Heparin and in-vitro experimental lung hypoplasia

 Pulmonary hypoplasia (PH) is a leading contributor to the lethality of congenital diaphragmatic hernia (CDH). Studies now suggest that PH arises prior to visceral herniation. Growth factors (GF) are pivotal to this embryonic lung growth. With striking in-vitro effects on lung morphogenesis, GF are under investigation as therapies for PH. Heparin modulates the kinetics of heparan-sulphate binding ligands that drive lung development. We hypothesised that heparin may rescue PH by favourable alteration of endogenous pulmonary GF activity. Normal and hypoplastic lung primordia were microdissected on day 13.5 of gestation and cultured for up to 78 h in plain media with and without heparin. In-vitro morphological development was studied by serial measurements of terminal bud count, lung area, and lung perimeter. Nitrofen-exposed lungs cultured with heparin showed no significant improvements in terminal bud count, lung area, and lung perimeter at 30, 54, and 78 h compared to untreated hypoplastic lungs maintained in vitro. In normal lungs heparin demonstrated no sustained significant morphological effects compared to untreated control lungs. In this study, heparin did not stimulate branching morphogenesis of normal or hypoplastic lungs in our organ culture system. Known at higher concentrations to inhibit smooth-muscle proliferation, heparin may ameliorate pulmonary vascular hypermuscularisation with the prospect of benefiting CDH infants on extracorporeal membrane oxygenation. Future studies will address the impact of exogenous GF on hypoplastic lung development in organ culture.     

Athetoid quadriplegia and literacy

OBJECTIVE: To compare literacy levels in athetoid quadriplegic (AQ) patients born in the 1960s and 1970s with those born in the 1980s and 1990s. METHODOLOGY: Nine patients with AQ born between 1966 and 1972 were compared with eight patients born between 1983 and 1991. RESULTS: Reading difficulties were found in almost all patients with AQ, despite normal intellect. Those in the earlier period were for the most part functionally literate, while those in the later period were functionally illiterate. CONCLUSIONS: Specific and intensive reading education may be required in patients with AQ to obtain functional literacy.     

Partial hepatectomy in the mouse: technique and perioperative management.

Hepatic surgery in mice is challenging because of the delicate nature of the liver, lack of intravenous access, and risk of hemorrhage. In order to study the ability of the liver to regenerate after surgical resection, we developed a novel, rapid, and safe technique for partial hepatectomy in mice. We determined the relative contributions of the seven lobes of the mouse liver and resected the three most anterior lobes for a 68% hepatectomy. We used general anesthesia, a small upper midline incision, silk suture to tie off the lobes to be resected, warming pads and lights, as well as subcutaneous saline injection to ensure minimal morbidity. We have performed a safe two-thirds hepatic resection in 288 of 300 C57BL6 mice (96%). Perioperative mortality was due to technical error. Minimal long-term morbidity was appreciated. This technique may be applied to any type of hepatic resection in mice. In addition, the general operative technique and perioperative management of these mice may be applied to all types of murine intra-abdominal procedures used for surgical research.     

Effect of pretreatment with carbimazole on early outcome following radio-iodine (131I) therapy

Of a group of 55 thyrotoxic patients given therapeutic radio-iodine (¹³¹I), 24 were made euthyroid with carbimazole before¹³¹I: the remainder were given¹³¹I alone. Carbimazole was discontinued 5 days before¹³¹I was administered. By 3 months after¹³¹I treatment there was a greater incidence of hypothyroidism in the group given¹³¹I alone (42% vs 25%), but a lower incidence of persistent thyrotoxicosis (16% vs 46%), (P>0.05). One year after treatment a similar proportion of each group had persistent thyrotoxicosis (21% vs 23%), but there remained a lower incidence of hypothyroidism in the group pretreated with carbimazole (25% vs 45%). It is suggested that pretreatment with carbimazole reduces the degree of radiation induced thyroid damage.     

Serum D-glutamyl transferase following myocardial infarction

D-glutamyl transferase (GMT) activity was measured in 49 patients with proven myocardial infarction. Twenty-three patients had normal GMT activity and 26 had increased GMT activity. Most of the patients with increased GMT had evidence of liver dysfunction and it is suggested that any increases in serum GMT activity following myocardial infarction are a result of secondary liver damage rather than a release of GMT from cardiac tissue.     

