The frailty syndrome in general practitioner care: a pilot study.

BACKGROUND: Knowledge about frailty among patients seen by general practitioners (GP) is currently limited. PATIENTS AND METHODS: Frailty assessment by the criteria of Fried and additional documentation was performed at a GP's office. RESULTS: Out of 119 participating patients, 14.3% were classified as frail, 52.1% as prefrail, and 33.6% as not frail. Frailty was associated with comorbidity, the number of drugs prescribed, depressive symptoms, cognitive function, and frequency of falls. CONCLUSION: The prevalence of frailty is high among the cohort of elderly persons seen by a GP. Routine frailty assessment will help to direct preventive and therapeutic interventions.

Molecular characterization of Polish patients with familial hypercholesterolemia: novel and recurrent LDLR mutations.

Autosomal dominant hypercholesterolemia (ADH) is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9). In this study, a molecular analysis of LDLR and APOB was performed in a group of 378 unrelated ADH patients, to explore the mutation spectrum that causes hypercholesterolemia in Poland. All patients were clinically diagnosed with ADH according to a uniform protocol and internationally accepted WHO criteria. Mutational analysis included all exons, exon-intron boundaries and the promoter sequence of the LDLR, and a fragment of exon 26 of APOB. Additionally, the MLPA technique was applied to detect rearrangements within LDLR. In total, 100 sequence variations were identified in 234 (62%) patients. Within LDLR, 40 novel and 59 previously described sequence variations were detected. Of the 99 LDLR sequence variations, 71 may be pathogenic mutations. The most frequent LDLR alteration was a point mutation p.G592E detected in 38 (10%) patients, followed by duplication of exons 4-8 found in 16 individuals (4.2%). Twenty-five cases (6.6%) demonstrated the p.R3527Q mutation of APOB. Our findings imply that major rearrangements of the LDLR gene as well as 2 point mutations (p.G592E in LDLR and p.R3527Q in APOB) are frequent causes of ADH in Poland. However, the heterogeneity of LDLR mutations detected in the studied group confirms the requirement for complex molecular studies of Polish ADH patients.

[Prolonged survival through combined treatment with radiofrequency ablation/ethanol instillation compared with radiofrequency ablation alone in the VX2 rabbit liver tumour model]. / Uberlebensvorteil durch Kombinationsbehandlung mit Radiofrequenzablation/Alkoholinstillation im Vergleich zur alleinigen Radiofrequenzablation im VX2-Lebertumormodell am Kaninchen.

UNLABELLED: Combination of radiofrequency ablation (RFA)/ethanol instillation (EI) leads to higher survival rates compared to single RFA for the treatment of VX2 liver tumours in a rabbit tumour model. INTRODUCTION: To improve the outcome and survival rates of RFA in treatment of liver tumours, a comparative study of RFA with or without EI was performed. MATERIAL AND METHODS: We implanted a single tumour in the liver of 46 rabbits. After 20 days, animals were treated with RFA/EI or RFA alone. The animals were observed for a maximum of 110 days, after which an autopsy was conducted. RESULTS: 30 animals of the RFA group and 16 of combination therapy were analysed. After interim analysis with the Kaplan-Meier method, a significantly higher survival rate for the combination therapy was observed (P = 0.004). Following the study design, the experiment was therefore terminated ahead of schedule. Rate of metastasis (M) and local recurrence (LR) did not differ between the combination or RFA alone. CONCLUSION: RFA/EI is superior to treatment with RFA alone with regard to survival rates.

Differences in risk factors for dementia with neurodegenerative traits and for vascular dementia.

In 229 patients with dementia and in 144 control subjects, polymorphisms of apolipoprotein E (ApoE), low-density-lipoprotein (LDL)-receptor-related protein, alpha(2)-macroglobulin, interleukin (IL) 1beta, angiotensin-converting enzyme and of methylene tetrahydrofolate reductase genes were investigated. In plasma, antibodies against Chlamydia pneumoniae and lipids were determined. Dementia was classified as probable Alzheimer's disease (AD), probable dementia of vascular origin (VaD) and mixed dementia (MD). An association of the disease with ApoE and IL-1beta polymorphism and increased levels of LDL cholesterol were observed in AD and in MD but not in VaD.

Dynamics of LDL oxidation in ischemic stroke patients.

