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Biomedical subjects

M A Short

Publications and source records attributed to M A Short.

At least 19 recordsLinked to original sources

Improved antimicrobial interventions have benefits.

Studies have shown benefits to patients from improved interventions involving antimicrobial therapy. The purpose of the present study was to evaluate prospectively the impact of improved interventions by (i) the use of TheraTrac 2, a computer software program which electronically links susceptibility testing results immediately to the pharmacy and alerts pharmacists of potential interventions, and (ii) the education of pharmacists involving microbiologic topics. The study group had the new intervention program. The control group had interventions performed the way that they had previously been done by manually reviewing hard copies of susceptibility testing data. In a 5-month period, all inpatients whose last names began with A to K were the study group; inpatients whose last names began with L to Z were controls. Three analyses were done; one analysis (analysis A) involved only patients with interventions, one analysis (analysis B) involved all patients for whom antimicrobial testing was done and who were matched for diagnosis-related groups (DRGs), regardless of whether an intervention occurred, and one analysis (analysis C) involved these DRG-matched patients by using severity-adjusted data. In analysis A, the study group had a 4.8% decreased rate of mortality, an average of a 16.5-day decreased length of stay per patient, and $20,886 decreased variable direct costs per patient. None of these differences was statistically significant. In analysis B, the study patients had a 1.2% higher mortality rate (P = 0.741), an average of a 2.7-day decreased length of stay per patient (P = 0.035), and $2,626 decreased variable direct costs per patient (P = 0.008). In analysis C, the study patients had a 1.4% lower mortality rate, a 1.2-day decreased length of stay per patient, and $1,466 decreased variable direct costs per patient. In conclusion, the institution of this program caused substantial cost savings.

Aged↗

The PNH phenotype cells that emerge in most patients after CAMPATH-1H therapy are present prior to treatment.

Paroxysmal nocturnal haemoglobinuria (PNH) cells are deficient in glycosylphosphatidylinositol (GPI) linked antigens due to a somatic mutation of the PIG-A gene in a haemopoietic stem cell. It appears that a PNH clone reaches detectable proportions only when there is selection in its favour. GPI-deficient T lymphocytes have been identified in patients treated with CAMPATH-1H, a monoclonal antibody against the GPI-linked CD52 molecule. CAMPATH-1H selects for cells that are deficient in CD52 (such as PNH-like cells) promoting the development of a PNH-like clone (analogous to PNH). We report that 10/15 patients with chronic lymphocytic leukaemia developed PNH-like lymphocytes after therapy with CAMPATH-1H. The remaining five patients developed no PNH-like cells at any stage, including one patient who received 12 weeks of therapy. The inactivating PIG-A mutation has been identified in one patient. This mutation was detectable by an extremely sensitive mutation-specific PCR-based analysis in the patient's mononuclear cells prior to CAMPATH-1H therapy. The frequency and phenotype of GPI-deficient lymphocytes after CAMPATH-1H and the detection of a PIG-A mutation in the lymphocytes prior to CAMPATH-1H therapy indicated that such mutations were present in a very small proportion of cells prior to selection in their favour by CAMPATH-1H. This suggests that a large proportion of individuals have cells with PIG-A mutations that are not detectable by flow cytometry and thus may have the potential to develop PNH.

Adult↗

Residual disease detection using fluorescent polymerase chain reaction at 20 weeks of therapy predicts clinical outcome in childhood acute lymphoblastic leukemia.

