MPS VII - Extending the classical phenotype.

Mucopolysaccharidosis VII (or Sly syndrome) is an autosomal recessive disorder characterised by a deficiency in the enzyme Beta-glucuronidase (GUSB). Partial degradation of glycosaminoglycans (GAGs); chondroitin sulfate (CS), dermatan sulfate (DS) and heparan sulfate (HS) results in the accumulation of these fragments in the lysosomes of many tissues, eventually leading to multisystem damage. In some cases, early diagnosis on clinical grounds alone can be difficult due to the extreme variability of the clinical presentation and disease progression. We present a case report of a 31-year-old male patient diagnosed with MPS VII at the age of 28, who multiple specialists saw without suspecting the diagnosis due to the unusual presentation. The patient presented with a history of developmental delay, scoliosis, kyphosis, corneal clouding, abnormal gait, short stature, hearing impairment, slightly coarse facial features and progressive deterioration of fine motor skills since childhood. The patient had inguinal hernia repair at around 12 months, bilateral hearing impairment with a left bone-anchored hearing aid, and spinal surgery. During spinal surveillance MPS VII was suspected by a spinal surgeon with interest in MPS, and the diagnosis confirmed with a deficiency in beta-glucuronidase in leucocytes and marginally elevated urinary GAGs. Next-generation sequencing identified two mutations in the GUSB gene (OMIM 611499), c.526C > T p.(Leu176Phe) and c.1820G > C p.(Gly607Ala). Although the patient exhibited features of the severe form of non-classical manifestations, his metabolic condition has remained reasonably stable, surviving into adulthood with only symptomatic treatment. We present the ever-expanding phenotypic spectrum of this ultra-rare disease.

Standardising clinical outcomes measures for adult clinical trials in Fabry disease: A global Delphi consensus.

BACKGROUND: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD. METHODS AND FINDINGS: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi procedure. The aim was to reach a consensus regarding clinical trial design, best treatment comparator, clinical outcomes, measurement of those clinical outcomes and inclusion and exclusion criteria. Consensus results of this initiative included: the selection of the adaptative clinical trial as the ideal study design and agalsidase beta as ideal comparator treatment due to its longstanding use in FD. Renal and cardiac outcomes, such as glomerular filtration rate, proteinuria and left ventricular mass index, were prioritised, whereas neurological outcomes including cerebrovascular and white matter lesions were dismissed as a primary or secondary outcome measure. Besides, there was a consensus regarding the importance of patient-related outcomes such as general quality of life, pain, and gastrointestinal symptoms. Also, unity about lysoGb3 and Gb3 tissue deposits as useful surrogate markers of the disease was obtained. The group recognised that cardiac T1 mapping still has potential but requires further development before its widespread introduction in clinical trials. Finally, patients with end-stage renal disease or renal transplant should be excluded unless a particular group for them is created inside the clinical trial. CONCLUSION: This consensus will help to shape the future of clinical trials in FD. We note that the FDA has, coincidentally, recently published draft guidelines on clinical trials in FD and welcome this contribution.

Assessing resilience of healthcare infrastructure exposed to COVID-19: emerging risks, resilience indicators, interdependencies and international standards.

In the moment of preparation of this paper, the world is still globally in grip of the Corona (COVID-19) crisis, and the need to understand the broader overall framework of the crisis increases. As in similar cases in the past, also with this one, the main interest is on the "first response". Fully appreciating the efforts of those risking their lives facing pandemics, this paper tries to identify the main elements of the larger, possibly global, framework, supported by international standards, needed to deal with new (emerging) risks resulting from threats like Corona and assess the resilience of systems affected. The paper proposes that future solutions should include a number of new elements, related to both risk and resilience. That should include broadening the scope of attention, currently focused onto preparation and response phases, to the phases of "understanding risks", including emerging risks, and transformation and adaptation. The paper suggests to use resilience indicators in this process. The proposed approach has been applied in different cases involving critical infrastructures in Europe (energy supply, water supply, transportation, etc., exposed to various threats), including the health system in Austria. The detailed, indicator-based, resilience analysis included mapping resilience, resilience stress-testing, visualization, etc., showing, already before the COVID-19, the resilience (stress-testing) limits of the infrastructures. A simpler (57 indicator based) analysis has, then been done for 11 countries (including Austria). The paper links these results with the options available in the area of policies, standards, guidelines and tools (such as the RiskRadar), with focus on interdependencies and global standards-especially the new ISO 31,050, linking emerging risks and resilience.

