Long-term molecular remission in promyelocytic transformation of myeloproliferative disease.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
K M Taylor
Publications and source records attributed to K M Taylor.
Effects of recombinant ovine interferon tau, placental lactogen, and growth hormone on the ovine uterus.
Studies were conducted to determine effects of intrauterine administration of recombinant ovine interferon tau (IFNtau), placental lactogen (PL), and growth hormone (GH) on endometrial function. In the first study, administration of IFNtau to cyclic ewes for one period (Days 11-15) resulted in an interestrous interval (IEI) of approximately 30 days, whereas administration for two periods (Days 11-15 and Days 21-25) extended the IEI to greater than 50 days. Administration of IFNtau from Days 11 to 15 and of PL or GH from Days 21 to 25 failed to extend the IEI more than for IFNtau alone. In the second study, effects of IFNtau, PL, and GH on endometrial differentiation and function were determined in ovariectomized ewes receiving ovarian steroid replacement therapy. Endometrial expression of mRNAs for estrogen receptor (ER), progesterone receptor (PR), and oxytocin receptor (OTR) were not affected by PL or GH treatment; however, uterine milk protein mRNA levels and stratum spongiosum gland density were increased by both PL and GH treatments. Collectively, results indicated that 1) PL and GH do not regulate endometrial PR, ER, and OTR expression or affect corpus luteum life span; 2) down-regulation of epithelial PR expression is requisite for progesterone induction of secretory gene expression in uterine glandular epithelium; 3) effects of PL and GH on endometrial function require IFNtau; and 4) PL and GH regulate endometrial gland proliferation and perhaps differentiated function.
Animals↗
Efficacy, safety and tolerability of anagrelide in the treatment of essential thrombocythaemia.
BACKGROUND: Essential thrombocythaemia (ET) has an associated risk of thrombotic and haemorrhagic complications, which can be minimised by control of the platelet count. Anagrelide selectively lowers the platelet count, however, there is little Australasian experience with its use and scant data on symptom control. AIMS: To evaluate the efficacy of anagrelide for platelet reduction and symptom control in a broad cohort of patients with well-defined ET, and to determine the safety and tolerability in such a population. METHODS: Seventeen patients with ET and a platelet count > 600 x 10(9)/L were prospectively enrolled. The evaluable four males and 12 females with a median age of 58 years (range 14-79) included ten patients (63%) previously treated with two or more agents and 12 patients (75%) who had failed other therapies. The median follow-up was seven months (range 15 days to 36 months). RESULTS: Anagrelide, in an average dose of 1.9 mg/day, reduced the platelet count from a mean of 728 x 10(9)/L (95% CI 611-845 x 10(9)/L) to 412 x 10(9)/L (95% CI 319-504 x 10(9)/L) (p < 0.001) and maintained it at this level. Fourteen patients (88%) had a platelet reduction to < 600 x 10(9)/L. All symptomatic patients had improvement in symptoms attributable to thrombocythaemia. There were three haemorrhagic and three thrombotic episodes in a total of three patients (19%), including one death from an intracerebral haemorrhage. Six patients (37%) were removed from therapy due to toxicity after a median of 151 days. Side effects included palpitations, abdominal pain and cough. CONCLUSIONS: Anagrelide is efficacious and safe in ET, both for platelet and symptom control. Minor side effects are common, however, tend to occur early and resolve spontaneously in most cases.
Adolescent↗
Hypercalcaemia caused by Pneumocystis carinii pneumonia while in leukaemic remission.
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Adult↗
A literature review of cardiopulmonary bypass models for rats.
Cardiopulmonary bypass (CPB) has improved a great deal since its first applications in the early 1950s. If improvements are to be continued, a preclinical model of CPB for small animals is desirable, mainly because of convenience of equipment and low costs. We review the different models of CPB for rats that have been designed, discuss their characteristics and points where improvements may be made. We give suggestions and requirements for a new up-to-date model that could be a useful tool in continued research on the pathophysiology and therapeutic strategies of CPB.
Animals↗
Position-dependent processing of peptides presented on the surface of cowpea mosaic virus.
