Surfactant protein D deficiency influences allergic immune responses.

BACKGROUND: The collectin surfactant protein D (SP-D) confers protection against pulmonary infection and inflammation. Recent data suggest a role for SP-D in the modulation of allergic inflammation. OBJECTIVE: The aim of this study is to characterize the immune responses of SP-D-deficient (SP-D(-/-)) mice in a kinetic model of allergic inflammation. We determined whether allergic parameters were enhanced in SP-D(-/-) mice in vivo. Further, we examined whether functional immune responses in vitro such as lymphocyte proliferation (LP) and cytokine production were modulated in the absence of SP-D. METHODS: In vivo, wild-type (WT) and SP-D(-/-) mice were sensitized and challenged with the allergen ovalbumin (OVA) and assessed for allergic parameters (bronchoalveolar lavage (BAL) eosinophils, IL-13 production, pulmonary IFN-gamma, IL-10 expression) at early time points (1 and 3 days of challenge) in comparison with late time points (7 days of challenge). In vitro, spleen cells from WT and SP-D(-/-) mice were stimulated with the mitogen concanavalin A (ConA) and lipid A (LpA) and analysed for LP, IL-13 and IFN-gamma production. Toll-like receptor 4 (TLR4), ligand for LpA, was assessed by mRNA expression and immunohistochemistry in vivo. RESULTS: Following allergen exposure in vivo, SP-D(-/-) mice expressed higher BAL eosinophils and IL-13 concentrations and lower IFN-gamma expression at early time points compared with WT mice. IL-10 expression was increased at early time points in SP-D(-/-) compared with WT mice. Allergen-induced TLR4 expression was increased in WT, but not in SP-D(-/-) mice. After stimulation with LpA and ConA in vitro LP was increased and IFN-gamma concentration was decreased in SP-D(-/-) mice. CONCLUSION: SP-D may be critical for the modulation of early stages of allergic inflammation in vivo.

Churg-Strauss syndrome in patients receiving montelukast as treatment for asthma.

STUDY OBJECTIVES: We previously reported eight patients who developed Churg-Strauss syndrome in association with zafirlukast treatment for asthma and postulated that the syndrome resulted from unmasking of a previously existing condition due to corticosteroid withdrawal and not from a direct drug effect. The availability of montelukast, a new leukotriene receptor antagonist with a different molecular structure, permitted us to test this hypothesis. Our goals were to ascertain whether the Churg-Strauss syndrome developed in patients taking montelukast and other novel asthma medications, and to describe potential mechanisms for the syndrome. DESIGN: Case series. SETTING: Outpatient and hospital practices of pulmonologists in the United States and Belgium. PATIENTS: Four adults (one man, three women) who received montelukast as treatment for asthma; two women who received salmeterol/fluticasone therapy, but not montelukast. RESULTS: Churg-Strauss syndrome developed in the four asthmatic patients who received montelukast. In each case, there was a long history of difficult-to-control asthma characterized by multiple exacerbations that had required frequent courses of oral systemic corticosteroids or high doses of inhaled corticosteroids for control. Two other asthmatics who received fluticasone and salmeterol but not montelukast therapy developed the same syndrome with tapering doses of oral or high doses of inhaled corticosteroids. CONCLUSIONS: The occurrence of Churg-Strauss syndrome in asthmatic patients receiving leukotriene modifiers appears to be related to unmasking of an underlying vasculitic syndrome that is initially clinically recognized as moderate to severe asthma and treated with corticosteroids. Montelukast does not appear to directly cause the syndrome in these patients.

Pathological jealousy appearing after cerebrovascular infarction in a 25-year-old woman.

