In some hypertensive patients, psychological stress makes blood pressure difficult to control and causes physical symptoms such as headache or dizziness. We report the case of a hypertensive man whose psychological stress-induced increase in blood pressure was attenuated by cilnidipine.The patient (a 72-year-old man) had hypertension and was on antihypertensive therapy. When mentally concentrating, he experienced occipital headaches and dizziness, and despite thorough testing, no abnormality was found. He was subsequently referred to our department. The mirror drawing test (MDT), a psychological stress test, increased blood pressure by about 40 mmHg, and the patient described occipital headache. Plasma noradrenaline level also increased from 212 to 548 pg/ml. We therefore switched the patient from nifedipine, an L-type calcium (Ca) channel blocker, to cilnidipine, an L-type/N-type Ca channel blocker with suppressive effects on sympathetic activity. Cilnipidine attenuated MDT-induced an increase in blood pressure and plasma noradrenaline level and prevented the development of headache during testing.These findings suggest that cilnidipine is a useful antihypertensive agent for hypertensive patients in whom psychological stress causes marked fluctuations in blood pressure. In hypertensive patients , the sympathetic nervous system is overreactive and stress-induced increases in blood pressure are greater in hypertensive than healthy subjects -3. Therevia L-type Ca channel inhibition, but it also suppresses the sympathetic nervous system via N-type voltage-dependent Ca channels [Cilnidipine  is a dihydropyridine calcium (Ca) antagonist, which like conventional Ca antagonists exhibits antihypertensive activities channels . Thus, cchannels . We, theWe present herein the case of a hypertensive man successfully treated for psychological stress-induced, marked blood pressure increases and occipital headaches that hindered his activities of daily living. The efficacy of cilnidipine was demonstrated using the mirror drawing test (MDT).A 74-year-old man.Occipital headache when concentrating.No family history of hypertension.Nothing of note.No history of smoking. About 350 ml/day of beer.The patient was diagnosed with hypertension at about 40 years of age, and he has since been taking slow-release nifedipine tablets. Blood pressure was controlled at about 130/80 mmHg, but in April 200X, he began to experience non-pulsatile occipital headaches and dizziness when concentrating on work or whenever mental focus was required. These conditions were severe enough to impair activities of daily living. For example, on several occasions he had to excuse himself from meetings. Occipital headaches had no relation to nifedipine administration. Also, when the patient experienced occipital headaches, systolic blood pressure was about 50 mmHg higher than usual. His family physician ordered blood tests and head magnetic resonance imaging (MRI), but no abnormalities were found. Since the involvement of psychological stress was suspected, the patient was referred to our department at the end of May and was admitted for thorough testing on June 5.Height 161.6 cm, body weight 59.7 kg, body temperature 36.5°C, blood pressure 120/64 mmHg, heart rate (HR) 60 beats/min and regular. No yellowing of the bulbar conjunctiva. No anemia using palpebral conjunctiva hue. No abnormalities in the chest, heart, or respiratory sounds. No abdominal abnormality. No leg edema. No neurological abnormality. Marked bilateral palmar sweating.The patient was very detail-oriented and a perfectionist. For several years, he had served as a board member of a company as well as a few community and elderly groups. In April, he was particularly busy and under great stress due to personal relationship issues involving some group members.No abnormal blood count findings. Blood biochemical analysis showed no abnormalities, including total cholesterol (205 mg/dl) and triglycerides (128 mg/dl). Endocrinological testing conducted at rest in the early morning showed no abnormalities: plasma rennin activity, 1.8 ng/ml/hr; aldosterone, 81.0 pg/ml; adrenaline, 27 pg/ml; and noradrenaline (NA) 162 pg/ml. There was no cardiac dilatation (by chest radiography), no adrenal abnormalities , no signs of carotid artery constriction (by US), no abnormality in the skull (by head MRI), and no stenosis (by MRA). The head-up tilt test did not confirm orthostatic hypotension.Even after admission, the patient experienced non-pulsatile pain accompanied by heaviness in the back of the head whenever thinking or frustrated. Before admission, the patient was taking four antihypertensive agents , but after admission, use of trichloromethiazide and temocapril was discontinued in that order. To investigate the effects of psychological stress on the patient, the first MDT was performed to measure changes in blood pressure, HR, and plasma NA (the MDT protocol is described below). At 2 min after starting MDT, systolic blood pressure (SBP) and diastolic blood pressure (DBP) increased by up to 38 and 36 mmHg, respectively, before gradually decreasing. In addition, occipital headache was experienced at 2 min after the start of MDT and persisted for 15 min  had been discontinued after the first MDT (after breakfast). Cilnidipine administration  was initiated on June 21, and the second MDT was performed on June 28. Starting on July 1, cilnidipine dosage was increased to 20 mg (after breakfast), and the third MDT was performed on July 7.The present study demonstrated that cilnidipine suppressed the MDT-induced increase in blood pressure, tachycardia, and NA in a dose-dependent manner in a hypertensive man.The sympathetic nervous system of hypertensive animals is overreactive to psychological stress. For example, when subjecting rats to emotional stress (shaking), sympathetic activity and blood pressure increased, but the degree of increase was greater for spontaneous hypertensive rats compared to normotensive rats . Unlike ++ influx from L-type Ca channels to suppress vasoconstriction, and at the same time suppresses excessive release of NA from sympathetic nerve endings by hindering Ca++ current via N-type Ca channels. The latter may account for the inhibitory effect of cilnidipine on stress-induced sympathetic hyperactivity in the present patient.While our patient was on nifedipine, his SBP, DBP, and HR during MDT increased 38 mmHg, 36 mmHg, and 48 beats/min, respectively. By comparison, mean increases in SBP, DBP, and PR for 10 normotensive subjects at our facility were 12.7 mmHg, 10.5 mmHg, and 7.7 beats/min, respectively. Thus, the sympathetic nervous system of the present patient clearly overreacted to psychological stress. As with conventional Ca antagonists, cilnidipine blocks the CaFurthermore, cilnidipine relieved headaches experienced during the MDT or activities of daily living in this patient. Among hypertensive patients, QOL may be impaired by physical symptoms accompanying hypertension, such as headache and dizziness. Cilnidipine may thus also make hypertensive patients less vulnerable to stress-induced physical complaints. As psychological stress-induced increase in blood pressure has been demonstrated to correlate positively with the left ventricular hypertrophy in hypertensive men ,4, the iHowever, when cilnidipine dosage was increased to 20 mg, the patient experienced an orthostatic blood pressure decrease. High-dose cilnidipine may suppress not only psychological stress-induced sympathetic hyperactivity, but also sympathetic reflexes occurring on standing. Caution must be exercised when administering high-dose cilnidipine.nd and the 3rd MDT are due to the habituation effect. As was described in the MDT section, we tried to avoid habituation to the test and the patient reported that the degree of frustration felt after each MDT was the same. Therefore, although the habituation effect cannot be totally excluded, it can be minimized. Secondly, it is possible that the following factors accompanying hospitalization affect the results, i.e., dietary changes especially Na intake, relief from daily stress, or reduced anxiety. As the patient was not overweight and his blood cholesterol level was within the normal range, he was served only a low Na diet during hospitalization. However, as the patient was well educated about Na intake, his intake of Na was the same before and after admission. The patient complained of headache even after hospitalization, for example, during his interview. These symptoms decreased after starting cilnidipine and the patient did not experience headache after discharge. Therefore, the involvement of these factors may also be minimum. A placebo effect may be excluded because the patient had an orthostatic decrease in blood pressure at the higher dose of cilnidipine, which could only be due to the pharmacologic effect of cilnidipine.There are several limitations in this study. Firstly, one criticism might be that the results of the 2These results suggest that cilnidipine is a useful antihypertensive agent in hypertensive patients experiencing marked increases in blood pressure following psychological stress. Cilnidipine may also improve stress-induced physical symptoms in hypertensive patients. However, further study is necessary to generalize the conclusions drawn from this case report.MDT, mirror drawing test; Ca, calcium; QOL, quality of life; MRI, magnetic resonance imaging; HR, heart rate; NA, noradrenaline; US, ultrasonography; SBP, systolic blood pressure; DBP, diastolic blood pressure.The author(s) declare that they have no competing interests.


We describe a diabetic patient who presented with acute renal failure as a result of acute bilateral emphysematous pyelonephritis. Initially, both an abdominal X-ray examination and a renal sonogram were unremarkable. Two days later, however, the previously visualized right kidney could not be demonstrated again by a repeat renal sonogram. A computed tomogram and a repeat abdominal X-ray study confirmed the diagnosis of emphysematous pyelonephritis. To our knowledge this is one of the few described cases of emphysematous pyelonephritis distinguished by a sonogram's inability to visualize a kidney because of interference with imaging by the gas produced by the bacteria that are responsible for the pyelonephritic infection. Emphysematous pyelonephritis is a severe, progressive, life-threatening infection of the renal parenchyma caused by gas-forming bacteria. Early diagnosis and aggressive therapy are the requisites of successful treatment. We describe herein a patient whose emphysematous pyelonephritic kidney could only be demonstrated by a plain X-ray examination and computed tomography (CT) but not by sonography.A 67-year-old man with a history of diabetes mellitus and hypertension was hospitalized in 1998 with complaints of nausea, vomiting and a falling urine output for two weeks. Two months prior to admission, his serum creatinine value was found to be 106 μmoles/L (1.2 mg/dL). On admission, he was febrile; pulse rate, 80 beats per minute; supine blood pressure, 122/72 mmHg; standing blood pressure, 84/60 mmHg. The rest of the physical examination was noncontributory.3/μL . Serum values: Na 126 mEq/L, K 5.9 mEq/L, total CO220 mmoles/L, creatinine 425 μmoles/L (4.8 mg/dL) and urea nitrogen 17 mmoles/L (48 mg/dL). An abdomen X-ray examination and a renal sonogram were unremarkable. The latter revealed that the right kidney measured 10.8 cm in length [Blood leukocyte count amounted to 19.9 × 10n length  and the n length . A repean length . A compun length .He underwent a bilateral nephrectomy as his condition had deteriorated despite the use of antibiotics, pressors and other supportive measures. Subsequently, he experienced septic shock and expired. The removed kidneys appeared brown, spongy and necrotic while the right kidney weighed 180 g and measured 11 × 7 × 3 cm. Microscopy of the kidneys showed evidence of acute emphysematous pyelonephritis.et al period first described emphysematous pyelonephritis in 1898 as a gas-forming renal infection presenting with pneumaturia.[Escherichia coli is the causative organism, with less frequent etiologic agents being Klebsiella, Candida and Pseudomonas species.[Kelly  species.The exact pathophysiology of emphysematous pyelonephritis is unclear. Poorly controlled diabetes mellitus is present in up to 90% of patients who develop emphysematous pyelonephritis. Urinary Many imaging modalities have been used in evaluating afflicted patients; however, these modalities often underestimate the extent of the disease. For example, a plain X-ray examination of the abdomen was diagnostic in only about 47% of afflicted patients. Sonography could confirm the presence of emphysematous pyelonephritis in about 80% of cases. Ultrasou4et al described a 78-year-old man with bilateral pyelonephritis.[Goyzueta ephritis. An initiet al reported the progressive disappearance of a previously visualized kidney in a patient with emphysematous pyelonephritis.[Eisencher ephritis. A 63-yeaTo summarize, sonography has often been used to diagnose emphysematous pyelonephritis, but the diagnosis can be missed by an inexperienced sonographer. A CT scan is mandatory to diagnose emphysematous pyelonephritis if the index of suspicion is high.