The plant virus cowpea mosaic virus (CPMV) has been developed as an epitope-presentation system. Numerous epitopes have been expressed in the betaB-betaC loop of the CPMV small coat protein, all of which undergo a cleavage reaction between their two carboxy-terminal residues. Although many peptides presented in this manner give an authentic immune response, this was not the case for the NIm-1A epitope from human rhinovirus-14. Crystallography revealed significant differences between the structure of NIm-1A on CPMV compared with its native configuration. The 3D structure of C PMV expressing NIm-1A was used to design alterations to the context of the NIm-1A graft.
Amino Acid Sequence↗
A phase I/II study of intensive dose escalation of cytarabine in combination with idarubicin and etoposide in induction and consolidation treatment of adult acute myeloid leukemia. Australian Leukaemia Study Group (ALSG).
To determine the safety and efficacy of the combination of idarubicin, cytarabine and etoposide ("ICE") for induction and consolidation treatment of acute myeloid leukemia (AML), and of dose-intensification of cytarabine in this setting, 54 previously untreated patients in three cohorts were studied by sequential dose escalation of cytarabine, in combination with standard doses of idarubicin and etoposide. Cytarabine was given to Cohort 1 at the conventional dosage of 100 mg/m2 per day by continuous infusion for 7 days in induction and 5 days in consolidation; to Cohort 2 at high-dose (HiDAC) (3 g/m2 intravenously twice daily on days 1, 3, 5 and 7) during induction with conventional dosage during consolidation; to Cohort 3 HiDAC was given for both induction and consolidation. In addition, Cohort 3 patients received lenograstim (Granocyte; rHuG-CSF) after both induction and consolidation courses. We found that there was no significant difference between the three cohorts in hematological toxicity in induction, but that HiDAC was associated with a greater incidence of gastro-intestinal toxicities. There was no difference in induction mortality between the three cohorts, which was 11% overall. Consolidation with HiDAC led to a significant increase in hematological toxicity. Overall, the complete remission (CR) rate was 80% with no significant difference between the three regimens. The estimated disease free survival at 3 years was 28%, 67% and 54% respectively for Cohorts 1, 2 and 3 with an estimated overall survival of 38%, 63% and 47%. We conclude that cytarabine dosage can be escalated safely in combination with idarubicin and etoposide in both induction and consolidation. The combination is effective for induction treatment of AML and its side-effects appear similar to those of standard regimens. Whether its use offers long-term benefits compared with standard regimens is the subject of ongoing controlled randomized studies.
Adolescent↗
Oedema, Starling and pulse reverse osmosis: towards a possible biochemical marker for oedema.
Several conflicting theories have been proposed to explain the development of oedema. Pulse reverse osmosis (PRO) suggests that oedema occurs when the mean pulse capillary pressure exceeds the osmotic gradient between the plasma and the interstitial fluid. In order to test this concept mean arterial blood pressures and colloid osmotic pressures were taken in a group of healthy volunteers, a group of patients with bilateral ankle oedema and a group of treated hypertensives. Patients with oedema were found to have colloid osmotic pressures (COP's) which were significantly less than those of the healthy volunteers (p <0.001) and the treated hypertensives (p <0.001). The results support the oedema mechanism proposed by PRO and indicate that the relationship between blood pressure and COP may be a useful biochemical marker of oedema and its treatment. Further study is required to numerically quantify this relationship.
Analysis of Variance↗
A profile of valve replacement surgery in the UK (1986-1997): a study from the UK Heart Valve Registry.
BACKGROUND AND AIM OF THE STUDY: Approximately 150,000 heart valves are implanted annually world-wide, of which 4% are implanted in the UK. We present a comprehensive profile of the trends in valve replacement (VR) surgery in the UK since 1986 based on data from the UK Heart Valve Registry (UKHVR). METHODOLOGY: The UKHVR is a computerized database collecting prospective data on VR surgery in all UK cardiac units. All patients are tracked by national agencies who register all deaths of UK residents. Thus, the Registry receives a copy of each patient's death certificate and enters the date, place and certified cause(s) of death on the database. RESULTS: Between January 1st 1986 and December 31st 1997, a total of 58,195 patients underwent first-time VR surgery and received 63,649 valves. Mean age at operation in 1986 was 58.7 years (range: 18-87 years) and this rose to 64.7 years (range: 18-94 years) in 1997. In 1986, 12% (n = 578) of patients who underwent VR surgery were aged >70 years compared with 36% (n = 5125) in 1997. There was a 4% decrease in double VR surgery and a 15% reduction in mitral VR between 1986 and 1997. The majority of patients received a mechanical valve; within this group the number of bileaflet valve implants increased significantly since 1986. There has been a reversal in the downward trend in pericardial valves implanted since 1993. Follow up was 96.1% complete, with a total of 342,993 patient-years. Mortality (30-day) fell from 6.9% in 1986 to 3.8% in 1995, but increased to 6.7% in the two years to 1997. Actuarial survival at 1, 5 and 10 years was 89.5%, 78.5% and 61.8%, respectively; confidence intervals of 0.5% reflect the enormity of the database and quality of the data. CONCLUSIONS: UKHVR data can provide comprehensive year-by-year and trend analyses in a database in excess of 63,000 valves. Changes in patient demographics, choice of implanted valve and the pattern of heart valve disease are evident within the UK over the past 11 years.
