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Biomedical subjects

J Morton

Publications and source records attributed to J Morton.

At least 37 records · Page 2Linked to original sources

Cytotoxic drug contamination on the outside of vials delivered to a hospital pharmacy.

We recently carried out a study of two UK hospital pharmacy units preparing cytotoxic drugs using isolators that showed low level contamination on floor surfaces and disposable gloves worn by staff. It has been suggested that this level of contamination may be related to some level of contamination on the drug vials as delivered from manufacturers rather than leakage from the isolators. We have investigated the level of cytotoxic drug contamination on the external surfaces of the drug vials as delivered to a hospital pharmacy stores. We monitored 30, randomly chosen vials for the drugs cisplatin, carboplatin, cyclophosphamide, ifosfamide and methotrexate using well-established methods. A 0.5 m2 floor area directly in front of the shelves used for storing the cytotoxic drugs was also wipe sampled and the disposable gloves worn while wiping the vials for each drug were also analysed. A significant number of vials had a quantifiable level of external contamination. Levels of contamination up to 344 ng/vial were found. Levels of glove and floor contamination for some drugs were found to be comparable with values found in our study of the clean rooms where the isolators were situated and the pharmacy staff prepared the cytotoxic drugs.

Antineoplastic Agents↗

A locus for asphyxiating thoracic dystrophy, ATD, maps to chromosome 15q13.

Asphyxiating thoracic dystrophy (ATD), or Jeune syndrome, is a multisystem autosomal recessive disorder associated with a characteristic skeletal dysplasia and variable renal, hepatic, pancreatic, and retinal abnormalities. We have performed a genome wide linkage search using autozygosity mapping in a cohort of four consanguineous families with ATD, three of which originate from Pakistan, and one from southern Italy. In these families, as well as in a fifth consanguineous family from France, we localised a novel ATD locus (ATD) to chromosome 15q13, with a maximum cumulative two point lod score at D15S1031 (Zmax=3.77 at theta=0.00). Five consanguineous families shared a 1.2 cM region of homozygosity between D15S165 and D15S1010. Investigation of a further four European kindreds, with no known parental consanguinity, showed evidence of marker homozygosity across a similar interval. Families with both mild and severe forms of ATD mapped to 15q13, but mutation analysis of two candidate genes, GREMLIN and FORMIN, did not show pathogenic mutations.

Asphyxia↗

Parallel replacement of the oxygenator that is not transferring oxygen: the PRONTO procedure.

We present here a technique to replace a failed oxygenator by inserting a second oxygenator in parallel (PRONTO) within the cardiopulmonary bypass (CPB) circuit. Oxygenator failure is a potential hazard that may result in patient injury or death. Although failures are rare, safety surveys conducted over the last 25 years suggest that the incidence of oxygenator failures is on the rise. This emergency procedure may be easily applied to any standard CPB circuit with a few minor alterations. The technique is simple; it can be carried out rapidly. An important advantage of this technique is that it may be executed without interrupting blood flow to the patient, which may reduce the incidence of patient injury or death.

Cardiopulmonary Bypass↗

Sulfur and chlorine play a non-acid base role in periparturient calcium homeostasis.

The increased risk of periparturient hypocalcaemia through offering high-K feeds in the precalving period has been reported previously. Two experiments (experiment 1 and 2) investigated the effect of KCl fertilizer on pasture mineral concentration, the dietary cation-anion difference (DCAD), and the subsequent effect of this on periparturient plasma and urine mineral status. Experiment 2 examined the effect of precalving Mg source (MgO, MgSO4, and MgCl2) and postcalving Ca supplementation on the concentration of Ca and Mg in plasma and urine. Unexpectedly, pasture DCAD increased (P = 0.06) from 434 to 535 mEq/kg DM in experiment 1 as pasture K concentration decreased from 4.2 to 3.5%, primarily because of a corresponding and greater decrease in pasture Cl concentration (from 1.9 to 1.3%). Plasma Ca or Mg concentrations were not affected by pasture K concentration. A linear decline (P < 0.10) in urine Mg suggested a decline in Mg absorption as pasture K increased. In experiment 2, pasture DCAD decreased (P < 0.05) linearly from 403 to 350 mEq/kg DM as pasture K concentration decreased from 3.8 to 3.3%. However, precalving urine pH was not affected by the declining DCAD. Postcalving plasma Ca concentration was affected by precalving Mg source with MgSO4 > MgCl2 > MgO. Differences in acid-base balance do not explain the difference between Mg salts. These results indicate that precalving dietary S and Cl concentration plays an important role in Ca homeostasis, in addition to its role in acid-base balance. Supplementation with Ca postcalving increased plasma Ca concentration for 2 d postcalving. Milk production was not affected.

