Progression of self-reported symptoms in laboratory animal allergy

BACKGROUND: Laboratory animal allergy is a common illness among workers exposed to laboratory animals and can progress to symptoms of asthma. OBJECTIVES: This study evaluates the continuum of disease from allergy symptoms to asthma symptoms in a dynamic cohort of workers exposed to animals in a pharmaceutical company. METHODS: Data arose from annual questionnaires administered to workers in a surveillance program established to monitor exposure to animals and the development of allergy. The life-table method was used to compare asthma-free survival between workers with and without symptoms of allergy. A Cox proportional hazards model was used to examine the effects of covariates on the development of asthma. RESULTS: A total of 603 workers contributed 2527.4 person-years to the study over the 12.3-year period. The probabilities of experiencing asthma symptoms by the 11th year of follow-up were 0.367 for workers with allergy symptoms and 0.052 for those without allergy symptoms. The hazard ratio for asthma symptoms when comparing workers with and without allergy symptoms was 7.39 (95% CI, 3.29-16.60) after adjustment for sex and family history of allergy. Female subjects developed asthma at a rate 3.4 times that of male subjects. CONCLUSIONS: This study supports the hypothesis that laboratory animal allergy symptoms are a major risk factor for the development of asthma. It also suggests a heightened risk of asthma for women who work with laboratory animals, a finding that has not been previously reported.     

Monte Carlo studies of x-ray scattering in transmission diagnostic radiology

Monte Carlo methods have been used to simulate the scattering of x rays in polystyrene and water phantoms. In particular, the ratio of the scattered to total x-ray fluence (scatter fraction) has been calculated for monoenergetic x-ray beams in the energy region relevant to diagnostic radiology and nuclear medicine (30-660 keV). Simulations have been made for representative values of the pertinent geometrical factors; phantom thickness from 5 to 21 cm, x-ray beam diameters of 10 and 25 cm, and scatterer-to-image-plane separations from 0 to 20 cm. As a function of x-ray energy, the scatter fraction was found to vary slowly between 30 and 100 keV, and to decrease between 100 and 660 keV. The present results were generated with a special transport code which included the effects of special geometries and the response of the x-ray detector. With the inclusion of these effects, the results resolved inconsistencies and showed good agreement with previous measured and calculated data.     

Histamine release during induction of anaesthesia and preparation for operation in patients undergoing general surgery: Incidence and clinically severe cases

Histamine release events were shown in a prospective randomized controlled trial in patients undergoing elective general surgery with an extraordinarily high incidence: 73 per cent. This high incidence was explained by several factors: — the sample size which was much greater than in previous studies — the improved plasma histamine assay — the precise definition of histamine release in clinical conditions and its measurement at the top of Bateman functions — the standardized induction of anaesthesia and preparation of the surgical patient — and finally the considerable number of cancer patients since more than 60% of the reactions >5 ng/ml occurred in this group which comprised only 20% of the study population.

Two cases of life-threatening anaphylactoid reactions occurred in this trial corresponding to an incidence of 1 per cent. This was — again — very high compared to previous epidemiological studies. Both cases were again cancer patients and occurred in the placebo group — information given by the external study advisory group for further treatment of the individual patient.

The data on the high incidence of histamine release including the high incidence of life-threatening reactions favourrationally a preoperative H₁ ⁻+H₂-prophylaxis with the drugs used in this study: dimetindene and cimetidine. The question of the incidence was one of the unsettled problems which led to this trial. Analysis of the first 180 patients already answered this question more than we had ever expected.

     

Metallic wires with an adherent lubricious and blood-compatible polymeric coating and their use in the manufacture of novel slippery-when-wet guidewires: possible applications related to controlled local drug delivery

A new procedure was developed for the controlled application of adherent hydrophilic and biocompatible coatings onto the surface of "endless" metallic wires. Use of copolymers of 1-vinyl-2-pyrrolidinone and alkylmethacrylates provided coatings with excellent adherence and lubricity, and markedly low thrombogenicity. Coated wires could be spiralized without damaging the coating; the resulting coils are potentially useful as lubricious guidewires for use in, for example, interventional cardiology or urology. This study demonstrates that the lubricity of the coating is dependent on the composition (hydrophilicity) of the coating biomaterial, as well as on the thickness of the coating. Furthermore, the results imply that the adherence of the hydrophilic coating is essentially due to entanglement of the binder polymer chains and the hydrophilic copolymer chains. Moreover, the idea to use the hydrophilic coating on the wire as a temporary depot for controlled local drug delivery was explored. The coating was loaded with the dye rhodamine, and release of the dye upon immersion of the coated wire in water was studied. This work revealed that release of the drug is dependent on the composition of the coating. The potential utility of such wires with a drug-charged coating for controlled local drug delivery is discussed briefly.     

