Two-stage designs for the logistic regression model in single-agent bioassays

In this paper we focus on the use of a two-stage procedure for logistic regression that emphasizes predicting response through the use of the Q-optimality criterion. The use of D-optimality in the first stage is primarily to allow best possible parameter estimates as one enters the second stage. However, it is important to understand that there are many ways to formulate the two-stage procedure. It may involve any optimality criterion in either stage. In fact, theoretically, one need not stop at two stages. It was our intention in this paper to demonstrate the potential in the two-stage procedure in cases in which good initial parameter estimates are not available. Those investigators who are interested in the software for the two-stage procedure described here should contact Dr. William R. Myers.     

Lung capillary albumin leak in oxygen toxicity. A quantitative immunocytochemical study

Uterine leiomyomas or fibroids are common among women of reproductive age, but their biology is poorly understood. The PTH-related protein (PTHrP) has been identified in a number of sites throughout the reproductive tract. We, therefore, examined whether fibroids express PTHrP mRNA and compared their level of expression with that in normal myometrium. Total RNA prepared from fibroid tissue and corresponding normal myometrium from seven patients was examined by RNase protection analysis. In all cases, fibroid and myometrial tissue expressed PTHrP, and in six of seven cases, PTHrP expression was higher in fibroids than in normal myometrium. Cultured fibroid cells from four patients also expressed higher levels of PTHrP mRNA than corresponding cultured normal myometrial cells. Tissue extracts from eight patients and conditioned medium from cultured cells from nine patients were examined for PTHrP immunoreactivity using a two-site immunoradiometric assay. In tissue extracts and conditioned medium, the mean PTHrP concentration was significantly higher in fibroids than normal myometrium. Immunohistochemical staining of fibroid and myometrial tissue was positive for PTHrP. Finally, PTHrP-(1-34) induced a dose-dependent increase in cAMP in fibroid and myometrial cells in vitro. These findings suggest that PTHrP may have an autocrine/paracrine function in regulating myometrial physiology and may play a role in regulating fibroid growth or differentiation.     

Accidental beta radiation burns from an electron accelerator

A 61-year-old man presented to the emergency department after accidental exposure to beta radiation and low dose x radiation from an industrial linear electron accelerator. Over 40 days he developed burns on the extremities, abdomen, and face which eventually healed with topical silver sulfadiazine treatment, but suffered no acute x or gamma radiation symptoms. Beta burns and other radiation effects are discussed.     

A novel phorbol ester from Excoecaria agallocha

The novel phorbol ester 12-deoxyphorbol 13-(3E,5E-decadienoate) [1] was isolated as the anti-HIV principle of Excoecaria agallocha leaves and stems collected in northwest Australia. The structure was determined by spectral means. Compound 1 was also a potent displacer of [3H]-phorbol dibutyrate from rat brain membranes.     

Effect of EGb 761, a ginkgo biloba extract, on early arrhythmia induced by coronary occlusion and reperfusion in dogs

EGb 761 is a preparation of Ginkgo biloba extract, which has complex biologic actions including free radical scavenging activity. To examine the anti-arrhythmic effect of EGb 761, a canine preparation of coronary artery occlusion-reperfusion was tested. Under intravenous anesthesia and open chest conditions, 32 dogs were subjected to 30 min of coronary occlusion, followed by reperfusion. Twelve received EGb 761 by intravenous injection, 1 mg/kg five minutes before coronary occlusion, followed by a continuous infusion of 0.1 mg/kg/min until five minutes after reperfusion. Immediately prior to reperfusion, an additional bolus dose of EGb 761 (1 mg/kg) was again injected (group A). The remaining 20 dogs received saline injection, and served as the control (group B). The electrocardiographic changes were recorded during the whole experimental course. The results showed that, during coronary occlusion, group A dogs had a lower count of ventricular premature beats than group B dogs. However, there was no difference in the incidence of ventricular tachycardia (VT) between the two groups. The duration of VT of the treated dogs was similar to that of the control dogs. The incidence of ventricular fibrillation (VF) was also similar. Upon reperfusion, the treated dogs were shown to be protected from VF. The duration of VT was also shorter in the treated group, although the incidence of VT was not different between the two groups. EGb 761 is effective in preventing early VF induced by coronary reperfusion while ineffective in protecting the ischemic VT and VF.     

Predictors of intracranial pathologic findings in patients who seek emergency care because of headache

BACKGROUND: Clinical criteria to select patients with headache in whom structural diagnostic studies (computed tomography) have a high yield disclosing intracranial pathologic findings, independent of abnormal findings on neurologic examination, have not been defined. OBJECTIVE: To determine which clinical characteristics predict the presence of intracranial pathologic findings, independently of neurologic examination, in patients with headache. DESIGN: Case-control, consecutive sample. SETTING: Major metropolitan trauma center emergency department. PATIENTS AND MATERIALS: Hospital records of 139 hospitalized and 329 randomly selected patients from 1720 nonhospitalized adult patients, consecutively evaluated for headache in the emergency department, were reviewed. Demographic data, clinical characteristics of the headache, results of neurologic and physical examinations, and diagnostic radiologic and laboratory results were correlated with final diagnosis and outcome at 6 months after emergency department visit. DATA ANALYSIS: Nonparametric statistical analysis. RESULTS: Intracranial pathologic findings were found in 18 (3.8%) of 468 patients. Acute onset and occipitonuchal location of headache, presence of associated symptoms, and patient age of 55 years or older were significantly associated with the finding of intracranial pathology, independently of the findings from neurologic examination. Abnormal findings on neurologic examination alone, whether focal or nonfocal, had a highly significant association and a positive predictive value for intracranial pathology of 39%. CONCLUSIONS: Abnormal results from neurologic examination are the best clinical parameters to predict structural intracranial pathology; however, in patients 55 years or older with headache of acute onset located in the occipitonuchal region that has associated symptoms, computed tomographic scan of the head is justified as part of their clinical evaluation independently of the findings of the neurologic examination.     

Dicationic furans inhibit development of Cryptosporidium parvum in HSD/ICR suckling Swiss mice

The efficacy of dicationic diarylfurans was evaluated against Cryptosporidium parvum by a suckling murine model. Candidate drugs were solubilized or suspended in deionized water and administered orally at a constant dose rate on days 0-5 (treatment day 0) to suckling ICR Swiss mice experimentally inoculated with oocysts of C. parvum. Efficacy was based on numbers of oocysts recovered from the intestinal tracts of mice subjected to necropsy examination on day 6. Numerous candidate furans significantly reduced the numbers of oocysts recovered from treated mice compared with control mice. Compounds 1, 2, 4, and 9 demonstrated superior efficacies (10% of controls or better) against C. parvum. Compounds 3, 5, 6, 7, 8, 11, 17, 18, and 19 also significantly reduced the numbers of oocysts recovered from treated mice but demonstrated efficacies ranging from 17 to 65% of controls. Compound 4 was particularly efficacious against C. parvum at a dosage as low as 8.5 mg/kg of body weight. Compound 4 is identified as a lead compound for additional studies in other animal models.