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.     

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.     

Direct evidence for the involvement of carbohydrate sequences in human sperm-zona pellucida binding

Several lines of evidence indicate that mammalian fertilization is initiated via a binding process that is dependent upon the recognition of oligosaccharide sequences associated with zona pellucida (ZP) glycoproteins. Here, specific chemical and enzymatic methods were employed to modify human ZP and to test their effects on sperm binding in the hemizona assay system (HZA). Periodate oxidation of human ZP under very mild conditions (10 min, 0 degrees C, 1 mM sodium m- periodate) that attacks only terminal sialic acid resulted in a 30% loss of human sperm binding in the HZA [hemizona index (HZI) = 70.2 +/- 10.9, n = 22; P < 0.05]. Periodate oxidation under mild conditions (1 h, 23 degrees C, 10 mM sodium m-periodate) caused a 40% decrease in binding (HZI = 60.8 +/- 10.3; n = 24; P< 0.01). Treatment of human ZP with neuraminidase caused a substantial increase in sperm binding to human ZP (HZI = 297 +/- 45, n = 22; P < 0.01). These findings indicate that there are sialic acid dependent binding sites coexisting with binding sites that are obscured by sialic acid. To determine the periodate sensitivity of these obscured sites, hemizona were first digested with neuraminidase and subsequently subjected to mild periodate oxidation. The combined enzymatic and chemical treatments caused a 79% decrease in sperm binding compared to control hemizona (HZI = 20.7 +/- 4.4, n = 16; P < 0.001). Human sperm-ZP interaction was also increased by digestion of human ZP with endo-beta-galactosidase (HZI = 710 +/- 232, n = 14; P < 0.01), indicating that potential binding sites for spermatozoa are also obscured by lactosaminoglycan sequences. These studies support a definitive role for the involvement of ZP-associated glycans in the binding of human spermatozoa to oocytes.      

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.