Biomedical subjects

A Marble

Publications and source records attributed to A Marble.

At least 19 recordsLinked to original sources

PubMed2000

Requirement of Bmp8b for the generation of primordial germ cells in the mouse.

In the mouse embryo, the generation of primordial germ cells (PGCs) from the epiblast requires a bone morphogenetic protein-4 (BMP4) signal from the adjacent extraembryonic ectoderm. In this study, we report that Bmp8b, a member of the Gbb-60A class of the BMP superfamily, is expressed in the extraembryonic ectoderm in pregastrula and gastrula stage mouse embryos and is required for PGC generation. A mutation in Bmp8b on a mixed genetic background results in the absence of PGCs in 43% null mutant embryos and severe reduction in PGC number in the remainder. The heterozygotes are unaffected. On a largely C57BL/6 background, Bmp8b null mutants completely lack PGCs, and Bmp8b heterozygotes have a reduced number of PGCs. In addition, Bmp8b homozygous null embryos on both genetic backgrounds have a short allantois, and this organ is missing in some more severe mutants. Since Bmp4 heterozygote embryos have reduced numbers of PGCs, we used a genetic approach to generate double-mutant embryos to study interactions of Bmp8b and Bmp4. Embryos that are double heterozygotes for the Bmp8b and Bmp4 mutations have similar defects in PGC number as Bmp4 heterozygotes, indicating that the effects of the two BMPs are not additive. These findings suggest that BMP4 and BMP8B function as heterodimers and homodimers in PGC specification in the mouse.

Animals↗

PubMed2000

Assessment of change in dynamic psychotherapy.

Five scales have been developed to assess changes that are consistent with the therapeutic rationales and procedures of dynamic psychotherapy. Seven raters evaluated 50 patients before and 36 patients again after brief dynamic psychotherapy. A factor analysis indicated that the scales represent a dimension that is discriminable from general symptoms. A summary measure, Dynamic Capacity, was rated with acceptable reliability by a single rater. However, average scores of three raters were needed for good reliability of change ratings. The scales seem to be sufficiently fine-grained to capture statistically and clinically significant changes during brief dynamic psychotherapy.

Adult↗

PubMed1994

Influence of systemic hypothermia on systolic and diastolic functional recovery after continuous warm antegrade blood cardioplegia.

Experimental observations in our laboratory indicate that myocardial recovery is similar following warm or cold antegrade blood cardioplegia when the core temperature is maintained at 37 degrees C. To determine the effects of hypothermia on myocardial recovery, 15 adult mongrel dogs were randomized to normothermic or hypothermic bypass (28 degrees C) during 60 min of continuous warm antegrade blood cardioplegia. The hypothermic group was rewarmed after releasing the aortic cross-clamp and bypass was discontinued at 30 min in both groups. Myocardial recovery was assessed at 60, 90, and 120 min after the arrest. Core temperature was maintained in the normothermic group but gradually decreased after bypass in the hypothermic group, reaching a low of 33.8 +/- 1 degrees C at 120 min. Myocardial functional recovery was preserved after normothermic bypass. The decrease in core temperature, however, that was observed after systemic hypothermia, was paralleled by significant decreases in the maximum rate of left ventricular pressure rise (dp/dt), the maximum elastance of the left ventricle, and preload recruitable stroke work. Diastolic function decreased slightly, but not significantly, during reperfusion following systemic hypothermia but was unaltered after normothermic bypass. Myocardial oxygen consumption was unchanged in both groups. Myocardial ultrastructure was preserved after normothermic bypass. In contrast, cellular oedema and mild ultrastructural changes were evident after systemic hypothermia. We therefore conclude that the use of systemic hypothermia during bypass is associated with lower core temperatures during early recovery which results in impaired functional recovery.

Animals↗

PubMed1992

Morphometric analysis on myocardial injury related to the use of high volume potassium cardioplegic solution during ischemic arrest.

