Micro-scale vertebral features in postmenopausal women with alcohol-associated and metabolic-associated fatty liver disease: ex vivo bone quality analyses.

PURPOSE: Although epidemiological studies indicate increased fracture risk in women with alcohol-associated liver disease (AALD) and metabolic-associated fatty liver disease (MAFLD), data about their micro-scale bone features are still limited. We aimed to characterize bone quality changes in the anterior mid-transverse part of the first lumbar vertebral body collected from 32 adult postmenopausal females. Based on pathohistological assessment of the liver tissue, individuals were divided into AALD (n = 13), MAFLD (n = 9), and control group (n = 10). METHODS: We analyzed trabecular and cortical micro-architecture (using micro-computed tomography), bone mechanical properties (using Vickers microhardness tester), osteocyte lacunar network and bone marrow adiposity morphology (using optic microscopy). Data were adjusted to elude the covariant effects of advanced age and body mass index on our results. RESULTS: Our data indicated a minor trend toward deteriorated bone quality in MAFLD women, presented in impaired trabecular and cortical micro-architectural integrity, which could be associated with bone marrow adiposity alterations noted in these women. Additionally, we observed a significant decline in micro-architectural, mechanical, and osteocyte lacunar features in lumbar vertebrae collected from the AALD group. Lastly, our data indicated that vertebral bone deterioration was more prominent in the AALD group than in the MAFLD group. CONCLUSION: Our data suggested that MAFLD and AALD are factors that could play a part in compromised vertebral strength of postmenopausal women. Also, our data contribute to understanding the multifactorial nature of bone fragility in these patients and highlight the necessity for developing more effective patient-specific diagnostic, preventive, and therapeutic strategies.

The micro-structural analysis of lumbar vertebrae in alcoholic liver cirrhosis.

Although vertebral fracture is more common among alcoholic liver cirrhosis patients when compared to general population, current data on three-dimensional micro-architecture are scarce. Our study showed significant trabecular deterioration in lumbar vertebrae obtained from alcoholic liver cirrhosis donors, suggesting that they should be advised to undergo early-stage screening for osteoporosis. PURPOSE: Recent studies showed an increased incidence of vertebral fractures in alcoholic liver cirrhosis (ALC) patients, while data about vertebral micro-structure are still limited. The aim of this study was to compare trabecular and cortical micro-architecture of lumbar vertebrae between ALC patients and healthy age- and sex-matched controls. METHODS: Our study included lumbar vertebral samples of male cadaveric donors, divided into ALC (n = 20, age: 59 ± 6 years) and control group (n = 20, age: 59 ± 8 years). Following pathohistological verification of liver cirrhosis, trabecular and cortical bone micro-architecture was analyzed by micro-computed tomography (micro-CT). RESULTS: Micro-CT evaluation of the trabecular bone in lumbar vertebrae showed a significant decrease in bone volume fraction, trabecular thickness, trabecular number, and connectivity (p < 0.01). In contrast to trabecular deterioration, prominent alteration in cortical parameters was not observed in lumbar vertebrae of ALC patients (p > 0.05). CONCLUSIONS: Our data indicate that susceptibility to non-traumatic fractures in ALC patients could be explained by alterations in trabecular bone micro-architecture. Thus, we genuinely recommend osteological screening of the lumbar spine for all ALC patients in order to evaluate individual fracture risk. Graphical abstract.

Vitamin D status, bone metabolism and bone mass in patients with alcoholic liver cirrhosis.

