Effect of HFA-flunisolide on peripheral lung inflammation in asthma

BACKGROUND: New hydrofluoroalkane (HFA) formulations of glucocorticoids have been shown to effectively control asthma. HFA glucocorticoids are deposited across all sizes of airways, including the small ones. However, it is not clear whether they can suppress peripheral airway inflammation. OBJECTIVE: We sought to determine whether HFA-flunisolide could suppress peripheral inflammation in asthma. METHODS: Twelve patients with mild to moderate asthma received HFA-flunisolide for 6 weeks. Transbronchial and endobronchial biopsy specimens were obtained before and after treatment, and spirometry was performed. Changes in inflammatory cells (eosinophils, neutrophils, lymphocytes, macrophages, basophils) and IL-5 and eotaxin were measured by using immunocytochemistry and in situ hybridization. RESULTS: Lung function significantly improved after treatment (P <.05). HFA-flunisolide significantly reduced eosinophils, IL-5, and eotaxin in both peripheral and central airways (P <.01). Neutrophils significantly increased after treatment in peripheral and central airways (P <.05). The numbers of lymphocytes remained unchanged. CONCLUSIONS: These results show that HFA-flunisolide effectively suppressed eosinophilic inflammation in peripheral and central airways. These changes were accompanied by improvement in lung function.     

Depletion of neuropeptides during wound healing in rat skin

The peptides substance P, calcitonin gene-related peptide and somatostatin are present in nerve fibres in mammalian, including human, skin. There is evidence that in addition to having a putative neurotransmitter role, they may be trophic agents: a study was therefore undertaken of peptide changes during wound healing in rat skin. A significant depletion of the neuropeptides was found in the region of the wound within two days, and this persisted for two weeks. A smaller and delayed depletion also occurred in intact skin of the same dermatome, but not in an adjacent dermatome.     

Detection of Borrelia burgdorferi, Ehrlichia chaffeensis, and Anaplasma phagocytophilum in ticks (Acari: Ixodidae) from a coastal region of California

A study was conducted in Santa Cruz County to estimate the prevalence and distribution of the agents of Lyme disease, human granulocytic (HGE), and human monocytic (HME) ehrlichiosis in 1,187 adult ixodid ticks collected from eight public-use recreation areas over a 2-yr period. Borrelia burgdorferi, the causative agent of Lyme disease, was detected by a polymerase chain reaction (PCR) in 44 of 776 (5.67%) Ixodes pacificus ticks and in 3 of 58 (5.17%) Dermacentor variabilis ticks. Anaplasma phagocytophilum, the causative agent of HGE, was detected by PCR in 48 (6.19%) I. pacificus ticks and 5 (8.62%) D. variabilis ticks. Ehrlichia chaffeensis, the causative agent of HME, was detected by nested PCR in just five (0.64%) I. pacificus ticks and four (6.9%) D. variabilis ticks. Interestingly, eight (1.03%) I. pacificus ticks were co-infected with B. burgdorferi and A. phagocytophilum, and just one (0.12%) tick was co-infected with B. burgdorferi and E. chaffeensis. Less than 1% of 353 Dermacentor occidentalis ticks showed evidence of infection with any of the agents tested. To our knowledge, this is the first reported identification of A. phagocytophilum and E. chaffeensis in D. occidentalis ticks from California This study represents the first extensive survey of Lyme and the ehrlichial diseases across multiple areas of Santa Cruz County, and suggests that prevalence of B. burgdorferi in Santa Cruz County may be higher than other areas of the state.     

Comparison of electrical field plethysmography with electrical impedance plethysmography

As a means for assessing cardiac function, electrical field plethysmography (EFP) has been shown to have some features quite different from electrical impedance plethysmography (EIP). Here the two techniques are compared by using the two systems simultaneously on a subject and also with independent use in different electrode configurations. The results conform with the view that EIP is related primarily to volumetric changes of the aorta, whereas EFP is affected predominantly by changes in cardiac dimensions and orientation. Because of this difference, the standard time differential formula used for EIP is not applicable for the computation of cardiac output from the EFP waveforms. An alternative method of computation based on the amplitude of the EFP waveform is suggested.     

PCR-Enzyme Immunoassay for Detection of Streptococcus pneumoniae DNA in Cerebrospinal Fluid Samples from Patients With Culture-Negative Meningitis

A PCR-based assay was developed to amplify a conserved region of the pneumococcal autolysin gene. The amplified product was labelled with digoxigenin-labelled dUTP and was detected with a biotin-labelled probe in an enzyme immunoassay (EIA). The assay was initially tested with suspensions of various serotypes of Streptococcus pneumoniae and other gram-positive and gram-negative bacteria and was then applied to cerebrospinal fluid (CSF) specimens from patients with meningitis and those with other neurological disorders. The assay detected all the serotypes of S. pneumoniae tested, whereas all the other bacterial strains tested were negative. Seven of the 8 CSF specimens positive for pneumococcus by culture or latex agglutination (LA) were positive by PCR-EIA, whereas all 10 specimens positive for other organisms were negative. Among 11 patients with clinically diagnosed meningitis but with negative culture and LA results, 5 were positive by PCR-EIA. The assay was negative for all but one patient without meningitis; it was positive with the CSF from a child with immunodeficiency and pneumococcal abscesses on the scalp. PCR-EIA is a useful tool for the diagnosis of meningitis, especially when culture and LA are negative because of prior antibiotic treatment.     

