尾部悬吊及恢复过程中大鼠动脉血管收缩反应的变化

目的 探讨模拟失重下动脉收缩反应变化的时程特征及其可逆性。方法 采用尾部悬吊大鼠模型模拟失重,利用离休动脉环测定血管收缩反应的变化。结果 尾部悬吊２ｗｋ后,大鼠的腹主动脉、肠系膜动脉和股动脉收缩反应明显降低,而颈总动脉无明显改变;悬吊４ｗｋ后,肠系膜动脉和股动脉的收缩反应与悬吊２ｗｋ相比有进一步的降低;悬吊８ｗｋ大鼠的动脉血管收缩反应性与悬吊４ｗｋ相比无明显差异;４ｗｋ尾部悬吊大鼠解除悬吊后５ｗｋ     

模拟失重大鼠比目鱼肌小动脉风各级血管内径的变化

目的 探讨模拟失重是否可引起后肢肌肉小动脉网各级血管内径发生改变及其可逆性。方法 采用墨汁灌注法观察尾部悬吊４ｗｋ（ＳＵＳ－４）,悬吊４ｗｋ后恢复１ｗｋ（ＲＥＣ－１）、恢复５ｗｋ（ＲＥＣ－５）,以及对照（ＣＯＮ）大鼠比目鱼肌小动脉网各组血管内径的变化。结果 在ＳＵＳ－４组,比目鱼肌的营养动脉、弓状小动脉及Ｖ、Ⅱ级模行小动脉的内径,较ＣＯＮ组分别减小了３１％、２９％、２８％及４１％（均为Ｐ〈０．０１     

轻、中度缺氧对事件相关电位的影响及不同刺激模式的比较

目的 观察轻、中度缺氧对脑事件相关电位（ＥＲＰ）的影响,比较不同刺激模式发的ＥＲＰ对缺氧的敏感性,方法１２名受试者在地面、２５００ｍ和４３００ｍ匠心同度（吸放低氧混合气）分别进行视觉Ｏｃｄｄｂａｌｌ、Ｓｔｅｒｎｂｅｒｇ记忆量（ＭＳＥＴ）为１ 和ＭＳＥＴ为３的任务测试,记录ＥＲＰ的Ｐ３潜伏期、波幅和反应时（ＲＴ）及反应错误率（ＥＲ）。结果 ４３００ｍ高度缺氧时Ｐ３潜伏期显著延长,任务难度较大时ＥＲ增     

Neovascularization of nucleus pulposus. A diagnostic feature of intervertebral disc prolapse

STUDY DESIGN: Seventy-five surgically excised prolapsed intervertebral discs were histopathologically evaluated. Fifteen prospective normal cadaveric discs were used as control specimens. OBJECTIVE: To compare the morphologic features between the prolapsed and normal discs. SUMMARY OF BACKGROUND DATA: The histologic criteria were edge neovascularization of the fibrocartilage, chondrocyte cloning, fibrillation with fraying, and granular change. METHODS: Sections stained with hematoxylin and eosin, Van Gieson's, and toluidine blue were studied. The presence or absence of edge neovascularization was noted. The other criteria were graded based on a semiquantitative scoring system. RESULTS: Edge neovascularization was observed in 56% of the discs in the test group and in none of the control specimens. Fibrillation with fraying was the most significant finding in the test group (P < 0.001). Although the mean grades were higher in the test group, they did not predict the presence of edge neovascularization. CONCLUSIONS: Edge neovascularization was the most significant finding to confirm disc prolapse. Fibrillation with fraying, was observed more frequently in prolapsed intervertebral discs and the grades of fibrillation with fraying, chondrocyte cloning, and granular change were significantly higher in the test group. Pathologists can usually agree on the presence or absence of a particular histologic characteristic but are rarely consistent when they estimate the degree. Simple, reproducible agreed-on criteria are needed before semiquantitative evaluations become reliable.     

