Estimating chronic hepatitis C prognosis using transient elastography-based liver stiffness: A systematic review and meta-analysis.

Chronic hepatitis C (CHC) is a leading cause of hepatic fibrosis and cirrhosis. The level of fibrosis is traditionally established by histology, and prognosis is estimated using fibrosis progression rates (FPRs; annual probability of progressing across histological stages). However, newer noninvasive alternatives are quickly replacing biopsy. One alternative, transient elastography (TE), quantifies fibrosis by measuring liver stiffness (LSM). Given these developments, the purpose of this study was (i) to estimate prognosis in treatment-naïve CHC patients using TE-based liver stiffness progression rates (LSPR) as an alternative to FPRs and (ii) to compare consistency between LSPRs and FPRs. A systematic literature search was performed using multiple databases (January 1990 to February 2016). LSPRs were calculated using either a direct method (given the difference in serial LSMs and time elapsed) or an indirect method given a single LSM and the estimated duration of infection and pooled using random-effects meta-analyses. For validation purposes, FPRs were also estimated. Heterogeneity was explored by random-effects meta-regression. Twenty-seven studies reporting on 39 groups of patients (N = 5874) were identified with 35 groups allowing for indirect and 8 for direct estimation of LSPR. The majority (~58%) of patients were HIV/HCV-coinfected. The estimated time-to-cirrhosis based on TE vs biopsy was 39 and 38 years, respectively. In univariate meta-regressions, male sex and HIV were positively and age at assessment, negatively associated with LSPRs. Noninvasive prognosis of HCV is consistent with FPRs in predicting time-to-cirrhosis, but more longitudinal studies of liver stiffness are needed to obtain refined estimates.

Defining the decision problem: a scoping review of economic evaluations for Clostridioides difficile interventions.

BACKGROUND: Clostridioides difficile infection is the leading cause of healthcare-associated infectious diarrhoea. Several preventative and treatment interventions exist; however, decisions for their use are typically made independent of other interventions along the care pathway. AIM: To assess how the scope of the decision problem is defined in economic evaluations of C. difficile interventions. METHODS: A scoping review was conducted following the Joanna Briggs Institute framework using a comprehensive literature search with C. difficile and economic evaluation as key search concepts. Study selection and extraction were performed independently by two reviewers. An in-depth analysis of all cost-utility and cost-effectiveness analyses was conducted. Care pathway domains (i.e. infection prevention and control, antimicrobial stewardship programmes, prevention, diagnostics, treatment) were defined iteratively, and each study was classified according to the scope of the decision problem: (i) one intervention, one domain; (ii) one intervention, multiple domains; (iii) multiple interventions, one domain; and (iv) multiple interventions, multiple domains. RESULTS: In total, 3886 studies were identified. Of these, 116 studies were included in the descriptive overview, and 46 were included in the in-depth analysis. Most studies limited the scope of the decision problem to one intervention (43/46; 93%). Only three studies (3/46; 7%) assessed multiple interventions - either as bundled vs standalone interventions for prevention (i.e. a single domain), or as sequences of treatments for initial and recurrent infection (i.e. multiple domains). No study assessed multiple interventions across prevention and treatment domains. CONCLUSIONS: Economic evaluations for C. difficile infection assess narrowly defined decision problems which may have implications for optimal healthcare resource allocation.

Human growth hormone receptor (GHR) expression in obesity: II. Regulation of the human GHR gene by obesity-related factors.

