Prevalence of autoimmune diseases in islet transplant candidates with severe hypoglycaemia and glycaemic lability: previously undiagnosed coeliac and autoimmune thyroid disease is identified by screening.

AIMS: Autoimmune diseases such as Addison's or coeliac disease can contribute to hypoglycaemia or malabsorption and are more common in Type 1 diabetes (T1DM). This brief report describes the prevalence of known and newly detected autoimmune disease in clinical islet transplant candidates with longstanding T1DM and severe hypoglycaemia and/or glycaemic lability who are routinely screened for coexisting autoimmune disease. METHODS: One hundred and twenty-four C-peptide negative T1DM subjects [77 (62%) female, mean age 44 +/- 9 years, diabetes duration 28 +/- 11 years, body mass index 24.9 +/- 3.5 kg/m(2)] with indications for clinical islet transplantation at the University of Alberta were screened for autoimmune disease by history and measurement of anti-transglutaminase antibodies (positive > 10 U/ml), 09.00 h cortisol (followed by adrenocorticotrophic hormone-stimulation if < 495 nmol/l) and thyroid-stimulating hormone to determine the prevalence of coeliac disease, Addison's disease and autoimmune thyroid disease, respectively. RESULTS: Forty per cent of subjects had one or more coexisting autoimmune disease. The prevalence of autoimmune disease was 35%, coeliac disease 8% and Addison's disease 1.6%. In 11 individuals (9%), one or more autoimmune disease were newly detected (seven coeliac disease and five thyroid disease). Seven of 10 cases of coeliac disease were newly detected. A gluten-free diet in individuals with newly diagnosed coeliac disease reduced gastrointestinal symptoms, but indications for clinical islet cell transplantation persisted. CONCLUSIONS: Coexisting autoimmune disease is common in candidates for clinical islet cell transplantation. Screening in this group identified a substantial number of previously unrecognized cases. Clinicians should consider the presence of autoimmune disease even in the absence of classical symptoms.     

Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain

The receptor mGluR5 is a metabotropic glutamate receptor with messenger RNA abundantly present throughout cortex, hippocampus, and caudate/putamen that is also coupled to phosphatidyl inositide hydrolysis and calcium mobilization. In this study, the distribution of mGluR5 was examined in rat brain by immunocytochemistry. The antibody utilized is highly specific and does not cross react with the most closely related other metabotropic glutamate receptor, as determined by Western blot analysis of nonneuronal cells transfected with metabotropic receptor coding sequences. The receptor mGluR5 is widely expressed with the highest density in olfactory bulb, caudate/putamen, lateral septum, cortex, and hippocampus, as confirmed with both immunocytochemistry and Western blot analysis. Electron microscopic studies in hippocampus and cortex indicate that the labeling is mostly on membranes of dendritic spines and shafts. Light and electron microscopic evidence indicates that some mGluR5 immunoreactivity is located in presynaptic axon terminals, suggesting that mGluR5 may function as a presynaptic receptor.     

Sensorineural hearing loss in patients with typical retinitis pigmentosa

We performed detailed audiologic testing in 45 patients with retinitis pigmentosa and 45 age- and sex-matched controls. Ten (22%) of the retinitis pigmentosa patients had a sensorineural hearing loss that varied from mild to severe. None of the control subjects had a hearing loss. Audiograms measured over a ten- to 30-year period were available for four patients with retinitis pigmentosa and each showed progressive hearing loss. The results indicate the important role of audiologic evaluation in treating patients with retinitis pigmentosa.     

Organic brain damage and occupational solvent exposure.

Three hundred and nine men with organic dementia, cerebral atrophy, or psycho-organic syndrome admitted for five nights or more to one of 18 Quebec hospitals were individually matched with patients admitted (1) with some other psychiatric diagnosis and (2) to a general hospital. Lifetime occupational histories were obtained by telephone. Occupational exposure to solvents was assessed blind to type of case by (1) individual ratings and (2) a job exposure matrix; men who worked in moderate or high solvent concentrations for at least 10 years were considered exposed. With the psychiatric referent series, an odds ratio of 1.4 (90% CI 1.0-2.0) was calculated by individual exposure ratings and 1.4 (90% CI 0.9-2.2) by job matrix. Increased risk was mainly in those with organic dementia or cerebral atrophy and an alcohol related diagnosis. The same pattern of risk was found against the general hospital referents. Adjustment for possible confounders did not alter the risk estimates appreciably. Also, lifetime job histories, compared in selected case-referent pairs, gave similar evidence of increased risk (odds ratio 2.3; 90% CI 1.0-5.5). It is concluded that the combined effect of occupational solvent exposure and alcohol intake is probably an important cause of organic brain damage.     

