Biomedical subjects

A Simon

Publications and source records attributed to A Simon.

At least 181 records · Page 10Linked to original sources

PubMed1998

Early atherosclerosis in human hypertension.

The detection of preclinical atherosclerosis may contribute to better identifying hypertensive subjects at high risk of complications. Three alterations can be diagnosed noninvasively: calcification, thickening, and stiffening of the arterial wall. Their prevalence is increased in asymptomatic hypertensives and their presence may have important prognostic significance, especially with respect to coronary artery disease. They are also ideal targets to test the efficacy of hypertensive therapy on the arterial wall. Finally, the detection of early atherosclerosis may help to improve the clinical management of hypertensive patients.

Arteries↗

PubMed1998

Thoracic computed tomography prior to redo coronary surgery.

OBJECTIVE: Median resternotomy in coronary redo surgery represents a specific risk for injury of adjacent retrosternal structures. Aiming at improved preoperative evaluation of retrosternal structures, computed tomography (CT) techniques were routinely applied in redo cases. METHODS: Of 99 patients undergoing coronary reoperations since April 93, thoracic CT scans were retrospectively analyzed for retrosternal vicinity of cardiovascular structures, condition of the ascending aorta and structural abnormalities of the sternum. RESULTS: The minimal median distance between the posterior sternum surface and the anterior aortic wall was measured at 1.9 +/- 0.9 cm, whereas the mean closest distance to the anterior right ventricular wall was 0.4 +/- 0.5 cm. In 28 cases, the distance between sternum and aorta was smaller than or equal to 1 cm. No measurable distance between the sternum and the right ventricle was noted in 41 patients. Calcification of the ascending aorta became obvious 56 times. With respect to potential injury of the ascending aorta or the right ventricle, a safe reentry by resternotomy was facilitated in all cases. However, following complete sawing, the innominate vein became injured during retrosternal dissection in two cases. Preventive femoral vessel exposure was not performed and urgent femoral cannulation (n = 1) was infrequent. CONCLUSIONS: Thoracic CT scanning prior to redo coronary surgery allows for detailed assessment of retrosternal relations and facilitates reopening of the sternum. Preventive femoral vessel exposure and lateral thoracotomies may be avoidable in many cases.

Aortography↗

PubMed1998

Interleukin-4 Modulation of Platelet-Derived Growth Factor-Induced Smooth Muscle Cell Urokinase Plasminogen Activator.

Platelet-derived growth factor (PDGF) stimulates smooth muscle cell (SMC) migration owing to stimulation of SMC tissue plasminogen activator (t-PA) production. In this study we examined the effects of the T-cell lymphokine interleukin-4 (IL-4) on PDGF induction of human aortic SMC antigen levels of urokinase-type plasminogen activator (u-PA) and those of plasminogen activator inhibitor-1 (PAI-1), the endogenous inhibitor of t-PA and u-PA, measured by enzyme-linked immunosorbent assays (ELISAs). u-PA antigen levels from human aortic SMC incubated with PDGF 100 ng/mL and IL-4 500 U/mL were significantly greater than those incubated with PDGF 100 ng/mL alone. Coincubation of PDGF with IL-4 did not significantly increase SMC u-PA antigen levels in cellular lysates. Coincubation with PDGF 100 ng/mL and IL-4 500 U/mL did not significantly affect SMC PAI-1 antigen levels in conditioned media or cellular lysates. Therefore, interleukin-4 modulates vascular SMC u-PA production induced by PDGF.

Journal Article↗

PubMed1998

The pathogenesis of ovarian hyperstimulation syndrome: a continuing enigma.

PURPOSE: Our purpose was to review the available literature concerning the pathogenesis of ovarian hyperstimulation syndrome and, in light of the most recent information, to attempt to provide further insight on this iatrogenic complication associated with the induction of ovulation. METHODS: Published studies related to this topic were identified through a computerized bibliographic search. CONCLUSIONS: The exact mechanism for the development of ovarian hyperstimulation syndrome is still obscure. It is well established that the syndrome is associated with the process of ovulation induced by either luteinizing hormone or human chorionic gonadotropin. Following ovulation, one or more substances produced by the ovary are liberated in excess, increasing capillary permeability, resulting in the clinical features of the syndrome. It may well be that the syndrome is not triggered by a single mechanism but by the production and secretion of several substances acting in concert. These may include prostaglandins, cytokines, the ovarian reninangiotensin system, vascular endothelial growth factor, and nitric oxide.

