Recombinant activated factor VII in patients with cancer and hemorrhagic disseminated intravascular coagulation.

Hemorrhagic disseminated intravascular coagulation (DIC) associated with the presence of underlying advanced or metastatic tumors are often difficult to control by conventional methods. We report the use of recombinant activated factor VII (rFVIIa) in patients with cancer and bleeding secondary to DIC. A total of 18 patients with cancer met pre-defined criteria for DIC. All patients had failed to respond to transfusion with blood products and treatment of the underlying malignancy prior to the introduction of rFVIIa. The median laboratory data at the time of treatment with rFVIIa were as follows: hemoglobin, 7.7 g/dl; platelets, 54 x 10(9)/l; prothrombin time, 21 s; activated partial thromboplastin time, 41 s fibrinogen, 83 mg/dl; D-dimer, 17 microg/ml; and antithrombin, 32%. The dose of rFVIIa was 90 microg/kg and the median number of doses administered was 5 (range, 3-10). Serial measurements of coagulation parameters were obtained at frequent intervals during treatment with rFVIIa. Of the 18 patients, 15 responded with cessation of bleeding and improvement in coagulation data. The prothrombin time and activated partial thromboplastin time normalized in all responding patients within 24 h of treatment. The median fibrinogen was 214 mg/dl while the median D-dimer was 6 microg/dl at 48 h following the administration of rFVIIa. No thromboembolic complications were observed following rFVIIa. Our data provide evidence that rFVIIa can be used successfully to control the hemorrhagic episodes associated with DIC. Although this type of treatment appears to be safe, close monitoring of the patients is warranted.     

The simultaneous measurement of plasma-aldosterone- and -renin-concentration allows rapid classification of all disorders of the renin-aldosterone system.

OBJECTIVE: The determination of the plasma aldosterone (PAC) to the plasma renin concentration (PRC) ratio is an accepted screening tool for primary hyperaldosteronism (PHyperA). DESIGN: To assess the diagnostic significance of this ratio for other disorders of the renin-aldosterone-system (RAS), we examined 60 patients with different adrenal diseases, 32 patients with essential hypertension and 76 normotensive healthy volunteers. The aldosterone (pmol/L) and renin (mU/L) concentrations were measured in one plasma sample by an automated chemiluminescence assay (Nichols Advantage). RESULTS: Patients with PHyperA (n=31) had a PAC/PRC ratio between 105 and 2328 and could be distinguished without overlap from the essential hypertension group (ratio: range 2.7-49) and normal healthy volunteers (ratio: range 0.9-71). Fourteen patients with primary hypoaldosteronism showed low PAC/PRC ratios (range 0.21-0.98) and low PAC values (range: 42-100). Seven patients with secondary hypoaldosteronism had normal PAC/PRC ratios (range 2.8-23.2) and low PAC values (range: 42-116). Eight patients with secondary hyperaldosteronism had normal PAC/PRC ratios (range 7.8-67.9) and elevated PAC values (range: 803-2917). The graphic presentation of these data allowed the differentiation of all major disorders of the RAS. CONCLUSIONS: The measurement of PAC/PRC ratios using this automated system provides a sensitive and rapid screening method for PHyperA. Moreover, the measurement of both the PAC and the PAC/PRC ratio allows differentiation of other disorders of the RAS.     

Septal-lateral annnular cinching perturbs basal left ventricular transmural strains.

