The association of fructose and lactose intolerance and malabsorption with the symptoms of different functional gastrointestinal disorders (FGID) remains unclear.To investigate the prevalence of fructose and lactose intolerance (symptom induction) and malabsorption and their association with clinical gastrointestinal (GI) as well as non-GI symptoms in FGID and the outcome of dietary intervention.Fructose and lactose intolerance (defined by positive symptom index) and malabsorption (defined by increased hydrogen/methane) were determined in 1372 FGID patients in a single centre using breath testing. Results were correlated with clinical symptoms in different FGID Rome III subgroups. The effectiveness of a targeted saccharide-reduced diet was assessed after 6–8 weeks.r = 0.35–0.61. P < 0.0001), but not with malabsorption. Non-GI symptoms occurred more commonly in patients with intolerances. Methane breath levels were not associated with constipation using several cut-off thresholds. Adequate symptom relief was achieved in >80% of intolerant patients, irrespective of malabsorption.Intolerance prevalence across all FGIDs was 60% to fructose, 51% to lactose and 33% to both. Malabsorption occurred in 45%, 32% and 16% respectively. There were no differences in intolerance or malabsorption prevalence between FGID subgroups. FGID symptoms correlated with symptoms evoked during testing (Fructose and lactose intolerances are common in FGID and associated with increased non-GI symptoms, but not with specific FGID subtypes. Symptoms experienced during breath testing, but not malabsorption, correlate with FGID symptoms. Effective symptom relief with dietary adaptation is not associated with malabsorption. Mechanisms relating to the generation of GI and non-GI symptoms due to lactose and fructose in FGID need to be explored further. Adverse reactions to food are common in the population and are claimed by up to 67% of individuals with Functional Gastrointestinal Disorders (FGID).In this study, the following issues were examined in a large single-centre cohort of successive FGID patients: (i) How common are lactose and fructose intolerance and malabsorption during breath testing in FGID and its subgroups? (ii) What is the relationship between clinical symptoms and breath test results? (iii) Are non-GI symptoms associated with intolerances? and (iv) What is the symptomatic outcome of a standardised dietary intervention and is this related to malabsorption? Our hypotheses were that fructose and lactose intolerance would be equally common across all FGID, that symptoms generated during breath testing would correlate with the patients' clinical symptoms and that intolerance would be more relevant than only malabsorption in the diagnosis and dietary treatment outcome of fructose and lactose intolerance. We expected a high incidence of non-GI symptoms in patients with intolerances.All successive patients referred to our gastroenterology practice by general practitioners between January 2008 and May 2011 for evaluation of FGID were eligible for inclusion in this prospective study, except those with evidence of organic disease, which was assessed by routine haematology and biochemistry blood testing and also stool testing for calprotectin and pancreas elastase determined in two stool samples in all patients. Parasite and bacterial stool cultures were performed if clinically indicated. Upper and lower endoscopies with biopsies were required in patients older than 40 years or in patients with diarrhoea or faecal blood.2 concentrations were measured within 72 h using the Quintron BreathTracker SC® (Quintron Instruments). Hourly testing was chosen based on our laboratory pilot data, where identical qualitative results were obtained as with sampling every 15 min and concentrations were stable in the tubes for 3 weeks. Malabsorption was defined as an increase of >20 ppm in hydrogen or >10 ppm in methane levels over baseline twice in succession. The numbers of patients with early rises (in the first 60 min) above the 20 ppm threshold in breath hydrogen concentration following fructose and lactose were calculated for comparison with other published data17Fructose and lactose breath tests were performed in all FGID patients by one laboratory technician (AM). No antibiotics, colonoscopy or laxatives were permitted within 14 days and a specific low-saccharide diet was adhered to 1 day before the tests. Patients arrived for testing in the morning after fasting overnight and without having smoked, chewed gum or performed vigorous exercise for at least 4 h. Chlorhexidine mouthwash was used and teeth were brushed before testing. The breath tests were performed in randomised, patient-blinded sequence on two separate occasions at least 4 days apart. Breath samples were collected in sealed glass tubes  before and hourly for 5 h after ingestion of lactose 50 g or fructose 35 g dissolved in 300 mL water. Hydrogen, methane and COAdditional methane threshold definitions for malabsorption of >3 ppm at baseline and an increase of >20 ppm over baseline at any time during the test were applied for correlations with stool patterns for comparison with previous publications.The 312 patients with positive intolerance tests after May 2010 were referred to an experienced dietician (CW) for a standardised 4-week dietary adaptation, consisting of a diet low in saccharides and polyols for 1 week and subsequent weekly introduction of defined classes and amounts of fructose-, fructan-, inulin- and lactose-containing food to determine individual tolerability thresholds. Patients were maintained on the level of saccharides and polyols below their threshold of symptoms. In general, four individual sessions were scheduled with patients and questionnaires regarding abdominal symptoms, bowel and dietary habits were completed before and after the dietary modification. Symptom scoring was performed using 10-point Likert scales. Dietary compliance was checked either by direct or telephonic interview by the dietician or the gastroenterologist 6–8 weeks after initiation of the dietary changes. Compliance was considered adequate if patients confirmed that they adhered to the dietary guidelines during at least 50% of the meals consumed.19anova tests, as appropriate. Categorical data were compared by Chi-squared test or, if between multiple groups, by logistical regression. Correlations were analysed using the Spearman–Rank test. A significance threshold of P < 0.05 was adopted. Analysis was performed using Statistica 7.1 .Group differences in clinical GI and non-GI symptoms and variables were compared by Kruskall–Wallis or n = 212), comprised of IBS with constipation , IBS with diarrhoea , IBS with alternating constipation and diarrhoea  and IBS unclassified , Functional Dyspepsia(n = 606), comprised of FD with postprandial distress  and FD with epigastric pain syndrome , and Functional Bloating (n = 109).Patient characteristics are shown in P < 0.01), and 33.2% and 29.5% had both intolerances (N.S.). Of males and females, 57.1% and 61.7% had fructose intolerance (N.S.), 43.6% and 53.3% had lactose intolerance (P < 0.01), and 27.6% and 35.2% had both intolerances (P < 0.05). Fructose was more common than lactose intolerance in all FGID subgroups (P < 0.001)(P < 0.05). 14.1% of patients with lactose intolerance and 6.9% of patients with fructose intolerance correctly suspected the target of their intolerance before breath testing.The prevalence of fructose, lactose and both intolerances in all FGID patients was 60.4%, 50.5% and 33.1% respectively. In Northern European and Mediterranean Caucasians, 61.0% and 59.4% had fructose intolerance (not significant-N.S.), 47.8% and 53.6% had lactose intolerance ( < 0.001), with noP < 0.001). Patients with both intolerances had significantly more problems with concentration, joint and muscle pain, nausea, gastro-oesophageal reflux and allergic reactions than those with no intolerances and generally also than patients with only one intolerance . Using a test cut-off time of 3 h instead of 5 h, 16% of fructose and 23% of lactose intolerance results would have changed from positive to negative.The incidence of symptoms r = 0.34–0.51, all P < 0.005).The incidence of several of the most commonly evoked symptoms during breath testing, specifically bloating, diarrhoea, abdominal pain, gastro-oesophageal reflux, tiredness, muscle pain and diminished concentration, correlated with patients' FGID symptoms , abdominal pain  and diarrhoea  during fructose and lactose  testing. The time-to-peak H2 and CH4 concentrations were 107.7 ± 71 min and 107.3 ± 76 min with fructose, and 164.2 ± 105 min and 168.5 ± 106 min with lactose respectively (both P < 0.001 vs. fructose). Peak concentrations of H2 and CH4 were reached after 3 h in 10.1% and 37.7% of fructose tests and in 9.8% and 33.8% of lactose tests respectively. There were no significant correlations between H2 and CH4 peak concentrations and any FGID symptoms. Peak concentrations of H2 >20 ppm in the first 60 min, so-called early rises in breath hydrogen, were seen in 12.9% of patients following fructose and in 6.0% of patients following lactose ingestion.H2 or CH4 thresholds, diarrhoea was more common than constipation  (2 (14.5% and 11.3%) and CH4 (1.2% and 1.2%) concentrations following fructose and lactose ((7.7% and 6.5%) and (1.4% and 1.6%)) respectively. Furthermore, a majority (69%) of IBS-C patients did not have elevated CH4 levels after either sugar.In patients with fructose or lactose malabsorption, as defined by any of the H < 0.05) . ConversP < 0.01). Symptomatic relief >3 on the 10-point scale was achieved in 90% of all fructose and 94% of all lactose intolerant, and in 93% and 96% of those with concurrent malabsorption, respectively. Average symptom relief was between 6 and 7 on the 10-point scale for all the above subgroups, except in constipated patients where the average was 3 (data not shown).Complete outcomes were available in 237 of the 312 patients (76%) with intolerances who received standardised dietary counselling once it was initiated. Thirty-six patients declined dietary counselling and 39 dropped out of the dietary programme and were lost to follow-up. Clinical characteristics did not differ between those having discontinued or completed the programme. Adequate symptomatic relief after 6–8 weeks was achieved in 84% of all patients with fructose intolerance and in 86% when fructose malabsorption was present with intolerance. Respective results for lactose intolerance were 89% and 90%. Eight-five per cent of all patients reported adequate dietary compliance. Adequate relief rates were 85% and 96% in patients with diarrhoea and bloating, respectively, compared to 51% in those patients with constipation  following sugar ingestion appears to be more relevant than malabsorption Dietary modification based on fructose and lactose intolerance testing was clearly beneficial. Over 80% of all FGID patients attained adequate global symptom relief and average relief was 7 on the 10-point symptom scale. Adequate symptom relief was lower at about 50% in patients with constipation. These data are consistent with an earlier study where 85% of 48 IBS patients compliant with a similar diet reported an improvement of >5 on the 10-point scale for pooled symptoms after 14 months and also a reduced response rate in constipated patients.Non-GI co-morbidity was common in FGID, especially in the central nervous, musculoskeletal and atopic categories. An elevated prevalence of non-GI functional syndromes, including fibromyalgia, migraine and chronic fatigue, is reported in FGID.The epidemiology of fructose intolerance is poorly characterised. In our FGID patients, fructose was more common than lactose intolerance and more frequent in Northern than Southern Europeans, in contrast to lactose