Anesthesia for Open Radical Retropubic Prostatectomy: A Comparison between Combined Spinal Epidural Anesthesia and Combined General Epidural Anesthesia.

BACKGROUND: Several anesthesiologic regimens can be used for open radical retropubic prostatectomy. The aim of this retrospective analysis was to compare the combined general epidural anesthesia and the combined spinal epidural anesthesia with regard to availability, efficacy, side effects, and perioperative time consumption in a high-volume center. METHODS: A retrospective analysis was performed by querying the electronic medical records of 1207 consecutive patients from the database of our online documentation software. All patients underwent open radical retropubic prostatectomy from 01/2008 to 08/2011 and met the study criteria. Linear and multivariate regression analyses were performed to identify differences in parameters such as time consumption in the operating unit, hemodynamic parameters, volume replacement, and catecholamine therapy. RESULTS: 698 (57.8%) patients have been undergoing open radical retropubic prostatectomy under combined spinal epidural anesthesia and 509 (42.2%) patients by combined general epidural anesthesia. Operating unit (p <0.0001) and post-anesthesia care unit stay (p <0.0001) as well as total hospital stay (p <0.0001) were significantly shorter in the combined spinal epidural anesthesia group. In addition, this group had reduced intraoperative volume need (p <0.0001) as well as lower need of catecholamines (p <0.0001). CONCLUSIONS: This retrospective study suggests that the combined spinal epidural anesthesia seems to be a suitable and efficient anesthesia technique for patients undergoing open radical retropubic prostatectomy. This specific approach reduces time in the operation unit and length of hospital stay.

Structural and electronic properties of V2O5 and their tuning by doping with 3d elements - modelling using the DFT+U method and dispersion correction.

New electrode materials for alkaline-ion batteries are a timely topic. Among many promising candidates, V2O5 is one of the most interesting cathode materials. While having very high theoretical capacity, in practice, its performance is hindered by its low stability and poor conductivity. As regards the theoretical descriptions of V2O5, common DFT-GGA calculations fail to reproduce both the electronic and crystal structures. While the band gap is underestimated, the interlayer spacing is overestimated as weak dispersion interactions are not properly described within GGA. Here we show that the combination of the DFT+U method and semi-empirical D2 correction can compensate for the drawbacks of the GGA when it comes to the modelling of V2O5. When compared to common PBE calculations, with a modest increase in the computational cost, PBE+U+D2 fully reproduced the experimental band gap of V2O5, while the errors in the lattice parameters are only a few percent. Using the proposed PBE+U+D2 methodology we studied the doping of V2O5 with 3d elements (from Sc to Zn). We show that both the structural and electronic parameters are affected by doping. Most importantly, a significant increase in conductivity is expected upon doping, which is of great importance for the application of V2O5 in metal-ion batteries.

Low psychological resilience is associated with depression in patients with cardiovascular disease.

BACKGROUND: Psychological resilience is associated with an improved capacity to cope with chronic health challenges such as cardiovascular disease. AIMS: The aim of this cross-sectional study was to examine the relationship between psychological resilience and symptoms of depression in a non-acute cardiac outpatient population. METHODS: A total of 419 adult cardiac outpatients (288 men; mean±SD age 66.26±14.04 years) attending cardiovascular clinics completed the Sense of Coherence (SOC13) scale as a measure of psychological resilience and the Cardiac Depression Scale (CDS26) prior to their consultation. RESULTS: The total SOC13 score (mean±SD 64.02±14.24, range 19-91) was within the moderate range. Older patients (⩾65 years) were significantly more resilient than those aged <65 ( p<0.01). Psychological resilience (SOC13) was negatively correlated with depression (CDS26) ( r=-0.79; p<0.001) and inversely associated with affective, cognitive and somatic symptoms of depression. Psychological resilience, particularly meaningfulness, accounted for more of the variance in affective features of depression than for somatic features. CONCLUSION: These findings show that low psychological resilience was related to depression in this cohort of cardiac outpatients, particularly affective symptoms such as anhedonia and hopelessness. The SOC13 scale offers a complementary measure of psychological status that could be used to monitor, and possibly predict, patient coping and response to treatment throughout the cardiovascular disease trajectory.

