved (but differently) in the 3 conditions, further suggesting viral involvement, although TLR activation could be secondary to tissue damage.

High activity and reduced neurotoxicity of bi-fractionated oxaliplatin plus 5-fluorouracil/leucovorin for elderly patients with advanced colorectal cancer.

BACKGROUND: The proportion of elderly within the general population is increasing and the incidence of colorectal cancer increases with age. Oxaliplatin and 5-fluorouracil (FU) combination is active in this disease. PATIENTS AND METHODS: This multicenter phase II study was designed to investigate feasibility, efficacy, activity of daily living (ADL) and instrumental activity of daily living (IADL) in elderly patients with metastatic colorectal cancer treated, as first-line chemotherapy, with a bi-fractionated oxaliplatin/5-FU based regimen. Treatment was oxaliplatin 45 mg/m2, leucovorin 200 mg/m2, 5-FU 400 mg/m2 and 22 h continuous infusion of 5-FU 600 mg/m2, all given intravenously on days 1 and 2, every 2 weeks. RESULTS: Seventy-eight patients were enrolled; median age was 75 years (range 70-85). Among 77 evaluable patients, we observed seven complete responses and 32 partial responses, for an overall response rate of 51% (95% confidence interval 40% to 62%). A stabilization of disease was observed in 25% of patients while 19 patients progressed. Canadian NCI grade 3/4 toxicities were: neutropenia in 32% of patients (febrile in two), diarrhea in 10%, mucositis in 4%, and fatigue in 4%. Sensory neuropathy was mild and occurred as grade 3 in 6% of patients. ADL and IADL scores did not change significantly during treatment. CONCLUSIONS: The bi-fractionated delivery of oxaliplatin plus 5-FU/leucovorin demonstrated high antitumor activity in elderly patients with advanced colorectal cancer. Splitting oxaliplatin administration might reduce incidence of severe neuropathy, although this has to be confirmed by further studies.

[Hypertension, hyperpotassemia and normal glomerular filtration (Gordon's syndrome): a case report]. / Ipertensione, iperpotassiemia e normale filtrato glomerulare (sindrome di Gordon): descrizione di un caso.

We describe a case of a 26 year old patient affected by a rare syndrome characterized by hyperkalemia, arterial hypertension and normal glomerular filtration rate (Gordon's syndrome), probably due to a renal tubular defect in the reabsorption of sodium or chloride. The patient, who had hyperkalemia since the age of 4 years, was referred to our Centre because of hypertension not well controlled with antihypertensive treatment. After drug therapy wash-out, we confirmed the existence of hypertension (180/100 mm Hg; ambulatory BP monitoring: 24-h mean BP = 151/91 mm Hg; 7 am-11 pm = 157/95; 11 pm-7 am: 133/82) and blood and urine tests showed hyperkalemia (6.6 mEq/L), hyperchloremia (115 mEq/L), mild metabolic acidosis (pH = 7.35, HCO3 = 19 mEq/L), low levels of plasma renin activity ( < 0.2 ng/ml/h), slight increase of plasma (1.08 nM/L) and daily urine aldosterone (129 nM) and normal serum creatinine (1.1 mg/dl) and glomerular filtration rate (91 ml/min). These data allowed to exclude the presence of renal failure and hyporeninemic hypoaldosteronism, which are the most common diseases with hypertension and hyperkalemia, and suggested the diagnosis of Gordon's syndrome. After 1 month of treatment with chlorthalidone (12.5 mg o.i.d) we observed the normalization of BP (130/80 mm Hg; ambulatory BP monitoring: 24-h BP: 132/76 mm), serum potassium (5,1 mEq/L) and the other blood and urine tests. These results were confirmed 6 months later and at present the patient has good clinical conditions.

[Hemiballism as a result of a focal hemorrhagic lesion of the subthalamic nucleus documented by CT]. / Emiballismo dovuto a lesione emorragica focale del nucleo subtalamico documentata dalla TC.

The authors relate a case of hemiballism with favourable evolution, suddenly arisen in an hypertensive subject, in whom the CT (Computer Tomography) pointed out a small hemorrhage at the level of the subthalamic nucleus (body of Luys), controlateral to hypercinesias. The authors underline the extreme rareness of such clinico-radiologic association since more than 10 years after the introduction of CT only another analogous observation has been related in literature. Cases of hemichorea and/or hemiballism, secondary to ischemic, hemorrhagic or angiomatous lesions, variously situated at the level of basal nuclei have been more often documented through CT.

Vascular risk factors linked to multiple lacunar infarcts.