intolerance.2 and CH4 concentrations peaked over 50 min earlier following fructose than lactose, and after 3 h in approximately 10% and 35% of tests respectively. The earlier exhaled gas and symptom peaks with fructose confirm an earlier report and may be due to differences in the location of absorption/digestion or of bacterial metabolism.39The optimal breath test methodology remains unclear despite attempts at standardisation.4 threshold definitions.4. Conversely, increased CH4 was equally prevalent in constipation and diarrhoea. Furthermore, in IBS-C, breath tests were significantly more frequently CH4 negative than positive. This discrepancy with previous publications may be explained by variations in the definition of constipation , test methodology  or patient selection . Further study is required given this wide heterogeneity and the positive associations described mainly in smaller subgroups.This study provides no corroboration for an association between exhaled methane and constipation using any of the common CHThe relationship and overlap between small intestinal bacterial overgrowth (SIBO) and sugar malabsorption is extensive and it is acknowledged that currently a reliable distinction is not possible.Study limitations are the absence of a blinded, placebo-controlled design with healthy controls. The choice of an inert placebo in this group of sensitive patients is challenging. Healthy controls were not included in this study aiming at comparisons within FGID. Comparisons with controls have been reported previously. An overlap between FGID subgroups is inevitable in all related studies. We chose the most prominent FGID for classifying each patient. Advantages of our single-centre study are the large number of successive patients with different FGID tested for both intolerance and malabsorption and treated in standardised fashion. Meta-analyses in this field are problematic due to the inherent variability in patient selection and in testing and treatment procedures.In conclusion, fructose and lactose intolerance are common and frequently overlap in FGID, with no differences in prevalence between subgroups. Non-GI symptoms are more common in FGID patients with intolerances. Effective symptom relief is achieved with standardised dietary adaptation. Clinical FGID symptoms correlate with the symptoms induced during testing and not with malabsorption, which consequently does not appear to be the main driver of symptoms. Mechanisms relating to carbohydrate intolerance and accompanying non-GI symptoms are of special interest for future research.Guarantor of the article: Clive H. Wilder-Smith.Author contributions: Clive Wilder-Smith designed the research. Andrea Materna and Corinne Wermelinger conducted the research. Jonathan Schuler and Clive Wilder-Smith analysed the data or performed the statistical analysis. Clive Wilder-Smith wrote the paper and had primary responsibility for the final content. All authors read and approved the final version of the manuscript.


Carotid sinus hypersensitivity has a high prevalence in the elderly and is a possible cause of falls. In carotid sinus hypersensitivity, external triggers cause sudden reductions in blood pressure, leading to dizziness or syncope, resulting in falls. Turning of the head is considered an important example of such an external trigger in everyday life, wherein rotation of the neck is thought to manipulate the hypersensitive carotid sinus. However, direct evidence for this is lacking. The aim of this study was to investigate the effects of head turning in elderly with carotid sinus hypersensitivity. We performed a prospective, observational study in 105 elderly patients who visited a geriatric falls clinic in a university teaching hospital and in 25 community dwelling healthy elderly subjects. Continuous measurements of blood pressure and heart rate (Finapres) were performed before, during, and after head turning. Head turning-induced hypotension was defined as a drop in systolic blood pressure of at least 20 mmHg during head turning. Carotid sinus hypersensitivity was examined with carotid sinus massage. We also tested for two other common geriatric hypotensive syndromes, orthostatic hypotension and post prandial hypotension, using active standing and a meal test. All three hypotensive syndromes were defined using consensus definitions. Head turning resulted in hypotension in 39% of patients (mean systolic blood pressure drop 36 mm Hg) and in 44% of the healthy elderly, irrespective of the direction of the head movement. Carotid sinus hypersensitivity was associated with head-turning induced hypotension . We conclude that head turning is indeed an important cause of sudden drops in blood pressure in elderly with carotid sinus hypersensitivity. Falls are common in elderly people, 30% of those aged 65 years and older fall at least once a year ; 2]. Th. Th2]. TAn important aspect of this multifactorial screening process is the evaluation of blood pressure instability. The elderly are prone to the so-called hypotensive syndromes . During hypotensive episodes, cerebral blood flow is temporarily reduced, which may manifest as dizziness or syncope. Through this mechanism, hypotensive syndromes contribute importantly to falls in the elderly ; 6]..6].Among these hypotensive syndromes, carotid sinus hypersensitivity (CSH) is thought to be an especially relevant contributing or causal factor in unexplained falls ; 7]. In. In7]. IIn elderly with CSH, mechanical manipulation of the carotid, as may occur when wearing a tight collar or during shaving, may cause a reduction in blood pressure and/or heart rate resulting in syncope and falls ; 10]..10].An additional and even more common trigger may be turning of the head. In case reports, clinically significant drops in blood pressure (sufficient to be considered a plausible cause of syncope) have been demonstrated when subjects turned their heads . This obThe objective of this study was therefore to investigate the effect of head turning in elderly with CSH. We have tested the hypothesis that head turning triggers hypotensive episodes in elderly with CSH. We have investigated this primarily in a population where this information has the highest clinical relevance, i.e in elderly with a history of falls. In addition, to further explore the effect of head turning on blood pressure, we also included a group of healthy elderly, where, as indicated above, CSH is also prevalent.The test protocol explained below was part of the standard care for patients who visited the Geriatric Falls Clinic and conformed to the Declaration of Helsinki, informed consent was asked and obtained for the tests. All healthy participants signed informed consent forms. The ethical review board (Commissie Mensgebonden Onderzoek region Arnhem-Nijmegen) approved the study.This prospective, observational study was carried out in the Geriatric Falls Clinic in a university teaching hospital. Between March 2006 and November 2008, all ambulatory patients older than 65 years were recruited who had been referred for falls, dizziness and/or syncope. Patients were excluded when they met any exclusion criterion for carotid sinus massage or when hospital admission was required.Functional performance was evaluated with the Groningen Activity Restriction Scale (GARS) ; 13]. I. I13]. IIn addition to this patient sample, a group of healthy elderly volunteers was recruited from the community. Their health status was examined including their medical history, drug use, functional performance, and a physical examination was performed. This group had no fall history.A ‘clinic’ blood pressure was recorded during the outpatient clinical evaluation using a sphygmomanometry device. During the test protocol, executed on a different day, beat-to-beat blood pressure and heart rate were continuously measured from the finger using the photoplethysmographic method . During the test protocol, ECG registration was used for safety reasons. The Finapres method is a non-invasive technique that measures beat-to-beat variations in blood pressure and heart rate that has been validated against intra-arterial recordings as well as conventional sphygmomanometry . After aThe Head turning test (HTT) was performed in all subjects that underwent the Finapres test protocol. After at least ten minutes of active standing (until blood pressure was stable for at least five minutes), each subject was asked to perform three different head movements during 10-15 seconds: rotation to the right, rotation to the left and hyperextension. Between the different head movements, the head was at ‘rest’ in a normal position (facing forward) until the blood pressure was again stable for at least one minute. Systolic blood pressure and heart rate before the HTT were calculated as the mean of the ten beats preceding HTT. For each head movement separately, the systolic blood pressure and heart rate during the HTT were calculated as the mean of the three beats with the lowest systolic blood pressure. A positive result was defined as a drop in systolic blood pressure of at least 20 mmHg during one or more of the head movements and was called ‘head turning-induced hypotension’ (HTIH). We considered that changes in systolic blood pressure less than 20 mmHg can fall within the normal range of blood pressure fluctuations , and theThe Finapres test protocol further consisted of a carotid sinus massage to assess CSH, an active standing test to evaluate orthostatic hypotension (OH), and a meal test to evaluate postprandial hypotension (PPH). During the tests, the subjects were asked whether they experienced symptoms.0-tilt position (CSH in tilt). CSH was defined as an R-R interval of at least three seconds (cardio-inhibitory type), a decrease of systolic blood pressure of 50 mmHg or more (vasodepressor type), or a combination of both (mixed type), irrespective of whether the subject was in a supine or tilted position . The question of whether a fall was ever preceded by shaving or head turning was answered affirmatively by 20 patients, but was not correlated with carotid sinus hypersensitivity; p=0.72, or HTIH; p=0.95.Finally, we performed a subgroup analysis of patients for whom the physician suspected a hypotensive syndrome as the cause of falls (prior to knowing the results of the tests) versus those patients where hypotension was not thought to play a role. In 45 patients the physician had stated that he suspected an hypotensive syndrome; HTIH was present in 17 of these 45 patients, whereas HTIH was present in 13 patients out of 33 patients in whom the physician did not suspect hypotension (p=0.89).The main finding of this study is that head turning triggers hypotension in nearly 40% of elderly patients referred for a fall or syncope. This head-turning induced hypotension appears to be a manifestation of carotid sinus hypersensitivity and can be added to the list of common hypotensive triggers in the elderly, including orthostatic and postprandial hypotension, as it is comparable both in prevalence and in its hypotensive effect ; 7]..7].The strength of this study is that the effect of head turning on blood pressure was investigated prospectively in consecutive patients irrespective of whether blood pressure instability (episodic hypotension) was suspected after clinical evaluation. Thus, patients with explanations for their fall other than hypotension were not excluded from this study. This approach reduced selection bias. Nonetheless, the study population was selective, as these patients were referred to a falls clinic for falls, dizziness and/or syncope. Therefore, the probability of finding hypotension was high and explains that more than half of this geriatric population met the criteria for orthostatic hypotension, postprandial hypotension or carotid sinus hypersensitivity. Nevertheless, in such a selected