The associations between physical activity, unhealthy dietary habits and cigarette smoking and blood pressure, overweight and obesity are well established in adulthood. This is not the case for similar associations in adolescence. Thus, the purpose of this study is to examine how physical activity, smoking status and dietary habits were related to overweight, obesity and blood pressure in a population of Norwegian adolescents.Weight, height, systolic (SBP) and diastolic blood pressure (DBP) were measured, and body mass index (BMI) was calculated among 8408 adolescents who participated in a population based study in 1995–97 in the county of Nord-Trøndelag. Internationally accepted cut-off values were used to determine if the adolescents were overweight or obese. The adolescents also completed a detailed questionnaire including dietary habits, physical activity and smoking habits. We calculated adjusted mean blood pressures and odds ratios for being overweight or obese for different exposure categories of life style variables.Low levels of physically activity were associated with increased odds of being overweight (odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1–1.8 in girls and OR, 2.0; 95% CI, 1.6–2.5 in boys) or obese . In addition, the least physically active girls had a 1.5 mmHg higher mean DBP compared with the most active (p-trend <0.001), and among boys this difference was 1.0 mmHg (p-trend < 0.001). Smokers were more likely to be obese  compared with non-smokers. Smokers also had lower mean SBP than non-smokers; however, this finding was restricted to smokers with the lowest smoking exposure. Associations between dietary habits and weight status largely disappeared after adjusting for weight losing behaviour.In this population of adolescents low levels of physical activity were associated with higher mean DBP and higher odds of overweight or obesity. Smoking was also associated with higher odds of overweight and obesity. The paradoxical associations between healthy dietary habits and overweight and obesity are most likely an effect of reverse causality. High blood pressure, overweight and obesity in adulthood are well-known risk factors for cardiovascular disease. The development of these risk factors starts early in life and may be present already in childhood and adolescence -4.Certain life style habits, including unhealthy dietary habits, cigarette smoking and inactivity are risk factors for cardiovascular disease that in part may be mediated or modulated through effects on blood pressure and body weight. These life style factors may also be established during childhood and adolescence, however, their associations with weight status and blood pressure in childhood and adolescence are less clear than in adulthood.Low consumption of vegetables and fruits has been reported to be associated with increased blood pressure in adults , whereasThus, the purpose of this study was to examine how physical activity, smoking status and dietary habits were related to cardiovascular risk factors, such as elevated blood pressure, overweight and obesity in a population of Norwegian adolescents.This population based cross sectional study comprises the youth part (Young-HUNT) of the second Nord-Trøndelag Health Study (HUNT II), carried out in 1995–1997. In Young-HUNT, all adolescents (13–19 years) in secondary or high school, living in the county of Nord-Trøndelag, Norway, were invited to participate. Among the 9917 adolescents who were invited to participate, 8950 (91%) accepted the invitation and completed a comprehensive self-administered questionnaire, including questions on life style and health. Moreover, 8408 (85%) of the adolescents chose to participate at a clinical examination that included measurements on height, weight and blood pressure by specially trained nurses.Adolescents younger than 13 (N = 127) or older than 19 years (N = 397) were excluded. Furthermore, all adolescents with incomplete data on blood pressure, height and weight were excluded, leaving 7908 (80% of the 9917 invited) eligible for analysis. The total number of adolescents within this age group in Nord-Trøndelag was 10281 in 1995 , which mBlood pressure was measured with the adolescent sitting comfortably in a chair. First, the upper arm circumference was measured to the closest centimetre. If the circumference was less than 24 cm, a small cuff was used, if it was between 24 cm and 34 cm a medium cuff was used, and if it was 35 cm or more, a large cuff was used. The measurements were done using an automatic oscillometric, upon inflation technique . The adolescents rested for two minutes before the first measurement, and the second and third measurements were done with one-minute intervals. Blood pressure was measured manually when an automatic recording could not be obtained. The mean value of the last two measurements was used in the analyses. If only one or two measurements were recorded, the single value (N = 7), or the mean of the two (N = 8) was used.Height and weight were measured by trained nurses using internally standardized meter measures and weight scales. The subjects wore light clothes (T-shirts and trousers) without shoes. Height was read to the nearest centimetre (cm) and weight to the nearest kilogram (kg). Waist circumference was measured at the height of the umbilicus, using a tape measure to the nearest centimetre. Body mass index (BMI) was calculated as body weight (kg) divided by the squared value of height (m). To define overweight and obesity, we used cut-off values for adolescents proposed by Cole et al .In the questionnaire, the adolescents were asked to indicate how often they consumed sweets and vegetables. Answer options were "more than once per day," "once per day," "every week, but not every day," "less than once per week" and "never." For the purpose of the present study, these responses were classified into three groups "once per day or more", "every week, but not every day" and "less than once per week." In addition the adolescents were asked to indicate whether they had breakfast "every day;" "4–6 days per week," "1–3 days per week" or "less than three days per week or never."The survey also had a question about weight loosing behaviour. The adolescents were asked to indicate their answer on the following question: "Are you trying to loose weight?" The options were "No, I'm comfortable with my weight," "No, but I need to loose weight" and "Yes."Physical exercise was recorded as "Not during the average school day: How many days a week do you play sports, or exercise to the point where you breath heavily an/or sweat?" Response alternatives were: "every day," "4–6 days a week," "2–3 days a week," "1 day a week," "not every week, but at least one day every two weeks," "not every 14 days, but at least once a months," "less than once a month" and "never" . The ansCurrent smokers were defined as those who answered "yes, I smoke daily" or "yes, I smoke occasionally, but not daily" to the question: "do you smoke?" with five response options: "yes, I smoke daily," "yes, I smoke occasionally, but not daily," "no, I don't smoke, but I used to smoke daily," "no, I don't smoke, but I used to smoke occasionally" and "no, I don't smoke." Those who answered that they smoked daily were also asked to indicate the number of cigarettes they smoked every day, and how long they had been smokers. This information was used to calculate pack-years of smoking exposure among the daily smokers, and to categorize the daily smokers into three groups; group 1: those with less than one pack year, group 2: 1 – 2 pack years and group 3: smokers who had more than 2 pack years of smoking exposure. Adolescents in high school (3487) were also asked if they ever had tried marijuana.All participants, and parents of adolescents under the age of 16, signed a written consent to take part in the study. The study was approved by the Regional Committee for Medical Research Ethics and the Norwegian Data Inspectorate Board.We computed mean diastolic and systolic blood pressure with 95% confidence interval (CI) within each category of the lifestyle factors, using a general linear model. In multivariable analysis, we adjusted for age and height, and in additional models we also evaluated potential confounding by BMI and smoking. In supplementary analysis, we assessed the independent effect of each lifestyle variable  and physical activity) on blood pressure by mutual adjustment in the regression model.Binary logistic regression was used to compute age-adjusted odds ratio (OR) with 95% CI for overweight or obesity associated with the different life style exposures. In additional multivariable analyses we adjusted for weight loosing behaviour, and we also examined the independent effect of each life style factor by mutual adjustment. Trend tests across exposure categories were calculated treating the categories as an ordinal variable in the regression model.Given the sample size of boys (N = 3926) and girls (N = 3982), and assuming a prevalence of an adverse life style in the population to be 20% (the case for smoking), the present study has a power of 80 % to detect a difference in mean systolic blood pressure of approximately one percent . All data were analyzed using SPSS 14.0 for Windows .Characteristics of the population are summarized in Table Blood pressure increased with increasing degree of overweight, both among girls and boys Table . Obese gSix hundred and thirty one (15.8 %) girls were trying to lose weight and 971 (24.4 %) girls indicated that they needed to lose weight, but did not actively try. Among boys, 183 (4.7 %) reported that they were trying to lose weight, while 462 (11.8 %) indicated that they needed to lose weight, but did not actively try to lose weight.There were smoking data on 7767 of the adolescents. Of these, 1586 (20 %) were classified as smokers. A higher proportion of girls (23 %) than boys (18 %) were smokers (p < 0.001). Among the 1586 smokers, we had detailed information on smoking exposure in 1518, and 766 (50.5 %) of these were occasional and 752 (49.5 %) were daily smokers. Among the daily smokers 434 (57.7 %) had less than one pack year, 188 (25 %) had between one and two, and 130 (17.3 %) daily smokers had more than two pack years of smoking exposure. Thus, only four percent (N = 318) of the total population had a smoking exposure of one pack year or more. Among adolescents in high school, 330 (9.4 %) had ever tried marijuana.To study clustering of adverse life style factors we used consumption of vegetables as a proxy for unhealthy diet, due to the observed inverse associations between consumption of sweets and breakfast frequency and high blood pressure or overweight. One unhealthy life style factor was present in 2615 (33.1 %) adolescents, whereas 1032 (13.1 %) had the combination of two and only 196 (2.5 %) adolescents had three unhealthy life style factors.Among adolescents with one adverse life style factor, unhealthy diet was more common among boys (p < 0.001), whereas a higher proportion of girls were less physical active (p < 0.001) and were more often smokers (p < 0.001). Among those with two adverse factors, smoking combined with low levels of physical activity was reported by 317 girls (8.0 %) compared with 190 boys , while physical activity combined with unhealthy diet was reported by 212 (5.4%) boys compared with 161 girls .Both in girls Table  and boysSmokers also had lower systolic blood pressure compared with non-smokers Tables  and 4. AWe also analyzed the association between dietary habits and blood pressure, and found increasing systolic and diastolic blood pressure with decreasing consumption of sweets both for girls Table  and for When BMI was added as a covariate increasing breakfast frequency was associated with increasing systolic blood pressure, both in girls (p-trend = 0.036) and boys (p-trend = 0.048), whereas among boys, the association between increasing diastolic blood pressure and decreasing breakfast frequency persisted (p-trend = 0.026). When BMI was included, all associations with sweets except systolic blood pressure in boys, and all associations except diastolic blood pressure in girls disappeared (data not shown). Adjusting for marijuana exposure did not affect the blood pressure estimates.Girls with three unhealthy life style factors had a mean diastolic blood pressure of 64.5 mm Hg (95% CI: 63.0 – 66.0) compared with 64.2 (95 % CI: 63.6 – 64.2) for those with two, and 63.3 mm Hg (95% CI: 62.9 – 63.6) among those with no unhealthy life style factors (p-trend = 0.003). A similar trend for boys was not present.Multiple regression analyses suggested that age and height explained 3% of the variance in systolic- and 5% of diastolic blood pressure in girls. In boys, age and height explained 17% of the variance in systolic- and 12% of the variance in diastolic blood pressure. In a model not including BMI, sweets and smoking contributed statistically significant to both mean systolic- as well as diastolic blood pressure in both sexes, whereas physical activity contributed to mean diastolic blood pressure in both sexes. However, adjusted R-square was only marginally affected, (~ one percent) by each of these life style factors. Consumption of breakfast and vegetables did not have independent effects in this model, except for a statistically significant effect of breakfast in diastolic blood pressure in boys.When BMI was included in the models, the explained variance increased to 28% of systolic- and to 14% of diastolic blood pressure in boys, and to 13% of systolic- and 7% of diastolic blood pressure in girls. The effects of current life style factors were essentially the same, with the exception that the association between blood pressure and frequency of sweet consumption now largely disappeared, and only persisted for systolic blood pressure in boys.Decreasing levels of physical activity were associated with increasing odds of being overweight or obese Table . Mean waFemale smokers had higher odds of being obese compared to non-smokers. A similar, but weaker trend was present among boys Table . SmokersThe OR of being overweight or obese increased with decreasing regularity of breakfast, and with decreasing frequency of sweets consumption Table . ConsistIn multiple logistic regression analyses the effects of each adverse life style factor had independent effects on overweight, although the odds ratio for overweight in adolescents who had breakfast less frequently, or who were smokers were slightly attenuated or even became borderline statistically insignificant (data not shown). However, the odds of being overweight for the least active adolescents were unchanged, and for adolescents who consumed sweets seldom, the odds were even strengthened (data not shown).In this population of adolescents we found that low frequency of physical activity was associated with higher mean diastolic blood pressure, and with increased prevalence of overweight and obesity. Smokers were more likely to be overweight and obese, but they had lower blood pressure compared with non-smokers; however, in this youth population smoking exposure was of short duration. The finding that those who reported infrequent consumption of breakfast and sweets had a lower prevalence of overweight and obesity could to a large extent be explained by adolescents who wanted to lose weight, or who felt that they needed to lose weight.The large sample size and the precision of the estimated associations make chance an unlikely explanation for the observed associations, and together with the proportions of exposed and unexposed individuals it ensures sufficient statistical power to detect very small differences.The high participation rate and the independent administration of the questionnaires and the physical examination reduce the possibilities of selection or information bias. None the less, it can not be excluded that adolescents who are overweight or obese want to report more healthy dietary habits than they in fact have. It may also be considered a limitation that the questions used to assess dietary habits have not been validated, however, similar questions have been used in comparable studies ,22. ThusThe homogeneity of the study population makes confounding by ethnicity and socioeconomic status unlikely. However, the results of the multivariable analyses suggested that the association between consumption of vegetables and blood pressure may have been confounded by other life style factors, and similar confounding may have contributed to the associations between smoking and overweight, and between irregular breakfast and overweight.in utero or early infancy) [The most consistent finding in this study was that high levels of physical activity were associated with lower diastolic blood pressure and reduced risks of being overweight or obese. The finding of a small reduction in diastolic blood pressure with increasing physical activity was independent of the adolescents' BMI, and of other life style factors, and is consistent with studies in adults ,24 and wThere was an association between low consumption of sweets and higher systolic and diastolic blood pressures, both among girls and boys. However, these relationships were significantly attenuated when BMI was included in the model. This fact, in addition to the similar relationship found between overweight and sweets consumption might indicate that this effect is mediated through BMI. We also found an association between less frequent breakfast consumption and increasing diastolic blood pressure in boys, and multivariable analyses suggested that this effect was independent of other life style factors. It may be reasonable to speculate that this effect could also be mediated via an effect on BMI; however, the association was weak, only among boys and only for diastolic blood pressure. Thus, the finding should be interpreted cautiously.The somewhat paradoxical finding that smokers have lower blood pressure than non-smokers has also been reported by others -30. The The finding that adolescents with low physical activity were more likely to be overweight or obese compared with adolescents who were most active is in agreement with several longitudinal studies ,33, as wThe inverse associations between regularity of breakfast and overweight and obesity are well known, and several explanations have been postulated -38. We hIn line with other studies , smokingIt may be considered a positive finding that only 15% of the adolescents had two or more unhealthy life style factors. However, among girls, higher diastolic blood pressure was associated with increasing number of unhealthy life style habits, and this may suggest a dose-response effect which may be a further indication of a cause – effect relation between these adverse life style factors and risk for later hypertension.The robust and consistent finding of this study is that low levels of physical activity were associated with higher mean diastolic blood pressure and with higher odds of being overweight and obese. Smokers also had higher odds of being overweight and obese, and smokers in addition had lower blood pressure than non-smokers; however, the latter finding may be a transitory phenomenon. The paradoxical associations between healthy dietary habits and overweight and obesity are most likely an effect of reverse causality.The author(s) declare that they have no competing interests.MHF analysed the data and drafted the article. TILN advised on statistics and critically revised the manuscript. TLH participated in the questionnaire preparation, discussion on the study design and critically revised the manuscript. TV advised on statistics, participated in the discussion on the study design and critically revised the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Pressure ulcers are a major problem, especially in nursing home patients, although they are regarded as preventable and there are many pressure relieving methods and materials. One such pressure relieving material is the recently developed Australian Medical Sheepskin, which has been shown in two randomized controlled trials ,2 to be The objective of this study is to assess the effects and costs of the use of the Australian Medical Sheepskin combined with usual care with regard to the prevention of sacral pressure ulcers in somatic nursing home patients, versus usual care only.In a multi-centre randomised controlled trial 750 patients admitted for a primarily somatic reason to one of the five participating nursing homes, and not having pressure ulcers on the sacrum at admission, will be randomized to either usual care only or usual care plus the use of the Australian Medical Sheepskin as an overlay on the mattress.Outcome measures are: incidence of sacral pressure ulcers in the first month after admission; sacrum pressure ulcer free days; costs; patient comfort; and ease of use. The skin of all the patients will be observed once a day from admission on for 30 days. Patient characteristics and pressure risk scores are assessed at admission and at day 30 after it.Additional to the empirical phase, systematic reviews will be performed in order to obtain data for economic weighting and modelling.The protocol is registered in the Controlled Trial Register as ISRCTN17553857. Some of their methods have been helpful; others have been failures. Sometimes old methods that were not 100 per cent effective have been put aside for new ones, and, occasionally, an old one is revived to be tried again. Such a method is sheepskin therapy  ."This historical quote is interesting, since it shows that pressure ulcers have been a major problem for many years. Furthermore it is interesting because it states that old therapies sometimes are revived, such as the sheepskin. More than 50 years later the sheepskin, now labelled as the 'Australian Medical Sheepskin', has its second revival.Pressure ulcers are highly prevalent, especially among elderly residing in nursing homes, where about 30% of the patients are suffering from these sores -7; a CanPressure ulcers are considered as a problem that to a large extent can be prevented by good care; therefore the incidence and prevalence rates are now put forward by many health care, professional and governmental organizations as an indicator of the quality of health care -20.The prevention and therapy of pressure ulcers are very costly ,21-25. Het al.