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Biomedical subjects

J Dixon

Publications and source records attributed to J Dixon.

At least 19 recordsLinked to original sources

Constriction bands and limb reduction defects in two newborns with fetal ultrasound evidence for vascular disruption.

Most structural anomalies attributed to vascular disruption have been inferred, though not proven, to be the result of disruptive events in utero. We report on 2 pregnancies with ultrasound evidence of disruptive events resulting in terminal limb "reduction" defects with constriction bands and other anomalies. In the first patient a fetal ultrasound study at 12 weeks post-LMP demonstrated a monochorionic (MC) twin pregnancy with a nonviable co-twin and no evidence of amniotic bands. At birth, there was a left cleft lip and palate, and terminal limb "reduction" defects with ring constrictions of the left hand and both feet. In the second patient, a routine fetal ultrasound study at 18 weeks post-LMP identified a subhepatic cyst which subsequently resolved. Fetal ultrasound examination and neonatal computed tomography (CT) scan of the liver were consistent with a hepatic infarct due to emboli from the umbilical vein. At birth, patient 2 had acrosyndactyly of the left hand with ring constrictions of the digits and reduction of the left big toe. There was no evidence of abnormal amnion. Postnatal development has been normal in both cases. We present ultrasound evidence supporting the hypothesis that vascular disruption from death of a co-twin or from in utero embolic infarcts can cause: 1) terminal limb "reduction" defects and possibly cleft lip and palate; and 2) ring constrictions similar to those of "amniotic band disruption sequence" in the absence of an abnormal amnion. Serial pregnancy ultrasound studies are recommended for evaluation of the development of fetal structural anomalies following ultrasound evidence of a disruptive event in utero.

Abnormalities, Multiple

Single and combined effects of methylphenidate and behavior therapy on the classroom performance of children with attention-deficit hyperactivity disorder.

Twenty-four boys with attention deficit-hyperactivity disorder (ADHD) participating in an intensive summer treatment program each received b.i.d. placebo and two doses of methylphenidate (MPH, 0.3 mg/kg and 0.6 mg/kg) crossed with two classroom settings: a behavior modification classroom including a token economy system, time out and daily home report card, and a "regular" classroom setting not using these procedures. Dependent variables included classroom observations of on-task and disruptive behavior, academic work completion and accuracy, and daily self-ratings of performance. Both MPH and behavior modification alone significantly improved children's classroom behavior, but only MPH improved children's academic productivity and accuracy. Singly, behavior therapy and 0.3 mg/kg PMH produced roughly equivalent improvements in classroom behavior. Further, the combination of behavior therapy and 0.3 mg/kg MPH resulted in maximal behavioral improvements, which were nearly identical to those obtained with 0.6 mg/kg MPH alone.

Achievement

Drug use and HIV risk-taking behaviour among clients in methadone maintenance treatment.

Current drug use and HIV risk-taking behaviour of a sample of 95 methadone maintenance clients was investigated. Subjects had been on their current programme for an average of 70.9 weeks with a mean daily dose of methadone of 65.6 mg. Two-thirds had injected heroin, and 82% had injected a street drug in the month prior to interview. Over 20% of subjects had shared a needle in the month before interview, all with only one other person. Subjects who had injected cocaine in the month before interview had significantly higher levels of injecting risk-taking behaviour than those subjects who had injected but not used cocaine. Condom use among subjects was low, particularly in regular relationships. While knowledge concerning HIV was high among subjects, there was no relation between level of knowledge and actual behaviour. It is concluded that knowledge alone is not sufficient to ensure behaviour change.

Adolescent

Genetic and physical mapping of the Treacher Collins syndrome locus: refinement of the localization to chromosome 5q32-33.2.

Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development, the locus for which has been chromosomally localized to 5q31-34. We have isolated four hypervariable microsatellite markers (heterozygosity values range from 0.70 to 0.89) which have been mapped to distal 5q. Fifteen unrelated TCOF1 families have been analyzed for linkage to these markers. There is strong evidence demonstrating linkage to all of these markers; the strongest support for positive linkage being provided by the marker IG52, with a maximum pairwise lod score of 9.77 at a recombination fraction of 0.055. Analysis of recombinant individuals, physical mapping by fluorescence in situ hybridization and genetic linkage analysis demonstrated that the TCOF1 locus was flanked proximally by the loci 2C7 and 2D10, and distally by the loci IG26 and IG52 with a maximum lod score of 14.4, as assessed by multipoint linkage analysis. The refinement of the localization of the TCOF1 locus to 5q32-33.2, with flanking markers, represents an important step towards the identification of the mutated gene itself.

Base Sequence

Priority setting: lessons from Oregon.

The state of Oregon has developed a unique method to set priorities for health services. The method is based on a cost-utility formula but also incorporates public attitudes and values. Using an explicit process, the Oregon Health Services Commission has completed the ranking of 714 condition-treatment pairs. The background, methods, and criticisms of the Oregon approach highlight key questions for managers and physicians in other health services when they allocate limited resources.

