Quality of life and bariatric surgery: a systematic review of short- and long-term results and comparison with community norms.

Currently the effects of bariatric surgery are generally expressed in excess weight loss or comorbidity reduction. Therefore the aim of this review was to provide insight in the available prospective evidence regarding the short and long-term effects of bariatric surgery on Quality of Life (QoL) and a comparison with community norms. A systematic multi-database search was conducted for 'QoL' and 'Bariatric surgery'. Only prospective studies with QoL before and after bariatric surgery were included. The 'Quality Assessment Tool for Before-After Studies with No Control Group' was used to assess the methodological quality. Thirty-six studies met the inclusion criteria. Most studies were assessed to be of 'fair' to 'good' methodological quality. Ten different questionnaires were used to measure QoL. Follow-up ranged from 6 months to 10 years, sample sizes from 26 to 1276 and follow-up rates from 45 to 100%. A significant increase in QoL after bariatric surgery was found in all studies (P⩽0.05), however, mostly these outcomes stay below community norms. Only outcomes of the IWQoL, SF-36 and OWQoL show QoL outcomes that exceed community norms. The QoL is increased after bariatric surgery on both the short and long term. However, due to the heterogeneity of the studies and the generality of the questionnaires is it hard to make a distinction between different surgeries and difficult to see a relation with medical profit. Therefore, tailoring QoL measurements to the bariatric population is recommended as the focus of future studies.

Inhibition of tissue factor:factor VIIa-catalyzed factor IX and factor X activation by TFPI and TFPI constructs.

BACKGROUND: TFPI is a Kunitz-type protease inhibitor that downregulates the extrinsic coagulation pathway by inhibiting factor Xa (FXa) and FVIIa. All three Kunitz domains (KD1, KD2, and KD3) and protein S are required for optimal inhibition of FXa and FVIIa. There is limited information on Kunitz domain requirements of the inhibition of TF:FVIIa-catalyzed FIX and FX activation by TFPI. AIM: To investigate the role of the Kunitz domains of TFPI and protein S in the inhibition of FX and FIX activation. METHODS: Inhibition of TF:FVIIa-catalyzed FX and FIX activation by full-length TFPI (TFPIFL ) and TFPI constructs was quantified from progress curves of FXa and FIXa generation measured with chromogenic substrates. RESULTS AND CONCLUSIONS: TFPIFL inhibited TF:FVIIa-catalyzed FIX activation with a Ki of 16.7 nmol L(-1) . Protein S reduced the Ki to 1.0 nmol L(-1) . TFPI1-150 and KD1-KD2 had 10-fold higher Ki values and were not stimulated by protein S. Single Kunitz domains were poor inhibitors of TF:FVIIa-catalyzed FIX activation (Ki >800 nm). FX activation was measured at limiting FVIIa and excess TF or vice versa. At both conditions, TFPIFL , TFPI1-150 , and KD1-KD2 showed similar inhibition of FX activation. However, at low phospholipid concentrations, TFPIFL was ~ 15-fold more active than TFPI1-150 or KD1-KD2. Apparently, excess phospholipids act as a kind of sink for TFPIFL , limiting its availability for TF:FVIIa inhibition. Preformed FXa:TFPIFL/1-150 complexes rapidly and stoichiometrically inhibited FIX and FX activation by TF:FVIIa, indicating that binary TFPI:FXa complex formation is the limiting step in TF:FVIIa inhibition. Protein S also enhanced inhibition of TF:FVIIa-catalyzed FX activation by TFPI.

Thyroid function, activated protein C resistance and the risk of venous thrombosis in users of hormonal contraceptives.