Knowledge about cervical cancer, Pap test, and barriers to women's participation in screening in Belgrade, Serbia.

INTRODUCTION: Cervical cancer (CC) is a serious public health concern in Serbia, due to opportunistic screening still being in force, which led to twice higher than the average incidence rate of cervical cancer in Europe. Despite the fact that early detection and treatment services of CC are available at no additional cost, majority of women use inadequate screening services in Serbia. OBJECTIVE: This study aimed to examine the link between the knowledge about CC and Papanicolaou (Pap) test and perception of barriers to women's participation in CC screening. MATERIALS AND METHODS: The study included 300 women aged 21 to 69, with a place of residence in the city of Belgrade (Serbia), who were attending for their medical examination to the University Clinic of Gynecology and Obstetrics - "Narodni front", from June through December 2014. A survey instrument to collect data was an adapted questionnaire for the assessment of knowledge about and barriers to CC and Pap test. Patients were divided into three groups: a study group consisted of women attending irregularly (over three years), women who never participated in screening, and a control group that included women regularly participating in screening. RESULTS: Women regularly participating in screening (52.7%) had adequate knowledge about CC and Pap test, while women who irregularly (79.4%) or never participated (71.9%) did not have any adequate knowledge. There was a significant statistical difference between the CC and Pap test awareness in a group of respondents who regularly participated in comparison to respondents who irregularly or never participated in screening (x²= 27.772, p = 0.000). Regarding knowledge about human papillomavirus (HPV), 80% of women did not know that Pap test cannot be used for detection of HPV, as well as that abnormal Pap test result may be due to HPV (61.7%). Majority of women (93.7%) had poor knowledge about Pap test role in CC early detection and considered Pap test to be used to diagnose CC. The authors found a significant statistical correlation between participation of women in screening and barriers. Women who were irregular or never participated, had barriers such as: lack of time (F = 9.51; p = 0,000), difficult access to Healthcare facilities (F = 11.29; p = 0.000), lack of knowledge about the Pap test procedure (F = 21.27,p = 0.000), discomfort (F = 9.36; p = 0.000), and anxiety of Pap test results (F = 3.35; p = 0.036). Women who regularly participated did not have prejudice when choosing a gynecologist, unlike the other two groups that preferred a female gynecologist (F = 3.61; p = 0.028). CONCLUSION: This study showed that the level of knowledge about CC and Pap test in women is an important factor associated with regular participation in screening. It is necessary to take educational measures in order to raise awareness of women regarding risk factors, as well as to overcome fear and shame, with the ultimate aim to reduce frequency and mortality rate caused by CC in Serbia.

Effects of Intracerebroventricularly (ICV) Injected Ghrelin on Cardiac Inducible Nitric Oxide Synthase Activity/Expression in Obese Rats.

The aim of this study was to examine the effects of ghrelin on regulation of cardiac inducible nitric oxide synthase (iNOS) activity/expression in high fat (HF), obese rats.For this study, male Wistar rats fed with HF diet (30% fat) for 4 weeks were injected every 24 h for 5 days intracerebroventricularly (ICV) with ghrelin (0.3 nmol/5 µl) or with an equal volume of phosphate buffered saline (PBS). Control rats were ICV injected with an equal volume of PBS. Glucose, insulin and nitric oxide (NO) concentrations were measured in serum, while arginase activity and citrulline concentrations were measured in heart lysate. Protein iNOS and regulatory subunit of nuclear factor-κB (NFκB-p65), phosphorylation of enzymes protein kinase B (Akt) at Ser(473), and extracellular signal-regulated kinases 1/2 (ERK1/2) at Tyr(202)/Tyr(204) were determined in heart lysate by Western blot. For gene expression of iNOS qRT-PCR was used.Results show significantly (p<0.01) higher serum NO production in ghrelin treated HF rats compared with HF rats. Ghrelin significantly reduced citrulline concentration (p<0.05) and arginase activity (p<0.01) in HF rats. In ghrelin treated HF rats, gene and protein expression of iNOS and NFκB-p65 levels were significantly (p<0.05) increased compared with HF rats. Increased phosphorylation of Akt (p<0.01) and decreased (p<0.05) ERK1/2 phosphorylation were detected in HF ghrelin treated rats compared with HF rats hearts.Results from this study indicate that exogenous ghrelin induces expression and activity of cardiac iNOS via Akt phosphorylation followed by NFκB activation in HF rats.

