Age-related changes in human RPE cell density and apoptosis proportion in situ

PURPOSE: To determine the effect of age on the proportion of apoptotic cells in the RPE and cellular density in human eyes in situ. METHODS: RPE flatmounts prepared from 22 adult human cadaver eyes (11 pairs; ages 19-87) were stained for apoptotic cells by a TUNEL technique. The density of RPE cells was also measured. The flatmount was divided into four concentric regions centered on the fovea (zone 1, 0-1.5 mm radius; zone 2, 1.5-3.0 mm; zone 3, 3.0-12.5 mm; and zone 4, >12.5 mm). RESULTS: There was a positive correlation between the donor's age and the proportion of apoptotic RPE cells per eye (r = 0.63; P = 0.04), which increased during the sixth decade and was higher in older (age range, 56-87 years) than in younger (age range, 19-48 years) eyes (0.56 +/- 0.14 vs. 0.07 +/- 0.07 cells per 100,000 cells, respectively; P = 0.03). Apoptotic RPE cells were located mainly in zone 1 in older eyes. Cell density decreased in the RPE as the distance from the fovea increased (r = 0.66, P < 0.05). The decrease was most prominent in zone 4 (r = -0.76, P = 0.007). CONCLUSIONS: The proportion of apoptotic human RPE increased significantly with age. Apoptotic RPE cells are confined mainly to the macula of older human eyes. The observation that RPE cell death occurs in the macula but the density of RPE cells remains unchanged in the macula and decreases in the periphery suggests that migration of peripheral RPE cells may compensate for the death of macular RPE cells.     

Frontal cortex atrophy predicts cognitive impairment in multiple sclerosis

The association between regional measures of cortical atrophy and neuropsychological (NP) dysfunction was studied in 35 multiple sclerosis (MS) patients. Patients underwent neurological examination, MRI, and NP testing. Blind quantitative MRI analysis yielded total T(2) lesion area (TLA) and third ventricle width (3VW). Cortical atrophy, rated by blind visual inspection, was more extensive in superior frontal and parietal cortices than in other regions. No MRI measures were correlated with depression scores. TLA and 3VW were significantly correlated with each NP test. Cortical atrophy measures for bilateral superior frontal cortex were retained in regression models predicting impairments in verbal learning, spatial learning, attention, and conceptual reasoning. The authors conclude that cerebral atrophy predicts NP impairment while accounting for the influence of TLA or 3VW. Regions of cortex most susceptible to atrophic and cognitive changes in MS are the right and left superior frontal lobes.     

Practice MRI: Reducing the need for sedation and general anaesthesia in children undergoing MRI

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.     

Whole body protein metabolism in children with cancer

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

Serum profiles of insulin-like growth factors and their binding proteins in adults with growth hormone receptor deficiency treated with insulin like growth factor I

Six adult patients with growth hormone receptor deficiency (GHRD) (2 men, 4 women) with an identical defect in the growth hormone receptor (GHR) gene, were treated with recombinant human insulin-like growth factor I (IGF-I), 40 μgikg S.C. twice daily, for 7 days. Serum concentrations of IGF peptide and IGF binding protein-3 (IGFBP-3) were measured by specific radioimmunoassays; serum IGFBPs were also measured by Western ligand blotting. The size distribution of both IGF-I and IGF-II was measured in serum following size-exclusion fast-performance liquid chromatography. IGF-I treatment resulted in a normalization of serum IGF-I levels on days 1–7 of treatment and a decrease in serum IGF-II levels. The fall in IGF-II levels and the simultaneous rise in IGF-I levels, however, resulted in an unchanged total serum IGF level. The low IGFBP-3 values did not significantly change during treatment, whereas there was a slight increase in IGFBP-2 levels. Preliminary analysis of size-fractionated sera suggested an increase in IGF-I levels in the 40 and 150 kDa regions at the expense of IGF-II levels. The results suggest that despite the failure of IGF-I treatment to increase IGFBPs significantly, serum IGFBP concentrations were sufficient to maintain normal levels of IGF-I. 0 Laron syndrome, growth hormone receptor deficiency, insulin-like growth factors, insulin-like growth factor binding protein     

Protein nutrition, faecal flora and iron metabolism: the role of milk-based formulae

This paper explores the role of milk-based formulae in achieving four aspects of nutritional health in infants and toddlers: in the suckling, to mimic the amino acid metabolism and the faecal flora of a breast-fed baby; in the weanling, to achieve adequate protein intakes in later infancy and beyond and to achieve satisfactory haemoglobin concentrations in the early toddler years. Milk-based formulae have two roles in infant nutrition: as so-called breast milk substitutes and as a safety net during the weaning period; the latter role may be the more important.     

PAROXYSMAL TACHYCARDIA IN INFANCY AND CHILDHOOD I. Paroxysmal Supraventricular Tachycardia

A 1 to 30 year follow-up study of 54 infants and children with paroxysmal supraventricular tachycardia is presented. In 28 cases the first attack occurred in infancy, and in 18 of these already in the first months of life. Nine patients had organic heart disease. The WPW syndrome was diagnosed in 30 cases. When first seen, most of the infants presented signs of incipient or manifest congestive heart failure, which was very unusual in the children, most of whom had only minor symptoms. Four children had experienced brief syncopes during attacks. Digitalis was effective against congestive heart failure and, when continued, may have prevented failure during subsequent attacks. Whether digitalis and other anti-arrhythmic agents facilitated conversion to sinus rhythm could not be established in this study. Vagal stimulation was only rarely effective. Preventive treatment with digitalis or other antiarrhythmic drugs seemed to have little if any effect on the frequency of recurrent attacks. Out of 23 infants who were followed for at least 5 years, 17 had been free from attacks during the last 3 years and 13 of these had had their last attack before the age of 6 months. Out of 23 children followed for 5 years or more, only 3 had been free from recurrences during the last 3 years. Patients with the WPW-syndrome had a somewhat higher incidence of recurrent attacks.     

Postoperative abnormalities of the choriocapillaris in exudative age-related macular degeneration.

AIMS: To study the incidence and possible cause of abnormalities of the subfoveal choriocapillaris after surgical excision of subfoveal choroidal neovascularisation in age-related macular degeneration (ARMD). METHODS: The postoperative fluorescein angiograms and colour photographs of 29 eyes of 29 patients were reviewed after surgical excision of subfoveal choroidal neovascularisation in exudative ARMD. Preoperative and postoperative fluorescein angiograms were examined for perfusion of the subfoveal choriocapillaris. The excised subfoveal choroidal neovascular membranes from eight eyes that demonstrated postoperative abnormalities of the choriocapillaris were embedded in paraffin, serially sectioned and examined for the presence of the choriocapillaris. RESULTS: Postoperative fluorescein angiograms revealed abnormal perfusion of the subfoveal choriocapillaris in 26 of the 29 eyes (90%) and in all eight eyes that had histopathological examination of the surgical specimens. Examination of serial sections demonstrated that none of the excised neovascular membranes contained choriocapillaris. CONCLUSIONS: Abnormal perfusion of the subfoveal choriocapillaris was frequently present following removal of the subfoveal neovascular membrane in ARMD. The histopathological study demonstrated that abnormalities of the choriocapillaris were not due to removal of the choriocapillaris at the time of surgery.