Capillary Permeability↗

PubMed1998

Decreased regional blood flow in patients with acromegaly.

BACKGROUND AND AIMS: One-third of acromegalic patients have hypertension. Acromegaly is also associated with intrinsic cardiac abnormalities known collectively as a hyperkinetic heart syndrome, which is characterized by an increased cardiac index and decreased systemic vascular resistance. As a result, blood flow should be increased in the regional vascular beds of acromegalic patients. The aim of the study was to measure, using direct methods, blood flow and vascular resistance at the level of the brachial artery in acromegalic patients with a confirmed hyperkinetic heart syndrome. PATIENTS AND CONTROLS: Twelve patients with active acromegaly (five females, seven males; mean (+/- SD) age, 43 +/- 10 years) were studied. Twelve age- and sex-matched normal subjects served as controls. METHODS: Right heart catheterization was used to measure the cardiac index and stroke volume and to calculate systemic vascular resistance in the acromegalic patients. Brachial haemodynamics were evaluated with a two-dimensional pulsed Doppler system (double transducer probe and range-gated time system of reception). The mean diameter of the brachial artery and mean blood velocity were measured and used to calculate mean blood flow. Vascular resistance was calculated in the brachial artery as the mean arterial pressure/blood flow ratio. RESULTS: Age, body weight, height, body surface area and heart rate were similar in the acromegalic patients and controls, while mean arterial pressure was higher in patients. The cardiac index and stroke volume were increased in the acromegalic patients, at 4.08 +/- 0.47 (mean +/- SD) l/min/m2 body surface area and 116.7 +/- 19.4 ml, respectively, while systemic vascular resistance was low (12.5 +/- 2.1 U). Brachial artery diameter was similar in the patients and controls. Brachial artery mean blood velocity (P < 0.01) and mean blood flow (P < 0.05) were lower in the patients than in the controls (3.35 +/- 1.26 vs. 5.12 +/- 1.74 cm/s, and 16.4 +/- 9.4 vs. 25.6 +/- 11.6 ml/min/m2, respectively). The higher mean arterial pressure and lower mean blood flow resulted in higher forearm vascular resistance in the patients than in the controls (132 +/- 61 vs. 83.8 +/- 47 mmHg/ml/s/m2, respectively, P < 0.01). CONCLUSION: While cardiac output is increased and systemic vascular resistance is decreased in active acromegaly, direct measurement of brachial artery haemodynamics showed lower regional blood flow and increased local resistance relative to healthy controls. These results suggest a heterogeneous distribution of cardiac output in acromegaly.

Acromegaly↗

PubMed1998

Surveillance of pneumococcal resistance in Belgium during winter 1996-1997.

This study tested 212 pneumococcal isolates from 9 institutions for their susceptibilities to penicillin, ampicillin, amoxycillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime, imipenem, tetracycline, erythromycin, and clarithromycin using NCCLS-standardized microdilution. Penicillin-insusceptibility was 12.3% [5.7% intermediate (0.12-1 microgram/ml) and 6.6% high-level (> or = 2 micrograms/ml)], tetracycline-insusceptibility (> or = 4 micrograms/ml) 31.1%, and erythromycin-insusceptibility (> or = 0.5 microgram/ml) 31.1% as well. Erythromycin-insusceptible isolates showed cross-insusceptibility to clarithromycin. Penicillin-susceptible isolates were susceptible to all beta-lactams. MICs of all beta-lactams rose with those of penicillin for penicillin-insusceptible isolates. Ampicillin and penicillin were equally potent against penicillin-insusceptible isolates, imipenem, cefotaxime, and amoxycillin +/- clavulanate were more potent (generally 5, 1, and 1 doubling dilution, respectively), and cefuroxime and cefaclor less potent (generally 1 and 6 doubling dilutions, respectively). Most penicillin-insusceptible isolates were high-level resistant to cefaclor (> or = 32 micrograms/ml). Although MICs of all beta-lactams rose with those of penicillin, resistance to penicillin was not absolute in terms of cross-resistance. Most penicillin-intermediate and high-level penicillin-resistant isolates remained fully susceptible and intermediate, respectively, to amoxycillin +/- clavulanate, cefotaxime, and imipenem, but not to cefuroxime. Penicillin-susceptible isolates were 76.9%, 42.3%, and 34.6% co-insusceptible to tetracycline, erythromycin, and tetracycline plus erythromycin, respectively. Most penicillin-, tetracycline-, and erythromycin-insusceptible isolates were of capsular types 23 >> 6 > 19 > 32, 19 > 6 > 28 > 23, and 19 > 6 > 14 > 23, respectively. Compared to winter 1994-1995, insusceptibility to penicillin, tetracycline, and erythromycin rose by some 4%, 4%, and 13%, respectively.