Systematic review of electronic remote blood issue.

BACKGROUND AND OBJECTIVES: The implementation of electronic remote blood issue (ERBI) may provide safety and efficiency gains for transfusion medicine. This systematic review's objective was to assess whether ERBI affects incidents of adverse events, time taken for blood issue and delivery, and cross-match to transfusion ratios, among other measures of safety and efficiency. The review also sought to uncover barriers and facilitators of ERBI implementation. MATERIALS AND METHODS: We searched four aggregated electronic databases (Medline, EMBASE, CINAHL and BIOSIS) up to 19 July 2012, with an updated search performed on 5 March 2014 for studies on ERBI. No specific study design criteria were used in the initial inclusion due to the low number of studies on ERBI. RESULTS: A total of 4758 citations were initially identified; after 1844 duplicates were removed, 2612 citations were excluded on the basis of the abstract. Two reviewers evaluated a total of 302 full-text articles independently; of these, seven citations were eligible for inclusion. An updated search and the authors' own collections confirmed an additional five citations, totalling 13 citations and six studies within these. CONCLUSION: There is insufficient evidence to demonstrate whether ERBI significantly impacts safety and efficiency of blood transfusion and delivery processes. Rigorously designed studies to assess safety and efficiency outcomes are required using proxy or corollary measures. A number of positive results were reported, however, and most studies included suggestions for facilitating ERBI implementation.

Dynamic changes of carotid artery intima-media thickness and mortality in hemodialysis patients.

INTRODUCTION: Intima-media thickness (IMT) of the carotid artery is a widely accepted parameter for detection and quantification of atherosclerosis. The aim of the study was the evaluation of the impact of changes of IMT on the mortality of patients on hemodialysis. METHODS: The study was organized as a prospective and observational one. Intima-media thickness was determined by ultrasound in 194 patients who were evaluated every year during a three-year period. We analyzed the mortality rate of patients on hemodialysis in relation to their biochemical parameters, demographic and anthropometric characteristics, type of dialysis, smoking habits and statin therapy. RESULTS: Female gender and hemodiafiltration emerged as good predictors of long-term survival. Baseline IMT values were significantly lower than those at the end of the second (p <0.001) and third years of the study (p <0.001). The baseline values positively correlated with uric acid levels (p =0.027) and body mass index (p =0.024), while at the end of the second year, IMT positively correlated with LDL-cholesterol (p =0.037) and triglyceride levels (p =0.018) and body mass index (p =0.045). Patients on hemodiafiltration had significantly higher values for erythrocytes (p =0.047), hemoglobin (p =0.005), creatinine (p =0.048), Kt/V (p =0.026), albumin (p =0.012), LDL-cholesterol (p <0.001), body mass index (p <0.001),and lower IMT values at the end of the first year (p =0.039), compared to patients on bicarbonate hemodialysis. Predictors of death were the duration of hemodialysis (p <0.001), and IMT at the end of the first (p =0.008) and second years of the study (p =0.005). CONCLUSION: Dynamic changes of IMT of the carotid arteries during the first two years were found in our study to be predictors of mortality in patients on hemodialysis. Hippokratia 2015; 19 (2):158-163.

Correlation of human papilloma virus infection with cytology, colposcopy and histopathological examination of the bioptic tissue in low- and high-grade intraepithelial lesions.