population there are also other evident explanations for falls . Female In agreement with our hypothesis, there was an association between HTIH and CSH, namely patients with CSH were more likely to have HTIH than patients without CSH, and CSH was diagnosed in 75% of patients with HTIH. It was a priori not expected to find a 100% association between HTIH and CSH. First, both tests can reveal false-negative test results and second, the actual effect on the carotid sinus during CS massage versus HTT may be different; CS massage may cause increased pressure on the carotid sinus, while head turning may cause stretching of the carotid sinus. It is therefore more likely that CSH was missed in some of the subjects with HTIH than that explanations other than CSH explain the hypotensive effect of head turning in these subjects.The pathophysiology of CSH remains debated . The barAlternative explanations for the hypotensive effect of head turning must be considered. Active head turning causes muscle activation and stimulation of the vestibular system. Activation of the neck afferents affects reflex autonomic cardiovascular control . The vesThe subclavian steal syndrome can rarely lead to symptoms such as syncope, due to arteriosclerotic occlusion of the proximal subclavian artery. Although the physical examination findings of the subclavian steal syndrome includes a blood pressure difference of greater than 20 mmHg between arms, subclavian steal rarely induces a hypotensive episode. This only occurs if subclavian steal leads to brain stem hypoperfusion and thereby affects autonomic blood pressure control . LikewisHTIH was associated with a lower body mass index, a higher systolic blood pressure and a diagnosis of CSH. Analysis of the data using a cut-off value of 30 mm Hg for HTIH, which created a subgroup of patients with more severe hypotensive episodes during head turning, did not change these findings. The association between HTIH and body mass index might suggest that increased neck tissue fat reduces the impact of head turning on the carotid sinus .The association between HTIH and high systolic blood pressure may be explained by the effect of elevated systolic pressure on the carotid wall and thereby on the carotid sinus stretch receptors involved in the baroreflex. This effect may predispose hypertensive elderly to CSH and HTIH.Although systolic blood pressure decreased in HTIH, heart rate remained stable. This finding suggests that head turning is associated with vasodepression but not bradycardia. However, heart rate was only measured together with the blood pressure nadir, and slowing of the heart rate prior to this blood pressure nadir may have been missed.A strength of our study is that our method of continuous blood pressure measurement generated many assessments of blood pressure, thereby increasing the method’s sensitivity to detect hypotension.A drawback of the observational design is that it does not allow for conclusions about the causal relationships among HTIH and syncope, and falls.There is a discrepancy between occurrence of HTIH and symptoms related to head turning, because HTIH was asymptomatic in the majority of patients. This finding is in agreement with findings in the established hypotensive syndromes , which often fail to produce symptoms during measurements. In addition, these hypotensive syndromes are frequently found in healthy elderly subjects, as is also the case in this study. We found a similar occurrence of HTIH in patients and healthy elderly. We speculate that the appearance of symptoms during a hypotensive episode depends on the magnitude of the reduction, the total duration of the hypotensive period, and the capacity of cerebral autoregulation to restore cerebral blood flow before blood pressure is fully restored .In conclusion, head turning may cause hypotensive episodes in the elderly. These data provide a plausible causal link to explain the well-established association between carotid sinus hypersensitivity and unexplained falls, and they provide evidence to support counselling patients with CSH about the effects of head rotation on blood pressure, with the advice to minimize extreme head turning.


The T-Line TL-200  is a noninvasive arterial blood pressure (BP) monitoring system allowing continuous beat-to-beat monitoring of systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP). It provides a real-time BP waveform like that obtained using an arterial catheter for BP monitoring. The aim of this study was to compare BP measurements obtained using the T-Line TL-200 system with simultaneous invasive BP measurements using a femoral arterial catheter in unselected critically ill medical patients.In 28 patients treated in a medical ICU of a German university hospital, BP values were simultaneously obtained using a femoral arterial catheter and the T-Line TL-200 device. All recorded data were included in the final analysis. For comparison of BP measurements, Bland-Altman analysis accounting for repeated measurements was performed.A total of 76,826 pairs of BP measurements  were analyzed. For MAP, Bland-Altman analysis revealed a mean difference of +0.47 mmHg (95% limits of agreement: -16.53 to +17.46 mmHg). For SAP and DAP, the bias and 95% limits of agreement were -9.01 mmHg (-37.47 to +19.45 mmHg) and +5.22 mmHg (-13.50 to +23.94 mmHg), respectively.The T-Line TL-200 system allows determination of MAP with a satisfactory agreement when compared to invasive assessment of MAP using a femoral arterial catheter in unselected critically ill medical patients. Higher mean differences and 95% limits of agreement for SAP and DAP measurements might be explainable by limited comparability of central  and peripheral  SAP and DAP measurements.


Background. Chronic kidney disease is frequently seen in patients with congestive cardiac failure and is an independent risk factor for morbidity and mortality. The aim of this study was to determine the prevalence of chronic kidney disease in patients with hypertension associated congestive cardiac failure. Method. One hundred and fifty patients with hypertension associated congestive cardiac failure were recruited consecutively from the medical outpatient department and the medical wards of the Nnamdi Azikiwe University Teaching Hospital Nnewi over a one year period, January to December 2010. Patients' biodata and medical history were obtained, detailed physical examination done and each patient had a chest X-ray, 12 lead ECG, urinalysis, serum urea and creatinine assay done. Ethical clearance was obtained from the Ethical Review Board of our institution and data analysed using SPSS-version 16. Results. There were 86 males and 64 females with mean age 62.7 ± 12.5 years. The mean blood pressures were systolic 152.8 ± 28.5 mmHg and diastolic 94.3 ± 18 mmHg. 84.7% had blood pressure ≥140/90 mmHg on presentation. The mean GFR was 70.1 ± 31.3 mls/min. 76% of subjects had GFR <90 mls/min and no statistical significant difference between males and females, P = 0.344. The mean serum urea was 7.2 ± 51 mmol/L while the mean serum creatinine was 194 ± 416.2 mmol/L. Conclusions. This study has demonstrated that majority of patients presenting with hypertension associated congestive cardiac failure have some degree of chronic kidney disease. Congestive heart failure (CHF) is common in North America with the prevalence being approximately 2% in adults older than 45 years . While cRenal dysfunction is recognised as an independent risk factor for morbidity and mortality in congestive cardiac failure , 8. The This is a cross-sectional study involving 150 adult patients aged 18–80 years in hypertension associated congested cardiac failure. They were recruited consecutively from medical outpatient clinic and the medical wards of Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, South East Nigeria. A diagnosis of hypertension associated congestive cardiac failure was made using the Framingham criteria  for diagpatient's age between 18 and 80 years;congestive cardiac failure using the Framingham criteria  and the congestive cardiac failure using the Framingham criteria  and the Inclusion criteria for the study wereobvious cause of congestive cardiac failure such as valvular heart disease, cardiomyopathy, and ischemic heart disease;congestive cardiac failure with other comorbidities such as diabetes mellitus, human immunodeficiency virus infection (HIV), chronic obstructive airway disease, infections of the urinary tract, trauma, or taking nonsteroidal anti-inflammatory agents (NSAID), or being involved in strenuous exercise prior to urine production;those found on renal imaging to have preexisting renal disease or suffering from diseases like multiple myeloma, systemic lupus erythematosus (SLE), and so forth.Exclusion criteria for the study wereEthical clearance for the study was obtained from the Ethical Review Board of the Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, South East Nigeria. t-test was used for continuous variables, and χ2 test was used for categorical variables. In the analyses a P value of <0.05 was considered statistically significant. Statistical analysis was carried out using SPSS version 16. Student's There were 86 (57.3%) males and 64 (42.7%) females. The mean age of the subjects was 62.7 ± 12.6. The majority (56.7%) were traders. The educational attainment of the subjects is shown in 127 (84.7%) of the patients were aware that they had hypertension. The mean systolic blood pressure was 152.8 ± 28.5 mmHg while the mean diastolic blood pressure was 94.3 ± 18 mmHg. The mean duration of hypertension was 7.6 ± 8.9 years. 37 (27.3%) of the subjects had blood pressure less than 140/90 mmHg on presentation.P = 0.344, 0.159, and 0.100, resp.). The mean GFR of the study population was 70.1 ± 31.3 mLs/min. 114 (76%) of the subjects had renal impairment (GFR < 90 mLs/min). Mean serum urea concentration was 7.2 ± 5.1 mmol/L while mean serum creatinine was 194 ± 416.2 mmol/L. Proteinuria was found in 52 (34.6%) of the subjects. Our study found impaired renal function in 76% of the subjects which confirms the assertion that chronic kidney disease is common in patients with congestive cardiac failure. The majority of subjects (43.3%) had mild chronic kidney disease . This compares favorably with the findings of 72% prevalence in Blacks and 69% in Whites found by Smith et al. . The 76% Obasohan and Ajuyah  in the NThe high values may also reflect the relatively lesser contribution of coronary artery disease to heart failure in Black hypertensive patients than Caucasian patients . Chronic kidney disease in congestive cardiac failure patients has become increasingly recognized as an independent risk factor for morbidity and mortality . HyperteIn view of the high prevalence of chronic kidney disease in hypertension associated congestive cardiac failure it is recommended that health awareness campaigns targeted at vulnerable groups be initiated, for the detection of chronic kidney disease in those with congestive cardiac failure and hypertension using the media (radio and television), health talks at town/village meetings, churches, and so forth.Also clinicians who provide care should be encouraged to screen hypertensive patients and those in congestive cardiac failure periodically by estimating the GFR to detect a decline in renal function and measures instituted to reduce the morbidity and mortality associated with chronic kidney disease in congestive cardiac failure.This study showed that there is a high prevalence of chronic kidney disease in patients in congestive cardiac failure and is in agreement with similar studies done in other countries. There are differences in the prevalence of chronic kidney disease in congestive cardiac failure in different studies done due to nonuniformity in the criteria for defining chronic kidney disease.