OBJECTIVE: To report pathological jealousy (Othello syndrome) occurring in a young woman with a right hemisphere cerebrovascular infarction and to review diagnosis and possible organic mechanisms for the generation of this syndrome. CLINICAL PICTURE: A 20-year-old woman was admitted to hospital with a right hemisphere stroke associated with a history of severe migraine and the use of oral contraceptives. The patient made a good recovery with minimal neurological deficits but 5 years later developed the syndrome of morbid jealousy with depression and a near fatal overdose. TREATMENT AND OUTCOME: Morbid jealousy subsided, almost completely disappearing over a 6-week period of treatment with a selective serotonin re-uptake inhibitor (SSRI). CONCLUSIONS: Case reports of the Othello syndrome and other content specific delusions following right hemisphere cerebrovascular infarction have appeared in geriatric psychiatry literature. The occurrence of a similar association in a young patient lends support to the suggestion of a causal relationship and has implications for diagnosis, clinical care and research.

Memory processes in depressed geriatric patients with and without subcortical hyperintensities on MRI.

In this study, 12 patients over age 60 with depression with moderate to severe subcortical hyperintensities (SH) localized to the periventricular white matter were identified by quantitative MRI. Using the California Verbal Learning Test, they were compared with 12 age-, education-, and severity-matched patients with depression with minimal white matter changes on specific aspects of memory performance. Patients with cortical lesions, neurologic or systemic illness affecting cognition, and history of substance abuse were excluded. Patients in the group with high SH showed reduced use of semantic encoding strategies (p < 0.05), reduced learning efficiency (p < 0.05), and a greater discrepancy between free recall and recognition discriminability (p < 0.05) than their low SH counterparts. This pattern of performance on memory tasks is similar to that found in previous studies to be associated with subcortical degenerative disorders such as Huntington's and Parkinson's diseases. Geriatric patients with depression with SH may represent a subgroup with greater subcortical involvement, with associated cognitive and functional decline.

Clinical features of obsessive-compulsive disorder in elderly patients.

There has been no systematic study of the clinical features of obsessive-compulsive disorder (OCD) in elderly patients. This study describes the symptoms and characteristics of OCD among 32 outpatients age 60 or older and 601 younger patients meeting DSM-III-R criteria and given the Yale-Brown Obsessive-Compulsive Scale (YBOCS), NIMH scale, and a 41-item symptom questionnaire. Elderly patients had a later age at onset compared with younger patients. No differences were found in severity of symptoms on the YBOCS. Elderly patients had fewer concerns about symmetry, need to know, and counting rituals. Handwashing and fear of having sinned were more common. There were few differences in clinical features of OCD among the elderly patients compared with younger OCD patients.

Neuropsychiatric factors in the illusion of visitors among geriatric patients: a case series.

The 'illusion of visitors' is a common phenomenon among geriatric patients presenting for psychiatric or neurologic evaluation and treatment. Although these illusory beliefs are etiologically diverse, patients may commonly have visual impairment and functional and/or structural disruption of frontal and right-hemisphere-mediated cognitive functioning. This article outlines eight cases of illusory beliefs among elderly patients, presenting psychiatric, neurologic, neuroimaging, and neuropsychological findings among these patients. Commonalities and differences among these cases are discussed, and a framework is provided for multidisciplinary assessment and treatment of patients presenting with illusory beliefs.

Subcortical hyperintensities on MRI and activities of daily living in geriatric depression.

Data from 30 elderly inpatients with major depression were analyzed to explore the relationship between subcortical hyperintensities (SH) on MRI and activities of daily living (ADLs). A comparison of subjects based on a median split of the severity of SH revealed that subjects with greater SH performed worse on both instrumental and physical ADLs. A hierarchical multiple regression revealed that age, depression severity, neuropsychological test performance, and SH variables accounted for a total of 53% of the variance in ADL functioning. Severity of SH accounted for an additional 18% of the variance over and above the other three variables. Results suggest that severity of subcortical disease measured by MRI improves prediction of functional impairment in elderly individuals.

MRI and neuropsychological differences in early- and late-life-onset geriatric depression.