INTRODUCTION: It is now believed that the majority of cervical cancer is preceded by long-term infection with high-risk types of the human papilloma virus (HPV). The presence of HPV high-risk types (HR-HPV) in the cells of intraepithelial change multiplies the possibility of its progressive development to high-grade cervical precancer and invasive disease. AIM: This study examined the correlation of HPV infection with cytology, colposcopy, and histopathological examination of the bioptic tissue in low- and high-grade cervical lesions. MATERIALS AND METHODS: This research was conducted as a study section. Data collection was performed during a ten-year period, at the University Clinic of Gynecology and Obstetrics - Narodni Front in Belgrade (Serbia). The basic set included 1,927 patients. Colposcopy, cytology, histopathology, and HPV test verification was made in all patients. Statistical analysis was performed using the SPSS program, version 17.0. Contingency tables were used to assess the degree of correlation of variables and chi-square test was used to determine the level of statistical significance in this study. A p value < 0.05 was considered statistically significant. RESULTS: Among 1,927 women studied, 635 (32.95 %) had abnormal cytological findings and among these, 272 (42.83%) were HR-HPV positive. There was a statistical difference between colposcopic and cytological findings in patients with HR-HPV (x2 = 35.33, p = 0.000). There was also a statistically significant difference between histophatological and colposcopical findings in patients with HR-HPV (x2 = 10,171, p = 0.001). Only HR-HPV types 16 and 18 showed a statistical significance compared to histopathological findings, unlike other HR-HPV. An important finding was that the authors found an abnormal colposcopy in 93.30% patients with low-grade intraepithelial neoplasia and 68.05% patients with low-grade squamous intraepithelial lesion (LSIL) had normal cytology and was 70.15 % HR-HPV negative. CONCLUSION: The findings imply that among high-grade intraepithelial neoplasias, the authors found a high presence of HPV type 16 and 18, and a statistical significant presence of HPV 16 in low-grade intraepithelial neoplasia, unlike other HR-HPV types in low-grade intraepithelial findings. The authors found a significant statistical correlation with abnormal cytology and presence of HPV type 16 in both groups (LSIL and high-grade squamous intraepithelial lesion (HSIL). The authors also found an abnormal colposcopy in 93.30% of patients with low-grade intraepithelial neoplasia, while 68.05% of patients with LSIL had normal cytology and were HR-HPV negative in 70.15% of the cases.

Mouse hypothalamic GT1-7 cells demonstrate AMPK-dependent intrinsic glucose-sensing behaviour.

AIMS/HYPOTHESIS: Hypothalamic glucose-excited (GE) neurons contribute to whole-body glucose homeostasis and participate in the detection of hypoglycaemia. This system appears defective in type 1 diabetes, in which hypoglycaemia commonly occurs. Unfortunately, it is at present unclear which molecular components required for glucose sensing are produced in individual neurons and how these are functionally linked. We used the GT1-7 mouse hypothalamic cell line to address these issues. METHODS: Electrophysiological recordings, coupled with measurements of gene expression and protein levels and activity, were made from unmodified GT1-7 cells and cells in which AMP-activated protein kinase (AMPK) catalytic subunit gene expression and activity were reduced. RESULTS: Hypothalamic GT1-7 neurons express the genes encoding glucokinase and ATP-sensitive K(+) channel (K(ATP)) subunits K ( ir ) 6.2 and Sur1 and exhibit GE-type glucose-sensing behaviour. Lowered extracellular glucose concentration hyperpolarised the cells in a concentration-dependent manner, an outcome that was reversed by tolbutamide. Inhibition of glucose uptake or metabolism hyperpolarised cells, showing that energy metabolism is required to maintain their resting membrane potential. Short hairpin (sh)RNA directed to Ampkα2 (also known as Prkaa2) reduced GT1-7 cell AMPKα2, but not AMPKα1, activity and lowered the threshold for hypoglycaemia-induced hyperpolarisation. shAmpkα1 (also known as Prkaa1) had no effect on glucose-sensing or AMPKα2 activity. Decreased uncoupling protein 2 (Ucp2) mRNA was detected in AMPKα2-reduced cells, suggesting that AMPKα2 regulates UCP2 levels. CONCLUSIONS/INTERPRETATION: We have demonstrated that GT1-7 cells closely mimic GE neuron glucose-sensing behaviour, and reducing AMPKα2 blunts their responsiveness to hypoglycaemic challenge, possibly by altering UCP2 activity. These results show that suppression of AMPKα2 activity inhibits normal glucose-sensing behaviour and may contribute to defective detection of hypoglycaemia.

Comparison of electrolytic status (Na+, K+, Ca2+, Mg2+) in preterm and term deliveries.

