World J Gastroenterol 2006 May 14; 12(18): 2923-7 (Read article online)

Ng W, Wong WM, Chen WH, Tse HF, Lee PY, Lai KC, Li SW, Ng M, Lam KF, Cheng X, Lau CP

AIM: The use of low-dose aspirin to prevent cardiovascular disease events is well established. However, the incidence and predictors of upper gastrointestinal bleeding (UGIB) with its use are unknown. We studied prospectively the incidence and outcome of peptic ulceration in low-dose aspirin users. METHODS: A total of 991 patients with coronary artery disease (CAD) on low-dose aspirin were prospectively followed-up for two years for the occurrence and clinical features of first hospitalized episode of UGIB. RESULTS: UGIB had a bimodal presentation with 45% occurring within four months of aspirin initiation and had an overall prevalence of 1.5% per year. There was no UGIB-related death. Hypertension (OR = 4.6, 95%CI 1.5 - 14.7, P = 0.009), history of peptic ulceration (OR = 3.1, 95%CI 1.1 - 9.0, P = 0.039), tertiary education (OR = 3.08, 95%CI 1.1- 9.0, P = 0.039) and higher lean body mass (P = 0.016) were independent factors associated with UGIB. Use of nitrate did not reduce UGIB. CONCLUSION: The incidence of UGIB in patients with CAD on long-term low-dose aspirin is low, but is accompanied with significant morbidity. With prolonged use of aspirin, UGIB continues to be a problem for those with risk factors and especially in patients with a history of peptic ulcers, in which UGIB tends to occur early after aspirin therapy.

Neurology 2006 May 23; 66(10): 1539-44 (Read article online)

Kubo M, Kiyohara Y, Ninomiya T, Tanizaki Y, Yonemoto K, Doi Y, Hata J, Oishi Y, Shikata K, Iida M

BACKGROUND: There is scant information on secular trends in the incidence and survival of ischemic stroke subtypes. METHODS: The authors established three cohorts of Hisayama residents age > or =40 years in 1961 (1,618 subjects), 1974 (2,038 subjects), and 1988 (2,637 subjects). They followed up with each cohort for 12 years, comparing the incidence and survival rate of ischemic stroke subtypes. Morphologic examinations by autopsy or brain imaging was performed on most of the ischemic stroke cases in all cohorts. RESULTS: The age-standardized incidence of lacunar infarction significantly declined by 59% for men and by 28% for women from the first to the second cohort. It continued to decline by 41% for men, but the decline decelerated for women between the second and third cohort. The age-standardized incidence of atherothrombotic infarction tended to decline from the first to the second cohort, whereas it was sustained between the second and third cohort for both sexes. The age-standardized incidence of cardioembolic infarction was unchanged throughout the cohorts. In these cohorts, mean blood pressure levels among hypertensive subjects and the prevalence of current smoker decreased with time, though the prevalence of hypertension remained stable. The 5-year survival rate after lacunar infarction significantly improved among the cohorts, but those of atherothrombotic and cardioembolic infarction did not. CONCLUSIONS: These data suggest that, in the Japanese population, the incidence of lacunar infarction steadily declined for the last 40 years. The improvement of hypertension control and decreasing prevalence of smoking might be responsible for this trend.

Anesth Analg 2006 Jun; 102(6): 1823-9 (Read article online)

Rasmussen M, Upton RN, Grant C, Martinez AM, Cold GE, Ludbrook G

The effect of indomethacin in reducing intracranial pressure (ICP) may be dependent on the choice of anesthetic regimen. We studied the effects of indomethacin on ICP and cerebral blood flow (CBF) during isoflurane or propofol anesthesia in a sheep model of intracranial hypertension. A crossover design was applied in which six sheep were anesthetized with isoflurane and propofol in a random order. Anesthetic depth was measured with response and state entropy. Changes in CBF, ICP, mean arterial blood pressure, arterio-venous oxygen difference, and Paco(2) were measured at specific times before and after an IV indomethacin bolus (0.2 mg/kg). Response and state entropy values during anesthesia were similar in both groups. Isoflurane and propofol reduced CBF by 11% and 34%, respectively. Indomethacin caused a reduction in ICP within 15 s during both anesthetic regimens, with the decrease in ICP being significantly more pronounced during isoflurane (P = 0.009). In both anesthetic groups, indomethacin caused a simultaneous increase in mean arterial blood pressure and a further 17% versus 14% decrease in CBF from predrug values for isoflurane and propofol, respectively. The reduction in CBF was significantly more pronounced for propofol (P = 0.02). The effect on ICP, however, was most pronounced during isoflurane anesthesia. We suggest that the effect of indomethacin is partly mediated by an autoregulatory response.