BACKGROUND AND METHODS: In our previous analyses, we found significantly lower levels of growth hormone receptor (GHR) mRNA in adipose tissues of obese than in those of lean individuals, suggesting that idiopathic obesity involves GH resistance due to decreased GHR availability. To understand the mechanism(s) behind this downregulation, we performed an in silico analysis of the three most relevant GHR gene promoters, which revealed putative response elements (REs) for a number of obesity adipose-associated factors, including tumor necrosis factor-alpha (TNFα), hypoxia-inducible factor-1-alpha (HIF-1α) and glucocorticoids. We then characterized the dose-dependent effects of these factors on GHR expression in HEK293 cells and in mature human SGBS (Simpson-Golabi-Behmel syndrome) adipocytes using quantitative reverse transcriptase-PCR and assessed the function of their putative REs by luciferase-reporter assays, site-directed mutagenesis and chromatin immunoprecipitation (ChIP) assays. RESULTS: TNFα treatments significantly reduced GHR mRNA levels and GHR promoter activities at doses ≥ 10 ng ml(-1) in both cell lines. Transient overexpression of HIF-1α or exposure to the hypoxia mimetic CoCl(2) significantly increased GHR mRNA levels and promoter activities. Dexamethasone had biphasic effects: there was a significant increase in GHR mRNA levels at 10(-10) M and in promoter activities at 10(-10) and 10(-8) M, whereas a significant decrease in both mRNA levels and promoter activities occurred at 10(-6) M. Site-directed mutagenesis of the putative nuclear factor-κB, HIF-1α and glucocorticoid REs resulted in the loss of these effects, whereas ChIP analysis confirmed specific transcription factor-promoter interactions. CONCLUSIONS: Our results suggest that the increased activity of TNFα, HIF-1α and glucocorticoids in obese adipose tissues could alter GHR gene transcription through specific REs and that TNFα may be involved in the development of GH resistance.

Human growth hormone receptor (GHR) expression in obesity: I. GHR mRNA expression in omental and subcutaneous adipose tissues of obese women.

OBJECTIVES: Growth hormone (GH)-deficient individuals display increased adiposity that can be effectively reduced by GH therapy because of GH's lipolytic effects. However, similar GH treatments of individuals with idiopathic obesity (not associated with an endocrinopathy/syndrome) have had little success. We hypothesized that this form of obesity may be associated with GH resistance at the level of the adipocyte because of reduced GH receptor (GHR) expression. SUBJECTS AND METHODS: We studied GHR expression in omental and subcutaneous fat tissues from a cohort of 55 women ranging from lean to obese by various adiposity parameters. mRNA levels of total GHR and the dominant-negative truncated GHR(1-279) (trGHR) form were assayed by quantitative reverse transcriptase-PCR. Associations between adiposity measures and GHR levels as well as trGHR/GHR ratios were analyzed. RESULTS: Total GHR mRNA expression was 2-3-fold lower in omental as well as subcutaneous adipose tissues of obese compared with lean women (P ≤ 0.05-0.001). Lean individuals expressed higher GHR mRNA levels in omental fat compared with subcutaneous (P ≤ 0.01); in obese women, this depot-specific difference was lost. Omental and subcutaneous adipose GHR mRNA levels displayed significant negative correlations with a spectrum of indicators of obesity while, in subcutaneous fat, there was a significantly higher trGHR/GHR ratio with increasing adiposity (P ≤ 0.05). CONCLUSION: These results support our hypothesis that, with obesity, there is lower GHR expression in the adipocyte, and suggest one possible explanation why GH supplementation is not an effective treatment for individuals with idiopathic obesity.

Superficial cell differentiation during embryonic and postnatal development of mouse urothelium.

After drastic urothelial destruction around birth and around postnatal day 6, mouse urothelial renewal starts each time de novo. The differentiation of superficial cells during urothelial restoration was followed for the first time from embryonic day 15 to postnatal day 6 by the detection of differentiation markers: cytokeratins, uroplakins and apical membrane specialization. The differentiation markers of short-lived superficial cells were studied before and after urothelial destruction. Three distinctive types of superficial cells, typical for certain developmental period, were characterised: cells at low differentiation stage with microvilli and cilia, expressing CK7 and CK18, detected on embryonic day 15; cells at advanced differentiation stage with star-like arrangement of prominent membrane ridges, expressing CK7 and CK20, present between the two urothelial destruction events; highly differentiated cells with typically jagged apical surface, expressing CK7 and CK20, found twice during development. This cell type appears for the first time on embryonic day 18 as the terminal stage of embryonic differentiation. It was found again on postnatal day 6 as an initial stage of differentiation, leading toward terminally differentiated cells of the adult urothelium. Our work proves that apical membrane specialization is the most valuable differentiation marker of superficial cells.

Risk factors for development of diabetic nephropathy and retinopathy in Jewish IDDM patients.

