Adult epiglottitis

Adult epiglottitis (or "supraglottitis") is an uncommon but increasingly recognized entity. Though prior studies emphasized the fulminant nature of the disease, recent evidence suggests that epiglottitis in adults may follow a relatively less severe clinical course, especially if Hemophilus influenza is not isolated. The records of 28 patients with adult epiglottitis were retrospectively analyzed to characterize the presenting features and clinical course of the disease. The diagnosis was established by laryngoscopy, lateral cervical radiographs, or both. Laryngoscopy did not precipitate airway obstruction in any patient. The majority of patients experienced a relatively benign clinical course and improved with medical management that consisted of ICU admission, intravenous antibiotics, hydration, inhaled mist, and corticosteroids. Only two patients (7%) required airway support with orotracheal intubation because of respiratory difficulty. There were no instances of respiratory arrest or airway obstruction. No tracheostomies were performed, and there were no deaths. It was concluded that adult epiglottitis can follow a less severe course than classically described.     

Malignant pleural effusions: pleurodesis using a small-bore percutaneous catheter

This study describes our experience using a percutaneously placed small-bore catheter for drainage of malignant pleural effusions and subsequent instillation of a sclerosing agent to obliterate the pleural space. We treated 15 consecutive patients with known metastatic cancer and a symptomatic pleural effusion. Twelve patients survived for more than four weeks after the procedure; 11 of these 12 patients had a successful objective clinical response. The procedure was well tolerated, with little or no discomfort during catheter placement and the maintenance period. No serious complications were encountered. We conclude that the use of a small-bore percutaneously placed "pneumothorax" catheter in the management of malignant pleural effusions is an effective and more comfortable alternative to large-bore closed-tube thoracostomy.     

Financing the medical management of mental disorders

In 1987 Medicare benefits for the mentally ill were expanded for the first time in 22 years. A major change was the removal of limits and copayments for the "medical management of psychopharmacologic agents." Payment for medical management recognizes the trend toward the remedicalization of psychiatry; however, medical management can be defined either broadly or narrowly. The authors suggest pricing strategies for both medical management of mental disorders and psychotherapy. Enlightened design of psychiatric benefits will cover all forms of treatment according to appropriate rules. Access to treatment for mental illness is at stake as these rules develop.     

Serum and testicular testosterone and androgen binding protein profiles following subchronic treatment with carbendazim

While the general toxicity of the benzimidazole pesticides for mammals is low, one of these compounds, carbendazim (MBC), causes degeneration of testicular tissue and decreases spermatogenic activity at doses well below the LD50 value. A study conducted by S. D. Carter, R. A. Hess, and J. W. Laskey (1987, Biol. Reprod. 37, 709-717) showed that treatment with 400 mg/kg/day MBC resulted in severe seminiferous tubular atrophy and infertility. Since spermatogenesis is an androgen-dependent process, we characterized the effects of MBC (0-400 mg/kg/day) on the endocrine function of the rat testes. Following subchronic (85 day) exposure, serum hormones (TSH, LH, FSH, and Prl) were measured as were androgen binding protein (ABP) and testosterone in testicular fluids (interstitial fluid and seminiferous tubule fluid). In addition, the functional capacity of the Leydig cell to secrete testosterone was assessed in vitro following an hCG challenge. Subchronic treatment with MBC at doses of 50-100 mg/kg/day had no effect on pituitary or testicular hormone concentrations: 200 mg/kg/day elevated the testosterone concentration in the seminiferous tubule fluid and the ABP concentration in both the interstitial fluid and the seminiferous tubule fluid without affecting serum testosterone or ABP concentrations. The 400 mg/kg/day dose resulted in increased concentration of both testosterone and ABP in the interstitial fluid and seminiferous tubule fluid and elevated serum ABP, with no change in serum testosterone. This endocrine profile is consistent with the testicular atrophy and "Sertoli cell-only" syndrome seen in these animals as reported by Gray et al. (1987, Toxicologist 7, 717). We conclude that seminiferous tubule fluid testosterone may be a result of two factors: (1) increased interstitial fluid testosterone concentrations and (2) decreased testosterone outflow from the testis to the general circulation. Also, increased ABP in the interstitial fluid may reflect a change in the relative secretion of ABP into the interstitial fluid and the seminiferous tubules.     

The mere exposure effect in patients with Alzheimer's disease

The mere exposure effect was examined in patients with mild to moderate Alzheimer's disease (AD). Twenty patients and 20 elderly controls judged the physical characteristics of faces. Implicit memory was tested later by presenting pairs of faces (old and new) and asking participants which faces they liked better. Patients and controls exhibited above chance preference for previously exposed faces. Experiment 2 evaluated whether the preserved implicit memory of patients was mediated by explicit memory. Patients and controls again judged faces but then later chose which faces they had seen before. Patients exhibited impaired recognition memory compared to controls. These findings suggest that a mere exposure effect for unfamiliar faces is present in mild to moderate AD. The results are discussed in terms of perceptual and conceptual priming and relatively spared occipital lobe functioning in early AD.     

Infection of P388D1 macrophages and respiratory epithelial cells by Histoplasma capsulatum: selection of avirulent variants and their potential role in persistent histoplasmosis.

