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.      

GST isoenzymes in matched normal and neoplastic breast tissue

The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore we investigated GST activity and the protein expression of glutathione S-transferases (GSTs) isoenzymes known to be involved in the metabolism of endogenous and exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression. The interindividual variation in the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and of 1,2-epoxy-3-(p-nitrophenoxy) propane (EPNP) with glutathione (GSH) by cytosolic glutathione S-transferases (GSTs) were investigated in human breast matched normal and tumor samples. The GSTA, GSTM, GSTP and GSTT isoenzymes from the crude extracts of matched breast normal and tumor tissues in terms of their immunological properties using western blotting were compared. In most of the samples, the GST activities were higher in the tumor than in the normal cytosolic fractions against both CDNB and EPNP. In the western blotting analysis, it was proved statistically that in normal and tumor epithelial cells, there was difference between GST pi and theta isoenzymes expressions (p0.05). In normal epithelium there was a stronger GST theta expression than in invasive tumor tissues (p=0.013). However, the stronger GST pi expression was observed in tumor epithelium than in normal epithelium in human breast cancers (p=0.000). We found the GSTP protein level and GST activities were higher in the breast tumor than in the normal cytosolic fractions against both CDNB and EPNP, thus implicating a certain biological importance.     

Levels of plasma fibrinogen and d-dimer in patients with impaired fasting glucose.

BACKGROUND: Cardiovascular risk associated with impaired fasting glucose has been examined in various studies with conflicting results. During the last 10 years, several risk markers for atherosclerosis such as fibrinogen and D-dimer have been identified. The present study was designed to evaluate plasma fibrinogen and D-dimer levels in patients with impaired fasting glucose compared with normal subjects and those with type 2 diabetes mellitus. METHODS: Age-, sex-, and body mass index-matched 30 normal subjects, 30 patients with impaired fasting glucose (fasting glucose 110 to 125 mg/dl), and 30 patients with type 2 diabetes mellitus (fasting glucose >/= 126 mg/dl) were included in the study. RESULTS: The levels of plasma fibrinogen in patients with type 2 diabetes mellitus, impaired fasting glucose, and normal subjects were 449 (306 - 605) mg/dl, 348 (264 - 468) mg/dl, and 216 (179 - 260) mg/dl, respectively. Patients with impaired fasting glucose had significantly lower plasma fibrinogen levels than patients with type 2 diabetes mellitus (p < 0.05). There were significantly higher plasma fibrinogen levels in patients with impaired fasting glucose than in normal subjects (p < 0.05). The levels of plasma D-dimer in patients with type 2 diabetes mellitus, impaired fasting glucose, and normal subjects were 615 (505 - 768) mg/l, 518 (412 - 664) mg/l, and 424 (356 - 557) mg/l, respectively. Patients with impaired fasting glucose had significantly lower plasma D-dimer levels than patients with type 2 diabetes mellitus (p < 0.05). There were significantly higher plasma D-dimer levels in patients with impaired fasting glucose than in normal subjects (p < 0.05). The levels of plasma fibrinogen and D-dimer were related to fasting glucose in type 2 diabetes mellitus and impaired fasting glucose groups (p < 0.05). We also detected positive correlation between plasma fibrinogen levels and age in study groups (p < 0.05). CONCLUSION: Our data suggest that patients with impaired fasting glucose pose a hypofibrinolytic status and cardiovascular risk, although this was lower than in patients with type 2 diabetes mellitus.     

The effect of weight loss on the mean platelet volume in obese patients

Obesity is a chronic metabolic disorder associated with cardiovascular disease and atherosclerosis. Platelet activation and aggregation are central processes in the pathophysiology of cardiovascular disease. Mean platelet volume (MPV), a determinant of platelet activation, is a newly emerging risk marker for atherothrombosis. Our objective was to evaluate the effect of weight loss on the MPV in obese patients. We selected 30 obese women patients and 30 non-obese healthy women subjects. All obese patients took the same content and caloric diet treatment for 3 months. Body mass index (BMI), metabolic parameters and MPV were measured at baseline and after 3 months diet treatment. Before diet treatment, obese group had significantly higher MPV levels than in the non-obese control group (8.18?±?1.09 fl vs. 8.01?±?0.95 fl, p?=?0.004). MPV showed positive correlations with BMI level in the obese group (r?=?0.43, p?=?0.017). BMI significantly decreased after diet treatment (36.2?±?3.2?kg/m² vs. 34.7?±?3.6?kg/m², p?<?0.001), in the obese group. MPV significantly decreased after diet treatment in the obese group (8.18?±?1.09 fl vs. 8.08?±?1.02 fl, p?=?0.013). There was a positive correlation between weight loss and reduction in MPV (r?=?0.41, p?=?0.024). In addition to its well-known positive effects on cardiovascular disease risk, weight loss may also possess significant anti-platelet activation properties that can contribute its antiatherogenic effects in obese patients.     