Free Radic Biol Med 2006 Jun 1; 40(11): 2028-39 (Read article online)

Chan SH, Tai MH, Li CY, Chan JY

A balance between production and elimination of reactive oxygen species such as superoxide anion (O(2)(-)) and hydrogen peroxide (H(2)O(2)) tightly regulates the homeostasis of cellular oxidative stress, which contributes to a variety of cardiovascular diseases, including hypertension. The present study assessed the hypothesis that O(2)(-) or H(2)O(2) levels augmented by the reduced molecular synthesis or enzyme activity of superoxide dismutase (SOD), catalase (CAT), or glutathione peroxidase (GPx) in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons that generate tonic vasomotor tone are located, contribute to the pathogenesis of hypertension. We found that copper/zinc SOD (SOD1), manganese SOD (SOD2), or CAT, but not GPx, mRNA or protein expression and enzyme activity in the RVLM of spontaneously hypertensive rats (SHR) were significantly lower than those in normotensive Wistar-Kyoto (WKY) rats, along with a significantly higher level of O(2)(-) or H(2)O(2). A causative relationship between these biochemical correlates of oxidative stress and neurogenic hypertension was established when gene transfer by microinjection of adenovirus encoding SOD1, SOD2, or CAT into the bilateral RVLM promoted a long-lasting reduction in arterial pressure in SHR, but not WKY rats, accompanied by an enhanced SOD1, SOD2, or CAT protein expression or enzyme activity and reduced O(2)(-) or H(2)O(2) level in the RVLM. These results together suggest that downregulation of gene expression and enzyme activity of the antioxidant SOD1, SOD2, or CAT may underlie the augmented levels of O(2)(-) and H(2)O(2) in the RVLM, leading to oxidative stress and hypertension in SHR.

Vascul Pharmacol 2006 May 19; (Read article online)

Dobrian AD

Obesity is frequently accompanied by insulin resistance, type II diabetes, hypertension and atherosclerosis, a cluster of pathologies that are the major components of the metabolic syndrome. Obesity is a known cause for renal dysfunction that leads to two major renal pathologies: hypertension and glomerular and tubulointerstitial injury. Peroxizome proliferator activated receptors (PPARs) are transcription factors belonging to the nuclear hormone receptor superfamily with important functions in the regulation of metabolism. The role of PPARgamma isoforms in adipogenesis and vascular inflammation associated to obesity has been vastly studied and is well recognized, albeit not completely mechanistically understood. Also, the effect of various PPARgamma agonists on blood pressure reduction in different forms of hypertension, including obesity related hypertension has been reported, but the mechanisms involved are only beginning to be studied. Even less clear is the concurrent beneficial effect of PPARgamma agonists thiazolinendiones (TZD) on blood pressure reduction in different forms of hypertension and, at the same time, in some cases, the significant water retention leading to edema and heart failure. The occurrence of both these apparently opposite effects on the renal water and sodium handling suggests a complex role of PPARgamma in the kidney that is likely related to the metabolic state. Also, PPARgamma activation leads to a reduction in mesangial cell proliferation while stimulating apoptosis. TZD treatment reduces albuminuria in obese and diabetic humans and rodent models suggesting protective effects against renal tubuloglomerular injury. The focus of this review is to present and critically discuss the recent findings on the roles of PPARgamma in the kidney in direct relation to renal function and renal injury in obesity and obesity-initiated diabetes.