[Pressure ulcers develop when capillary circulation is obstructed by prolonged pressure. Also shear and friction are contributing factors for the development of pressure ulcers. Therefore many interventions are in use to minimize pressure on bony prominences, such as repositioning and different kinds of pressure relieving devices ,27,28. Set al. found prThis new Australian Medical Sheepskin has been tested extensively on pressure relieving characteristics, laundry procedures, disinfection, wear-and-tear, patient comfort and other aspects . The necHowever, the question arises as to whether these results in acute hospital patients can be replicated in the more chronic and vulnerable nursing home patients, who are generally at higher risk for developing pressure ulcers. In addition, in the Australian studies the cost-effectiveness was not assessed.We therefore consider it is worthwhile to study the effects in nursing home patients and to assess the cost-effectiveness of the Australian Medical Sheepskin.The purpose of this study is to assess the costs and effects of the Australian Medical Sheepskin combined with usual care in the prevention of sacral pressure ulcers in nursing home patients, versus usual care only.Research questions are:1. What are the effects of the application of Australian Medical Sheepskins on the incidence rates of sacral pressure ulcers in somatic nursing home patients in the first month after admission compared to usual care?2. What are the costs of the application of the Australian Medical Sheepskin?3. What are the costs of the treatment for eventually developed pressure ulcers in the two study groups?4. What is the cost-effectiveness of the Australian Medical Sheepskin compared to usual care?5. What adverse effects do Australian Medical Sheepskins have?6. How do patients and nursing and care personnel rate the (dis)comfort of Australian Medical Sheepskins and the ease of use of Australian Medical Sheepskins?The proposed study concerns a prospective multi-centre randomised controlled trial with one experimental and one control group. The starting point is a superiority design with the research hypothesis that Australian Medical Sheepskins are a better pressure relieving device than usual care; that they will reduce the incidence rates of sacral pressure ulcers; and will also reduce costs involving pressure ulcer treatment.Data will be gathered primarily in an empirical way and additionally through systematic literature searches with regard to the cost-effectiveness question.For assessing the cost-effectiveness, the Australian Medical Sheepskin will be compared only to usual care and not to other pressure relieving materials. The perspective of the health care organisation will be considered to measure the cost-effectiveness.The study population will concern patients newly admitted for a primarily somatic condition to one of the five participating nursing homes. Only patients who are free of sacral pressure ulcers on admission will be included. Further inclusion criteria are: adult; not having darkly pigmented skin (because of difficulty in diagnosing grade 1 pressure ulcer); having an expected stay of more than one week; and consenting to the research.For practical reasons and because 74% of nursing home patients in the Netherlands are at risk for pressure ulcer development [The patients will be recruited from 5 different Dutch nursing home care groups  involving seven different geographical locations and 18 wards. The selection of the nursing homes was made on the basis of the customer list of the laundry company that we contacted, and which is able to do the washing and drying of the sheepskin, according to the Australian Standard .st 2007 and will proceed until the targeted number of patients is reached, for a maximum of 1.5 years. It is expected that enough patients will be admitted during this period to reach the necessary number as was calculated by power-analysis.Inclusion of patients started on May 1In Dutch nursing homes the prevalence of pressure ulcers is about 30% for all grades and about 12% for grade 2 to 4 . The firFor this study we will consider the Australian Medical Sheepskin to be effective and clinically significant if the incidence rate in the first month after admission is at least (in absolute terms) 10 percentage points lower in the experimental group than in the control group. This means that with an expected maximum incidence rate of 18% in the experimental group and about 28% in the control group, 750 patients (2 × 375) are needed to find such differences with a power of at least 80% and a two-sided alpha of 0.05.et al.[Halfens et al. state thAll newly admitted patients will be checked by the nurse in charge at admission to ascertain whether they fit the inclusion criteria. If so, they will be given research information in written format and verbally by the same nurse at admission. On the next day they will be asked for informed consent (by the same nurse) and if they agree, the nurse will immediately call the central research office to find out to which group the patient has been randomized. Thus, the therapy according to randomization status will start immediately and within less than 48 hours after admission.To ensure concealment of allocation, a randomization scheme was created in SPSS by assigning the intervention to a random sample of circa 50% in a list of 1,500 numbers and assigning the control group to the rest. This allocation of the group  was then blinded on a paper list numbered 1 through 1,500 by a secretary not further involved in the project. Each time a patient is admitted, the principal investigator located at the central research office is called. The above list with numbers and blinded allocation is held at this office. This central research office registers each patient identity for every consecutive number and discloses the group allocation to the nurse and patient.Only the patient allocation itself is blinded to all parties involved, because it is impossible to blind health professionals or patients to whether someone is in the sheepskin group or not.The experimental condition consists of the application of the Australian Medical Sheepskin as an overlay on top of the standard/usual mattress in the area of the buttocks and in the (wheel)chair, combined with all care as usual. An extra Australian Medical Sheepskin at the bottom of the bed is also permitted. The intervention will start no later than 48 hours after admission. The Australian Medical Sheepskin will be applied during the first 30 days after admission . The period of 30 days is chosen because most pressure ulcers develop in the first weeks after admission ,10,36,37Besides the use of the Australian Medical Sheepskin, all other usual pressure ulcer preventative interventions such as mobilization and repositioning may be added as co-interventions, in so far as they are normally used in the participating nursing homes. All other nursing care can be continued as usual .The control group will receive usual care, including all the pressure relieving interventions and other preventive actions, normally taken in the participating nursing homes. The application, in any way, of the Australian Medical Sheepskin is forbidden in this group.A distinction can be made between variables relating to the effectiveness  and variables relating to costs . Both of these are necessary to compute cost-effectiveness.The primary outcomes for this study are:- the incidence of sacral pressure ulcers in the first 30 days after admissions,- the costs of appliance of the sheepskin, and- the costs related to treatment of the pressure ulcers that have developed.Secondary outcomes are the presence of pressure ulcers on other places, quality of life, comfort of the sheepskin as experienced by the patients and ease of use of the sheepskin as experienced by the care personnel.Influencing factors that will be measured are patient characteristics, the application of other pressure relieving interventions and materials and the use of incontinence materials.These outcomes, as well as influencing factors, will be measured by appropriate instruments, as far as possible we will use already existing and validated instruments. The EPUAP grading system is used to assess the presence and severity of pressure ulcers .To this end a 'daily observation checklist' has been developed. Nurses use this checklist during the first 30 days after admission to report the presence/absence of sacral pressure ulcers, as well as the ulcer grade; the presence/absence of pressure ulcers on other locations and whether a sheepskin, repositioning, other support surfaces and incontinence material are applied.When nurses feel uncertain about their observations they are instructed to call another specialized nurse, experienced in observing pressure ulcers.Furthermore, a photographic series of the various pressure ulcer grades is available on each ward, as well as special glasses that can be used in order to differentiate better between blanchable and non-blanchable erythema. Finally, all nursing homes are offered a lesson in pressure ulcer observation.The daily skin observations by nurses during routine care will be checked weekly by an experienced nurse observator from the nursing home itself and bimonthly by the principal investigator from the central research office.Influencing patient factors that will be measured are age, gender, principal medical diagnosis category, surgery in the last month, presence of pressure ulcers at admission on other places than the sacrum, incontinence status, nutritional status (including body mass index), activity of daily living level (Barthel-index) and pressure ulcer risk score . These are measured twice: at admission and at day 30 after it.Furthermore the patients in the sheepskin group are asked at the end of the research period to rate the (dis)comfort of the sheepskin. For this purpose, a self-developed 7-item questionnaire with a 5-point rating answer structure was developed.Data about costs that will be gathered are the costs of buying sheepskins, costs of washing sheepskins, costs of treatment of pressure ulcers .For this purpose, invoices from the firms in question will be used, or the best approximations as far as these are available in Dutch  sites/organizations.In summary, in order to register the above-mentioned data, the following five forms were created: admission form, daily observation form, end of research period form, sheepskin comfort questionnaire and the pressure ulcer therapy cost form (these forms in Dutch can be obtained on request from the first author).The initial assessment at admission is completed for all patients that fulfill the inclusion criteria, in order to conduct a post hoc check as to whether there was selective attrition in patients not willing to participate.Ease of use of the sheepskin for carers will be measured by group interviews to be held on three occasions during the research period.First of all the primary outcomes will be analyzed using descriptive methods.Statistical testing of differences in incidence and prevalence between experimental and control groups will be conducted by a two-sided Chi-square test. In addition, differences in number of pressure ulcer free days will be tested with a two-sided t-test for independent samples; and differences in onset of pressure ulcers will be analyzed with Kaplan Meier curves. All analyses will be controlled for influencing factors. Moreover, a multi level analysis will be performed because of the fact that data are gathered from several organizations and nursing wards.Both intention-to-treat-analysis and per-protocol-analysis will be carried out.The economic data about costs will be used in a model approach to show the economic consequences on a higher level. The aim is to develop a model that can show the consequences of implementing improved pressure ulcer care for an average nursing home and/or the national level.Patients will be informed verbally and in written format about the research project before they are asked to participate and before they sign the informed consent form, which will also be signed by the nurse in charge at admission. At all times patients are free to stop their participation without having to give a reason for doing so.The study protocol has been reviewed and approved by the certified Medical Ethical Review Board of the University Medical Centre of Utrecht (protocol number 06/287), on behalf of all the participating nursing homes.The Board of directors of each participating nursing home signed a form in which they state they have read and understood the research protocol and that there are no obstacles at all to perform the research in their organizations.The scientific merits of the study protocol have been reviewed in the consecutive phases of research funding process by the independent reviewers of the funding organization ZonMw, the Netherlands Organization for Health Research and Development . The ZonNext to this, the research protocol, and more specifically the washing procedure of the sheepskins, has also been judged by the Dutch Working Party on Infection Prevention  and has In addition to the empirical data gathering, systematic