Metformin is first-line therapy for people with type 2 diabetes. Due to potential lactic acidosis it is contraindicated in patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2, although little is known about its use among patients with chronic kidney disease (CKD). The objective of this study was to determine the association between kidney function and mortality among incident metformin users.http://www.akdn.info; Alberta, Canada) were used to identify a cohort aged 66 and older with diabetes who were incident metformin users from November 1, 2002 until March 31, 2008. The cohort was stratified on frequency of creatinine measurements prior to initiating metformin: none; a pre measurement only (6 months prior to metformin initiation); a post measurement only (within 1 year after); and both pre and post measurements. Patients were categorized by stage of CKD: 1 & 2 ; 3a (45 - 59 mL/min/1.73m2); 3b (30 -44 mL/min/1.73m2); 4 & 5 (< 30 mL/min/1.73m2); and no measurements. A Cox proportional hazards model was used to determine the association between kidney function and mortality, controlling for demographics, Charlson morbidity scores, hypertension, and visits to general practitioners.Databases of the Alberta Kidney Disease Network  did not have a creatinine measurement before or after metformin initiation. Baseline characteristics were similar across groups stratified by frequency of creatinine measurements. A larger proportion of patients who had no creatinine measurements were rural-residing (31.3%) compared to those with pre (17.5%), post (21.1%) and both (15.8%) measurements. Of the subset with a measured eGFR, 25% of incident metformin users had eGFR <60ml/min. There was a small significant increase in the risk of mortality in incident metformin users with CKD stage 3b only  compared to people with an eGFR of ≥60 mL/min/1.73m2.Metformin was commonly prescribed to patients with decreased kidney function, and did not appear to be associated with an increased risk of death.


There were 67 patients with and 95 without patent vascular access. Both study groups were comparable with respect to gender, age, duration of dialysis therapy, and time after transplantation, kidney graft function, and cardiovascular comorbidities. Patients with patent vascular access were characterized by significantly elevated LVM and significantly greater percentage of LVH, based on LVMI/BSA . OR for LVH in patients with patent vascular access was 2.39 (1.19–4.76), P = 0.01. Regression analyses confirmed an independent contribution of patent vascular access to higher LVM and increased prevalence of LVH. We concluded that long-lasting patent hemodialysis vascular access after kidney transplantation is associated with the increased prevalence of LVH in kidney transplant recipients.Left ventricular hypertrophy (LVH) is frequently observed in chronic dialysis patients and is also highly prevalent in kidney transplant recipients. This study evaluates the impact of long-functioning hemodialysis vascular access on LVH in single center cohort of kidney transplant recipients. 162 patients at 8.7 ± 1.8 years after kidney transplantation were enrolled. Echocardiography, carotid ultrasound, and assessment of pulse wave velocity were performed. LVH was defined based on left ventricular mass (LVM) indexed for body surface area (BSA) and height Left ventricular hypertrophy (LVH) is commonly observed in patients with chronic kidney disease  and consFollowing successful kidney transplantation, left ventricular mass (LVM) usually decreases, although the prevalence of LVH remains high , 7. One This study enrolled 162 KTRs, operated on in one center between 1998 and 2004, with known history of their VA and who were still attending our out-patient clinic between 2010 and 2011. The study protocol, adherent to Declaration of Helsinki, was accepted by local bioethics committee (KNW/0022/KB1/24/10), and all participants gave their written informed consent. In addition to data retrieved from the center-operated transplant patient registry, the study protocol comprised blood sample withdrawal during the routine ambulatory visit and the performance of echocardiography, carotid ultrasound, and the assessment of pulse wave velocity (PWV). All ultrasound studies were performed by one experienced sonographer.n = 8).Patients with a recent history of acute infection, cancer, or liver cirrhosis were excluded from this study. Additionally, to better separate the study groups, we excluded patients with their VAs closed surgically or spontaneously more than 2 years after transplant  or tacrolimus (n = 46), antimetabolic drug (mainly mycophenolate mofetil or mycophenolate acid), and steroids.Most patients received the immunosuppression therapy, based on cyclosporine (2. Body surface area (BSA), in m2, was calculated according to the DuBois formula (0.20247 × weight (kg)0.425  × height (m)0.725) [Weight and height were measured following standard procedures, and BMI was calculated in kg/mm)0.725) .Resting arterial blood pressure (BP) was measured three times in the sitting position on the arm without the vascular access, at the end of the physical examination. Patients with BP equal to or above 140/90 mmHg or those who received antihypertensive medication were diagnosed with hypertension.Diabetes was determined in accordance with the American Diabetes Association criteria.α) were measured using ELISA . Serum N-terminal prohormone of the brain natriuretic peptide (NT-proBNP) was measured using electrochemiluminescence method (ECLIA), using commercially available kits  and Cobas E411 analyzer.Routine laboratory measurements were performed in the hospital laboratory . Serum high-sensitivity C-reactive protein (CRP) was measured using nephelometry , with a lower limit of sensitivity of 0.02 mg/L. Plasma concentrations of interleukin 6 (IL-6) and tumor necrosis factor-alpha , equipped with 2.5–4.0 MHz micro-convex-array transducer. All subjects were examined using two-dimensional and M-mode echocardiography while lying down on their left side, using the parasternal long-axis sternal window. M-mode and 2D measurements were performed according to the American Society of Echocardiography recommendations . These mCarotid ultrasound was performed using Siemens machine , equipped with 4.0–9.0 MHz linear transducer. Carotid arteries were examined with a patient in the supine position with the neck extended. The evaluation included the common, internal, and external carotid arteries and the carotid bifurcation on each side. The common carotid artery intima-media thickness (IMT) was measured manually within 2 cm proximal to the carotid bulb, away from all identified plaques. The results from three separate measurements on each side were averaged.The measurements were performed in the morning, after at least 15 min of rest in the supine position, using automatic noninvasive method . PWV was calculated as the time of pulse wave between the diagnosed points (distance (m)/time (s)). The signal of the pulse wave was received by a probe  placed over the carotid and femoral arteries and connected with the automatic processor. All measurements were performed by one investigator.2.7). Thus, patients were diagnosed with LVH based on two separate criteria: LVMI/BSA > 110 g/m2 for women and >134 g/m2 for men [2.7 > 45 g/m2.7 for women and >49 g/m2.7 for men [LVM was calculated according to Devereux formula . LVM was for men  or LVMI/ for men .Posttransplant major adverse cardiac events (MACEs) were defined as the episode of myocardial infarction, stroke, or cardiac artery stenting/surgery.Plasma concentration of NT-proBNP was used as diagnostic marker of heart failure, as exemplified by the European Society of Cardiology Heart Failure Guidelines from 2008 . A normaKidney graft function was assessed by estimating glomerular filtration rate (eGFR), which was calculated according to abbreviated MDRD formula .P” values below 0.05 were considered statistically significant.Statistical analyses were performed using STATISTICA 10.0 PL for Windows software package  and MedCalc 12.3.0.0. . Values are presented as means and 95% confidence intervals. For comparison of groups, we used the chi-squared test  and ANOVA, followed by Tukey's test (quantitative variables). Correlation coefficients were calculated according to Pearson. Multivariate regression analysis (stepwise backward model) was performed for LVM, including potential explanatory variables: recipient age, gender, duration of pretransplant dialysis therapy, time after transplantation, eGFR, PWV, BMI, and the presence of hypertension and of patent VA. Factors potentially related to the occurrence of LVH were included into multiple logistic regression (stepwise forward model) analyses . In all statistical tests, the “At the time of the study, there were 67 patients with functioning vascular access and 95 subjects without functioning VA. The majority of patients had VA located in the wrist region; only 9% and 5% of patients, respectively, had their VA located in cubital fossa. Of note, 21 patients without functioning fistula had never had this type of vascular access. Both study groups were comparable with respect to gender, age, duration of pretransplant dialysis therapy, and time after transplantation, kidney graft function, and cardiovascular comorbidities .P = 0.02). The OR for LVH in patients with patent VA was 2.39 (1.19–4.76), P = 0.01. The occurrence of LVH based on LVM indexed for height2.7 was also higher in patients with patent VA  . Pretransplant dialysis modality  had no significant influence on LVM and both LVM indexes in patients without patent VA.Patients with patent vascular access were characterized by significantly elevated LVM  and grea = 0.06)  and withα) were similar in both groups, except for slightly higher plasma IL-6 concentration in patients with patent VA (4.82 (3.58–6.05) versus 3.42 (2.88–3.96) pg/mL, P = 0.02). There was no significant difference in plasma NT-proBNP levels between groups (432 (226–1012) versus 416 (210–1055) pg/mL ). The percentage of patients with plasma NT-proBNP concentration exceeding 2000 ng/mL was 12.1% in patent VA group and 6.8% in group without patent VA. However, the difference was statistically not significant.Plasma concentrations of inflammatory markers , duration of pretransplant dialysis therapy , time after transplantation , NT-proBNP levels , eGFR , and plasma TNF-α concentration . Additionally, LVMI/BSA was associated with PWV , whereas LVMI/height2.7 was associated with CRP  and BMI . Of note, there was inverse correlation between eGFR and log NT-proBNP values .Both LVM indices were significantly correlated with age , with high prevalence of hypertension (85%). Of importance, we have examined all kidney graft recipients, transplanted between 1998 and 2004, who have still attended our transplant outpatient clinic in the time of the study. Moreover, two analyzed groups were clearly separated in terms of long-lasting fistula patency, by exclusion of those patients, in whom VA was functioning for more than 