We sought to determine whether geriatric patients with late-life-onset major depression have more subcortical hyperintensities on MRI and greater cognitive impairment than age-matched geriatric patients with early-life-onset major depression, suggesting that subcortical disease may be etiologic in late-life depression. Most negative studies of the clinical significance of subcortical hyperintensities on MRI in geriatric patients have sampled from a restricted range of subjects, have employed limited batteries of neuropsychological tests, or have not quantified MRI changes; the present study attempted to address these limitations. Thirty subjects from a geriatric psychiatry inpatient service who were over 60 years of age and presented with major depression were divided into groups with onset of first depression after age 60 (mean = 72.4 years, 15 women, 0 men), and onset of first depression before age 60 (mean = 35.8 years, 12 women, 3 men). Quantitative analysis of MRI yielded the volume of: periventricular hyperintensities (PVH) and deep white-matter hyperintensities (DWMH). Subjects were administered a neuropsychological battery and measures of depression by raters blind to age of onset. The late-onset group had significantly more PVH and DWMH. They were also more impaired on executive and verbal and nonverbal memory tasks. Discriminant analysis using the severity or subcortical signal hyperintensities on MRI, cognitive index, and depression scores correctly predicted late versus early onset of depression in 87% of the early-onset group and 80% of the late-onset group. These findings suggest that late-life-onset depression may be associated with an increased severity of subcortical vascular disease and greater impairment of cognitive performance.

"Grievous bodily harm:" gamma hydroxybutyrate abuse leading to a Wernicke-Korsakoff syndrome.

Gamma-hydroxybutyrate (GHB) is a naturally occurring GABA-like drug used illicitly by bodybuilders. Although there are reports of several cases of GHB abuse, with a variety of nervous system complications, we present the first case associated with a Wernicke-Korsakoff syndrome.

Relationship between sleep spindles and hypersomnia.

Sleep spindles (SS) and K complexes constitute the physiological markers of stage 2 sleep. Because sleep allows a spontaneous thalamic manifestation in the form of SS, one could hypothesize that there is some kind of relationship between SS and the complaint of hypersomnia. To investigate this possible relationship we compared nonhypersomnolent subjects with hypersomnolent patients who carried a diagnosis of narcolepsy or idiopathic hypersomnia. SS were counted in well-defined nocturnal stage 2 sleep segments, and the average SS density (number of SS in stage 2/minute stage 2) was tabulated for the entire night. Agreement between two independent scores was higher than 95%. The results show that the average SS density is higher in both cerebral hemispheres in the hypersomnolent group, especially in the idiopathic hypersomnia patients. At the beginning and at the end of the nocturnal sleep time, SS density is increased in this group compared with the normal one. These findings support the complaint of hypersomnia, mainly in idiopathic hypersomnia patients. This is in agreement with the notion that SS are generated by thalamic structures that serve a gatekeeping function during nonrapid eye movement sleep, and further suggests that their relative abundance expresses the power of that control.

Personality disorder diagnoses and age in inpatients with major depression.

To ascertain the prevalence of personality disorder in elderly patients with major depression and to explore issues of diagnostic practice and bias, the authors reviewed triaxial diagnoses of 2322 psychiatric hospital inpatients with Axis I diagnoses of major depression. They found that Axis II diagnoses had been made in 367 cases (15.8%). Patients older than 65 years of age had a significantly lower rate of Axis II diagnoses. The age effect was greatest for women with comorbid physical illness. In contrast to the age-related decline in rate of Axis II diagnoses in general, the diagnosis of compulsive personality disorder increased with age and comprised 46% of all Axis II comorbidities in patients 65 years or older. Possible explanations and implications for future research are discussed.

An outbreak of acute rheumatic fever in Tennessee.

