NON-IgE-MEDIATED ASTHMA IN CHILDREN

ABSTRACT. Among 586 children with asthma, 484 (82 %) were found to have IgE-mediated ("extrinsic") asthma, and seventy-two (12 %) non-IgE ("intrinsic") asthma. The remaining 30 patients (6%) were classified as "intermediate", as they had serum IgE within or above serum IgE levels of healthy children but no allergy to common allergens. During a three-year study period, the seventy-two patients with intrinsic asthma as opposed to 84 patients with extrinsic asthma had significantly 1) more hyperinflation of the lungs, 2) more episodes of acute hospital admissions due to asthma and/or pneumonia, 3) more elevated serum IgG and IgM, and 4) more cultures from secretions of lower airways of Haemophilus influenzae and pneumococci. Further, although treated with corticosteroids, eleven of the children with intrinsic asthma showed progressive disease, judged from fixed and/or declining forced vital capacity followed by signs of lung fibrosis on repeated pulmonary X-rays. It is emphasized that children with intrinsic asthma may represent an entity of childhood asthma, in some cases with severe progression of disease within a few years.     

Complex fractures of the proximal humerus: role of CT in treatment

The authors reviewed the computed tomography (CT) scans, plain radiographs, and subsequent treatment of 17 patients with complex proximal humeral fractures. CT scans and radiographs were compared in the demonstration of fracture lines, displacement of fracture fragments, rotation of fragments relative to their normal positions, and status of the head and articular surface of the humerus. The impact of CT findings on the decision to treat with surgery versus closed reduction and on the choice of surgical procedure was assessed. Surgery was not performed in nine patients because CT scans showed no significant displacement of fragments previously judged displaced or "indeterminate" on radiographs. Surgery was performed in eight patients; CT demonstrated significant abnormalities not definitely shown with radiography. In six of these eight patients, CT scans demonstrated unsuspected abnormalities that directed the choice of surgical procedure. CT scans provide clinically useful information for the treatment of complex proximal humeral fractures when radiographs provide inadequate or indefinite information.     

FUNCTIONAL RESPONSES OF THE RAT ISOLATED SEMINAL VESICLE TO ELECTRICAL FIELD STIMULATION: A PHARMACOLOGICAL ANALYSIS

• 1 Electrical field stimulation (EFS) of the rat isolated seminal vesicle elicited frequency-dependent and tetrodotoxin sensitive contractions which were unaltered by hexamethonium or mecamylamine.
• 2 Prazosin alone was not sufficient to abolish these responses, but a combination of atropine and prazosin was fully effective, indicating involvement of both noradrenergic and cholinergic mechanisms.
• 3 Responses were predominantly cholinergic (blocked by atropine, potentiated by ecothiopate but not significantly altered by prazosin or guanethidine) at 1–8 Hz but became increasingly noradrenergic (blocked by prazosin or guanethidine but relatively unaltered by atropine or ecothiopate) with increasing frequencies of stimulation.
• 4 Electrical field stimulation of seminal vesicles removed from reserpine or 6-hydroxydopamine (6-OHDA)-pretreated rats produced contractions that were clearly cholinergic in nature.
• 5 After exposing the seminal vesicles to guanethidine, or after pretreatment of rats with 6-OHDA, responses to EFS remained, indicating that activation of discrete cholinergic and noradrenergic innervations seem to underlie the contractile responses observed.
• 6 Yohimbine and prazosin potentiated the predominantly cholinergic responses at 1,2 and 4 Hz in tissues from untreated rats, but not in those from animals pretreated with reserpine or 6-OHDA, indicating the possibility of an interaction between the two innervations.
• 7 No inhibitory responses to EFS could be demonstrated in tissues precontracted with KCI in the presence of a combination of atropine and prazosin suggesting the absence of a non-adrenergic, noncholinergic inhibitory innervation.

     

Monoclonal Human B Lymphoma Cells Respond by DNA Synthesis to Anti-Immunoglobulins in the Presence of the Tumour Promotor TPA

Monoclonal human B lymphoma cells were triggered in vitro to DNA synthesis with F(ab')2 fragments of rabbit IgG antibodies specific for different human immunoglobulin (Ig) light and heavy chains. The specificity of the responses corresponded to surface Ig (sIg) present on tumour cells. Anti-mu chain, anti-delta chain, and antibodies to light chains were found to mediate this effect. However, to induce DNA synthesis, the tumour promotor 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was usually required. TPA alone induced cytoplasmic protrusions and increases in cellular volume. These observations should provide new opportunities to study the triggering of B cells with anti-Ig in well-defined cell populations.     