PURPOSE: Ninety-five percent of children with acute lymphoblastic leukemia (ALL) will achieve a remission, but approximately 25% will relapse. Identifying these patients is difficult, as patients with adverse prognostic features at presentation are rare and the majority are standard risk. Analysis of minimal residual disease (MRD) may be able to determine those at risk of relapse, but the best method by which this can be accomplished has yet to be defined. The object of this study was to determine the predictive value of residual disease detection in a group of standard-risk patients with precursor-B ALL at a fixed point in therapy (week 20) using a simple fluorescent consensus immunoglobulin H (IgH) heavy chain polymerase chain reaction (PCR). PATIENTS AND METHODS: Forty-two patients who presented with precursor-B ALL with standard-risk clinical features and treated according to either the Medical Research Council (MRC) UKALL X or XI protocols were assessed using a combination of both fluorescent consensus framework I and framework III Ig heavy-chain PCR. The results of the PCR were analyzed on an ABI 373 gene sequencer with genescan software (Applied Biosystems, Foster City, CA). Clonal rearrangements detected at presentation were looked for at week 20. RESULTS: Of 42 patients, 35 had a clonal population detectable at presentation; of these, seven had more than two clonal rearrangements; this latter group showed a similar disease-free survival (DFS) to the group as a whole. Thirty of 35 patients were analyzed before their second course of intensification therapy at week 20. At this point, nine of 30 had a detectable clonal rearrangement, eight (89%) of whom have since relapsed with a median DFS of 27.5 months. Of the rest of the group (n=21), in whom no clonal rearrangement was detectable, only six (21%) have relapsed. CONCLUSION: Fluorescent IgH PCR at week 20 provides a sensitive and specific means to predict ultimate relapse (57% and 89%, respectively) and is a simple yet promising technique for the identification of patients at risk of poor outcome.

Adolescent↗

A comparison of temperature in VLBW infants swaddled versus unswaddled in a double-walled incubator in skin control mode.

PURPOSE: To determine differences in temperature for very low birth weight (VLBW) infants when swaddled and unswaddled in heated, double-walled incubators. DESIGN: A crossover design was used with infants receiving both the swaddled and unswaddled conditions. SAMPLE: 15 very low birth weight infants (< 1,500 gms) with postconceptional ages of 29.1 +/- 1.5 weeks. MAIN OUTCOME VARIABLE: Infant temperature in swaddled and unswaddled conditions. RESULTS: Abdominal temperatures during swaddling were 0.2 degree C higher than the unswaddled condition. In the swaddled condition, infants required a lower incubator temperature (mean = 26.9 +/- 0.4) than when unswaddled (mean = 29.8 +/- 0.5).

Body Temperature↗

Detection and quantitation of the CBFbeta/MYH11 transcripts associated with the inv(16) in presentation and follow-up samples from patients with AML.

We have developed a competitor-based RT-PCR technique which will detect and quantitate the CBFbeta/MYH11 transcripts associated with inv(16)(q22;p13) and have used it to study presentation and follow-up samples of acute myeloid leukaemia (AML). The levels of the leukaemia-specific transcripts are expressed as a ratio to a ubiquitously expressed mRNA species (Abl) which controls for RNA degradation. This technique has been applied to 75 consecutive patients presenting with either de novo AML or tMDS; 6/75 patients analysed were positive for the inv(16), all were confirmed by conventional cytogenetics. The inv(16) has a strong association with M4Eo, but we found only 2/6-positive patients to have this diagnosis (two patients with M2, one patient M1 and one patient had MDS). At presentation the levels of CBFbeta/MYH11 transcripts were 0.1-10/Abl transcript (mean 3.3/Abl transcript). Seventeen follow-up samples were available on 5/6 of these patients, and on two further patients in whom stored material was available. Following the first cycle of chemotherapy the level of transcripts was at least 10(-2) lower (0.1-10 x 10(-2)/abl transcript) than their presentation sample. Subsequent samples on these patients when in remission gave transcript levels in the range (1.0 x 10(-4) - 2 x 10(-3)/abl transcript), and three long-term follow-up samples were negative. We have developed a quantitative test which opens the possibility of predicting relapse by detecting changes in the numbers of leukaemia-specific transcripts.

Acute Disease↗

The rapid diagnosis of acute promyelocytic leukaemia using PML (5E10) monoclonal antibody.

