Successful treatment of oral linear IgA disease using mycophenolate.

Linear IgA disease (LAD) is a rare acquired autoimmune bullous disorder, characterized by linear deposition of IgA along the dermoepidermal basement membrane zone. The clinical presentation of LAD consists of vesiculobullous lesions affecting the skin and mucosal surfaces. The present case report presents a rare presentation of this vesiculobullous disorder. Although more than 50% of LAD patients present with oral lesions, there are few reported cases of involvement of the mouth as the sole manifestation. A 79-year-old female presented with a sore mouth and erosions affecting the palate. The symptoms resolved following the provision of mycophenolate, an antiproliferative immunosuppressant which has not previously appeared to have been reported in the long-term successful management of linear IgA disease limited to the mouth. We found that mycophenolate is a useful adjunct to the successful treatment of oral linear IgA when the uses of other immunosuppressants are contraindicated.     

Characterization of glial subpopulations in cultures of the ovine central nervous system

The cellular composition and in vitro development of glial cultures derived from the rat CNS has been well studied. However, less information is available on similar cultures from other species, particularly higher mammals. To study ovine glial development in vitro, cultures from 50-day fetal to adult animals were characterized with various immunocytochemical markers, which are frequently used to define neural cell subsets in rat cultures. As in rats, both A2B5+ and A2B5- astrocytes can be identified in ovine cultures. However, ovine A2B5+ and A2B5- could not be reliably differentiated by their morphology, which was more influenced by whether the cells were in serum-free or serum-containing media than by their A2B5-positive or -negative status. In addition, ovine A2B5+ astrocytes were present in cultures from early fetal brain before the development of identifiable oligodendrocytes, unlike rat type II astrocytes, which develop only after the appearance of oligodendrocytes. An A2B5+ cell, morphologically similar to the rat 02-A cell, can be found in cultures from fetal ovine cerebrum or cerebellum. A2B5+/glial fibrillary acidic protein (GFAP)- cells in cultures from 100- to 115-day ovine cerebellum appeared to differentiate into A2B5+ astrocytes in serum-containing media. However, in serum-free media, although the A2B5+ cells assumed a more "oligodendroglial-like" morphology, they did not express galactocerebroside or myelin basic protein, suggesting that these cells may not be bipotential as is the rat 02-A cell. Oligodendroglial differentiation was not induced by treatment with dibutyryl cyclic AMP or insulin-like growth factor I. Many cells in cultures from a variety of fetal ages did not label with any of the immunocytochemical markers used, suggesting the need for more cell-type-specific markers to identify neural cell subsets in higher mammals.     

Psychiatric morbidity in patients with life-threatening asthma: initial report of a controlled study

Thirteen patients who have suffered a "near-miss" death of asthma have been compared to 36 patients with asthma who had not experienced such an episode. Contrary to expectations, there were no differences between the groups in their levels of psychiatric morbidity, their degree of life-style and social restrictions or in their levels of compliance with prescribed medication. However, both groups did show higher than expected levels of psychiatric morbidity, severe life-style and social restrictions and an unexpectedly-high compliance with prescribed medication. The main psychiatric diagnoses that were noted were anxiety disorders. It is concluded that more comprehensive asthma education and close medical follow-up are likely to improve the physical and psychological health of asthmatic patients. The high-risk patients in this study who received such follow-up have shown hospital-admission rates that have been reduced by a half while maintaining good asthma control. This South Australian longitudinal study is continuing.     

RU-486. Termination of a pregnancy in the privacy of one's home

This is an outline of the therapeutic uses of RU-486, followed by clarification of the term "contragestion", and analyses of the theological, legal, and corporate-political issues confronting acceptance of this drug. RU-486 is a computer-designed progesterone antagonist with no known side effects other than those predicted by its endocrinological action. It has been used to terminate pregnancy (with prostaglandin) up to 41 days amenorrhea, and has been shown to terminate pregnancy with fetal demise, to cause luteolysis in the late menstrual cycle, to facilitate management of ectopic pregnancy, to induce term labor (in primates), to soften the cervix prior to mechanical abortion, and to reverse symptoms of causing a syndrome.     

Simulation studies of data classification by artificial neural networks: Potential applications in medical imaging and decision making

Artificial neural networks are being investigated in the field of medical imaging as a means to facilitate pattern recognition and patient classification. In the work reported here, the effects of internal structure and the nature of input data on the performance of neural networks were investigated systematically using computer-simulated data. Network performance was evaluated quantitatively by means of receiver operating characteristic analysis and compared with the performance of an ideal statistical decision maker. We found that the relatively simple neural networks investigated in this study can perform at the level of an ideal decision maker. These simple networks were also found to learn accurately even when the training data are extremely unbalanced with respect to the prevalence of actually positive cases and to differentiate input data patterns by recognizing their unique characteristics.     