Clinical trial: transcutaneous interferential electrical stimulation in individuals with irritable bowel syndrome - a prospective double-blind randomized study

Background: The exact etiology of irritable bowel syndrome (IBS) remains unclear. Curative treatment is not available and current treatment modalities are mainly directed against the predominant symptoms. There are a few studies reporting the beneficial effects of transcutaneous electrical stimulation in patients with chronic constipation, gastroparesis, and functional dyspepsia. Aim: To investigate whether transcutaneous electrical stimulation is an effective procedure in IBS patients. Methods: IBS patients were randomly placed in vacuum interferential current (IFC) and placebo groups. Both treatments consisted of 12 sessions administered over 4 weeks. Symptoms due to IBS were documented via questionnaires, including the IBS Global Assessment of Improvement Scale, numeric rating scales, visual analogue scale, and IBS Quality of Life Scale at the beginning of, end of, and 1 month after the treatment. Results: Patients in the therapy (29 cases) and placebo (29 cases) groups were homogeneous with respect to demographic data and gastrointestinal system symptoms. When compared to the beginning scores, severity of abdominal discomfort, bloating, and abdominal distension and rumbling improved significantly in either interference or placebo groups at both the end of treatment and 1 month after treatment. In the IFC group, severity of symptoms continued to decrease significantly at 1 month after treatment when compared to scores at just the end of treatment, whereas in the placebo group severity of these symptoms did not change significantly on numeric severity scales. Also, the visual analogue scale of the first month after treatment continued to decrease significantly when compared to the level at the end of treatment in the IFC group. Total quality score increased significantly in the IFC group. Conclusions: Vacuum IFC therapy can significantly improve symptoms and quality of life in patients with IBS. It may represent a novel treatment modality for drug-refractory IBS patients.     

Will a second biopsy sample affect treatment decisions in patients with chronic hepatitis B?

Background and aim

Liver biopsy is the gold standard for assessment of fibrosis in patients with hepatitis B. However, it has some disadvantages, including inter-observer and intra-observer variability in biopsy interpretation and specimen variation. A standard biopsy specimen represents only about 0.0002 % of the whole liver. It has been shown that two biopsy samples collected during a procedure have significant influence on the diagnostic performance of interpretation in patients with hepatitis C or non-alcoholic steatohepatitis. Therefore, we aimed to assess the influence of collecting two liver biopsy samples during a single procedure for staging and grading chronic hepatitis B.

Patients and methods

27 patients were included in the study. The median age of the patients was 43.51 ± 11.69. Fifteen patients were female, 12 patients were male. In the biopsy procedure, two samples of liver lobes were obtained. Grade and stage scores were compared between the two samples. Fibrosis staging and grading were assessed according to the Ishak scoring system.

Results

Numbers of portal tract and biopsy size were equal in the two samples. There was a significant difference between the samples in terms of histological activity index (p value = 0.04). However, the difference was not enough to distinguish the mild and moderate stages. On the other hand, no significant difference in fibrosis staging between the two samples was found.

Conclusions

With this relatively small size of patients, in this study, we showed that a proper liver biopsy size is sufficient to predict treatment decisions in chronic hepatitis B patients. However, further studies are needed to show the association of sampling variability in patients with hepatitis B.

     

The utility of serum receptor-binding cancer antigen expressed on SiSo cells in gastrointestinal tract cancers.

BACKGROUND: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a novel tumour marker that has been described in various kinds of cancer. The majority of observations include immunohistochemical studies; however, there are not enough data about the utility of this antigen as a serum tumour marker and its tumour specificity. AIM: To measure the serum levels of RCAS1 in patients with gastrointestinal (GI) tract cancers and compare them with other GI tract tumour markers. PATIENTS AND METHODS: Sera collected from patients with GI cancers (14 esophagus, 32 gastric and 36 colon) and from healthy volunteers (30 individuals) were analyzed for RCAS1 and compared with carcinoembryonic antigen (CEA) and cancer antigen 19-9. The relationship between serum RCAS1, tumour stage and tumour grade was also evaluated. RESULTS: Mean serum RCAS1 level was higher in patients with GI tract cancers compared with the control group (P=0.001). Among GI tract cancers, RCAS1 had lowest and highest sensitivity for esophagus and colon cancer diagnosis, respectively. Serum RCAS1 had a higher sensitivity for malignancy, except in the colon, and lower specificity in all groups compared with CEA. In comparison with cancer antigen 19-9, serum RCAS1 was more sensitive but less specific for all GI cancer groups. Mean serum RCAS1 levels were not statistically significant among histopathological tumour types (P>0.05). Although serum RCAS1 levels were significantly higher in cases with lymph node involvement compared with lymph node-negative cases (P=0.009), there was no difference between cases with and without serosal involvement, vascular invasion and distant metastasis; no correlation was found between tumour size and RCAS1 levels. CONCLUSIONS: RCAS1 may be used and combined with CEA as a tumour marker in GI tract cancers.