Return to durable donor haematopoiesis after blast phase relapse of chronic myeloid leukaemia following marrow transplantation.
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Adult↗
Biomedical subjects
K S Robinson
Publications and source records attributed to K S Robinson.
A regional autologous bone marrow transplant network: transfers to designated centers on the day after transplant.
Autologous bone marrow transplantation (ABMT) is becoming increasingly prevalent for treatment of advanced malignant disease. In order to increase the availability and utility of this therapy, we assessed the feasibility of transferring patients to their regional referral centers on the day after marrow infusion (day 1), for management post-transplant. This prospective study compares the outcome of 77 patients either transferred the day after marrow transplant for subsequent management at one of six selected Canadian regional centers closest to their domicile, or treated entirely at The Toronto Hospital, according to a common protocol. Study end-points included frequency of complications during transfer, transplant-related morbidity and mortality and hematopoietic recovery. Assessment of eligibility for transplant, bone marrow harvesting, autograft cryopreservation, administration of intensive therapy and marrow infusion were conducted in all cases at The Toronto Hospital. Thirty patients received marrow transplants and were transferred on day 1. There were no complications during transfer. Compared with 47 consecutive patients treated entirely at The Toronto Hospital, there were no differences in treatment-related morbidity or mortality, use of intravenous antifungal therapy or total days of hospitalization. We conclude that day 1 transfer of patients after ABMT to designated centers is feasible and safe. The operation of a regional ABMT network appears to benefit patients, relatives, referring physicians, the transplant center and may also improve health care delivery.
Adolescent↗
Cochlear permeability of neomycin and gentamicin: an immunohistochemical study.
Aminoglycoside antibiotics (AGAs) target specifically the cochleo-vestibular hair cells, but with varied ototoxicity. Differences in their penetration and clearance rates into the membranous labyrinth may play a role. This in turn may be related to a difference in the number of amine groups, the cationic nature, as well as the molecular weight and size of the AGA molecule. Immunohistochemical labeling techniques were used to study the pathways of gentamicin and neomycin from the perilymph into cochlear tissues and target cells. The more cochleotoxic AGA, neomycin, penetrated into cochlear tissues faster than the less cochleotoxic AGA, gentamicin.
Animals↗
Effects on cochlear morphology of repeated insults to the stria vascularis.
The interrelationship of stria vascularis and organ of Corti integrity was investigated. Strial morphology was altered by repeated injections of ethacrynic acid in the chinchilla. Although prolonged temporary strial damage was created, neither strial atrophy nor organ of Corti damage resulted.
Animals↗
Dependence of the bilayer to hexagonal phase transition on amphiphile chain length.
Several series of amphiphiles of increasing chain length were tested for their abilities to modify the L alpha-HII transition of dielaidoylphosphatidylethanolamine using differential scanning calorimetry. Acylcarnitines, alkyl sulfates, alkylsulfobetaines, and phosphatidylcholines, with chain lengths between about 6 and 12 carbon atoms, show an increasing capacity to raise the L alpha-HII phase transition temperature of phosphatidylethanolamine. This is ascribed to increased partitioning of the added amphiphile from water into the membrane as the chain length increases. Alkyl sulfates and alkyltrimethylammonium bromides have diminished capacities to raise the L alpha-HII transition temperature as the chain length is increased from 12 to 16. This is caused by an increase in the hydrophobic portion of the amphiphile leading to a change in the intrinsic radius of curvature and a decrease in the hydrocarbon packing constraints in the HII phase relative to the shorter chain amphiphiles. The L alpha-HII transition temperature of phosphatidylethanolamine with acylcarnitines of chain length 14-20 carbon atoms, alkylsulfobetaines above 14 carbon atoms, and phosphatidylcholines with acyl groups having above 10 carbon atoms is relatively insensitive to chain length. We suggest that this is caused by a balance between increasing hydrocarbon volume promoting the HII phase through decreased intrinsic radius of curvature and greater relief of hydrocarbon packing constraints vs greater intermolecular interactions favoring the more condensed L alpha phase. This latter effect is more important for amphiphiles with large headgroups which can pack more efficiently in the L alpha phase. The phosphatidylcholines show a gradual decrease in bilayer stabilization between 10 and 22 carbon atoms.(ABSTRACT TRUNCATED AT 250 WORDS)
Calorimetry, Differential Scanning↗
Local vs systemic effects of acoustic trauma on cochlear structure and transport.
Whether certain effects of acoustic trauma on cochlear structure and function were due to local or systemic agents was investigated in the chinchilla. After unilateral ossicular disarticulation, the animals were given a noise exposure known to cause cochlear damage and vessel transport changes in the stria vascularis. The cochleas with disarticulated ossicular chains received an effective exposure well below one that causes pathologic damage. Only the cochleas with intact ossicular chains showed an increase in the permeability of the strial vessels to horseradish peroxidase tracer and manifested strial edema and organ of Corti damage. These results indicate that the effects of acoustic trauma on cochlear structure and strial vessel transport are induced locally, not systemically. In addition, the minimum time of exposure to 120-dB, 700- to 2800-Hz noise that causes massive cochlear damage in the chinchilla was shown to be between five and ten minutes.
