Right ventricular growth potential in neonates with pulmonary atresia and intact ventricular septum

The cardiac catheterization data and angiograms of 30 infants with pulmonary atresia and intact ventricular septum were reviewed to evaluate the growth potential of the right ventricle after transventricular pulmonary valvotomy. An index of right ventricular size based upon the tricuspid valve anulus, right ventricular inlet, and right ventricular outlet dimensions was used. Fourteen infants (Group I) were treated with systemic-pulmonary arterial shunts only, whereas 16 infants (Group II) underwent pulmonary valvotomy and 14 had shunting as well. Follow-up studies demonstrated the lack of right ventricular growth in Group I (right ventricular index of 7.0 +/- 3.2 preoperatively versus 7.0 +/- 2.0 postoperatively) and persistence of severe right ventricular hypertension (systolic pressure of 121 +/- 31 versus 120 +/- 48 mm Hg). In contrast, the right ventricular cavity increased in nine of 11 Group II infants who underwent valvotomy. Right ventricular index increased from 7.7 +/- 1.6 to 11.0 +/- 3.1 (p less than 0.01) and systolic pressure fell from 132 +/- 31 to 83 +/- 50 mm Hg (p less than 0.1). Early and late mortality in Group I was 50% (7/14), whereas only three of 16 Group II infants died (p greater than 0.1). It is concluded that pulmonary valvotomy should be attempted in all neonates with pulmonary atresia and intact ventricular septum in whom an outflow tract is identified angiographically to maximize the potential for right ventricular growth and increase its functional contribution to normal circulation.     

Delayed surgery and bone marrow transplantation for widespread neuroblastoma.

From 1983 to 1986, 21 patients with poor prognosis neuroblastoma were treated with bone marrow transplantation. This regimen included induction chemotherapy, delayed surgical resection, local irradiation, and intensive chemoradiotherapy followed by infusion of allogeneic or autologous marrow. This therapeutic approach resulted in a 57% long-term survival rate (follow-up: 14-48 months), which appears to be approximately three times superior to conventional chemotherapy in a comparable group of children. In addition, complete resection was possible in 11 of 17 patients operated on after induction therapy. Recurrence in the primary site after bone marrow transplantation occurred in only one of 18 evaluable patients. Thus, this approach almost always eradicates primary tumor in patients with neuroblastoma with advanced disease.     

The dexamethasone suppression test in bulimia before and after successful treatment with desipramine

Recent reports have suggested that normal-weight bulimic patients without clinical evidence of major depressive disorder will have an abnormal response to dexamethasone. Of 23 normal-weight bulimic patients without clinical evidence of major depressive disorder, 11 had abnormal results on their dexamethasone suppression tests (DSTs). This finding closely matches those of other reports. After successful treatment with desipramine, repeat DSTs showed conversion to normal suppression in 6 of the 7 patients tested. Pretreatment DST results failed to predict the response to medication. The striking similarity of these findings to those reported in patients with major depression suggests that bulimia may be a consequence or an equivalent of major affective disorder.     

Total energy expenditure and body composition in early infancy.

In adults greater energy expenditure, primarily on physical activity, is associated with greater leanness. Such an association has proved more difficult to demonstrate in infants, partly due to the difficulty of measuring fatness and free living energy expenditure in this age group. Stable isotope techniques now make such investigations more viable. OBJECTIVE: The relationship between body composition and energy expenditure was investigated in 12 week infants. METHODS: Total energy expenditure and fat mass were estimated using the doubly labelled water technique. SUBJECTS: 92 normal healthy infants. RESULTS: Fat mass was correlated with both triceps and subscapular skinfold thicknesses (p < 0.001). After controlling for body size, age was a significant predictor of fat mass (p = 0.003), whereas total energy expenditure was not (p = 0.463). CONCLUSIONS: The cross sectional link between activity level and fatness in young infants, reported previously, does not persist when energy expenditure is considered.     

Prion protein immunohistochemical staining in the brains of monkeys with transmissible spongiform encephalopathy

Prion protein (PrP) immunohistochemical staining of the brains of common marmosets (Callithrix jacchus) with experimental transmissible spongiform encephalopathy is described. The monkeys ( n =17) had been injected, intracerebrally, 17–49  months previously with homogenates of brain tissue taken post mortem from a cow with BSE ( n =2 monkeys), a sheep with natural scrapie ( n =2 monkeys), human cases of growth hormone related Creutzfeldt–Jakob disease (CJD) ( n =2 monkeys), sporadic CJD ( n =5 monkeys), or Gerstmann–Sträussler–Scheinker disease (GSS) ( n =4 monkeys), or from monkeys with spongiform encephalopathy resulting from injection with brain tissue from these last two cases ( n =1 monkey from each case). Only diffuse PrP-staining was seen in monkeys injected with CJD-material whereas more aggregated deposits of PrP were seen in monkeys injected with BSE-, scrapie-and GSS-brain tissue. There were no patterns of staining specific to the brains injected with BSE-material that could be used to identify the origin of that inoculum. BSE-and scrapie-injected monkey brains could be distinguished from each other because in BSE-injected monkey brain the spongiform vacuolation was largely confined to subcortical structures whereas in scrapie-injected monkey brain the spongiform vacuolation was also prominent in the neocortex. The patterns of PrP deposition differed markedly between those seen in monkey brains injected with BSE-material or CJD-material, but the patterns of PrP staining seen in monkey brains injected with BSE-material were also seen in monkey brains injected with scrapie-or GSS-material. Overall there was a correlation between the length of the incubation period and the amount of aggregated PrP-staining, but no correlation between the neuropathological picture and the clinical presentation of neurological signs.     