INTRODUCTION: Osteoporosis is seen in some 12-50 % patients with liver cirrhosis. Detrimental effects of alcohol are exerted directly on the bone cells and indirectly on hormones. Vitamin D is involved in osteoblast differentiation, bone matrix synthesis and bone mineralization, as well as in its decomposition. Vitamin D deficiency has been reported in about 2/3 patients with liver cirrhosis. OBJECTIVE: Determination of vitamin D status, bone metabolic activity and bone mass in patients with alcoholic liver cirrhosis (ALC). METHODS: Thirty male patients with ALC were investigated in the period October 2011- March 2012. Total vitamin D, parathormone, osteocalcin and CrossLaps were determined by the ECLIA method (electrochemiluminiscence immunoassay) using Elecsys 2010 analyzer. Bone mineral density was measured by means of dual-energy x-ray absorptiometry (DXA) using the Lunar Prodigy. Result analysis was performed using descriptive statistics and hypothesis testing, as well as nonparametric one-way analysis of variance, Kruskal-Wallis test, Mann-Whitney U-test, Pearson correlation coefficient. RESULTS: Deficiency in vitamin D (< 50 nmol/l) was noted in 66.66 % patients, with highest prevalence in Child-Pugh C class patients (chi-square = 5.878, p < 0.05). Osteocalcin levels were below the lower limit of normal in 86.7 % patients. CrossLaps was increased in only 20 % patients, but a significant increase was noted in Child-Pugh C class patients. Osteoporosis was diagnosed in 20 % of patients, with no correlation with disease severity and vitamin D status. CONCLUSIONS: Vitamin D deficiency is present in patients with ALC. Decrease in bone formation and bone mass is most probably multicausal (Tab. 2, Fig. 1, Ref. 30).

Waiting a few extra minutes before measuring blood pressure has potentially important clinical and research ramifications.

Office blood pressure (BP) is recommended to be measured after 5 min of seated rest, but it may decrease for 10 min of seated rest. This study aimed to determine the change (and its clinical relevance) in brachial and central BP from 5 to 10 min of seated rest. Office brachial and central BP (measured after 5 and 10 min), left ventricular (LV) mass index, 7-day home and ambulatory BP were measured in 250 participants with treated hypertension. Office brachial and central BP were significantly lower at 10-min compared with 5-min BP (P<0.001). Seven-day home systolic BP (SBP) was significantly lower than office SBP measured at 5 min (P<0.001), but was similar to office SBP at 10 min (P=0.511). From 5 to 10 min, the percentage of participants with controlled BP increased and the percentage of participants with high central pulse pressure (PP) decreased (P<0.001). Moreover, brachial and central PP were significantly correlated with LV mass index measured at 10 min (r=0.171, P=0.006 and r=0.139, P=0.027, respectively), but not at 5 min (r=0.115, P=0.068 and r=0.084, P=0.185, respectively). BP recorded after 10 min is more representative of true BP control. These findings have relevance to appropriate diagnosis of hypertension and design of clinical trials.

Prognostic factors for longer disease free survival and overall survival after surgical resection of isolated liver metastasis from breast cancer.

PURPOSE: Isolated liver metastases (LMs) from breast cancer (BC) occur in only 1-3% of the cases. Resection of isolated LMs improves survival. We examined the prognostic factors for time to LM development, disease free survival (DFS) and overall survival (OS) after BCLM resection. METHODS: From 2006 to 2009, 32 patients underwent LM resection. All of them had breast cancer surgery for their primary tumor and developed resectable LMs as the first and only site of disease progression. RESULTS: LMs developed after a median of 25 months. With a median follow up of 37 months (range 7-66) after metastases resection, median DFS and OS (with 95% CI) were 22.5 (12-40) and 37 (≥23) months, respectively. Tumor size ≥3 vs <3 cm and adjuvant chemotherapy vs no adjuvant chemotherapy correlated with shorter time to LM development (p<0.01 for both parameters). These parameters and BC negative estrogen (ER)/ progesterone receptors (PR) (ER?/PR? vs other) were related with shorter DFS. Positive (vs negative) axillary lymph nodes and BC negative ER/ PR (ER?/PR? vs other) status correlated with shorter OS (p<0.01 for both parameters). A period to metastases development ≥ 24 months (vs ≤24) and single (vs multiple) metastases were related with longer DFS and OS (p<0.01 for both conditions). CONCLUSION: Despite the relatively small number of patients in this study, we believe that positive ER/PR status for both BC and LMs, negative axillary lymph nodes, time to liver metastases development >24 months and single liver metastases predict longer DFS and OS after LM resection.

Persistent elevation of central pulse pressure during postural stress in patients with type 2 diabetes mellitus.