Adolescent↗
Informed consent for clinical trials: is simpler better?
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Educational Status↗
Code for collagen's stability deciphered.
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Circular Dichroism↗
Brain damage during cardiopulmonary bypass.
The development of systems that allow cardiopulmonary bypass have been responsible for the growth of our specialty. In recent years continuing reduction in the mortality associated with cardiac operations has reinforced our confidence in the reliability and safety of perfusion equipment. Cardiac surgeons are aware that the mortality for most cardiac surgical procedures has decreased dramatically and overall morbidity has been reduced significantly. However, it is still clear that cardiopulmonary bypass techniques are not perfect. Indeed, it is fair to say that the period of bypass still contributes to significant morbidity in most patients. In particular, cerebral injury, the focus of this review, is a significant problem for patients and their caregivers and for funding of health-care systems. Incidence rates for stroke are around 2% to 3%, with increased risk in elderly patients and other high-risk groups. This relatively low incidence of what is universally recognized as a serious complication may be contrasted with the much higher reported incidence of cognitive defects assessed by neuropsychologic testing. The incidence of cognitive defects is as high as 60% at 8 days postoperative with reduction to 25% to 30% incidence at 8 weeks and 12 months. There are a variety of ways, at least potentially, in which the brain may be injured during an operation with cardiopulmonary bypass, including reduced cerebral blood flow, microembolism and macroembolism, and a systemic inflammatory response. These mechanisms interrelate and produce synergistic, cumulative effects on brain function during and after the operation. Reducing the incidence and effects of this altered brain function will rely on both preventive and therapeutic strategies. These, in turn, must be based on an understanding of the pathophysiology of these mechanisms of cerebral injury and directed toward ways to optimize cerebral perfusion, minimize embolic vascular occlusion, and develop pharmacologic approaches to modify the systemic inflammatory response.
Cardiac Surgical Procedures↗
Effects of cardiopulmonary bypass on leukocyte and endothelial adhesion molecules.
During the inflammatory response, triggered by cardiopulmonary bypass, interaction between activated leukocytes, platelets, and endothelial cells is mediated through the expression of three main groups of adhesion molecules: the selectins, the integrins, and the immunoglobulin superfamily. The selectins, which mediate the initial rolling of the leukocyte on the endothelium, are divided in three subgroups: L-selectin is expressed on all three leukocyte types, P-selectin is expressed on platelets and endothelial cells, and E-selectin is only expressed on endothelial cells. Integrins can be found on most cell types, consist of an alpha and a beta subunit and mediate firm adhesion of the leukocyte and migration into the tissues. They are classified into subgroups according to the type of their beta subunit. Immunoglobulins such as ICAM-1 and VCAM-1 are expressed mainly on endothelium and act as ligands for certain integrins. This review article summarizes the existing, and rapidly expanding, literature concerning the effects of cardiopulmonary bypass on the expression of leukocyte and endothelial adhesion molecules. Deeper understanding of the, behavior and the role of adhesion molecules during cardiopulmonary bypass may facilitate effective intervention in the inflammatory response process and suppression of its adverse effects.
Animals↗
The platelet in cardiopulmonary bypass.
Platelets are the smallest of the blood cells and are known to be activated during cardiopulmonary bypass. They play a role in many associated complications. Both quantitative and qualitative platelet defects have been demonstrated, resulting in microvascular hemorrhage and thromboembolism. As their interactions with endothelium and other blood cells are unraveled, the important contribution they make toward the systemic inflammatory response to operation seen in cardiopulmonary bypass is increasingly evident. In this review, we consider platelet activation during cardiopulmonary bypass, the resultant clinical effects, and potential approaches to therapy and prevention.