Adolescent↗

PubMed1998

Transfer of frozen-thawed embryos in artificially prepared cycles with and without prior gonadotrophin-releasing hormone agonist suppression: a prospective randomized study.

Transfer of frozen-thawed embryos is usually carried out in a natural cycle or in a programmed cycle in which the endometrium is exogenously stimulated following down-regulation of the hypophysis. To analyse the possibility that the programmed cycle for embryo transfer can still be hormonally manipulated without the use of gonadotrophin-releasing hormone agonist (GnRHa) we have conducted a prospective randomized study that compared the outcome of frozen-thawed embryo transfer cycles using micronized 17beta-oestradiol and micronized progesterone preparations with and without the concomitant use of GnRHa. One hundred and six patients were randomly divided into two groups. In group A (53 patients) 4 mg/day of micronized 17beta-oestradiol was initiated following down-regulation of hypophysis. In group B (53 patients) oestrogen stimulation started on day 1 of the cycle without prior pituitary down-regulation using a dose of 6 mg/day for 7 days. In both groups, micronized progesterone in a dose of 900 mg/day was administered vaginally after at least 12 days of oestrogen stimulation. Embryo transfer embryo transfer took place 48-72 h thereafter according to the cryopreserved embryonic stage. Overall, none of the patients had any follicular development and only one cycle in group B had to be cancelled because of premature progesterone secretion. The two groups did not differ in age (31+/-5.6 and 31+/-5.0 years), number of embryos transferred per patient (3.4+/-1.2 and 3.3+/-1.0), and day of progesterone initiation (15+/-2.2 and 15+/-1.9 for groups A and B respectively). The endometrial thickness on the day of progesterone initiation was comparable in both groups (11 +/-1.6 and 10+/-1.6 mm for groups A and B respectively). Similarly, the pregnancy rate per embryo transfer and implantation rate in group A (26.4% and 9.5%) were comparable to those of group B (21.1% and 9%). These results indicate that programmed cycles can be successfully applied by administering a high dose of micronized 17beta-oestradiol starting on day 1 of the cycle. Compared to GnRHa programmed cycles, this approach is simpler, more convenient for both the patient and medical staff, and results in a similar success rate at a lower cost.

Adult↗

PubMed1998

Preclinical changes of extracoronary arterial structures as indicators of coronary atherosclerosis in men.

BACKGROUND: Carotid artery structure change was associated with coronary artery stenosis by angiography of subjects who were for the most part symptomatic. OBJECTIVE: To determine whether structural changes at multiple extracoronary sites were associated with noninvasively detected coronary calcium for 94 asymptomatic high-risk men. METHODS AND RESULTS: B-mode ultrasonography allowed us to detect plaque at three sites (carotid, femoral, and abdominal aorta) and to measure intima-medial thickness both in common carotid and in femoral arteries. Ultrafast computed tomography determined the presence and amount of coronary calcification. After adjustment for age, plaques at two or three sites were associated with extensive amounts of coronary calcium [odds ratio 4.94 (95% confidence interval 1.08-23)], but not with the presence of coronary calcium; increase in carotid intima-medial thickness was not associated with presence and extent of coronary calcium; and increase in femoral intima-medial thickness was associated with presence of coronary calcium [odds ratio 1.44 (95% confidence interval 1.03-2)] and extensive coronary calcium [odds ratio 1.50 (95% confidence interval 0.97-2.33)]. Adjustment for cardiovascular risk factors attenuated these associations. CONCLUSIONS: Femoral intima-medial thickness predicted presence of coronary calcium whereas femoral intima-medial thickness and overall multiple plaques predicted extensive coronary calcium. Because coronary calcium is a marker of atherosclerosis and a predictor of coronary events, B-mode ultrasonography could be of clinical value for stratifying coronary risk.