OBJECTIVE: Septal-lateral annular cinching ('SLAC') corrects both acute and chronic ischemic mitral regurgitation in animal experiments, which has led to the development of therapeutic surgical and interventional strategies incorporating this concept (e.g., Edwards GeoForm ring, Myocor Coapsys, Ample Medical PS3). Changes in left ventricular (LV) transmural cardiac and fiber-sheet strains after SLAC, however, remain unknown. METHODS: Eight normal sheep hearts had two triads of transmural radiopaque bead columns inserted adjacent to (anterobasal) and remote from (midlateral equatorial) the mitral annulus. Under acute, open chest conditions, 4D bead coordinates were obtained using videofluoroscopy before and after SLAC. Transmural systolic strains were calculated from bead displacements relative to local circumferential, longitudinal, and radial cardiac axes. Transmural cardiac strains were transformed into fiber-sheet coordinates (X(f), X(s), X(n)) oriented along the fiber (f), sheet (s), and sheet-normal (n) axes using fiber (alpha) and sheet (beta) angle measurements. Results: SLAC markedly reduced (approximately 60%) septal-lateral annular diameter at both end-diastole (ED) (2.5+/-0.3 to 1.0+/-0.3 cm, p=0.001) and end-systole (ES) (2.4+/-0.4 to 1.0+/-0.3 cm, p=0.001). In the LV wall remote from the mitral annulus, transmural systolic strains did not change. In the anterobasal region adjacent to the mitral annulus, ED wall thickness increased (p=0.01) and systolic wall thickening was less in the epicardial (0.28+/-0.12 vs 0.20+/-0.06, p=0.05) and midwall (0.36+/-0.24 vs 0.19+/-0.11, p=0.04) LV layers. This impaired wall thickening was due to decreased systolic sheet thickening (0.20+/-0.8 to 0.12+/-0.07, p=0.01) and sheet shear (-0.15+/-0.07 to -0.11+/-0.04, p=0.02) in the epicardium and sheet extension (0.21+/-0.11 to 0.10+/-0.04, p=0.03) in the midwall. Transmural systolic and remodeling strains in the lateral midwall (remote from the annulus) were unaffected. CONCLUSIONS: Although SLAC is an alluring concept to correct ischemic mitral regurgitation, these data suggest that extreme SLAC adversely effects systolic wall thickening adjacent to the mitral annulus by inhibiting systolic sheet thickening, sheet shear, and sheet extension. Such alterations in LV strains could result in unanticipated deleterious remodeling and warrant further investigation.     

腹腔镜和开腹肝切除对机体肝脏功能的影响

目的 研究腹腔镜肝切除（LH）和开腹肝切除（OH）两种手术方式对机体肝脏功能的影响，评估LH的创伤反应。方法 将8个月内收治的40例行肝切除患者，随机分为LH组和OH组，比较两组手术前后部分肝功能指标的变化。结果 两组术后ALT，AST和LDH均迅速升高，与术前相比差异显著，而且OH组明显高于LH组。两组手术前后ALP及γ—GT变化不大，但术后该两指标值OH组明显高于LH组。两组术后TBIL和DBIL均有所增高，但相差不明显，而与术前比较，OH组升高幅度大于LH。结论LH对肝功能的影响小于OH，提示LH对机体的创伤小于OH，有利于减少LH术后肝衰竭。     

Cardinal points and image–object magnification with an accommodative lens implant (1 CU)

A simple mathematical method for the determination of the cardinal points of pseudophakic eyes after implantation of an accommodative intraocular lens [posterior chamber intraocular lenses (PCIOL)] is presented. The purpose of this study was to explore the changes during pseudophakic accommodation (PAC) in (1). the positions of the cardinal points, (2). the distance of the object conjugate with the retina, and (3). the image-object magnification. These theoretical accommodation data are compared with clinical measurements. METHODS AND PATIENTS: Using biometrical measurements of the axial length, equivalent power of the cornea and the anterior chamber depth (ACD) in the non-accommodated state we used linear geometric optics for determination of the cardinal points and object distance as well as lateral magnification (the ratio of image to object size). With the measurement of ACD decrease (following pharmacological stimulation of the ciliary muscle with 2% pilocarpine eye drops) we determined the changes of the cardinal points and magnification to assess PAC amplitude from the shortening of the object distance. Calculated values of PAC amplitude were compared with the respective measured values derived from amplitude measures by accommodometer, defocusing and streak retinoscopy. We analysed the results of a prospective study on 35 eyes of 28 patients after cataract surgery (target refraction: -0.2 D) and accommodative PCIOL implantation (1 CU, Human Optics AG, Erlangen, Germany) 3 months after surgery. RESULTS: After pilocarpine eye drops, ACD (mean +/- S.D., range; median) decreased by 0.88 +/- 0.48 mm (0.51-1.91; 0.66). Distance of the in-focus object decreased from the non-accommodated state (-5.62 +/- 1.83 m, -25 to -1.1; -4.83 m) to the accommodated state (ACD decrease) (-0.81 +/- 0.21, -2.11 to -0.65; -0.79 m). For a theoretical ACD decrease of 1.0 mm (the intrinsic limitation of the PCIOL design) it was -0.59 +/- 0.28, -1.31 to -0.51; -0.63 m and resulted in an objective accommodative response of 1.49 +/- 0.16, 1.21-1.81; 1.46 D, depending on the actual geometry of the individual eye. On average, magnification as induced by PAC in contrast to that induced by adequate spectacle addition differed by only about 1%. Accommodation measured with defocusing and the accommodometer correlated significantly with the theoretical value based on IOLMaster measurement of ACD decrease (r = 0.752, p = 0.005 and r = 0.676, p = 0.02). Likewise, accommodation measured with streak retinoscopy correlated weakly with the theoretical value based on IOLMaster ACD decrease (r = 0.465, p = 0.05). CONCLUSIONS: Using geometrical optics, PAC can be derived from the biometric data of the eye and the measured ACD decrease. This approach may be an additional indicator for the accommodative response in pseudophakic patients and may allow a subdivision of the measured accommodation into true PAC and pseudoaccommodation, for example, because of increased depth of focus induced by pupillary constriction.     