Blood Loss, Surgical↗
Central nervous system effects of cardiopulmonary bypass.
BACKGROUND: The spectrum of approaches to the issue of brain injury in cardiac surgical practice ranges from refusal to acknowledge that the problem exists to an overemphasis on cerebral risks that can unduly frighten patients. An appropriate approach to therapeutic and preventive strategies requires a fitting sense of proportion and an understanding of the mechanisms of cerebral injury. METHODS: This article reviews the incidence and severity of cerebral injury during cardiopulmonary bypass, the identification of high-risk patients, and the mechanisms of injury, including hypoperfusion, microemboli, and inflammatory response. It discusses the influences of alpha-stat and pH-stat strategies on cerebral blood flow during cardiopulmonary bypass; the use of retinal angiography to image the retinal circulation, thus providing a window on the cerebral microcirculation during bypass; magnetic resonance imaging evidence of an inflammatory response in the brain during bypass; and current efforts to gain better understanding of the molecular mechanisms involved in the inflammatory response. RESULTS: The current incidence of stroke during cardiopulmonary bypass is somewhat lower than in the 1980s but still remains a significant problem. Levels of cognitive impairment also are unacceptably high. Recognized predictors enable us to identify patients at particularly high risk of stroke. Hypertensive patients are particularly susceptible to ischemic injury during bypass and should be perfused at mean perfusion pressures higher than those for normotensive patients. Under conditions of hypothermia, a pH-stat strategy causes loss of cerebral blood flow autoregulation, and the cerebral blood flow becomes pressure-passive. With both the pH-stat and alpha-stat strategies, cooling of the patient greatly increases the flow to metabolism ratio of the cerebral blood flow; however, this luxury perfusion brings to the brain not just an excess supply of oxygen but also an increased quantity of microemboli. Current investigative efforts are focused on the endothelial cell-leukocyte adhesion cascade, attempting to characterize beta2 and beta1 adhesion molecule expression in patients undergoing cardiac surgery. Hammersmith Hospital is about to complete a study of the effects of high-dose aprotinin on the inflammatory response pattern and on cerebral infarction. CONCLUSIONS: Further progress in the development of therapeutic and preventive strategies with respect to cerebral injury during cardiac bypass depends on an increase in the understanding of the mechanisms involved. Current strategies should include optimizing cerebral perfusion and minimizing macroembolic and microembolic damage. The possibility of modifying the systemic inflammatory response is the most interesting challenge of the next few years.
Brain↗
Tricuspid valve replacement: UK Heart Valve Registry mid-term results comparing mechanical and biological prostheses.
BACKGROUND: Little is known of time-related outcome and comparative performance of biological and mechanical prostheses following tricuspid valve replacement (TVR). METHODS: A retrospective UK Heart Valve Registry study (Jan 1, 1986 to June 30, 1997) identified 425 patients who underwent TVR. Two-hundred twenty-five (52.9%) received biological and 200 (47.1%) received mechanical valves. One-hundred sixty (38%), 158, and 76 had isolated, double, and triple valve replacements, respectively. The follow-up was 96% complete with a total of 1,585 patient-years. RESULTS: Thirty-day mortality for TVR was 17.3% (73 deaths). One-, 5-, and 10-year survival rates were 72.2%, 59.9%, and 42.9%, respectively. Year of operation (p = 0.04), age (p = 0.04), and number of valves implanted (p = 0.0 3) predicted overall mortality. Age (p<0.001) and year of operation (p = 0.002) predicted overall survival. Thirty-day mortality for biological and mechanical prostheses was 18.8% and 15.6%, respectively. One-, 5-, and 10-year survival rates were 70.5%, 61.5%, and 47.7% for biological and 74.0%, 57.9%, and 33.9% for mechanical prostheses, respectively. Freedom from reoperation at 1 and 10 years was 98.7% and 97.4%. Freedom from death or reoperation was 71.2% at 1 year and 41.9% at 10 years. None of the above outcomes was significantly different between the type of valve prostheses. CONCLUSIONS: TVR carries a high 30-day mortality and a poor longer term survival. No superiority could be identified for biological or mechanical prostheses in the tricuspid position for either survival or reoperation.