2 years after transplant and was surgically or spontaneously closed thereafter.It is worth noting that there were no significant differences between groups in terms of PWV and IMT values and no differences in the incidence of coronary artery disease or cardiovascular adverse episodes observed before and after transplant, as well as in the prevalence and duration of arterial hypertension and the number of antihypertensive medications used at the time of examination. Thus, at the time of the study, there was no obvious evidence of worse status of the vascular system in patients with functioning VA. Furthermore, some patients from the group without patent vascular access were advised to close it surgically within the first 2 years after transplant, and they did so. Presumably, these patients had the highest blood flow and seriously increased cardiovascular risk; thus, they had the most to gain by closing the vascular access. Nevertheless, being several years after transplant, patients without patent vascular access had significantly lower LVM and lower prevalence of LVH, which could further suggest the particular importance of early VA closure for promoting the advantageous changes in cardiac morphology.Limitations: unfortunately, in our study, we did not measure the vascular access blood flow in patients with patent VA or before VA closure; however, only 6.2% of all patients have had a fistula located within the cubital fossa, which is usually characterized by higher blood flow. The majority of patients had a patent or occluded vascular access within their wrist region. Additionally, we assume that the retrospective study design may be a source of bias, related to previous loss to followup of patients with severe LVH and heart failure, who died because of MACE during their first posttransplant years.In conclusion, the long-lasting presence of patent vascular access after kidney transplantation is associated with the higher prevalence of LVH in these patients. As the multivariate regression analysis revealed the patency of vascular access as the only potentially modifiable independent variable, which may influence the prevalence of LVH in this population , the closure of still functioning vascular access should be considered in patients with adequate kidney graft function, to reduce the risk of heart failure in long-term posttransplant period.


The study aim was to assess sympathetic vasomotor response (SVR) by using pulsed wave Doppler (PWD) ultrasound in patients with multiple system atrophy (MSA) and correlate with the tilt table study. We recruited 18 male patients and 10 healthy men as controls. The SVR of the radial artery was evaluated by PWD, using inspiratory cough as a provocative maneuver. The response to head-up tilt was studied by a tilt table with simultaneous heart rate and blood pressure recording. The hemodynamic variables were compared between groups, and were examined by correlation analysis. Regarding SVR, MSA patients exhibited a prolonged latency and less heart rate acceleration following inspiratory cough. Compared with the tilt table test, the elevation of heart rate upon SVR was positively correlated to the increase of heart rate after head-up tilt. The correlation analysis indicated that the magnitude of blood pressure drop from supine to upright was positively associated with the SVR latency but negatively correlated with the heart rate changes upon SVR. The present study demonstrated that blunted heart rate response might explain MSA's vulnerability to postural challenge. PWD may be used to predict cardiovascular response to orthostatic stress upon head-up tilt in MSA patients. Multiple system atrophy (MSA), a neurodegenerative disease , manifesα adrenergic pathways in diseases presented with autonomic disturbance [ Sympathetic vasomotor response (SVR) indicates arteriolar vasoconstriction following sympathetic stimuli , and theturbance , 7. Laseturbance , but mayturbance , 10. Pulturbance , 12. ConEighteen patients were recruited from the outpatient Department of Neurology, National Taiwan University from September 2010 to March 2011. All patients met the diagnostic criteria of possible MSA established in the consensus conference in 2008 , comprisThe participants rested quietly for 15 minutes on an armchair in an air-conditioned room set between 25°C to 28°C. The vasomotor response was measured by one experienced investigator (K.V.C.), using a pulsed wave Doppler ultrasound  with a multifrequency transducer . Subject's right forearm was in supination with a pillow placed under right wrist. The probe was placed on the ventral wrist to parallel the long axis of the forearm, using the color mode to localize the deep palmar branch of right radial artery. The measurements were collected at the segment 5 mm distal to the radial styloid process. Due to slight wrist dorsiflexion, the desired segment deviated 20–30 degrees from the horizontal plane. The investigator steered the color window to 30 degrees and corrected the Doppler angle of insonation to less than 60 degrees for Doppler spectrum analysis. We averaged three waves at rest to represent the basal hemodynamic status and then asked the participants to produce a strong cough following a deep breath. An artifact caused by this muscle activity indicated a sufficient effort to excite the sympathetic system . After sVmax– Vmin/Vmax mean [Vmax is the peak systolic velocity, and Vmin is the minimum forward diastolic velocity in unidirectional flow or the maximum negative velocity in diastolic reversal. Vmax mean and Vmean are the maximal and mean flow velocity averaged over 1 cardiac cycle, respectively. The arterial diameters were obtained under duplex ultrasound mode with dual imaging, coincident with the peak systolic velocity on the Doppler spectrum. The vessel diameter was determined by Image J , measuring from the outer vessel wall to the opposite inner wall. The blood flow volume per second was calculated as follows: (diameter/2)2 × Vmean × π. The heart rate in beats per minute was calculated to be 60 seconds divided by the peak-to-peak interval during 1 cardiac cycle. Pulsatility index (PI) was used to indirectly depict vascular resistance, derived from the following calculation: ax mean . Vmax The dopaminergic medication and therapy for OH were withheld 12 hours before the test. The study was carried out 15 minutes following the SVR test. Blood pressure and heart rate were recorded by a tonometric device  placed at the brachial artery distal to right elbow crease. Mean arterial pressure was defined as two-third of diastolic blood pressure plus one-third of systolic blood pressure. The blood flow and arterial diameters of right common femoral artery were assessed at a 3-minute interval at the point 2 cm proximal to its bifurcation by the same ultrasound machine. The value of the concurrent mean arterial pressure divided by the blood flow represented vascular resistance of right femoral artery. Five-minute supine rest was required prior to the initial 5 minutes of baseline measurement. Then the electrically powered tilt table was tilted up to 60 degrees within 15 seconds for 10 minutes and returned to the horizontal plane with continuous observation for additional 5 minutes. If the participant complained neurological or cardiovascular discomfort related to fall of blood pressure, he would be reclined to the supine position immediately without completing 10 minutes of head-up tilt.U test. We compared the parameters before and after cough or before and after head-up tilt by employing repeated measures analysis of variance. The association of measurements between SVR and the tilt table test was explored by Pearson's correlation methods. All the analyses were performed by using SPSS software version 12 . Statistical significance was assumed when P values were less than 0.05.The hemodynamic variables and basic characteristics between controls and MSA patients were analyzed by using Mann-Whitney Vmax, Vmin, Vmax mean, and Vmean) and blood flow and the elevation in pulsatility index in both groups. However, the corresponding heart rate changes after sympathetic stimulation were significantly higher in controls, whereas the SVR latency was more prolonged in MSA patients  but negatively with the difference of systolic blood pressure from supine to tilt . The latency in SVR exhibited similar tendency, demonstrating a positive correlation with the drop of systolic and mean blood pressure during head-up tilt   .This study employed PWD to investigate the hemodynamic alternations upon SVR between healthy participants and patients with possible MSA. Patients with MSA presented with a prolonged SVR latency and a reduced magnitude of heart rate acceleration following sympathetic stimulation. Compared with the measurements in the tilt table test, the elevation of heart rate upon SVR was positively proportional to the increase of heart rate after head-up tilt. The correlation analysis indicated that the degrees of blood pressure drop during postural challenge was positively associated with the SVR latency, but negatively correlated with its corresponding heart rate change upon SVR. In this study, inspiratory cough during SVR accelerated heart rates significantly more in healthy controls than in MSA patients, whereas no statistical difference was identified between both groups regarding parameters like pulsatility index, velocity, and flow. Previous studies using continuous wave Doppler ultrasound to assess SVR in patients with diabetic neuropathy or carpal tunnel syndrome indicated that reduced elevations in pulsatility or resistive index after stimulation implied impairment in the corresponding sympathetic circuits , 16. How Our result showed that MSA patients exhibited a reduced magnitude of heart rate elevation upon head-up tilting, which was positively correlated with the heart rate change observed upon SVR. Elevation of heart rate mediated by baroreflex is a normal physiological response against orthostatic stress. The reflex loop is responsible for the prompt withdrawal of parasympathetic inhibition and subsequent augmentation of sympathetic outflows once the baroreceptors sense the blood pressure decrease. Previous research reported that baroreflex sensitivity was blunted in MSA patients and the impairment was related to the disease severity . Another In this study, the systolic blood pressure was higher in MSA patients in supine position but dropped more after tilting up. We also found that the drop of blood pressure correlated positively with the period of SVR latency but negatively with the magnitude of heart rate elevation during SVR and head-up tilt. Supine hypertension appears common in MSA patients and is usually derived from medication against OH , whereas The results may have some clinical implications. First, though previous research using 45 degrees head-up tilt found similar heart rate changes between MSA patients and controls [There were some limitations in this study. Regarding the participants, males are included and difference in autonomic systems is known to exist between genders . Therefo In conclusion, our data suggested that patients with MSA had a prolonged SVR latency and reduced heart rate elevation after inspiratory cough. The blunted heart rate response upon SVR correlated with the magnitude of blood pressure drop in the tilt table test, leading SVR measured by PWD to become a useful alternative to predict the response upon orthostatic stress in MSA patients. Further study focusing on patients with Parkinsonism or other extrapyramidal syndromes is needed to evaluate the usefulness of SVR.


