Multi-center, double-blind, placebo-controlled trial of fluocortin butyl in perennial rhinitis

Fluocortin butyl (FCB) is a newly synthesized corticosteroid with a high ratio of topical to systemic activity. FCB was studied in a multi-center, double-blind, placebo-controlled trial of therapy of perennial rhinitis. The study was conducted between January and May 1981. Patients evaluated suffered from either chronic allergic or chronic nonallergic rhinitis or both. A total of 306 patients from 16 investigative centers were evaluated by comparing FCB to placebo. Three separate dosage regimens were employed. Patients received a total daily dose of 2, 4, or 8 mg. FCB was found to be an effective therapeutic agent. It reduced symptoms of nasal congestion, rhinorrhea, postnasal drainage, and sneezing. It also markedly reduced the use of concomitant medications (chlorpheniramine maleate and/or pseudoephedrine). Relief of symptoms was noted as early as the first week of therapy, and the degree of improvement increased progressively during the study. There was little difference between the relief produced by the 4 mg and 8 mg regimens. Both of these were superior to the 2 mg regimen. The drug was well tolerated; no significant side effects were noted.     

Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion

Submicroscopic deletions of the Y chromosome and polymorphisms of the androgen receptor (AR) gene in the X chromosome have been observed in men with defective spermatogenesis. To further define the subregions/genes in the Y chromosome causing male infertility and its relationship to polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of 202 subfertile males and 101 healthy fertile controls of predominantly Chinese ethnic origin. Y microdeletions were examined with 16 sequence-tagged site (STS) probes, including the RBM and DAZ genes, spanning the AZFb and AZFc subregions of Yq11, and related to the size of trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions were detected and confirmed in three out of 44 (6.8%) of azoospermic and three out of 86 (3.5%) severely oligozoospermic patients. No deletions were detected in any of the patients with sperm counts of >0.5 x 10(6)/ml, nor in any of the 101 fertile controls. All six affected patients had almost contiguous Y microdeletions spanning the entire AZFc region including the DAZ gene. The AZFb region, containing the RBM1 gene, was intact in five of the six subjects. Y deletions were not found in those with long AR polyglutamine tracts. Our study, the first in a Chinese population, suggest a cause and effect relationship between Y microdeletions in the AZFc region (possibly DAZ), and azoospermia or near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear to be independent contributors to male infertility.      

Effect of adrenergic compounds, aminophylline and hydrocortisone, on in vitro immunoglobulin synthesis by normal human peripheral lymphocytes

Suspensions of normal human peripheral lymphocytes were exposed briefly to various concentrations of propranolol, isoproterenol, epinephrine, or aminophylline (both without and with added hydrocortisone) and then incubated for 72 hours at 37 ° C. After this incubation the amount of immunoglobulin (Ig) synthesized and secreted into the cultured supernatants was quantitated by radiaimmunoassay. Significantly increased Ig formation compared to controls was observed with the following concentrations of the experimental compounds (without hydrocortisone): 10^?9 to 10^?7M propranolol, 10^?10 to 10^?7M isoproterenol, 10^?8M epinephrine, and 10^?7 to 10^?5M aminophylline. When cell suspensions were exposed briefly to these same compounds but with hydrocortisone added, the following concentrations of compounds significantly increased Ig synthesis: 10^?10 to 10^?8M propranolol, 10^?10 to 10^?6M isoproterenol, 10^?9 to 10^?7M epinephrine, and 10^?8 to 10^?5M aminophylline. Of the four compounds studied, only the epinephrine data suggest that hydrocortisone enhanced the stimulation of Ig synthesis by this catecholamine.     

Counter-immunoelectro-osmophoresis for the detection of infantile gastroenteritis virus (orbi-group) antigen and antibody.

A moderatley sensitive, rapid, and economical test scheme for the detection of infantile gastroenteritis virus (IGV) in stool or antibody in serum has been developed and evaluated. The test scheme with minor modifications was an adaptation of a counter-immunoelectro-osmophoresis system we once used for the detection of hepatitis B antigen. Large numbers of stool samples may be screened during half a working day for the presence of IGV using reference antiserum to IGV prepared in guinea-pigs. Serological studies of a diagnostic but not epidemiological nature may also be performed with equal facility by this same test scheme using highly purified IGV antigen derived from stool.     

