Incidence and factors associated with overweight and obesity, and hypertensive disorder, among staff in a private healthcare setting: a retrospective cohort study.

OBJECTIVE: To determine the incidence and factors associated with overweight and obesity, and hypertensive disorder, among staff in a private healthcare setting. MATERIAL AND METHOD: The present retrospective cohort study examined the computerized data of Bumrungrad International (BI) Hospital staff that had undergone pre-employment and annual/bi-annual check-ups, between January 2000 and June 2006. RESULTS: Data for the 3,678 staff surveyed comprised 7,338 visits, with a median follow-up time of 1.9 years; 81.9% were females, and the mean age (SD) was 27.1 (6.8) years. On their first visit, 8.5% could be classified as overweight or obese (Body Mass Index-[BMI] of 25.0+ kg/m2). The overall incidence of these conditions was 22.2/1,000 person-years (95%; Confidence Interval [CI] = 18.8-26.1). Cox's regression analysis revealed that incidence increased with age (Relative Hazard [RH] = 4.4 for age 20-44 years [95% -CI 1.6-12.2], and RH = 8.2 [95% CI 2.4-27.5] for age > or = 45 years, reference: < 20 years), but decreased among the registered nurses and ancillary professional staff (RH = 0.3, 95% CI 0.2-0.6). At cohort entry, 41.0% could be classified as pre-hypertensive (blood pressure 120-139/> 80-89 mmHg) and 1.9% as stages I and II hypertension. The overall incidence of hypertensive disorder was 16.9/1,000 person-years (95%; CI 13.6-20.9). Baseline pre-hypertensive (RH 4.9, 95%; CI 2.6-9.3), males (RH 1.7, 95%; CI 1.1-2. 7), age > or = 45 years (RH3.2, 95%; CI 1.0-10.5), and BMI (RH ranges 3.3-6 4) were identified as independent risk factors for incident hypertension. In addition, 2.5% were HBsAg-positive, and 33.3% had HBsAb antibody CONCLUSION: The present retrospective cohort study was instituted in a private healthcare setting, information generated resulted in changes to the health-promotion programs of the organization.

Prostacyclin protects against elevated blood pressure and cardiac fibrosis.

Specific inhibitors of COX-2 have been associated with increased risk for cardiovascular complications. These agents reduce prostacyclin (PGI2) without affecting production of thromboxane (Tx) A2. While this abnormal pattern of eicosanoid generation has been implicated in the development of vascular disease associated with COX-2 inhibition, its role in the development of hypertension, the most common cardiovascular complication associated with COX-2 inhibition, is not known. We report here that mice lacking the receptor for PGI2 (IPKOs) develop salt-sensitive hypertension, cardiac hypertrophy, and severe cardiac fibrosis. Coincidental deletion of the TxA2 (TP) receptor does not prevent the development of hypertension, but cardiac hypertrophy is ameliorated and fibrosis is prevented in IPTP double knockouts (DKOs). Thus, deletion of the IP receptor removes a constraint revealing adverse cardiovascular consequences of TxA2. Our data suggest that adjuvant therapy that blocks unrestrained Tx actions might protect against end-organ damage without affecting blood pressure in patients taking COX-2 inhibitors.

Increased blood pressure in mice lacking cytochrome P450 2J5.

The cytochrome P450 (CYP) enzymes participate in a wide range of biochemical functions, including metabolism of arachidonic acid and steroid hormones. Mouse CYP2J5 is abundant in the kidney where its products, the cis-epoxyeicosatrienoic acids (EETs), modulate sodium transport and vascular tone. To define the physiological role of CYP2J5 in the kidney, knockout mice were generated using a conventional gene targeting approach. Cyp2j5 (-/-) mice develop normally and exhibit no overt renal pathology. While renal EET biosynthesis was apparently unaffected by the absence of CYP2J5, deficiency of this CYP in female mice was associated with increased blood pressure, enhanced proximal tubular transport rates, and exaggerated afferent arteriolar responses to angiotensin II and endothelin I. Interestingly, plasma 17beta-estradiol levels were reduced in female Cyp2j5 (-/-) mice and estrogen replacement restored blood pressure and vascular responsiveness to normal levels. There was no evidence of enhanced estrogen metabolism, or altered expression or activities of steroidogenic enzymes in female Cyp2j5 (-/-) mice, but their plasma levels of luteinizing hormone and follicle stimulating hormone were inappropriately low. Together, our findings illustrate a sex-specific role for CYP2J5 in regulation of blood pressure, proximal tubular transport, and afferent arteriolar responsiveness via an estrogen-dependent mechanism.

Diarrhea among children admitted to a private tertiary-care hospital, Bangkok, Thailand: a case series.