Three-Dimensional Echocardiographic Reconstruction of the Left Ventricle by a Transesophageal Tomographic Technique: In Vitro and In Vivo Validation of its Volume Measurement

Accurate determination of left ventricular (LV) volume has important therapeutic and prognostic implications in patients with cardiac disease. Volume estimations by two-dimensional techniques are not very accurate due to geometric assumptions. OBJECTIVES: To validate LV volume determinations by a new transesophageal three-dimensional echocardiographic technique. We performed three-dimensional reconstruction of the LV using an echo-computed tomographic (CT) technique based on serial pullback parallel slice imaging technique in both in vitro and in vivo settings. Fourteen latex balloons with various sizes (30-235 mL) and shapes (conical, pear shaped, round, elliptical, and aneurysms in various locations) filled with known volumes of water were imaged in a water bath. From the static three-dimensional image, the LV long axis was defined and the LV was sectioned perpendicular to this axis into 2-mm slices. The volume of each slice was calculated with the observer blinded to the actual volume as the product of the slice thickness and the manually traced perimeter of the slice and the LV volume as the sum of the volumes of the slices (Simpson's method). The calculated LV volume closely correlated with the actual volume (r = 0.99, P < 0.0001, calculated volume = 1.06x - 11.3, Deltavolume = -5.7 +/- 10.0 cc). Using the same system, transesophageal echocardiographic (TEE) images of the LV were obtained in 15 patients gated to respiration and ECG. Satisfactory dynamic three-dimensional reconstruction of the LV was possible in ten patients. The three-dimensional LV volumes (systolic and diastolic) using Simpson's method correlated well with those obtained from biplane or multiplane TEE images using the area length method (r = 0.89, p < 0.0001, y = 12.7 + 0.84x, Deltavolume = 1.3 +/- 18.1 cc). The LV major-axis diameters by the two methods showed very close correlations as well (r = 0.86, P < 0.0001, y = 19 + 0.74x, Deltadiameter = 1.0 +/- 7.2 mm). We conclude that three-dimensional LV volume calculation by the echo-CT technique is intrinsically sound, is independent of LV geometry, and with some limitations, is applicable in vivo. (ECHOCARDIOGRAPHY, Volume 13, November 1996)     

Characterization of AUCs from Sparsely Sampled Populations in Toxicology Studies

Purpose. The objective of this work was to develop and validate blood sampling schemes for accurate AUC determination from a few samples (sparse sampling). This will enable AUC determination directly in toxicology studies, without the need to utilize a large number of animals. Methods. Sparse sampling schemes were developed using plasma concentration-time (Cp-t) data in rats from toxicokinetic (TK) studies with the antiepileptic felbamate (F) and the antihistamine loratadine (L); Cp-t data at 13–16 time-points (N = 4 or 5 rats/time-point) were available for F, L and its active circulating metabolite descarboethoxyloratadine (DCL). AUCs were determined using the full profile and from 5 investigator designated time-points termed critical time-points. Using the bootstrap (re-sampling) technique, 1000 AUCs were computed by sampling (N = 2 rats/point, with replacement) from the 4 or 5 rats at each critical point. The data were subsequently modeled using PCNONLIN, and the parameters (k_a, k_e, and V_d) were perturbed by different degrees to simulate pharmacokinetic (PK) changes that may occur during a toxicology study due to enzyme induction/inhibition, etc. Finally, Monte Carlo simulations were performed with random noise (10 to 40%) applied to Cp-t and/or PK parameters to examine its impact on AUCs from sparse sampling. Results. The 5 time-points with 2 rats/point accurately and precisely estimated the AUC for F, L and DCL; the deviation from the full profile was ~10%, with a precision (%CV) of ~15%. Further, altered kinetics and random noise had minimal impact on AUCs from sparse sampling. Conclusions. Sparse sampling can accurately estimate AUCs and can be implemented in rodent toxicology studies to significantly reduce the number of animals for TK evaluations. The same principle is applicable to sparse sampling designs in other species used in safety assessments.     

Friday,December 8, 1995 8Th Annual San Antonio flow cytometry forum

Summary Pseudomonas exotoxin has been genetically modified so that it targets cancer cells. This was accomplished by deleting its cell binding domain and replacing it with Fv fragments of antibodies that react with breast, colon, and other cancers. Several recombinant immunotoxins are now in clinical trials.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.     

Effect of Flumazenil on Ventilatory Drive during Sedation with Midazolam and Alfentanil

Background: Patients who receive a combination of a benzodiazepine and an opioid for conscious sedation are at risk for developing respiratory depression. While flumazenil effectively antagonizes the respiratory depression associated with a benzodiazepine alone, its efficacy in the presence of both a benzodiazepine and an opioid has not been established. This study was designed to determine whether flumazenil can reverse benzodiazepine-induced depression of ventilatory drive in the presence of an opioid.

