The anencephalic fetus and newborn as organ donors.
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Biomedical subjects
Publications and source records attributed to A J Bennett.
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The initial results of trigeminal somatosensory evoked potentials (TSEPs) which were recorded in 17 patients, age range 16-64 years, presenting with established unilateral sensory impairment to the face or oral cavity, are described. Nerve potentials were evoked by stimulation of the normal healthy side and compared with those recorded from the side with disturbed sensation. The recorded waveforms allowed identification of a prominent sequence of events. Significant increases in the latencies compared to the events previously determined in normal subjects at 20, 30 and 39 msec. were found, and considered to be associated with clinical sensory impairment.
Oro-facial sensory impairment is a common event following third molar extractions, osteotomies and maxillo-facial trauma. Trigeminal somatosensory-evoked potentials (TSEPs) may offer an objective means of assessing neuronal function in such cases. TSEPs may be recorded non-invasively in man following peripheral stimulation of the trigeminal nerve, the principal nerve of oro-facial sensation. TSEP recording has gained popularity over the last decade and it is thus timely to review experimental methods and proven clinical applications in the light of recent interest in this technique within oral and maxillo-facial surgery.
Disturbances of oro-facial sensation may frequently complicate dental surgical procedures, including the extraction of impacted third molars and osteotomies, and are often associated with fractures of the facial bones. The development and refinement of an objective measure of this clinical problem is highly desirable, particularly as it is increasingly being raised as a medico-legal issue. Evoked potential techniques have attracted considerable attention as a means of assessing the function and integrity of nervous pathways. An investigation of the trigeminal somatosensory evoked potential (TSEP) has been undertaken, in the hope of providing a safe, simple objective test of oro-facial sensibility that is acceptable to the patient. The 'normal' TSEP response has been standardised in 23 healthy volunteers, and the typical evoked waveform was found to be in line with the findings of other investigators. The TSEP waveform begins with a positive deflection at 20 ms (P20), followed by a negative deflection at 29 ms (N29) and then a second positive deflection at 37 ms (P37). In all cases, standard stimulation and recording procedures were followed. Stimulation of the maxillary or mandibular branches of the trigeminal nerve at the lip or the gingiva was employed. Evoked potentials were recorded at scalp loci overlying the oro-facial representation area of the post-central gyrus. Averaging and display of data was governed by microcomputer. A standardised method for recording trigeminal evoked responses was satisfactorily achieved and it is suggested that the technique may be useful in the clinical assessment of oro-facial sensory loss.
Bivalent metal ions have multiple roles in subunit association and ATPase regulation in scallop adductor-muscle myosin. To help elucidate these functions, the rates of Ca2+ and Mg2+ dissociation from the non-specific high-affinity sites on the regulatory light chains were measured and compared with those of rabbit skeletal-muscle myosin subfragments. Ca2+ dissociation had a rate constant of about 0.7 s-1 in both species, as measured by the time course of the pH change on EDTA addition. Mg2+ dissociation had a rate constant of 0.05 s-1, as monitored by its displacement with the paramagnetic Mn2+ ion. It is concluded that the exchange between Ca2+ and Mg2+ at the non-specific site, on excitation of both skeletal and adductor muscles, is too slow to contribute to the activation itself. The release of bivalent metal ions from the non-specific site is, however, the first step in release of the scallop regulatory light chain (Bennett & Bagshaw (1986) Biochem. J. 233, 179-186). In scallop myosin additional specific sites are present, which can bind Ca2+ rapidly, to effect activation of the ATPase. In the course of this work, Ca2+ dissociation from EGTA was studied as a model system. This gave rates of 1 s-1 and 0.3 s-1 at pH 7.0 and pH 8.0 respectively.
The dissociation of the regulatory light chains from scallop myosin subfragments, on addition of EDTA, was investigated by using the fluorophore 8-anilinonaphthalene-1-sulphonate as a probe. The rate of this process (0.014 s-1) was partially limited by the rate of Mg2+ dissociation (0.058 s-1) from the non-specific high-affinity site. The dissociation of the regulatory light chain subfragment 1 was less extensive than from heavy meromyosin. Reassociation of the scallop regulatory light chain was induced on addition of Mg2+, but it appeared to be limited by a first-order step. The nature of this step was revealed by the kinetics of Mercenaria regulatory light chain association. Scallop heavy meromyosin, denuded of its regulatory light chains, exists in a refractory state, whose reversal to the nascent state limits the rate of light chain association (0.006 s-1). The formation of the refractory state is the driving force for the net dissociation of regulatory light chains from scallop heavy meromyosin. This mechanism is discussed with reference to existing structural information on light-chain-denuded myosin.
