Nebulized thiocyanate improves lung infection outcomes in mice.

BACKGROUND AND PURPOSE: Nebulized saline solutions are used in the treatment of multiple pulmonary diseases including cystic fibrosis (CF), asthma and chronic obstructive pulmonary disease (COPD). The benefits of these therapies include improved lung function, phlegm clearance and fewer lung infections. The thiocyanate anion (SCN) is a normal component of the airway epithelial lining fluid (ELF) secreted by pulmonary epithelia with antioxidant and host defence functions. We sought to test if SCN could be nebulized to combat lung infection by bolstering innate immune defence and antioxidant capacity. EXPERIMENTAL APPROACH: We established an effective antioxidant concentration of SCN in vitro using a bronchiolar epithelial cell line. We then developed a nebulization method of SCN in mice that increased ELF SCN above this concentration up to 12 h and used this method in a prolonged Pseudomonas aeruginosa infection model to test if increasing SCN improved host defence and infection outcomes. KEY RESULTS: SCN protected against cytotoxicity in vitro from acute and sustained exposure to inflammation-associated oxidative stress. Nebulized SCN effectively reduced bacterial load, infection-mediated morbidity and airway inflammation in mice infected with P. aeruginosa. SCN also sustained adaptive increases in reduced GSH in infected mice. CONCLUSIONS AND IMPLICATIONS: SCN is a dually protective molecule able to both enhance host defence and decrease tissue injury and inflammation as an antioxidant. Nebulized SCN could be developed to combat lung infections and inflammatory lung disease.

Serological evidence for swine hepatitis E virus infection in Australian pig herds.

Hepatitis E virus (HEV) is an enterically transmitted human pathogen, with some similarities to caliciviruses. A variant of HEV was recently identified in pigs in the USA, infecting almost 100% of animals in commercial herds. Phylogenetic analysis suggests that this is a true 'swine HEV' distinct from the human virus, but the swine virus may also infect man. Using an in-house ELISA based on a highly conserved, recombinant HEV protein, we have examined collections of sera from Australian pigs for evidence of HEV infection in local pig herds. Sera from one research herd (n = 32) were uniformly non-reactive, and this was used to establish an assay cut-off (= mean + 3 SD of reference pig serum reactivities). Screening of sera from other herds demonstrates that swine HEV is present in Australia, with reactivity observed in 30% (12/40) of random samples from two piggeries, 92-95% of pigs by the age of 16 weeks in two other piggeries (n = 45), and 17% (15/59) of wild-caught pigs. Further studies are required to examine whether HEV causes disease in pigs and to determine the risk of swine HEV transmission to man.

Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus.

The induction of human immunodeficiency virus (HIV)-specific T-cell responses is widely seen as critical to the development of effective immunity to HIV type 1 (HIV-1). Plasmid DNA and recombinant fowlpox virus (rFPV) vaccines are among the most promising safe HIV-1 vaccine candidates. However, the immunity induced by either vaccine alone may be insufficient to provide durable protection against HIV-1 infection. We evaluated a consecutive immunization strategy involving priming with DNA and boosting with rFPV vaccines encoding common HIV-1 antigens. In mice, this approach induced greater HIV-1-specific immunity than either vector alone and protected mice from challenge with a recombinant vaccinia virus expressing HIV-1 antigens. In macaques, a dramatic boosting effect on DNA vaccine-primed HIV-1-specific helper and cytotoxic T-lymphocyte responses, but a decline in HIV-1 antibody titers, was observed following rFPV immunization. The vaccine regimen protected macaques from an intravenous HIV-1 challenge, with the resistance most likely mediated by T-cell responses. These studies suggest a safe strategy for the enhanced generation of T-cell-mediated protective immunity to HIV-1.

Psychogenic catatonia with elevated creatine kinase and autonomic hyperactivity.

A case is presented in which a young man with no psychiatric history and no previous exposure to psychotropic medication rapidly developed severe catatonia and autonomic hyperactivity, and an elevated creatine kinase level. He was treated with electroconvulsive therapy and recovered completely. This case suggests that a subgroup of patients who presented with symptoms resembling those of neuroleptic malignant syndrome and who have been treated with neuroleptics may suffer from severe psychogenic catatonia.

Propranolol treatment of akathesia in Tourette's syndrome.

Akathesia is a common side effect of neuroleptic medication and has been reported to occur in patients with Tourette's Syndrome (TS). In TS, the differentiation between untreated hyperactivity and akathesia can be difficult. A case of neuroleptic treated TS with hyperactivity versus akathesia is presented in which propranolol was successfully used to treat the akathesia. The akathesia reappeared when the propranolol was withdrawn. This case illustrates an alternative to neuroleptic dose reduction in the management of akathesia in TS.

Head CT in new geriatric psychiatry patients: a prospective study.

