Interferon-alpha2b induction treatment with or without ribavirin in chronic hepatitis C: a multicenter,randomized, controlled trial

We aimed to compare the efficacy of interferon-_2b (IFN) induction treatment in combination with ribavirin to IFN induction alone in chronic hepatitis C. In total, 125 patients (66 male, 59 female, mean age: 48 ± 9, range: 21–70) were enrolled and randomized into two arms: In the first, patients received 5 MU/day of IFN for 4 weeks followed by 3 MU/day for the next 4 weeks. Treatment was continued with 3 MU three times a week IFN for an additional 40 weeks. Ribavirin was administered 1000–1200 mg/day according to the body weight for the entire 48-week period. In the second arm, patients received placebo in addition to IFN. Fifty-nine patients were placed in the ribavirin arm and 66 in placebo arm. All patients were genotype 1. At week 48, 24/66 (36%) from the placebo and 31/59 (52%) from the ribavirin group responded (P < 0.05). However, during the 24-week untreated follow-up period, 13/24 (54%) from the placebo, and 8/31 (26%) from the ribavirin group relapsed (P = 0.002.), resulting in a sustained virologic response (SVR) rate of 17% in the placebo and 39% in the ribavirin group (P = 0.005.) In conclusion, IFN induction treatment in combination with ribavirin is superior to IFN induction treatment alone in genotype 1 patients, and the SVR rate of 39% is encouraging.     

Effect of low- and high-dose levothyroxine on thyroid nodule volume: a crossover placebo-controlled trial

OBJECTIVE: The efficacy and the effective dose of levothyroxine suppressive therapy in the treatment of benign thyroid nodules are controversial. In this study, we aimed to determine the response of solitary thyroid nodules to low- or high-level TSH suppression in a placebo-controlled, randomized crossover trial. DESIGN: Forty-nine patients with solitary thyroid nodules on palpation were randomized to high-level and low-level TSH suppression groups. In each group, patients were further randomized to placebo and active levothyroxine subgroups. Patients in each subgroup were crossed over to placebo or active levothyroxine at the end of the first year and were then followed up for an additional year. METHODS: TSH levels were suppressed to 0.4-0.6 mIU/ml and < or = 0.01 mIU/ml in the low-level and high-level TSH suppression groups, respectively. Nodule volumes were measured at baseline and every 6 months after the desired level of TSH was reached if the patients were in the active levothyroxine treatment group or every 6 months if they were in the placebo group. RESULTS: In high-level TSH suppression groups, nodule volume decreased significantly at the end of the active treatment periods (4.99 +/- 2.02 ml vs. 3.20 +/- 1.50 ml, P < 0.01, in Group 1; and 3.72 +/- 1.79 ml to 2.05 +/- 0.64 ml, P < 0.001, in Group 2). In the low-level TSH suppression groups, nodule volume also decreased significantly at the end of the active treatment periods (4.43 +/- 1.76 ml vs. 3.04 +/- 1.32, P < 0.05, in Group 3; and 3.59 +/- 0.89 ml to 2.22 +/- 0.59 ml, P < 0.01, in Group 4). Nodule volumes regained their original volumes during the placebo treatment periods. The percentage decline in clinically relevant nodule volume reduction (> or = 50%) was similar in the low-level and high-level TSH suppression groups. CONCLUSION: Low- and high-level TSH suppression were equally effective in reducing nodule volume and thus, considering the complications of high-level TSH suppression, low-level TSH suppression should be used if one considers levothyroxine suppressive therapy to reduce thyroid nodule size.     

Two-year interferon therapy with or without ribavirin in chronic delta hepatitis

The only beneficial agent for the treatment of chronic delta hepatitis (CDH) is interferon (IFN). However, there is no consensus on the best dosage or duration of IFN therapy. As ribavirin (RBV) increases the sustained response when added to IFN in chronic hepatitis C, probably because of its immunomodulatory effect, we aimed to investigate the efficacy of 2-year IFN treatment and whether RBV had any additive effect to IFN in CDH. METHODS: Patients (n = 31) with CDH were randomized with a 1:2 ratio as 10 patients (3 females/7 males, age 39 +/- 9) receiving IFN monotherapy (9 MU IFN-alpha2a three times weekly) and 21 patients (8 females/13 males, age 38 +/- 11) receiving IFN plus RBV for 2 years (IFN at the same dosage and RBV at 1000-1200 mg/day). Alanine transferase normalization and hepatitis delta virus (HDV) RNA negativity at the end of treatment and at the end of the follow-up period (at least 6 months following 2-year treatment) were primary endpoints of the study. In addition, virological response and biochemical response were determined separately. RESULTS: Eight of 31 patients (25%) had cirrhosis in liver biopsies. Six patients from the IFN monotherapy group and 12 patients from the combination group had biochemical response. Five patients from the IFN monotherapy group and 11 patients from the combination group had virological response at the end of therapy. Two patients from the IFN group and five patients from the combination group had sustained biochemical response at the end of the follow-up period. Hepatitis B virus (HBV) activations with HBV DNA positivity were observed in two patients (one from the IFN monotherapy group, one from the combination group). Two patients (20%) in the IFN group and five patients (23.5%) in IFN plus RBV group remained as virological responders at the end of the follow-up period (P > 0.05). None of the patients with liver cirrhosis were responsive at the end of the follow-up period. CONCLUSION: Almost 20% of the patients with CDH were responsive to 2-year IFN treatment at the end of the follow-up period and no additional effect of RBV was observed. Patients with advanced liver disease failed to respond to treatment.     