Risk factors associated with diabetic microvascular complications, with special reference to ethnic origin, were looked for in 231 young Jewish insulin-dependent diabetes mellitus (IDDM) patients with duration of diabetes greater than or equal to 10 yr. Median age at diagnosis of diabetes was 9.2 yr (range 0.04-26.2 yr), and median duration of the disease was 15.3 yr (range 10.0-37.2 yr). Sixty-three percent of the patients were Ashkenazi Jews, and 37% were non-Ashkenazi Jews. HbA1 was evaluated every 3 mo in the last 10 yr of follow-up, and albumin excretion rate was tested in three 24-h urine collections. Direct and indirect ophthalmoscopy was performed every year since diagnosis of diabetes, and if retinal pathology was suspected, color photographs were taken. Microalbuminuria was detected in 31% and macroalbuminuria in 7% of the patients. Nonproliferative and proliferative retinopathy was found in 44 and 12% of the patients, respectively. On logistic regression analysis, two variables were significantly and independently associated with diabetic nephropathy--non-Ashkenazi origin and mean HbA1 values over the first 5 of 10 yr of follow-up. Variables significantly and independently related to diabetic retinopathy were non-Ashkenazi origin, mean HbA1 values over the last 10 yr of follow-up, and duration of diabetes. Because non-Ashkenazi Jews in Israel are of lower socioeconomic status than Ashkenazi Jews, we stratified our patients according to their socioeconomic parameters, median HbA1 values, and duration of diabetes. Non-Ashkenazi patients were at a higher risk to develop complications in all strata.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma concentrations, renal excretion, and tissue release of prostaglandins in the rat with dexamethasone-induced hypertension.

This study was designed to investigate whether the hypertension produced by dexamethasone in the rat is associated with a deficit in circulating and renal prostaglandin E2 (PGE2) and PGI2, PGs that are presumed to contribute to antihypertensive mechanisms. The administration of dexamethasone (2.5 mg kg-1 week-1, sc) increased systolic blood pressure by 41 +/- 6 mm Hg (P less than 0.05) after 14 days of treatment, associated with elevations of urine volume and fluid intake and loss of body weight. The glucocorticoid, however, had no effect on the plasma concentration, urinary excretion, or vascular and renal tissue release of immunoreactive 6-keto-PGF1 alpha, a PGI2 metabolite. In contrast, dexamethasone increased (P less than 0.05) the plasma PGE2 concentration by 157% and PGE2 urinary excretion by 134% after 14 days of treatment. However, the basal release of immunoreactive PGE2 as well as the angiotension II-induced release of radiolabeled arachidonic acid and PGs from renal medulla slices incubated in Krebs solution were diminished in rats receiving dexamethasone. The steroid also reduced to about 60% (P less than 0.05) of the control value the activity in renal homogenates of 15-hydroxyprostaglandin dehydrogenase (PGDH), a major PG-catabolizing enzyme, without affecting the activity of the enzyme in the lung. Hence, the increased plasma concentration and renal excretion of PGE2 caused by dexamethasone in the face of reduced renomedullary production of the PG is presumably related to diminished degradation in the kidney and perhaps in other extrapulmonary tissues. Altogether, this study demonstrates that the hypertension induced by dexamethasone in the rat is not associated with a deficit in circulating and renal PGE2 and PGI2.

Biphasic effect of dexamethasone on urinary prostaglandins in rats: relation to alterations in renal medulla triglycerides and prostaglandin metabolism.

This study was designed to characterize the time course of the effects of dexamethasone (2.5 mg kg-1 week-1, sc) on the renal arachidonate-prostaglandin (PG) system and to define the effect of the steroid on the interstitial cells of the renal inner medulla (RIC). The RIC are rich in triglycerides, which, due to their high content of arachidonic acid, may be a source of arachidonate for PG synthesis during conditions of phospholipase inhibition. After 1 day of dexamethasone treatment, the urinary excretion of PGE2 and PGF2 alpha was reduced to about 50% of the control value (P less than 0.05), and angiotensin II-induced release of arachidonic acid and PGs from renal medulla slices was blunted (P less than 0.05). In contrast, dexamethasone treatment did not affect ionophore A23187-induced release of PGs and arachidonic acid from renal medulla slices. By day 3 of dexamethasone treatment, urinary excretion of PGE2 and PGF2 alpha had returned to control levels, and by days 5 and 14 the excretion rates of both were clearly increased (P less than 0.05). The rise in urinary PG excretion was accompanied by a reduction of renal 15-hydroxyprostaglandin dehydrogenase activity, augmentation of renal medulla microsomal PG synthetase activity, and diminution of renal medulla triglycerides, the latter associated with a reduction in the number of RIC and of RIC osmiophilic granules. This study demonstrates that the effects of dexamethasone on urinary PG are biphasic; this may reflect the changing balance between the opposing actions of the steroid on renal PG-synthesizing and catabolizing enzymes and the inhibitory effect on the synthesis of renal PG that is linked to activation of specific renal lipases by endogenous factors such as angiotensin II.

