Enzyme immunochromatography--a quantitative immunoassay requiring no instrumentation

We describe a novel test-strip immunoassay for quantifying drugs in biological fluids. This enzyme immunochromatographic ("immunograph") method combines many features of the enzyme-channeling homogeneous immunoassay with immunochromatography and capillary migration to provide a non-separation, non-instrumental assay for theophylline in which quantification is based on the spatial distribution of enzyme label rather than on the modulation of enzyme activity. Sample antigen and hapten-enzyme conjugate are combined and moved by capillary action up a paper strip on which specific antibody has been immobilized. After color development, the assay result is evaluated by measuring the height of the colored zone on the test strip. Quantification is not a function of enzyme activity, so the method is relatively insensitive to sample matrix effects, enzyme instability, temperature, and incubation timing. Either whole blood or plasma can be used as sample. Results correlate well with those by established instrumental methods. The simple, rapid (15 min), two-incubation protocol is well suited for on-site testing in non-laboratory environments.     

A randomized trial of high-dose methotrexate versus standard-dose methotrexate following cyclophosphamide, doxorubicin (adriamycin), vincristine, and prednisone with or without bleomycin in the therapy of diffuse large cell lymphoma: preliminary report of Cancer and Leukemia Group B Study 7851

Between 1979 and 1985, 166 patients with diffuse large cell (histiocytic) lymphoma were randomized to receive therapy with 3 courses of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and prednisone (CAVP), with or without low-dose bleomycin, by continuous iv infusion. Responders were further randomized to 3 weeks of therapy with either high-dose methotrexate (3 g/m2 iv weekly with leukovorin rescue) or low-dose methotrexate (30 mg/m2 orally weekly without rescue). Therapy was concluded with 3 additional courses of CAVP. No significant differences among the 4 treatment programs were observed in complete response rates (ranging from 46% to 51%) or in failure-free survival. Of the 38 relapses that have occurred in patients treated with low-dose methotrexate, 5 included relapse in the central nervous system in conjunction with systemic relapse. However, none of 31 relapses observed in patients receiving high-dose methotrexate have occurred with involvement of the central nervous system. Patients entering this study with "B" symptoms had significantly poorer treatment results than those patients entering study without "B" symptoms.     

Antenatal differentiation of the human intervertebral disc

Summary To study the antenatal differentiation of the human intervertebral disc, the columns of forty eight embryos and fetuses were examined histologically. The primitive disc is composed of two structures: the notochord which shows a progressive expansion into the disc, and the fibrocartilaginous perinotochordal disc. No histological sign of interaction between notochordal and perinotochordal cells, which may explain the notochordal expansion into the discs, was seen. On the other hand, the notochordal intervention in the cartilaginous differentiation of the inner zone is probable.

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Différenciation anténatale du disque intervertébral humain

Résumé Cette étude de la différenciation anténatale du disque intervertébral humain repose sur l'examen de coupes histologiques de quarante huit colonnes vertébrales d'embryons et de foetus. Le disque primitif est composé de deux structures : la notochorde, qui présente une expansion progressive de son diamètre au sein du disque, et le disque périnotochordal, d'abord mésenchymateux puis fibrocartilagineux. Il n'a pas été mis en évidence de signe histologique témoignant d'une interaction entre les cellules notochordales et les cellules périnotochordales qui puisse expliquer l'expansion de la notochorde au sein des disques. Le rôle de la notochorde dans la différenciation cartilagineuse de la zone centrale est par contre probable.

     

温血心停跳液与冷晶体心停跳液对狗心率变异性的影响

为探讨体外循环（ＣＰＢ）导致心脏植物神经系统（ＣＡＳ）损伤的机理,了解温血心停跳液能否防止ＣＰＢ后心率变异性（ＨＲＶ）的降低,采用对照方法观察了温血心停跳液与冷晶体心停跳液对狗ＨＲＶ的影响。结果显示：ＣＰＢ后温血心停跳液组（ＷＢ组）和冷晶体心停跳液组（ＣＣ组）的全频谱（ＴＰ）、低频（ＬＦ）和高频（ＨＦ）均较术前明显降低（Ｐ＜０．０５）,而且ＣＣ组比ＷＢ组降低更明显（Ｐ＜０．０５）,但ＬＦ／ＨＦ在组内及组间均无明显变化（Ｐ＞０．０５）。ＣＰＢ后２４小时平均心率（ＭＨＲ）明显增加（Ｐ＜０．０５）,且ＣＣ组高于ＷＢ组（Ｐ＜０．０５）。本研究表明：采用温血心停跳液或冷晶体心停跳液的ＣＰＢ不会干扰ＣＡＳ平衡,但均能使ＨＲＶ降低,温血心停跳液不能防止ＨＲＶ损害。     

Influence of early posttraumatic hypothermia therapy on local cerebral blood flow and glucose metabolism after fluid-percussion brain injury