Living donor liver transplantation for hepatitis B cirrhosis

BACKGROUND AND AIM: Living donor liver transplantation (LDLT) has particular advantages for Turkey where hepatitis B virus (HBV) infection is the most common cause of cirrhosis, both because LDLT circumvents the difficulties encountered in the emerging world in providing deceased donor organs, and because it allows preemptive antiviral therapy. The aim of this study was to review one institution's experience with LDLT in patients with chronic HBV infection. METHODS: A total of 109 patients with chronic HBV infection underwent LDLT between September 1999 and June 2005, of whom 40 were coinfected with hepatitis D virus and 23 had hepatocellular carcinoma. Antiviral prophylaxis was attempted in all, beginning prior to transplantation with lamivudine or adefovir, and continuing after transplantation with low dose intramuscular hyperimmune B immunoglobulin (HBIg) plus lamivudine or adefovir. RESULTS: In a median follow up of 20 months (range 1-66 months), there was no donor mortality. One-year recipient survival was 90%, and in total 16 recipients died. None of the deaths was related to HBV. Recurrence of HBV infection was detected by reappearance of serum hepatitis B surface antigen in six patients (5.5%) at 5, 8, 12, 17, 34 and 46 months after transplantation, respectively. There was no influence of donor hepatitis B core antibody status on the likelihood of recurrence of HBV in the allograft. CONCLUSION: The results indicate that LDLT with antiviral treatment and low dose HBIg provides excellent results for donors and recipients.     

Synthesis and characterization of photocrosslinkable hydrogels from bovine skin gelatin

Hydrogels that mimic native tissues chemically and structurally have been increasingly sought for a wide variety of tissue engineering applications. Gelatin can be naturally derived from different sources and functionalized to fabricate hydrogels that exhibit high cytocompatibility and favorable biodegradable properties. The amino groups on the gelatin backbone can be substituted by adding varying proportions of methacrylic anhydride (MAA) to create biomimetic hydrogels which can be used as tissue engineering scaffolds. Gelatin from different sources yields hydrogels with distinctive physical, chemical, and biological properties. In this work, gelatin from bovine skin was used to fabricate hydrogels with varying degrees of crosslinking content using 1, 4, 7, and 10 mL MAA. The material properties of these hydrogels were characterized. The cytocompatibility of the gelatin-based hydrogels was studied using L6 rat myoblasts. The hydrogels from bovine skin gelatin exhibit mechanical properties that are conducive for applications which require substrates to propagate cell growth, migration, and proliferation rapidly. These hydrogels exhibit exceptional tunability behavior which makes them useful and applicable to culture different cell types.

Gelatin from bovine skin was chemically modified to synthesize biocompatible photolabile hydrogels for tissue engineering applications.     

Bath‐related thunderclap headache: Case report of a male patient

Bath‐related thunderclap headache (BRTH) is a rare entity, closed to reversible cerebral vasoconstriction syndrome. It is only described in middle‐aged women and mainly Asiatic ethnic origins. Role of estrogen is consequently discussed. We report here a case of a 36‐year‐old man, admitted for five episodes of thunderclap headaches, triggered by hot shower. This is the first male case of BRTH, opposing only a hormonal hypothesis. Furthermore, this African patient consolidates the non‐exclusivity of this affection to Asian ethnic origins.     

The effects of rosiglitazone and metformin on inflammation and endothelial dysfunction in patients with type 2 diabetes mellitus

Diabetic patients have a markedly increased risk of cardiovascular disease compared with non-diabetics. Two drug groups today target insulin resistance; biguanides and thiazolidinediones. In addition, these may have other effects on cardiovascular risk factors. The aim of this study was to evaluate the effects of metformin and rosiglitazone on non-traditional cardiovascular risk factors. Forty type 2 diabetic patients were randomized into metformin and rosiglitazone groups. After receiving the optimal doses, the patients were monitored for 12 weeks. Biochemical parameters, lipid parameters, CRP, insulin, c-peptide, and HbA1c levels were analyzed. VWF, PAI-1, ICAM-1, TNF-α, IL-6, E-selectin, and fibrinogen levels were measured in order to assess coagulation status and endothelial dysfunction. In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-α levels were significantly decreased after 12 weeks compared with the basal levels. IL-6 levels decreased from 75 pg/ml ± 20 to 42 pg/ml ± 9 (P 0.023) and TNF- α levels from 61 pg/ml ± 31 to 39 pg/ml ± 10 (P 0.018). In the rosiglitazone group, FPG, PPG, HbA1c, insulin, HOMA-IR, IL-6, and TNF-α levels decreased significantly after 12 weeks compared with the basal levels. IL-6 levels decreased from 78 pg/ml ± 21 to 41 pg/ml ± 9 (P 0.028) and TNF-α levels from 62 pg/ml ± 19 to 37 pg/ml ± 10 (P 0.012). At the end of the study, no significant differences were determined between groups. Insulin resistance and type 2 diabetes are strongly associated with low grade inflammation. Both metformin and rosiglitazone were effective in controlling inflammatory markers in addition to metabolic parameters.     