Ovarian angiotensin-converting enzyme activity in humans: relationship to estradiol, age, and uterine pathology.

The present study was designed to measure angiotensin-converting enzyme (ACE) activity in the human ovary and in serum and to relate this activity to age, serum estradiol levels, and uterine and endometrial pathology. ACE activity was determined in 56 females by a radiometric assay using [3H]hippuryl-glycyl-glycine as substrate. Ovarian ACE activity, but not serum ACE, was found to increase with age (P < 0.01) and was significantly greater in postmenopausal subjects (n = 31; 1.35 +/- 0.05 nmol/mg.min) than in subjects with active ovaries (n = 21; 0.65 +/- 0.2 nmol/mg.min; P = 0.0033). Ovarian ACE activities in fertile women in the preovulatory phase (n = 14) and the postovulatory phase (n = 7) were not statistically different (0.66 +/- 0.23 and 0.63 +/- 0.17 nmol/mg.min, respectively). Serum ACE activities were similar in females with active and nonactive ovaries (87.6 +/- 5.0 vs. 81.7 +/- 5.3 nmol/mL-min, respectively). Serum estradiol levels in fertile women were significantly higher than those in postmenopausal women (P = 0.0023). Serum estradiol levels were negatively correlated with age (r = -0.46; P = 0.0041) and were not correlated with either serum ACE activity (r = 0.080; P = NS) or ovarian ACE activity. In summary, human ovarian ACE activity, but not serum ACE, is positively correlated with age. Serum estradiol levels decrease with age, but are not correlated with either ovarian or serum ACE activity. Endogenous serum estradiol levels had no apparent effect on ovarian or serum ACE activity. The presence of uterine pathology affects ovarian ACE activity. The cause of the increased ovarian ACE activity is not clear, but may be related to the aging process.

Diurnal rhythm of prostanoid secretion from bone/marrow organ in the rat.

The secretion of prostanoids from an adult diaphysial rat bone organ was assessed throughout a 24 h period at 4 h intervals as well as the 24 h activities of bone alkaline phosphatase isoenzyme and serum corticosterone levels. Femurs were removed from 16 rats at each interval and incubated in the absence or presence of indomethacin (100 micrograms). The levels of prostaglandin E2 (PGE2) prostaglandin F2 alpha (PGF2 alpha), and the stable metabolites of thromboxane and prostacyclin, thromboxane B2 (TxB2), and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) were measured by radioimmunoassay (RIA). The patterns for each of the variables was subjected to cosinor analysis for predetermined various periods. The chronograms obtained indicated that PGF2 alpha, PGE2, and TxB2 showed 24 h rhythms with computed peak hour acrophases at 1700, 1800, and 2200 h, respectively, and prostacyclin demonstrated a 19 h rhythm with a peak secretion at 1100 h. Corticosterone levels and bone alkaline phosphatase isoenzyme activity in the serum were at peak at 1630 and 2200 h, and at nadir at 0500 and 1000 h, respectively, both exhibiting 24 h rhythms similar to those of PGF2 alpha, PGE2, and TxB2. Bone alkaline phosphatase isoenzyme activity in the femurs' incubation media showed a 12 h diurnal rhythm with peaks at 1230 and 2330 h and nadirs at 0600 and 2330 h (p < 0.01). In summary, this study demonstrated for the first time a 24 h rhythm of prostanoid secretion from diaphysial bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of angiotensin converting enzyme by ramipril in serum and tissue of man.