OBJECT: Using autoradiographic image averaging, the authors recently described prominent foci of marked glucose metabolism-greater-than-blood-flow uncoupling in the acutely traumatized rat brain. Because hypothermia is known to ameliorate injury in this and other injury models, the authors designed the present study to assess the effects of posttraumatic therapeutic hypothermia on the local cerebral metabolic rate of glucose (LCMRglu) and local cerebral blood flow (LCBF) following moderate parasagittal fluid-percussion head injury (FPI) in rats. METHODS: Either cranial hypothermia (30 degrees C) or normothermia (37 degrees C) was induced for 3 hours in matched groups of rats immediately after FPI; LCMRglu and LCBF were assessed 3 hours after concluding these temperature manipulations. In rats subjected to FPI, regardless of whether normothermia or hypothermia ensued, LCBF was reduced relative to the sham-injury groups. In addition, when FPI was followed by hypothermia (FPI-30 degrees C group), the subsequent LCBF was significantly lower (35-38% on average) than in FPI-37 degrees C rats. Statistical mapping of LCBF difference imaging data revealed confluent cortical and subcortical zones of significantly reduced LCBF (largely ipsilateral to the prior injury) in FPI-30 degrees C rats relative to the FPI-37 degrees C group. Local glucose utilization was reduced in both hemispheres of FPI-37 degrees C rats relative to the sham-injury group and was lower in the right (traumatized) hemisphere than in the left. However, LCMRglu values were largely unaffected by temperature manipulation in either the FPI or sham-injury groups. The LCMRglu/LCBF ratio was nearly doubled in FPI-30 degrees C rats relative to the FPI-37 degrees C group, in a diffuse and bihemispheric fashion. Linear regression analysis comparing LCMRglu and LCBF revealed that the FPI-37 degrees C and FPI-30 degrees C data sets were completely nonoverlapping, whereas the two sham-injury data sets were intermixed. CONCLUSIONS: Despite its proven neuroprotective efficacy, early posttraumatic hypothermia (30 degrees C for 3 hours) nonetheless induces a moderate decline in cerebral perfusion without the (anticipated) improvement in cerebral glucose utilization, so that a state of mild metabolism-greater-than-blood-flow dissociation is perpetuated.     

Duration and recovery profile of cisatracurium after succinylcholine during propofol or isoflurane anesthesia

Study Objective: To determine the duration and recovery profile of maintenance doses of cisatracurium besylate following succinylcholine, and during propofol or isoflurane anesthesia.

Design: Randomized, open-label study.

Setting: Operating suite of a university-affiliated medical center.

Patients: Forty ASA physical status I and II adult patients having elective surgery with general anesthesia lasting longer than 90 minutes.

Interventions: Following a standardized induction sequence, a baseline electromyogram (EMG) was obtained. An intubating dose of intravenous (IV) succinylcholine 1.0 mg/kg was administered. Ventilation was maintained with a face mask until the first twitch (T₁) of the evoked train-of-four (TOF) reached 10% of control when tracheal intubation was performed. Spontaneous recovery from neuromuscular blockade was allowed to occur until the first twitch returned to 25% of control. Patients then were randomized to receive cisatracurium as follows. Group 1: 0.025 mg/kg [0.5 × 95% effective dose (ED₉₅)]; Group 2: 0.05 mg/kg (ED₉₅); Group 3: 0.05 mg/kg (ED₉₅); and Group 4: 0.1 mg/kg (2×ED₉₅). Anesthesia for Groups 1 and 2 were maintained with isoflurane 1% to 2%, 66% nitrous oxide (N₂O) in oxygen (O₂), and in Groups 3 and 4, anesthesia was maintained with propofol 80 to 160 μg/kg/min, 66% N₂O in O₂. The TOF-evoked EMG was recorded at 10-second intervals. The time for the evoked EMG to spontaneously return to 25%, 50%, and 75% of the original baseline was recorded.

Measurements and Main Results: There were 10 patients in each of the four groups. The duration of action of cisatracurium 0.05 mg/kg (ED₉₅) after an intubating dose of succinylcholine is 24.5 ± 10 minutes and 21.3 ± 9 minutes during anesthesia maintained with isoflurane and propofol, respectively. Doubling the dose of cisatracurium resulted in approximately twice the duration of action (40.2 ± 7 min) during propofol anesthesia. Following a dose of cisatracurium 0.025 mg/kg (0.5×ED₉₅), the T₁ of the EMG-evoked response did not decrease below 25% in 7 of 10 patients.

Conclusion: Following succinylcholine, the duration of action of a single dose of cisatracurium 0.05 mg/kg is 20 to 25 minutes during anesthesia maintained with propofol or isoflurane. The duration and recovery profile of cisatracurium is dose dependent during propofol and isoflurane anesthetics. Cisatracurium 0.025 mg/kg is an inadequate maintenance dose following recovery from succinylcholine and it fails to provide adequate surgical relaxation.     

Resection of lung metastases: long-term results and prognostic analysis based on 5206 cases--the International Registry of Lung Metastases

The International Registry of Lung Metastases was established in 1991 to asses the long-term results of pulmonary metastasectomy. The Registry has accrued 5206 cases of lung metastasectomy, from 18 departments of thoracic surgery in Europe (n = 13), USA (n = 4) and Canada (n = 1). Of these patients 4572 (88%) underwent complete surgical resection. The primary tumor was epithelial in 2260 (43%), sarcoma in 2173 (42%), germ cell in 363 (7%), and melanoma in 328 (6%) patients. The disease-free interval was 0 to 11 months in 1729 (33%) cases, 12 to 35 months in 1857 (36%) and more than 36 months in 1620 (31%). Single metastases accounted for 2383 (46%) cases and multiple lesions for 2726 (52%). Mean follow up was 46 months. Analysis was performed by Kaplan-Meier estimates of survival, relative risk of death and multivariate Cox model. The actuarial survival after complete metastasectomy was 36% at 5 years, 26% at 10 years and 22% at 15 years (median 35 months); the corresponding values for incomplete resection were 13% at 5 years and 7% at 10 years (median 15 months). Among complete resections, the 5-year survival was 33% for patients with a disease free-interval of 0 to 11 months and 45% for those with a disease-free interval of more than 36 months; 43% for single lesions and 27 for four or more lesions. Multivariate analysis showed a better prognosis for patients with germ cell tumors, disease-free interval of 36 months and more and single metastases. These results confirm that lung metastasectomy is a safe and potentially curative procedure.