Methods: Twelve healthy volunteers completed this randomized, double-blind, crossover study. Ventilatory responses to carbon dioxide and to isocapnic hypoxia were determined during four treatment phases: (1) baseline, (2) alfentanil infusion; (3) combined midazolam and alfentanil infusions, and (4) combined alfentanil, midazolam, and "study drug" (consisting of either flumazenil or flumazenil vehicle) infusions. Subjects returned 2-6 weeks later to receive the alternate study drug.

Results: Alfentanil decreased the slope of the carbon dioxide response curve from 2.14 +/- 0.40 to 1.43 +/- 0.19 l [dot] min sup -1 [dot] mmHg sup -1 (x +/- SE, P < 0.05), and decreased the minute ventilation at PET CO2 = 50 mmHg (V with dotE 50) from 19.7 +/- 1.2 to 14.8 +/- 0.9 l [dot] min sup -1 (P < 0.05). Midazolam further reduced these variables to 0.87 +/- 0.17 l [dot] min sup -1 [dot] mmHg sup -1 (P < 0.05) and 11.7 +/- 0.8 l [dot] min sup -1 (P <0.05), respectively. With addition of flumazenil, slope and V with dot sub E 50 increased to 1.47 +/- 0.37 l [dot] min sup -1 [dot] mmHg sup -1 (P < 0.05) and 16.4 +/- 2.0 l [dot] min sup -1 (P < 0.05); after placebo, the respective values of 1.02 +/- 0.19 l [dot] min sup -1 [dot] mmHg sup -1 and 12.5 +/- 1.2 l [dot] min sup -1 did not differ significantly from their values during combined alfentanil and midazolam administration. The effect of flumazenil differed significantly from that of placebo (P < 0.05). Both the slope and the displacement of the hypoxic ventilatory response, measured at PET CO2 = 46 +/- 1 mmHg, were affected similarly, with flumazenil showing a significant improvement compared to placebo.     

Back to the future for wound care?

The European Renaissance was a time of enormous change and rapid progress in the arts, sciences, and medicine. A glimpse of wound care in the last phase of the European Renaissance is provided by the analysis of work by Wilhelm Fabry, the "father of German surgery," as provided in his book De Combustionibus ("Burns") which details his range of treatments for the burn wound, as well as his approach to the later problems of scarring and contracture. We describe some of the historic events which may have stimulated Fabry's writings, in particular, the influences passed down from the medical school of Padua which thereby advanced the cause of wound care and surgery. Finally, we briefly explore the potential of such an approach to the works of our medical forefathers.     

Barriers to follow‐up of abnormal screening mammograms among low‐income minority women

Objective. To describe factors related to compliance diagnostic follow‐up among minority women of low socioeconomic status with abnormal screening mammograms.

Methods. A retrospective cross‐sectional survey using a structured telephone interview. Three cancer screening clinics at an urban inner‐city public hospital. All women with abnormal screening mammograms between September 1990 and January 1992 were eligible; women were interviewed in August 1992. Abnormal mammograms were those requiring specific, non‐routine clinical follow‐up; non‐compliance was defined as delayed follow‐up (four to six months after the date of the mammogram), or no follow‐up at the time of interview (more than 6 months after abnormal).

Results. Sixty‐two of 442 screened women had abnormal results; the overall rate of non‐compliance with follow‐up was 50%. Among the 42 (68%) women who agreed to be interviewed, non‐compliers were less likely to state that they had been told to receive follow‐up than compilers (65% versus 100%; p = 0.008). Non‐compliant women were less likely to have suspicious mammography interpretations (p = 0.05), and more likely to report barriers to follow‐up, such as cost of lost wages and medical care, system barriers, or fears, than compliant women (61.9% versus 9%, p = 0.01). There were no differences between the two groups for age, education, insurance, source of care, family history, knowledge or attitudes.

Conclusions. These preliminary results suggest that follow‐up of low income, minority women with abnormal screening mammograms could be enhanced by improved communication of results. Future studies should extend these findings with larger samples and in other settings and populations.