Fatty acid incorporation depicts brain activity in a rat model of Parkinson's disease

Following pulse labeling with [3H]arachidonic acid ([3H]AA), its incorporation pattern in brain reflects regional changes in neurotransmitter signal transduction using phospholipase A2, that is, functional activity. In a rat model of Parkinson's disease, unilateral 6-hydroxydopamine lesion in the substantia nigra, [3H]AA acid incorporation from blood was increased in cerebral cortex, caudate putamen, globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata ipsilateral to the lesion. This increased [3H]AA incorporation likely reflects disinhibition of basal ganglia and cortical circuits secondary to absent inhibitory nigrostriatal dopaminergic input.     

A comparison of psychopathology in eating disorder patients from France and the United States

Patients with osteoarthritis of the hip were treated with a conservative therapy of heel lifting. Orthoses were applied on 35 hips in 33 subjects and the cases were followed for 23 months on average. Dramatic pain relief was reported, but the time required to reduce or completely relieve pain increased according to the stage of osteoarthritis. The radiological results were not satisfactory. During the follow-up, only two hips showed improvement, 22 showed no change, and 11 deteriorated. The mechanism of heel lifting in relation to the hip joint was analysed, showing that pelvic obliquity was achieved and the trunk stabilized. In conclusion this simple orthosis was effective as a palliative therapy for osteoarthritis of the hip.     

Role of cytopathology in the diagnosis of ocular malignancies

OBJECTIVE: To determine the positive predictive value of ocular cytologic specimens and to describe the cytopathologic findings encountered in ocular samples from patients with intraocular neoplasms. STUDY DESIGN: Intraocular fluids and ocular fine needle aspirates (FNAs) cytologically diagnosed as either suspicious or positive for malignancy during a 15-year period were reviewed, and follow-up was obtained. RESULTS: Seventeen patients with intraocular samples diagnosed as suspicious or positive for malignancy (9 vitreous, 6 anterior chamber, 3 FNAs) were identified. The mean patient age was 58 years (range, 3-91). Cytologic diagnoses included: lymphoma (5), suspicious for lymphoma (2), melanoma (6), suspicious for melanoma (2), carcinoma (2) and retinoblastoma (1). Clinical and/or surgical follow-up was available in 12 cases and was consistent with the presence of malignancy in all but one case, which proved to be fungal endophthalmitis. One of two patients with a cytologic diagnosis of carcinoma had melanoma on follow-up. Cytologic samples suspicious or positive for lymphoma showed single, large cells with scant cytoplasm and prominent nucleoli. Cytologic samples suspicious or positive for the epithelioid type of melanoma showed loosely cohesive groups or single cells, marked cellular pleomorphism, large nucleoli, scant to moderately abundant cytoplasm and variable amounts of melanin. Cytologic samples from spindle cell melanomas showed spindle cells without nuclear or cellular pleomorphism, without hyperchromasia, and with inconspicuous nucleoli and occasional nuclear grooves. Loose aggregates of small cells with hyperchromatic nuclei and scant cytoplasm characterized the retinoblastoma samples. CONCLUSION: The positive predictive value of intraocular fluid cytology was 92%. Reactive lymphoid processes may be difficult to differentiate from lymphoma and epithelioid melanoma from carcinoma in intraocular cytologic specimens.     

Calcified embolus of the left coronary ostia after aortic valve replacement

A patient with a left coronary calcified embolus causing acute myocardial dysfunction immediately after aortic valve replacement is described. Prompt diagnosis by transesophageal echocardiogram was made, which led to removal of the embolus and a subsequent satisfactory course.     

Neighborhood risk factors for low birthweight in Baltimore: a multilevel analysis

OBJECTIVES: Past research on low birthweight has focused on individual-level risk factors. We sought to assess the contribution of macrolevel social factors by using census tract-level data on social stratification, community empowerment, and environmental stressors. METHODS: Census tract-level information on social risk was linked to birth certificate records from Baltimore, Md, for the period 1985 through 1989. Individual level factors included maternal education, maternal age, medical assistance health insurance (Medicaid), and trimester of prenatal care initiation. Methods of multilevel modeling using two-stage regression analyses were employed. RESULTS: Macrolevel factors had both direct associations and interactions with low birthweight. All individual risk factors showed interaction with macrolevel variables; that is, individual-level risk factors for low birthweight behaved differently depending upon the characteristics of the neighborhood of residence. For example, women living in high-risk neighborhoods benefited less from prenatal care than did women living in lower-risk neighborhoods. CONCLUSIONS: Multilevel modeling is an important tool that allows simultaneous study of macro- and individual-level risk factors. Multilevel analyses should play a larger role in the formulation of public health policies.     