Unilateral injury of posterior parietal cortex and spatial learning in hooded rats

The influences of bilateral or unilateral injuries within the posterior parietal cortex (PPC) upon spatial learning in a water maze were examined in three experiments. Place-learning and response-learning were investigated in a four-alley ‘Greek-cross’ shaped water maze with extra-maze visual cues available. No differences were detected on any of several measures sensitive to learning between the lesion groups on the place-learning task. Microanalysis of behavior within trials revealed that animals with either bilateral or right unilateral PPC injuries committed significantly more total errors, initial alley entrance (‘reference memory’) errors, and re-entry (‘working memory’) errors in the response-learning paradigm than did either the control or left PPC-injured rats. No differences were detected between the latter two groups on these measures. Unilateral lesions resulted in asymmetrical placing responses ipsilateral to the injury 10 days after surgery whereas bilateral injuries resulted in asymmetrical placing with mixed directionality. The acquisition of the response-learning problem in the absence of visual cues was studied on animals prepared with unilateral lesions and housed post-operatively either in isolation or in a ‘complex environment.’ In the absence of visual cues both right and left PPC-injured rats committed more errors than sham controls, and differential post-surgical housing did not attenuate these impairments. These same animals were trained on the landmark navigation task. Although no differences appeared between the lesion groups, a generalized but transient facilitation of learning was observed in animals housed in the ‘complex’ environment. Unilateral injuries placed in sham controls failed to disturb retention of the landmark navigation strategy. Because none of the PPC-injured animals were deficient in the landmark task, a result which is contrary to observations in other laboratories, the influence of post-surgical recovery interval upon acquisition of the landmark navigation strategy was explored. Animals were prepared with right PPC injuries and trained following either a 5 or 35 day recovery interval. Only those animals limited to the short recovery interval proved to have a spatial deficit in the landmark task. It is concluded that injuries in the PPC of either hemisphere disturb egocentric spatial functions. However, animals with left PPC injuries are able to compensate by using allocentric visual cues if they are available. It is due to the special role played by the right PPC in complex visuospatial functions that animals with this injury are unable to compensate.     

Levels of vascular endothelial growth factor are elevated in the vitreous of patients with subretinal neovascularisation.

BACKGROUND: Vascular endothelial growth factor (VEGF) has been shown to play a major role in intraocular neovascularisation in ischaemic retinal diseases. Subretinal neovascularisation is an important cause of central visual loss, but little is known about the role of this growth factor in its pathogenesis. The aim of this study was to investigate the possible role of VEGF in the development of subretinal neovascularisation. METHODS: Undiluted vitreous samples were obtained from patients undergoing vitrectomy for removal of non-age-related subfoveal neovascular membranes (SFNM). For comparison vitreous from patients undergoing vitrectomy for idiopathic full thickness macular holes (FTMH) and proliferative diabetic retinopathy (PDR) was used. Indirect enzyme linked immunosorbent assay (ELISA), with an antibody directed against the conserved N-terminal region of human VEGF165, was used to determine vitreous levels of VEGF. The growth factor was also localised in the vitreous of patients with SFNM by western blot analysis. RESULTS: The mean (SE) VEGF concentration in the vitreous of patients with SFNM was 27.78 (2.22) ng/ml (n = 8), FTMH was 16.62 (0.9) ng/ml (n = 18), and PDR was 37.77 (3.28) ng/ml (n = 16). The differences between the PDR group and SFNM group versus the FTMH group were both significant (p = 0.0001 and p = 0.0015) as analysed by the Wilcoxon rank sum test). CONCLUSIONS: Vitreous levels of VEGF are significantly elevated in eyes with non-age-related subretinal neovascularisation compared with eyes with FTMH but not as elevated as in PDR. This suggests that VEGF is involved in subretinal angiogenesis.     

Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessivedisorder with a high spontaneous mutation rate and no effectivetreatment, hence development of genetic based therapies is animportant goal. We report that expression of a recombinant humanminidystrophin cDNA, compatible with current viral vectors,can significantly reduce the myopathic phenotype in transgenicmdx mice, even when expressed at only 20–30% of endogenousdystrophin levels at the sarcolemma. To the extent that dataobtained in mouse studies are applicable to DMD, the virtualelimination of morphological and biochemical abnormalities inthe mdx mouse supports the use of this cDNA in somatic genetherapy protocols for DMD.