Research guidelines: changes urged.
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Advisory Committees↗
Biomedical subjects
J M Appel
Publications and source records attributed to J M Appel.
Ethics: English high court orders separation of conjoined twins.
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Catholicism↗
[Thromboembolism following cardioversion of atrial flutter].
The risk of thromboembolism following cardioversion of atrial flutter (AFL) is considered low and anticoagulant treatment (ACT) is not recommended. Nevertheless echocardiographic findings in patients with AFL and several case stories in literature suggest that the risk has been underestimated. Two cases of cerebral embolism are described after cardioversion of AFL in patients without concomitant ACT. Until further studies are available the authors recommend that patients with AFL scheduled for cardioversion receive ACT according to the recommendations for atrial fibrillation.
Aged↗
Systemic delivery of human growth hormone or human factor IX in dogs by reintroduced genetically modified autologous bone marrow stromal cells.
Canine bone marrow stromal cells were expanded to numbers in excess of 10(9) cells from the initial 10-20 ml of marrow aspirates and transfected to express high levels of human growth hormone (hGH) in vitro. Ex vivo-modified marrow stromal cells were used in a gene therapy model system for the systemic delivery of transgene products in dogs. Adherent bone marrow stromal cell cultures, established and expanded from iliac crest marrow aspirates from each of 8 dogs, were transfected with a hGH gene plasmid expression vector and shown to express from 0.54-3.84 micrograms/10(6) cells per 24 hr hGH in vitro. The transfected plasmid vector does not possess a eukaryotic origin of replication nor does it possess sequences required for efficient integration into the host cell genome. As such, expression was expected to be transient. Transfected cells were autologously reintroduced into each dog by either infusion into a foreleg vein or directly into iliac crest marrow. In two cases, the stromal cells were cryopreserved following transfection, and subsequently thawed and infused. In one case, the expanded stromal cells were first cryopreserved, and then thawed, recultured, transfected, and infused. Reintroduced cell numbers ranged from 2.2 x 10(7) to 2.6 x 10(9), with total hGH expression capacities ranging from 62 to 1,400 micrograms/24 hr. Plasma of each of the dogs contained detectable hGH for a mean of 3.1 days (SD +/- 0.8 day) ranging from 2 to 5 days following reinfusion of cells. Peak plasma levels ranged from 0.10 to 1.76 ng/ml. Similar hGH expression values, based upon total expression capacity of the cells infused and dog body weight, were obtained for all dogs. Vector-modified stromal cells were detectable, by polymerase chain reaction (PCR) analysis, in the peripheral circulation following reinfusion in all 4 dogs analyzed. In 3 of the dogs, modified stromal cells were detected for 8.5-15 weeks. In addition, modified stromal cells were detected in iliac crest marrow of 2 dogs for 9 and 13 weeks, respectively, following reinfusion. In another experiment, cultured bone marrow stromal cells were transfected with a human factor IX (hFIX) plasmid vector. Modified cells (5.57 x 10(8)), with a total hFIX expression capacity of 281 micrograms/24 hr, were reinfused, resulting in detectable hFIX in plasma continuously for 9 days with a peak level of 8 ng/ml on day 1. These results demonstrate that the ex vivo bone marrow stromal cell system is a potentially powerful method by which to deliver secreted transgene product to the systemic circulation of large animals.
Animals↗
[Torsade de Pointes tachycardia during sotalol treatment of a patient with normal potassium levels].
Proarrhythmia in the form of Torsade de Pointes tachycardia (TdP) is a well-known complication of sotalol treatment. It most often occurs in the setting of sotalol overdosing, renal impairment, bradycardia, hypokalaemia, hypomagnesiaemia or lengthening of the QT-interval due to other drugs. TdP is reported without these predisposing factors. In the described case, TdP might be facilitated by bradycardia and by potassium depletion without concomitant hypokalaemia after diuretic treatment.
Aged↗
[Venous gas embolisms].
The risk of creating a venous gas embolism (VGE) exists, whenever surgery is performed in areas where venous pressures are below atmospheric pressure, or when the pressure of an insufflation gas exceeds venous pressures. Anaesthesia using N2O should be avoided in these situations. The patients should be monitored by systems offering sensitivity and specificity: Doppler, ECHO, ETCO2 and PAP-measurements are the methods providing the highest sensitivities. ETCO2 monitoring is recommendable. In addition, attention should be directed towards common clinical signs: Tachypnoea, tachycardia, systemic hypotension, cardiac arrhythmias and cardiac "mill wheel" murmurs. When a diagnosis of VGE is made, further embolization must be avoided. Let the patient inhale pure oxygen. Attempt to aspirate gas through a central venous line. Put the patient in a combined Durant's and Trendelenburg's position. (During caesarean section however, use the anti-Trendelenburg's position.) Consider hyperbaric oxygen treatment in case of arterial gas embolism.
Anesthetics, Inhalation↗
Enhanced growth of canine bone marrow stromal cell cultures in the presence of acidic fibroblast growth factor and heparin.
The ex vivo establishment, expansion, transduction, and reintroduction of autologous bone marrow stromal cells offers a potential efficacious system for somatic cell gene therapy. It is likely that any ex vivo system will require the use of large numbers of cells which express high levels of transgene products. We present a method for routine expansion of canine bone marrow stromal cells, established from initial 10-20 ml marrow aspirates, to greater than 10(9) cells. This high level expansion of cell cultures uses the stimulatory effect of acidic fibroblast growth factor (aFGF) and heparin. In the absence of these factors, stromal cell cultures grow actively for only 1 to 2 passages, become flattened in morphology, and expand to only 10(8) cells. In the presence of heparin (5 U/ml), aFGF exerts its effect over a wide range of concentrations (0.1-10 ng/ml) in a dose-dependent manner. The stimulatory effect is dependent on the presence of both aFGF and heparin. Immunocytochemical and cytochemical analyses phenotypically characterize these stromal cells as bone marrow stromal myofibroblasts. Stromal cells grown in the presence of aFGF and heparin grow actively and maintain a fibroblast-like morphology for a number of passages, transduce efficiently with a human growth hormone (hGH) expression vector, and express and secrete high levels of hGH. Human marrow stromal cells were also established and expanded by the same culture method. This culture method should be of great value in somatic cell gene therapy for the delivery of secreted gene products to the plasma of large mammals.
Animals↗