World J Gastroenterol 2006 May 7; 12(17): 2737-41 (Read article online)

Li T, Ni JY, Qi YW, Li HY, Zhang T, Yang Z

AIM: To investigate the interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy by observing splenic arterial and venous pathological changes and the ro1e of extra-cellular matrix in the pathogenesis of portal hypertensive vasculopathy by measuring the expression of type I and type III procollagen mRNA in splenic venous walls of portal hypertensive patients.METHODS: Morphological changes of splenic arteries and veins taken from portal hypertensive patients (n=20) and normal controls (n=10) were observed under optical and electron microscope. Total RNA was extracted and the expression of type I and type III procollagen mRNA in splenic venous walls of portal hypertensive patients (n=20) was semi-quantitatively detected using reverse transcription-polymerase chain reaction (RT-PCR).RESULTS: Under optical microscope, splenic arterial intima was destroyed and internal elastic membrane and medial elastic fibers of the splenic arterial walls were degenerated and broken. Splenic venous intima became remarkably thick. Endothelia1 cells were not intact with formation of mural thrombus. The tunica media became thickened significantly due to hypertrophy of smooth muscles. Fibers and connective tissues were increased obviously. Under electron microscope, smooth muscle cells of the splenic arteries were degenerated and necrotized. Phenotypes of smooth muscle cells changed from constrictive into synthetic type. Red blood cells and platelets accumulated around the damaged endothelial cells. Synthetic smooth muscle cells were predominant in splenic veins and their cytoplasma had plentiful rough endoplasmic reticulum ribosomes and Golgi bodies. Along the vascular wall, a lot of collagen fibers were deposited, the intima was damaged and blood components accumulated. There was no significant difference in the expression of type I procollagen mRNA in splenic venous wall between the patients with portal hypertension and those without portal hypertension (P>0.05), but the expression of type III procoagen mRNA was significantly stronger in the patients with portal hypertension than in those without portal hypertension (P<0.01).CONCLUSION: Type III procollagen and collagen might be important extra-cellular matrix resulting in neointimal formation and vascular remodeling in the pathogenesis of portal hypertensive vasculopathy. The pathological changes in splenic arteries and veins exist in portal hypertension patients. There might be an interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy.

Pediatr Clin North Am 2006 Jun; 53(3): 493-512 (Read article online)

Mitsnefes MM

Hypertension is one of the most common health problems in the United States and a powerful independent risk factor for cardiovascular and renal disease. Until recently, the incidence of persistent hypertension in children has been low, with a range of 1% to 3%. Recent data indicate that over the last decade, however, average blood pressure levels have risen substantially among American children. Obesity and other lifestyle factors, such as physical inactivity and increased intake of high-calorie, high-salt foods, are thought to be responsible for this trend. Hypertension in children is currently recognized as an important health issue. There is increasing evidence that hypertension has its antecedents during childhood, because adult blood pressure often correlates with childhood blood pressure. Hypertension in children also is viewed as a significant risk factor for the development of cardiovascular disease in adulthood.

Anesth Analg 2006 Jun; 102(6): 1836-46 (Read article online)

White H, Cook D, Venkatesh B

The past decade has witnessed a resurgence of interest in the use of hypertonic saline for low-volume resuscitation after trauma. Preliminary studies suggested that benefits are limited to a subgroup of trauma patients with brain injury, but a recent study of prehospital administration of hypertonic saline to patients with traumatic brain injury failed to confirm a benefit. Animal and human studies have demonstrated that hypertonic saline has clinically desirable physiological effects on cerebral blood flow, intracranial pressure, and inflammatory responses in models of neurotrauma. There are few clinical studies in traumatic brain injury with patient survival as an end point. In this review, we examined the experimental and clinical knowledge of hypertonic saline as an osmotherapeutic agent in neurotrauma.

Heart 2006 May 22; (Read article online)

McElduff P, Jaefarnezhad M, Durrington PN

Objective To compare national and international recommendations for statin treatment in the primary prevention of cardiovascular disease in middle aged men. Design Application of the current American, British and European recommendations to results of a prospective study. Participants Men aged 49-65 years (n=1653), who participated in the Caerphilly Prospective Study. Main outcome measures Proportion who would receive statin treatment, the number needed to treat (NNT) to prevent one first cardiovascular (CVD) event (myocardial infarction and stroke) over 10 years and the potential number of events prevented over 10 years in the whole population (population impact) by the use of statins in accordance with each set of guidelines, assuming a reduction of risk in the range 10-50% using the observed events and base-line risk factors. Results There were 212 events. For an anticipated reduction in first CVD events of 30% with statin treatment, the NNT was 26.0, if the whole population was treated. The lowest NNT was 12.1 for the National Health Service Framework (NSF), achieved when only 14% of the men received a statin. However, this prevented the lowest number of events (19.2/212) and had the smallest population impact on CVD incidence (-9.1%). The American and earlier Joint British Societies guidelines, although giving NNT's of around 21 prevented more events and had a greater population impact of -21.6 to - 23.3%. They did, however, target some 60% of the male population. The British Hypertension Society guidelines and new Joint British Societies recommendations achieved the greatest population impact of -27% whilst maintaining the NNT at 22.2. They did, however, target three quarters of this population. Conclusion Even effective preventive therapy will have little impact in preventing disease if its deployment does not include those at typical risk. Whether cholesterol-lowering on such a scale should be attempted with medication raises philosophical, psychological and economic considerations, particularly in view of the high likelihood of individual benefit from statin treatment. More effective nutritional policies to reduce serum cholesterol on a population level and reduce the requirement statins in primary prevention should also be considered.