Studies in animal models have indicated that ramipril is a potent inhibitor of angiotensin converting enzyme (ACE) in serum and tissue. In our study, the normal range of ACE activity and the inhibitory effect of short-term oral administration of ramipril on ACE activity in human serum and tissue samples of renal cortex, heart and blood vessels were determined. ACE activity in the renal cortex (125.2 +/- 11.5 nmol/mg per min) was greater than 600 times that of the heart (0.20 +/- 0.01 nmol/mg per min), greater than 500 times that of the veins (0.23 +/- 0.09 nmol/mg per min) and greater than 150 times that of the arteries (0.80 +/- 0.23 nmol/mg per min). ACE activity in the renal cortex and arteries 2 h after last dosing was almost completely inhibited by ramipril whereas ACE activity in the veins and heart was inhibited to a lesser extent. Our results demonstrate in man, for the first time, an inhibition of tissue ACE following short-term oral treatment with an ACE inhibitor.

Phospholipase A2 inhibitors. Differential inhibition of fatty acid acylation into kidney lipids by mepacrine and p-bromophenacyl bromide.

Mepacrine and p-bromophenacyl bromide, in addition to their inhibitory effect on lipolysis, are also potent inhibitors of fatty acid acylation into renal medullary lipids. Significant qualitative and quantitative differences in the inhibition by the two drugs were seen. p-Bromophenacyl bromide exerted a non-selective effect inhibiting the incorporation of saturated and unsaturated fatty acids into all phospholipid classes and triacylglycerols. In contrast, mepacrine selectively inhibited the incorporation of both saturated and unsaturated acids into phosphatidylcholine, phosphatidylethanolamine and triglycerides, and concurrently markedly enhanced their incorporation into phosphatidylinositol. Quantitative analysis of these mepacrine effects, together with the known inhibitory effects of this compound on phospholipase A2 and phosphatidylinositol-specific phospholipase C, suggests that mepacrine also inhibits phosphatidic acid phosphatase, thereby shunting the flux of phosphatidic acid away from diglyceride formation and into synthesis of phosphatidylinositol.

Prostaglandin biosynthesis in rabbit kidney: mepacrine inhibits renomedullary cyclooxygenase.

Mepacrine was found to exert a dose-dependent inhibition of prostaglandin E2 synthesis in rabbit kidney medulla slices and in medullary microsomes. Mepacrine at 0.5 mM produced 90% inhibition of microsomal prostaglandin E2 biosynthesis from added arachidonic acid. This effect results from inhibition of medullary cyclooxygenase; the activities of the prostaglandin G2 hydroperoxidase and the prostaglandin H2 isomerases are unaffected. In experiments with medulla slices prelabelled with [14C]arachidonate, the effect of mepacrine on the inhibition of [14C]prostaglandin generation was significantly higher (2.5 to 3.5-fold) than its inhibition of [14C]arachidonate release. Hence, although mepacrine reduces prostaglandin production by decreasing the lipolytic release of arachidonate from medullary lipids, its inhibitory effect on prostaglandin cyclooxygenase activity is substantial and appears to contribute significantly to its overall inhibition of prostaglandin generation in kidney medulla. Mepacrine is thus not only a non-selective antilipolytic agent but also a potent cyclooxygenase inhibitor.

The role of eicosanoids in cyclosporine nephrotoxicity in the rat.

Nephrotoxicity is the most troublesome complication of cyclosporine (CSA) therapy. The present study was designed to investigate the effects of chronic treatment with CSA on the 24-hr urinary excretion of prostanoids (PGs) and thromboxane (Tx) and on the renal function in the absence or presence of indomethacin. CSA administration to Wistar rats (20 mg/kg/day, i.p.) for 14 days caused a significant increase in plasma creatinine, blood urea nitrogen (BUN), urine osmolality, fractional excretion of sodium and potassium and a reduction in creatinine clearance (CCr) and urine volume. These changes were associated with a significant reduction in urinary excretion of PGE2 (21.1 +/- 3.3 vs 33.0 +/- 2.5 ng/24 hr) and PGF2 alpha (13.4 +/- 1.4 vs 27.9 +/- 3.8 ng/24 hr) and an increase in TxB2 (12.1 +/- 3.0 vs 4.6 +/- 0.5 ng/24 hr), and 6-keto PGF1 alpha (56.2 +/- 7.7 vs 27.7 +/- 1.9 ng/24 hr). However, the synthesis of TxB2 and 6-keto PGF1 alpha by renal medullary and cortical slices prepared from CSA treated rats was not different from values obtained for vehicle treatment. In contrast, PGE2 synthesis by cortical slices prepared from the CSA group was increased. A single injection of indomethacin (10 mg/kg) to vehicle and CSA treated rats resulted in a significant reduction in PGs and TxB2 excretion. This, was associated with a further reduction in CCr (0.81 +/- 0.06 vs 1.03 +/- 0.04 ml/min) and an increase in BUN (38.5 +/- 5.2 vs 28.2 +/- 1.4 mg%) only in the CSA group. We suggest that the vasodilating PGs attenuate the renal toxic effects induced by CSA.