The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection

We studied the development of respiratory syncytial virus (RSV)-specific IgE and the release of histamine in nasopharyngeal secretions from 79 infants with various forms of respiratory illness due to RSV. RSV-IgE was measured by an enzyme-linked immunosorbent assay; specificity was confirmed by appropriate blocking experiments. Histamine content in the secretions was determined by fluorimetric methods. RSV-IgE was detectable in only one of 19 patients with RSV infection without wheezing, but was detectable in the majority of 60 patients with wheezing (P less than 0.01). Titers of RSV-IgE were significantly higher in patients with wheezing (P less than 0.05). Histamine was detectable in secretions of some patients with all forms of illness but was detected significantly more often (P = 0.05) and in higher concentrations in patients with wheezing. Peak titers of RSV-IgE and concentrations of histamine correlated significantly with the degree of hypoxia (P less than 0.001). Formation of RSV-specific IgE and release of histamine may adversely affect the outcome of RSV infection.     

Detection of Antibodies in Human Sera to Streptococcal Groups A and C Carbohydrates by a Radioimmunoassay

The human lymphokine, leucocyte migration-inhibitory factor (LIF), appears to be a serine esterase and protease by virtue of its susceptibility to the irreversible enzyme inhibitor, phenylmethylsulfonyl fluoride (PMSF), and by the ability of arginine esters and amides to protect LIF against PMSF-induced inactivation. In this paper, three methods are described by which putative substrates for LIF may be investigated. Thus, molecules satisfying the substrate specificities of this lymphokine should (1) protect LIF against inactivation by PMSF, (2) reduce LIF activity in vitro on polymorphonuclear leucocytes, and (3) reduce the esterolytic activity of purified LIF-rich supernatants. The first two reactions were tested by means of the leucocyte migration agarose technique; the third reaction was tested by a sensitive enzyme assay using tritiated tosyl arginine methyl ester as substrate. Guanosine 3',5'-cyclic monophosphoric acid, which is capable of protecting LIF against PMSF-induced inhibition, also inhibited the esterolytic activity of the purified LIF preparation. Four synthetic oligopeptide substrates for trypsin, thombin and plasmin were investigated. Only one, the thrombin- and trypsin-specific benzoyl-phenylalanyl-valyl-agarine-p-nitroanilide, possessed high affinity for the LIF molecule and may therefore prove to be a potent substrate for this lymphokine.     

Cytokines, thyroid autoantibody synthesis and thyroid cell survival in culture

In autoimmune thyroid disease lymphoid cells infiltrating the thyroid gland occur in conspicuous aggregates or as a diffusely distributed population invading the thyroid follicles. Consequently cytokines secreted by activated T cells or macrophages could influence neighbouring thyroid cells as well as other lymphocytes. We have investigated this possibility using recombinant cytokines. Thyroid cell survival was assessed in terms of mitochondrial dehydrogenase activity in monolayers exposed to tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1 (IL-1 alpha and beta) and interleukin-2 (IL-2) in the presence or absence of thyroid-stimulating hormone (TSH). Neither TNF-alpha nor IL-2 affected thyroid cell survival, IFN-gamma was usually inhibitory and IL-1 alpha slightly enhanced cell survival in some experiments. However, the effects were small and variable and were not enhanced by potentially synergistic combinations of cytokines, longer periods of exposure, or different culture conditions. In contrast, IFN-gamma, IL-2 and TNF-alpha inhibited the ability of thyroid lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis to synthesize autoantibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg). Comparison of lymphoid populations isolated by digestion and/or mechanical disaggregation indicated that a population of activated B cells, plasma cells and T cells, intimately associated with thyroid cells since they could only be extracted by digestion, was influenced by cytokines. Our studies suggest that in addition to its well-recognized ability to induce MHC class II antigens on thyroid cells, IFN-gamma may inhibit thyroid cell proliferation and TNF-alpha, IFN-gamma and IL-2 may down-regulate thyroid autoantibody synthesis.     

Bereavement. State of the art and state of the science

For bereavement research to fulfill its potential, its practical applications with defined patient groups needs to demonstrate a superiority over treatment based largely on intuition and common sense. The "art" of the therapist needs science to move beyond the present impasse in the management of bereavement.