Objective. To determine and describe the pathophysiological aspects of oropharyngeal swallowing in patients with Parkinson's disease more accurately, a pilot study of qualitative as well as quantitative parameters of swallowing was performed using videofluoroscopy (VFS). Methods. Ten patients with a diagnosis of idiopathic Parkinson's disease having dysphagic complaints and ten healthy age- and gender-matched control subjects underwent a standardized videofluoroscopic swallowing protocol. Information on the swallowing function was derived from temporal, spatial, and descriptive visuoperceptual parameters. Intra- and interrater reliability was calculated. Results. No significant differences were found between Parkinson patients and healthy control subjects for the majority of the reliable variables. Conclusions. It was concluded that swallowing function seemed to be preserved in the early stages of Parkinson's disease. Furthermore, the reliability of many quantitative as well as qualitative swallowing parameters proved insufficient, raising questions about the interpretation of study outcomes in videofluoroscopy. Dysphagia is a common symptom of Parkinson's disease . In 75–1The purpose of this study is twofold: to determine the reliability of timed as well as spatial parameters in videofluoroscopy of swallowing necessary to interpret the study outcome and to determine the differences in swallowing function between patients with Parkinson's disease and healthy control subjects, matched for age and gender. Qualitative assessment of swallows was based on visuoperceptual evaluation of videofluoroscopic signs by an expert panel, whereas quantitative assessment was obtained by means of a specialized computer software application that allowed capturing and digitizing frames in videofluoroscopic recordings. Using the manual input of anatomical references determined by an expert panel, parameters could be measured. Patients with idiopathic Parkinson's disease (diagnosed by a neurologist) having subjective clinical complaints of dysphagia were recruited from several neurological departments in the Netherlands. All patients reported dysphagic complaints ranging from mild to severe, for example, these included slow eating, oral or pharyngeal passage disorder, coughing while drinking, and a diminished quality of life as a direct consequence of dysphagia. None of them suffered from any neurological disease except Parkinson's. All patients were able to perform a swallow. Other exclusion criteria were deep brain stimulation (DBS), a Mini Mental State Examination (MMSE) score below 23, severe dyskinesia of head and neck (resulting in problems with VFS recording), mental depression, head and neck cancer, severe cardiopulmological disease, speech therapy during the past six months, or surgery of the swallowing mechanism or the central nervous system . All patAll patients underwent a detailed clinical examination by an experienced laryngologist and a speech and language pathologist. Before the VFS examination the presence and severity of dysphagia were assessed using the Functional Oral Intake Scale (FOIS) and a fiberoptic endoscopic evaluation of swallowing (FEES) , 14. FolSwallows were analyzed using a specific software application  to capture, digitize, and measure the videofluoroscopic swallowing sequences . All varQuantitative measurements were determined for each swallow by two experienced raters with extensive training in the analysis of VFS studies of normal and disordered swallowing. Kahrilas et al. used more physiologic references to calculate timed variables in contrast with fixed anatomical landmarks, like the point where the mandible crosses the tongue base . In thisy-axis was defined by the anterior/inferior corner of the third and fifth cervical vertebral bodies. The x-axis crosses the y-axis at the anterior/inferior corner of the third vertebral body. By marking these reference points in each frame, movements of the subject in any plane were corrected  and swallow trials were scored in randomized order. The consensus training in visuoperceptual evaluation was accompanied by a manual including strict, well-defined guidelines to rate these ordinal variables. The exact interpretation per level of each of the three or five point scales was trained during five separate sessions with intervals of one week. During these intervals the expert raters had to accomplish test trials separately that were discussed the next session. To obtain the intrarater reliability each rater performed repeated measurements of all temporal, spatial, and visuoperceptual variables in all swallows within a period of two weeks. U test  or the Chi-Square test . All statistical analyses were performed using SPSS version 16.0 for Windows . Statistical analysis was conducted stepwise. First, Intraclass Correlation Coefficients (ICC) and Cronbach's alphas (>0.65) were computed for all quantitative parameters to determine the reliability and the degree of intra- and interrater (absolute) agreement. For all ordinal parameters Cohen's Kappa index of agreement was used. Second, for each reliable temporal, spatial, and visuoperceptual variable, group comparisons were performed over the averaged data of the expert raters. Differences between the Parkinson and the healthy control populations were tested for significance by means of the Mann-Whitney Ten mentally competent dysphagic patients  with a diagnosis of idiopathic Parkinson's disease were included. The H&Y staging scale ranged from mild to moderate (median II). In Tables U test, no significant differences were found regarding the spatial variables. The Chi-Square test did not reveal significant group differences for the visuoperceptual variables. The temporal variable VPJc showed a significant difference between the two groups. Patients with Parkinson's disease showed a significantly delayed velopharyngeal junction closure compared to healthy controls. Tables Before interpreting the present study outcome, the intrarater and interrater reliability was determined. Despite the thorough consensus training using well-defined guidelines as well as the strict methodological protocol for repeated measurements by the expert raters to calculate the intra- and interrater reliability in the present study poor reliability was observed for several parameters. Diverse situations may have contributed to this finding. First, despite their high expertise, the raters may have lacked consensus on a definition of, for example, delayed initiation of the pharyngeal reflex or maximum horizontal (anterior) hyoid motion. Second, patients were found to be rather homogeneous with respect to several of the variables being measured; that is, some of them, such as preswallow anterior spill and preswallow posterior spill, always scored zero. Finally, it cannot be excluded that the lack of internal consistency may have resulted from the nature of the measurement scales and/or instruments; for instance, visuoperceptual variables were scored on three or five point scales. As worldwide no strict guidelines exist, some scope for subjectivity was left to the rater in the discrimination of these ordinal variables. Consequently, these variables were less reliable compared to the temporal or spatial variables that were defined frame by frame using specific software . This soDespite the presence of a disturbed swallow physiology in Parkinson patients, few significant differences were found between the two pilot groups. Velopharyngeal junction closure (VPJc) was different, being significantly delayed in the Parkinson group. The remaining temporal, spatial, or visuoperceptual variables did not show significant differences or tendencies between the groups. The lack of significant group differences can be the result of the nature and sensitivity of the assessment tool (VFS). As described in the study of Ertekin et al. conflicting results obtained from radiological and manometric studies in Parkinson patients were found . Also noIn order to design therapy effect studies for dysphagia in Parkinson's disease, it is necessary to understand the pathophysiology of swallowing in this patient group. In previous studies, several authors investigated pathological mechanisms of oral-pharyngeal dysphagia in Parkinson patients , 19. SevN = 60 swallows in total) thirty variables were assessed, resulting in 1800 measurements. The selection of parameters in follow-up studies should be based on sufficient intra- and interrater reliability as well as on a patient data distribution using the full range of the parameters' scale. The literature on swallowing assessment usually provides only limited information on the definitions of the parameters being used, the exact description of the protocol applied during videofluoroscopy, the number of raters or the explanation of the concept of an “expert” or “experienced” rater, the intra- and interrater reliability, and the effect of training on reliability coefficients. Interpretation of any study outcome lacking such information may be hazardous. Dysphagic Parkinson patients could potentially benefit from improved diagnostic swallowing assessment by implementing well-defined videofluoroscopic parameters with sufficient intra- and interrater reliability.In this pilot study, few restrictions were placed on the kind and number of parameters to use. Per swallow  was found, particularly for the visuoperceptual variables. The reliable variables could only reveal very few significant differences between both pilot groups. Swallowing seems relatively preserved in the early stages of Parkinson's disease. Recommendations for future research on pathophysiological aspects of swallowing in Parkinson's disease may include study designs with larger numbers of dysphagic patients and healthy control subjects. It may be interesting too to include patients with a more severe degree of Parkinson's disease  to determine differences between such a patient population and the patients who visit speech therapists as described in this study. The present study has found relatively low intrarater and interrater reliability for many of the variables used despite thorough training and high level of the raters' expertise. In the literature, information on reliability is usually lacking. After training, raters should have maximum consensus about the exact definition of the variables included and be familiar with the rating scales being used as well as with their levels, preferably anchored in detailed descriptions. Any swallowing study should provide information on training and the intrarater and the interrater reliability in order to allow accurate interpretation of the study outcome. Maybe the suggestion that data described in earlier studies may lack sufficient reliability and, therefore, may not be useful in determining therapy outcome, has been rather unexpected. Still, the problems with reliability in outcome studies such as described in this paper may also be the most interesting as well as the most important finding. Newly developed research will need to take this issue into account so that in the near future, in research on the physiology of swallowing in Parkinson's disease, the complementary benefits of using qualitative as well as quantitative variables in videofluoroscopy can be studied more thoroughly.