Biosci Biotechnol Biochem 2006 May; 70(5): 1118-26 (Read article online)

Nakano D, Ogura K, Miyakoshi M, Ishii F, Kawanishi H, Kurumazuka D, Kwak CJ, Ikemura K, Takaoka M, Moriguchi S, Iino T, Kusumoto A, Asami S, Shibata H, Kiso Y, Matsumura Y

Sesame peptide powder (SPP) exhibited angiotensin I-converting enzyme (ACE) inhibitory activity, and significantly and temporarily decreased the systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) by a single administration (1 and 10 mg/kg). Six peptide ACE inhibitors were isolated and identified from SPP. The representative peptides, Leu-Val-Tyr, Leu-Gln-Pro and Leu-Lys-Tyr, could competitively inhibit ACE activity at respective Ki values of 0.92 muM, 0.50 muM, and 0.48 muM. A reconstituted sesame peptide mixture of Leu-Ser-Ala, Leu-Gln-Pro, Leu-Lys-Tyr, Ile-Val-Tyr, Val-Ile-Tyr, Leu-Val-Tyr, and Met-Leu-Pro-Ala-Tyr according to their content ratio in SPP showed a strong antihypertensive effect on SHR at doses of 3.63 and 36.3 mug/kg, which accounted for more than 70% of the corresponding dosage for the SPP-induced hypotensive effect. Repeated oral administration of SPP also lowered both SBP and the aortic ACE activity in SHR. These results demonstrate that SPP would be a beneficial ingredient for preventing and providing therapy against hypertension and its related diseases.

Circulation 2006 May 22; (Read article online)

Elliott CG, Glissmeyer EW, Havlena GT, Carlquist J, McKinney JT, Rich S, McGoon MD, Scholand MB, Kim M, Jensen RL, Schmidt JW, Ward K

BACKGROUND: Vasoreactivity tests are fundamental in evaluating pulmonary arterial hypertension (PAH). Mutations of the transforming growth factor-beta type II receptor gene, BMPR2, predispose to the development of pulmonary hypertension and may alter the response to vasodilators. Previous investigations have not examined the relationship of BMPR2 mutations to vasoreactivity. METHODS AND RESULTS: We identified 133 consecutive unrelated patients with either idiopathic or familial PAH. Sixty-six patients were excluded because we lacked either DNA samples (n=18) or complete data from a vasoreactivity test (n=48). The remaining 67 patients were screened for BMPR2 DNA sequence variations, and specific variations were confirmed by gene sequencing. The vasoreactivity of patients with nonsynonymous BMPR2 variations was compared with that of patients without nonsynonymous BMPR2 variations. We found nonsynonymous BMPR2 variations in 27 of 67 patients with idiopathic (n=16 of 52) or familial (n=11 of 15) PAH. Vasoreactivity was identified in 3.7% of 27 patients with nonsynonymous BMPR2 variations and in 35% of 40 patients without nonsynonymous BMPR2 variations (P=0.003). Five of the 27 nonsynonymous variations occur commonly in healthy individuals. None of the remaining 22 patients with BMPR2 variations demonstrated vasoreactivity, and the analysis remained unchanged when we assumed that nonsynonymous BMPR2 variations were present in all 15 patients with familial PAH. CONCLUSIONS: Patients with familial or idiopathic PAH and nonsynonymous BMPR2 variations are unlikely to demonstrate vasoreactivity. Further trials are required to determine whether long-term therapy can be directed by tests for BMPR2 variations.