OBJECTIVE: Oxidative modification of human low density lipoprotein (LDL) plays an important role in the development of atherosclerosis. The aim of this study was to evaluate the oxidative modification of LDL in the group of patients with ischemic stroke. MATERIAL AND METHODS: In the group of 43 patients 3 months after ischemic stroke and in the age and sex-matched control group, the kinetics of LDL oxidation and level of vitamin E were estimated. The susceptibility of LDL to oxidation was evaluated in isolated LDL exposed to in vitro oxidation. In 26 patients, after diet change, clinical and laboratory investigations were repeated 9 months later. RESULTS: In the patient group, susceptibility of LDL to oxidation was enhanced, lag phase was significantly shorter in comparison with the control group. After a change in diet, significant elongation of the lag phase was observed. CONCLUSION: Diet change improves LDL resistance to oxidation and may influence prognosis in stroke patients.

[Determination of lipoprotein (a) [Lp(a)] in patients with ischemic stroke. Preliminary communication]. / Oznaczanie lipoproteiny (a) [Lp(a)] u pacjentow z niedokrwiennym udarem mozgu. Doniesienie wstepne.

The aim of this work was the determination of apolipoprotein(a) [Lp(a)] in the patients three months after the onset of ischaemic stroke. A group of 56 patients was investigated. Stroke was diagnosed as caused by atherosclerotic changes in main cerebral arteries in 32 patients and in 11 by changes in cervical arteries. In 13 persons a lacunar stroke was recognised. The mean Lp(a) level and the median value were significantly higher in the group of patients after stroke as compared with 45 controls. A more frequent occurrence of Lp(a) level over 30 mg/dl considered as pathological was observed more often in the patients. No correlation was seen between Lp(a) and the resistance of LDL to oxidation nor between Lp(a) and the amount of products of LDL oxidation in vitro.

Apolipoprotein E genotype, lipid levels and coronary heart disease in a Polish population group.

Genotype of apolipoprotein E has been identified in a group of randomly selected Polish subjects participating in a cross-sectional study performed within the POL-MONICA Program, the part of international study WHO-MONICA Project. The investigated group consisted of 170 persons, 92 males and 78 females aged 41-69 years (mean age 62.0+/-5.11). The observed frequency of apolipoprotein E alleles was: epsilon2 - 7.6%, epsilon3 - 81.8% and epsilon4 - 10.6%, which was similar to frequencies in the neighbouring European countries. Statistically significant lower means of total cholesterol (TC) and of low density lipoprotein cholesterol (LDL-C) levels in epsilon2 carriers and higher means of TC, of LDL-C and of triglycerides in epsilon4 carriers were observed as compared with noncarriers of respective alleles. Some nonlipid cardiovascular risk factors (hypertension (HT) and obesity) and coronary heart disease (CHD) showed a tendency to lower prevalence in the epsilon2 allele carriers as compared to noncarriers. In the epsilon4 allele carriers a tendency to higher prevalence of HT, but not of CHD was observed as compared to noncarriers of this allele.

Familial defective apolipoprotein B-100 in a group of hypercholesterolaemic patients in Poland. Identification of a new mutation Thr3492Ile in the apolipoprotein B gene.

The prevalence of the familial defective apolipoprotein B-100 (FDB) Arg3500Gln mutation in 525 unrelated hypercholesterolaemic Polish subjects was evaluated. DNA samples were screened for FDB mutation using SSCP method. Presence of mutation was confirmed using a mismatch MspI PCR strategy. Plasma lipid levels and clinical characteristics of 13 patients identified as carriers of the mutation and of their 23 affected relatives were analysed and compared with non-affected ones. In the affected individuals a variable expression of lipid concentrations and of atherosclerosis symptoms were observed. The prevalence of FDB Arg3500Gln mutation in hypercholesterolaemic Polish subjects (3.7%) seems to be similar to the frequency reported in other Caucasian hypercholesterolaemic populations. The estimated prevalence of the mutation in general Polish population is relatively high being 1/250. The same haplotype at the apoB locus in the carriers of this mutation in Poland as in other populations from Western Europe suggests its common origin. In one hypercholesterolaemic subject a non-hitherto described mutation was identified. It consisted in C-->T transition in apoB codon 3492 leading to threonine to isoleucine substitution in 3492 position of apoB gene (Thr3492Ile).

The level of serum lipids, vitamin E and low density lipoprotein oxidation in Wilson's disease patients.