Metabolic syndrome has been shown to be associated with lower levels of plasma N-terminal pro-B-type natriuretic peptide (Nt-proBNP) in the general population. We sought to elucidate the relationship between Nt-proBNP and components of metabolic syndrome in patients with congestive heart failure (CHF).Fasting blood samples were obtained from 93 patients in our institution. Plasma levels of Nt-proBNP and other biochemical data were measured. The New York Heart Association (NYHA) classification system (I-IV) was used to define the functional capacity of CHF. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation.Forty-nine patients (52.7%) had CHF. There was a positive correlation between plasma Nt-proBNP levels and NYHA functional capacity in CHF patients. Plasma Nt-proBNP levels increased significantly with each increasing NYHA class of the disease. The prevalence of metabolic syndrome in CHF patients was higher than that in patients without CHF. Most importantly, we found that plasma Nt-proBNP levels were lower in CHF patients with metabolic syndrome attributable to inverse relationships between plasma Nt-proBNP and body mass index (β = −0.297), plasma triglyceride (β = −0.286) and homeostasis model assessment of insulin resistance . Fasting glucose to insulin ratio  was positively associated with plasma Nt-proBNP levels (β = 0.491), and was the independent predictor of plasma Nt-proBNP levels in CHF patients.Plasma Nt-proBNP levels are inversely associated with metabolic syndrome in CHF patients. Reduced plasma Nt-proBNP levels in CHF patients may lead to impaired lipolysis and metabolic function, and may contribute to the development of metabolic syndrome in CHF patients. B-type natriuretic peptide (BNP) is synthesized in the cardiomyocyte as a response to increased wall stress in relation to heart failure or myocardial ischemia CHF is a complex clinical syndrome that can result from any structural or functional cardiac disorders, including coronary artery disease, hypertensive heart disease, myocardial disease and valvular heart disease. Metabolic syndrome is a pathological condition with clustering of metabolic components, including glucose intolerance, elevated blood pressure, elevated triglyceride levels, low high-density lipoprotein-cholesterol (HDL-C) levels and obesity It has been shown that metabolic syndrome is associated with lower levels of Nt-proBNP in the general population This prospective study was conducted in our institution during October 1st to December 31st, 2009. Ninety-three consecutive clinic patients, who had regularly followed up at the cardiology outpatient department every three months, were enrolled into this study . All participants were ambulatory patients, and their estimated daily activities exceeded three metabolic equivalents. Patients were excluded if they had any acute infection, acute myocardial infarction, pulmonary edema, chronic renal failure (serum creatinine ≥1.2 mg/dL) at the time of blood sampling or if they refused to provide informed consent for the study. This study was approved by the Protection of the Human Subjects Institutional Review Board of Buddhist Tzu Chi General Hospital. All participants had signed the written informed consent to participate in this study. The ethics committee also approved our consent procedure.The New York Heart Association (NYHA) classification system  was used to define the functional capacity of congestive heart failure, and the stage  of congestive heart failure was based on the American College of Cardiology Foundation and the American Heart Association 2005 guidelines Body weight was measured in light clothing and without shoes to the nearest half-kilogram. Height was measured to the nearest 0.5 cm. Waist circumference was measured to the nearest 0.5 cm at the shortest point below the lower rib margin and the iliac crest. The BMI was calculated as weight (kilograms) divided by height squared (meters). Bioimpedance measurements of fat mass were performed according to the standard, tetrapolar, whole body (hand-foot) technique, using a single-frequency (50-kHz) analyzer . Measurements were carried out by the same operator; fat mass was collected and analyzed by specific formulas provided by the manufacturer.g for 10 min. Serum levels of blood urea nitrogen, creatinine, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), albumin, globulin, and C-reactive protein (CRP) were obtained and measured using an autoanalyzer  by our central laboratory in our institution.Fasting blood samples of approximately 10 ml for measuring complete blood count  and other factors were immediately centrifuged at 3000 Fasting plasma Nt-proBNP levels were determined with an Elecsys 20.10 bench top analyzer (Roche Diagnostics) with proBNP reagent pack (Roche Diagnostics) Serum insulin levels were measured using the microparticle enzyme immunosobent assay (MEIA) method by an autoanalyzer . Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), calculated as fasting plasma glucose (mg/dL)×fasting serum insulin (µU/mL)/405. Pancreatic β-cell function was estimated by homeostasis model assessment of β-cell function (HOMA-β), calculated as fasting serum insulin (µU/mL)×360/fasting plasma glucose (mg/dL) −63 The prevalence of metabolic syndrome was defined using the International Diabetes Federation definition t test (two-tailed) for normally distributed data or the Mann-Whitney U test for parameters that presented with non-normal distribution . The significance of differences of Nt-proBNP between groups  was analyzed by the Kruskal-Wallis analysis of variance (AVONA) test. Clinical variables that correlated with plasma Nt-proBNP levels in CHF patients were evaluated by univariable linear regression analysis. Variables that were significantly associated with Nt-proBNP in CHF patients were tested for independency by multivariable linear regression analysis. Data were analyzed using SPSS for Windows . A p value of less than 0.05 was considered statistically significant.Data were expressed as means ± standard deviation (SD) and were tested for normal distribution by Kolmogorov-Smirnov statistics. Categorical variables were analyzed by the Chi-square test. Comparisons between patients were performed using Student’s independent p = 0.037) and higher plasma Nt-proBNP levels  than patients without CHF. In addition, there was no difference of other clinical variables  between patients with and without CHF . These results demonostrated that plasma Nt-proBNP levels were inversely associated with metabolic syndrome in CHF patients.In all 49 CHF patients, 23 patents (46.9%) met criteria for the metabolic syndrome, whereas the remaining 26 patients (53.1%) did not. In contrast, there were only 6 patients (13.6%) with metabolic syndrome in all 44 patients without CHF. The prevalence of metabolic syndrome in CHF patients was thus more than triple compared with patients without CHF. Furthermore, the CHF patients with metabolic syndrome had lower plasma Nt-proBNP levels than those without metabolic syndrome , body weight , BMI , triglyceride , and HOMA-IR  were negatively correlated with plasma Nt-proBNP levels among the CHF patients. On the other hand, FGIR  was positively correlated with plasma Nt-proBNP levels among the CHF patients. We then put these six significant variables together and performed a multivariable linear regression analysis. The result showed that FGIR  was the independent predictor of plasma Nt-proBNP levels . Insulin sensitivity index  is positively associated with plasma Nt-proBNP levels and is the independent predictor of the plasma Nt-proBNP levels in CHF patients.The prevalence of CHF increases with age and is expected to rise as a result of the increased life expectancy in communities in vitro for a long period and drop significantly over the first 24 hours following collection BNP and Nt-proBNP are well known to derive from a common precursor (proBNP). The half-life of BNP is only 18 minutes due to active clearance from the circulation via natriuretic peptide receptors and degradation by neutral endopeptidases in the blood stream Obese individuals in the cohorts of the Framingham Heart Study were found to have lower plasma BNP levels than those with normal weight p<0.05), suggesting that metabolic components may have a substantial effect on the development of CHF. One recent large registry study in Japan also has shown that the prevalence of metabolic syndrome in CHF patients is more than double compared with the general population The heart and adipose tissue are both endocrine organs, and there is increasing evidence for cross talk between them, although precise mechanisms remain unclear. Of particular importance is the role that such cross talk could play in both total body metabolism and cardiac metabolism By now the cardiovascular community is well aware that atrial natriuretic peptide (ANP) and BNP promote vasodilation and natriuresis, improve diastolic function, suppress aldosterone, and inhibit cardiac hypertrophy and fibrosis Our study has some limitations. First, this study was of cross-sectional design. Therefore, our results should be investigated in long-term prospective studies before a causal relationship between plasma Nt-proBNP and metabolic syndrome in CHF patients can be established. Second, most studies have focused on effects of BNP, but not Nt-proBNP, on lipolysis and adipose tissue. Further studies are needed to evaluate the Nt-proBNP effects on metabolic syndrome in CHF patients.Our results show that there is a positive correlation between plasma Nt-proBNP levels and NYHA functional capacity in CHF patients. Plasma Nt-proBNP levels increase significantly with each increasing NYHA class of the disease. Also, the prevalence of metabolic syndrome in CHF patients is higher than that in patients without CHF. Most importantly, we find that there is an inverse association of Nt-proBNP with metabolic syndrome in CHF patients. Also, FGIR is positively associated with plasma Nt-proBNP levels, and is the independent predictor of plasma Nt-proBNP level in CHF patients. Reduced plasma Nt-proBNP levels in CHF patients may lead to impaired lipid and glucose metabolism, and may contribute to the development of metabolic syndrome in CHF patients.