PURPOSE OF INVESTIGATION: The objective of this study was to evaluate the electrolytic status of Na+, K+, Ca+, and Mg2+ in serum and red blood cells in idiopathic preterm and term deliveries. METHODS: The study included 105 pregnant women diagnosed with idiopathic premature delivery (study group) and 36 pregnant women with physiologically term delivery (controls). Samples of mother's blood were collected and analyzed for the level of electrolytes in the serum/plasma and red blood cells. RESULTS: Measured values of magnesium in red blood cells in the study group were far lower than physiological values, intracellular calcium levels were higher in the study group compared to levels measured in the controls. Sodium concentrations in cells were significantly lower in subjects with premature delivery. CONCLUSION: The magnesium intracellular level is the best representative value of magnesium in the body.

Effects of mental health on quality of life in children and adolescents living in residential and foster care: a cross-sectional study.

AIMS: This study was conducted in order to evaluate the effects of mental health and quality of life (QOL) in children and adolescents living in residential and foster care. METHODS: Two hundred and sixteen children and adolescents, aged 8-18 years, from residential and foster care participated. QOL was assessed using the Pediatric Quality-of-Life Inventory (PedsQL), levels of anxiety and depressive symptoms using the screen for child anxiety-related emotional disorders (SCARED) questionnaire and the short mood and feeling questionnaire (SMFQ), and general mental health through use of the strengths and difficulties questionnaire (SDQ). RESULTS: The children and adolescents from residential care had significantly low QOL and more frequently had mental health problems. A stepwise linear regression was performed to test the associations between the SCARED, SMFQ and SDQ scores, and PedsQL (QOL). Anxiety, depressive symptoms and general mental difficulties account for significant variations in QOL (p < 0.001). CONCLUSIONS: Mental health problems have significant negative effects on the QOL of children and adolescents living in residential and foster care.

Assessment of obesity beyond body mass index to determine benefit of treatment.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: • Weight or weight loss per se may not indicate health status or health benefit. • There is no gold standard for assessing which patients would benefit most from weight-loss interventions. • The King's Criteria is one of several recently proposed obesity classification systems. WHAT THIS STUDY ADDS: • The King's Criteria can capture health problems related to obesity and health benefits after weight loss. • The King's Criteria is a reproducible scoring system. • Using the King's Criteria may help shift the focus of patients and clinicians from weight loss to health gain. SUMMARY: Body mass index (BMI) alone does not reflect health status in individuals. The King's Obesity Staging Criteria is a clinical tool for the assessment of patients with complex obesity. We assessed the performance of a modified version of the King's Criteria by scoring 144 obese patients before and 1 year after bariatric surgery. We also evaluated inter-observer variability by having 11 clinicians score the same 12 patients. The King's Obesity Staging Criteria comprise nine health domains: Airways, Body mass index, Cardiovascular disease, Diabetes, Economic complications, Functional limitations, Gonadal axis, Health status (perceived), and body Image. For each domain, a person's health is assigned a score of 0 ('normal health'), 1 ('at risk'), 2 ('established disease') or 3 ('advanced disease'). The patient's mean BMI decreased from 48 ± 7 to 37 ± 7 kg m(-2) post surgery. Before surgery, 84% of patients were either in stage 2 ('established disease') or stage 3 ('advanced disease') for one or more domains other than BMI. The modified King's Criteria showed significant health improvements after surgery, with a higher proportion of patients scored in stage 0 ('normal health') within each health domain (P < 0.001 for all). Observers assigned the same score in >75% of cases for all domains except Health status perceived (71%) and body Image (65%). In conclusion the King's Criteria captured morbidity in obese patients and health gains after weight loss. Different clinicians mostly assigned similar scores. The King's Criteria is a clinical tool that may help shift the focus of patients and clinicians towards improving health and not only losing weight. REGISTRATION NUMBER: NCT01112228 (http://www.clinicaltrials.gov).

Diagnosis of Fanconi's Anemia by Diepoxybutane Analysis in Children from Serbia.