Animals↗

Granulocyte-colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: significantly less graft-versus-host disease and comparable engraftment to G-CSF-mobilized peripheral blood stem cells.

Prospective studies have shown rapid engraftment using granulocyte-colony-stimulating factor-mobilized peripheral blood stem cells (G-PBSCs) for allogeneic transplantation, though the risks for graft-versus-host disease (GVHD) may be increased. It was hypothesized that the use of G-CSF to prime bone marrow (G-BM) would allow rapid engraftment without increased risk for GVHD compared with G-PBSC. Patients were randomized to receive G-BM or G-PBSCs for allogeneic stem cell transplantation. The study was designed (beta <.8) to detect a difference in the incidence of chronic GVHD of 33% (alpha <.05). The plan was to recruit 100 patients and to conduct an interim analysis when the 6-month follow-up point was reached for the first 50 patients. Fifty-seven consecutive patients were recruited (G-BM, n = 28; G-PBSC, n = 29). Patients in the G-PBSC group received 3-fold more CD34(+) and 9-fold more CD3(+) cells. Median times to neutrophil (G-BM, 16 days; G-PBSC, 14 days; P <.1) and platelet engraftment (G-BM, 14 days; G-PBSC, 12 days; P <.1) were similar. The use of G-PBSC was associated with steroid refractory acute GVHD (G-BM, 0%; G-PBSC, 32%; P <.001), chronic GVHD (G-BM, 22%; G-PBSC, 80%; P <.02), and prolonged requirement for immunosuppressive therapy (G-BM, 173 days; G-PBSC, 680 days; P <.009). Survival was similar for the 2 groups. Compared with G-PBSC, the use of G-BM resulted in comparable engraftment, reduced severity of acute GVHD, and less subsequent chronic GVHD.

Acute Disease↗

Defining an exacerbation of pulmonary disease in cystic fibrosis.

Despite the importance of pulmonary exacerbations in CF in both clinical and research settings, both published evidence and consensus are lacking concerning the criteria used to define an exacerbation. The use of hospitalization as a surrogate measure presupposes uniformity among clinicians in diagnosis and treatment of exacerbations. Our aims were to evaluate consensus among clinicians about the variables considered helpful in diagnosing an exacerbation requiring treatment. A comprehensive list of symptoms, signs, and investigations used to define exacerbations was compiled from published trials. A written self-administered questionnaire included the list in age-appropriate groups to survey opinion about the helpfulness of each item, and the estimated proportion of patients admitted within a month of diagnosis of an exacerbation. This was sent to all clinicians managing CF patients in Australia. There were replies from 59/91 clinicians (65%), 41/60 (68%) from those managing children and 18/31 (58%) from those managing adults. Responses of those managing children and adults differed for 7/32 variables (Mann-Whitney test, P < 0.05). Clinic grouping did not show greater consensus among responses of pediatricians (Kruskal-Wallis test, P = 0.362). Consensus, >74% or <26% of respondents rating a variable helpful/very helpful, was found in only 50% of variables listed. Estimated admission rate within a month of diagnosis was 61% (30-100%) for those managing adults and 48% %5-100%) for pediatricians. A lack of consensus was found among clinicians managing CF about the variables considered in diagnosing an exacerbation. The estimated proportion admitted within a month of diagnosis was very variable. This demonstrated inhomogeneity in approach to diagnosis and management of an exacerbation suggests a significant heterogeneity of clinical care.

Adolescent↗

Defending against patients' pain: a qualitative analysis of nurses' responses to children's postoperative pain.