An abnormal increase or decrease in blood pressure (BP) in response to postural stress is associated with increased risk of developing hypertension and stroke. However, the haemodynamic responses contributing to changes in central BP with postural stress are not well characterised. We aimed to determine this in controls compared to patients with type 2 diabetes mellitus (T2DM), whom we hypothesised would have an abnormal postural response. 41 participants (20 control, 21 T2DM) underwent measurement of brachial and central BP (by radial tonometry), with simultaneous bioimpedance cardiography (to determine stroke volume (SV) and cardiac output (CO)) and heart rate variability in seated and standing postures. Systemic vascular resistance (SVR; mean arterial pressure/CO), and arterial elastance (EA; end systolic pressure/SV) were calculated. Postural changes were defined as seated minus standing values. Central pulse pressure (PP) was higher in patients with T2DM and did not change from seated-to-standing positions, whereas there was a significant decrease upon standing in controls (P<0.05). The change in central systolic BP (SBP) correlated with change in SVR and EA in controls (r=0.67 and 0.68, P<0.05, respectively), but not in patients with T2DM (r=-0.05 and r=0.03, P>0.05, respectively). SV was the only significant correlate of change in central SBP in T2DM patients (r=0.62, P<0.05) and this was not observed in controls (r=-0.08 P>0.05). We conclude that central haemodynamic responses to postural stress are altered in patients with T2DM and result in persistent elevation of central PP while standing. This may contribute to increased cardiovascular risk associated with T2DM.

A case of pregabalin intoxication.

Pregabalin, or S-(+)-3-isobutylgaba, is a lipophilic analogue of GABA. Although pregabalin is structurally related to GABA, it is inactive at GABA receptors and does not appear to mimic GABA physiologically. Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system. It is currently being licensed for epilepsy, neuropathic pain, and generalized anxiety disorder. There are few case reports that have demonstrated safety of pregabalin in case of intoxication. We report here a case of pregabalin toxicity with a moderate pregabalin concentration that was successfully managed with conservative treatment only. The case report describes a 54-year-old man who was treated with pregabalin for generalized anxiety disorder. After having experienced a significant stress on a job the patient ingested huge amount of pregabalin (4,2 r) together with bromazepam (21 mg) and chlorimipramine (125 mg). On presentation he was conscious and alert with a stable condition of cardiovascular and respiratory systems. The serum pregabalin concentration was 20.8 mg/L but the patient did not have any signs of toxicity. Thanks to his good and stable somatic condition the patient was managed with supportive treatment only. Although anecdotal, our case report points toward safety of pregabalin following deliberate self-poisoning. Our observation is in accordance with the recent international literature underlining that pregabalin was listed as the drug ingested in only 1% of fatalities, usually in combination with other drugs.

Skin photoprotection improvement: synergistic interaction between lipid nanoparticles and organic UV filters.

A photoprotective formulation was developed with an increased sunprotection factor (SPF), compared to a conventional nanoemulsion, but having the same concentration of three molecular sunscreens, namely ethylhexyl triazone, bis-ethylhexyloxyphenol methoxyphenyl triazine, and ethylhexyl methoxycinnamate. The sunscreen mixture was incorporated into nanostructured lipid carriers (NLCs). The ability of nine different solid lipids to yield stable aqueous NLC suspensions was assessed. After the production by hot high pressure homogenization, the NLC were analyzed in terms of particle size, physical state, particle shape, ultraviolet absorbance and stability. The particle size for all NLC was around 200 nm after production. The NLC suspension with carnauba wax had superior UV absorbance, NLC from bees wax showed similar efficiency as the reference emulsion. The NLC formulations were incorporated into hydrogel formulations and the in vitro SPF was measured. This study demonstrated that approximately 45% higher SPF values could be obtained when the organic UV filters were incorporated into carnauba wax NLC, in comparison to the reference nanoemulsion and bees wax NLC. The data showed that the synergistic effect of NLC and incorporated sunscreens depends not only on the solid state of the lipid but also on its type.

Potential use of nanostructured lipid carriers for topical delivery of flurbiprofen.