Increased production of beta2-microglobulin after heart transplantation.

Serum beta2-microglobulin (beta2m) levels were measured to evaluate the state of immunoactivation in stable heart transplant recipients. Serum beta2m and renal function of 29 heart transplant recipients were compared with 16 control subjects, who were age and sex matched, and 11 patients with chronic kidney failure. Serum creatinine and 24-hour urine collection for albuminuria were used as markers of renal impairment. Heart transplant recipients with normal renal function (n = 7) had significantly elevated beta2m levels compared with control subjects: 2.6 +/- 0.9 vs 1.66 +/- 0.32 microg/ml, p < or = 0.05. Heart transplant recipients with impaired renal function (n = 22) had significantly elevated beta2m compared with the chronic kidney failure group: 4.42 +/- 1.3 vs 3.49 +/- 0.66 microg/ml (p < or = 0.05); although there was no significant difference in serum creatinine levels. Albuminuria excretion was significantly elevated in the chronic kidney failure group compared with the heart transplant recipients with impaired renal function (p < or = 0.05). Elevated serum beta2m in heart transplant recipients suggests increased beta2m production, reflecting increased immunoactivation. This observation could be useful in monitoring long-term immunosuppressive therapy.

Thromboxane production in human lung during cardiopulmonary bypass: beneficial effect of aspirin?

BACKGROUND: Increased systemic levels of thromboxane (Tx) during cardiopulmonary bypass (CPB) in humans have been reported. It is not known whether this reflects a general systemic response to the surgical procedure or an increased pulmonary production of Tx in response to ischemia and reperfusion. METHODS: Thromboxane B2 levels were measured in the right atrium and left atrium of 14 patients undergoing coronary artery bypass grafting for angina. Eight patients (group 1) were without aspirin for at least 15 days before operation, and 6 patients (group 2) were treated with aspirin (100 mg/day) for at least 1 month before operation. Levels of TxB2 were determined by enzyme immunoassay after lipid extraction and separation. RESULTS: Thromboxane B2 levels were elevated throughout CPB. In group 1, left atrial TxB2 levels were significantly higher (p < 0.05) than right atrial levels at all study points during CPB. After pulmonary reperfusion, TxB2 levels in both atria increased significantly (p < 0.02) compared with the levels before cross-clamping of the aorta, and there was an increasing gradient between the two atria (p < 0.05). Mean plasma TxB2 levels during CPB in group 2 were significantly reduced (p < 0.0001) in the right atrium (by 73%) and in the left atrium (by 69%) compared with levels in group 1. CONCLUSIONS: The rise in TxB2 levels in the left atrium after CPB in humans reflects production of Tx mainly in the lungs, most probably by ischemic pulmonary tissue and intravascular hematologic components. Aspirin markedly reduces Tx production during CPB, and it might play a major role in preventing pulmonary injury after operations with CPB in humans.

Albumin determination in frozen urines--underestimated results.

Albumin determination by radioimmunoassay in fresh and frozen urine collections from 73 patients were performed. The values for albumin in fresh urines were 1-200 mg/24 h and were significantly higher (p less than 0.001) than the corresponding values in urines frozen for seven days (40.7 mg/24 h +/- 5.0 vs. 32.0 mg/24 h +/- 4.3). Similar results were obtained for protein determination, using turbidimetry, in urine collections from 45 proteinuric patients. Iodinated human albumin added to urine specimens was higher (p less than 0.001) in the pellets from frozen urines compared to urines kept at 4 degrees C for 1 and/or 7 days. By contrast, the radioactivity in the pellet of fresh urines kept at 4 degrees C for 1 or 7 days did not show any significant change. We suggest that freezing results in a partial albumin and protein sedimentation. Thus, determination of albumin in frozen urine specimens underestimates the real value by about 20%. This underestimation will limit our ability to diagnose borderline cases of microalbuminuria.