We correlated the effects of high volumes of K+ cardioplegic solution on myocardial structure and function in 16 dogs following open-heart surgery. Eight animals received high volume potassium cardioplegic solution (25 cc/kg body weight, every 30 min) during 90 min of ischemic arrest (HVK-C group). The others received sufficient cardioplegic solution to maintain complete electrical arrest as defined by voltage monitoring criteria (VM group). Cardiac index (CI), left ventricular stroke work index (LVSWI), and myocardial contractility (dp/dt) were determined before arrest and after 90 min of ischemia and 45 min of reperfusion. Biopsies were taken for EM ultrastructure and ATP estimation. Morphometric analysis of EM micrographs found increased volume of damaged mitochondria (DMR) (p less than 0.025), damaged myofibrils (DMF) (p less than 0.001), intermyofibrilar edema (p less than 0.005), T-tubule and sarcoplasmic reticulum (p less than 0.05) in the HVK-C group. Left ventricular (LV) function was more depressed in animals receiving HVK-C. CI decreased by 1.8 +/- 0.4 l/min/square meter (p less than 0.01), LVSWS fell by 3.3 +/- 0.8 gm-m/beat/Kg (p less than 0.01), dp/dt decreased by 684 +/- 135 (p less than 0.0025). ATP decreased by 26% in HVK-C and by 12% in VM group (0.1 less than p less than 0.05). Structural damage (scores of injured volume of mitochondria and myofibrils) correlated with post-ischemic depression of LV function (Cardiac output and myocardial contractility), r = -0.72 and -0.66 (p less than 0.001 and 0.004).

Adenosine Triphosphate↗

PubMed1989

In vivo biostability of four types of arterial grafts with impervious walls; their haemodynamic and pathological characteristics.

We describe the haemodynamic and pathological characteristics of four types of four impervious arterial prostheses, two alloplastic (Mitrathane and Gore-Tex), and two chemically processed bovine heterografts (Solcograft and Solco P). They were implanted in the thoracic aortae of dogs for durations of 24 hours, 48 hours, one week, two weeks, one month, three months and six months. Haemodynamic analyses showed no relation between the shear rate index, I.gamma, and compliance, CD. The observed shear rates are 6.5 times lower than those likely to damage the endothelial cell layer. Macroscopic and microscopic observations of explanted grafts showed the presence of obstructive thrombi at the anastomoses of Mitrathane grafts as early as one week. Gore-Tex grafts develop in the area of anastomoses parietal-thrombi which reorganize and become covered with pseudo-endothelial cells. The bovine heterografts show a similar behaviour. However, whereas Solcograft has an irregular thin wall, Solco P had improved characteristics except in the graft implanted for three months which demonstrated, some manufacturing weaknesses. Both types showed the development of anastomotic pannus covered with endothelial-like cells. All grafts, whether alloplastic or chemically processed, suffered from an absence of healing of the middle part of the prosthesis. The cause of this problem will be found in the analysis of the biochemical and enzymatic reactations between the material used and its physiological surrounding.

Anastomosis, Surgical↗

PubMed1984

Effects of oral amiodarone on left ventricular function in dogs: clinical implications for patients with life-threatening ventricular tachycardia.

Twenty-four mongrel dogs were divided into two equal groups to determine the effects of orally administered amiodarone on left ventricular function. Measurements of left ventricular function included left ventricular contractility as denoted by maximum rate of rise of left ventricular pressure (dP/dtmax), cardiac index (CI), left ventricular stroke work index (LVSWI), and peripheral vascular resistance (PVR). Left ventricular function was measured in 6 of the 12 animals in Group 1 before and after 14 days of amiodarone administered orally; the remaining animals served as controls. The dP/dtmax was reduced from 2,855 to 1,291 mm Hg/sec (p less than 0.01), and LVSWI fell from 1.6 to 0.74 gm-m/beat/kg (p less than 0.05) in the 6 animals given amiodarone. The 12 animals in Group 2 underwent 30 minutes of ischemic arrest. Six animals in Group 2 underwent 30 minutes of ischemic arrest. Six animals were given amiodarone orally for 14 days prior to cardiopulmonary bypass and ischemic arrest; the other 6 served as controls. Before cardiopulmonary bypass, the dogs administered amiodarone had significantly greater depression of dP/dtmax (p less than 0.01) and LVSWI (p less than 0.05). Thirty minutes of ischemia produced significant depression of left ventricular function in all animals in Group 2. However, a significantly greater reduction in dP/dtmax and LVSWI occurred in those animals receiving amiodarone. Furthermore, 4 of the 6 dogs receiving amiodarone were unable to sustain sufficient cardiac output following cardiopulmonary bypass to permit long-term survival (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1984