From January, 1987, until July, 1988, a significant increase in newly diagnosed cases of acute rheumatic fever was noted at our hospital. In sharp contrast to the 3 cases seen in 1986, 14 cases were diagnosed in 1987 (a significant increase from 1985 to 1986, P = 0.001). In the first 6 months of 1988 an additional 12 new cases were diagnosed (a further significant increase from 1987, P = 0.02). No further cases were diagnosed between July, 1988, and September, 1989. The major clinical manifestations were carditis in 73%, polyarthritis in 58% and chorea in 31%. In 15 of 26 patients an antecedent illness which included pharyngitis was noted; the remainder of patients were asymptomatic. Group A beta-hemolytic streptococci were isolated from 13 of 19 children cultured. Isolates from two patients with acute rheumatic fever were submitted for M typing: one isolate was mucoid M18/T18; the other isolate was a mucoid nontypable strain. The demographic characteristics of the 26 patients agree with classic descriptions in that patients were more likely to be urban, to come from large families and to have low incomes; racial breakdown of the group mirrored the Tennessee pediatric population. These characteristics stand in contrast to reports of recent outbreaks which describe suburban high income patients. These data suggest that practitioners should be again aware of acute rheumatic fever and that aggressive identification and treatment of streptococcal pharyngitis should continue to be a relevant public health concern.

Ventilatory response to isocapnic hypoxia in parents of victims of sudden infant death syndrome.

Ventilatory response to progressive isocapnic hypoxia was measured in 14 parents of victims of sudden infant death syndrome (SIDS) and 12 matched control parents. Controls had a value for a measure of ventilatory responsiveness (parameter A) of 200.8 +/- 46.4, while SIDS parents had a significantly lower value of 64.4 +/- 16.2 (P less than 0.01). Since degree of hypoxic ventilatory drive is a hereditary characteristic, it is concluded that a relatively low ventilatory responsiveness to hypoxia might have been present in the SIDS victims.

Urate nephrolithiasis in ranch mink.

Urate nephrolithiasis with epistaxis and bleeding around foot pads was diagnosed in ranch mink. Investigation of affected, unaffected-related, and unaffected-unrelated mink did not disclose the cause of these problems but did eliminate inherited bleeding disorders as a cause of the bleeding. All affected mink were males, had been sired by related sires, and were affected in the 1st year of life. Elimination of affected mink and their parents from the breeding stock eliminated the condition from the herd. The findings were consistent with an inherited defect in uric acid metabolism or excretion.

Ventilatory control in parents of victims of sudden-infant-death syndrome.

Since a defective ventilatory-control mechanism may have a role in the sudden-infant-death syndrome (SIDS), and hereditary factors influence the degree of ventilatory drive, we measured ventilatory responsiveness to carbon dioxide with and without increased airway resistance in 12 parents of SIDS victims and 12 control parents matched for age and size. Ventilatory response (delta VI/delta PCO2) and "respiratory drive" (delta P100/delta PCO2) were measured both with and without added resistance to inspiratory flow. SIDS parents had significantly lower ventilatory response with added resistance (P less than 0.05) and without it (P less than 0.01) and significantly lower respiratory drive with added resistance (P less than 0.001) and without it (P less than 0.05). Control parents had significantly increased respiratory drive when the resistance was added (P less than 0.005), whereas SIDS parents did not. The data suggest that a low ventilatory response to carbon dioxide and a diminished compensatory response to increased airway resistance may increase a potential parent's risk of having a child susceptible to SIDS.

The behavioral control of obesity: a descriptive analysis of a large-scale program.

Evaluated a behavoiral treatment program for 147 obese patients in a Weight Control Clinic. Weight losses during treatment averaged 11.01 pounds with large inter-S variability. Unlike past studies, patients continued to lose weight during a 6-month follow-up period. Weight loss was associated with age and initial degree of obesity, but other demographic and psychological variables failed to predict success in treatment. A critical examination of the attrition problem was carried out to determine the relationship between patient variables and the propensity to terminate treatment prematurely. Results demonstrate the utility of bahvioral treatment procedures for obesity, yet further research is needed to reduce attrition and to facilitate long-term maintenance of weight loss.