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1.  Effects of a metalloproteinase inhibitor on osteochondral angiogenesis, chondropathy and pain behavior in a rat model of osteoarthritis 
Osteoarthritis and Cartilage  2010;18(4):593-600.
Summary
Objective
To investigate the effects of a matrix metalloproteinase (MMP) inhibitor on joint pathology and pain behavior in the rat meniscal transection (MNX) model of osteoarthritis (OA) and evaluate which aspects of structural disease modification contribute to symptom improvement.
Methods
OA pathology was induced in male Lewis rats, by transecting the medial collateral ligament with (MNX) or without (SHAM) a full thickness cut through the meniscus. MNX animals were orally administered an equipotent MMP 2, 8, 9, 12, 13 inhibitor (0.25, 1 and 5 mg/kg/day) or vehicle from day 1. Chondropathy, osteophytosis, osteochondral vascularity were assessed from toluidine blue stained coronal sections of the total knee joint and weight-bearing asymmetry by incapacitance. Group differences were evaluated using 1-way analysis of variance (ANOVA) and associations as Spearman's correlation coefficients.
Results
Treatment with the MMP inhibitor reduced weight-bearing asymmetry from day 14 onwards, and attenuated chondropathy (both P < 0.05). Osteochondral vascularity was elevated in MNX compared with SHAM-operated animals (P < 0.001) and reduced, dose-dependently, by MMP inhibitor treatment (r = −0.89, P < 0.05). Reduced osteochondral vascularity and chondropathy were associated with the amelioration of weight-bearing asymmetry (both P < 0.05).
Conclusion
Here we show that treatment with a MMP inhibitor reduces joint damage, osteochondral angiogenesis and behavioral evidence of pain. The association between osteochondral angiogenesis and pain behavior may be explained by perivascular nerve growth or stimulation of subchondral nerves following loss of osteochondral integrity. Our data suggest that targeting angiogenesis may have utility in the treatment of pain associated with structural damage in OA.
doi:10.1016/j.joca.2009.12.006
PMCID: PMC2853084  PMID: 20067755
Osteoarthritis; Rat model; Pain behavior; Chondropathy; Osteochondral angiogenesis
2.  Steatocystoma simplex of the caruncle 
PMCID: PMC1771506  PMID: 12543760
steatocystoma simplex; caruncle
3.  Severe interferon associated retinopathy 
PMCID: PMC1771489  PMID: 12543766
interferon; retinopathy
5.  Emergency admission of patients to general surgical beds: attitudes of general practitioners, surgical trainees, and consultants in Liverpool, UK. 
OBJECTIVES: To determine (a) whether doctors involved in the process of emergency surgical admission could agree about which patients should be admitted, (b) whether there were consistent differences between doctors in different specialty groups, and (c) whether these opinions were greatly influenced by non-clinical factors. DESIGN: Independent assessment of summarised case histories by three "expert" clinicians (two consultant surgeons and one general practitioner (GP)), by a group of 10 GPs, and by a group of 10 junior and senior surgeons. Experts, but not other observers, scored admissions both independently and as a consensus group. Observers indicated for each patient whether they would admit, would not admit, or were unsure. SETTING: An urban general hospital with teaching status. SUBJECTS: Fifty consecutive patients admitted to the general surgical unit as emergencies during 1995. MAIN OUTCOME MEASURES: Proportion of admissions considered unnecessary or uncertain: agreement between observers on these proportions: effect of social and procedural factors on the admission decision. RESULTS: Between 8 and 34% of admissions were considered unnecessary and 20-38% of unclear necessity. Agreement between the groups of clinicians was not good. GPs and consultant surgeons showed the poorest agreement (kappa = 0.08 to 0.25, 4 comparisons), and the GPs scored a higher percentage of admissions as unnecessary (34 v 8-12%). After discussion, the consensus group achieved good to very good agreement (kappa 0.61-0.84). CONCLUSIONS: Different groups of doctors vary widely in their views about the need for emergency surgical admission. Good agreement can be reached by consensus discussion. GPs are less likely than surgeons to consider emergency surgical admission necessary.
PMCID: PMC1060479  PMID: 9229063
6.  Objective confirmation of crying durations in infants referred for excessive crying. 
Parents commonly seek clinicians' help for infant crying that they judge to be excessive. To date there is no independent evidence whether such babies actually cry more than average. To assess this, maternal diary and 24 hour audiotape recordings of the crying periods of 16 infants referred for excessive crying were compared with equivalent measures of a normative sample. The overall amounts of crying measured by the two methods were similar. The referred infants cried substantially more over 24 hours and in the afternoon and evening. The difference approached significance in the morning but was insignificant at night time. Some qualifications to the findings are indicated.
PMCID: PMC1029186  PMID: 8435015
7.  Effective pulmonary blood flow in normal children at rest. 
Thorax  1988;43(12):972-977.