A unique method by which to quantitate synchrony with equilibrium radionuclide angiography

Background

Cardiac resynchronization therapy (CRT) improves symptoms and the survival rate in patients with advanced heart failure by improving synchrony. However, CRT is not always successful, is costly, and is applied without individualization. There is no specific measure of synchrony. The goal of this study was to analyze new quantitative parameters of synchrony and compare them with established measures.

Methods and Results

Equilibrium radionuclide angiography, phase angle (Ø), and amplitude quantitate regional contraction timing and magnitude and are the basis for new synchrony (S) and entropy (E) parameters. S is the vector sum of all amplitudes based on the angular distribution of Ø divided by the scalar sum of the length of all vectors. Complete S equals 1, and its absence equals 0. E measures the disorder in the region of interest, is 1 with random contraction and 0 with full synchrony, and differentiates among differing contraction patterns. Left ventricular S and E were measured in 22 normal equilibrium radionuclide angiography studies, where regions of interest were drawn from the left ventricle, left atrium, and background to analyze model ventricles with normal wall motion (N), ventricles with aneurysm (An), ventricles with severe diffuse dysfunction (Diff), and ventricles with severe regional dysfunction (Reg). The new S and E parameters were highly reproducible and well differentiated among N, An, Diff, and Reg, which were not separated by SD Ø (SD of ventricular phase), which has gained popularity as a measure of synchrony.

Conclusion

Unique scintigraphic parameters for the evaluation of ventricular synchrony were derived, and their added value was determine compared with established measures.Indications for pacemaker therapy now include the treatment of severe congestive heart failure (CHF). Atrial triggered biventricular pacemakers reduce CHF symptoms¹ and prolong life² in patients with cardiomyopathy, severe CHF, left ventricular (LV) ejection fraction (EF) lower than 35%, and QRS greater than 120 milliseconds. Such pacing, or cardiac resynchronization therapy (CRT), seeks to reduce the heterogeneity and increase the synchrony of ventricular activation, conduction, and contraction. CRT has improved hemodynamics, increased exercise tolerance, reduced symptoms and the need for hospitalization,^1,32 reversed ventricular remodeling, and^4,5 reduced the all-cause mortality rate² in CHF. However, CRT is costly, fails to improve symptoms or activity level in more than 30% of patients,^2,3,6 and is applied blindly without individualization or consideration of lead placement sight.⁷A variety of echocardiographic methods have sought to measure synchrony and its serial changes with CRT.^4,8-16 A recent study presented evidence of the poor reproducibility of several widely applied echocardiographic measurements by which to determine ventricular synchrony.¹⁷ Magnetic resonance imaging has excellent resolution of regional wall motion and has been applied to assess ventricular synchrony and its response to pacing therapy.¹⁸ However, these methods are complex and are not well established or widely available, and magnetic resonance imaging has not been widely applied after pacing. An accurate and reproducible method is needed by which to objectively measure regional ventricular synchrony.¹⁹Phase image analysis, a functional method based on the first Fourier harmonic fit of the gated blood pool time versus radioactivity curve, generates the parameters of amplitude (A), which parallels the extent of regional ventricular contraction or stroke volume, and phase angle (Ø), which represents the timing of regional contraction. It was applied early with demonstrated reproducibility²⁰ to show the linkage between electrical and mechanical dyssynchrony21 and to characterize the contraction pattern in heart failure and its alteration with CRT.^22,23 The SD of ventricular Ø, applied as a marker of synchrony, has been shown to demonstrate the beneficial effects of biventricular pacing,²⁴ and its strong prognostic value has been shown in patients with congestive cardiomyopathy and CHF, superior to LVEF.²⁵ The SD Ø may not be optimal for synchrony evaluation.We sought improved, more sensitive parameters to better differentiate synchrony among the spectrum of possible patterns of dyssynergy. We derived, initially evaluated, and here present new synchrony (S) and entropy (E) parameters, based on the phase method, to quantitate regional and global ventricular synchrony and applied them in simulation and clinical protocols.