Adult↗

PubMed1998

Charge heterogeneity of LDL in asymptomatic hypercholesterolemic men is related to lipid parameters and variations in the ApoB and CIII genes.

This study was carried out to examine the relationship between the charge on low density lipoproteins (LDLs) and lipid and clinical parameters in 104 asymptomatic dyslipidemic men and to identify biochemical and genetic factors that could contribute to the charge variability of LDL. LDL charge heterogeneity was evaluated by relative electrophoretic mobility (REM) on preformed 0.5% agarose gels and by chromatographic quantification of a minor electronegative LDL subfraction designated LDL(-). The mean REM value for LDL was 0.147+/-0.016 and the mean LDL(-) subfraction percentage was 5.6+/-2.8%. Both were positively correlated with common atherosclerotic risk factors, especially total cholesterol [for REM, r=0.27, P<0.005; for LDL(-), r=0.28, P=0.008] and LDL cholesterol [for REM, r=0.27, P=0.007; for LDL(-), r=0.26, P=0.01)] levels, and REM was positively correlated with triglycerides (r=0.27, P<0.005) and negatively with apoAI levels (r=-0.30, P<0.002). The variations in LDL charge were not due to oxidation, as measured by the lag phase and binding to the LDL receptor. The results of the 2 methods used to measure LDL charge were significantly correlated and had some identical characteristics (eg, association with LDL apoCIII content and plasma triglyceride levels in borderline and IIb dyslipidemic subjects); these methods reflect different specific features of LDL charge. The percentage of LDL(-) was correlated positively with the LDL sialic acid content (P<0.0001), whereas the REM was related to at least 2 distinct chromosomal loci. Multiple logistic analysis showed that individuals carrying minor alleles of BsrDI (P<0.05), apoCIII/SacI (P<0.01), as well as the frequent allele of XbaI (P<0.05) at the apoB and CIII gene loci had high REMs. This result suggests that LDL charge heterogeneity, which is positively correlated with the atherogenic lipid profile, is influenced by both genetic and biochemical factors.

Apolipoprotein C-III↗

PubMed1998

Sex and topographic differences in associations between large-artery wall thickness and coronary risk profile in a French working cohort: the AXA Study.

Previous reports have investigated associations between carotid intima-media thickness (IMT) and cardiovascular risk factors. Our objective was to investigate this question in greater depth by measuring both femoral and carotid IMT in relation to sex and multifactorial coronary risk. We investigated carotid and femoral artery IMT by using ultrasonography in 326 men and 462 women, 17 to 65 years old. We also evaluated body mass index, blood pressure, blood lipids, glucose, smoking, and Framingham coronary risk. In both vessels, IMT was lower in women than in men. Significant relations between carotid and femoral IMT existed with age and most risk factors in both sexes. After adjustment for age, carotid IMT was related to risk factors in both sexes except for diastolic blood pressure, HDL cholesterol, and smoking in women, whereas femoral IMT was related to triglycerides and smoking in both sexes, systolic blood pressure and blood glucose in men, and total and HDL cholesterol in women. Significant unadjusted and age-adjusted relations of Framingham risk existed with carotid and femoral IMT in both sexes, but slopes of these relations were greater (1) before than after age adjustment, (2) in men than in women at both sites, except the femoral artery after age adjustment, and (3) at the carotid than at the femoral site in both sexes before age adjustment. Carotid IMT in men appears to be a more powerful predictor than it is in women and femoral IMT in both sexes in reflecting multifactorial coronary risk burden, but these differences are partly conditional on age.

Adolescent↗

PubMed1998

Carotid wall viscosity increase is related to intima-media thickening in hypertensive patients.