Computerized analysis of mammographic parenchymal patterns for assessing breast cancer risk: effect of ROI size and location

The long-term goal of our research is to develop computerized radiographic markers for assessing breast density and parenchymal patterns that may be used together with clinical measures for determining the risk of breast cancer and assessing the response to preventive treatment. In our earlier studies, we found that women at high risk tended to have dense breasts with mammographic patterns that were coarse and low in contrast. With our method, computerized texture analysis is performed on a region of interest (ROI) within the mammographic image. In our current study, we investigate the effect of ROI size and ROI location on the computerized texture features obtained from 90 subjects (30 BRCA1/BRCA2 gene-mutation carriers and 60 age-matched women deemed to be at low risk for breast cancer). Mammograms were digitized at 0.1 mm pixel size and various ROI sizes were extracted from different breast regions in the craniocaudal (CC) view. Seventeen features, which characterize the density and texture of the parenchymal patterns, were extracted from the ROIs on these digitized mammograms. Stepwise feature selection and linear discriminant analysis were applied to identify features that differentiate between the low-risk women and the BRCA1/BRCA2 gene-mutation carriers. ROC analysis was used to assess the performance of the features in the task of distinguishing between these two groups. Our results show that there was a statistically significant decrease in the performance of the computerized texture features, as the ROI location was varied from the central region behind the nipple. However, we failed to show a statistically significant decrease in the performance of the computerized texture features with decreasing ROI size for the range studied.     

Activation of brain neurons by circulating angiotensin II: direct effects and baroreceptor-mediated secondary effects

Circulating angiotensin II acts on neurons in circumventricular organs, leading to activation of central pathways involved in blood pressure regulation and body fluid homeostasis. Apart from this primary effect, an increase in the level of circulating angiotensin II may also activate brain neurons as a secondary consequence of the associated increase in blood pressure, which will stimulate arterial baroreceptors and thus activate central neurons that are part of the central baroreceptor reflex pathway. The aim of this study was to identify the population of neurons that are activated as a consequence of the direct actions of circulating angiotensin II on the brain, independent of secondary baroreceptor-mediated effects. For this purpose, we have mapped the distribution of neurons in the brainstem and forebrain that are immunoreactive for Fos (a marker of neuronal activation) following intravenous infusion of angiotensin II in conscious rabbits with chronically denervated carotid sinus and aortic baroreceptors. The distribution was compared with that evoked by the same procedure in two separate groups of barointact rabbits, in which angiotensin II was infused either at a rate similar to that in the barodenervated group, or at a rate approximately five times greater. In barodenervated rabbits, angiotensin II infusion evoked a significant increase in Fos expression, compared to control animals infused with the vehicle solution alone, in several forebrain nuclei (organum vasculosum of the lamina terminalis, subfornical organ, median preoptic nucleus, supraoptic nucleus, paraventricular nucleus, bed nucleus of the stria terminalis and suprachiasmatic nucleus), but little or no increase in Fos expression in any lower brainstem region. In barointact rabbits infused with angiotensin II at a similar rate to that in barodenervated rabbits, a similar degree of Fos expression was evoked in all of the above forebrain regions, but in addition a significantly greater degree of Fos expression was evoked in several medullary regions (nucleus tractus solitarius, area postrema, and ventrolateral medulla), even though the angiotensin II-evoked increase in mean arterial pressure (17 +/- 3 mmHg) was less than that evoked in the barodenervated rabbits (26 +/- 2 mmHg). In barointact rabbits infused with angiotensin II at the higher rate, the increase in mean arterial pressure was 29 +/- 3 mmHg. In these animals, the pattern of Fos expression was similar to that evoked in barointact rabbits infused at the lower rate, but the degree of Fos expression in all medullary regions and in some forebrain regions was significantly greater. The results of the present study, together with those of previous studies from our laboratory in which we determined the effects of phenylephrine-induced hypertension on brain Fos expression [Li and Dampney (1994) Neuroscience 61, 613-634; Potts et al. (1997) Neuroscience 77, 503-520], indicate that in conscious rabbits circulating angiotensin II activates primarily circumventricular neurons within the organum vasculosum of the lamina terminalis and subfornical organ, but not the area postrema, and this in turn leads to activation of neurons in other forebrain regions, including the median preoptic, supraoptic, paraventricular and suprachiasmatic nucleus as well as the bed nucleus of the stria terminalis. In contrast, the activation of neurons in medullary regions evoked by an increase in the level of circulating angiotensin II is primarily a secondary effect resulting from stimulation of arterial baroreceptors.     

Thoracic aortic dissection in a patient with autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease is one of the most common hereditary diseases, and frequently has well defined extrarenal manifestations. Very few cases of aortic aneurysms associated with this disorder are described in literature. We report a 42-year-old male with autosomal dominant polycystic kidney disease presenting with dissecting aneurysm of the thoracic aorta.