literature reviews will be performed to retrieve adjuvant data concerning:- costs of pressure ulcer treatment,- pressure ulcer incidence and duration per grade in nursing home patients, and- influence of pressure ulcers on quality of life.These reviews will be conducted in order to compare the empirically found cost-effectiveness data to other studies, and to improve economic modelling and scenarios.For these systematic reviews a protocol has been written including databases to be searched, search strategies, inclusion criteria and process, methodological assessment and data-analysis. These review protocols (in Dutch) can be obtained from the authors.All results from this study will be submitted to suitable peer reviewed journals and will be presented at appropriate international conferences.st 2007 and is expected to continue until the end of 2008. First results are not expected earlier than mid-2009.The patient inclusion process started on May 1A grant (number 945-07-513) was obtained in a competitive application process of the efficacy research program, round 2007, of the Netherlands Organization for Health Research and Development ZonMw .This study is innovative because it is the first to assess the cost-effectiveness of the Australian Medical Sheepskin in nursing home patients and also because current opinions and guidelines ,41-44 opA difficult point in this research is that the usual care can not be standardized. Although nurses and nursing homes may have pressure ulcer protocols and say that they are following these, there is a chance that the usual care differs from nursing home to nursing home, or even from nursing ward to nursing ward, and that individual nurses may deviate from the protocol. Moreover, it is known that different mattresses are in use in and between nursing homes. Since standardization is in no way possible, a registration of mattresses and devices applied will be conducted.With regard to possible contamination between experimental and control group, the following measures will be taken: clear instruction to all nursing and care personnel and patients, a limited stock of sheepskin on the ward, daily inspection of the skin by the research team in both groups, and a concise control and observation to ascertain whether the patients are still being nursed in the condition they were randomized to. Moreover it is not very likely that patients from both groups will be nursed on the same room during the same period (1.2 admissions per bed); therefore it is improbable that patients from the control group will ask for a sheepskin.Finally, in the information sessions with nurses, it will be stressed that the Australian Medical Sheepskin is NOT a replacement for the normal pressure relieving interventions such as repositioning and other methods.With regard to treatment adherence, patients from the intervention group are asked only to keep the sheepskin in their bed for 30 days. No other action is required from patients other than actions that are also asked in the control group. However it remains possible that some patients after a few days will refuse the sheepskin : in these cases the use of the Australian Medical Sheepskin will be stopped without persuading patients to continue, but they will be asked if the daily skin observations can be continued. Records will be kept of patients that have discontinued the use of the Australian Medical Sheepskin (including reasons to stop), and they will be analyzed in the group they were randomized, according to intention to treat analysis principles.The Australian Medical Sheepskin is a new pressure relieving overlay, which has been proven to be effective to prevent pressure ulcers in two randomized controlled trials among hospital patients. However, it is not known yet if the Australian Medical Sheepskin is also an effective prevention for pressure ulcers in nursing home patients; nor is it known what the cost-effectiveness characteristics are of the Australian Medical Sheepskin are. This study will attempt to answer these questions.The author(s) declare that they have no competing interests.The sheepskins were purchased, after having requested trade offers from three different companies, at regular market prices from Yellow Earth, Laverton North, Australia.The washing procedures of the sheepskins are carried out at regular market prices by Lips Textile Services, Tiel, The Netherlands.These two firms do not contribute in any way to the funding of this study, and none of the authors have commercial or financial interests with these companies.All authors contributed substantially to the development of the study protocol and the drafting of this paper. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Korematsu S, Yamamoto K, Nagakura T, Miyahara H, Okazaki N, Akiyoshi K, Maeda T, Suenobu S-i, Izumi T. The indication and effectiveness of low-dose erythromycin therapy in pediatric patients with bronchial asthma. Pediatr Allergy Immunol 2010: 21: 489–492. © 2010 John Wiley & Sons A/SCmax− Cmin)/Cmin, from 1.3 ± 0.5 to 0.5 ± 0.3, which led to the maintenance of effective serum levels. These results indicated that IL8 and VEGF affect the severity of standard therapies resistance intractable bronchial asthma. Through the suppression of these chemokines and maintenance of effective theophylline levels, low-dose EM therapy improves the symptoms of bronchial asthma.To elucidate the mechanisms of intractable pediatric bronchial asthma and the indication of low-dose erythromycin (EM) therapy, the serum chemokine levels of and the angiogenic factor were evaluated in 55 pediatric patients with bronchial asthma; 7.4 ± 3.5 yr old, who had been treated with inhaled steroid, leukotriene receptor antagonist, theophylline and others for more than a year. Both the levels of interleukin (IL) 8 (p = 0.036) and vascular endothelial growth factor (VEGF) (p = 0.005) were higher in patients with severe type than those of patients with the milder type, while other chemokine levels such as serum eotaxin and MCP1 did not show the correlation with the severity of bronchial asthma. Induction of therapy with low-dose EM induced improvement of the clinical symptoms in patients with severe type and decrease of their serum chemokine levels: IL8; from 736 ± 88 to 75 ± 85 pg/ml (p < 0.0005), and VEGF; from 352.0 ± 160.5 to 132.2 ± 59.9 pg/ml (p = 0.021) within the next 6 months. Moreover, low-dose EM resulted in a decreased daily peak-trough fluctuation rate of the serum theophylline concentration; ( Low-dose erythromycin (EM) has been administered to patients with chronic respiratory diseases, such as diffuse panbronchiolitis and chronic pansinusitis to suppress the neutrophilic inflammation process of interleukin (IL) 8 . RegardiIn this study, to elucidate the effectiveness and the indication of low dose EM therapy, serum chemokine characterization and the theophylline metabolism in pediatric patients with bronchial asthma were evaluated.Fifty-five pediatric patients with bronchial asthma; 7.4 ± 3.5 yr old and 10 age-matched non-allergic non-febrile disease controls were included in this study after obtaining the informed consent from both the children and their parents. The diagnosis and severity of bronchial asthma were evaluated using the global initiative for asthma (GINA) guidelines ; a positMycoplasma, Chlamydia and respiratory syncytial virus were ruled out in all asthma patients by their serum antibody titers. The serum levels of IL8; neutrophilic chemokine, eotaxin; eosinophilic chemokine, monocyte chemoattractant protein (MCP) 1; monocytic chemokine, vascular endothelial growth factor (VEGF) were examined using enzyme linked immunosorbent assays (ELISA) kit . The detection limits were 5.0, 5.0, 25.0 and 5.0 pg/ml, respectively.Patient blood samples were collected during a stable state without any infections or fever at least the previous 2 wk. Infections such as Low-dose EM (10 mg/kg/day divided twice) was added on their current medications such as inhaled steroid, leukotriene receptor antagonist and theophylline for four severe-type patients; two of four patients also suffered from allergic pansinusitis. In addition, their clinical symptoms and serum chemokines levels were compared before and after 6 months of low-dose EM therapy.Cmax− Cmin)/Cmin.Moreover, three of four patients with severe-type asthma had been administered theophylline 16 mg/kg/day divided twice for more than a year. Before and 6 months after the co-administration of low-dose EM and theophylline, theophylline clearance, half-time and AUC (area under the curve) were calculated using the THEOPREDICT-III  based on 4–6 samples of the serum theophylline concentrations such as trough levels, and 4 and 6 h after administration. The daily peak-trough fluctuation rate of theophylline level was calculated using the formula; /Cmin, from 1.3 ± 0.5 to 0.5 ± 0.3  increased from 168.7 ± 74.4 to 261.7 ± 149.5 mg/CL × Wt. Such an altered theophylline metabolism resulted in a decreased daily peak-trough fluctuation rate of the serum theophylline concentration; (.5 ± 0.3 .Long-term low dose EM therapy has been introduced for the treatment of diffuse panbronchiolitis and chronic pansinusitis . Low-dosOn the other hand, VEGF; one of the angiogenic factors, is produced by neutrophil . It has Because of their immaturity regarding expiratory procedures, examinations using sputum tend to be difficult to perform in pediatric patients. Therefore, serum chemokine examinations were instead performed in this study.Our results showed the severity of bronchial asthma and the serum levels of IL8 and VEGF to demonstrate a positive correlation; yet, there was no significant difference was observed in terms of both serum eosinophilic chemokine eotaxin and monocytic chemokine MCP1. Based on the findings of eotaxin, eosinophilic inflammation might already be inhibited by such long-term medications as inhaled steroids, leukotriene receptor antagonist, theophylline and others. And thereafter, both IL8 and VEGF levels in patients with severe-type were decreased after 6 months of the low-dose EM treatment regimen, and followed by the improvement in clinical symptoms of bronchial asthma.Mycoplasma, Chlamydia and respiratory syncytial virus, which cause acute neutrophilic inflammation followed by transient wheezing (These results suggest that the neutrophilic inflammation thus plays a role in the severity of standard therapies resistance bronchial asthma. Because only two of four patients with severe type asthma suffered from allergic pansinusitis, the effectiveness of low-dose EM therapy might not only be due to the improvement of nasal symptoms . Althougwheezing , were ruFurthermore, an inhibition in the theophylline metabolism, which was considered to be a ‘side effect’ of EM, also demonstrated a beneficial effect. In severe-type patients, it was found to be difficult to maintain the serum theophylline levels within the therapeutic range; it therefore helped to decrease the daily fluctuations of the levels. Since an increased dose of theophylline alone would not help to induce an altered their daily fluctuation rates, this unexpected discovery might thus be the second important mechanism of low-dose EM therapy. Although theophylline should be administered carefully because it lowers the seizure threshold, especially in infantile and/or febrile patients , it mighIn this study, only four patients with severe-type were examined because most pediatric patients have become easier to control with standard therapies such as inhaled steroids, leukotriene receptor antagonist, theophylline and others. For this limitation, a further large scale double blind placebo control study should be needed next. In patients with still intractable asthma, low-dose EM therapy might be effective through the suppression of IL8 and VEGF and maintenance of effective theophylline levels.