J Pharmacol Exp Ther 2006 May 22; (Read article online)

Pridjian G, Pridjian C, Danchuk S, Ianosi-Irimie M, Vu HV, Puschett JB

Preeclampsia is a disorder, which continues to exact a significant toll with respect to maternal morbidity and mortality as well as fetal wastage. Furthermore, the treatment of this disorder has not changed significantly in 50 years and is unsatisfactory. The use of diuretics in this syndrome is controversial because there is a concern related to potential baleful effects of volume contraction leading to a possible further decrement in the perfusion of the maternal-fetal unit. Metolazone is a diuretic/antihypertensive agent, which has a therapeutic effect on blood pressure (BP) in human essential hypertension without causing a natriuresis. We administered the drug in non-diuretic doses in a rat model of preeclampsia previously developed in this laboratory. The drug reduced BP without an accompanying natriuresis. Although there was a trend toward an improvement in intrauterine growth restriction (IUGR), as determined by litter size and the number of pups demonstrating malformations, the values did not reach statistical significance. We conclude that metolazone, in low dosage, is an effective antihypertensive in this rat model. These studies have implications for the treatment of the human disorder.

Mol Cell Biochem 2006 May 23; (Read article online)

Husain K, Mejia J, Lalla J

The study aim was to investigate the interaction of physical conditioning and chronic ethanol ingestion on blood pressure (BP), heart rate (HR), nitric oxide (NO) and oxidants/antioxidants balance in the plasma of rats. Male Fisher rats were divided into four groups of seven animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks; (2) ethanol (4 g kg(-1), orally) daily for 12 weeks; (3) exercise training on treadmill plus sucrose daily for 12 weeks and (4) exercise training on treadmill followed by ethanol (4 g kg(-1), orally) daily for 12 weeks. The body weight, BP and HR were recorded every week. The animals were sacrificed under ether anesthesia after 12 weeks, blood collected in heparinzed vials, plasma isolated and analyzed. The results show that exercise training significantly lowered the weight gain 6-12 weeks in ethanol treated rats compared to ethanol alone or control rats. The mean arterial BP was significantly elevated 6-12 weeks after ethanol ingestion without significant alterations in HR. Exercise training lowered the BP close to the normal control values in ethanol fed rats. Ethanol significantly decreased the plasma NO levels, reduced to oxidized glutathione ratio (GSH/GSSG) and antioxidant enzymes-superoxide dismutase (CuZn-SOD, and Mn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities while plasma NADPH oxidase activity and malondialdehyde (MDA) levels were significantly elevated compared to control. Exercise training significantly restored the depletion of plasma NO levels, GSH/GSSG ratio, and antioxidant enzyme activities and normalized the MDA levels and NADPH oxidase activity in the plasma of ethanol treated rats. The study concluded that physical conditioning attenuates the chronic ethanol-induced hypertension by augmenting the NO bioavailability and reducing the oxidative stress response in the plasma of rats.

J Head Trauma Rehabil 2006 May/June; 21(3): 260-271 (Read article online)

Kennedy RE, Livingston L, Marwitz JH, Gueck S, Kreutzer JS, Sander AM

OBJECTIVE: To determine characteristics of patients with complicated mild traumatic brain injury (CMTBI) on the inpatient rehabilitation unit and to accentuate limits of current classification systems for patients with mild TBI. DESIGN: Multicenter analysis of individuals with a Glasgow Coma Scale (GCS) score of 13 to 15 (lowest score in 24 h) and positive computed tomography findings admitted to inpatient rehabilitation for TBI. SETTING: 16 TBI Model System centers funded by the National Institute on Disability and Rehabilitation Research. PARTICIPANTS: 373 adults with CMTBI. MAIN OUTCOME MEASURES: Functional Independence Measure (FIM) and Disability Rating Scale (DRS) scores, length of stay, and medical complications. RESULTS: 16% of the sample experienced serious cranial complications (eg, cerebrospinal fluid leak, intracranial hypertension), with seizures being the most common during the course of inpatient rehabilitation. Most patients demonstrated substantial improvements on functional outcome measures during rehabilitation (mean admission FIM 68.2, discharge FIM 100.6; admission DRS 9.1, discharge DRS 4.8). Age, acute length of stay, and FIM score on rehabilitation admission were significant predictors of rehabilitation length of stay. Factors not predictive of rehabilitation duration were GCS score, ethnicity, gender, incidence of fractures, and incidence of cranial/noncranial complications. CONCLUSION: Despite favorable GCS scores, some patients with CMTBI suffer a variety of serious cranial and noncranial complications. Such patients appear to benefit from additional brain injury services offered in inpatient rehabilitation. Further study of the unique treatment needs of these patients is warranted.