UNLABELLED: The aim of this study was to estimate the level of lipids and of the main serum antioxidant, alpha-tocopherol (vitamin E), and to evaluate the susceptibility of low density lipoprotein (LDL) to oxidation in Wilson's disease patients. It was assumed that enhanced LDL peroxidation caused by high copper levels could contribute to the injury of liver and other tissues. The group investigated comprised 45 individuals with Wilson's disease treated with penicillamine or zinc salts and a control group of 36 healthy individuals. Lipids were determined by enzymatic methods, alpha-tocopherol by high performance liquid chromatography, the susceptibility of LDL to oxidation in vitro by absorption changes at 234 nm during 5 h and end-products of LDL lipid oxidation as thiobarbituric acid reacting substances. In Wilson's disease patients total cholesterol, LDL cholesterol and alpha-tocopherol levels were significantly lower compared with the control group. No difference in LDL oxidation in vitro between the patients and the controls was stated. CONCLUSION: enhanced susceptibility of isolated LDL for lipid peroxidation in vitro was not observed in Wilson's disease patients. One cannot exclude, however, that because of low alpha-tocopherol level lipid peroxidation in the tissues can play a role in the pathogenesis of tissue injury in this disease.

[In vitro oxidation of low density lipoproteins in patients after ischemic stroke]. / Utlenianie in vitro lipoprotein niskiej gestosci u osób po przebytym niedokrwiennym udarze mózgu.

The aim of this work was the evaluation of low density lipoprotein (LDL) susceptibility to oxidation in the survivors of ischaemic stroke. The investigations were performed in 65 individuals at least three months after the onset of acute symptoms. In 24 patients stroke was caused by alterations in main cerebral arteries, in 19 by considerable narrowing of carotid artery, in 15 by alterations in small cerebral arteries with often accompanying hypertension and/or diabetes (lacunar stroke) and in 7 by embolism of cardiac origin in individuals with cardiac arrhythmia and coronary artery disease. The control group comprised 25 age matched persons without pathological symptoms. Plasma lipids and apolipoprotein B levels were determined as well as two antioxidants: alpha-tocopherol level and superoxide dismutase activity. The evaluation of lipid peroxidation was performed by determining thiobarbituric acid reacting substances (TBARS) and lipid peroxides (LPO) increase after 5 hours oxidation of isolated LDL in vitro in the presence of copper ions. The level of IgG directed against modified LDL was also evaluated. In the patients decreased HDL cholesterol level was observed as well as increased apolipoprotein B. In the group of thrombotic strokes high triglycerides were observed. alpha-tocopherol level was decreased in the group of cerebral strokes. The amounts of oxidation products did not differ between the whole group of patients after stroke and the controls. A significant increase concerned only the group of lacunar strokes. The evaluation of LDL susceptibility to oxidation in patients after stroke by measuring absorption at 234 nm and determining the time period necessary to the onset of intensive LDL oxidation will be the subject of a separate publication.

Apolipoprotein E genotype and lipid and lipoprotein levels in dementia.

In 64 individuals with dementia (26 Alzheimer type, 34 of vascular origin and 4 other types of dementia) apolipoprotein E genotype was identified. Frequency of epsilon4 allele was 36.5% in Alzheimer patients and 32.4% in vascular dementia ones. In a group of 39 nondemented individuals of the same age the epsilon4 frequency was 11.5%. In demented patients, carriers of epsilon4, a tendency to higher plasma levels of atherogenic lipids (total cholesterol and low-density lipoprotein cholesterol) as compared with noncarriers was observed. It is possible that the epsilon4 form may aggravate the course of dementia through a moderate influence on the atherogenic lipoprotein level. The results showed that both Alzheimer disease and vascular dementia shared the same risk factors which is consistent with current opinion about a link existing between these two types of dementia.

Anti-low-density lipoprotein antibodies in alcoholics without and with liver disease and in social drinkers.

Antibodies directed to native and to in-vitro acetaldehyde-modified (ethylated) low-density lipoproteins (LDL) were determined in 28 alcoholic subjects divided into two groups: one with no clinical nor laboratory evidence of liver involvement and the second with histologically proven alcohol-related liver disease. The control group consisted of 18 individuals who drank alcohol socially. In the individuals with alcoholic liver disease IgG reactivity against both native and ethylated LDL was significantly higher than in alcoholic individuals without liver injury. High levels of IgG reactivity in individuals with alcoholic liver disease were also observed against malondialdehyde-modified, methylated, acetylated and carbamylated LDL. A selective high anti-ethylated LDL IgG reactivity was observed in 11% of control subjects.

[Urinary beta-hexosaminidase activity as a marker for the monitoring of sobriety]. / Aktywnosc beta-heksozoaminidazy w moczu jako maker naduzywania alkoholu u osób uzaleznionych.