P < 0.0000); and 114.13 ± 7.11, 106.52 ± 3.50, and 100.89 ± 2.80 mmHg (P < 0.0000) in amlodipine and lisinopril groups, respectively. Urinary albumin excretion (mean ± SEM) at baseline, after four, and after eight weeks was 79.30 ± 3.74, 62.03 ± 3.61, and 52.02 ± 3.05 (P < 0.0000); and 73.96 ± 4.10, 72.39 ± 3.74, 66.12 ± 3.94 (P = 0.1742) in lisinopril and amlodipine groups, respectively. Lisinopril but not amlodipine, reduced the urinary albumin excretion significantly despite their similar antihypertensive efficacy. The clinical and prognostic significance of these observations need to be established.Microalbuminuria can be present in 25–100% of patients with essential hypertension and is associated with increased incidence of cardiovascular events. Our goal was to evaluate the effect of a commonly used calcium channel blocker, amlodipine, and an angiotensin converting enzyme inhibitor, lisinopril on urinary albumin excretion in patients with mild to moderate essential hypertension. We screened 324 patients with essential hypertension for microalbuminuria and documented it in 120 patients. These 120 patients with microalbuminuria were randomly divided into two groups of 60 each, matched for age, sex, arterial pressure, creatinine clearance, and urinary albumin excretion so as to receive amlodipine or lisinopril. We prospectively measured their urinary albumin excretion and creatinine clearance prior to treatment and, four and eight weeks after treatment with amlodipine or lisinopril. Mean arterial pressure (mean ± SD) at baseline, after four weeks, and after eight weeks was 113.01 ± 4.38,104.93 ± 3.12, and 98.89 ± 1.75 mmHg ( The conventional methods of detecting renal damage in hypertension which include the measurement of blood urea nitrogen and creatinine, and proteinuria, are relatively insensitive, and only show abnormalities when the disease process is fairly advanced. Essential hypertension (EHT) produces clinical proteinuria and significant reduction in renal function in 5-15% of patients.–6Several epidemiological studies have shown that proteinuria as well as microalbuminuria are independent predictors of cardiovascular morbidity and mortality in patients with EHT. The hypo15Since 25% of patients with end-stage renal disease (ESRD) have hypertension as the primary diagnosis and moreWe screened 324 patients with EHT, who attended General Medicine and Cardiology out-patient clinics of tertiary care hospital in north India. Hypertensive patients were included in the study if they met the following criterion.Diastolic blood pressure (DBP) persistently between 90 and 100 mmHg on three successive visits to the outpatient clinic.UAE was between 30-300 mg/24 hrs; we chose the level of 30 mg/24 hrs to define the presence of microalbuminuria because in a previous study it was shown that all the normal subjects had UAE below this value.[2 in three different measurements.A creatinine clearance (Clcr) level greater than 80 ml/ min/l.73 mNo antihypertensive therapy in the past.We enrolled 120 patients who met the above criteria. Females on birth control pills were excluded from the study. The diagnosis of secondary hypertension was excluded with regular laboratory analysis. Patients with clinical or laboratory evidence of hepatic, renal, thyroid or any other major illness like diabetes mellitus were excluded. This group of 120 patients was randomly divided into two subgroups of 60 each matched for age, sex, arterial pressure, Clcr and UAE. One subgroup received an ACE inhibitor lisinopril, other received a CCB amlodipine. The dose of drugs was gradually increased to maximum desirable dose.Aimed target blood pressure was <130/80 mmHg. The administration of the drugs was open labelled, and these drugs were administered at 8 am daily except on the day of study when the drugs were given only after blood pressure measurement and drawing of sample. 24-hour urine was collected before the start of the study and after four and eight weeks of treatment to measure UAE, creatinine, sodium and potassium. At baseline, and after four and eight weeks of treatment during the study creatinine clearance, serum sodium and potassium were also measured. Blood and urine creatinine were estimated by autoanalyser. Urinary albumin excretion was estimated by an immunoturbidometry method using an automated Biochemistry Analyzer (Hitachi704).P value of < 0.05 was taken as statistically significant.Statistical analysis was performed by using statistical package for social science (SPSS) version 11.5 for PC windows. A 2-tailed P < 0.0000). We observed significant reduction in DBP and MAP after four and eight weeks of therapy in amlodipine group compared to lisinopril group . However, SBP was comparable between the two groups at four and eight weeks of therapy [Patients on amlodipine or lisinopril did not differ with respect to their age, sex, BMI, smoking, and severity of HT . Also th therapy .Serum creatinine, serum sodium, serum potassium, and urinary sodium, and potassium levels were comparable between amlodipine group and lisinopril group prior to treatement, four and eight weeks after the treatment. These parameters did not change significantly over eight weeks of therapy with amlodipine or lisinopril , we did P = 0.0000). In amlodipine group, there was no significant reduction in UAE rate after four and eight weeks of therapy compared to baseline value (P > 0.1742) [There was a significant reduction in UAE rate after four and eight weeks of treatment with lisinopril, compared to baseline value ( 0.1742) .P < 0.04) and eight weeks (P < 0.005) of therapy compared to that of amlodipine group [We observed significant reduction of UAE rate in lisinopril group after four weeks  despite good and comparable blood pressure control.[Theoretically, proteinuria, in the subject with hypertension, can be diminished by way of regression of the structural renal alterations or modifications of the hemodynamics of the afferent arteriole, glomerulus, efferent arteriole system or through mechanisms that re-establish normal glomerular permeability. The resu21 control.In previous studies conducted both on animals and human, ACE inhibitors were shown to be able to reduce urinary excretion of proteins in various types of renal disease including those associated with diabetes.924 The m924Microalbuminuria in EHT reflects systemic dysfunction of vascular endothelium, a structure intimately involved in the permeability, hemostasis, fibrinolysis, and blood pressure control. Inhibition of angiotensin II conversion and preservation of nitric oxide production are considered to underlie the favorable effects of ACE inhibition on endothelial function and potentially on cardiovascular events. Both angiotensinII and nitric oxide are involved in the balance of thrombosis, and fibrinolysis, via changes in platelet aggregation plasminogen activator, as well as changes in the matrix synthesis of plaques.28 Hence,We did not observe any significant modifications in microlbuminuria with amlodipine. Calcium acts as a second messenger to mediate the vasoconstriction effect of angiotensin and nor epinephrine. If, in subjects with hypertension, the efferent arteriole is further constricted by these hormonal regulators, then a positive response by calcium antagonists appears justified. The modifications of hemodynamics with calcium antagonists are related to different factors, such as, the type of calcium antagonist, the way in which it is administered, basal vascular tone, and the basal levels of vasoconstrictors, such as angiotensin II. In this We did not observe any change in creatinine clearance in hypertensive patients treated with lisinopril or amlodipine. Similar results have been observed in the past.29Since microalbuminuria in EHT reflects systemic vascular endothelial dysfunction, its reduction by ACE inhibitor lisinopril points towards the favorable effects of ACE inhibition on vascular endothelium. Recently, HOPE trial has also revealed beneficial effects of ACE inhibitors on vascular endothelium resulting in reduction of cardiovascular morbidity and mortality. The implIn conclusion, this study has shown that eight weeks of therapy with lisinopril reduces UAE in patients with mild to moderate EHT, whereas amlodipine had no measurable effect on UAE, despite similar antihypertensive efficacy.


Suckling can be a peaceful or vulnerable event for goats and kids, whereas, separation is suggested as stressful. The aim of this study was to investigate physiology and behaviour in these two different situations in dairy goats.Four studies were performed with seven goats kept with their first-born kid in individual boxes. The goats were videotaped and heart rate and arterial blood pressure were recorded every minute by telemetry from parturition until 24 hours after separation. One to two days after parturition, Study 1 was performed with analyses of heart rate and blood pressure around a suckling. In Study 2, performed 3-5 days after parturition, blood sampling was done before, during and after suckling. Study 3 was performed 4-6 days post partum, with blood sampling before and after a permanent goat and kid separation. In addition, vocalisations were recorded after separation. Blood samples were obtained from a jugular vein catheter and analysed for plasma cortisol, β-endorphin, oxytocin, and vasopressin concentrations. Study 4 was performed during the first (N1) and second nights (N2) after parturition and the nights after Study 2 (N3) and 3 (N4). Heart rate, blood pressure and time spent lying down were recorded.The kids suckled 2 ± 0.2 times per hour and each suckling bout lasted 43 ± 15 s. In Study 1, heart rate and blood pressure did not change significantly during undisturbed suckling. In Study 2, plasma cortisol (P ≤ 0.05 during suckling and P ≤ 0.01 five minutes after suckling) and β-endorphin (P ≤ 0.05) concentrations increased during suckling, but oxytocin and vasopressin concentrations did not change. In Study 3, the goats and kids vocalised intensively during the first 20 minutes after separation, but the physiological variables were not affected. In Study 4, heart rate and arterial blood pressure declined gradually after parturition and were lowest during N4 (P ≤ 0.05) when the goats spent longer time lying down than during earlier nights (P ≤ 0.01 during N1 and N3 and P ≤ 0.05 during N2).Suckling elevated plasma cortisol and β-endorphin concentrations in the goats. The intensive vocalisation in the goats after separation, earlier suggested to indicate stress, was not accompanied by cardiovascular or endocrine responses. The mostogether . In the In goats, an exclusive bond between mother and young develops rapidly after birth, mainly due to olfactory cues from the kids -6. A visIn a stressful situation, the sympathetic nervous system and the hypothalamic-pituitary-adrenal-axis become activated. Heart rate and blood pressure increase when an activation of the sympathetic nervous system occurs. During the last 10 years, surgically implanted devices for continuous telemetric registrations of heart rate and blood pressure have been used by us, who may be the only group using this methodology in the goat. The method enables unique studies on the undisturbed, conscious goat. Therefore, changes in heart rate and blood pressure during suckling and separation were investigated, and the variables were recorded both during daytime and night time. During the nights, the effects of separation could be studied when the goats were undisturbed by daily management procedures. This was of interest since earlier results have shown that the heart rate gradually declines, but blood pressure does not change during the first week after parturition in goats where the goats and kids were permanently separated immediately post partum .Change in plasma cortisol concentration is a variable commonly measured as an indicator of stress. In goats, cortisol is reported to increase i.e. at transportation -20 and iThe hypothesis of this study was that suckling is a peaceful event, whereas, sudden and permanent separation causes stress in goats with established bonding to their kids. The aim was to investigate the physiology and behaviour of dairy goats during both suckling and permanent separation of goats and kids.