Oral hypoglycaemic agents. An update.

Despite the availability of oral hypoglycaemic agents for nearly 30 years, their precise mode of action and role in the management of diabetes mellitus remains poorly defined and controversial. They are regarded by many, though not all, clinicians as helpful adjuncts in the treatment of patients with non-insulin-dependent diabetes who have failed to respond satisfactorily to an adequate programme of dietary treatment. Their initial effectiveness is greatest in those patients who have had diabetes for less than 5 years, are overweight at the time of initiation of therapy, and whose fasting blood glucose levels are not unduly raised (less than 200 mg/dl). If they are receiving treatment with insulin and a shift to oral compounds is contemplated, success in the changeover is more likely if the daily dose has been less than 20 to 30 units daily. While their efficacy in maintaining adequate glycaemic control over the short term in responsive patients is unquestioned, the long term benefit of oral hypoglycaemic agents in reducing morbidity and mortality of late complications remains to be substantiated. In this regard, where long term efficacy is difficult to quantify, physician vigilance for chronic toxicity assumes a special importance. Notwithstanding the potential for interaction between sulphonylureas and numerous other drugs, significant adverse effects are uncommon. Hypoglycaemia is the major health concern associated with the use of sulphonylureas, and lactic acidosis has been the major problem with biguanides. Careful patient selection is thus the key to ensuring efficacy and avoiding toxicity. Recent evidence suggests that while the insulinotropic action of the sulphonylureas may explain the short term hypoglycaemic effect of these compounds, their reported action in enhancing insulin sensitivity, both at the receptor and post-receptor levels, more likely accounts for the long term maintenance of improved carbohydrate tolerance. The relatively new ('second generation') sulphonylurea compounds have not been shown to possess clearly defined advantages over the older preparations; the potentially beneficial effects of gliclazide on the microangiopathic changes of diabetes require considerable further evaluation.

Animals↗

PubMed1983

Should oral amiodarone be used for sustained ventricular tachycardia in patients requiring open-heart surgery?

A patient with sustained ventricular tachycardia was operated on after an unsuccessful trial of amiodarone. Profound myocardial depression and low cardiac output became evident as he was weaned from cardiopulmonary bypass. Despite inotropic support, use of the intra-aortic balloon pump and left heart assist device, he died. Because of this experience, the authors developed a canine model to determine the effects on left ventricular function of amiodarone given orally. Left ventricular stroke work, cardiac output, ventricular contractility (maximum dP/dt) and peripheral vascular resistance were measured in 12 mongrel dogs at a heart rate of 150 beats/min and at a constant preload of 10 mm Hg. Six animals received the drug orally and the remaining animals were used as sham-operated controls. Maximum dP/dt decreased from 2855 mm Hg/s to 1291 mm Hg/s (p less than 0.01) and left ventricular stroke work was reduced from 48.7 g-m/beat to 21.8 g-m/beat (p less than 0.05) after the administration of amiodarone. Cardiac output and peripheral vascular resistance did not differ significantly. Amiodarone severely depressed left ventricular function in this experiment. The prolonged half-life of this antiarrhythmic combined with its adverse effect on myocardial function suggests that it should not be used in patients with refractory life-threatening ventricular tachycardia who are good candidates for electrophysiologic evaluation and endocardial resection.

Amiodarone↗

PubMed1981