Which cuff size is preferable for blood pressure monitoring in most hypertensive patients?

The accuracy of blood pressure (BP) measurements in obese hypertensives is still controversial. We investigated whether a large sized cuff could be appropriate for BP measurements in patients with different arm circumferences. Fifty hypertensive patients (23 males and 27 females, mean age 54 +/- 12 years, mean weight 75 +/- 12 kg) underwent BP measurements under standardised conditions using both a standard cuff (23 x 12 cm) and a large cuff (34 x 15 cm). Ambulatory blood pressure monitoring (ABPM) was subsequently performed in each subject using a large cuff. The average of two measurements performed in the clinic was compared with the mean daytime measurements. Thirty-one subjects had an arm circumference of < 30 cm (group 1) and weighted 68 +/- 10 kg, while 19 (group 2) had a larger arm circumference (> or = 30 cm) and were overweight (86 +/- 8 kg). BP in group 1 was 149 +/- 23/91 +/- 12 mmHg with the standard cuff and 143 +/- 24/88 +/- 13 mmHg with the large cuff (P < 0.003). In group 2, the respective readings were 153 +/- 22/100 +/- 16 mmHg (standard cuff) and 144 +/- 19/93 +/- 16 mmHg (large cuff; P < 0.0004). These findings suggest that in overweight hypertensives, the use of the standard cuff results in overestimation of BP and that large cuffs should be used exclusively in this population. The use of a large cuff in lean patients has yet to be clarified.

Microalbuminuria as an early marker of severity in hypertensive pregnant women.

The value of microalbuminuria in predicting hypertensive complications in pregnant patients at high risk was tested in a prospective trial. A total of 276 patients were studied (142 in the study group vs 134 controls). Albumin was measured in 8-h overnight urine collection throughout pregnancy using radioimmunoassay technique. The pregnant women, in both the study and control groups demonstrated a statistically significant increase in albumin excretion rate in the second and third trimester compared with the first. Using logistic and linear regression models, the presence of microalbuminuria in the early third trimester was proven to be predictive of severe disease (odds ratio 2.1, confidence interval (CI) 1.26-3.53) and birth weight (R2 = 0.7, P < 0.05) in the study group. Intrauterine growth retardation and neonatal outcome were less predictable. With the introduction of radioimmunoassays, we believe severe disease can be predicted by detecting microalbuminuria in the early third trimester of pregnancy in high risk patients.

Beta2-microglobulin and hypertensive complications in pregnant women at risk.

BACKGROUND AND AIM: Beta2-microglobulin (beta2-m) is a polypeptide, which is freely filtered through the glomerular basement membrane and absorbed almost entirely by the proximal tubular cells. Preeclampsia, a common complication of pregnancy, is characterized by pathological renal changes, mainly glomerular lesions. The aim of the present study was to investigate whether serum beta2-m measured in the early stages of pregnancy could be used as a marker to predict hypertensive complications in women at increased risk. PATIENTS AND METHODS: Serum beta2-m concentrations were prospectively measured in 75 pregnant women with history of chronic hypertension, chronic renal disease, chronic vascular disease or preeclampsia and compared with those in 16 healthy pregnant women. RESULTS: Of the 75 women in the study group, 10 (13%) developed preeclampsia and 20 (26%) had other complications, such as intrauterine growth restriction (n = 8), fetal or neonatal loss (n = 9) and delivery before 30 weeks of gestation (n = 8). Gestational age at delivery, birth weight and cesarean section rate were significantly worse in the patients with complications than in those without and in the healthy controls. No significant difference was detected in early serum beta2-m concentrations between the women who later developed preeclampsia or other complications and those who did not. There was a significant positive correlation of beta2-m concentrations with serum creatinine level (R2 = 0.394, p < 0.001), but not with gestational week at blood collection. CONCLUSION: Serum beta2-m concentrations are not predictive of the development of preeclampsia or other complications in woman at risk.