The potential use of nanostructured lipid carriers (NLC) composed of a fatty acid [stearic acid (SA)] or a triglyceride (glyceryl behenate) as solid lipids, and a mixture of medium chain triglycerides and castor oil as liquid lipids, for skin administration of flurbiprofen (FB), has been explored. Two different optimized NLC formulations (FB-SANLC based on SA vs. FB-C888NLC based on glyceryl behenate), with respect to the morphometrical properties (particle size and polydispersity index) and the entrapment efficiency, were used in this study. The ex vivo permeation profiles of FB-C888NLC, FB-SANLC and conventional FB solution were evaluated using human skin. An improved FB permeation was observed when the drug was delivered by skin application of FB-C888NLC, attributed to the particle size and matrix crystallinity. The differential scanning calorimetry and X-ray diffraction studies suggested major polymorphic transitions in the lipid matrix of FB-C888NLC. A good correlation between polymorphic transitions and increased drug permeation was observed. However, both NLC dispersions showed a penetration-enhancing ratio (ER) higher than conventional FB solution. The in vitro and in vivo irritancy and local tolerability were assessed by running, respectively, the SKINTEX™ and Draize test. Both FB-C888NLC and FB-SANLC were classified as nonirritant.

Profile of handicap situations in cancer patients.

PURPOSE: The aim of this study was to assess the level of difficulty when performing a life habit, the type of assistance required and the person's level of satisfaction in relation to the accomplishment of each life habit, to establish a profile of handicap situation in cancer patients and to assess the relationship between the level of accomplishment and the level of satisfaction. PATIENTS AND METHODS: The study sample consisted of 100 cancer patients. The Life Habits Assessment was used to measure the degree of accomplishment in 12 categories of life habits - daily living and social roles. RESULTS: Disruptions in the accomplishment of all life habit categories were revealed. The highest disruptions were observed in the following categories: education, recreation, and employment. The highest accomplishments were observed in communication, personal care, and fitness. Human assistance was required in the accomplishment of responsibility, community, employment and recreation. The highest person's level of satisfaction was observed in communication, personal care and interpersonal relations. The highest correlation between the level of accomplishment and the level of satisfaction were in mobility and residence, and the lowest correlation was in communication. CONCLUSION: The established profile of handicap situation in cancer patients should help specify rehabilitation objectives and may be a frame for individual treatment plan in accomplishing better social participation of cancer patients.

The facial-bone fractures among fatally injured car occupants in frontal collisions.

The retrospective study was performed of all deceased car-occupants in frontal car collisions in order to identify persons with facial-bone fractures. The sample consisted of 482 cases: 378 males and 104 females, average age of 39.59+/-16.01 years. There were 239 car-drivers, 194 front-seat passengers, and 49 rear-seat passengers. In 46 of 482 cases, single fracture of upper facial bones was established: nasal fractures were the most common, followed by zygomatic. In 118 of 482 cases, fracture of upper facial bones was established, as well as 70 cases of jawbone. The fractured facial bones either of the upper or lower face could not be a factor that predicts the position of the deceased in the motor vehicle at the moment of injury (lambda=0.989, p>0.05). The multi-fractured facial-bones were very often associated with the multi-fractured cranial bones - 85 cases (chi(2) =138.75, df=8, p<0.001), as well as jawbone fracture - 35 cases (chi(2) =20.52, df=4, p<0.001). Brain injuries were more present and more severe (coup and contrecoup-contusion and brain laceration) if more facial-bone fractures were involved (chi(2) =147.99, df=8, p<0.001). Cases with only contrecoup brain contusions, associated with multi-fractured facial-bones, were rare - 6 of 118. These fractures are very often associated with cranial fractures, as well as with brain injuries and were caused by intensive contact of the deceased's head with the car's pillar.

Concentration of carbon-monoxide in carbonized bodies--forensic aspects.

The aim of this paper is to determine the correlation between carbonized fire victims' carbon-monoxide (CO) blood concentration and the cause of death. We have reevaluated and analyzed the causes of death over a 10-year period regarding CO concentrations and atherosclerosis. We have considered the possible usefulness of low CO concentrations as a vital sign in smokers and non-smokers. The study included the retrospective analyzes of 73 autopsy reports of carbonized bodies. All the autopsies were carried out in the Institute of Forensic Medicine in Belgrade over a 10-year period (1990-1999). The investigation included 53 men and 20 women (chi(2)=19.83, p<0.001) with an average age of 41.40+/-21.35 years. We found 10 cases of deadly carbon-monoxide poisoning, but further analysis of CO concentrations revealed 6 more cases in which CO poisoning could be considered. We found a statistically significant relationship between carboxyhaemoglobin concentration above 10% and the aspiration of soot (chi(2)=6.41, p<0.01). In five cases with serious atherosclerosis, the concentration of carboxyhaemoglobin was above 20%, although these concentrations can be accepted as the cause of death. Half of the deceased, in the moment of death were under the influence of alcohol and 19 of them had a blood alcohol concentration above 1 pro mille.