Development of polyclonal ELISA for the N-methylcarbamate insecticide bendiocarb

A polyclonal antibody-based enzyme-linked immunosorbent assay (ELISA) method was developed for the N-methylcarbamate insecticide bendiocarb (2,2-dimethyl-1,3-benzodioxol-4-yl methylcarbamate). Two novel haptens having dimethylbenzodioxyl and dimethylbenzofuranyl groups connected to oxyacetyl-γ-aminobutanoic acid and oxyacetyl-β-alanine spacer arm respectively were synthesised. The first hapten was conjugated to carrier proteins to make antigens that were used to raise polyclonal antibodies in rabbits. The antibodies specifically recognised bendiocarb and its metabolite 2,2-dimethyl-1,3-benzodiox-4-ol with an IC₅₀ value of 9 ppb (ng ml^-1). The assay was standardised using the competitive ELISA format at 0.0625 µg antibody concentration and at 1/10k pesticide-HRP dilution. Matrix effect studies were carried out in four vegetable and cereal food samples. Matrix effect elimination in cabbage, cauliflower and rice was achieved by simple dilution of the extract. Five different approaches were attempted to achieve matrix clean up in paddy rice. C-18 column and gel permeation column chromatography (GPC) helped in the matrix removal. The spike and recovery studies for all the four food samples gave a recovery in the range of 75-95%, thus indicating the efficiency of the matrix elimination procedures developed.     

Mature teratoma arising from the middle cranial fossa

A 25-year-old man presented with a sudden spurt in size of a bony swelling around the external ear, which was present since birth. This was associated with a painful swelling of the right half of the face and pain, redness, and decreased vision in the right eye. Neurologic examination showed decreased visual acuity in the right eye and paresis of the fifth, seventh, and eighth cranial nerves. Neuroimaging showed an extra-axial, partly cystic tumor of mixed density, located entirely within the middle cranial fossa scalloping the temporal bone and extending into the right infratemporal fossa and the right middle ear and impinging on the ipsilateral cavernous sinus. The right temporal lobe was elevated and compressed. Histopathologic examination confirmed a mature teratoma.     

Diagnostic impact of core-needle biopsy on fine-needle aspiration of non-Hodgkin lymphoma

We retrospectively reviewed 74 fine-needle aspiration (FNA) cases of presumptive non-Hodgkin lymphoma (NHL). All the cases had cytology and core-needle biopsy and 53 cases had concurrent flow cytometric analysis. FNA (cytology and flow cytometry) and core-needle biopsy were evaluated independently. FNA was diagnostic of diffuse large B-cell lymphoma (DLBL) in 25% (13/53) of cases and small B-cell NHL in 15% (8/53) of cases, whereas core-needle biopsy was diagnostic of DLBL in 37% (27/74) of cases and small B-cell NHL in 8% (6/74) of cases. Subclassification of small B-cell NHL was reached in 3/6 cases by core-needle biopsy. Insufficient cases were observed in both FNA (47%; 25/53) and core-needle biopsy (28%; 21/74) groups. With the combination of FNA and core-needle biopsy, diagnostic cases of DLBL increased to 43% (32/74) and insufficient samples were reduced to 16% (12/74). There was no clear advantage in the diagnosis and classification of small B-cell NHL by adding core-needle biopsy to FNA (14%; 10/74). We conclude that core-needle biopsy is a useful adjunct to FNA in the diagnosis of DLBL and shall be encouraged. In small B-cell NHL, core-needle biopsy does not add to the diagnostic ability of FNA. Cases insufficient for diagnosis may be seen in both core-needle biopsy and FNA. A combined approach reduces the number of insufficient cases and is recommended in routine FNA practice.     

Nuclear receptor NR2E3 gene mutations distort human retinal laminar architecture and cause an unusual degeneration

Mutations in the nuclear receptor gene, NR2E3, cause a disorder of human retinal photoreceptor development characterized by hyperfunction and excess of the minority S (short wavelength or blue) cone photoreceptor type, but near absence of function of the majority rod receptor. NR2E3 disease can also progress to blindness. How the human retina accommodates mis-specified types and numbers of neurons and advances to retinal degeneration are unknown. We studied the retinal organization in vivo of patients with NR2E3 mutations. Early human NR2E3 disease with S cone hyperfunction showed thickened retinal layers within an otherwise normally structured retina. With visual loss, however, lamination was coarse and there was a strikingly thick and bulging appearance to the retina, localized to an annulus encircling the central fovea. This pattern was not found in other retinal degenerations. The abnormal laminar retinal architecture of early NR2E3 disease may be due in part to larger cells with an S cone phenotype in place of rods that failed to differentiate. The later-stage dysplastic appearance suggests a previously unrecognized proliferative response in human retinal degeneration.