Effective pulmonary blood flow was measured with a soluble inert gas uptake method (10% argon, 3.5% freon-22, 35% oxygen, balance nitrogen) in 98 apparently healthy children aged 5-14 years. None had any evidence of cardiorespiratory disease and all had normal values for absolute and dynamic lung volumes and transfer factor for carbon monoxide. Values of blood flow measured by a rebreathing method correlated reasonably closely with height, weight, body surface area, and lung volumes, and to a lesser extent with hand and foot size. The mean (SD) effective pulmonary blood flow index was 2.7 (0.31) 1 min-1 m-2. Small children found a single breath method of measuring flow more difficult to perform and the results were more variable.
PMCID: PMC461603  PMID: 3238641
8.  Capillary haemangioma presenting as a lung pseudocyst. 
Archives of Disease in Childhood  1990;65(10):1162-1164.
A girl who developed a lung cyst at 24 hours of age during gentle ventilation for respiratory distress syndrome is reported. Instead of resolving as expected of a pseudocyst it continued to expand. Resection at 1 year of age showed a cyst entirely surrounded by capillary haemangioma. Aspiration of this cyst would have been dangerous.
Images
PMCID: PMC1792324  PMID: 2248511
9.  Exercise ability after Mustard's operation. 
Archives of Disease in Childhood  1990;65(8):865-870.
Twenty children who were well six to 12 years after undergoing Mustard's operation for transposition of the great arteries were studied. Each child performed a graded maximal treadmill test with measurements of gas exchange and oxygen saturation, and had electrocardiography carried out. Nineteen were also catheterised, and oxygen consumption was measured so that pulmonary and systemic flow could be calculated. Compared with 20 age and size matched controls, seven of the patients had normal exercise tolerance (as judged by a maximal oxygen consumption of greater than 40 ml/kg/min), 10 showed a moderate reduction (30-39 ml/kg/min), and three were more seriously limited. None of the patients with normal exercise tolerance had obstruction of venous return but six of those with mild impairment of exercise ability had partial or complete obstruction of one or both of the vena cavas. More severe limitation was associated with pulmonary vascular disease and fixed ventricular outflow tract obstruction. Formal exercise testing of apparently well children who have undergone Mustard's operation identifies those with haemodynamic abnormalities that may require intervention.
PMCID: PMC1792495  PMID: 2400223
10.  Effect of long term oxygen treatment at home in children with pulmonary vascular disease. 
British Heart Journal  1986;55(4):385-390.
Inhalation of 100% oxygen by nine children with pulmonary vascular disease increased pulmonary blood flow measured at cardiac catheterisation; there was no significant change in pulmonary artery pressure. Fifteen children with pulmonary vascular disease that was severe enough to preclude corrective cardiac operation were studied to determine the effect of long term oxygen treatment on pulmonary vascular disease. Nine received long term domiciliary oxygen for a minimum of twelve hours a day for up to five years. Though the untreated group closely resembled the treated group their survival was significantly less good. All nine treated children are alive whereas five of the six children who did not receive oxygen have died.
PMCID: PMC1236743  PMID: 3964507
11.  Variations in clinical presentation of Fallot's tetralogy in infancy. Angiographic and pathogenetic implications. 
British Heart Journal  1975;37(9):946-955.
Striking variability has been observed in the presenting features in infancy of patients subsequently shown to have tetralogy of Fallot. Some patients presented with severe cyanosis in the neonatal period while others had a systolic murmur and cyanosis only on crying. In these latter patients cyanosis became present at rest over the subsequent months. Yet others presented with episodic attacks of unconsciousness, and a final group presented with dyspnoea and heart failure, accompanying a left-to-right shunt. Angiography demonstrates corresponding variations in the anatomy of the ventricular outflow tracts. In the severely cyanosed patients, the conus septum was deviated so as to obstruct the pulmonary outflow tract, and was best visualized in the lateral projection. In the patients with increasing cyanosis or episodic attacks of unconsciousness, the conus septum again obstructed the pulmonary infundibulum, but was obliquely orientated, not being seen clearly on either lateral or frontal projections. The episodic attacks were considered to be related to infundibular spasm, as previously shown to occur in Fallot's tetralogy. In contrast, increasing cyanosis was believed to be related to hypertrophy of infundibular musculature. In the patients with an initial left-to-right shunt, the arteries were orientated side-by-side so that the conus septum was observed in the frontal projection. Again, subsequent cyanosis was related to ventricular hypertrophy producing outflow tract obstruction. These findings are interpreted in the setting of a recent study, indicating that Fallot's tetralogy is produced by rotation of the embryonic conus together with sinistro-anterior deviation of the conus septum.
Images
PMCID: PMC482902  PMID: 1191455

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