BACKGROUND: The pathogenesis of lacunar infarcts is still incompletely established. Data from the literature suggest that vascular risk factors differ among patients with multiple (MLI) and single lacunar infarcts (SLI). We reexamined this hypothesis using stricter inclusion criteria and a less selected study population. METHODS: We evaluated 136 patients consecutively admitted for first-ever minor stroke to a general hospital with the characteristics of a community hospital. Vascular risk factors were studied by univariate and multivariate statistical analyses among the following subgroups of patients, classified according to CT findings: (a) with lacunar infarct; (b) with nonlacunar infarct (NLI); (c) with SLI; (d) with MLI; (e) with single, either lacunar or nonlacunar, infarct. RESULTS: No significant difference was observed between patients with lacunar infarcts and patients with NLI. Compared to patients with SLI or NLI, patients with MLI had significantly more often a family history of hypertension, cardiomegaly on the chest radiograph and CT leukoaraiosis as well as a higher systolic and diastolic blood pressure on admission. Logistic regression analysis selected CT leukoaraiosis, Rx cardiomegaly and admission diastolic blood pressure as independent, significant predictors of MLI. CONCLUSION: In patients with first-ever minor stroke, the risk factor profile differs according to the evidence of SLI or MLI on the CT scan. In terms of risk factors, patients with SLI seem more similar to those with NLI than those with MLI. Based on the predicting effect of variables linked with type and severity of arterial hypertension, the CT appearance of MLI might express a more univocal and specific cerebrovascular pathology (hypertensive arteriolosclerosis).

The influence of smoking on von Willebrand factor is already manifest in healthy adolescent females: the Floren-teen (Florence Teenager) Study.

The early onset of atherosclerosis and the involvement of physiological biochemical, and environmental factors in its pathogenesis is well documented. Few data are available on the role of risk factors related to hemostasis in the pathogenesis of atherosclerosis in the young and, in particular, little information is available on adolescent populations. In the Study of Preventive Medicine and Education Program (Floren-teen Study), von Willebrand factor, a risk factor for cardiovascular disorder, was studied, together with classical cardiovascular risk factors, in apparently healthy students from two high schools in Florence. Familial and personal history, physical examination, and cardiovascular risk factors were evaluated in 144 students (aged 17-19 years). Blood was withdrawn to assess von Willebrand factor (ELISA) and lipid parameters. Levels of von Willebrand factor were significantly higher (P<0.044) in smokers than in nonsmokers and were correlated with the number of cigarettes per day in the whole group (P=0.01) and in females (P=0.006). In females a positive correlation was observed between von Willebrand factor and high-density lipoprotein cholesterol (P=0.0365). There was no significant correlation between von Willebrand factor and blood pressure or between von Willebrand factor and physical activity. In conclusion, this study shows an association between levels of von Willebrand factor and smoking habits and is the first show that even a brief period of smoking affects levels of von Willebrand factor in healthy adolescent females independently of other risk factors. These results stress the relevance of extending prevention programs to reduce smoking in high school students.

Determinación del RNA genómico y replicativo del virus de la hepatitis C en pacientes tratados con interferón / Determination of genomic RNA and replicative hepatitis C viruses in patients treated with interferon

En este ensayo se trató de correlacionar la evolución clínica e histológica de un grupo de pacientes tratados con IFN, con la presencia del RNA genómico y replicativo del HCV en plasma y tejido hepático. Se estudiaron 11 pacientes con hepatitis crónica "C" diagnosticada por elevación de transaminasas durante los últimos 6 meses, anti-HCV positivo "(Elisa II)", y cuadro histológico compatible. En todos ellos se efectuó biopsia hepática y extracción de sangre en paralelo, inmediatamente antes y después de finalizar el tratamiento con 4.5 millones de IFN Alfa2a administrado 3 veces por semana, durante 6 meses. El tecijo hepático se almacenó a-80§c y el plasma a-20§c hasta su procesamiento. La extracción de RNA se realizó a partir de 100microliter de plasma y de 20mg de tejido hepático con isotiocianato de guanidinio (Chomcznski). La transcripción reversa se llevó a cabo "primers" sense o antisense para detectar la hélice replicativa (-) o genómica (+) respectivamente. El cDNA de la región 5' no codificante fue amplificado por el sistema "nested". Antes del tratamiento los 11 pacientes evidenciaron la presencia de la hélice genómica en tecijo hepático y plasma. En cambio la hélice replicativa se detectó en 5 casos en hígado, 7 pacientes se revelaron como respondedores y 4 como no respondedores. En los pacientes respondedores las hélices genómica y replicativa en hígado desaparecieron en un 43 por ciento y 57 por ciento respectivamente, y en plasma se observó un descenco del 71 por ciento para la hélice genómica y de un 100 por ciento para la hélice replicativa. En los 4 pacientes no respondedores la hélice genómica permaneció en tecijo hepático y plasma, en cambio la replicativa se mantuvo en tejido hepático y se negativizó en un 75 por ciento en plasma. El índice de Knodell, que determina el estadío histológico, disminuyó en 5 de lo 7 respondedores y permaneció igual en 3 de los 4 no respondedores...