INTRODUCTION: Use of combined hormonal contraceptives is associated with a three- to eight-fold increased risk of venous thrombosis compared with non-use. The thrombotic risk depends on the estrogen dose as well as the progestogen type. Use of hormonal contraceptives leads to resistance to activated protein C (APC), which may serve as marker for the risk of venous thrombosis. Hyperthyroidism is also associated with an increased risk of venous thrombosis, due to increased free Thyroxine (FT4) levels which cause a hypercoagulable state. MATERIALS AND METHODS: The objective of this study was to evaluate the effects of hormonal contraceptives on levels of FT4, thyroid stimulating hormone (TSH) and thyroxine binding globulin (TBG), and to investigate the effects on APC resistance per contraceptive group. We measured FT4, TBG and TSH levels and APC resistance in 231 users of oral contraceptives. RESULTS: Users of the most thrombogenic hormonal contraceptives, i.e. containing desogestrel, cyproterone acetate or drospirenone, had higher TBG levels than users of less thrombogenic hormonal contraceptives, i.e. the levonorgestrel-containing intrauterine device. TSH levels were not significantly elevated and FT4 levels did not change. TBG levels were also associated with APC resistance. CONCLUSION: Use of hormonal contraceptives lead to elevated TBG levels, slightly elevated TSH levels and unchanged FT4 levels without causing a hyperthyroid state. Thus, the increased thrombotic risk during the use of hormonal contraceptives cannot be explained by a hyperthyroid state caused by use of these hormonal contraceptives.

Resistance to APC and SHBG levels during use of a four-phasic oral contraceptive containing dienogest and estradiol valerate: a randomized controlled trial.

BACKGROUND: The use of combined oral contraceptives is associated with a 3- to 6-fold increased risk of venous thrombosis. This increased risk depends on the estrogen dose as well as the progestogen type of combined oral contraceptives. Thrombin generation-based activated protein C resistance (APC resistance) and sex hormone-binding globulin (SHBG) levels predict the thrombotic risk of a combined hormonal contraceptive. Recently, a four-phasic oral contraceptive containing dienogest (DNG) and estradiol valerate (E2V) has been marketed. The aim of this study was to evaluate the thrombotic risk of the DNG/E2V oral contraceptive by comparing APC resistance by measuring normalized APC sensitivity ratios (nAPCsr) and SHBG levels in users of oral contraceptives containing dienogest and estradiol valerate (DNG/E2V) and oral contraceptives containing levonorgestrel and ethinyl estradiol (LNG/EE). METHODS: We conducted a single-center, randomized, open label, parallel-group study in 74 women using DNG/E2V or LNG/EE, and measured nAPCsr and SHBG levels in every phase of the regimen of DNG/E2V. RESULTS: During the pill cycle SHBG levels did not differ between DNG/E2V users and LNG/EE users. nAPCsr levels were overall slightly lower in DNG/E2V users than in LNG/EE users, mean difference -0.44 (95% CI, -1.04 to 0.17) for day 2, -0.20 (95% CI, -0.76 to 0.37) for day 7, -0.27 (95% CI, -0.81 to 0.28) for day 24 and -0.34 (95% CI, -0.91 to 0.24) for day 26. CONCLUSION: No statistical significant differences in nAPCsr and SHBG levels were found between users of the oral contraceptive containing DNG/E2V and LNG/EE, suggesting a comparable thrombotic risk.