The current pilot study compares the impact of an intravenous infusion of Ringer’s lactate to an acetate-based solution with regard to acid–base balance. The study design included the variables of the Stewart approach and focused on the effective strong ion difference. Because adverse hemodynamic effects have been reported when using acetate buffered solutions in hemodialysis, hemodynamics were also evaluated.Twenty-four women who had undergone abdominal gynecologic surgery and who had received either Ringer’s lactate  or an acetate-based solution  according to an established clinical protocol and its precursor were included in the investigation. After induction of general anesthesia, a set of acid–base variables, hemodynamic values and serum electrolytes was measured three times during the next 120 minutes.3- concentration decreased slightly but significantly only with Ringer’s lactate. In addition, the acetate-based solution kept the plasma effective strong ion difference more stable than Ringer’s lactate.Patients received a mean dose of 4,054 ± 450 ml of either one or the other of the solutions. In terms of mean arterial blood pressure and norepinephrine requirements there were no differences to observe between the study groups. pH and serum HCO3- are clinically relevant, needs to be investigated in a larger randomized controlled trial.Both of the solutions provided hemodynamic stability. Concerning consistency of acid base parameters none of the solutions seemed to be inferior, either. Whether the slight advantages observed for the acetate-buffered solution in terms of stability of pH and plasma HCO In the fields of surgery and intensive care, hyperchloremic acidosis is a well-known problem in patients receiving large amounts of standard crystalloids, especially 0.9% sodium chloride solutions. A series of investigations has emphasized the disadvantageous effects of hyperchloremic acidosis on various organ systems, for example, hemodynamics, NO-production, renal blood circulation, urinary output or hemostasis -4. BalanDespite their future perspective, to date the routine use of balanced crystalloids is still infrequent in anesthesia. Large randomized, controlled clinical trials (RCT’s) investigating possible advantages as well as adverse effects of balanced crystalloids for routine use in the operating theater are sparse. The aim of the current study was to provide a preliminary comparison of two differently buffered balanced infusion solutions by reviewing data obtained from two established clinical protocols and,in addition, to test the feasibility of a future large RCT. The main target of interest was to investigate the influence of a solution containing a plasma-like SID  and a solution with a comparably low SID  on the variables of Stewart’s acid–base approach including the effective strong ion difference (SIDe). The impact of the acetate-based infusion solution on hemodynamic stability was also studied. In order to guide a future RCT, primary and secondary variables of interest were determined and sample size estimation was performed.TM , an acetate-based infusion solution (ABIS), as a standard intraoperative infusion solution in our institution. In a before and after analysis we studied acid–base balance and hemodynamics in 24 women without obvious cardiac, pulmonary or renal diseases  who underwent major, open gynecologic cancer surgery. The study comprised two arms: the first consisted of patients who had received solely Ringer’s lactate  and the second of women who were treated only with the ABIS . The composition of both infusion solutions is listed in Table In 2009 Ringer’s lactate  was replaced by IonosterilaCO2, electrocardiography, central venous pressure, arterial blood pressure, pulseoximetry and esophageal temperature. During the operative period, the patient’s temperature was kept constant in any case. Urinary output as well as the blood loss during the time course of the investigation was noted. In order to obtain blood pH, base excess (BE), HCO3- and PaCO2, a standard blood gas analyzer  was used. Serum electrolyte and lactate concentrations, as well as hemoglobin, hematocrit and albumin concentrations were assessed in the central laboratory of our institution. Depending on the results of the laboratory measurements the following variables were calculated:General anesthesia was induced with intravenous propofol, sufentanil, and cis-atracurium. After tracheal intubation, anesthesia was maintained with propofol (6 to 10 mg/kg/hour) and additional doses of sufentanil and cis-atracurium as appropriate. Mechanical ventilation was performed to maintain an adequate oxygenation and to preserve normocapnia. Intraoperative monitoring included end-tidal P43-] ionized (Pi) (mmol/L): = [PO43-] (mg/dL) · 0.3229· [PO+] – [Cl-] – [HCO3-]· Anion gap (mmol/L): = [Nae) (mmol/L): = [A-] + [HCO3- = [A-] + (0.0304 · PCO2 · 10(pH-6.1)) according to Figge [· Effective Strong Ion Difference : = [Albumin · (0.123 · pH – 0.631)] + [Pi · (0.309 · pH - 0.469)] according to Figge  could be noticed during the time course in the RL-group . In addition, the SIDe declined as well. In contrast to  significantly decreased in the RL-group. Because RL does not contain magnesium, this can best be explained by a simple dilution effect. We consider these changes to be of minor clinical importance. However, for patients suffering from liver or metabolic diseases or cardiac arrhythmias ABIS might be the preferable infusion solution.Slightly elevated lactate levels were observed in the RL-group. These increases were only moderate (but significant) and hardly exceeded our institutions’ range of normal values (0.5 to 1.5 mmol/L). In contrast to ABIS  and SIDe changes than lactated Ringer, but whether these differences will turn out to be of clinical relevance has to be investigated in a larger RCT. With regard to SIDe and [A-] neither ABIS nor Ringer’s lactate seem to be ‘ideally balanced’, because both of these values decreased dose dependently in both groups. A future RCT might provide important data concerning the on-going search for an ideal balanced solution.43-] ionized; RCT: randomized controlled trial; RL: Ringer’s lactate; SID: strong ion difference; SIDe: effective strong ion difference; SIG: strong ion gap.: serum-concentration of the ion between the brackets; [A-]: serum-concentration of week acids; ABIS: acetate-based infusion solution; ABP: arterial blood pressure; BE: base excess; CVP: central venous pressure; HR: heart rate; MAP: mean arterial pressure; Pi: [POThis study was performed using research funding provided by Fresenius Medical Care . Fresenius Medical Care did not have any influence on study design or manuscript approval. Klaus Hofmann-Kiefer, Matthias Jacob and Markus Rehm have lectured for Baxter Deutschland GmbH , Fresenius Kabi Deutschland GmbH , B Braun, Melsungen AG , Serumwerk Bernburg AG  and CSL Behring GmbH . In addition, they received unrestricted research grants from Serumwerk Bernburg AG , CSL Behring GmbH  and Fresenius Kabi Deutschland GmbH . All authors declare they have no competing interests.KH-K made substantial contributions to the development of the study design, wrote the manuscript and performed the statistics. DC participated in data acquisition and analysis and critically revised the manuscript. TK and MP participated in data acquisition and patient coordination. MJ and PC critically revised and helped to draft the manuscript. MR participated substantially in the design and coordination of the study and gave final approval of the version to be published. All authors read and approved the final manuscript.