Community Participation

The gene for Treacher Collins syndrome maps to the long arm of chromosome 5.

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. We have studied 12 unrelated TCS families with multiple affected individuals for linkage to five chromosome 5 markers. There is strong evidence demonstrating linkage to three of these markers. Multipoint linkage analysis places the mutation causing TCS in the interval between the gene for the glucocorticoid receptor and the anonymous marker D5S22, with a maximum multipoint lod score of 9.1.

Chromosome Mapping

Study of the possible interaction between fentanyl and propofol using a computer-controlled infusion of propofol.

A computer-controlled infusion of propofol designed to achieve a target blood concentration of propofol 3 microgram ml-1 was used to investigate the possibility of an interaction between propofol and fentanyl in 32 patients undergoing body surface surgery. In 16 patients who were not receiving a neuromuscular blocker during maintenance anaesthesia with 67% nitrous oxide, there were no significant differences in blood concentrations of propofol between eight patients who received fentanyl 5 micrograms kg-1 before induction of anaesthesia, and eight patients who did not. In a further 16 patients who received vecuronium during maintenance anaesthesia with 67% nitrous oxide, there were no significant differences in blood propofol concentrations between eight patients who received fentanyl 5 micrograms kg-1 before induction of anaesthesia, and eight patients who did not. Fentanyl administered i.v. immediately before a computer-controlled infusion of propofol resulted in more satisfactory anaesthetic conditions than when fentanyl was not used, but did not significantly prolong the recovery time.

Adult

SPECT for acute knee pain.

In the assessment of acute knee pain following recent trauma frequently related to sporting activities, bone scintigraphy was performed on 52 patients; in 40 of these patients, scintigraphy immediately preceded arthroscopy. SPECT was critical in providing delineation and sitting of the abnormalities; this would not have been feasible with conventional planar imaging in 45 of the patients. Multiple sites of focal uptake were frequently visualized at ligamentous insertions or in intra-articular areas of cartilaginous erosion. Damaged anterior cruciate ligaments were only identified in 5 out of 10 patients, occurring when there was avulsion of the tibial attachment, but changes resulting from patellar injury were demonstrated in all 8 patients. The most characteristic scintigraphic change resulted from meniscal tears, which was diagnosed in 31 out of 35 patients in whom the lesion had been suspected clinically. In the identification of this common injury, SPECT had a sensitivity of 88%, specificity of 87%, and diagnostic accuracy of 88%. Thus, although trauma readily induces scintigraphic abnormalities in and around the knee, the patterns of alteration associated with particular lesions can be identified by SPECT and can provide considerable assistance in management, particularly in determining the need for arthroscopy.

Anterior Cruciate Ligament Injuries

Insulin-treated diabetes in Tasmania: population-based clinical characteristics and their possible implications for diabetic health care in Australia.

The Tasmanian Insulin-treated Diabetes Register recruited 1233 eligible (treatment with insulin on May 1, 1984) subjects with insulin-treated diabetes, which enabled the description of a population-based profile of clinical characteristics. Approximately one-third of both the male and female subjects who were recruited was considered to have insulin-dependent diabetes mellitus. As would be expected, subjects with insulin-dependent diabetes mellitus were considerably younger, had a longer average duration of disease, and had had fewer hospital admissions compared with subjects with non-insulin-dependent diabetes mellitus. However, in some cases, both forms of diabetes were of long duration and had resulted in multiple hospital admissions. More than 90% of subjects with insulin-dependent diabetes mellitus and approximately half the subjects with non-insulin-dependent diabetes mellitus were hospitalized at diagnosis; an absence of a secular trend in diabetes-stabilization practices was noted, which suggested a low utilization of facilities for ambulatory stabilization in Tasmania to date. To monitor metabolic control, approximately half the subjects performed self-monitoring of their blood glucose levels exclusively, which indicated the widespread acceptance of this form of evaluation (which has been introduced into Australia only within the past decade). Approximately one-quarter of the subjects continued to perform urine testing exclusively and a small proportion of subjects did not monitor their metabolic control in any way.

Adolescent

Location of breakpoints within the major breakpoint cluster region (bcr) in 33 patients with bcr rearrangement-positive chronic myeloid leukemia (CML) with complex or absent Philadelphia chromosomes.

We report the sublocalization of the breakpoint in chromosome 22 in 33 patients with chronic myeloid leukemia (CML) who also had unusual marrow cytogenetics. In 23 patients, the leukemic clones were characterized by Philadelphia (Ph1) chromosomes that arose through complex translocations that involved three or more chromosomes. In the remaining ten patients, there were no detectable Ph1 chromosomes despite molecular evidence for the presence of rearrangements in the major breakpoint cluster region (bcr) of chromosome 22 in all cases. There was no significant difference between the two groups with respect to location of the breakpoints within the bcr. When these two groups of patients were combined, there was a significant excess of breakpoints in one segment of the bcr when compared to the distribution of breakpoints seen in 119 patients with simple 9;22 translocations. The difference in breakpoint distributions did not appear to be entirely attributable to differences between groups in disease duration at the time of study. These data support the notion that the unusual genetic recombinations that give rise to BCR/ABL fusion genes in CML involve specific DNA sequences of BCR (and possibly ABL) and additional, recombinogenic sequences, at least some of which are present in loci known to be nonrandomly involved in complex Ph1 translocations.