Direct inhibition of factor VIIa by TFPI and TFPI constructs.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a multi-Kunitz domain protease inhibitor that down-regulates the extrinsic coagulation pathway by inhibiting FXa and FVIIa. OBJECTIVES: To investigate the role of the three Kunitz domains (KDs) of TFPI in FVIIa inhibition using full-length TFPI (TFPIfl ) and truncated TFPI constructs. METHODS: Inhibition of FVIIa with/without relipidated tissue factor (TF) or soluble TF (sTF) by TFPIfl /TFPI constructs was quantified with a FVIIa-specific chromogenic substrate. RESULTS AND CONCLUSIONS: TFPIfl inhibited TF-FVIIa via a monophasic reaction, which is rather slow at low TFPIfl concentrations (t½  ≈ 5 min at 2 nm TFPI) and has a Ki of 4.6 nm. In the presence of sTF and without TF, TFPIfl was a poor FVIIa inhibitor, with Ki values of 122 nm and 1118 nm, respectively. This indicates that phospholipids and TF significantly contribute to FVIIa inhibition by TFPIfl . TFPI constructs without the KD3-c-terminus (TFPI1-150 and KD1-KD2) were 7-10-fold less effective than TFPIfl in inhibiting TF-FVIIa and sTF-FVIIa, indicating that the KD3-C-terminus significantly contributes to direct inhibition of FVIIa by TFPI. Compared with KD1-KD2, KD1 was a poor TF-FVIIa inhibitor (Ki =434 nm), which shows that the KD2 domain of TFPI also contributes to FVIIa inhibition. Protein S stimulated TF-FVIIa inhibition by TFPIfl (Ki =0.7 nm). In the presence of FXa, a tight quaternary TF-FVIIa-TFPI-FXa complex is formed with TFPIfl , TFPI1-150 and KD1-KD2, with Ki values of < 0.15 nm, 0.5 nm and 0.8 nm, respectively, indicating the KD3-C-terminus is not a prerequisite for quaternary complex formation. Phospholipids and the Gla-domain of FXa are required for quaternary complex formation.

Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives.

BACKGROUND: It takes many years to obtain reliable values for the risk of venous thrombosis of hormonal contraceptive users from clinical data. Measurement of activated protein C (APC) resistance via thrombin generation is a validated test for determining the thrombogenicity of hormonal contraceptives. Sex hormone-binding globulin (SHBG) might serve as a marker for the risk of venous thrombosis, and can be easily and rapidly measured in routine laboratories. OBJECTIVE: To determine whether SHBG is a useful marker for the thrombotic risk of hormonal contraceptive users by comparing plasma SHBG levels with normalized APC sensitivity ratio (nAPCsr) values and thrombosis risks reported in the recent literature. METHODS: We conducted an observational study in 262 users of different contraceptives, and measured nAPCsr and SHBG levels. RESULTS: Users of contraceptives with a higher risk of causing venous thrombosis, i.e. combined hormonal contraceptives containing desogestrel, cyproterone acetate or drospirenone, and the transdermal patch, had higher SHBG levels than users of combined hormonal contraceptives containing levonorgestrel, which carry a lower thrombosis risk. Users of the patch had the highest SHBG levels, with a mean difference of 246 nmol L(-1) (95% confidence interval 179-349) from that in users of levonorgestrel-containing combined hormonal contraceptives. SHBG levels were positively associated with both the nAPCsr and the risks of venous thrombosis reported in the recent literature. CONCLUSION: SHBG is a useful marker with which to estimate the thrombotic safety of a preparation.

Should blood flow during cardiopulmonary bypass be individualized more than to body surface area?

Blood flow during cardiopulmonary bypass (CPB) is calculated on body surface area (BSA). Increasing comorbidity, age and weight of today's cardiac patients question this calculation as it may not reflect individual metabolic requirement. The hypothesis was that a measured cardiac index (CI) prior to normothermic CPB is a better estimate. A cross-over study, with random allocation to CPB blood flow for 20 minutes based on either a calculation (2.4 L/min/m(2)) or on CI, with a switch to the opposite flow for another 20 minutes, was performed. Twenty-two elective cardiac surgery patients with normal ventricular function were included. Effect parameters were cerebral oxygenation, mixed venous saturation and arterial lactate. CI varied from 1.9 to 3.1 L/min/m(2) (median 2.4 L/min/m(2)). No differences in effect parameters were seen. In conclusion, a CPB blood flow based on an individual estimate did not improve cerebral and systemic oxygenation compared to a blood flow based on BSA.

Serum cystatin C as a marker of the renal function in patients with spinal cord injury.

