Argon laser lesions of the retina; occurrence and origin of macrophages.

Macrophage infiltration is frequent in the early stages of various proliferative eye disorders, including subretinal neovascularization. In this study, we set out to establish the origin of macrophages found in an animal model of laser-induced subretinal neovascularization. One primate received several intravenous injections of a colloidal carbon suspension. We then applied standard argon laser lesions to the retina of both eyes, which were enucleated eight days later and sectioned serially for histological examination. A quantitative estimate of carbon-laden and non-laden leukocytes was made based on morphological criteria. Mononuclear leukocytes accumulated in the laser lesions and the percentage of carbon-laden mononuclear leukocytes in relation to the total leukocyte number was higher in the extravascular area of the laser sites than in the systemic circulation. These findings indicate that the majority of mononuclear leukocytes that accumulate at the sites of laser lesions are derived from the systemic circulation.     

Necrotizing staphylococcal pneumonia in a neonate.

Hospitalized neonates are commonly colonized soon after birth with Staphylococcus aureus. The majority of neonates do not develop infectious sequelae; however, premature neonates appear to be more susceptible to serious infections, such as pneumonia. We report a case of an extremely low birth weight infant who developed necrotizing pneumonia due to methicillin-resistant Staphylococcal aureus (MRSA). The MRSA isolate from this neonate is identical to the strains that have been causing primarily community-associated skin and soft tissue infections. The severe course of this patient may be attributed to the presence of the Panton-Valentine leukocidin gene, a well-known virulence factor leading to soft tissue and pulmonary infections.     

Decreased amygdala CRF-binding protein mRNA in post-mortem tissue from male but not female bipolar and schizophrenic subjects.

Stressful life events are commonly associated with the onset and maintenance of psychopathology and much research has focused on the role of the corticotropin-releasing factor (CRF) system in mediating psychopathology. Since CRF serves to integrate the stress response, it is possible that the CRF system plays a role as a neurochemical linkage between stress and psychopathology. CRF-binding protein (CRF-BP) is thought to modulate CRF activity by decreasing its actions. Therefore, in some psychopathological states, alterations in CRF-BP function may contribute to dysregulation of the CRF system. Since the amygdala CRF system mediates stress- and anxiety-related behaviors and alterations in amygdala function are associated with psychopathology, we examined amygdala CRF-BP gene expression in post-mortem brains from subjects with major depression, bipolar disorder, and schizophrenia as well as in controls. In addition to characterizing the anatomic distribution of CRF-BP mRNA in the human amygdala and medial temporal lobe region, we found a significant decrease in CRF-BP mRNA levels in the basolateral amygdala of male bipolar and male schizophrenic subjects and the lateral amygdala of male bipolar subjects. These results raise the possibility that men with decreased amygdala CRF-BP may be more vulnerable to the effects of stress exposure on the etiology or maintenance of bipolar disorder or schizophrenia.     

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.     

Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro

To determine if transforming growth factor alpha (TGFα) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10⁻³M) exposure either with or without growth factor pretreatment. After TGFα (500ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGFα in organ of Corti explants.     

Hirschsprung's disease: associated abnormalities and demography.

We here examine the demographic parameters of patients with Hirschsprung's disease. The study population includes all patients with histologically confirmed disease treated at the Children's Hospital Medical Center of Boston over the 25-year period extending from 1961 through the first quarter of 1986. There were 179 cases. Overall, children with Hirschsprung's disease were found less likely to be first born (P less than .01). This relationship was seen to persist irrespective of maternal age, maternal race, or type of disease. The implications of this finding are discussed. Overall, 22% of these children had one or more associated abnormalities involving the neurological, cardiovascular, urological, and gastrointestinal systems. Many of the disorders appeared to be related to neurocrestopathies. Frequent associations included Down's syndrome, defects in cardiac septation, tetralogy of Fallot, and Dandy-Walker syndrome. These conditions occurred more frequently than would have been predicted through chance alone. This study found no association between an increased maternal age and the occurrence of Hirschsprung's disease. This study also found that approximately 7% of the affected children had been born prematurely.