Genetic and physical mapping of the McKusick-Kaufman syndrome

McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos. This syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and variable expressivity. Homozygosity mapping and linkage analyses were conducted using two pedigrees derived from a larger pedigree published in 1978. The PedHunter software query system was used on the Amish Genealogy Database to correct the previous pedigree, derive a minimal pedigree connecting those affected sibships that are in the database and determine the most recent common ancestors of the affected persons. Whole genome short tandem repeat polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and D20S894 , an area that includes the Alagille syndrome critical region. The peak two-point LOD score was 3.33, and the peak three-point LOD score was 5.21. The physical map of this region has been defined, and additional polymorphic markers have been isolated. The region includes several genes and expressed sequence tags (ESTs), including the jagged1 gene that recently has been shown to be haploinsufficient in the Alagille syndrome. Sequencing of jagged1 in two unrelated individuals affected with McKusick-Kaufman syndrome has not revealed any disease- causing mutations.      

The Apex polyester fibre anterior cruciate ligament implant: operative procedure and early results

This paper describes the surgical method and instruments for placing and anchoring the Apex polyester fibre anterior cruciate ligament (ACL) reconstruction. It then reviews the early clinical findings and describes recent developments. At the time of review, 172 Apex replacements had been implanted in the UK in arthroscopically proven chronic ACL-deficient knees. These had been inserted at eight centres since 1987, and follow up was by a single observer assessing patients by questionnaire, clinical examination, stress X-ray and KT 1000 arthrometer. Patients less than 12 months from surgery were excluded, leaving 95 with a mean follow up of 27 months (range 13 to 66 months) on whom results are based. Assessment showed improved stability after operation and the Apex implant appears to provide a reliable method of stabilizing the ACL deficient knee within the confines of this short-term review. The authors feel that further trials are justified.     

Full genetic rescue of adenosine deaminase-deficient mice through introduction of the human gene

We have shown recently that adenosine deaminase (ADA)-deficient mice die perinatally with severe liver cell degeneration. In addition to enzyme substitution, we report the restoration of viability through introduction of the human ADA gene. The ADA gene is subject to complex developmental and tissue-specific regulation. To include the cis- regulatory elements necessary for correct regulation of the human ADA gene, a large transgenic locus constituting the human ADA gene with 10 kb of 5' and 4 kb of 3' flanking sequences was generated by co- injection of two overlapping DNA fragments into murine zygotes. Probably as a result of extrachromosomal (homologous) recombination between the fragments, one of the two transgenic lines contained a reconstituted, functional human ADA gene. As in man, human ADA expression generally was low in these transgenic mice, but high in the thymus, spleen and gastro-duodenal part of the gut. Apparently, all cis- regulatory elements essential for a human expression pattern were incorporated in the transgene and were functional in the murine background. Similarly to man, the upper alimentary tract of the transgenic mice revealed low human ADA activity in contrast to extremely high levels of murine ADA. The human gene probably lacks the cis-regulatory elements that target high level murine ADA expression to the murine upper alimentary tract. ADA-deficient mice rescued by introduction of the human ADA transgene appeared histologically and immunologically normal. Apparently, human ADA can complement murine ADA in all tissues, even in the epithelium of the upper alimentary tract where human ADA activity is as much as 70-fold lower than murine ADA activity in wild-type mice. Clearly, the lethal phenotype of ADA- deficient mice is due to the absence of ADA.      

Placental protein 14 in endometrium during menstrual cycle and effect of early luteal phase mifepristone administration on its expression in implantation stage endometrium in the rhesus monkey

Placental protein 14 (PP14) is a glycoprotein which is secreted by secretory phase endometrium and decidua in women. Despite the suggestion that PP14 is involved in the process of endometrial maturation for blastocyst implantation, our understanding in this regard is poor. In the present study, the concentrations and distribution patterns of immunodetectable PP14 in the endometrium during proliferative and secretory phases of normal ovulatory menstrual cycles, as well as in implantation stage endometrium in naturally mated ovulatory cycles with or without early luteal phase mifepristone treatment, were investigated using the rhesus monkey as a primate model. Immunopositive PP14 was observed mainly in epithelial cells of glands and it was detected in one major immunopositive band at Mr 28 kDa in tissue homogenate and spent medium. The area of immunopositive precipitation of PP14 in glands was minimal in follicular phase endometrium, and was higher (P < 0.01) in early, mid- and late luteal phase endometrium compared with that in pre- and periovulatory phases of the cycle, but there was no change in its area profile in the glandular compartment throughout the luteal phase. Immunopositivity for PP14 in luminal contents of gland displayed an increasing profile from early to late secretory phases. Thus, the concentrations and the distribution of immunodetectable PP14 in luteal phase endometrium of the rhesus monkey showed marked similarity with those of human endometrium during the natural menstrual cycle. Although there was no marked change in the band characterstics for the protein in implantation stage endometrium following early luteal phase mifepristone treatment, it was markedly decreased (P < 0.01) in tissue homogenate and in vitro spent medium along with a lesser (P < 0.02) degree of immunoprecipitation in the glands in implantation stage samples of mifepristone treatment group compared with that in control group samples. Thus, the contragestional effect of early luteal phase mifepristone treatment appears to be associated with a decrease in the concentration of immunodetectable PP14 in implantation stage endometrial glands and its secretion in the rhesus monkey. It remains to be seen whether this decline is caused from direct antiprogesterone action on endometrial glands during progesterone dominance, or secondarily from associated retarded development of endometrium.