OBJECTIVE: To investigate the relationship between serum cystatin C, serum creatinine, and (51)Cr-EDTA-clearance in patients with spinal cord injury. SETTING: The Spinal Cord Unit, Viborg-Kjellerup County Hospital. METHODS: Twenty-four men and seven women aged 20.3 to 68.0 years with motor complete spinal cord injury (ASIA A or B) were included. Serum cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring), serum creatinine by an enzymatic method (Vitros 950), and (51)Cr-EDTA-clearance by a multiple plasma sample method. RESULTS: A linear relationship was found between (51)Cr-EDTA-clearance and the reciprocal values of cystatin C and creatinine. The correlation coefficient between (51)Cr-EDTA-clearance and 1/cystatin C was 0.72 compared to the correlation coefficient between (51)Cr-EDTA-clearance and 1/creatinine being 0.26. Comparison of the area under the curves in the non-parametric receiver operating characteristics (ROC) plots for serum cystatin C (area under the curve (AUC)=0.912; SE=0.065), and serum creatinine (AUC=0.507; SE=0.115) revealed significant differences (P-values=0.0005). CONCLUSION: In patients with spinal cord injury serum cystatin C is a better marker of the renal function compared to serum creatinine.

Functional and molecular characteristics of Na(+)-dependent nucleoside transporters.

Nucleoside transporters play a critical role in the absorption, disposition, and targeting of therapeutically used nucleosides and nucleoside analogs. This review is focused on the Na(+)-dependent, concentrative nucleoside transporters which are found in a variety of cells including renal, intestinal and hepatic epithelia. Five major Na(+)-dependent nucleoside transporter subtypes have been characterized in isolated tissue preparations: N1 is purine selective; N2 is pyrimidine selective and N3-N5 exhibit variable selectively for both purine and pyrimidine nucleosides. The recent cloning of N1 and N2 nucleoside transporters has provided the first information on the molecular function and structure of concentrative nucleoside transporters. In this manuscript we review the characteristics of the various subtypes of nucleoside transporters and the molecular structure, functional properties, and tissue distribution of the cloned Na(+)-dependent nucleoside transporters. In addition, the interactions of nucleosides and nucleoside analogs with the cloned transporters in mammalian and amphibian expression systems are presented. Mammalian expression systems may be particularly useful during drug development in screening potential compounds for improved bioavailability and tissue specific targeting. Finally, we present our view of future ares of study in the field of nucleoside transporters.

The effects of 'in-use' surgical handwashing on the pre- and postoperative fingertip flora during cardiothoracic and orthopaedic surgery.

Two operating teams (25 persons) were followed for two months with fingerprint samples taken preoperatively; before and after 'in-use' surgical handwashing; and immediately postoperatively, with and without surgical gloves. The mean time for handwashing for the cardiothoracic team (CT) was 2 min and for the orthopaedic team (OT) was 3.5 min. A closer observation of 10 persons revealed a great individual variation in washing techniques, in spite of standard guidelines. The CT team performed eight, and the OT team nine sterile operations with an average duration of 3 h and 20 min and 2 h and 40 min, respectively. Surgical handwashing resulted in fingertip sterility in 111/118 (94.1%) cases; in 61/66 (92.4%) samples from the surgeons and in 50/52 (96.2%) samples from the assistants. Postoperative fingerprinting with gloves on showed sterile conditions in 85/91 (93.4%) samples; 57/59 (96.6%) from the surgeons and 28/32 (87.5%) from the assistants. Immediately after removal of the gloves, 43/67 (64.2%) of fingerprint samples from the surgeons and 13/48 (27.1%) from the assistants were still sterile. Coagulase-negative staphylococci (CNS) and Bacillus species predominated in fingerprint samples. Of the 105 CNS strains tested, 11.4% were methicillin resistant. Only five strains of Staphylococcus aureus were isolated; in 4/5 cases from the OT. This study illustrates that in spite of standard guidelines, there is great individual variation in surgical handwashing. However, in most instances, the bacteria are eradicated from the fingertips. Even after surgery for 2-3 h, there may still be a residual effect of the hand disinfecting agent in half of the cases.