(Capra hircus), 2-3 years old, were studied. The goats were routinely kept together in a large pen with straw and wood shavings as bedding and were accustomed to handling. The goats were fed hay and concentrates at 7.30 h and 15.00 h and water and mineral stones were freely available. During night hours (18.00-06.00 h), the light was switched off and the goats were undisturbed by management routines. The goats gave birth on separate days, between 11.00 h and 20.30 h, from late February to early April. Six goats delivered two kids and one goat delivered one kid. When parturition was close, the goats were moved to individual boxes (1.2 × 1.5 m) in an adjacent room, in which all experiments were performed. The walls of the boxes consisted of a 30 cm solid edge with horizontal bars above so the animals could see out. In this herd, the goats usually deliver 1-3 kids. Therefore, to standardise the experiment, it was decided in advance that only the first-born kid would stay with its mother in the box. The second-born kid was moved before the goat had licked it, so only one mother-kid bond was established. None of the goats delivered three kids. The care of the animals and the experimental design were approved by the Animal Ethics Committee in Uppsala, Sweden.The study was conducted on an experimental herd at the Swedish University of Agricultural Sciences, Uppsala, Sweden. Seven female goats of the Swedish domestic breed Heart rate and diastolic, mean, and systolic arterial blood pressure values were recorded telemetrically every minute. The telemetric device was implanted in each goat at least three months before the study. As reported by Hydbring and colleagues , a trans®, Astra, Södertälje, Sweden) into one of the jugular veins of the goat when blood samples were taken. The catheter was inserted at least 30 minutes before the first blood sample to avoid the effects of insertion and was provided with an extension tube fixed to the neck of the goat with adhesive tape, so that it was possible to draw blood without restraining the animal. After insertion, and after each blood sample, the catheter was flushed with sodium citrate.A catheter  was inserted under local anaesthesia (XylocainBehaviour was recorded by video cameras mounted above each box and connected to a time-lapse video recorder (Panasonic). The videotapes were analysed by the same person. Vocalisation of the goats was recorded with a Compact VHS video camera (JVC), and vocalisation by the kids was recorded by direct observation.The first study Study 1) was performed 1-2 days after parturition  was performed 3-5 days after parturition Figure , and in The third study (Study 3) was performed the day after Study 2, 4-6 days after parturition Figure . Heart r"the goat lying with its legs folded and its chest in contact with the floor". Latency time from separation until lying down was defined as "time from the moment the kid was separated from the mother until the goat laid down the first time".Vocalisation rate was defined as "every vocalisation with a pause between two occurrences". The vocalisation rate was counted during 120 minutes after separation, divided into twelve 10-minutes periods. For each 10-minutes period, the mean for both goats and kids was calculated. Lying down was defined as The fourth study (Study 4) was a comparison of the mean values of heart rate, blood pressure and total duration time spent lying down between the first and second nights after parturition, and the nights after Study 2 and Study 3 Figure . The tot3-EDTA and aprotinin  and was centrifuged . The plasma was stored at -20° for 24 hours and thereafter at -70° until assayed. Analyses of plasma cortisol, β-endorphin, oxytocin, and vasopressin were validated for goat plasma and performed with radio-immuno-assay methods described by Hydbring et al. [Blood was drawn into ice-chilled tubes containing Kg et al. . The intBehavioural and hormonal data are presented as means ± standard error of the mean (S.E.M). Data were examined by repeated measurement ANOVA (mixed procedure) of the Statistical Analysis System (SAS Institute Inc. 2003). Hormonal differences within studies were tested through differences in least squares means against the first control sample. Differences in heart rate and blood pressure values within days were analysed with Bonferroni's Multiple Comparison Test. The coefficient of variation (CV) values for heart rate and mean blood pressure were compared during periods with and without blood sampling. The difference between respective CV values was tested by t-test. Differences in behavioural data were tested with the non-parametric Wilcoxon Signed Ranks test. Differences in heart rate, blood pressure and time spent lying down were tested during the nights (18.00 h-06.00 h) when goats were undisturbed. The level of significance was set at P ≤ 0.05.During the first 24-48 hours post partum, the kids suckled on average 2 ± 0.2 times per hour and each suckling bout lasted approximately 43 ± 15 seconds. The average time until a suckling was observed after 10.30 h, without other suckling 30 minutes before and after, was 88 ± 18 minutes in the undisturbed goats. Both heart rate and blood pressure fluctuated during the day with individual differences, but there were no significant changes in heart rate or blood pressure related to suckling Figure .It took 70 ± 10 minutes until a single suckling was observed. Heart rate (P ≤ 0.001) and blood pressure (P ≤ 0.05) fluctuated more and the individual differences were higher than in study 1, performed on the previous day Figure . No chanThere were no changes in heart rate and blood pressure at separation Figure . The plaDuring the first 10 minutes period after separation, both goats and kids vocalised intensively and vocalisation rate remained high during the subsequent 10 minutes period. During the remaining periods, vocalisation rate was lower in both goats and kids, except for 31-40 minutes and 61-70 minutes after separation in the goats  Figure . Mean blSuckling in goats was accompanied by increased cortisol and β-endorphin concentrations, but with no significant changes in heart rate and blood pressure. Permanent separation caused no changes in arterial blood pressure, heart rate, or plasma concentrations of cortisol and β-endorphin, although intensive vocalisation occurred during the first 20 minutes.i.e the activity in the animal facilities might have made the goats more alert, which affected the cardiovascular variables. No change in heart rate in response to suckling was observed. These results can be compared with an increase of about 6% in blood pressure and about 10% in heart rate, respectively, during hand milking [A small but not significant increase in blood pressure was observed at suckling, when the recordings were taken in undisturbed goats. When suckling was combined with blood sampling, there was more variation in both blood pressure and heart rate. Possibly, a more general arousal in the goats occurred during these days,  milking . In thatBoth plasma cortisol and β-endorphin increased during suckling and in the sample taken 5 minutes after suckling, which supported that suckling activated the hypothalamic-pituitary-adrenal axis. Increased plasma cortisol concentrations have been found during and immediately after milking in suckled cows ,27, in cThere was no elevation of either plasma oxytocin or vasopressin concentrations. This contrasted with the study by Olsson and Högberg  who deteSudden and permanent separation did not alert the sympathetic nervous system as indicated by the unchanged heart rate and blood pressure. The lack of cortisol response was in accordance with earlier separation studies in goats , cows 3, and ewei.e. during the night after separation). The goats were milked in the afternoon and the kids fed, which meant they were not suffering from a distended udder or hunger.One explanation for the lack of change in the physiological variables during and after separation could be that goats and kids, unlike lambs which are followers, have only contact for nursing the first days after parturition ,8 and maHeart rate is higher during daytime than night time during both pregnancy and lactation, but with no diurnal variation in blood pressure . In the In conclusion, suckling elevated plasma cortisol and β-endorphin concentrations in the goats. The intensive vocalisation in the goats after separation, earlier suggested to indicate stress, was not accompanied by cardiovascular or endocrine responses.The authors declare that they have no competing interests.The study was designed by LWvW, EHS and LL. LWvW and EHS carried out the study. LWvW, EHS and LL analysed the data and AM performed the statistical analyses. LWvW and EHS drafted the manuscript and LL, KD and AM participated in the writing. All authors read, revised and approved the final manuscript.


The current study was conducted to determine the effect of adiposity on vascular distensibility in Gujarati Indian adolescents as research indicating the pathogenesis of hypertension among overweight and/or obese Indian adolescents is scant and ethnic differences exist in the pathogenesis of hypertensionA cross-sectional study was conducted on 488 Gujarati Indian adolescents of 16-19 years age group. Adiposity was assessed in terms of BMI, Body Fat %, Fat Mass, Fat Mass Index and Waist Circumference. Arterial blood pressure was recorded and pulse pressure (PP) was calculated using the standard equation based on the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP). Pearson’s correlation coefficient was determined to find the association between the markers of adiposity and SBP, DBP and PP.A significant positive correlationship was found between adiposity and PP in boys. However, no significant correlationship was found between adiposity and PP in girls.An increase in total as well as visceral adiposity is probably associated with a decrease in vascular distensibility in the Gujarati Indian adolescent boys but not in girls, thus indicating a protective role of female sex hormone estrogen which has been shown earlier to protect the vasculature from atherosclerosis, endothelial dysfunction which occurs with increase in adiposity. Studies from various communities across India indicate an increase in prevalence of hypertension among the children and adolescents. An increSeveral patho-physiological changes like increase in sympathetic activity, decrease in arterial elasticity and hyperinsulinaemia associated with increase in body mass and unhealthy lifestyle have been implicated in the pathogenesis of hypertension. However,6We studied the association of adiposity with pulse pressure, a reliable indicator of vascular distensibility with theA cross-sectional study was conducted on 488 Gujarati Indian adolescents (Boys=296 and Girls =192) of 16 to 19 years age group, studying at the schools and colleges in the local population after the approval of institution’s human research ethics committee and obtaining informed consent from the participants or the guardian.2). WC was measured at the midpoint between the lower costal margin and the iliac crest to the nearest 0.5 cm at the end of normal expiration. BF % and FM were assessed by bioelectrical impedance technique using Omron Body Fat Monitor HBF -302. FMI was calculated as the fat mass (kg) divided by the square of height in meters (m2).(Adiposity was assessed in terms of Body Mass Index (BMI), Body Fat % (BF %), Fat Mass (FM), Fat Mass Index (FMI) and Waist Circumference (WC). BMI was calculated as the weight (kg) divided by the square of height in meters (mers (m2).Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded at the brachial artery in the left arm using the Omron T8 with Intellisense (HEM757A4-C1) Automatic Blood Pressure Monitor  according to the recommended guidelines. Blood pressure was recorded at intervals of 1 minute till the difference between two consecutive BP readings was less than 5 mm Hg. The average of the two consecutive readings was used for statistical analysis. Pulse pressure (PP) was obtained by calculating the difference between the average systolic blood pressure and average diastolic blood pressure.–12Pearson’s correlation coefficient was used to determine the correlationship of markers of adiposity with SBP, DBP and PP.A significant correlationship was found between adiposity and SBP, DBP and PP among boys while adiposity showed a significant correlationship with SBP and DBP in girls, but not with PP as shown in et al.(et al.(The present study indicates that adiposity decreases vascular distensibility among the Gujarati adolescent boys at an age as early as 16-19 years. These results are consistent with earlier reports that relate adiposity to vascular distensibility in adolescents. Whincup et al. found a l.(et al. investiget al.(The study showed that arterial diameter increased with BMI in all territories, with an opposite trend for arterial distensibility. In men and women, the relationships of brachial and femoral properties with BMI were consistent across the whole age range. In men and women, carotid distensibility decreased more with BMI at young than old age. In middle-aged and older women, but not in men of any age, pulse wave velocity increased with higher BMI. Urbina et al. conducteet al.(The probable reason for this gender difference observed in the relationship of adiposity with PP is the fact that the female sex hormone estrogen is believed to protect the post-pubertal female vasculature from atherosclerosis and make the blood vessels more distensible while the male sex hormone testosterone predisposes the male vasculature to endothelial dysfunction and atherosclerosis. Ahimastos et al. reportedet al.(Herman et al. have demHowever, though we have not studied the stroke volume in our study population and since stroke volume is the other determinant of pulse pressure apart from vascular distensibilty, the finding that adiposity has strong and equal correlationship with SBP in both boys and girls probably reflects the fact that adiposity associated rise in stroke volume due to volume expansion may not be the reason for the presence of a strong correlationship between adiposity and PP in boys and absence of such relationship in girls.This study shows that adiposity affects vascular distensibility in Gujarati Indian adolescents and that the male vasculature is prone to the adverse effects of adiposity in comparison to female vasculature at an age as early as adolescence.We have indirectly assessed the vascular distensibilty in this study and therefore a much detailed study is required in this population to understand the finer details regarding the effect of adiposity on vascular distensibility.