Acute promyelocytic leukaemia (APL) is characterized cytogenetically by t(15;17)(q22:q21) which results in the production of a PML/RAR alpha fusion protein. Detection of the translocation or the fusion gene product is required for objective diagnosis of APL. This can be accomplished by conventional cytogenetic methods, fluorescence in situ hybridization or RT-PCR. Such techniques are time consuming and not universally available. The intracellular distribution of the PML protein in promyelocytes is characteristically altered in APL and this can be detected by immunocytochemistry. We have assessed two immunocytochemical methods, immunofluorescence and alkaline phosphatase-anti-alkaline phosphatase staining (APAAP), with regard to sensitivity, specificity and rapidity of diagnosis. 85 patients with AML including 15 cases of APL were studied. Immunofluorescence PML detection was concordant with RT-PCR for t(15:17) in 14/15 (93.3%) cases with no false positives. The negative APL case in our series was a patient with a 5' PML breakpoint who did not express the reciprocal t(17;15) fusion product. APAAP was concordant in only 6/13 (46%) APL cases with one false positive. In conclusion, immunofluorescent localization of PML using 5E10 monoclonal antibody is a rapid, sensitive and specific diagnostic tool for APL.

Antibodies, Monoclonal↗

32P-incorporation PCR for the detection of rearrangements at the TCR-gamma locus.

We have adapted and developed a PCR (polymerase chain reaction)-based technique for the T-cell receptor (TCR)-gamma chain gene, which has subsequently been used for routine diagnosis. Variable-region oligonucleotide primers were chosen from subgroups I and II, and the joining region primer was from the J2 segment. The primers were used to perform a 32P-incorporation PCR, and the products were then separated on an 8% denaturing polyacrylamide gel. In our hands, this technique is more reliable than cold methods, when separation is performed on either agarose or nondenaturing polyacrylamide. The radioactive technique was used to look at 102 T-cell proliferations, of which eight of eight T-acute lymphoblastic leukemia (ALL), 24 of 34 T-non-Hodgkin's leukemia (NHL), and 35 of 60 large granular lymphocyte (LGL) expansions were clonal. Of 122 B-cell proliferations investigated, including 72 cases of B-cell lineage ALL, 36 demonstrated a T-cell rearrangement (33 ALLs and three myelomas). Samples from nonlymphoid tumors were tested and produced a normal distribution ladder of PCR products after autoradiography, a pattern also observed with antenatal and preoperative patients. The radiolabel-incorporation method detected an abnormal pattern of a ladder with prominent dark bands in 29 of 122 B-cell and 27 of 102 T-cell cases and in 0 of 49 of the nonlymphoid and normal samples. The abnormal banding patterns obtained in a proportion of the B- and T-cell cases was not readily discernible by nondenaturing-acrylamide or agarose-separation methods.

Blotting, Southern↗

The effects of swaddling versus standard positioning on neuromuscular development in very low birth weight infants.

A randomized control design was used to compare the effect of swaddling to standard positioning on neuromuscular development in very low birth weight (VLBW) infants (< 1,250 gm). The outcome of neuromuscular development was measured at 34 weeks postconceptional age using the Morgan Neonatal Neurobehavioral Exam (MNNE). The sample included 50 infants who met criteria for birth weight, age and who were classified as appropriate for gestational age. Exclusion criteria were also used. The infants were randomly assigned to the experimental group or the comparison group. Data analysis included descriptive and inferential statistical techniques. The results demonstrated that swaddled infants had higher total scores on the MNNE as compared to infants with standard positioning. Swaddling appears to be a positioning technique that can enhance neuromuscular development of the very low birth weight infant.

Bedding and Linens↗

Kinesthetic recall of children with athetoid and spastic cerebral palsy and of non-handicapped children.