Adult

Cholecystokinin and tyrosine hydroxylase messenger RNAs in neurons of rat mesencephalon: peptide/monoamine coexistence studies using in situ hybridization combined with immunocytochemistry.

The cellular localization of neurons expressing cholecystokinin (CCK) and tyrosine hydroxylase (TH) mRNAs was analysed in rat ventral mesencephalon using in situ hybridization techniques with both complementary DNA and synthetic oligonucleotide probes. Cell bodies distributed throughout the substantia nigra, ventral tegmental area, interfascicular nucleus, midline raphe nuclei, and central and ventral periaqueductal grey matter were found to contain CCK mRNA or TH mRNA as indicated by high densities of grains overlying the perikarya. The in situ hybridization technique was combined with immunocytochemistry on the same tissue section to localize the peptide or enzyme within its respective mRNA-containing somata. In addition, the presence of TH immunoreactivity was demonstrated within cell bodies labeled for CCK mRNA and immunostaining for CCK was detected within TH mRNA-containing neurons. In the medial geniculate nucleus a strong labeling for CCKmRNA was observed, in spite of the fact that so far no CCK-like immunoreactivity has been demonstrated in perikarya in this nucleus. The specificity of the probes was verified by RNA blot hybridization. These results confirm recent double-labeling immunocytochemical studies and further characterize the coexistence of CCK and TH at the level of their mRNAs as well as their post-translational products in a large population of mesencephalic dopamine neurons known to project to forebrain areas.

Animals

The role of single photon emission computed tomography in bone scintigraphy.

The increasing availability for routine nuclear medicine studies of single photon emission computed tomography (SPECT) reflects the realisation of its ability to improve lesional detection and the assessment of location. This is achieved by removing unwanted surrounding radioactivity and thus delineating with greater clarity deeper areas of preferential accumulation. By removing the super-imposition of structures, SPECT offers considerable potential for improved diagnostic accuracy in suspected bone and joint disease. Time and cost, however, necessitate a selective use of the technique. The maximum advantages arise from studies of the head, spine, skull and knees. The role of SPECT does, in some instances, lie in providing increased sensitivity in the detection of focal uptake while in others it complements alternative imaging modalities by identifying the functional status of an abnormality and thus may demonstrate its clinical significance. Since such information may be obtained by planar scintigraphy using techniques such as pinhole collimation, continuing evaluation is essential to ascertain the precise indications for SPECT imaging.

Bone Diseases

Computer controlled infusion of propofol.

A computer controlled infusion pump was used to deliver propofol to two groups of eight patients undergoing body surface surgery. The patients were premedicated with morphine sulphate i.m. and anaesthesia was supplemented with 66% nitrous oxide in oxygen. Patients in group 1 breathed spontaneously, whereas patients in group 2 underwent artificial ventilation to a normal PaCO2. The computer program was designed to achieve and maintain a blood concentration of propofol 3 micrograms ml-1 as rapidly as possible, basing calculations on a three-compartment pharmacokinetic model. Mean blood propofol concentrations were found to be close to the predicted target from 10 to 120 min in group 1, but were 5-20% higher from 20 min in group 2.

Adult

Liver insulin receptor tyrosine kinase activity in a rat model of type II diabetes mellitus and obesity.

Spontaneous hypertensive-corpulent rats (SHR/N-corpulent), homozygous for the corpulent gene (cp/cp), are obese, hyperinsulinemic and exhibit abnormal glucose tolerance and thus represent a model for type II diabetes and obesity. In view of their overall insulin resistance, we examined liver insulin receptor binding and tyrosine kinase activity from corpulent rats and lean littermates fed purified diets containing 54% sucrose or starch for about 12 wk. Specific 125I-insulin binding to crude liver membranes from female corpulent rats fed either starch or sucrose was reduced to approximately 50% of that seen in lean rats (14 vs. 7%). Affinity of insulin receptors was similar in all groups, suggesting that hyperinsulinemic corpulent rats possess fewer hepatic insulin receptors than do lean rats. Using similar numbers of wheat germ agglutinin-agarose (WGA)-purified insulin receptors with similar affinities for insulin, it was found that basal and insulin-stimulated phosphorylation of the synthetic tyrosine-specific kinase substrate poly(Glu, Tyr)4:1 was similar in lean and obese rats fed sucrose or starch. It is suggested that the contribution of the liver to the insulin resistance in obese SHR/N-cp rats probably lies distal to the insulin receptor tyrosine kinase.

Animals