Sex differences in spontaneous respiratory recovery following chronic C2 hemisection.

Respiratory deficits after C2 hemisection (C2Hx) have been well documented through single-sex investigations. Although ovarian sex hormones enable enhanced respiratory recovery observed in females 2 wk post-C2Hx, it remains unknown if sex impacts spontaneous respiratory recovery at chronic time points. We conducted a longitudinal study to provide a comprehensive sex-based characterization of respiratory neuromuscular recovery for 8 wk after C2Hx. We recorded ventilation and chronic diaphragm electromyography (EMG) output in awake, behaving animals, phrenic motor output in anesthetized animals, and performed diaphragm muscle histology in chronically injured male and female rodents. Our results show that females expressed a greater recovery of tidal volume and minute ventilation compared with males during subacute and chronic time points. Eupneic diaphragm EMG amplitude during wakefulness and phrenic motor amplitude are similar between sexes at all time points after injury. Our data also suggest that females have a greater reduction in ipsilateral diaphragm EMG amplitude during spontaneous deep breaths (e.g., sighs) compared with males. Finally, we show evidence for atrophy and remodeling of the fast, fatigable fibers ipsilateral to injury in females, but not in males. To our knowledge, the data presented here represent the first study to report sex-dependent differences in spontaneous respiratory recovery and diaphragm muscle morphology following chronic C2Hx. These data highlight the need to study both sexes to inform evidence-based therapeutic interventions in respiratory recovery after spinal cord injury (SCI).NEW & NOTEWORTHY In response to chronic C2 hemisection, female rodents display increased tidal volume during eupneic breathing compared with males. Females show a greater reduction in diaphragm electromyography (EMG) amplitude during spontaneous deep breaths (e.g., sighs) and atrophy and remodeling of fast, fatigable diaphragm fibers. Given that most rehabilitative interventions occur in the subacute to chronic stages of injury, these results highlight the importance of considering sex when developing and evaluating therapeutics after spinal cord injury.

Twelve-year analysis of microbial keratitis trends at a UK tertiary hospital.

PurposeTo investigate the frequencies, trends, and in vitro drug susceptibilities of the causative pathogens in microbial keratitis in Manchester Royal Eye Hospital.Patients and methodsCorneal scrape results recorded by the microbiology service between 2004 and 2015 were extracted from an established database. A total of 4229 corneal scrape specimens were identified from an established database. First-line antibiotic treatment in our centre during the study period was ofloxacin and second line was cefuroxime and gentamicin.ResultsMean age was 45.9±21.0. A total of 1379 samples (32.6%) were culture positive. One hundred forty-eight (10.7%) specimens cultured multiple organisms. Of the 1539 organisms identified, 63.3% were Gram-positive bacteria, 27.3% Gram-negative bacteria, 7.1% fungi, and 2.3% Acanthamoebae. A decreasing trend in Gram-positive isolates was found together with a stable trend in Gram negatives and an increasing trend in Acanthamoeba and fungi. There appeared to be a significant increasing trend of Moraxella infection (P=0.001). In all, 83.1 and 90.8% of Gram-positive and -negative isolates tested were susceptible to ofloxacin, respectively. Cefuroxime covered 86.6% of Gram-positive and 61.4% of Gram-negative isolates, whereas gentamicin covered 88.8 and 96.5% of Gram-positive and -negative isolates, respectively.ConclusionWe found a change in the type of Gram-negative organisms isolated over time, with the Moraxella species on the rise. Reassuringly, no significant increase in resistance was observed in vitro for any of the commonly used antibiotics. Ofloxacin remains a good first-line antibiotic treatment but duo-therapy does have broader coverage and should be considered in non-responsive cases.

An in depth analysis of histopathological characteristics found in keratoconus.