Efficacy of melatonin, mercaptoethylguanidine and 1400W in doxorubicin- and trastuzumab-induced cardiotoxicity

Doxorubicin (DOX) and Trastuzumab (TRAST) are effective agents for the treatment of many neoplastic diseases. Cardiotoxicity is a major side effect of these drugs and limit their use. In this study, the possible protective effects of melatonin (MEL), mercaptoethylguanidine (MEG), or N-(3-(aminomethyl) benzyl) acetamidine (1400W) against the cardiotoxicity of DOX and TRAST were tested. Male Sprague-Dawley rats received an injection of DOX (20 mg/kg) alone or in combination with TRAST (10 mg/kg) to induce cardiotoxicity; daily treatments with MEL (10 mg/kg × 2), MEG (10 mg/kg × 2), or 1400W (10 mg/kg × 2) were begun 36 hr before and continued for 72 hr after DOX and TRAST administration. Oxidant/antioxidant indices of the cardiac tissue, namely, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as serum levels of creatine phosphokinase (CK-MB) were measured. Additionally, the injury scores were evaluated histopathologically. Malondialdehyde levels were significantly higher, while SOD and GSH-Px activities were significantly reduced in rats with DOX- or DOX+TRAST-induced cardiotoxicity compared to normal values. All three treatment agents significantly reversed oxidative stress markers. Serum CK-MB levels were significantly increased after treatment with DOX and DOX+TRAST; these changes were also reversed by each of the treatments and resulted in near normal levels. Both the DOX- and DOX+TRAST-treated rats presented similar histopathologic injuries; in the animals treated with the protective agents, histologic protection of the cardiac tissue was apparent. These results suggested that MEL, MEG, as well as 1400 W are effective in preventing DOX- or DOX+TRAST-induced cardiotoxicity.     

Lupus vulgaris in a pediatric patient: a clinicohistopathological diagnosis

Lupus vulgaris is the most common form of cutaneous tuberculosis which usually occurs in patients previously sensitized to Mycobacterium tuberculosis. We present a case of a 10-year-old boy who was diagnosed as lupus vulgaris clinically and histopathologically. He had well demarcated, irregularly bordered, pink, infiltrated plaques on his left cheek showing apple-jelly appearance on diascopy. The histopathological examination showed tuberculoid granulomas with Langhans type giant cells. The Mantoux reactivity was in normal limits, and no acid-fast bacilli was found in the lesion, either by direct stained smears or by culture. The lesions showed marked improvement on anti-tuberculosis treatment. We want to emphasize that histopathological examination has diagnostic value in lupus vulgaris in correlation with clinical appearance, when direct analysis or culture is negative.     

Relationship between the serum sCD40L level and aspirin-resistant platelet aggregation in patients with stable coronary artery disease

BACKGROUND: Current evidence supports the central role of inflammation in all phases of the atherosclerotic process, including its thrombotic complications. Increased serum sCD40L may trigger platelet activation, so the aim of the present study was to determine the relation between sCD40L levels and aspirin-resistant platelet aggregation in patients with coronary atherosclerosis. METHODS AND RESULTS: A total of 167 consecutive patients (39-85 years old, 35.9% women) with stable coronary artery disease was enrolled in the study. Platelet function was evaluated by a Platelet Function Analyzer 100 device (PFA-100) with collagen and epinephrine (Col/Epi) and collagen and adenosine diphosphate (ADP) (Col/ADP) cartridges. Aspirin resistance was defined as a closure time (CT) <186 s with Col/Epi cartridges, despite regular aspirin therapy. Serum sCD40L level was determined quantitatively with an ELISA method. Fifty-seven (34.1%) patients had aspirin resistance according to the PFA-100. Mean CT measured with the Col/ADP cartridges was 83+/-18 s (65-101 s). Mean serum sCD40L was 157 pg/ml (6-700 pg/ml) in the entire cohort. Patients with aspirin resistance had a mean serum sCD40L level of 166 pg/ml and patients with aspirin-sensitive platelet aggregation had an sCD40L level of 152 pg/ml (p=0.582). CONCLUSION: The sCD40L level is similar in patients with aspirin-resistant and aspirin-sensitive platelet aggregation according to the PFA-100. There is still need for further studies to elucidate the relationship between aspirin-resistant platelet aggregation and sCD40L, which is now known to be prothrombotic, proinflammatory and to be a risk factor for cardiovascular events.