The high sensitivity of Fanconi's anemia (FA) cells to drug induced DNA interstrand crosslinks (ICL) such as diepoxybutane (DEB) was used as a part of FA screening in the children with clinical suspicion of FA. The study considered a total of 66 children with the hematological and/or congenital phenotypic symptoms reminiscent of FA. Blood samples from patients with clinical suspicion of FA and controls were collected for chromosome fragility evaluation by the DEB test. According to the results of DEB test, the patients were divided into two subgroups: FA displaying typical DEB sensitive cellular response and non FA. In this study, 10 out of 66 patients were found to have a FA cellular phenotype. The percentage of DEB-induced aberrant cells was increased more than 26 times in FA patients (range 22.00-82.00% with a mean of 48.32%) when compared to non FA patients (range 0.00-12.00% with a mean of 1.84%). The number of DEB-induced breaks/cells was more than 68 times higher in FA patients (range 0.26-4.39 with a mean of 1.37 breaks/cell) when compared to non FA patients (range 0.00-0.20 with a mean of 0.02 breaks/cell). The spontaneous chromosome fragility values in FA patients were overlapping those in non FA patients. Our results indicate that the DEB sensitivity test is the most reliable in vitro method for verification of the FA cellular phenotype.

Ovarian carcinoma patients--life quality analysis in the postoperative period--how to improve it?

PURPOSE OF INVESTIGATION: The objective of this research was to analyze the quality of life of patients with advanced ovarian carcinoma in the period following radical surgery and application of chemotherapy. METHODS: A random selection method was used to choose 30 patients who had previously filled out the QLQ-C30 health questionnaire. Data obtained from questionnaires were statistically analyzed. RESULTS: The percentage of the general health scores were the highest in the bottom third of the scale, where 21.9% of the patients self-scored at 0. Financial difficulties were scored the lowest at 65.6%. The impairment of physical functioning was reported by 21.9% of patients, where the score for impact of this physical impairment was reported at 0 by 18.8%, and the impact of cognitive impairment was scored at 0 by 56.3%. Nausea, vomiting and loss of appetite were completely affecting normal daily functioning of 40.6% patients, constipation was present in 59.4% cases and diarrhea in as many as 71.9% patients; 15.6% patients reported being in continuous pain. CONCLUSION: Health questionnaires should be used because they can help identify patients prone to develop psychological problems and symptoms. Early recognition of patients prone to psychosomatic problems would allow doctors to help maintain and/or improve on patients' quality of life.

[Vertical distraction osteogenesis of the extremely resorbed edentulous mandible. A retrospective description of 16 patients]. / Verticale distractieosteogenese van de extreem geresorbeerde edentate onderkaak. Een retrospectieve beschrijving van 16 patiënten.

This study's objective is to assess long-term results of vertical distraction osteogenesis for the extremely resorbed edentulous mandible by clinically measuring and taking x-rays from the beginning of the treatment of 16 subsequent patients to its final moment in the follow up period (ranging from 2-62 months). Bone height, nerve sensitivity, complications and loss of implant were registered. Average bone resorption after 3 years was 11.2%. Out of 16 patients 5 experienced sensory nerve disturbance; 3 suffered complications. The implant success rate was 89.2%. Distraction osteogenesis appears to be a reliable technique, with which stable bone tissue is developed. Risk of sensory nerve disturbance and complications however, must be taken into consideration.

Phaeochromocytomas presenting as acute crises after beta blockade therapy.

OBJECTIVE: Phaeochromocytoma crisis is a life-threatening emergency that may be undiagnosed because of its numerous, nonspecific manifestations. We analysed, retrospectively, the presentation, management and outcome of patients who were admitted to our institution with phaeochromocytoma crises over a 5-year period. RESULTS: Five patients (two males, three females; mean age 34.6 years, range 19-51 years) who presented as emergencies requiring intensive care, with multiple non-specific manifestations and previously undiagnosed pheochromocytoma, were identified. The initial presentation included features of cardiomyopathy (n = 3), atypical pneumonia with myocarditis (n = 1) and acute abdomen (n = 1). Only one of the five cases had a raised blood pressure at the time of the acute presentation. Initiation of beta blockers in four patients was associated with further deterioration in haemodynamic status, labile blood pressure and cardiac arrhythmias, which led to the diagnosis of the underlying phaeochromocytoma. Following intensive supportive therapy and alpha blockade, all five patients recovered and underwent elective surgical removal of phaeochromocytoma, uneventfully. CONCLUSION: Unexplained cardiopulmonary dysfunction, particularly after the institution of beta blockers, should alert clinicians to the possibility of phaeochromocytoma. A high index of suspicion is essential to reduce morbidity and mortality in these patients through early diagnosis and aggressive management.