Bioprosthesis↗
Cerebral functional changes following cardiac surgery: Neuropsychological and EEG assessment.
OBJECTIVE: Some form of organic and functional cerebral deficit may occur in up to one third of patients following cardiopulmonary bypass surgery. This study was designed to assess cerebral functional deficit in cardiac surgical patients. METHODS: Neuropsychological and quantitative electroencephalographic (EEG) changes were assessed in 62 first time coronary artery bypass graft surgery patients before surgery and within 1 week and 2 months after surgery. Patients underwent surgery with a standard Hammersmith Hospital anaesthesia and hypothermic cardiopulmonary bypass (28 degrees C), using either bubble (Harvey 1700, n = 28) or membrane (Cobe CML, n = 34) oxygenators with arterial line filters (Pall 40 microm). Neuropsychological performance was assessed using a well established battery of ten tests. Four EEG relative power frequency bands; delta (1-3.5 Hz), theta (4-7.5 Hz), alpha (8-11.5 Hz), and beta (12-23 Hz), were determined using Fast Fourier Transformation (FFT). RESULTS: Neuropsychological and EEG deficits were found in 48% of patients 1 week after surgery and in 34% 2 months after surgery. Post-operative deficits were not associated with duration of perfusion, type of oxygenator used in surgery or patient age. Neuropsychological and EEG deficits were associated 2 months after surgery, but not 1 week after surgery. Post-operative EEG deficit was associated with pre-operative deficit. CONCLUSIONS: Cerebral functional deficit was found following CABG surgery using quantitative EEG and neuropsychological assessments. Patients who had neuropsychological deficit were also more likely to show EEG deficit. EEG deficit before and after surgery suggests vulnerability of patients with already compromised cerebral function to the effects of CPB procedure.
Adult↗
Thirty-day mortality and long-term survival following surgery for prosthetic endocarditis: a study from the UK heart valve registry.
OBJECTIVE: To assess the 30-day mortality, long-term survival and freedom from reoperation following surgery for prosthetic endocarditis (PVE). METHOD: A retrospective analysis of data from the UK Heart Valve Registry of 322 patients who had undergone single mechanical/bioprosthetic valve replacement for PVE between 1 January 1986 and 31 December 1996. The mean age was 54.9 +/- 12.8 years and 213 (66.1%) were males. There were 170 aortic and 152 mitral valve implantations. Eighty-five (26%) of the infected valves were bioprosthetic and 237 (74%) were mechanical. Of the new prostheses implanted 53 (17%) were bioprosthetic and 269 (83%) were mechanical. Of those with infected bioprostheses, 50 (15.2%) had mechanical valves at redo surgery, whilst 219 (68.3%) of infected mechanical prostheses were re-replaced by mechanical prostheses. The follow-up was 98% complete with a total of 1084.9 patient years. RESULTS: The 30-day mortality was 63 (19.9%; 95%CI 15.9-24.7%). There were 85 late deaths. One, 5 and 10 year survival rates were 67.1% (61.6-72.0%), 55.0% (49.0-60.7%) and 37.6% (27.9-47.2%), respectively. Age was the only significant determinant of 30-day mortality (P = 0.04). Age (P = 0.001) and explanting of infected bioprosthesis and replacement by mechanical valve (P = 0.04) determined long-term survival (P = 0.001). The incidence of re-reoperation was 9.9%. Freedom from reoperation for PVE was 88.4, 87.3 and 87.3% at 1, 5 and 10 years, respectively. Explanting of bioprosthesis and replacement by mechanical valve (P < 0.001) and reoperation within 60 days of native valve replacement (P = 0.02) were determinants of reoperation for PVE. Freedom from death or reoperation was 61.1, 50.6 and 34.2% at 1, 5 and 10 years, respectively. Age (P = 0.003), explanting of bioprosthesis and replacement by mechanical valve (P = 0.002) and the period between prosthetic re-replacement (P = 0.04) determined freedom from death or reoperation. CONCLUSION: Operation for PVE carries a high 30-day mortality and reduced long-term survival. There is no evidence that type of prosthesis used for re-reoperation determines survival or freedom from re-reoperation.
Bioprosthesis↗