Comparison of the use of nalbuphine and fentanyl during third molar surgery

In a double-blind, randomized plan of drug administration, nalbuphine, fentanyl, and a placebo were compared for efficacy in sedation and analgesia during third molar removal. Fifty-eight patients participated in this study. Using accepted intravenous sedation and surgical techniques, fentanyl and nalbuphine were found to be better than placebo for anxiety and pain control in third molar surgery. Fentanyl had a longer duration of pain relief postoperatively than did nalbuphine. The study confirmed the need for a narcotic supplement to sedation techniques for third molar surgery.     

Organization of amygdaloid projections to the mediodorsal thalamus and prefrontal cortex: a fluorescence retrograde transport study in the rat

Previous studies have shown that the amygdala projects to both the mediodorsal thalamic nucleus (MD) and its cortical projection area, the prefrontal cortex (PFC). In this investigation rats received injections of different fluorescent retrograde tracers (true blue and diamidino yellow) into MD and either the lateral, polar, or medial PFC in order to examine the relationship of amygdaloid neurons with cortical and/or thalamic projections. PFC injections labeled neurons in the basolateral (BL), basomedial (BM), ventral endopiriform (EnV), and rostral lateral nuclei as well as the periamygdaloid cortex (PAC) and the medial part of the amygdalohippocampal area (AHA). In BL, which contained the great majority of neurons projecting to PFC, most labeled cells were concentrated in particular parts of the nucleus and were topographically organized. The overwhelming majority of labeled neurons in BL were large pyramidal or piriform cells that correspond to class I neurons described in Golgi studies. Occasional small neurons with thin dendrites were also observed; these cells may be class II neurons. MD injections labeled numerous cells in the anterior division of the cortical nucleus, medial nucleus, and caudomedial part of the central nucleus. Moderate numbers of labeled cells were found in caudal portions of BM and PAC, whereas scattered cells were observed throughout the rest of the amygdala with the exception of the lateral nucleus. In BL and AHA many MD-projecting neurons were observed along nuclear boundaries and in the adjacent white matter. Neurons in BL, BM, and AHA usually had large elongated or irregular somata and two to four primary dendrites that branched sparingly. Other cells had smaller ovoid somata. The morphology and distribution of MD-projection cells in the basolateral amygdala indicate that they are primarily large class II neurons. Double-labeled amygdaloid neurons, labeled by both cortical and thalamic injections, were observed only in a small number of animals. Control experiments suggest that most of the double-labeled cells in these cases were artifacts caused by spread of the thalamic injectate into the third ventricle with subsequent uptake by fibers in the anterior commissure. Thus the findings of this study suggest that different neuronal populations in the amygdala project to the two poles of the MD-PFC system. In the basolateral amygdala class I neurons are the predominant cell type involved in PFC projections, whereas a subpopulation of class II neurons, hitherto thought to be primarily local-circuit neurons, project to MD.     

Neurotransmitters and neuropeptides in Alzheimer's disease.

The neurotransmitter and neuropeptide changes in Alzheimer's disease are outlined in Table 1. Many of the changes, such as decreases in CSF ACh and SRIF, are well documented and correlate with the severity of the dementia; however, they are relatively nonspecific. The changes in neurotransmitter availability have offered new insight into both the pathophysiology and possible treatment strategies in Alzheimer's disease. It is evident that the disease is characterized by pathologic involvement of multiple neurotransmitter systems, including those that utilize ACh, SRIF, CRF, and, most probably, monoamines and excitatory amino acids. The role each system has in the signs and symptoms of Alzheimer's disease remains obscure.     

Complications of endodrainage retinotomies created during vitreous surgery for complicated retinal detachment

The authors report nine cases of endodrainage retinotomy site complications that occurred after vitreous surgery for complicated retinal detachments (RDs). Postoperative subretinal neovascularization developed in four eyes at the retinotomy drainage site. In two eyes, postoperative proliferation at a posteriorly placed endodrainage site created traction macular detachments. Redetachment due to retinotomy opening caused by postoperative drainage site proliferation developed in three eyes. The retinas of all nine eyes were eventually reattached, and vision improved from the preoperative level. These complications are related to retinal pigment epithelium and/or Bruch's membrane damage during internal subretinal fluid drainage and retinotomy endolaser photocoagulation. Careful evaluation of extrusion instruments, drainage techniques, retinotomy placement, and subsequent endolaser treatment is necessary to minimize these complications.