OBJECTIVE: Cognitive approaches to clinical communication attribute deficits in communication to lack of skill. We examined, instead, emotional influences on communication by finding out how nurses construed patients who were in pain, and how these constructions were related to the emotional challenge of patients' pain and to deficits in clinical communication. METHODS: Data, analyzed qualitatively, included: (i) direct observations of verbal interactions of 13 nurses with 16 children after orthopedic surgery; (ii) standardized open-ended interviews with the nurses, patients and parents. RESULTS: Nurses tried to prevent children from displaying pain behavior. When pain behavior did occur, they construed pain as unreal, unwarranted or not deserving help. These findings were apparent in observations of, and interviews with, nurses and also in parents' and children's accounts of nurses' behavior. CONCLUSION: We identified behavioral and cognitive strategies whereby clinicians defend themselves emotionally against patients' pain, and which compromise communication with patients in pain.

Adolescent↗

Lactogenesis. The transition from pregnancy to lactation.

The most important factors in initiation of the cascade of changes in the mammary epithelium that constitute lactogenesis stage II seem to be a prepared mammary epithelium, progesterone withdrawal, maintained plasma prolactin (in most species), and removal of milk from the breast within an undefined interval after birth. Although the molecular mechanisms by which prolactin regulates milk protein synthesis are the subject of intense and productive studies, the specific mechanisms by which progesterone and milk removal interact with the mammary epithelial cell at parturition have not been studied, perhaps because no in vitro model system exists that mimics lactogenesis stage II, or because of the complexity of the changes that must be coordinated during this process, or because of a lack of general understanding of the complex progression of changes in the function of the breast as it goes from the quiescent state of pregnancy to the active secretory state of lactation. With new technologies designed to investigate the biology of complex systems arising from the growing knowledge of the genome of human and animal species and the growing availability of animal and tissue culture models for these processes, physicians can expect a rapid increase in the molecular understanding of lactogenesis in the near future. These fundamental studies must be coupled with good prospective clinical studies if physicians are to obtain a useful, comprehensive understanding of lactogenesis in women.

Female↗

Bone mineral density in prepubertal asthmatics receiving corticosteroid treatment.

OBJECTIVE: To examine whether bone mass is reduced in prepubertal, asthmatics receiving high doses of inhaled corticosteroids. METHODOLOGY: A cross-sectional comparison of lumbar spine-bone mineral density (LS-BMD) was undertaken in 76 subjects after stratifying them according to dosage and administration route of corticosteroid. RESULTS: Weight was the only independent predictor of LS-BMD (r(2) = 0.38). Children receiving greater than 800 microg/day of inhaled corticosteroid plus intermittent oral corticosteroid had a significantly lower weight-adjusted LS-BMD than children treated with 400-800 microg/day of inhaled corticosteroid (mean difference: 0.06 g/cm(2), 95% confidence interval (CI): - 0.02 to - 0.10). A significant difference in weight-adjusted LS-BMD persisted when all children receiving greater than 800 microg/day of inhaled corticosteroid, irrespective of additional oral corticosteroid treatment, were compared with children receiving 400-800 microg/day of inhaled corticosteroid (mean difference: - 0.05 g/cm(2), 95%CI interval: -0.02 to - 0.09). Bone mass was similar in children not receiving any inhaled corticosteroid and those treated with 400-800 microg/day of inhaled corticosteroid. CONCLUSIONS: A reduced bone mass in prepubertal asthmatic children receiving high doses of inhaled corticosteroids may predetermine a compromised peak bone mass and increase osteoporotic fracture risk in adulthood.

Absorptiometry, Photon↗

Single institution outcomes of treatment of severe aplastic anaemia.

