Breakdown of the round window membrane permeability barrier evoked by streptolysin O: possible etiologic role in development of sensorineural hearing loss in acute otitis media.

Sensorineural hearing loss is a common sequela of acute and chronic otitis media, and the round window membrane (RWM) is currently being considered as a major route for noxious agents to pass from the middle ear cavity to the cochlea. Streptococcus pneumoniae, a major causative agent of otitis media, and Streptococcus pyogenes A produce molecularly related toxins, pneumolysin and streptolysin O (SLO), that form large pores in target membranes. In this study, we analyzed the effects of SLO on the permeability of the RWM. Resected RWMs from a total of 104 guinea pigs were embedded between two chambers of an in vitro system. One chamber was designated as the tympanal (cis) compartment, and the other was designated as the inner ear (trans) compartment. The permeability of normal and SLO-damaged RWMs towards Na+, [14C]mannitol, and proteins was investigated. SLO evoked permeability defects dose dependently in the RWM with fluxes of both Na+ and [14C]mannitol being demonstrable over a time span of up to 8 h. Serum proteins and radioiodinated SLO were also shown to pass through the damage RWM. Scanning electron microscopy revealed the morphological correlates to these results. We propose that damage to the RWM by potent pore-forming cytolysins leads to leakage of ions from the perilymph. Ionic disequilibrium and passage of noxious macromolecules to the cochlea could contribute to disturbances of the inner ear function.     

Antibiotic-resistant infections in primary care are symptomatic for longer and increase workload: outcomes for patients with E.coli UTIs

BACKGROUND: Antimicrobial resistance is considered to be one of the major threats to public health. However, the practical implications for patients and workload in primary care are largely unknown. AIM: To determine outcomes for patients managed in primary care with an antibiotic resistant compared to an antibiotic sensitive Escherichia coli (E. coli) urinary tract infection (UTI). DESIGN: Nested case control study with prospective measurement of outcomes. SETTING: Ten general practices in South Wales. METHOD: Patients consulting with symptoms suggestive of UTI identified through systematic sampling, and with a laboratory proven E. coli infection, were followed up by interview 1 month after their consultations and by searching of their medical records. RESULTS: Nine hundred and thirty-two patients were interviewed and had their medical records reviewed. The risk of patients reporting 'feeling poorly', 'frequency or pain on urinating' and being 'out of action' for more than 5 days after consulting was significantly increased for patients with resistant compared to sensitive infections. After adjusting for risk factors, there was an increased risk of 'frequency or pain on urinating' and 'being out of action' for those infected with a resistant E. coli. The median number of maximum reported days with at least one symptom was 12 days for patients with E. coli infections resistant to trimethoprim, 7 days for infections resistant to ampicillin, 7 days for infections resistant to any antibiotic, and 5 days for infections sensitive to all tested antibiotics. Even if treated with an appropriate antibiotic, infections caused by a resistant strain were symptomatic for longer. For those infected with an organism resistant to at least one antibiotic, the odds ratio (OR) for re-visiting their GP within the next 30 days for the UTI was 1.47 (95% confidence interval [CI] = 1.10 to 1.95). The OR was 1.49 (95% CI = 1.11 to 2.00) for ampicillin resistance and 2.48 (95% CI = 1.70 to 3.59) for trimethoprim resistance. CONCLUSIONS: Resistant E. coli UTIs are symptomatic for longer and cause increased work load in general practice.     

A system for measuring total body calcium in man using the 40Ca(n, alpha)37 Ar reaction.

A technique to measure total body calcium using the 40Ca(n, alpha)37 Ar reaction has been developed. The technique is based on collecting 37Ar exhaled in the breath following a 10 mrad uniform total body irradiation by 14 MeV neutrons. The 37Ar in the exhaled breath is extracted by selective absorption and its radioactivity is measured inside a low-background proportional detector. The facilities developed include an activation facility providing a +/-2.7% activation uniformity, a closed circuit rebreathing and gas collection system, and a gas purification and counting system. The technique provides a precision of +/-2.4% as determined by repetitive measurements of human volunteers and has an accuracy for determination of total body calcium in grams of +/-5%.     

The vascular territories (angiosomes) of the body: experimental study and clinical applications

The blood supply to the skin and underlying tissues was investigated by ink injection studies, dissection, perforator mapping and radiographic analysis of fresh cadavers and isolated limbs. The results were correlated with previous regional studies done in this department. The blood supply is shown to be a continuous three-dimensional network of vessels not only in the skin but in all tissue layers. The anatomical territory of a source artery in the skin and deep tissues was found to correspond in most cases, giving rise to the angiosome concept. Arteries follow closely the connective tissue framework of the body. The primary supply to the skin is by direct cutaneous arteries which vary in calibre, length and density in different regions. This primary supply is reinforced by numerous small indirect vessels, which are "spent" terminal branches of arteries supplying the deep tissues. An average of 374 major perforators was plotted in each subject, revealing that there are still many more potential skin flaps. Our arterial roadmap of the body provides the basis for the logical planning of incisions and flaps. The angiosomes defined the tissues available for composite transfer.     

Autoimmunity to insulin, beta cell dysfunction, and development of insulin-dependent diabetes mellitus

Circulating insulin autoantibodies (INSAAb) were measured in discordant monozygotic twins, first-degree relatives, and other groups at "high risk" for the development of insulin-dependent diabetes mellitus (IDDM), and these results correlated with both islet cell antibody (ICAb) status and beta cell function. INSAAb were positive in 31.6% (12 of 38) ICAb-positive subjects but in only 3.1% (3 of 97) ICAb-negative subjects (X2 = 22.4; P less than 0.001). Elevated levels of INSAAb tended to correlate with younger age and were observed in individuals irrespective of the prevailing degree of their beta cell function. Eight of 15 subjects detected to be INSAAb positive have thus far progressed to clinical IDDM (X2 = 18.3; P less than 0.001). Thus, autoantibodies reactive with the insulin molecule (1) appear to constitute an additional serologic marker of ongoing autoimmunity and development of IDDM, and (2) may reflect heterogeneity in the pathogenesis of IDDM.