High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia

Lipid targets can be difficult to attain in familial hypercholesterolaemia. To compare atorvastatin with simvastatin- fenofibrate and simvastatin-cholestyramine therapy, we studied 54 patients with familial hypercholesterolaemia over periods of 2-6 months on each therapeutic regimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/- 11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, and increased HDL by 2.3 +/- 37.0%. Simvastatin- fenofibrate therapy achieved reductions of 33.9 +/- 8.5% in cholesterol, 42.0 +/- 12.2% in LDL, 34.7 +/- 38.3% for triglycerides, and a 25.4 +/- 55.1% increase in HDL. Simvastatin-cholestyramine gave a reduction of 31.3 +/- 11.8% in cholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a 1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but not significantly better than simvastatin-fenofibrate in improving the LDL:HDL ratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%) had side- effects: two discontinued atorvastatin due to side-effects; two patients had rashes; six had myalgia and two had diarrhoea. Gastrointestinal side-effects were described in 16 (30.1%) patients on simvastatin-cholestyramine therapy and four cases of myalgia (11.2%) were seen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%) a 30% or greater fall in HDL was observed, compared to five patients with resin therapy (9.2%) and two with fibrate therapy (5.5%). There were no significant differences in liver or muscle biochemistry between the regimens, but atorvastatin did raise transaminase and creatine kinase concentrations significantly compared to pre-treatment values (p = 0.001). Atorvastatin significantly improves the lipid profile in most patients compared with other regimens. It has a comparable incidence of side-effects to combination therapy regimens.      

Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

Background

To treat viral infection of chronic hepatitis C (CHC) is a main strategy to prevent progression of liver disease, and cancer. Some patients with CHC have failed to respond to the common antiviral therapy in different populations.

Objectives

In the current study it was aimed to find out the possible role of multiple drug resistance gene1 (MDR1) in non-responder patients with CHC infection in Turkish population.

Patients and Methods

Peripheral blood-EDTA samples were used for total genomic DNA isolation. In total of 55 patients with chronic hepatitis C and positive results for genotype 1 [31 male (56.4%), 24 female (43.6%) and mean age-min-max; 56.9 ± 9.66 (39-71)]; 19 responder (34.5%), 21 non responder (38.2%), and 15 recurrence (27.3%) were included in the presented results. Functional MDR1 gene was genotyped by multiplex PCR-based reverse-hybridization Strip Assay method, and some samples were confirmed by direct sequencing.

Results

Our results indicate that MDR1 gene polymorphism is strongly associated with non-responder patients and those with recurrent chronic hepatitis C during conventional drug therapy when compared to the responder patients. Homozygous of the TT genotype for MDR1 exon 26 polymorphism was at 2.0-fold higher risk of non-responder than patients with CC and CT.

Conclusions

The homozygous MDR1 3435TT genotype which encodes the xenobiotic transporter P-glycoprotein may be associated with a poor antiviral response in HCV chronicity during conventional therapy, and large-scale studies are needed to validate this association.     

A randomised,multinational study with sequential therapy comparing ciprofloxacin twice daily and ofloxacin once daily

Summary In a multinational, open, randomised, controlled clinical study, 474 hospitalised patients with moderate or severe infections were treated with sequential regimens of ofloxacin or ciprofloxacin. Ofloxacin 400 mg once daily or ciprofloxacin 200 mg twice daily were given intravenously for at least 3 days followed by oral treatment with ofloxacin 400 mg once daily or ciprofloxacin 500 mg twice daily. Overall cure rates of 86.8% (85.7%) in the ofloxacin group and 89.6% (89.5%) in the ciprofloxacin group were achieved in the intention-to-treat analysis (per protocol analysis). The overall bacteriological response rate (ofloxacin 89.5%, ciprofloxacin 89.0%) was comparable to the clinical cure rate. Both drugs were well tolerated and adverse events were rarely observed. It is concluded that ofloxacin and ciprofloxacin can be used successfully in the treatment of hospitalised patients with aerobic gram-positive and gram-negative infections. Ofloxacin has the advantage of a oncedaily regimen, compared to the twice-daily regimen with ciprofloxacin.