We report here a case series of pediatric diarrhea cases admitted to a private tertiary-care hospital in Bangkok, Thailand. Retrospective data were collected from computerized medical records of 2,001 children with diarrhea (80.9% Thai), ages birth to 14 years, admitted to our facility during 2000-2005. The most common symptom leading to admission was vomiting (34.6%), while the most common sign was dehydration (63.6%). The largest proportion was comprised of toddlers (45.4%), followed by infants (24.2%). Of the total 2,564 admissions, 1,874 (73.1%) stool samples were collected and examined for red blood cells (RBC) and white blood cells (WBC); 57.1% and 70.6% were negative for RBC and WBC, respectively. Of the 1,878 blood specimens collected for electrolytes, 21.6% show acidosis. Of 1,793 stool specimens collected, the majority revealed normal flora (72.9%). Enteropathogenic Escherichia coli (EPEC) were seen in 10.8%. Campylobacter jejuni was found in only 2.9% of specimens, while of 1,065 specimens tested for rotavirus antigen, 23.9% were positive. In addition to bacterial cultures and their anti-microbial sensitivities, factors associated with rotavirus infection, C. jejuni, and metabolic acidosis, were also explored in this study. Rotavirus infections were more likely to be associated with children older than toddlers (3-14 years old), being admitted within the first day of the symptoms, those who were more acidotic, and was more common in the first 3 months of each year. Our data were little different from community-acquired infections reported among the general population.

Anabolic effects of a G protein-coupled receptor kinase inhibitor expressed in osteoblasts.

G protein-coupled receptors (GPCRs) play a key role in regulating bone remodeling. Whether GPCRs exert anabolic or catabolic osseous effects may be determined by the rate of receptor desensitization in osteoblasts. Receptor desensitization is largely mediated by direct phosphorylation of GPCR proteins by a family of enzymes termed GPCR kinases (GRKs). We have selectively manipulated GRK activity in osteoblasts in vitro and in vivo by overexpressing a GRK inhibitor. We found that expression of a GRK inhibitor enhanced parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor-stimulated cAMP generation and inhibited agonist-induced phosphorylation of this receptor in cell culture systems, consistent with attenuation of receptor desensitization. To determine the effect of GRK inhibition on bone formation in vivo, we targeted the expression of a GRK inhibitor to mature osteoblasts using the mouse osteocalcin gene 2 (OG2) promoter. Transgenic mice demonstrated enhanced bone remodeling as well as enhanced urinary excretion of the osteoclastic activity marker dexoypyridinoline. Both osteoprotegrin and OPG ligand mRNA levels were altered in calvaria of transgenic mice in a pattern that would promote osteoclast activation. The predominant effect of the transgene, however, was anabolic, as evidenced by an increase in bone density and trabecular bone volume in the transgenic mice compared with nontransgenic littermate controls.

Hypertension and impaired glycine handling in mice lacking the orphan transporter XT2.

A family of orphan transporters has been discovered that are structurally related to the Na(+)-Cl(-)-dependent neurotransmitter transporters, including the dopamine transporter. One member of this family, the mouse XT2 gene, is predominantly expressed in the kidney and has 95% homology to rat ROSIT (renal osmotic stress-induced Na(+)-Cl(-) organic solute cotransporter). To study the physiological functions of this transporter, we generated XT2-knockout mice by gene targeting. XT2(-/-) mice develop and survive normally with no apparent abnormalities. To attempt to identify potential substrates for XT2, we screened urine from XT2-knockout mice by high-pressure liquid chromatography and mass spectrometry and found significantly elevated concentrations of glycine. To study glycine handling, XT2(+/+) and XT2(-/-) mice were injected with radiolabeled glycine, and urine samples were collected to monitor glycine excretion. After 2 h, XT2(-/-) mice were found to excrete almost twice as much glycine as the XT2(+/+) controls (P = 0.03). To determine whether the absence of the XT2 transporter affected sodium and fluid homeostasis, we measured systolic blood pressure by computerized tail-cuff manometry. Systolic blood pressure was significantly higher in XT2(-/-) mice (127 +/- 3 mmHg) than in wild-type controls (114 +/- 2 mmHg; P < 0.001). This difference in systolic blood pressure was maintained on high and low salt feeding. To examine whether the alteration in blood pressure and the defect in glycine handling were related, we measured systolic blood pressure in the XT2(-/-) mice during dietary glycine supplementation. Glycine loading caused systolic blood pressure to fall in the XT2(-/-) mice from 127 +/- 3 to 115 +/- 3 mmHg (P < 0.001), a level virtually identical to that of the wild-type controls. These data suggest that the XT2 orphan transporter is involved in glycine reabsorption and that the absence of this transporter is sufficient to cause hypertension.