Increases in arterial wall viscosity and intima-media thickness (IMT) were found in hypertensive patients. Because smooth muscle cells are responsible for the viscous behavior of the arterial wall and they are involved in the process of thickening of the intima-media complex, this study evaluates the relationship between carotid thickness and wall viscosity. The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. This technique was contrasted against sonomicrometry in sheep, showing that the waveforms obtained by both methods were similar. The common carotid arteries of 11 normotensive subjects (NTA) and 11 patients with mild to moderate essential hypertension (HTA) were measured noninvasively by using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure and diameter loops. A viscoelastic model was used to derive the wall viscosity index (eta) using the hysteresis loop elimination criteria. In NTA, eta was 2.73+/-1.66 (mm Hg x s/mm) and IMT was 0.58+/-0.08 (mm), whereas in HTA, eta was 5.91+/-2.34 (P<.025) and IMT was 0.70+/-0.12 (P<.025), respectively. When all data of eta versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r=.71 (P<.05) was obtained. Partial correlation between eta and IMT holding constant pressure was r=.59 (P<.05). In conclusion, wall viscosity increase was associated with a higher IMT even maintaining blood pressure fixed, suggesting that the intima-media thickening might be related to smooth muscle alterations manifested as an increase in viscous behavior.

Algorithms↗

PubMed1998

Erythrocyte disaggregation shear stress, sialic acid, and cell aging in humans.

Erythrocyte aggregation, which plays an important role in the physiological behavior of blood fluidity, was found to be enhanced in hypertension and hypercholesterolemia. While the role of macromolecule bridging force has been widely described, cellular factors related to membrane sialic acid content, which might contribute to the negative charge of cell surface causing the repulsion of erythrocytes, have been less studied. Cell age-dependent changes in membrane sialic acid content (in micromoles per gram of integral membrane protein) were investigated in 24 normotensive and 24 hypertensive matched subjects, each divided into 2 identical subgroups according to a cutoff of 6.2 mmol/L serum cholesterol. A progressive and significant (P<0.001) decrease in membrane sialic acid content associated with an increase (P<0.001) of disaggregation shear rate threshold (laser reflectometry in the presence of dextran) were observed with increased erythrocyte density (erythrocytes fractionated by density using ultracentrifugation) in both normotensive and hypertensive groups regardless of the cholesterol level. However, disaggregation shear rate threshold was significantly higher and sialic acid content was lower (P<0.001) in both hypertensive and normotensive subjects with hypercholesterolemia compared with either normotensive or hypertensive subjects with low cholesterol, respectively. A high membrane sialic acid content variance, beginning in the younger erythrocytes, was due mainly to triglyceride and LDL cholesterol levels (R2=0.49 for low, R2=0.43 for middle, and R2=0.54 for high densities, ie, young, mean, and senescent erythrocytes, respectively). We conclude that an early decrease in erythrocyte sialic acid content may influence the rheological properties of blood by increasing the adhesive energy of erythrocyte aggregates.

Adult↗

PubMed1998

Manual versus mechanical compression for femoral artery hemostasis after cardiac catheterization.

BACKGROUND: Most cardiac catheterizations are performed via femoral artery access. Reported rates of both peripheral vascular complications and success rates for the use of manual and mechanical compression techniques to achieve femoral artery hemostasis after cardiac catheterization vary. OBJECTIVE: To determine is use of a mechanical clamp is as effective as standard manual pressure for femoral artery hemostasis after cardiac catheterization. METHODS: Subjects consisted of 720 patients from 2 community hospitals who had elective diagnostic cardiac catheterization via the femoral artery. The control group (n=343) received manual compression for hemostasis; the study group (n=377) received mechanical compression. Standard protocols were used for the 2 compression techniques. Pressure was applied for a minimum of 10 minutes for 5F and 6F sheaths and catheters and for a minimum of 15 minutes for 7F and 8F sheaths and catheters. Prospective data were collected and analyzed for each patients, including sheath or catheter size, blood pressure, height, weight, age, time from administration of local anesthetic to successful cannulation of the femoral artery, anticoagulation status, total compression time, physician performing the catheterization procedure, nurse or technician who obtained hemostasis, and complications. In follow-up, patients were asked site-specific and functional status questions 1 to 2 days after the catheterization procedure and again 3 days after the catheterization procedure. RESULTS: Data were analyzed by using frequency distributions, measures of central tendency, and measures of variability. Only 1 difference between the 2 groups was significant: manual compression time was 14.93 +/- minutes, whereas mechanical compression time was 17.13 +/- minutes. CONCLUSION: Mechanical compression is as effective as manual compression for femoral artery hemostasis after cardiac catheterization.