The aim of this study was to check the usefulness of urine beta-hexosaminidase activity determination as a tool of monitoring sobriety in alcohol dependent individuals. The examinations were performed in 93 patients undergoing detoxification treatment after heavy drinking and in 29 individuals who were starting psychotherapeutic treatment after declaring at least 2 weeks abstinence period. Enzyme activity was determined using a spectrofluorimetric method and was referred to urine creatinine level. In the detoxification group the abnormally high beta-hexosaminidase activity was decreasing gradually toward normal values within 2 weeks. In less than 10% of the patients atypical increase was observed in the course of treatment, what could be attributed to an, influence of nonspecific factors or possibly to misbehavior (alcohol drinking or urine samples substitution). Among individuals who declared at least 2 weeks abstinence period (psychotherapeutic group) in 25% of cases abnormally high enzyme activity was detected, what suggested their more recent alcohol drinking.

Apolipoprotein E in alcoholics.

In 31 alcohol addicted patients entering detoxication treatment and in 14 social drinkers apolipoprotein E (Apo E) was assayed by radial immunodiffusion in the whole serum and after phosphotungstate Mg2+ precipitation. Serum Apo E level in the intoxicated individuals was increased compared with the controls. The Apo E increase was mostly due to the very low and low density (VLDL + LDL) fraction. The Apo E/cholesterol ratio in this fraction was increased. It is possible that increased Apo E concentration in VLDL contributes to their enhanced uptake by the liver.

[Activity of beta-hexosaminidase in serum of patients with alcoholic and nonalcoholic liver diseases]. / Aktywnosc beta-heksozoaminidazy surowicy w chorobach watroby pochodzenia alkoholowego i niealkoholowego.

The total activity and thermostable activity of serum beta-hexosaminidase were determined in alcohol-dependent patients with liver damage, in non-drinking hepatic patients, in alcohol-dependent presently drinking patients who had no hepatic symptoms and signs, and in healthy persons drinking alcohol occasionally in moderate quantities who served as the control group. The enzyme activity was determined by the spectrofluorometric method using 4-methylumbelliferone derivative as substrate. The activity of beta-hexosaminidase in both groups with liver disease of both alcoholic and non-alcoholic origin exceeded significantly the control values. In those alcohol-dependent patients with liver disease who did not stop drinking, the activity was higher after recent drinking in relation to that after a period of abstinence. The determination can thus serve as a marker of alcohol abuse also in alcohol-dependent patients with liver damage. The share of thermostable component in the total increase of beta-hexosaminidase activity in alcohol-abusing persons was higher than that in the case of hepatic diseases of non-alcoholic origin.

Acetaldehyde adducts and autoantibodies against VLDL and LDL in alcoholics.

Alcohol consumption markedly increases the hepatic output of very low density lipoprotein (VLDL), whereas it decreases the resulting low density lipoprotein (LDL) levels and apolipoprotein B. As ethylation of apoB-lysine renders LDL immunogenic and accelerates their clearance, and as alcoholics develop antibodies against acetaldehyde-protein adducts, we searched for antibodies against lipoproteins. We measured serum IgG, IgA, and IgM titers against VLDL, LDL and high density lipoprotein (HDL) in 10 non-alcoholics and 35 recently drinking alcoholics by ELISA assay. Alcoholics had higher IgG titers than non-alcoholics against VLDL and LDL; these were higher with VLDL than LDL or HDL. Using VLDL and LDL (but not HDL) from alcoholics gave the greatest response. There was no difference in IgA and IgM reactivity. To search for acetaldehyde adducts, we measured the reactivity of VLDL, LDL, HDL, and residual serum proteins against a rabbit anti P4502E1-acetaldehyde adduct IgG, which recognizes the adducts but not the unmodified proteins (except for P4502E1). ApoB-containing lipoproteins from alcoholics (and to a lesser extent non-lipoprotein proteins) reacted with anti-adduct IgG more strongly than those of non-alcoholics. The difference was striking for VLDL, less for LDL, and not detectable for HDL. This suggests that acetaldehyde reacts with apoB prior to its secretion from the liver and that the altered VLDL are partially removed prior to their conversion to LDL. In conclusion, alcoholics develop acetaldehyde adducts in apoB-containing lipoproteins, particularly VLDL. The immune response to these neoantigens could result in accelerated clearance of VLDL and LDL and decreased conversion of VLDL to LDL.