Heart 2006 May 22; (Read article online)

Ingelsson E, Arnlöv J, Lind L, Sundström J

OBJECTIVE: The relation of the metabolic syndrome to incident heart failure (HF) is unknown. Thus, our aim was to explore the metabolic syndrome as a possible risk factor for development of HF. DESIGN: Community-based cohort study. SETTING: Uppsala, Sweden. PARTICIPANTS: We enrolled 2314 50-year-old men free from HF, myocardial infarction and valvular disease at baseline between 1970 and 1974, and they were followed until the age of 70. We used a modified National Cholesterol Education Program (NCEP) definition of the metabolic syndrome with body mass index in the place of waist circumference. MAIN OUTCOME MEASURE: First hospitalisation for heart failure. RESULTS: In multivariable Cox proportional hazards models adjusted for established risk factors for HF (hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking and body mass index), the presence at baseline of the metabolic syndrome (hazard ratio, 1.66; 95% confidence interval, 1.02-2.70) was a predictor of subsequent HF. This relation was even stronger when adjusting for the presence of an acute myocardial infarction during follow-up in addition to the other established risk factors for CHF (hazard ratio 1.80, 95% confidence interval 1.11-2.91). CONCLUSION: The metabolic syndrome was a significant predictor of HF, independent of established risk factors for HF including an interim myocardial infarction, during two decades of follow-up in a community-based sample of middle-aged men. This implies that the metabolic syndrome provides important risk information beyond that carried by established risk factors for HF.

Int J Obes (Lond) 2006 May 23; (Read article online)

Huang RC, Burke V, Newnham JP, Stanley FJ, Kendall GE, Landau LI, Oddy WH, Blake KV, Palmer LJ, Beilin LJ

Background:Features of the metabolic syndrome comprise a major risk for cardiovascular disease and will increase in prevalence with rising childhood obesity. We sought to identify early life influences on development of obesity, hypertension and dyslipidemia in children.Methods and results:Cluster analysis was used on a subset of a longitudinal Australian birth cohort who had blood samples at age 8 (n=406). A quarter of these 8-year-olds fell into a cluster with higher body mass index, blood pressure (BP), more adverse lipid profile and a trend to higher serum glucose resembling adult metabolic syndrome. There was a U-shaped relationship between percentage of expected birth weight (PEBW) and likelihood of being in the high-risk cluster. The high-risk cluster had elevated BP and weight as early as 1 and 3 years old. Increased likelihood of the high-risk cluster group occurred with greatest weight gain from 1 to 8 years old (odds ratio (OR)=1.4, 95% confidence interval (CI)=1.3-1.5/kg) and if mothers smoked during pregnancy (OR=1.82, CI=1.05-3.2). Risk was lower if children were breast fed for >/=4 months (OR=0.6, 95% CI=0.37-0.97). Newborns in the upper two quintiles for PEBW born to mothers who smoked throughout pregnancy were at greatest risk (OR=14.0, 95% CI=3.8-51.1) compared to the nadir PEBW quintile of non-smokers.Conclusion:A U-shaped relationship between birth weight and several components of the metabolic syndrome was confirmed in a contemporary, well-nourished Western population of full-term newborns, but post-natal weight gain was the dominant factor associated with the high-risk cluster. There was a prominence of higher as well as lowest birth weights in those at risk. Future health programs should focus on both pre- and post-natal factors (reducing excess childhood weight gain and smoking during pregnancy), and possibly the greatest benefits may arise from targeting the heaviest, as well as lightest newborns, especially with a history of maternal smoking during pregnancy.International Journal of Obesity advance online publication, 23 May 2006; doi:10.1038/sj.ijo.0803394.

