Developmental changes in diaphragm muscle function in the preterm and postnatal lamb.

RATIONALE: The preterm diaphragm is structurally and functionally immature, potentially contributing to an increased risk of respiratory distress and failure. We investigated developmental changes in contractile function and susceptibility to fatigue of the costal diaphragm in the fetal lamb to understand factors contributing to the risk of developing diaphragm dysfunction and respiratory disorders. We hypothesized that the functional capacity of the diaphragm will vary with maturational stage as will its susceptibility to fatigue. METHODS: Lambs were studied at 75, 100, 125, 145, 154, 168, and 200 days postconceptional age (term = 147 days). Lambs were euthanized (sodium pentobarbitone, 100 mg/kg) either at delivery or immediately prior to post-mortem for postnatal lambs. Contractile function was assessed on longitudinal strips of intact muscle fibers and the remaining tissue frozen in liquid nitrogen for analysis of myosin heavy chain (MHC) mRNA expression and protein content. RESULTS: Fetal development of diaphragm function was characterized by a significant increase in maximum specific force, increased susceptibility to fatigue, reduced twitch contraction times, and a progressive increase in MHCI and MHCII protein content. Postnatally, there was a progressive decrease in the susceptibility to fatigue that coincided with an increase in the MHC I:II protein ratio. CONCLUSION: These data indicate that the functional capacity of the diaphragm varies with maturational age and may be an important determinant of the susceptibility to preterm respiratory failure.

Investigations into the role of ST2 in acute asthma in children.

The ST2 gene is a member of the interleukin-1 receptor family and is located on chromosome 2q12, an area of the genome that has been associated with asthma. The soluble product of the ST2 gene, serum ST2 (sST2), has previously been shown to be elevated in adult asthmatic patients. This study investigated the potential role of ST2 in children with acute asthma. Children aged 2-16 years (n = 186) were recruited on presentation with acute asthma in the emergency department. Blood was obtained on presentation and during convalescence. Variables assessed included sST2 levels, a comprehensive assembly of clinical parameters and two polymorphisms in the ST2 gene, -26999G/A, located in the distal promoter region, and ala78glu polymorphism, on exon 3. The A allele of the -26999G/A polymorphism occurred more frequently in asthmatics compared with an unselected control group (P = 0.031). Serum ST2 levels were substantially higher during acute asthma compared with levels after the attack: 0.29 ng/ml (95% confidence interval: 0.23-0.36) and 0.14 ng/ml (0.12-0.17), respectively (P = 0.001) and were inversely related to eosinophil counts during an acute asthma attack (P = 0.002). The -26999AA genotype, as well as the AC haplotype, was associated with asthma severity scores (P = 0.05 and 0.02) compared with the -26999GA and GG genotypes. Serum ST2 levels were not associated with any of the studied genotypes or haplotypes. The observed associations of ST2 genotypes and haplotypes with acute asthma and asthma severity scores as well as the phenotypic differences associated with ST2 polymorphisms suggest that ST2 may play a role in the pathophysiology of asthma.

FGF-2 is bound to perlecan in the pericellular matrix of articular cartilage, where it acts as a chondrocyte mechanotransducer.

OBJECTIVE: We have shown previously that cutting or loading articular cartilage resulted in a fibroblast growth factor-2 (FGF-2) dependent activation of the extracellularly regulated kinase (ERK), and induction of a number of chondrocyte regulatory proteins including tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases 1 and 3. An extracellular matrix-bound pool of FGF-2 was apparent, which could be liberated from the tissue by heparitinase (Vincent et al., Proc Natl Acad Sci U S A 2002;99(12):8259-64, Vincent et al., Arthritis Rheum 2004 Feb;50(2):526-33). Our objectives were to determine where FGF-2 was stored in articular cartilage, to which proteoglycan it was bound, and to elucidate its role in chondrocyte mechanotransduction. METHODS: Immunohistochemistry and confocal microscopy were used to localise FGF-2 in the tissue. In vitro binding studies were performed using IASYS surface plasmon resonance. To study the role of pericellular FGF-2 in mechanotransduction cartilage explants or articular chondrocytes encapsulated in alginate were loaded using an in house loading rig. The loading response was assessed by the activation of ERK, in the presence or absence of a specific FGFR inhibitor. RESULTS: Here we have identified perlecan as the heparan sulphate proteoglycan that sequesters FGF-2 in articular cartilage. Perlecan and FGF-2 co-localised within the type VI collagen-rich pericellular matrix of porcine and human articular cartilage. Chondrocytes encapsulated in alginate were able to accumulate pericellular perlecan and FGF-2 in culture, and deliver an FGF-dependent activation of ERK when loaded. CONCLUSION: Loading-induced ERK activation was dependent upon the presence and concentration of pericellular FGF-2, suggesting a functional role for this matrix-bound growth factor in chondrocyte mechanotransduction.

The management of orbital cysts associated with congenital microphthalmos and anophthalmos.

AIMS: To study the management of the orbital cysts present in a group of patients with anophthalmos and microphthalmos. METHODS: A retrospective study of 34 patients (40 orbits) treated for orbital cyst associated with microphthalmos and anophthalmos. RESULTS: The two largest treatment groups comprised 17 orbits (42.5%) where the cyst was removed surgically and 17 orbits (42.5%) where the cyst was retained and conformers were used. The remaining cases comprised two orbits (5%) where the cyst was aspirated initially; two orbits (5%) with large cysts which will need to be excised after further orbital growth; one orbit (2.5%) in which a silicone expander was used initially, and one orbit (2.5%) in which a mildly microphthalmic eye had some vision and was monitored but required no surgery. CONCLUSION: In this study 33 out of 34 patients had a good cosmetic result which illustrates that the orbital cyst in microphthalmos or anophthalmos performs a useful role in socket expansion and that the majority of patients with this condition can expect a good cosmetic outcome.