Characteristics of chest injury in falls from heights.

This study included 660 victims injured due to high fall. All cases are with injuries caused by the free-fall model of high fall. The range of the heights was from 0 to 70 m. The sample was divided into three groups of growing height: low falls up to 7 m, high falls from 7 to 30 m, and very high falls above 30 m. Statistical analysis was performed using two way ANOVA according to Scheirer-Ray-Hare in complete uneven block. Males were 71% (469), females 29% (191). In the analyzed sample, apart from the height of fall, the number of accidents is about 44% (290 cases) and suicides about 56% (370 cases). Thirty six percent, i.e., 238 of 660 victims had consumed alcohol before death (alcoholemia >0.5 per thousand). The objective of our study was to analyze characteristics of chest injuries made by falling from a height. The frequency of thoracic injuries is statistically significantly related to the height of fall (p<0.05); it increases constantly in falls from heights beyond 3m, so that the rib fractures were present in all falls from heights beyond 40m. The aortic ruptures were found in 21%, and the heart injuries in 16% of all cases. The frequency of aortic and heart ruptures was not statistically significantly related to the height of fall (p>0.05). A rupture of the aorta was the most commonly located on its arch (82%). The heart ruptures were the most commonly located on the atrial posterior wall (70%).

Dark Hanle resonances from selected segments of the Gaussian laser beam cross-section.

We present the Hanle EIT resonances obtained from the various segments of the Gaussian laser beam cross-section, selected by moving the small aperture (placed in front of the detector) radially along the laser beam. Significant differences in the Hanle lineshapes are observed depending on whether the central or outer parts of the Gaussian laser beam are detected. The line narrowing and two counter-sign peaks occur at outer, less intense parts of the beam. The theoretical model suggests that the EIT lineshapes in the laser wings are result of the interference of the laser light and coherently prepared atoms coming from the central part of the beam. By blocking the central part of the laser beam in front of the detector, narrower, and for high laser intensities, even more contrasted Hanle resonances are obtained.

Education of cancer patients--a psychosocial support in the holistic anticancer treatment.

PURPOSE: To assess the readiness for education and the learning needs of cancer patients, and to assess the correlation between the information and different aspects of quality of life (QoL). PATIENTS AND METHODS: 70 cancer patients were enrolled. All of them answered a questionnaire specifically designed to assess the readiness and needs for education, and the level of the information among them. The Rotterdam Symptom Checklist (RSCL) was used for QoL estimation. RESULTS: 28 (40%) out of 70 patients had high motivation for education, while 62 (88%) expressed positive attitudes toward learning. Sixty-three (90%) patients needed to know more about nutrition. The topics about alternative and complementary cancer treatments interested 59 (84%) patients. Forty-two (60%) patients wanted to learn about changing of the life habits and about their own active participation of adaptation to their new situation due to cancer. There was significant (r=-0.33, p<0.005) correlation between the information and global QoL, and borderline significance between the information and physical aspects of QoL (r=-0.233, p=0.052). CONCLUSION: We showed that better understanding knowledge, and skills in the rearrangement of treatment goals and making changes in plans for future might have great impact on QoL. Education of cancer patients in this direction has to be systematic and planned according to the patient's wishes and learning needs. Only in this way education could be a powerful means in coping for better QoL and a psychosocial support in the holistic treatment of cancer patients.

Kinetic-photometric determination of iodide based on its inhibitory effect on the bromate oxidation of Victoria Blue 4-R.

A new sensitive kinetic method has been developed for the determination of trace amounts of I- over the range of 50-300 ng cm(-3). The method was based on the inhibitory effect of iodide on the oxidation of Victoria Blue 4-R by KBrO3. The reaction is monitored spectrophotometrically at 596.3 nm. Method development includes optimization of reagent concentration and temperature. The kinetic parameters of the reaction were reported and a rate equation was suggested. The effects of certain foreign ions upon the reaction rate were determined for the assessment of the selectivity of the method. The proposed method was successfully applied to the determination of iodide in real samples. The new developed method was found to have fairly good selectivity, sensitivity, simplicity and rapidity.