Biomedical subjects
D Hoffman
Publications and source records attributed to D Hoffman.
Use of videocinematography to assess morphological qualities of conventionally cultured and cocultured embryos.
Videocinematography and image analysis procedures were utilized to evaluate the effect of conventional and coculture methodologies on morphological parameters in human embryos derived from in-vitro fertilization (IVF). Following 24-30 h of in-vitro development, cocultured embryos had more acceptable morphological features and less fragmentation present than embryos cultured in medium alone. Cocultured embryos were more advanced at the time of replacement when compared with conventionally cultured embryos. Zona pellucida variation (> or = 20%) also occurred more frequently in cocultured embryos. The morphological characteristic most enhanced after coculture was blastomere expansion. Patients who became pregnant across both culture treatments had a higher proportion of morphologically normal embryos replaced than patients who failed to achieve an ongoing pregnancy. Clinical pregnancy rate for patients following coculture was 49%, which was greater (P < 0.05) than the 29% detected for patients with embryos in the conventional culture group.
Prodrugs of anthracycline antibiotics suited for tumor-specific activation.
The two novel prodrugs 4 and 11 have been prepared from tetra-O-acetyl-D-galactopyranose and doxorubicin in three and six steps, respectively. Their low cytotoxicity, high stability in plasma and, in the case of 11, efficient hydrolysis in the presence of alpha-galactosidase, fulfill preliminary conditions for their use in combination with monoclonal antibody-enzyme conjugates.
The dropped head syndrome with chronic inflammatory demyelinating polyneuropathy.
The dropped head syndrome occurs in a variety of neuromuscular disorders. We present a woman with chronic inflammatory demyelinating polyneuropathy who developed this syndrome, likely reflecting severe demyelination of nerves to cervical paraspinal muscles.
Graduate training in thoracic surgery.
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Surgery for membranous subaortic stenosis. Long-term follow-up.
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Allergen nomenclature. WHO/IUIS Allergen Nomenclature Subcommittee.
This is a revision of the allergen nomenclature system which was proposed in 1986. The nomenclature is for allergens which induce IgE-mediated allergy in humans. A table of allergens with known partial or complete sequences as of December 1993 is given.
Left-to-right ventricular interaction with a noncontracting right ventricle.
UNLABELLED: Left ventricular systole is known to contribute to generation of right ventricular pressure and stroke volume. To study the interactions in a dilated noncontractile right ventricle after cardiopulmonary bypass we created a variable volume, neo-right ventricle by excision and replacement of the right ventricular free wall with a xenograft pericardial patch. We investigated the interactions in eight dogs with neo-right ventricle, instrumented to measure cardiac pressures and cardiac output in control conditions (n = 69) and during partial pulmonary artery occlusion (n = 50). RESULTS: The size of the neo-right ventricle was increased from original right ventricular volume V0 to V1 (V1 = V0 + 54 +/- 23 ml), V2 (V2 = V0 + 124 +/- 85 ml), and V3 (V3 = V0 + 223 +/- 162 ml). Cardiac output increased with increasing left ventricular end-diastolic pressure, indicating that the Frank-Starling mechanism was operating in the left ventricle. However, cardiac output decreased with increasing neo-right ventricular size (p < 0.001) and during pulmonary artery occlusion (p < 0.001). Maximal neo-right ventricular pressure was a linear function of the maximal left ventricular pressure at each neo-right ventricular size and decreased with the increase in neo-right ventricular size (p < 0.001), both in control conditions and during pulmonary artery occlusion (p < 0.004). Stroke work of the neo-right ventricle and left ventricle decreased with increasing neo-right ventricular size (p < 0.002). The relationship between neo-right ventricular stroke work and left ventricular stroke work at different neo-right ventricular sizes was linear both in control conditions and during pulmonary artery occlusion: in control Y = 0.24X (r = 0.968, n = 69); in pulmonary artery occlusion Y = 0.35X (r = 0.986, n = 50). In both conditions the intercept of the linear relationship was not significantly different from zero (p < 0.974 in control; p < 0.614 in pulmonary artery occlusion). The slope was significantly increased in pulmonary artery occlusion (p < 0.001). CONCLUSION: Left ventricular contraction contributes 24% of left ventricular stroke work to the generation of right ventricular stroke work via the septum in the absence of a contracting right ventricle; this increases to 35% in the face of increased pulmonary afterload. This mechanism can maintain adequate global cardiac function in the case of a noncontracting right ventricle while right ventricular volume is kept small and afterload is not increased. The interventricular interaction of the ventricles must be considered when patients with postbypass right ventricular failure are treated.
Transplantation of a polymer-encapsulated cell line genetically engineered to release NGF.
The delivery of nerve growth factor (NGF) to the lateral ventricle of a fimbria-fornix-lesioned rat prevents the lesion-induced reduction in choline acetyltransferase (ChAT) expression by medial septal cells. Although delivery has been achieved through neural grafting of genetically engineered cell lines which release NGF, transplanted cells have grown beyond the implantation site and formed tumors. The encapsulation of cells within a permselective polymer capsule prior to transplantation allows cell growth only within the capsule space, while allowing molecular exchange between the host tissue and enclosed cells. Rat fibroblasts from the parent cell line (R208F) or fibroblasts genetically modified to produce NGF (R208N.8) were loaded within a thermoplastic hollow fiber-based capsule. Only the capsules loaded with the genetically engineered cells released measurable amounts of NGF in culture. Adult rats received unilateral aspirative fimbria-fornix lesions, followed by intraventricular implantation of a R208F capsule (n = 6) or a R208N.8 capsule (n = 6). After 2 weeks, rats receiving encapsulated cells showed no undue reaction to the implants. With both cell types, the cells remained viable and confined to the capsule space. R208N.8 capsules released sufficient NGF to prevent the lesion-induced loss of septal ChAT expression, whereas R208F capsules did not. This study suggests that encapsulated genetically engineered cells can provide an efficient means for future applications involving delivery of neurotrophic factors.
