Growth after ventricular septal defect repair: does defect size matter? A 10‐year experience

Aim: To evaluate whether the ventricular septal defect (VSD) size, along with the degree of preoperative growth impairment and age at repair, may influence postoperative growth, and if VSD size can be useful to identify children at risk for preoperative failure to thrive. Methods: Sixty‐eight children submitted to VSD repair in a Brazilian tertiary‐care institution were evaluated. Weight and height measurements were converted to Z‐scores. Ventricular septal defect size was normalized by dividing it by the aortic root diameter (VSD/Ao ratio). Results: Twenty‐six patients (38%) had significantly low weight‐for‐height, 10 patients (15%) had significantly low height‐for‐age and 13 patients (19%) had both conditions at repair. Catch‐up growth occurred in 82% of patients for weight‐for‐age, in 75% of patients for height‐for‐age and in 89% of patients for weight‐for‐height. Weight‐for‐height Z‐scores at surgery were significantly lower in patients who underwent repair before 9 months of age. The VSD/Ao ratio did not associate with any other data. On multivariate analysis, weight‐for‐age Z‐scores and age at surgery were independent predictors of long‐term weight and height respectively. Conclusion: The VSD/Ao ratio was not a good predictor of preoperative failure to thrive. Most patients had preoperative growth impairment and presented catch‐up growth after repair. Preoperative growth status and age at surgery influenced long‐term growth.     

Medicinal therapy for hearing loss resulting from noise exposure

A large-scale review of the literature concerning the effects of noise on hearing, published primarily during the 1970s, was initiated by the National Institute of Neurological and Communicative Disorders and Stroke in 1981. This review demonstrated a continuing search for medicinal treatment for the adverse effects of noise on hearing. The present article focuses on the results of investigations of human subjects. The literature in this area is primarily European and deals principally with treatment of acoustic trauma, although a few reports have described attempts to render the ear less susceptible to the hazards of chronic noise exposure. Much of the published information is of questionable value because of inadequate experimental design and control. To date, the search for effective medicinal treatment for hearing loss caused by noise has been unsuccessful. Results reported from studies of the effects of carbogen are encouraging and suggest that continued rigorous investigation of this agent is warranted.     

Laryngeal aerodynamics associated with selected voice disorders

Measures of estimated subglottal air pressure and laryngeal air flow during speech production are compared for adults with normal laryngeal function and those with laryngeal abnormalities. The most traditional measure, air flow during sustained vowel production, is not a strong predictor of laryngeal function during speech production. Subglottal air pressure and laryngeal air flow offer insight into voice disorders and provide directions for therapy as well as a method for the quantitative assessment of treatment outcomes.     

Radiochemical and biological characteristics of 99mTc-UBI 29-41 for imaging of bacterial infections

A technetium-99m-labeled peptide derived from ubiquicidine, further referred to as 99mTc-UBI 29-41, targets bacterial and fungal infections, but not sterile inflammatory processes, in experimental animals. This paper reports on the radiochemical and biological features of this radioactive agent and the importance of the amino acid sequence of UBI 29-41 for imaging of infections.Radiochemical analyses of 99mTc-UBI 29-41 and a radiolabeled scrambled version of this peptide, i.e. 99mTc-Sc-UBI 29-41, revealed that both peptides were labeled rapidly (within 10 min) and effectively with little colloid formation (less than 5% of the total radioactivity) and very little free pertechnetate (or radioactive intermediates) in the preparations containing radiolabeled peptide. Furthermore, association of the peptides with bacteria could be competed with excess unlabeled peptide and this association proved to be temperature-dependent. Based on this in vitro data we concluded that labeling of peptides with 99mTc by this direct method is rapid, efficient, and safe.Scintigraphy demonstrated that radioactivity is rapidly removed from the circulation (half-lifes of UBI 29-41 and Sc-UBI 29-41 were 16 and 21 min, respectively) mainly by renal clearance. Analysis of murine blood revealed that only a small proportion of the intravenously injected 99mTc-peptides is associated with blood cells. Although both radiolabeled peptides accumulated rapidly at sites of infection, the values for 99mTc-UBI 29-41 were higher (P < 0.05) than for 99mTc-Sc-UBI 29-41. Moreover, injection of excess unlabeled UBI 29-41, but not Sc-UBI 29-41, into Staphylococcus aureus-infected mice prior to injection of 99mTc-UBI 29-41 significantly (P < 0.05) reduced the accumulation of this radiopharmaceutical at the site of infection. In addition, we observed significantly (P < 0.01) higher amounts of 99mTc-UBI 29-41 at the site of infection in mice using a carrier-free radiolabeled UBI 29-41 as compared with unpurified preparations containing radiolabeled UBI 29-41. This in vivo data indicates that the amino acid sequence of 99mTc-UBI 29-41 contributes to its accumulation at the site of infection.     