Rheum Dis Clin North Am 2006 May; 32(2): 275-93 (Read article online)

Becker MA, Jolly M

After introduction of urate-lowering therapy, asympotomatic hyperuricemia was treated with allopurinol or uricosuric agents in the belief that hyperuricemia and/or gout caused chronic kidney disease. Epidemiologic studies in the 1970s, however, failed to confirm the view that hyperuricemia and gout were independent risk factors for chronic kidney disease. As a result, urate-lowering pharmacotherapy is generally not recommended at the present time in the management of asymptomatic hyperuricemia even though recent epidemiological, experimental, and clinical studies have prompted reexamination of a causal role for hyperuricemia (with or without gout) in chronic kidney disease as well as other important disorders including cardiovascular disease, hypertension, and metabolic syndrome. The issue of such a role remains unresolved and this article reviews the current status of the relationship between hyperuricemia and associated disorders.

Endocr J 2006 May 23; (Read article online)

Makino S, Iwata M, Fujiwara M, Ike S, Tateyama H

A 55-year-old female was admitted to our hospital with severe hypertension (274/140 mmHg). Endocrinological examination revealed that her plasma levels of norepinephrine (NE) was elevated with high levels of urinary NE, normetanephrine and vanillylmandelic acid (VMA), suggesting the presence of pheochromocytoma. However, neither computed tomography nor MIBG scintigraphy detected any catecholamine-producing tumor in or outside the adrenal glands. She was screened with full polysomnography because of heavy snoring, and the diagnosis of severe obstructive sleep apnea syndrome (OSAS) was made. She was treated with calcium channel blocker for three weeks, but severe hypertension persisted. After treatment with nasal continuous positive airway pressure (CPAP) was added, her blood pressure gradually lowered week by week. Concomitantly, the levels of plasma and urinary NE, urinary normetanephrine and urinary VMA were normalized following nasal CPAP therapy for 2 weeks. Additional treatments with alpha-adrenergic blocker further decreased her home blood pressure. After a year, she continued nasal CPAP therapy and her blood pressure was nearly below 160/100 mmHg. Urinary NE level was slightly above normal range and other catecholamines stayed within the normal range. This case shows that patients with OSAS could develop severe hypertension through elevated sympathetic tone, mimicking pheochromocytoma. Nasal CPAP therapy is recommended not only to improve hypertension and catecholamine excess but also to distinguish the condition from pheochromocytoma.

J Hum Hypertens 2006 May 18; (Read article online)

Conen D, Zeller A, Dieterle T, Martina B

The aim of this study was to assess the contribution of increased concentrations of high-sensitivity C-reactive protein (hsCRP) and echocardiography to risk stratification according to the 2003 European guidelines for the management of arterial hypertension in patients with untreated hypertension. A total of 207 consecutive medical outpatients with untreated hypertension were included. History and clinical examination, electrocardiography, laboratory analyses including the measurement of hsCRP and echocardiography were performed in all patients. Patients were classified into four risk groups with and without using echocardiography and hsCRP concentrations of at least 10 mg/l according to the 2003 guidelines for the management of hypertension. The majority of the 207 patients (81%) were at moderate or high cardiovascular risk before adding echocardiography and/or hsCRP to the risk stratification process. When echocardiography was included, only three patients were reclassified from the moderate added risk to the high added risk group. Adding hsCRP concentrations of at least 10 mg/l had no impact on risk stratification. Using an hsCRP cutoff level of 3 mg/l, one patient was at moderate instead of low added risk, eight patients were at high instead of moderate added risk and one patient was at very high instead of high added risk. We conclude that hsCRP at the proposed cutoff level of 10 mg/l has no impact on risk stratification in outpatients with untreated hypertension. An hsCRP cutoff level of 3 mg/l may be more suitable for risk stratification. Finally, our data suggest that depending on the population studied, there is minimal impact of echocardiography on risk stratification.Journal of Human Hypertension advance online publication, 18 May 2006; doi:10.1038/sj.jhh.1002048.

Acta Diabetol 2006 May; 43(1): 19-21 (Read article online)

Papanas N, Heliopoulos I, Piperidou H, Maltezos E

Combined palsies of cranial nerves, especially of the oculomotor nerves, are distinctly uncommon, even in patients with diabetes mellitus. We present a patient with type 2 diabetes mellitus, arterial hypertension and hyperlipidaemia, who had simultaneous oculomotor and trochlear nerve palsies. An MRI scan showed multiple brainstem ischaemic infarcts. The patient was treated with intensified insulin regimen and clopidogrel. Symptoms gradually improved, and at 9 months there was no further improvement.