AIMS: The aims of this study were to re-assess the histopathology of the disease by introducing more modern measuring techniques and to determine if axial stromal thinning, which is the most apparent change, is related to the other alterations observed. METHODS: Recipient keratoconic corneas from 36 patients following corneal transplantation were studied. Haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were used to identify breaks in Bowman's layer and Descemet's membrane. Thickness of corneal layers was measured by Leica QWin software. Epithelial and stromal thickness were measured in each sample at the periphery of the corneal button and at the area of maximal stromal thinning. The presence of apoptotic cells in Bowman's layer breaks was detected by terminal deoxynucleotidyl transferase mediated dUTP-X nick end labelling. RESULTS: In all 36 corneal samples the central stroma, at the apex of the cone, was thinner than the peripheral. There was a negative correlation between central stromal and central epithelial thickness (p = 0.009). Bowman's layer breaks were found in 92% of corneas. Apoptotic cells were detected at the level of Bowman's breaks membrane. We found a positive correlation between epithelial thickness and the number of Bowman's layer breaks (p = 0.009 for central epithelial thickness and p = 0.003 for peripheral epithelial thickness). Descemet's membrane deformities were observed in 19% of corneas and central stromal thickness of these corneas was significantly less than corneas without breaks (p = 0.006). CONCLUSIONS: There are various different histopathological features associated with keratoconus and some of them are very subtle and not very well studied. Accurate measurements also suggest some correlations between them. Stromal thinning is associated with the number of breaks in Descemet's membrane, but it is the thickening of the epithelium which is associated with breaks in Bowman's layer.

The influence of donor and recipient factors in allograft rejection of the human cornea.

UNLABELLED: The health of the corneal endothelium is essential in maintaining the clarity of the transplanted human cornea. Immune-mediated endothelial rejection is a complex series of events, which may culminate in the decompensation of the donor button. It is the commonest instigator of failure in penetrating corneal transplantation. METHODS: This retrospective case note review of 203 penetrating keratoplasties with adequate follow-up data during a 5-year study period from 1 January 2000 to 31 December 2003 at Manchester Royal Eye Hospital, were used for analysis. RESULTS: Forty-three of the 203 donor grafts underwent at least one single episode of immune-mediated endothelial rejection, an incidence of 21% over a 5-year follow-up. Recipient's age was inversely associated with the risk of rejection. The average age for the cohort of 58.7 years and average age for rejecting patients of 47.6 years were strongly significantly different (P=0.009). Rejection in keratoconic patients accounted for 30% of cases. Death to enucleation time (P=0.03) was also associated with an increased risk of rejection. CONCLUSION: Although penetrating keratoplasty is an effective long-term treatment option for improving visual function, the endothelial rejection rate in our study was 21% over a mean follow-up of over 5 years. Host vascularisation, regrafts, younger recipient age group, and donor factors were found to be significantly associated with a risk of rejection. Rejection in keratoconic recipients was more common than expected.

Penetrating keratoplasty: indications, outcomes, and complications.

PURPOSE: Corneal transplantation is the most common form of transplantation with approximately 2500 grafts undertaken annually in the United Kingdom. The modern day success of transplantation is attributed to eye bank storage techniques, ocular pharmacology, and improved surgical techniques. METHODS: This retrospective case note review identified 203 penetrating keratoplasties (PKs) performed during a period from 1 January 2000 to 31 December 2003 at Manchester Royal Eye Hospital. Preoperative risk factors, surgical technique, postoperative complications, and Snellen acuity were analysed. RESULTS: The mean age of the recipient group was 56.7 years, with 107 right eyes and 96 left eyes. The mean follow-up was 61 months. The overall 5-year survival was 82%, with keratoconus and corneal dystrophies at 93 and 89%, respectively. Visual acuity had improved to 6/12 or better in 48% of patients postoperatively, compared with 8% preoperatively. Forty-three donor grafts (21%) underwent at least a single episode of endothelial rejection. Glaucoma was a finding in 37 (18%) of patients following PK. In all, 16 grafts of 15 patients were noted to have suffered microbial keratitis (MK), an incidence of 8%. CONCLUSIONS: PK is currently an effective long-term treatment option for improving visual function. An overall survival rate of 82% over 5 years is comparable with other published studies and is largely dependent on recipient factors. This report emphasises the significant complications of immunological rejection, glaucoma, and microbial keratitis, which continue to limit success.