BACKGROUND: In severe aplastic anaemia, the treatment of choice for young patients with a human leucocyte antigen-matched sibling is now established as allogeneic bone marrow transplantation (BMT). In older patients and in those without a matched sibling donor, immunosuppressive therapy is the usual first option. 'Alternative' marrow donors are emerging as an option for those without a matched sibling donor. AIMS: To review 10 years of local experience in treating severe aplastic anaemia with BMT and immunosuppressive therapy with emphasis on long-term outcomes. METHODS: A retrospective analysis was performed of all patients with severe aplastic anaemia presenting to the Royal Brisbane and Royal Children's Hospitals between 1989 and 1999. Data were abstracted regarding patient demographics, pretreatment characteristics and outcome measures, including response rates, overall survival and long-term complications. RESULTS: Twenty-seven consecutive patients were identified, 12 treated with immunosuppression alone and 15 with BMT. In these two groups, transfusion independence was attained in 25% and 100%, respectively, with overall survival being 36% and 100%, respectively. Those treated with immunosuppression were significantly older (median 41.5 versus 22 years, P = 0.008). Long-term survivors of either treatment had extremely low morbidity. Three patients carried pregnancies to term post-transplant. Three patients received alternative donor BMT with correspondingly excellent survival. CONCLUSIONS: Patients treated with allogeneic BMT for severe aplastic anaemia enjoyed extremely good long-term survival and minimal morbidity. Patients treated with immunosuppressive therapy had a poorer outcome reflecting their older age and different usage of therapies over the past decade. Optimal treatment strategies for severe aplastic anaemia remain to be determined.

Adolescent↗

First-trimester prenatal diagnosis of a familial subtelomeric translocation.

A new fluorescent in situ hybridization (FISH) technique utilizes a complete set of telomeric probes to screen for deletions or rearrangements within the subtelomeric regions of all chromosomes on a single slide. Such cryptic chromosome rearrangements would otherwise remain undetected by standard cytogenetic analysis. In this case report, we describe the first-trimester prenatal diagnosis of an unbalanced rearrangement in a family where such a cryptic subtelomeric rearrangement is segregating. Interestingly the fetus was also noted to have an increased nuchal translucency at the time first-trimester chorionic villus sampling was performed and a FISH diagnosis made. The result was subsequently confirmed on fetal material obtained after elective termination of the pregnancy. We believe this to be the first report in the literature (as by Medline, December 1999) of a first-trimester prenatal diagnosis using such subtelomeric probes where confirmation by conventional cytogenetic analysis was not possible.

Abnormalities, Multiple↗

Physiology and endocrine changes underlying human lactogenesis II.

Lactogenesis stage II, the onset of copious milk secretion, takes place during the first 4 d postpartum in women and involves a carefully programmed set of changes in milk composition and volume. The evidence is summarized that progesterone withdrawal at parturition provides the trigger for lactogenesis in the presence of high plasma concentrations of prolactin and adequate plasma concentrations of cortisol. Although the process is generally robust, delayed lactogenesis does occur with stressful deliveries and in poorly controlled diabetes. Failure of early removal of colostrum from the breast is associated with high milk sodium and poor prognosis for successful lactation in many women. We speculate that this problem may result from accumulation of a substance in the mammary alveolus that inhibits lactogenesis, even in the face of appropriate hormonal changes after parturition.

Female↗

Intra-operative quality assessment of coronary artery bypass grafts.

Early coronary artery bypass graft (CABG) failure is a troubling complication that may result in a wide range of problems, including refractory angina, myocardial infarction, low cardiac output, arrhythmia, and fatal heart failure. Early graft failures are related to poor quality and size of the distal native vascular bed, coagulation abnormalities, or technical problems involving the graft conduits and anastomoses. Unfortunately, graft failure is difficult to detect during surgery by visual assessment, palpation, or conventional monitoring. We evaluated the accuracy and utility of a transit-time, ultrasonic flow measurement system for measurement of CABGs. There were no differences between transit-time measurements and volumetric-time collected samples in an in vitro circuit over a range of flows from 10 to 100ml/min (Bland and Altman Plot, 1.96 SD). Two hundred and ninety-eight CABGs were examined in 125 patients. Graft flow rate was proportional to the target vessel diameter. Nine technical errors were detected and corrected. Flow waveform morphology provided valuable information related to the quality of the anastamosis, which led to the immediate correction of technical problems at the time of surgery.

Anastomosis, Surgical↗

Patency of radial arterial catheters.