Animals↗
Effects of prenatal nitrofen exposure on cardiac structure and function in the rat.
The herbicide nitrofen was administered to pregnant Fischer-344 and Sprague-Dawley rats on Days 10-13 of gestation (po, 20 or 40 mg/kg daily) and its effects on cardiac structure and function were investigated in the offspring. In the 21-day fetuses, nitrofen did not influence intrauterine growth or basal heart rate. In contrast, the herbicide produced a marked depression of heart rate and abnormal electrocardiographic (ECG) profiles in the newborn rats, in conjunction with labored respiratory movements and a profound increase in postnatal mortality. A few animals displayed cardiac ventricular septal defects and diaphragmatic hernias but these malformations did not appear to be associated with the ECG changes. The chronotropic deficiencies seen in the nitrofen-treated pups were reversible by acute hyperoxia (40% oxygen). These results suggest that the teratogenic effects of nitrofen on cardiac physiology and on postnatal mortality cannot be accounted for solely by specific gross anatomical damages to the rat heart and diaphragm; rather, other more subtle morphological and physiological factors which contribute to improper systemic delivery and cellular utilization of oxygen may be involved.
Animals↗
A computer-assisted electrocardiographic analysis system: methodology and potential application to cardiovascular toxicology.
An automated analysis of electrocardiographic (ECG) waveforms, based on a precise one-dimensional analysis of features within a generalized computer-enhanced ECG waveform, has been developed in our laboratory. ECG signals are monitored, amplified, and recorded using standard techniques. The recorder output signal is distributed to a microcomputer system. Software developed for the microcomputer slows the signal playback rate and permits operator review of the slowed signal for arrhythmia analysis. The analysis program identifies and superimposes 10-40 individual ECG complexes, depending on the heart rate, and generates an "ensembled" waveform. Operator interaction permits delineation of specific points on the displayed waveform and calculation of heart rate and duration of components within the ECG complex. The primary advantages of this system include (1) extensive automation--computer support decreases analytical time, increases precision, and permits rapid screening of large numbers of animals; (2) enhanced sensitivity--the use of functional parameters should provide a more sensitive index of toxicity than morphological parameters; (3) broad utility--this system provides the capability to utilize a variety of animals, both anesthetized and unanesthetized, ranging in age from fetuses to geriatrics, and permits studies of block as well as longitudinal design; and (4) ease of replication--standardization of equipment and techniques facilitates replication by other laboratories.
Animals↗
Electrocardiographic responses of rat fetuses with clamped or intact umbilical cords to acute maternal uterine ischemia.
Uterine ischemia results in severe cardiac disturbances in the fetus. It has been postulated that these effects are due to interaction between the fetus and the ischemic uterus or placenta, and not to hypoxia or buildup of metabolites in the fetus. Rat fetal cardiac responses to uterine clamping and umbilical cord clamping were compared by electrocardiography. On day 21 of gestation, fetuses in a total of 14 pregnant rats were exposed to umbilical clamping, uterine clamping, or no clamping. Electrocardiograms were recorded for each fetus immediately after clamping and at 10, 20, and 30 minutes after clamping. Immediately after clamping, the uterine clamping group alone showed severe sinus bradycardia. At all other observation times, fetuses exposed to uterine or umbilical clamping showed bradycardia and other electrocardiographic changes typically associated with hypoxia. Therefore, umbilical clamping protected the fetuses from the adverse effects of uterine clamping for only a very short time.
Animals↗
Electrocardiographic studies of developing rodents exposed in utero to trypan blue.
Techniques, based on computer-assisted analyses of ensembled ECG waveforms, have been developed in this laboratory to serve as a screening procedure for potentially cardiotoxic substances. This procedure was tested on fetal and neonatal rats exposed in utero to two levels of trypan blue, a known cardiovascular teratogen. The offspring of the treated animals exhibited decreased viability, as well as significant levels of both cardiac and noncardiac malformations. Qualitative assessment of ECG irregularities demonstrated an increased number of abnormalities in the treated groups. Correlations were also obtained between observed morphological defects and ECG irregularities in the trypan blue treated groups.
Abnormalities, Drug-Induced↗
Multigeneration study of 1,2,4-trichlorobenzene in rats.
