Inhibition of interleukin-2-stimulated enhancement of human natural killer (NK) cell activity by carbaryl, an anticholinesterase insecticide.

The potency of the anticholinesterase (antiCHE) insecticides as serine hydrolase inhibitors, and evidence for serine hydrolase activity in interleukin-2 (IL2) signalling suggest that the natural killer (NK) cell may be a target for dysregulation by antiCHE insecticides. NK cells are large granular lymphocytes (LGL) that respond to IL2 by proliferating and increasing their cytolytic efficiency. In the present study, we assessed the effects of carbaryl (CA, an antiCHE insecticide) and alpha-naphthol (NA, the major metabolite of CA) on both target cell killing per se and IL2 enhancement of target cell killing by human NK cells. Human LGL, collected from the peripheral blood of normal donors, were cultured for 4 days with human recombinant IL2 (HRIL2), then assayed by a 51Chromium (51Cr) release assay for lytic activity against human K562 cells. When added at the beginning of the culture period, CA inhibited enhancement of cytolytic efficiency in a concentration-dependent manner; at concentrations (0.5 and 5.0 microM) compatible with no cholinergic toxicity. Reduction of the effector/target cell (E/T) ratio in the 51Cr release assay markedly enhanced the observed inhibition by CA. In one experiment, inhibition increased from 6% to 20%, 17% to 35%, and 53% to 73% at 0.5, 5.0, and 50 microM CA, respectively, when E/T was reduced from 10:1 to 2.5:1. This result is consistent with reduced cytolytic efficiency of individual NK cells exposed to CA. NA had no effect at 0.5 or 5.0 microM but caused some inhibition at 50 microM. Neither CA nor NA produced LGL death. When CA or NA was added directly to the 51Cr release assay, inhibition was not observed. The mechanism of inhibition of IL2-stimulated enhancement of target cell killing is not yet known, however, the results are consistent with impairment of IL2 signalling, by CA.     

Dislodgement of a submandibular gland sialolith during nasal intubation. A case report

A case of dislodgement of a submandibular sialolith into the oropharynx during nasal intubation is presented. The deleterious effect of the patient aspirating the stone into the lungs was averted by the taking of a lateral skull radiograph and localization and removal of the sialolith.     

Cocaine abuse, attention deficit disorder, and bipolar disorder

Cocaine is a potent dopamine agonist that frequently stimulates the central nervous system and is often manifested by increased psychomotor activity, impulsivity, euphoria, and rapid thoughts. Attention deficit disorder (ADD) and bipolar disorder also present with physical restlessness, racing thoughts, distractibility, and mood instability. Although these three disorders rarely appear in the same individual, they are important differential diagnoses when considering any one illness with the above symptom complexes. We report two cases of cocaine abuse with ADD residual type in patients who were previously diagnosed as having atypical bipolar disorder. The adverse effects were reversed by the dopamine agonist bromocriptine.     

Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells

Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients.     

Alcohol consumption, ACTH level, and family history of alcoholism

Plasma levels of ACTH were evaluated in 18 sons of alcoholics and 18 sons of nonalcoholics before and after they consumed placebo, 0.75 ml/kg of ethanol, and 1.1 ml/kg of ethanol. The analyses revealed significant changes in ACTH levels over time, an effect of ethanol on ACTH overall, and significantly lower ACTH levels in the sons of alcoholics than in the control subjects following the high-dose ethanol challenge. The data corroborate the earlier finding that sons of alcoholics have less intense responses to ethanol and are consistent with the conclusion that changes in cortisol level associated with drinking include a pituitary response as well as effects on the adrenal glands.