Intussusception in a private tertiary-care hospital, Bangkok, Thailand: a case series.

This was a retrospective case series study of patients with intussusception at a private tertiary-care hospital in Bangkok, Thailand. The computerized hospital records of all 94 children aged 0-14 years diagnosed with intussusception from 2000 to 2005 were reviewed. About half (51.1%) were males, 23.4% were less than 1 year old. Most (78.7%) were Thai nationals. The highest case frequency was in August (n=12, Poisson means = 7.8, 95% confidence interval 6.3-9.6). Of these, none had the classical triad of vomiting, colicky pain, and mucous bloody stools. Only 12.8% had fever; abdominal mass was detected in 4.3%, and 4.3% had increased bowel sounds, while 34.0% had no specific signs. The most frequent site of intussusception was the ileocolic (62.6%). Stool cultures for bacteria and stool for rotavirus antigen obtained in some cases revealed no significant findings. Of the cases, 10 (10.6%) had spontaneous reduction, 84 (89.4%) underwent barium enema intervention, 10 of the latter (11.9%) required further surgical intervention. There were no mortalities during the observation period. There were 10 recurrent events in this series. The 7-day recurrence-free probability was 84.9% (95% CI 49.2, 96.3%). This study provides baseline data regarding intussusception in Thailand which may be useful for future epidemiological and/or clinical studies.

Galphaq-dependent signaling cascades stimulate water-seeking behavior.

We used the mouse nephrin promoter to express a constitutively active Galphaq [Galphaq(Q>L)] transgene in mice. As previously reported, the transgene was expressed in kidney, pancreas, and brain, and the kidney phenotype was characterized by albuminuria and reduced nephron mass. Additional studies revealed a second phenotype characterized by polyuria and polydipsia. The polyuric phenotype was not caused by abnormal glucose metabolism or hypercalcemia but was accompanied by reduced urinary concentrating ability. Additional studies found that 1) water restriction was associated with an appropriate increase in serum vasopressin levels in transgenic (TG) mice; 2) the urinary concentrating defect was not corrected by administration of desamino-d-arginine vasopressin (DDAVP); and 3) papillary length was similar in TG and non-TG mice. To examine the renal response to DDAVP at the molecular level, we monitored aquaporin 2 (AQP2) and vasopressin V2 receptor (V2R) mRNA levels in mouse kidney. Consistent with the known effects of vasopressin, administration of DDAVP caused a decrease in V2R mRNA levels and an increase in AQP2 mRNA levels in both TG and non-TG animals, suggesting an appropriate renal response to DDAVP in the TG mice. To determine whether the urine concentrating abnormality was the result of primary polydipsia, water intake by TG mice was restricted to the amount ingested by non-TG animals. After 5 days, urinary concentrating ability was similar in TG mice and non-TG littermate controls. These data are consistent with the notion that expression of the Galphaq(Q>L) transgene in the brain induced primary polydipsia in the TG mice.

Role for thromboxane receptors in angiotensin-II-induced hypertension.

To evaluate the role of thromboxane in hypertension and its complications, we studied mice with targeted disruption of the TXA2 receptor gene in an angiotensin-II-dependent model of hypertension. To determine whether genetic background might alter the physiological actions of the TP receptor, we studied two lines of TP knockout (Tp-/-) mice with distinct genetic backgrounds (C57BL/6 and BALB/c). During chronic angiotensin II infusion (1000 ng/kg per minute x 28 days by subcutaneous osmotic pump), TP deficiency prevented mortality in the C57BL/6 background but not in the BALB/c strain. Chronic angiotensin II infusion also caused a rapid and significant increase in blood pressure in wild-type (WT) C57BL/6 and BALB/c animals, which was significantly attenuated in Tp-/- mice on either background. After 28 days of infusion, cardiac hypertrophy only occurred in the C57BL/6 strain: heart/body weight ratio increased by 57%+/-8% in WT mice compared with 17%+/-6.5% for the Tp-/- mice (P<0.01). Chronic angiotensin II infusion caused albuminuria only in the C57BL/6 strain, and TP deficiency did not alter its development. Cyclooxygenase-1 knockout mice also had attenuated blood pressure increase during chronic angiotensin II infusion, suggesting that cyclooxygenase-1 metabolites are involved in angiotensin-II-dependent hypertension. Thus, on the C57BL/6 background, TP receptors contribute to cardiac hypertrophy but not proteinuria. However, irrespective of genetic background, the TP receptor makes a robust contribution to the pathogenesis of angiotensin II-dependent hypertension.