Safety and intracardiac function of a silicone-polyurethane elastomer designed for vascular use.
No ideal prosthetic heart valve exists. While polyurethane copolymers possess excellent physical properties, thrombosis and embolism remain a problem and compounds designed to be less thrombogenic have been prone to biodegradation and failure ('cracking'). We tested a new material which has an elastomeric silicone applied to the polymer surface. A hydrophilic film of protamine and gelatin is covalently bonded to the silicone--this obviates the need for preclotting and should permit endothelial growth. The material was tested by implantation during cardiopulmonary bypass as patches in the mitral valve of six weanling sheep (weanling sheep provide a standard model of accelerated calcification for bioprosthetic heart valves). Prosthetic valves constructed from the material were implanted in an additional four animals, but all of these died within 30 days with heavily calcified valves. Four of the six animals with patches survived and were sacrificed 180 days after surgery when the patches were found to be well healed to native tissue, with collagenous ingrowth and partial endothelial covering. Scanning electron microscopy confirmed good healing, tissue ingrowth and good surface endothelium. The material functioned well as a patch in the mitral valve, allowing tissue ingrowth and endothelial growth on the surface of the patch. The material is not able to resist the strains experienced by a mitral valve prosthesis. Prospects for improved polymers for intravascular applications are good.
Spontaneous host endothelial growth on bioprosthetic valves and its relation to calcification.
We studied host endothelial growth and calcification of bovine pericardial valve prostheses treated with: (A) 0.625% glutaraldehyde + 4% formaldehyde, (B) 99.5% glycerol or (C) 99.5% glycerol + 4% formaldehyde. Twenty-three stentless chordally supported bileaflet pericardial mitral valves with treatments A (n = 6), B (n = 6) or C (n = 11) were implanted in juvenile sheep for 125-273 days. After sacrifice, the anterior cusp from the annulus to papillary muscle of each valve was examined by scanning electron microscopy for the presence of endothelial cells, and the intrinsic calcification of each valve was determined by measuring calcium (micrograms/mg dry weight) from another 1 cm2 piece of grossly normal cusp. Sixty pieces of 1 cm2 pericardium with treatment A, B or C (n = 20 in each group) were implanted in 30 rats for 70 days. Calcium analysis and histology study of the implants were performed. In sheep, within a similar range of implantation periods, the endothelial growth rate of the valves was the highest in group B, 100% (6/6); group C was 45.5% (5/11) and A 16.7% (1/6). There were no significant differences in calcium among groups A, B and C. In rat implants, the calcium of group B was much lower than that of A or C (B = 6.92 +/- 4.46 vs A = 144.52 +/- 27.66 or C = 240.54 +/- 13.47, P < 0.05) although its histology showed more severe degeneration and inflammatory changes. Pericardial mitral valves treated with glycerol show satisfactory biocompatibility with regard to host endothelial growth and prevention of calcification; however, these tissues show evidence of rapid degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)
A cephalometric hard tissue assessment of maxillary and mandibular relationships in complete unilateral cleft lip and palate patients requiring orthognathic surgery.
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Isolated coronary artery bypass grafting in one hundred octogenarian patients.
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Myocardial protection in diffuse coronary artery disease. Intermittent retrograde cold-blood cardioplegia at systemic normothermia versus intermittent antegrade cold-blood cardioplegia at moderate systemic hypothermia.
In order to determine the comparative merits of antegrade cardioplegia at moderate systemic hypothermia versus retrograde cardioplegia at systemic normothermia, we performed coronary artery bypass grafting using intermittent oxygenated blood cardioplegia in 2 sets of 50 consecutive patients with triple-vessel disease (complete occlusion of 1 coronary artery and greater than 90% narrowing of the other 2, with poor distal runoff). Group 1 had antegrade cardioplegia at moderate systemic hypothermia (28 degrees C). Group 2 had retrograde cardioplegia at systemic normothermia. This resulted in no deaths and in no differences in complication rates. Group 2's postoperative need for inotropic agents or vasodilators was significantly less (epinephrine, p < 0.0009; dopamine, p < 0.002; nitroglycerin, p < 0.001). Elevations of CKMB fraction were significantly more common in Group 1: 46% had CKMB levels greater than 9%, versus 16% of Group 2 patients (p < 0.0001). Intraoperative transesophageal echocardiography was performed in 39 Group-1 patients and in 42 Group-2 patients. Development of a new wall-motion abnormality after bypass was significantly only in Group 1 (p < 0.009, by chi 2 analysis). We conclude that retrograde cardioplegia at normothermia provides myocardial protection that equals or surpasses that of antegrade delivery at moderate systemic hypothermia, while avoiding the possible deleterious side effects of hypothermia.
Endothelial covering of biological artificial heart valves.
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Cardiothoracic surgery training.
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Emergency: an urgent problem emergent?
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