Twenty-four children with spastic or athetoid quadriplegic cerebral palsy were paired according to severity of motor disability and age, then matched with 12 non-handicapped children of similar ages. The children were tested with a standard kinesthesiometer and two kinds of scores were recorded. Absolute Error scores reflected the children's deviation from the target and Total Movement scores reflected their over-all range of movement. There were significant differences between groups in Absolute Error scores, with the cerebral-palsied children performing worse than the controls and the spastic children worse than the athetoid children. All three groups tended to underestimate the targets and there were no significant differences in Total Movement scores.

Adolescent↗

Effects of physical conditioning on self-concept of adult obese males.

The purpose of the study was to investigate possible psychological changes in obese men after participating in an eight-week nutrition and physical conditioning program. The subjects, 45 male, metropolitan policemen who were considered at least 20 percent over their optimum body weights, were placed on diets and received weekly instruction on topics of nutrition and exercise. The subjects were randomly divided into two groups, one that participated in aerobic conditioning and one that did not. The amount of oxygen consumption, as an index of physical fitness, and performance on selected subscales of the Tennessee Self-concept Scale (TSCS) were measured before and after the training and conditioning programs. Both groups displayed significant increases in oxygen consumption and on the Physical Self and Self-satisfaction subscales, but on all these measures, the Conditioning Group increased significantly (2 to 3 times) more. For both groups, the Total Variability measure from the TSCS showed significant reductions, which have been associated with personality integration. These results demonstrate that physical conditioning and dietary educational sessions or educational sessions alone are associated with positive changes in self-concept in obese individuals and also corroborate other studies that show links between physical and psychological fitness.

Adult↗

Vestibular-proprioceptive functions in 4 year olds: normative and regression analyses.

Normative data were obtained for 156 pre-school children's performances on measures of muscle tone, muscle co-contraction, standing balance, prone extension posture, flexion supine posture, asymmetrical tonic neck reflex, and postrotary nystagmus. Regression analysis indicated that these combined variables accounted for only 13.5 percent of the variance of postrotary nystagmus of 145 four year olds. However, if the data are examined only for children exhibiting nystagmus that is lower than 1 standard deviation below the mean, then these variables account for 50 percent of the variance of nystagmus. Prone extension posture, standing balance-eyes closed, and muscle tone account for 37 percent of the variance within this low-nystagmus population. These results are considered in light of the authors' previous studies demonstrating that, in learning-disabled children, vestibular-proprioceptive measures can be used clinically to predict which children will respond to sensory integration therapy with changes in postrotary nystagmus. These changes, according to sensory integration theory, reflect positive responses to therapy.

Child, Preschool↗

Nystagmus duration changes of learning disabled children during sensory integrative therapy.

Sensory integrative therapy was administered to 43 learning disabled children categorized according to their pretherapeutic duration of postrotary nystagmus. The duration then was recorded after relatively short or long treatments. Children displaying initial subnormal nystagmic functioning responded to therapy with increases in duration while others displayed decreases, and these effects were more apparent after long therapy. These data support the claims that learning disabled children can be meaningfully categorized according to their nystagmic responses and that attention to their interoceptive sensory functioning may be of clinical significance.

Child↗

Association between nystagmus hyporesponsivity and behavioral problems in learning-disabled children.

This study explored the hypothesis that an association exists between postrotary nystagmus hyporesponsivity and behavioral problems in learning-disabled children. Supporting this conclusion was the finding that the learning-disabled boys rated by teachers as displaying the most socially inappropriate behaviors had significantly lower postrotary nystagmus durations than other learning-disabled boys. In addition, near significant associations were obtained between subnormal nystagmus functioning and socially inappropriate responding for boys and girls combined. Learning-disabled girls were evaluated as responding significantly more appropriately than learning-disabled boys, while having significantly shorter postrotary nystagmus durations; thus, sex of a child may be an important variable in determining relationships between psychological characteristics and hyporesponsive nystagmus. Additional research is needed in this area because of a number of limitations to this study; however, these results present further suggestive evidence that learning-disabled children can be categorized according to characteristics of their postrotary nystagmus.

Child↗