Technetium-99m labelled antimicrobial peptides discriminate between bacterial infections and sterile inflammations

The aim of this study was to select technetium-99m labelled peptides that can discriminate between bacterial infections and sterile inflammations. For this purpose, we first assessed the binding of various 99mTc-labelled natural or synthetic peptides, which are based on the sequence of the human antimicrobial peptide ubiquicidin (UBI) or human lactoferrin (hLF), to bacteria and to leucocytes in vitro. In order to select peptides that preferentially bind to bacteria over host cells, radiolabelled peptides were injected into mice intraperitoneally infected with Klebsiella pneumoniae (K. pneumoniae) and the amount of radioactivity associated with the bacteria and with the leucocytes was quantitated. The next phase focussed on discrimination between bacterial infections and sterile inflammatory processes using 99mTc-labelled peptides in mice intramuscularly infected with various bacteria (e.g. multi-drug-resistant Staphylococcus aureus) and in animals that had been injected with lipopolysaccharides (LPS) of bacterial origin to create a sterile inflammatory process. Also, we studied the distribution of 99mTc-labelled UBI 29-41 and UBI 18-35 in rabbits having an experimental thigh muscle infection with K. pneumoniae and in rabbits injected with LPS. Based on the results of our in vitro and in vivo binding assays, two peptides, i.e. UBI 29-41 and UBI 18-35, were selected as possible candidates for infection imaging. The radiolabelled peptides can detect infections with both gram-positive and gram-negative bacteria in mice as early as 5-30 min after injection, with a target-to-non-target (T/NT) ratio between 2 and 3; maximum T/NT ratios were seen within 1 h after injection. In rabbits, high T/NT ratios (>5) for 99mTc-labelled UBI 29-41 were observed from 1 h after injection. No accumulation of the selected 99mTc-labelled UBI-derived peptides was observed in thighs of mice and rabbits previously injected with LPS. Scintigraphic investigation into the biodistribution of 99mTc-labelled UBI peptides revealed that these peptides were rapidly removed from the circulation by renal excretion. Similar data were observed for 99mTc-labelled defensin 1-3. Our data for 99mTc-labelled hLF and related peptides indicate that these compounds are less favourable for infection detection. Taken together, 99mTc-labelled UBI 18-35 and UBI 29-41 enable discrimination between bacterial infections and sterile inflammatory processes in both mice and rabbits. Based on their characteristics, we consider these peptides the candidates of preference for detection of bacterial infections in man.     

Prevalence and aetiology of neurological impairment in extremely low birthweight infants

Objective : To determine the prevalence and perinatal predictors of cerebral palsy, intellectual impairment, visual impairment and deafness in a cohort of extremely low birthweight (ELBW) infants at two years of age.
Methodology : The study population comprised 199 of the 224 (89%) ELBW infants managed at the Mater's Mothers Hospital, Brisbane, between July 1977 and February 1990 and who survived to two years. The prevalence of cerebral palsy, intellectual impairment, blindness and deafness was measured by clinical, psychometric and audiological assessment and the association with 24 risk factors examined.
Results : Cerebral palsy occurred in 20 children (10%). Risk of cerebral palsy was associated with ventricular dilatation, intraventricular haemorrhage, necrotizing enterocolitis and multiple birth, though only ventricular dilatation (OR 4.41; 95% Cl 1.32-14.8) remained significant in the adjusted analysis. Intellectual impairment occurred in 20 children (10%) and was independently associated with ventricular dilatation (OR 15.0; 95% Cl 2.2-102.8), ventilation F _iO₂ >80% (OR 3.4; 95% Cl 1.01-11.5), vaginal delivery (OR 3.5; 95% Cl 1.09-11.4) and male sex (OR 6.1; 95% Cl 1.67-22.3). No perinatal predictor was statistically associated with risk of deafness. Retinopathy of prematurity (OR 36.9; 95% Cl 2.8-495.5) was associated with risk of later visual impairment.
Conclusions : Intellectual impairment was associated with a broad range of perinatal variables. Cerebral palsy was associated with fewer variables, all of which were also associated with intellectual impairment. Neurologic injury was associated with male sex and multiple birth, which are not biological insults themselves, but may be markers of susceptibility to injury.     

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.     

Spatiotemporal Effects of Syncytial Heterogeneities on Cardiac Far-Field Excitations During Monophasic and Biphasic Shocks

Far-Field Excitation Via Syncytial Heterogeneities. Introduction: It has recently been postulated that syncytial (anatomic) heterogeneities inherent within cardiac tissue might represent a significant mechanism underlying field-induced polarization of the bulk myocardium. This simulation study examines and characterizes the spatiotemporal excitatory dynamics associated with this newly hypothesized mechanism. Methods and Results: Two-dimensional regions of syncytially heterogeneous cardiac tissue were simulated with active membrane kinetics. Heterogeneities were manifested via random spatial variations of intracellular volume fractions over multiple length scales. Excitation thresholds were determined for uniform rectangular monophasic (M) and symmetric biphasic (B) far-field stimuli, from which strength-duration and strength-interval relationships were constructed. For regions measuring 5.4 × 5.4 mm, baseline diastolic thresholds for longitudinal (L) and transverse (T) shocks of 5-msec total duration averaged (in V/cm, n = 10) M-L = 2.87 ± 0.26. M-T = 6.71 ± 0.83, B-L = 3.22 ± 0.25, and B-T = 7.93 ± 0.51. These thresholds decreased by 15% to 25% when the region sizes were increased to 10.8 × 10.8 mm. Strength-duration relationships correlated strongly with the Weiss-Lapicque hyperbolic relationship, with rheobases and chronaxies of 2.33 V/cm and 1.15 msec for M-L stimuli, and 2.28 V/cm and 2.04 msec for B-L stimuli. Strength-interval relationships for M-I. and B-L stimuli decreased monotonically with increasing coupling intervals, with similar minimum coupling intervals at absolute refractoriness. However, the B-L thresholds were substantially less sensitive to changes in coupling intervals than their M-L counterparts. Conclusion: This study provides strong additional support for and understanding of the syncytial heterogeneity hypothesis and its manifested properties. Furthermore, these results predict that syncytial heterogeneities of even modest proportions could represent a significant mechanism contributing to the far-field excitation process.