Cardiac Catheterization↗

PubMed1998

[Euthanasia--attempt at an ethical approach].

A categorical refusal of active euthanasia, as presently being reflected by the Austrian euthanasia debate, has, by a closer examination, proved ethically unfounded. As to all moral judgement in matters of practised euthanasia, the most important question here certainly is whether the aid for dying has been granted on request or not, or even without the ill person's consent--rather than whether that person granting euthanasia is doing this is an active, passive or possibly indirect way. However, the possibility of a moral justification for the so-called killing on request will not consequently permit the legalization of its practice due to practical reasons speaking against such a step.

Advance Directives↗

PubMed1997

Coronary risk estimation and treatment of hypercholesterolemia.

BACKGROUND: Evidence-based treatment of hypercholesterolemia currently recommended for rationalizing drug prescription requires justification of treatment by randomized trials, such as the West of Scotland Coronary Prevention Study (WOSCOPS) or the Scandinavian Simvastatin Survival Study (4S), and evaluation of its benefit from the estimation of the coronary risk of each patient. METHODS AND RESULTS: The latest European guidelines and Sheffield tables apply these principles and justify the decision to treat hypercholesterolemia if the Framingham coronary multivariate risk estimate is high enough, ie, >20% risk of coronary event at 10 years in the former and >1.5% risk of coronary death per year in the latter. Nevertheless, the practice of these two recent guidelines results in discrepancies in the decision to treat, because coronary morbidity was considered in one but mortality was considered in the other, and the risk required for treating may be extrapolated from different trials (4S or WOSCOPS). CONCLUSIONS: Although the principle of targeting lipid-lowering treatment to high-risk subjects is unquestioned, further studies are needed to demonstrate that the Framingham risk profile is useful in selecting persons who are likely to benefit and to determine the place of newer risk factors and that of early noninvasive detection of atheroma in the risk estimation-based treatment.

Coronary Artery Disease↗

PubMed1997

Sites of reaction of the gastric H,K-ATPase with extracytoplasmic thiol reagents.

The vesicular gastric H,K-ATPase catalyzes an electroneutral H for K exchange allowing acidification of the intravesicular space. There is a total of 28 cysteines present in the alpha subunit of the gastric H,K-ATPase, of which 10 are found in the predicted transmembrane segments and their connecting loop, and 9 are present in the beta subunit, of which 6 are disulfide-linked. To determine which of these was accessible to extracytoplasmic attack, the enzyme was inhibited by four different substituted 2-pyridylmethylsulfinyl benzimidazoles, 5-methoxy-2-[(4-methoxy-3, 5-dimethyl-2-pyridyl)methylsulfinyl]-1H-benzimidazole (omeprazole), 2-[(4-trifluoroethoxy-3-methyl-2-pyridyl)methylsulfinyl]-1H-ben zimida zole (lansoprazole), 5-difluoromethoxy-2-[3, 4-methoxy-2-pyridyl)methylsulfinyl]-1H-benzimidazole (pantoprazole), and 2-[(4-(3-methoxypropoxy)-3-methyl)-2-pyridyl)methylsulfinyl]-1H-++ +benzi midazole (rabeprazole), under acid transporting conditions. All of these compounds are weak bases that accumulate in the acidic space generated by the pump and undergo an acid catalyzed rearrangement to a cationic sulfenamide, which forms disulfides with accessible cysteines. The relative rates of acid activation of these compounds corresponded to the relative rates of inhibition of ATPase activity and acid transport. Fragmentation of the enzyme by trypsin followed by SDS-polyacrylamide gel electrophoresis showed that omeprazole bound covalently to one of the two cysteines in the domains containing the fifth and sixth transmembrane segments and their extracytoplasmic loop and to cysteine 892 in the loop between the seventh and eighth transmembrane segments, but inhibition correlated with the reaction with cysteines in the fifth and sixth domain. Lansoprazole bound to the cysteines in these two domains as well as to cysteine 321 toward the extracytoplasmic end of the third transmembrane segments. Pantoprazole bound only to either cysteine 813 or 822 in the fifth and sixth transmembrane region. The inhibition of Rabeprazole correlated also with its binding to this part of the protein, but this compound continued to bind after full inhibition, eventually binding also to cysteines 321 and 892. No binding was found to any of the cysteines in the seventh to tenth transmembrane segments. Thermolysin digestion of the isolated omeprazole-labeled fifth and sixth transmembrane pair showed that cysteine 813 was the site of labeling. It is concluded that binding of these sided reagents to cysteine 813 in the loop between transmembrane (TM)5 and TM6 is sufficient for inhibition of ATPase activity and acid transport by the gastric acid pump. Of the 10 cysteines present in the membrane and extracytoplasmic domain, only three are exposed sufficiently to allow reactivity with these cationic thiol reagents. The binding to cysteine 813 defines the location of the extracytoplasmic loop between TM5 and TM6 and places the carboxylic acids 820 and 824 conserved between the gastric H,K- and the Na,K-ATPases in TM6, consistent with their assumed role in cation binding.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1997