Rats were continuously exposed to 0, 25, 100, or 400 ppm 1,2,4-trichlorobenzene (TCB) in the drinking water, beginning with birth of the F0 generation and continuing through weaning of the F2 generation. The treatment did not affect fertility, growth, viability, locomotor activity, or blood chemical analysis. Adrenal gland enlargement was observed in both the F0 and F1 animals at 95 d of age. To further examine the adrenal enlargement found in the reproduction study, an acute toxicity study was undertaken in which immature females were given ip injections of 0, 250, or 500 mg/kg TCB on 3 consecutive days. It was found that TCB had no estrogenic activity and that the livers and adrenals of treated females were significantly larger than those of controls. Rather than being estrogenic, TCB in this treatment regimen resulted in a decrease in uterine weight. These two studies demonstrate that chronic or acute doses of TCB can produce adrenal enlargement in rats.
Adrenal Glands↗
Effect of topical hyaluronic acid on experimental cholesteatoma.
PURPOSE: Inflammation and connective tissue hyperplasia are believed to be important etiological factors in cholesteatoma pathogenesis. Previous work has shown that topically applied hyaluronic acid can reduce connective tissue proliferation in healing wounds and accelerate healing of tympanic membrane perforations. This study was undertaken to determine whether the antiproliferative effect of hyaluronic acid may inhibit propylene glycol-induced cholesteatoma in an animal model. MATERIALS AND METHODS: A 60% propylene glycol solution was injected bilaterally into the middle ear cavities of 20 adult chinchillas. The control group (N = 10) received propylene glycol alone. In addition to propylene glycol injections, the experimental group (N = 10) received repeated bilateral topical applications of 1.5% hyaluronic acid onto the tympanic membranes. Animals were killed at 4 weeks for gross and light microscopic examination. RESULTS: Seven control and 10 experimental animals survived the full 1-month study period. At the end of that time, cholesteatoma was found in 71% (10/14) of control ears and 70% (14/20) of experimental ears. Tympanic membrane structure did not differ significantly between groups by light microscopy and, in all animals, cholesteatomas originated by migration of hyperplastic epidermis through the tympanic membrane, as has been observed in previous studies using this animal model. CONCLUSION: Under the conditions of this study, topical hyaluronic acid had no significant effect on cholesteatoma formation.
Administration, Topical↗
Value of assessment of pretest probability of deep-vein thrombosis in clinical management.
BACKGROUND: When ultrasonography is used to investigate deep-vein thrombosis, serial testing is recommended for those who test negative initially. Serial testing is inconvenient for patients and costly. We aimed to assess whether the calculation of pretest probability of deep-vein thrombosis, with a simple clinical model, could be used to improve the management of patients who present with suspected deep-vein thrombosis. METHODS: Consecutive outpatients with suspected deep-vein thrombosis had their pretest probability calculated with a clinical model. They then underwent compression ultrasound imaging of proximal veins of the legs. Patients at low pretest probability underwent a single ultrasound test. A negative ultrasound excluded the diagnosis of deep-vein thrombosis whereas a positive ultrasound was confirmed by venography. Patients at moderate pretest probability with a positive ultrasound were treated for deep-vein thrombosis whereas patients with an initial negative ultrasound underwent a single follow-up ultrasound 1 week later. Patients at high pretest probability with a positive ultrasound were treated whereas those with negative ultrasound underwent venography. All patients were followed up for 3 months for thromboembolic complications. FINDINGS: 95 (16.0%) of all 593 patients had deep-vein thrombosis; 3%, 17%, and 75% of the patients with low, moderate, and high pretest probability, respectively, had deep-vein thrombosis. Ten of 329 patients with low pretest probability had the diagnosis confirmed, nine at initial testing and one at follow-up. 32 of 193 patients with moderate pretest probability had deep-vein thrombosis, three diagnosed by the serial (1 week) test, and two during follow-up. 53 of 71 patients with high pretest probability had deep-vein thrombosis (49 by the initial ultrasound and four by venography). Only three (0.6%) of all 501 (95% CI 0.1-1.8) patients diagnosed as not having deep-vein thrombosis had events during the 3-month follow-up. Overall only 33 (5.6%) of 593 patients required venography and serial testing was limited to 166 (28%) of 593 patients. INTERPRETATION: Management of patients with suspected deep-vein thrombosis based on clinical probability and ultrasound of the proximal deep veins is safe and feasible. Our strategy reduced the need for serial ultrasound testing and reduced the rate of false-negative or false-positive ultrasound studies.
Algorithms↗
Cochlear vessel permeability to horseradish peroxidase after diuretic administration in the chinchilla.
The permeability of strial vessels to the small protein, HRP, was examined after administration of diuretics to determine if increased vascular permeability is a factor in the development of strial edema as it is in acoustic trauma. Chinchillas were injected with HRP and either ethacrynic acid, a loop-inhibiting diuretic, or mannitol, an osmotic diuretic. There was no increased vascular permeability to HRP. Therefore, unlike the increased vessel permeability of HRP seen after an acoustic insult, increased vessel permeability of HRP is not a factor in the formation of strial edema after either mannitol or ethacrynic acid administration.
Animals↗