Influence of handedness on calcaneal ultrasound: Implications for assessment of osteoporosis and study design

Calcaneal ultrasound has been increasingly studied for its potential in the assessment of osteoporotic fracture risk. The accuracy of such an assessment is, in part, dependent on the reproducibility of the measurement. This study examines the impact of handedness on ultrasound measurements [broadband ultrasound attenuation (BUA) and velocity of sound (VOS)] in the calcaneus. Two hundred and sixty-four subjects (57 men and 297 women) aged 51.1+13.6 years (mean ± SD) were studied. For each subject, calcaneal ultrasound measurements were performed on both heels with a McCue CUBA ultrasound densitometer. Right-handed dominance (94.7%) was determined by structured interview. In men, BUA measurements were significantly higher on the dominant side: mean difference 4.1±1.5 dB/MHz (mean ± SD;p=0.009), equivalent to 4.2+1.5% and more than 4 times the average rate of annual change in BUA. The difference between sides was greater in young (<50 years) than old men (>50 years). Among the women, the difference was not statistically significant (0.7±0.9 dB/MHz;p=0.4); however, it was significant in younger women (20–30 years) (99±4 vs 90±4 dB/MHz,p=0.01). By contrast VOS did not differ between sides in either men or women irrespective of age. Within-subject standard deviation of BUA was 9.8 dB/MHz for men and 8.6 dB/ MHz for women and the component due to right and left difference was 8.4 dB/MHz for men and 6.9 dB/MHz for women. This variability of BUA between right and left heels could increase the false-positive rate by up to 28% for a cut-off of 2 SD below the mean. These data indicate that variation between left and right heel measurements of BUA is higher than that of random error measurements, particularly in men and younger, presumably more physically active subjects. Although VOS measurements were not side dependent, in the smaller number of studies examining VOS and fracture risk, VOS appears to have a weaker predictive power than BUA. Clinical and epidemiological studies involving calcaneal BUA measurements should standardize the side measured to either the dominant or non-dominant heel, to reduce within-subject variation and increase their power.     

Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants

Background: Only few data exist on pharmacokinetics of tacrolimus in children. Patients: In 1995 and 1996, 14 children (mean age 13 years, range 5-23 years) received tacrolimus after renal transplantation; 10 of these after biopsy-proven steroid-resistant rejection (2 with vascular rejection), two for cyclosporin A (CsA)-induced severe nephrotoxicity, one for untreatable gingival hyperplasia on CsA, and one child was treated primarily after transplantation because of severe liver involvement in nephronophthisis. Pharmacokinetic investigations were performed after establishing a stable maintenance dose with trough levels in the desired window of 5-12 ng/ml. Results: Mean follow-up time was 6 months (range 3-25 months). Eleven patients were still on tacrolimus. Two were discontinued because of severe aggravation of chronic persistent hepatitis C (one of them also developed diabetes mellitus),and one patient was subsequently switched to conventional immunosuppression because of tacrolimus-associated nephrotoxicity. All tacrolimus levels were measured by a modified assay (MEIA, Tacrolimus, Abbott) with improved sensitivity. At the time of switch, median serum creatinine was 234±82 7mgr;mol;l and 6 months after switch 201±99 &mgr;mol/l. All grafts are still functioning. Mean FK-506 dose was 0.16 mg/kg body weight/day (range 0.036-0.30 mg/kg). Mean trough level was 7.1±2.6 ng/ml in the morning and 6.5±2.0 ng/ml in the evening. Median time of maximum concentration (tmax) was 120 min after application, and the mean maximum concentration (Cmax) was 15.2±6.7 ng/ml. Mean area under the curve (AUC) was 104±33 ng * h/ml, with a range from 65 to 169 ng * h/ml. No patient had unsatisfactorily low trough levels during the study. There was only a weak but significant (P<0.05) correlation between dose per kg body weight and AUC and, as expected, an excellent correlation (r²=0.73, P<0.001) between AUC and trough level. Conclusion: Because of interindividual variation between patients, therapeutic drug monitoring of tacrolimus is mandatory. In this study, a daily dose of 0.15 mg/kg was sufficient in most patients. We recommend the performance of at least one pharmacokinetic study after establishing stable FK 506 trough levels to ascertain a safe profile.