Postherpetic lacrimal obstruction.

OBJECTIVE: The purpose of the study was to review the surgical management of postherpetic lacrimal obstruction. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred sixty patients (111 female, 49 male) with a mean age at presentation of 31 years. All had a history typical of primary herpes simplex blepharoconjunctivitis. INTERVENTION: Open lacrimal surgery was performed on 158 patients (171 eyes), of whom 99 patients (108 eyes) had undergone no surgery before being seen at Moorfields. The most common primary procedure was dacryocystorhinostomy (DCR) with anterograde or retrograde intubation (94 eyes, 54%), and primary placement of a Lester Jones tube (conjunctivo-DCR) was performed in 56 eyes (32%). A secondary procedure was required in 43 eyes (26%), the most common being closed placement of a Lester Jones tube (40 eyes). MAIN OUTCOME MEASURES: Persistent symptoms of impaired lacrimal drainage and need for additional surgery. RESULTS: Reduction of epiphora was good or complete in 171/173 eyes (98%). CONCLUSIONS: This study shows that there is a justification for procedures that use any remaining unaffected portion of canaliculi, such as DCR, with anterograde or retrograde intubation, as well as the more commonly used Lester Jones tube.

Rhinostomies: an open and shut case?

AIMS: To analyse bone fragments from rhinostomies of patients undergoing revisional dacryocystorhinostomy, looking for evidence of new bone formation. METHODS: 14 consecutive patients undergoing secondary lacrimal surgery were included in this study. In each case the existing rhinostomy was enlarged with bone punches, care being taken to use the punches with the jaws cutting perpendicularly to the edge of the rhinostomy, to allow accurate orientation of the specimens. The fragments were examined histologically for evidence of new bone formation. RESULTS: Histological sections showed fragments of bone with variable fibrosis at the edge of the rhinostomy. There was evidence of only very little new bone formation. CONCLUSION: This study has clearly shown that, at the edge of a rhinostomy, healing is predominantly by fibrosis and there is only very limited new bone formation.

Ocular superglue injury.

OBJECTIVE: To determine the incidence of ocular injuries associated with superglue. METHODS: A retrospective review of patients attending an accident and emergency department over a 12 month period with ocular superglue injuries. RESULTS: 14 patients who suffered ocular injuries due to superglue were identified. No patients had long term complications from their injury. Management is discussed. CONCLUSIONS: Superglue eye injuries do not appear to cause long term morbidity.

A new tonometer prism stand.

A tonometer prism holder is presented herein that can be quickly constructed from a readily available eyedrops bottle. The advantage of the stand is that only the tip of the tonometer prism is immersed in disinfectant, preventing damage to the proximal end of the prism. Consistent sterilization is ensured by renewing the disinfectant around the tonometer tip from an adjoining reservoir after each use. The stand is also leakproof, and if it is accidentally knocked over, disinfectant will not spill out.

The effect of high altitude on saliva aldosterone and glucocorticoid concentrations.

Saliva was collected from six healthy young men at hourly intervals at sea level and after 1-2, 8-9 and 15-16 days at 4450 m on Mount Kenya for measurement of aldosterone (SA) and glucocorticoid (SGC, cortisol + cortisone) concentrations. Blood samples were collected simultaneously with some of the saliva samples and analysis of these showed that plasma and saliva concentrations of aldosterone and glucocorticoids were highly correlated (r = 0.91 and 0.75 respectively; p less than 0.01 for both hormones). Mean SA for the group was reduced to approximately 50% of the sea-level value (p less than 0.05) by the time the first saliva samples were collected at altitude, and remained at this depressed level throughout the 2-week period on Mount Kenya, although there was considerable inter-subject variation. SGC concentration also tended to be lower on Mount Kenya than at sea level. Though SA was lower throughout the day at altitude compared to sea level, the principal difference in the temporal pattern of SA was the reduction or complete absence of the marked rise in SA that normally occurs in the first few hours after rising. SA and SGC responses to exercise, which consisted of stepping on and off and 0.4-m high stool 60 times/min for 25 min, were assessed at sea level and after various periods at 4450 m.(ABSTRACT TRUNCATED AT 250 WORDS)

Patterns of Care Study. Analysis of outcome survey data-anterior two-thirds of tongue and floor of mouth.

The Patterns of Care Study, begun in 1973, carried out its second outcome survey from December 1978 through April 1979. The review of patients with epidermoid carcinomas of the anterior two-thirds of tongue and floor of mouth included patients treated between January 1973 and June 1975 so that a minimum follow-up period of 2 years was evaluable. Records of 434 patients from 96 facilities were available for analysis, although not every patient could be evaluated for every variable. Almost three-fourths (320) were treated with radiation alone. In these data, four patient and disease characteristics were strongly related to recurrence rates including stage at presentation, deep ulceration, deep infiltration, and age. Treatment variables significantly affecting recurrence included use of interstitial therapy in Stages I and II, use of surgery in Stages III and IV, and a facility's best equipment.