Effect of influenza A virus on leukocyte histamine release

Viral respiratory infections provoke asthma in many patients. In the following study we examined the effect of an in vitro incubation of influenza A on leukocyte histamine release. After incubation with a live influenza A (H3N2) virus, calcium ionophore A23187 (0.5, 1.0, and 1.5 microgram/ml)-induced leukocyte histamine release (HR) was enhanced (p less than 0.05). This effect was also found with heat- or ether-inactivated virus. Similarly, influenza A-exposed leukocytes had augmented leukocyte HR during subsequent incubation with ragweed AgE. Incubation of the leukocyte suspension with interferon (800 IU/ml) for 24 hr was also associated with enhanced HR to ragweed AgE. In contrast, interferon did not alter the calcium ionophore A23187 HR. Therefore, although interferon may mediate the enhanced leukocyte HR when ragweed AgE is the inciting stimulus, it does not change HR to the calcium ionophore.     

Prediction of clinical course of bipolar manic depressive illness treated with lithium

A group of bipolar manic depressive patients attending a routine lithium clinic were investigated. The results suggest that, when on treatment with lithium, manic depressive patients with a good prognosis tend to have a higher erythrocyte Na-K ATPase and higher plasma and erythrocyte lithium concentrations than those with a poor prognosis. There was no evidence to suggest that the erythrocyte: plasma lithium ratio was useful in predicting clinical response to lithium therapy. There was also a positive correlation between plasma lithium concentration and Na-K ATPase activity, confirming that in manic depressive subjects lithium produces a rise in erythrocyte Na-K ATPase activity.     

Identification of a large insertion and two novel point mutations (3671del8 and S1221X) in tuberous sclerosis complex (TSC) patients. Mutations in brief no. 119. Online

Important symptoms of tuberous sclerosis complex (TSC), an autosomal dominant disorder, are hamartomata in several organs, mental retardation and epilepsy. Either one of two loci can be involved (TSC1 and TSC2), of which the TSC2 gene has been cloned. To date, only 35 mutations in the TSC2 gene have been described ranging from large deletions to point mutations. Southern blot analysis using cDNA clones of the TSC2 gene was performed on a cohort of 160 unrelated TSC patients and revealed a 10 kb insertion. The insertion was also present in DNA of the affected father. Both patients showed renal angiomyolipoma, hypomelanotic macules and epilepsy. SSCP analysis of exons 1,2,3,9,12,14,30a and 36 identified two mutations in exon 30a: 3671del8 and S1221X. Symptoms of the sporadic patient with the 3671del8 mutation are cortical tubers, subependymal nodules, facial angiofibroma, ungual fibroma, renal angiomyolipoma, hypomelanotic macules, epilepsy and mental retardation. Clinical symptoms of the patient with the S1221X mutation are facial angiofibroma, ungual fibroma, hypomelanotic macules, epilepsy and mental retardation. His parents were negative for the S1221X mutation, although a germline mosaicism can not be excluded. Besides the previously described polymorphism 1596C->T, two rare variants were observed, a substitution of C->T at position 1294 and at position 1299 C->A.     

A block in glycoprotein processing correlates with small plaque morphology and virion targetting to cell-cell junctions for an oral and an anal strain of herpes simplex virus type-1

Summary The characteristics of two clinical isolates of HSV-1 obtained from an oral (424) and an anal (490) lesion were compared with the highly passaged KOS strain. In contrast to KOS, the clinical isolates produced small plaques, were more cell-associated and the predominant viral glycoprotein species for gC and gD in infected cell lysates was the precursor, high mannose glycoform. Total virus production in Vero cells was equivalent for the three virus strains in one-step growths. Pulse-chase studies of glycoprotein C processing showed a reduction in rate at 7.5h post infection and a significant block in processing at 10.5h post infection for 424 and 490 but not KOS. Similar results were obtained for gD. The significant reduction in glycoprotein processing for 424 and 490 suggests a block in transport of viral glycoproteins or virions to and through the Golgi apparatus. Extracellular virions and the cell surface, prior to cell lysis, contained the processed gC glycoform suggesting a competent cellular glycan processing system. Upon co-infection of 424 or 490 with KOS or a gC^– KOS strain, gC was processed to levels equivalent to KOS indicating that 424 and 490 are not inhibitory but that an activity(s) encoded by KOS facilitates maturation of gC from 424 and 490. Unlike KOS infected Vero cells, virion-containing vacuoles were observed in the cytoplasm at 12h p.i. and extracellular virions were concentrated at cell-cell junctions of 424 or 490 infected cells but not in the perinuclear region. These results suggest that intracellular transport of viral glycoproteins and virions in 424 and 490 infected cells is different from KOS infected cells. The reduced level of viral glycoprotein maturation, virus release, cell surface presence and presence of virions at cell-cell junctions are consistent with small plaque production in tissue culture cells.Portions of this work were presented in the 17th International Herpesvirus Workshop, Pittsburgh, PA, 1993.