Nitric oxide (NO) in peripheral venous blood has been shown to be elevated in experimental portal hypertension. This study aims to determine the serum NO levels in patients with extrahepatic portal venous hypertension (EHPVO) pre- and postoperatively and to analyze whether these can serve as a reliable and early indicator of shunt blockage or malfunction.During the period 2006–2010, 48 children with EHPVO were included in this prospective study; 40 underwent porto-systemic shunt and eight underwent splenectomy with devascularization. NO was evaluated preoperatively, 14 days after surgery, at 3 months and then 6 monthly thereafter. The median follow-up duration was 21 months. Shunt patency was confirmed with Doppler and computed tomography portography. Forty-eight age-matched children with hypospadias served as controls.μmol/l) (P = 0.0001). There was a significant decline in the NO levels (4.64 ± 3.18 μmol/l) following shunt surgery (P = 0.0001), and it continued to remain low till the shunt was patent. A shunt block was indicated by rising NO levels in all five patients. The devascularization group also demonstrated a significant decline in the NO levels (27.06 ± 3.56 μmol/l) (P = 0.002), but it was less as compared with the shunted patients. The decline in the portal pressure after shunt surgery was found to correlate with the decline in the serum NO levels.NO was higher in EHPVO patients as compared with controls (43.16 ± 16.27 vs. 5.76 ± 2.62 The blood levels of NO can be used in the diagnosis of portal hypertension, and are useful for monitoring the patency of the shunt. Definitive management of extrahepatic portal venous obstruction (EHPVO) involves creation of a porto-systemic shunt to decompress the portal venous system. Children are at a high risk of shunt blockage due to the small caliber of the veins; the reported shunt patency rates from centers experienced with complex vascular reconstruction of the portal system vary from 83 to 100%.1 The postThe splanchnic and systemic circulations experience increased cardiac output and hyperdynamic circulation in portal hypertension. This has4The aims of this study were to determine the levels of NO in the peripheral venous blood of the patients of EHPVO pre- and postoperatively and also to determine whether these can serve as a reliable and early indicator of shunt blockage or malfunction. A similar study has not been reported earlier.All the patients of EHPVO who underwent surgical management during July 2006 to January 2010 under the care of a single surgeon were included in this prospective study. Appropriate approval from the Institute’s Ethics Committee and parental consent were obtained. Age-matched patients of hypospadias formed the control group.Forty-eight patients were included in the study. The age varied from 4 years to 14 years, with a mean of 9.84 (± 3.13) years. There were 36 boys and 12 girls. Forty patients underwent porto-systemic surgery . Eight patients underwent splenectomy and devascularization of the gastro-esophageal junction. The postoperative follow-up varied from 1 month to 39 months, with a mean follow-up of 21.08 (± 10.65) months. The median follow-up duration was 21 months.The patients were evaluated for blood levels of NO preoperatively, 14 days after surgery, 3 months after surgery and at a gap of every 6 months subsequently. The shunt patency was confirmed with a simultaneous Doppler evaluation. A blocked shunt was confirmed by a computed tomography (CT) portogram. The control group was evaluated for NO only once.Intraoperatively, a venous tributary of the gastro-epiploic arcade was cannulated with a 20-gauge intravenous cannula and connected to the pressure transducer for measurement of the portal pressure before and after splenectomy and the creation of the shunt.Peripheral venous blood was collected in heparinized tubes, centrifuged  and preserved at -70°C. During analysis, nitrate was reduced to nitrite by nitrate reductase and then the plasma level of NO was quantified spectrophotometrically (540 nm) by the Greiss reaction.t-test. The serial levels of NO were also compared with the paired t-test. However, the levels between the patients who underwent shunt surgery and those who underwent devascularization were compared using the Mann–Whitney U test. The correlation between the postoperative drop in the NO levels and portal pressures was calculated using the Spearman rank correlation coefficient. A P-value <0.05 was considered statistically significant.The statistical analysis was performed using SPSS 14.0 and Stata 9.0. Data were presented as number (%) or mean (± SD)/median (range) as appropriate. The levels of NO were compared between EHPVO patients and the controls using the paired μmol/l in the patients of EHPVO and 5.76 ± 2.62 μmol/l in the control population. The difference between the two values is significant (P = 0.0001). Following shunt surgery, there is a significant decline in the levels of NO.The mean level of NO was 43.16 ± 16.27 The levels of NO after the shunt surgery are comparable to the levels of NO in the control population .After a successful shunt surgery, the NO levels continue to remain low till the patency of the shunt is maintained .Five patients had a blocked shunt in the postoperative period. The first patient  had a shunt block at 6 months after surgery. The second patient  was re-explored at 3 months post shunt surgery for adhesive intestinal obstruction. At that time, the shunt was evaluated and found to be patent. However, at 6 months of follow-up, the shunt was blocked. Two patients  had a shunt block on postoperative day 14. In all these patients, the NO levels had shown an initial decline after the shunt surgery and a subsequent rise . The fifThe patients who underwent devascularization also showed a significant decline in the NO levels . HoweverP = 0.002).The mean preoperative portal pressure was 34.19 ± 5.90 mmHg, which fell to 20.88 ±± 6.51 mmHg after splenectomy and creation of the porto-systemic shunt. The correlation between the drop in the blood levels of NO and the drop in the portal pressures  was founP = 0.010) [No correlation could be established between the preoperative levels of NO and the preshunt portal pressures. However, there was a negative correlation between the preoperative levels of NO and the postshunt portal pressure, which was statistically significant (= 0.010) .The splanchnic and systemic circulations experience increased cardiac output and hyperdynamic circulation in portal hypertension. This has4Based on these observations, it was hypothesized that the levels of NO in the patients of EHPVO should be elevated. The study has shown that the levels of NO are elevated in the peripheral venous blood of patients with EHPVO. After surgical correction, the levels of NO have shown a decline. The levels of NO become comparable to the controls after porto- systemic shunt surgery.The levels of NO also come down after splenectomy and devascularisation, which suggests that the procedure is effective in lowering the portal pressure. However, in these patients, NO levels are still higher than the age-matched controls. This is possibly due to the portal pressure still remaining higher than normal after devascularization and an equilibrium being reached with some collaterals remaining open. On the other hand, in the case of porto-systemic shunting, the portal pressure normalized and the collaterals possibly obliterate spontaneously. With blockage of the shunt, the portal pressures rise dramatically in the absence of the collaterals. This is reflected by the rise in the NO levels.The authenticity of NO is further confirmed by correlating it with the portal pressures measured intraoperatively. High levels of NO are associated with high levels of portal pressure. The magnitude of fall in the levels of NO with the shunt surgery has been found to correlate with the magnitude of fall in the portal pressure.Children undergoing porto-systemic shunting are at a high risk of shunt blockage due to the small caliber of the veins. They need to be evaluated for the patency of the shunt regularly, using ultrasound Doppler as the first line of investigation for this purpose. However, its usefulness is limited by its operator dependence, poor reproducibility and the problem associated with ascites or overlying gas-filled bowel loops. Medical personnel other than the radiologist find it difficult to interpret the images. CT portogram was used to confirm the shunt block in all the patients. Its use is limited by its cost, availability of equipment and technical expertise, radiation hazards, need for intravenous contrast material, artefacts from surgical clips, technically poor images due to motion artefacts and inability to quantify the venous flow across the anastomosis. MR imaging is also limited by its availability, cost, occasionally artefacts and the time taken.During the follow-up of these patients, the patency of the porto-systemic shunt has been found to correlate with the NO levels in our study. NO shows a steep rise after the blockage of the shunt, and continues to rise for a few months initially, thereby showing a plateau. In this way, it has served its role as a marker of shunt patency. Estimation of NO is a simple and relatively inexpensive laboratory procedure; the only requirement is 2 ml or perhaps even lesser amount of peripheral venous blood from the patient. No special equipment or manpower training is required.The blood levels of NO could be utilized as a marker of portal hypertension and may also be used as a marker for the patency of the shunt in the follow-up of these patients.