We evaluated P388D1 macrophagelike cells as model host cells for studying the intracellular survival and strain-specific virulence of Histoplasma capsulatum. Previously characterized strains which were virulent for mice destroyed monolayers of these cells within a few days. In contrast, related avirulent "smooth" variants failed to do so even after 20 days, although they persisted within P388D1 cells for at least 7 days. On the basis of this observation, we developed a quantitative radiolabel assay to use as an initial screen for virulence. Another cell type lining the respiratory tract was then examined as a potential host for H. capsulatum. Hamster trachea epithelial (HTE) cells readily internalized a variety of strains lacking alpha-(1,3)-glucan in their cell walls; however, the tracheal cells were only rarely infected by organisms possessing this polysaccharide. We subsequently inoculated HTE cells with alpha-(1,3)-glucan-positive strains and enriched for the few yeasts infecting these cells. The progeny resembled smooth variants in terms of colony morphology, the absence of alpha-(1,3)-glucan in their cell walls, and their inability to kill macrophages. Did the HTE cells select for these variant yeasts from the parent inoculum or instigate a change from the parental phenotype? Following a 3-h uptake period, only 2% of the ingested yeasts lacked alpha-(1,3)-glucan. One day later, nearly half of the intracellular organisms lacked this polymer. This rapid conversion of a large proportion of the inoculum suggests some type of environmentally triggered change, perhaps analogous to phase variation seen in many other pathogens. Infection of epithelial cells or some other nonprofessional phagocyte during natural histoplasmosis might give rise to similar variants, thus establishing a reservoir of organisms capable of causing chronic or latent infections.     

Developmental changes in pre-adult behavior in confined colonies of golden hamsters.

Eight litters of hamsters living in a large enclosure were observed from birth to 120 days. For the first 65 days each litter was confined to a separate compartment. Basic motor coordination was reached by the 3rd week. Marking was seen during the 6th week when males began to mount their mothers sexually, but lordosis was not seen in female pups before the 7th week. Fighting appeared at this time with the females being the more aggressive. At 65 days the litters were combined into 2 groups of 4.A gradual shift followed in the relative aggressiveness of the sexes. Females, which had previously initiated over 90% of attacks, became less aggressive, whereas attacks by males increased to the former female level. This unusual behavior for hamsters, where females are normally dominant, may have been due to crowding. Also, severe disruption of maternal behavior occurred with marked infanticidal tendencies.     

T helper type 2-like cells and therapeutic effects of interferon-γ in combined immunodeficiency with hypereosinophilia (Omenn's syndrome)

We characterized the defects of CD4+ cells in a 17-month-old girl suffering from combined immunodeficiency with hypereosinophilia (Omenn's syndrome). Because the vast majority of peripheral blood CD4⁺ cells expressed the CD45R0 isoform, we purified circulating CD4⁺ CD45R0⁺ cells from the patient and healthy individuals in order to compare their production of cytokines. The patient's CD4⁺ CD45R0⁺ cells spontaneously produced high levels of interleukin-5 (IL-5) in vitro (1600 pg/ml after 24 h of culture) and this was associated with the presence of IL-5 in serum (323 pg/ml). After stimulation with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187, they produced higher levels of IL-4 (306 vs. 55 ± 4 pg/ml) and IL-5 (2900 vs. 213 ± 72 pg/ml) and lower levels of IL-2 (17 vs. 63 ± 17 IU/ml) and interferon-γ (IFN-γ) (16 vs. 299 ± 70 IU/ml) than controls CD4⁺ CD45R0⁺ cells. This T helper type 2 (Th2) pattern was confirmed by the detection using reverse polymerase chain reaction of IL-4, IL-5 and IL-10 mRNA within peripheral blood mononuclear cells. During a therapeutic trial with human IFN-γ (40 μg/day) which ameliorated the clinical status of the patient, we observed a down-regulation of the in vivo expression of IL-5 and IL-10, a normalization of the eosinophil count and an improvement of the Tcell response to phytohemagglutinin. This observation indicates for the first time that Th2-like cells might be involved in certain forms of congenital immunodeficiency and that IFN-γ might down-regulate their activities in vivo.     

Impaired responses to toll-like receptor 4 and toll-like receptor 3 ligands in human cord blood

Toll-like receptor (TLR)-4 signaling pathway plays an essential role in host defense against gram-negative bacteria while TLR-3-mediated signaling is critically involved in anti-viral immunity. To gain insight into the defects responsible for impaired Th1 responses in human newborns, we investigated the responses of human cord blood cells to lipopolysaccharide, LPS, and to polyinosinic-polycytidylic acid, Poly (I:C), ligands of TLR-4 and TLR-3, respectively. Measurement of cytokine levels revealed a profound defect in IL-12 (p70) synthesis and an increased release of IL-10 in cord blood exposed to LPS or Poly (I:C), as compared to adult blood. Moreover, Poly (I:C)-induced IFN-alpha production was found to be significantly impaired in cord blood. Phenotypic maturation of myeloid DC in response to LPS or Poly (I:C) was next compared in cord and adult blood. We observed that neonatal myeloid DC displayed decreased upregulation of CD40, CD80 whereas CD86 and HLA-DR upregulation did not differ significantly between adults and neonates. Taken together, these findings might be relevant to the increased vulnerability of human newborns to intracellular pathogens and to their inability to develop efficient Th1-type responses.