Computed tomography of the head (HCT) was studied prospectively in 42 new geriatric psychiatry patients. Scans were obtained in 88% of the sample. Subjects underwent a complete evaluation by a geriatric psychiatrist who was blind to the HCT results. The HCT was abnormal in 32 (86%) of the 37 patients who had a scan. The most frequent finding was atrophic changes, which were discovered in ten (27%) of the 37 patients. Subcortical vascular disease was found in 14 patients (38%). Mixed pictures with both vascular disease and atrophic changes were found in nine (24%). The only statistically significant predictor of an abnormal HCT was an abnormal neurobehavioral examination. While the information gained from the HCT did not add appreciably to the clinical evaluation in determining whether there was an organic or idiopathic psychiatric syndrome, it was crucial in determining the location and nature of the central nervous system lesions.

Cognitive screening tests for organic mental disorders in psychiatric inpatients. A hopeless task?

Bedside cognitive screening tests have been suggested as a way to quickly determine the likelihood of a patient's having an organic mental disorder (OMD). The Mini-Mental State (MMS) examination and a number of separate bedside neurobehavioral tests were administered to 206 patients who were consecutively admitted to the University of Iowa Psychiatric Hospital. Both examinations were completed by 150 subjects. Of the sample, 7% had an OMD diagnosis. The most frequent neurological causes of OMD were probable Alzheimer's and closed head trauma. The predictive value positive, predictive value negative, specificity, and sensitivity of the MMS were examined for a number of different cutoff scores. The maximum sensitivity was 75% with a cutoff score of 30. The maximum specificity was 100% with a cutoff of 12. However, only two OMD patients had scores less than 12. There was no cutoff that resulted in a clinically useful screening test. A stepwise multiple logistic regression model using the separately administered bedside tests as independent variables and OMD as the dependent variable resulted in two significant predictors of an OMD diagnosis: the alternating sequence test and a reading test. This model was not appreciably better than the MMS in predicting an OMD diagnosis. A number of problems make the development of a clinically useful cognitive screening test for OMD in inpatients unlikely. These include poor cooperation of the patients, the rarity of OMD in psychiatric inpatients, the heterogeneity of OMD etiologies, and the confounding neuropsychological deficits of a number of common psychiatric disorders.

Memory complaints and memory deficits in young and old psychiatric inpatients.

Memory complaints and memory deficits were investigated in 206 consecutively admitted psychiatric inpatients at the University of Iowa Psychiatric Hospital. Forty-five percent of patients over age 60 years and 29% of patients less than 60 years old had severe memory complaints. Patients with complaints of memory loss were no more likely than patients without such complaints to have a memory deficit. In patients over age 60 years, memory complaint was more common in depression than in dementing and amnestic disorders (73% v 43%), while in younger patients memory complaint was slightly more common in dementing and amnestic disorders than in depression (57% v 41%). Increasing age was significantly correlated with increasing likelihood of memory complaint for depressed patients but not for nondepressed patients. As a result of these findings, memory complaint was found to be a statistically significant marker for depression in the elderly (sensitivity = 73%, specificity = 75%) but not in younger patients. Our results confirm the clinical observation that memory complaints are a useful marker for depressed states in the elderly.

The prevalence of neuropsychiatric disorders in a nursing home population.

The prevalence of neuropsychiatric disorders and other medical illnesses was investigated in 65 nursing home residents. The authors found neuropsychiatric disorders to be present in 94% of the sample. The neuropathologic causes of these syndromes were found to be more diverse than in previous studies. The most frequent causes were degenerative, vascular, and toxic. The most common psychiatric syndromes that resulted from these neuropathologic disorders were dementia syndrome (72%), organic personality syndrome (14%), and organic psychotic disorders (12%). The most common behavioral problems, agitation and aggression, most likely reflected the high prevalence of frontal lobe damage and affected 48% of the sample. Other non-neuropsychiatric medical problems were significantly less common. While only 4% of the sample had no neuropsychiatric diagnosis, 39% had no other non-neuropsychiatric diagnosis. These results suggest that the nursing home is not used as a referral source for chronic medical conditions in general but almost exclusively for the care of chronic neuropsychiatric disorders.

Somatization, depression and medical illness in psychiatric inpatients.

In a study to determine the relationship between somatic symptoms and psychiatric diagnosis, 206 consecutively admitted inpatients at the University of Iowa Psychiatric hospital were given a structured medical history (MH) and physical examination (PE). Depressed patients were significantly older, had an increase in number of medical diagnoses (NDX), and were found to have a significant increase in somatic symptoms in which there was no confirmatory evidence on the PE and in which there was confirmation on the PE. When age, sex, and NDX were controlled for, depressed patients did not have an increase in either of the types of somatic symptoms noted above but did have a slight increase in the vague somatic symptoms in which PE findings would be unlikely. Our results suggest that the majority of the increases in somatic symptoms in depressed patients may not be due to depressive psychopathology but rather to their increased number of medical problems and increased age.

Geriatric psychiatry.

This article discusses the diagnostic and therapeutic problems that are unique to psychogeriatric patients in a primary care setting. Practical guidelines for the evaluation and treatment of dementia and depression, psychosis and agitation, and insomnia are presented.