Prospective evaluation of the effect on initial brain metastases from small cell lung cancer of platinum-etoposide based induction chemotherapy followed by an alternating multidrug regimen

BACKGROUND:: During the 1980s reports describing the effect of systemic chemotherapyon brain metastases from chemosensitive tumours emerged, includinga few retrospective reports on small cell lung cancer (SCLC)patients. DESIGN:: Previously untreated SCLC patients with no other malignancy,but in some cases with mixed histological subtype, who had symptomaticbrain metastases verified by contrast enhanced CT-scan, weretreated with a multidrug combination chemotherapy regimen andno cranial irradiation. Radiotherapy was optional at cranialrelapse or progression at the discretion of the physician incharge. The intracranial effect was evaluated by 4-weekly CT-scanand neurological examination, according to a standardized scoringsystem. END POINTS:: Intracranial response, duration of response, neurological score,terminal CNS status, and survival. RESULTS:: 21 patients were included, corresponding to 8.6% of consecutiveSCLC patients at our institution. 8 patients died before follow-upleaving 13 evaluable for response. In the former group, allpatients had WHO performance status of 3–4 compared to6/13 in the latter group. Of the 13 evaluable patients, 1 hadearly progression in the CNS and 1 had no change. 11 had CT-scanverified response, with a median duration of 135 days. Mostpatients, including all complete responders, had improvementin their neurological score. 6 out of 11 responders died withoutactive CNS disease. The crude median survival was 111 days,whereas the median survival(early deaths excluded) was 197 days. CONCLUSION:: Systemic combination chemotherapy was effective for palliationof initial brain involvement in the majority of patients ina small consecutive series. The role of consolidating cranialirradiation in responders should be assessed by a randomizedtrial. small cell carcinoma, brain metastases, chemotherapy     

Tibial hypo-/aplasia with preaxial syn- and polydactyly

Summary Tibial hypo-/aplasia with preaxial syn- and polydactyly is a rare autosomal dominant condition. Fewer than 20 cases have so far been described. One is presented here.     

Neural classifier construction using regularization, pruning and test error estimation

In this paper we propose a method for construction of feed-forward neural classifiers based on regularization and adaptive architectures. Using a penalized maximum likelihood scheme, we derive a modified form of the entropic error measure and an algebraic estimate of the test error. In conjunction with optimal brain damage pruning, a test error estimate is used to select the network architecture. The scheme is evaluated on four classification problems.     

Vesico-anal influences in healthy intact humans: Quantificated by responses in the external anal sphincter following transcranial cortical stimulation

EMG responses in the external anal sphincter (EAS), the rectus abdominis muscle (RA), and the anterior tibial muscle (TA) were recorded following single magnetic transcranial cortical stimulations (TCCS) in seven healthy volunteers. The responses in the EAS differed from the responses in the other muscles. They had comparatively long durations ranging from 1 to 2 seconds, no inhibitory periods were observed, and there was no tendency for habituation to occur following a limited number of stimuli. The responses recorded in the EAS were used as test responses in order to evaluate the excitability changes in the EAS motoneurons occurring during bladder filling. Cystometries with filling rates of 15, 50 and 200 ml/min were done. During these cystometries TCCS were applied repeatedly, with constant strength, after each 50 ml of filling up to bladder capacity. The responses following TCCS changed in a highly reproducible way during bladder filling. After 100–200 ml of filling, the responses had longer latencies, diminished sizes, and shorter durations. When the filling reached a level 50–150 ml below capacity, the responses in most subjects again became greater and the latencies shorter. The changes were believed to be physiological. It was concluded that the EAS motoneurons are under both inhibitory and facilitatory influence during bladder filling in intact healthy humans. Facilitatory influences are often observed when the bladder is filled close to capacity. At lower bladder volumes the observed influence is always inhibitory. A decrease in the EMG activity of the EAS during filling cystometry should consequently not be regarded as a pathological response.     

Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat,and the effect of type I and type II corticosteroid receptor antagonists

The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms.     

Effects of amrinone on thrombin-induced platelet-derived growth factor-like protein secretion from endothelial cells

Endothelial cells (EC) secrete platelet-derived growth factor (PDGF)-like protein, which is a potent mitogen to smooth muscle and connective tissue cells. The purpose of this study was to determine if amrinone, a phosphodiesterase inhibitor, could inhibit PDGF-like protein secretion on the basis of its ability to increase cAMP. Human umbilical artery endothelial cells (HUAEC) (n = 7) were preincubated for 4 h with amrinone (10 micrograms/mL) before coincubation with thrombin (10 IU/mL) and amrinone (10 micrograms/mL) for 18 h. The supernatant was then assayed for the presence of both PDGF-like protein by using a competitive 125I-PDGF radioreceptor inhibition assay, and cAMP by using an RIA. Thrombin-induced PDGF-like protein secretion from HUAEC was significantly inhibited by amrinone (7.8 +/- 1.6 fmol/10(6) EC) when compared with thrombin alone (12.1 +/- 2.4 fmol/10(6) EC) (p less than 0.05). Amrinone alone had no effect on baseline PDGF-like protein secretion. Amrinone inhibition of thrombin-induced PDGF-like protein secretion was comparable whether amrinone was added to HUAEC 4 or 0 h before thrombin, and it was dose dependent with a maximal inhibition of 82.7% by amrinone (160 micrograms/mL). In contrast, IL-1 alpha (10 micrograms/mL) and tumor necrosis factor (100 ng/mL) induced less secretion of PDGF-like protein from HUAEC, and this secretion was not inhibited by amrinone. Amrinone (10 micrograms/mL) significantly increased secretion of cAMP from HUAEC from a baseline value of 6.4 +/- 0.4 pmol/10(6) EC to 10.6 +/- 0.1 pmol/10(6) EC (p less than 0.01). We conclude that amrinone inhibits thrombin-induced PDGF-like protein secretion from HUAEC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recurrent wheezing in relation to environmental risk factors in infancy

Clinical course and environmental factors were recorded in a prospective study of 276 unselected infants followed from birth to the age of 18 months. The study was performed with a questionnaire at the age of 6 and 12 months and a physical examination at 18 months. Fifty-nine (21%) of the children had greater than or equal to 2 episodes of wheezing before they were 18 months old. A total of 58 (21%) of the children belonged to the lowest social class V, 182 (66%) were daily exposed to passive tobacco smoking at home and/or in daycare, 164 (59%) were breastfed greater than or equal to 3 months, 192 (70%) were in daycare, 62 (22%) lived in flats and 167 (61%) were in daily contact with furred pets at home and/or in daycare. In social class V a preponderance of children were exposed to passive tobacco smoking, a majority were living in flats and a minority were breastfed greater than or equal to 3 months. Linear logistic regression analysis was used for the purpose of assessing the causal effect of environmental risk factors on the risk of recurrent episodes of wheezing before the age of 18 months. The study demonstrated that male sex and daily exposure to passive tobacco smoking were significant risk factors with estimated odds ratios 1.9 and 2.4, respectively. Maternal tobacco smoking seemed to be associated with the highest risk. There was a tendency--though not significant--indicating that breastfeeding greater than or equal to 3 months had a protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)