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Randomisierte, multinationale Studie mit einer sequentiellen Therapie, die Ciprofloxacin zweimal täglich mit Ofloxacin einmal täglich vergleicht

Zusammenfassung In einer multinationalen, offenen, randomisierten, kontrollierten klinischen Studie wurden 474 hospitalisierte Patienten mit mittelschweren oder schweren Infektionen mit einer sequentiellen Therapie behandelt. Für mindestens 3 Tage wurde Ofloxacin 400 mg 1× täglich oder Ciprofloxacin 200 mg 2× täglich intravenös verabreicht. Anschließend wurde die Therapie oral fortgesetzt mit 400 mg Ofloxacin 1× täglich oder 500 mg Ciprofloxacin 2× täglich. Die Heilungsrate betrug 86,8% (85,7%) in der Ofloxacin- und 89,6% (89,5%) in der Ciprofloxacin-Gruppe in der intention-to-treat-Analyse (per-protocol-Analyse). Die bakteriologische Wirksamkeit (Ofloxacin 89,5%, Ciprofloxacin 89,0%) war der klinischen Heilungsrate vergleichbar. Nebenwirkungen wurden selten beobachtet, die Verträglichkeit der beiden Therapien war gut. Die Ergebnisse haben gezeigt, daß Ofloxacin und Ciprofloxacin erfolgreich in der Behandlung hospitalisierter Patienten mit grampositiven (Aerobier) und gramnegativen Infektionen eingesetzt werden kann. Ofloxacin hat den Vorteil der Einmalgabe, Ciprofloxacin muß 2× am Tag verabreicht werden.

     

Hepatic involvement of disseminated actinomycosis

A 35-year-old woman was admitted for weight loss, fatigue, and epigastric and back pain. She had undergone uterine myomectomy 6 weeks previously, and light microscopic examination revealed actinomycosis. Radiologic examination showed 5×4×4 cm and 2×2×2 cm solid lesions in the left liver lobe. Ultrasound-guided fine-needle aspiration biopsy could not exclude the possibility of malignancy. We decided to perform an explorative laparotomy. Frozen sections indicatedEchinococcus alveolaris infection or granulomatous inflammatory disease, and left hepatic lobectomy was performed. Histologic examination revealed hepatic actinomycosis. After 6 months' penicillin treatment, there was no sign of recurrence. This case of hepatic actinomycosis following uterine infection without gross involvement of any other abdominal organ raises questions on the dissemination pathway. The other interesting feature of this case is the short interval from the presumed initiatory event to the presence of the hepatic deposits.     

Prevalence of pleural effusions post orthotopic heart transplantation

BACKGROUND AND OBJECTIVE: The prevalence and natural history of pleural effusions occurring after orthotopic heart transplantations (OHT) are essentially unknown. The objective of this study was to determine the prevalence, laterality, size and prognosis of pleural effusions occurring after OHT. METHODS: Eighty-three patients who underwent OHT between August 1997 and January 2003 were screened retrospectively. CXR and chest CT scans of all patients were reviewed. Chart review was performed for patients with large effusions (occupying 25% or more of a hemithorax) with specific attention to thoracentesis results. RESULTS: Seventy-two patients were included in the study. Sixty-one (85%) developed an effusion at some time during the first 365 postoperative days. The majority of post-OHT effusions were bilateral and small, occupying less than 25% of the hemithorax. Pleural effusions occupying 25% or more of a hemithorax occurred in 17% (12/72) of the patients within 12 months of OHT. Overall, the majority of effusions resolved within the first year after transplantation. CONCLUSIONS: The prevalence of pleural effusions within 12 months following OHT is high (85%). Most effusions are small, bilateral and resolve within 1 year.     

Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model

D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; β-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5 % w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats.     

In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia

The absence of mutations in the IgV genes, together with the presence of ZAP-70 and CD38, are the most reliable negative prognostic markers for chronic lymphocytic leukemia (CLL) patients. Several lines of evidence indicate that CD38 may be not only a diagnostic marker but also a key element in the pathogenetic network in CLL. First, CD38 is a receptor that induces proliferation and increases survival of CLL cells. Second, CD38 signals start upon interaction with the CD31 ligand expressed by stromal and nurse-like cells. Third, CD38/CD31 contacts up-regulate CD100, a semaphorin involved in sustaining CLL growth. Fourth, evidence that nurselike cells express high levels of CD31 and plexin-B1, the high-affinity ligand for CD100, offers indirect confirmation for this model of receptor cross-talk. Elements of variation in the clinical course of CD38(+) CLL patients include (1) potential intersection with ZAP-70, a kinase involved in the CD38 signaling pathway in T and natural killer (NK) cells, and (2) the effects of genetic polymorphisms of the receptors involved, at least of CD38 and CD31. Consequently, CD38 together with ZAP-70 appear to be the key elements of a coreceptor pathway that may sustain the signals mediated by the B-cell receptor and potentially by chemokines and their receptors. This would result in acquisition of increased survival potential, providing clues to the poorer prognosis of CD38(+) patients.