BACKGROUND: Data on the influence of flush methods, blood-sampling methods, and site location on the patency of radial arterial catheters used for pressure monitoring are sparse. OBJECTIVES: To determine the effects of flush and blood-sampling methods, insertion site, and sex of patients on catheter patency. METHODS: In a randomized trial, 174 patients requiring radial arterial pressure monitoring were assigned to 4 groups: fast flush as needed and nonwaste blood sampling; fast flush as needed and waste blood sampling; fast flush every 4 hours and waste blood sampling; and fast flush every 4 hours and nonwaste blood sampling. All site locations were evaluated for patency, and all monitoring systems were maintained with isotonic sodium chloride solution. RESULTS: Nonpatent catheters were 4.23 times more likely in patients with insertion sites 3 cm or higher above the bend of the wrist than in patients with lower sites (P = .01). Duration of patency did not differ between catheters maintained with fast flush every 4 hours and those flushed as needed or between catheters according to the method of blood sampling. Women were 3.05 times more likely than men to have nonpatent catheters (P = .02). With insertion sites 3 cm or higher above the radiocarpal joint, nonpatency was 7.3 times more likely in women than in men (P < .001). CONCLUSIONS: Insertion sites closest to the bend of the wrist increase chances of maintaining patency. Catheters can be maintained with as-needed flushes, and either waste or nonwaste blood sampling can be used.

Aged↗

The separate but related origins of the recency effect and the modality effect in free recall.

The recency effect found in free recall can be accounted for almost entirely in terms of the recall of ordered sequences of items. It is such sequences, presented at the end of the stimulus list but recalled at the very beginning of the response protocol, which produce a recency effect. Such sequences are recalled at the beginning of the response protocol equally often following auditory and visual presentation. These same stimulus sequences are also frequently recalled other than initially in the response protocol following auditory presentation. However, such responses are rarely found following visual presentation. The modality effect in free recall, the advantage of auditory over visual presentation, can be substantially accounted for in these terms. Theoretical and procedural implications of these data are discussed.

Adult↗

Keeping track: the function of the current state buffer.

The Current State Buffer has been proposed to account for our ability to keep track of significant stimuli in our immediate environment. The three experiments reported here were designed to test the independence of the Current State Buffer from the established components of Working Memory. Pre-schoolers were used in order to minimize the possible interference of other memory structures and complex strategies on the part of the subjects, thus allowing a cleaner test of the hypotheses. In the experiments, 180 pre-schoolers watched an Emu glove puppet tidy away toys into receptacles (the 'Tidy Emu Paradigm'), such that the number of pairings just exceeded their capacity for recall of the locations of toys in receptacles. We take this task to be a prototypical visuospatial Working Memory task. In the Object condition of Experiment 1, a Teddy was an object and was tidied away with the other toys. In the Character condition the Teddy was an animated character who interacted with the children and then went to sleep in one of the receptacles. Where Teddy was a character, all children remembered his location even though they had not been asked to; when he was an object only half of the children were correct despite explicit instructions to remember. More crucially, the location of the other toys was better recalled for children in the Character condition than those in the Object condition. These data are taken as evidence for the independence of the Current State Buffer from the Visuospatial Sketchpad. Other explanations, such as a von Restorff effect, are considered, and Experiments 2 and 3 test and reject these as possibilities.

Child, Preschool↗

Tissue specific expression of PKR protein kinase in aging B6D2F1 mice.

A decline in the rate of protein synthesis is a common biochemical change observed with aging in a wide variety of cells and organisms. The double stranded RNA-dependent protein kinase PKR has been shown to phosphorylate eukaryotic initiation factor 2 alpha (eIF-2alpha), a well-characterized factor for down-regulating protein synthesis, in response to environmental stress conditions. Therefore, we were interested in evaluating the role of PKR in the aging process. Tissues from 2- and 20-month-old B6D2F1 male mice were evaluated by Western blot analysis. PKR was detected in all tissues of aging mice confirming its ubiquitous nature. Tissues examined from young mice showed little evidence of PKR expression, suggesting an age-associated up-regulation. P58(IPK), a cellular inhibitor of PKR, was expressed in tissues from both age groups but to a greater extent in tissues of aging mice suggesting an up-regulation to control PKR activity. Hyperphosphorylated eIF-2alpha was increased in selected tissues from older mice compared with tissues from younger mice indicating a possible correlation between PKR expression and kinase function. The data suggest that translational activity is slowing down in a tissue specific manner during the aging process in mice, possibly as the result of increased levels of PKR, and could be a factor in the reduction of the rate of protein synthesis during senescence seen in specific tissues of many organisms.

Aging↗