Observer variability in the diagnosis and management of the hysterosalpingogram.

OBJECTIVE: To determine the reproducibility of hysterosalpingogram (HSG) interpretation and clinical management recommendations among trained observers. DESIGN: Fifty HSG films were distributed to five fertility practitioners with a mean of 20 years clinical experience. Each observer evaluated components of uterine and tubal status and provided clinical recommendations for hysteroscopy and laparoscopy. SETTING: University hospital-affiliated reproductive endocrine practice. INTERVENTION(S): None MAIN OUTCOME MEASURE(s): The level of agreement among observers for each uterine and tubal category as determined by the kappa(kappa) statistic. Determinants of clinical recommendation for further diagnostic studies were assessed. RESULT(S): The level of agreement between observers as determined by kappa ranged from 0.645 in the hydrosalpinx category, indicating fair reliability, to 0.111 for pelvic adhesions, indicating poor reliability. The composite kappa for uterine status was 0.345 whereas the composite kappa for tubal status was 0.430. Agreement among observers concerning management showed marginal reproducibility with a kappa of 0.261. Overall, more than one abnormality of either the cavity or the fallopian tubes led to a diagnostic recommendation for further workup in > or = 90% of cases. CONCLUSION(S): In a group of five experienced clinicians, there was considerable variability in the interpretation as well as the clinical management of the HSG. Physicians caring for infertile couples should be aware of this discrepancy and should, if possible, review carefully both the original films as well as the report of the attending radiologist in formulating their diagnostic evaluation and management plan.

Adolescent↗

PubMed1997

Detection of preclinical atherosclerosis may optimize the management of hypertension.

Because of the limited ability of blood pressure elevation to predict risk, the mass drug treatment of hypertension above an arbitrary threshold may result in many subjects being overtreated. One potential way to overcome this problem is to noninvasively detect preclinical atherosclerosis. Hypertension has been shown to be associated with 1) increased intima-media thickness and more frequent plaques in extracoronary arteries, 2) more frequent calcifications in coronary arteries, 3) increased wall rigidity in the aorta and peripheral arteries, and 4) impaired endothelium dependent vasodilation and abnormal blood rheology, which are capable of promoting the conversion of atherosclerosis into atherothrombosis. The prognostic significance of these markers of preclinical atherosclerosis is supported by evidence of their association with numerous risk factors, and prevalence and incidence of cardiovascular damages. Preclinical arterial lesions also constitute ideal targets to test whether antihypertensive treatment can reverse or slow down arterial disease, and whether such a reversal produces better prevention than simply lowering blood pressure. Finally, the detection of atherosclerosis applied to large populations of mildly hypertensive subjects safely and at relatively low cost could help to better target the pharmacological treatment, given that a substantial proportion of subjects without evidence of preclinical disease may be suitable for nondrug treatment.

Arteriosclerosis↗