Intravenous immune globulin therapy for neurologic diseases

High-dose intravenous immune globulin (IVIg) has emerged as an important therapy for various neurologic diseases. Different interpretations of clinical trial results; the expected benefit of IVIg compared with that of alternate therapies; and issues about IVIg's safety, cost, and mechanisms of action have raised concern and uncertainty among practitioners. To clarify these areas, this paper examines the clinical, serologic, and immunologic data on more than 110 patients with various autoimmune neurologic diseases who received IVIg during the past 6 years at the National Institute of Neurological Disorders and Stroke. It also reviews work by other investigators on the efficacy, risks, benefits, and mechanisms of the action of IVIg in these diseases. In controlled clinical trials, IVIg has been effective in treating the Guillain-Barré syndrome, multifocal motor neuropathy, chronic inflammatory demyelinating polyneuropathy, and dermatomyositis. In other controlled or open-label trials and case reports, IVIg produced improvement in several patients with the Lambert-Eaton myasthenic syndrome and myasthenia gravis but had a variable, mild, or unsubstantiated benefit in some patients with inclusion-body myositis, paraproteinemic IgM demyelinating polyneuropathy, certain intractable childhood epilepsies, polymyositis, multiple sclerosis, optic neuritis, and the stiff-man syndrome. The primary adverse reaction was headache; aseptic meningitis, skin reactions, thromboembolic events, and renal tubular necrosis occurred rarely. The most relevant immunomodulatory actions of IVIg, operating alone or in combination, are inhibition of complement deposition, neutralization of cytokines, modulation of Fc-receptor-mediated phagocytosis, and down-regulation of autoantibody production. Therapy with IVIg is effective for certain autoimmune neurologic diseases, but its spectrum of efficacy has not been fully established. Additional controlled clinical trials are needed.     

The relationship between loneliness, social support, and decline in cognitive function in the hospitalized elderly

To determine the effects of preexisting levels of loneliness and social support on cognitive decline during hospitalization, 145 elderly subjects 65 to 92 years old without impaired cognition were tested for levels of loneliness, social support, and cognitive status on admission to an acute care hospital. Five days later, cognitive status was again measured in the remaining 86 patients. Loneliness was found to be inversely related to cognitive status on admission. In those with high loneliness scores on admission, cognitive status had improved significantly 5 days later. High social support was correlated with high cognitive status on admission and significant cognitive decline during hospitalization.     

A report of the use of the Dynamic Objective Risk Assessment (DORA) score in the changing pediatric intensive care environment

Several nonsurgical approaches to the treatment of postradiation proctitis have been described, but no effective conservative treatment has yet been established. As an alternative to the usual treatment, three cases of chronic postradiation proctitis with hemorrhage were successfully treated with oral administration of sucralfate, with resultant decreased bleeding in long term follow-up period. Oral sucralfate may provide a novel approach to the treatment of intractable postradiation proctitis.     

Multiple resistance modulators combined with carboplatin for resistant malignancies: a pilot study

BACKGROUND: Chemotherapy resistance is probably multifactorial; hence, we assessed the feasibility of adding to carboplatin 6 concurrent resistance modulators in 53 patients with resistant cancers. METHODS: Pentoxifylline and dipyridamole were added to carboplatin 400 mg/m2 in cohort 1, and metronidazole was also given in cohort 2. Mannitol and saline were administered in each cohort with the theoretical objective of improving carboplatin delivery to tumors by reducing blood viscosity. Because of excessive toxicity in cohort 2, cohort 3 received the same modulators as in cohort 2 but with a reduced dose of carboplatin (200 mg/m2). Subsequent patients had the following drugs added to those in the previous cohort: novobiocin (cohort 4), tamoxifen (cohort 5), ketoconazole (cohort 6). Cohort 7 patients received the 6 cohort 6 modulators along with carboplatin 300 mg/m2. RESULTS: Thrombocytopenia was excessive in early cohorts with a carboplatin dose of 400 mg/m2, but was minimal at lower doses. Other toxicity was generally tolerable and reversible, particularly at carboplatin doses < or = 300 mg/m2, although gastrointestinal and neurological toxicity tended to worsen as additional modulators were added. No major responses (but 4 minor responses) were seen in this patient population with heavily pretreated or primarily resistant cancers. CONCLUSIONS: Acceptable doses for phase II studies are carboplatin 300 mg/m2, 20% mannitol 250 ml plus normal saline 500 ml over 1 hr prior to carboplatin, pentoxifylline 700 mg/m2/day p.o. from 3 days before carboplatin to cessation of therapy, dipyridamole 100 mg/m2 p.o. q6h x 6 days starting 24 hr before carboplatin, metronidazole (750 mg/m2 p.o. 12 hr and immediately before, and 24 hr after carboplatin; 250 mg/m2 suppository p.r. 12 hr and immediately before, and 6 and 24 hr after carboplatin; and 500 mg/m2 i.v. right after carboplatin), novobiocin 600 mg/m2 p.o. q12h x 6 days starting 24 hr before carboplatin, and tamoxifen 100 mg/m2/day plus ketoconazole 700 mg/m2/day x 3 days starting the day before carboplatin, with oral dexamethasone and ondansetron as antimetics.     

An immune cell-selective interleukin 4 agonist

Interleukin 4 (IL-4) is a pleiotropic cytokine. Of the cell types responsive to IL-4, T cells express one IL-4 receptor (IL-4R) type, IL-4Ralpha/IL-2Rgamma (class I IL-4R), whereas endothelial cells express another type, IL-4Ralpha/IL-13Ralpha (class II IL-4R). It was hypothesized that IL-4 variants could be generated that would be selective for cell types expressing the different IL-4Rs. A series of IL-4 muteins were generated that were substituted in the region of IL-4 implicated in interactions with IL-2Rgamma. These muteins were evaluated in T cell and endothelial cell assays. One of these muteins, containing the mutation Arg-121 to Glu (IL-4/R121E), exhibited complete biological selectivity for T cells, B cells, and monocytes, but showed no activity on endothelial cells. Receptor binding studies indicated that IL-4/R121E retained physical interaction with IL-2Rgamma but not IL-13Ralpha; consistent with this observation, IL-4/R121E was an antagonist of IL-4-induced activity on endothelial cells. IL-4/R121E exhibits a spectrum of activities in vitro that suggest utility in the treatment of certain autoimmune diseases.