Clinical Acumen: Brief Report: Therapeutic Manipulations in Severe Nocturnal Asthma. A Nonconventional Approach in a Severe High-Risk Asthmatic

A patient with severe nocturnal asthma of multifactorial pathogenesis with high-risk features leading to several episodes of nocturnal respiratory arrests is described. Despite aggressive conventional therapy with broncho-dilators and glucocorticoid agents, the patient had progressive worsening within the year prior to admission. After a nonconventional approach consisting of: high-dose inhaled steroids, afternoon dose of prednisone, addition of troleandomycin therapy, high-dose inhaled ipratropium at bedtime, maximizing serum theophylline concentrations in the early morning, and nasal CPAP through the night; the patient's pulmonary functions were optimized with minimal or no reduction in morning FEV₁, and decreased airways hyperresponsiveness to methacholine.     

Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

Disorders of perfusion of the anterior segment of the eye

Background: We have investigated the vascular perfusion of a wide variety of conditions of the anterior segment using fluorescein angiography.
Methods: The conditions were classified and findings reported according to the system set out below. Patients underwent full ocular examination. Fluorescein angiography of the anterior segment was carried out when indicated to investigate iris atrophy and neovascularisation. Specular microscopy of the corneal endothelium was used to detect changes in this tissue.
Results: The hypoperfusion was variable in degree and accompanied by varying degrees of iris hypoplasia and atrophy with neovascularisation. The degree of neovascularisation depended upon its rapidity of development, the pre-existing state of vascular perfusion and the underlying pathological condition.
Conclusions: Hypoperfusion with resultant ischaemia and neovascularisation is common in conditions of the anterior segment. An understanding of the changes is valuable in treating many conditions affecting the anterior segment. The changes observed may also occur elsewhere in the physical system and may be a significant part of the ageing process, either as scattered, disparate processes or as part of a general disease process.     

Postoperative radiation therapy in the management of lung cancer

Postoperative radiation therapy for lung cancer is still controversial. In a 9-year period, 69 patients with non-oat-cell carcinoma of the lung (16% stage I, 26% stage II, and 58% stage III) received such therapy. The radiation dose was less than 5,000 cGy in 42 patients, 5,000-5,900 cGy in 16, and 6,000 cGy or more in 11; follow-up ranged from 24 to 64 months. Actuarial survival at 2 and 4 years was 50% and 16%, respectively, for squamous cell carcinoma, and 40% and 26% for adenocarcinoma. The 5-year survival for stages I, II, and III cancer was 29%, 17%, and 19%, respectively. Histologic findings and type of surgery did not affect survival, but the radiation dose apparently did. The 3-year survival for patients who received less than 6,000 cGy was 35%, compared with 73% for patients who received higher doses. In eight patients, treatment failed within the irradiated volume: all had received doses of less than 6,000 cGy, and the volume in three was judged to be inadequate.     

Antibodies produced in response to Cryptococcus neoformans pulmonary infection in mice have characteristics of nonprotective antibodies

Murine cryptocococcal pulmonary infection elicited serum immunoglobulin M (IgM) and IgG to the capsular polysaccharide, but only IgG stained yeast cells in alveoli. Both isotypes produced punctuate immunofluorescence patterns on yeast cells like those of nonprotective antibodies. The difficulties involved in associating humoral immunity with protection in murine cryptocococcal infection could reflect nonprotective antibody responses.     

Induction of capsule growth in Cryptococcus neoformans by mammalian serum and CO(2)

The pathogenic fungus Cryptococcus neoformans has a polysaccharide capsule that is essential for virulence in vivo. Capsule size is known to increase during animal infection, and this phenomenon was recently associated with virulence. Although various conditions have been implicated in promoting capsule growth, including CO(2) concentration, osmolarity, and phenotypic switching, it is difficult to reproduce the capsule enlargement effect in the laboratory. In this study, we report that serum can induce capsule growth, and we describe the conditions that induce this effect, not only by serum but also by CO(2). Capsule enlargement was dependent on the medium used, and this determined whether the strain responded to serum or CO(2) efficiently. Serum was most effective in inducing capsule growth under nutrient-limited conditions. There was considerable variability between strains in their response to either serum or CO(2), with some strains requiring both stimuli. Sera from several animal sources were each highly efficient in inducing capsule growth. The cyclic AMP (cAMP) pathway and Ras1 were both necessary for serum-induced capsule growth. The lack of induction in the ras1 mutant was not complemented by exogenous cAMP, indicating that these pathways act in parallel. However, both cAMP and Ras1 were dispensable for inducing a partial capsule growth by CO(2), suggesting that multiple pathways participate in this process. The ability of serum to induce capsule growth suggests a mechanism for the capsular enlargement observed during animal infection.     

Emerging Trichosporon asahii in elderly patients: epidemiological and molecular analysis by the DiversiLab system

Trichosporon asahii has been recognized as an emerging opportunistic agent for invasive infections, mainly in immunocompromised patients. Urinary tract infections by this pathogen may also occur, especially in patients with urinary obstruction or those undergoing vesical catheterization and antibiotic treatment. Many outbreaks of Trichosporon spp. have been detected after urinary catheter manipulations. We report the molecular–epidemiological characterization of T. asahii in our institution using the DiversiLab system for the molecular strain typing and compare three different methods for susceptibility testing. Our results present T. asahii as an emergent pathogen in elderly patients with urinary drainage devices that can be adequately treated with triazoles, with voriconazole being the most active. Broth dilution and Vitek 2 had good concordance, while Etest showed more discrepancies. In addition, the DiversiLab system for clonal strain typing may be a useful tool for fast and accurate management of nosocomial outbreaks.