Regulatory light chain (RLC) dissociation from scallop myofibrils, myosin or its subfragments was accompanied by an increase in binding of the hydrophobic fluorophore, 8-anilino-1-naphthalene-sulphonate (ANS) to the denuded proteins. The binding was monitored by the large increase in fluorescence emission at 460 nm when excited directly at 380 nm or via energy transfer from nearby tryptophan residues at 295 nm. ANS thus provides a convenient probe for following the kinetics of RLC dissociation in the presence of EDTA and its association in the presence of divalent metal ions. The observed RLC dissociation rate constant for myosin at 20 degrees C was 7.5 X 10(-3)S-1. The association rate constant, which was independent of the RLC concentration, was 5 X 10(-3) S-1. Subfragment 1, prepared by digestion of myosin in the presence of divalent metal ions to protect the light chains [S1(+LC)], showed reversible ANS binding qualitatively similar to the parent molecule. However when prepared in the presence of EDTA, subfragment 1 lacked RLC [S1(-LC)], its heavy chain molecular weight was reduced by about 4000 and it lacked the ANS binding region attributed to the RLC site. The tryptic digestion pattern of of S1(+LC) and S1(-LC) suggested that the 4000 difference peptide is at the C-terminus. Tryptic digestion of S1(+LC) has been shown to lead to the production of a regulatory peptide, comprising the two light chains and a heavy chain fragment, which displayed reversible ANS binding on addition of EDTA. Evidence is presented which suggests that this domain is at the C-terminus of subfragment 1.
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Hemostatic function was studied sequentially in 12 children receiving L-asparaginase, vincristine, and prednisone as remission induction chemotherapy for acute lymphoblastic leukemia. The three-week period of L-asparaginase therapy was characterized by progressive decreases in plasma antithrombin, plasminogen, and fibrinogen concentrations, and by progressive increases in plasma clotting times (prothrombin time, partial thromboplastin time, thrombin time). Platelet counts rose rapidly during the third and fourth weeks of therapy as bone marrow remission was achieved. Factor V levels increased steadily during a five-week period, perhaps related to vincristine or prednisone therapy. Recent reports of thrombosis and hemorrhage in children and adults receiving L-asparaginase may be explained by this complex set of abnormalities in coagulation and coagulation control.
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Eighty-four children presenting with acute lymphoblastic leukaemia were entered into a trial designed to test the effect on host toxicity of regular drug-free periods during chemotherapy. Patients received the same total dose of drugs either continuously (daily), intermittently (a 5 d course every 3 weeks) or in an intermediate way between these two (a 14 d course followed by a 7 d gap). Mean neutrophil counts were lower in the intermittent group and fell significantly at 6 week intervals, after courses which included prednisolone and vincristine in addition to methotrexate and 6-mercaptopurine. Mean lymphocyte counts, mitotic response to phytohaemagglutinin and plasma immunoglobulin levels were significantly lower in the continuous group. The results in the intermediate group fell between those of the other two groups. All six remission deaths occurred in the 42 patients in the continuous group, who had a much higher incidence of infections (mostly viral and protozoal) than the other two groups. It is concluded that the intermittent chemotherapy schedule permits the maintenance of a lymphocyte population size and function which provides a satisfactory level of defence against infection without prejudice to its anti-leukaemic effect.
1 Locally administered commercial hog pancreatic kallikrein (Depot-Glumorin) and bovine pancreatic trypsin both increased vascular permeability in the skin and paws of rats. 2 By the use of numerous antagonists and enzyme inhibitors, this vascular response was found to be the result not of kinin formation but of a direct action mostly on histamine receptors. 3 Highly purified kallikrein did not increase vascular permeability in rats, suggesting either that the effect was due to an impurity in the commercial preparation or that a structural change in the enzyme occurred on purification. 4 Soya bean trypsin inhibitor prevented the trypsin response when both were injected locally. On intraperitoneal injection, the inhibitor was effective only against local kallikrein. 5 The kallikrein inhibitor, aprotinin (Trasylol), was not effective against local kallikrein but it reduced the trypsin response when both were injected locally.
A comparison was made of the activities of clinical dextran and bradykinin in rats. Chiefly by using antagonists, major differences were identified and the study confirmed that bradykinin is unlikely to play a major role in the dextran anaphylactoid reaction.
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Factor V deficiency has been identified in 8 of 8 patients 7--20 yr of age, with Philadelphia-positive (Ph1+) chronic myelogenous leukemia (CML). In these 8 patients, factor V deficiency was not due to hepatic dysfunction, factor V inhibitors, or disseminated intravascular coagulation. In 3 patients, factor V activity rose 10%--12% (0.10--0.12 U/ml) after the infusion of 28--31 ml/kg body weight of fresh frozen plasma (FFP). The rise persisted less than 14 hr. The mean measured postinfusion rise in factor V was 18% of the expected rise calculated from the volume of FFP infused in the patients' plasma volume. In 4 patients, a small transient rise in factor V activity occurred after splenectomy or plateletpheresis. Factor V deficiency was completely corrected after a marked reduction in bone marrow cellularity in 2 patients with Ph1+ CML treated with extensive chemotherapy, total body irradiation, and bone marrow transplantation. Factor V deficiency was retrospectively observed in 6 of 20 patients, ages 20--80 yr, with Ph1+ CML and 3 of 6 patients with other myeloproliferative disorders. The factor V deficiency appears to be associated with the large myeloid-megakaryocytic cell mass characteristic of CML and other myeloproliferative disorders.