IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development.

Interleukin-9 is a cytokine produced by Th2 cells and is a candidate gene for asthma and atopy. We have generated IL-9-deficient mice to delineate the specific roles of IL-9 in Th2 responses. Using a pulmonary granuloma model, we have demonstrated a distinct requirement for IL-9 in the rapid and robust generation of pulmonary goblet cell hyperplasia and mastocytosis in response to lung challenge. In contrast, eosinophilia and granuloma formation were not affected. IL-9 was not required for T cell development or differentiation, the generation of naive or antigen-driven antibody responses, or the expulsion of the intestinal parasitic nematode Nippostrongylus brasiliensis. Thus, deletion of IL-9 manifests as a highly defined phenotype in Th2 responses modulating mucus production and mast cell proliferation.

Risk of suicidality in depression with serotonergic antidepressants.

Since depression is a risk factor for suicidal thoughts and behaviors, and since suicidal behaviors are associated with low serotonin activity, are selective serotonin reuptake inhibitors (SSRIs) more effective than other antidepressants in treating suicidality in depressed patients? There is inconclusive evidence for and against this hypothesis. However, all studies suggest that antidepressants are effective treatments of suicidal ideations and behaviors, and SSRIs have been shown to have prophylactic effects in preventing suicidal behaviors. Although some reports suggest that SSRIs might increase suicidal ideations and behaviors, the results of large, double-blind studies do not suggest a causal relationship between pharmacotherapy and the emergence of suicidality. Undertreatment of depression and therapeutic failure are more significant problems with the use of antidepressants in suicidal patients than the risk of using antidepressants in overdose. Prescribing inadequate doses of antidepressants is therefore a source of overlooked risk.

Appearance and rapid growth of retinal tumor (reactive astrocytic hyperplasia?).

BACKGROUND: Tumors of the retina are often seen in association with systemic syndromes such as neurofibromatosis, tuberous sclerosis, and von Hippel-Lindau disease. These masses are either astrocytic hamartomas or capillary hemangiomas. Retinal tumors unassociated with other systemic disease have also been reported. METHODS: The ophthalmologic evaluation and clinical course of a 65-year-old woman who developed an epiretinal membrane followed by a vascularized retinal mass in the macular area are described. RESULTS: Appearance and rapid growth of the lesion were documented with fundus photography and fluorescein angiography. The lesion was treated with photocoagulation following growth that threatened the foveal region. Choroidal neovascularization subsequently developed toward the fovea, and visual acuity has remained poor. After 4 years of follow-up no local recurrence or systemic disease possibly related to the tumor has occurred. CONCLUSIONS: This is the first report of documented appearance and rapid growth of a retinal tumor that resembles a reactive astrocytic hyperplasia.

The acute effects of a loading dose of phenylalanine in unipolar depressed patients with and without tardive dyskinesia.

The effects of a loading dose of 100 mg/kg phenylalanine (PHE) were assessed in three groups of DSM-III-R diagnosed unipolar depressed patients: patients with tardive dyskinesia (TD) (n = 11); patients exposed to neuroleptics (NLs) but without TD (n = 10); and patients never exposed to NLs (n = 10). No significant differences were obtained in fasting and 2 hour postloading PHE plasma levels between the groups. A statistically significant correlation was found between Abnormal Involuntary Movements Scale total scores and postloading PHE plasma levels (p less than .05). Three TD patients showed unusually large increases in PHE plasma levels and PHE:large neutral amino acid ratios. Abnormalities in PHE metabolism may contribute to the development and severity of TD in some NL-treated unipolar depressed patients.

Quantitative assessment of psychomotor activity in patients with neuroleptic-induced akathisia.

1. An ambulatory activity monitor with solid-state memory was employed to obtain 24-hour activity data in 29 neuroleptic-treated hospitalized patients and 9 normal controls. 2. The activity monitor is a piezoelectric device which was strapped to the non-dominant ankle. Activity was recorded in 5-minute epochs throughout the 24-hour period. 3. In contrast to patients with mania (N = 15) and schizophrenia (N = 4), depressed patients (N = 9) had higher clinical ratings of akathisia and lower levels of daytime activity. 4. Manic and depressed patients showed a delay of peak activity (= acrophase). 5. Quantifiable alterations in rest-activity rhythms may occur in neuroleptic-induced akathisia but measurement of activity may be complicated by the patient's psychiatric disorder.

Outer retinal toxoplasmosis.

Toxoplasma gondii is a neurotrophic organism that affects the neurosensory retina in humans. Typical ocular toxoplasmosis involves the inner retina and is associated with marked vitreous reaction. A subset of this clinical spectrum is characterized by gray-white macular lesions at the level of the outer retina. This outer retinal lesion is associated with little or no vitreous reaction. The authors report five additional cases of outer retinal toxoplasmosis. Recognition of this variation is important; prompt treatment, before serologic confirmation, resulted in marked visual improvement in all cases.

Macular halos associated with Niemann-Pick type B disease.

Macular halos describe a striking clinical finding of bilaterally elevated, doughnut-shaped, white rings around th fovea. This paper presents the third well-documented report of the association of macular halos with Niemann-Pick type B disease, demonstrated by color photographs and subtle fluorescein angiographic findings. The systemic association with Niemann-Pick type B disease was confirmed by bone marrow biopsy and enzyme assay. Of 13 family members examined, only the proposita had macular halos; 10 were found to be carriers by sphingomyelinase assay. Recognition of this pathognomonic eye finding warrants more widespread awareness as a presenting sign of Niemann-Pick type B disease.

Gastric outlet obstruction secondary to a distal duodenal stenosis.

A case is presented where gastric outlet obstruction was found to be secondary to carcinoma of the distal duodenum in a patient with acute on chronic duodenal ulceration. The fallibility of barium studies in this condition is discussed.

Human plasma beta-endorphin-like peptides: a rapid, high recovery extraction technique and validation of radioimmunoassay.

This is a report of the development, calibration, and validation of a series of techniques required to measure beta-endorphin (beta-END)-like immunoreactivity in human plasma, including sieve and affinity chromatography. The RIA, which uses the antibody Brenda, is very sensitive (IC50 = 5-15 fmol/tube at a final concentration of 1:40,000). The extraction process, which uses the Sep-Pak C18 cartridge (Waters Associates, Inc.), is simple and rapid and has a recovery rate of more than 90%. It extracts proopiomelanocortin, beta-lipotropin, and beta-END. Physiological validation was provided by the measurement of beta-END-like immunoreactivity in a pool of plasma of normal humans (2.25 fmol/ml plasma), two pregnant women at term (9.5 and 10.75 fmol/ml), and one patient with Nelson's disease (2 pmol/ml plasma).

Symptomatic sarcoidosis of skeletal muscle.

Two patients with chronic sarcoid myopathy are described. Both were middle-aged females and both showed the features of pseudohypertrophy. In other aspects they contrasted markedly. In one (A.R.) the sheer volume of granuloma and its effect on muscle fibres was sufficient to explain the muscle weakness and electromyography confirmed a pure myopathy. In the other (J.W.) the muscle granuloma was sparsely distributed and an associated neuropathy contributed importantly to the disability. There was no clinical evidence of sarcoidosis of other organs in one (A.R.) but necropsy showed multisystem involvement. There was clinical and radiographic evidence of widespread sarcoidosis in the other (J.W.). Both patients showed an initial dramatic response to prednisolone. The reported literature of symptomatic muscle sarcoidosis is reviewed briefly.