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Biomedical subjects

D Wheeler

Publications and source records attributed to D Wheeler.

At least 37 records · Page 2Linked to original sources

The 'chef's hat' appearance of the femoral head in cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is inherited as an autosomal dominant disorder characterised by failure of membranous ossification. The condition is due to a mutation of the cbfa1 gene on chromosome 6 which has a role in the development of osteoblasts from the mesenchymal cells. In their growing years, these patients have an unusual shape of the femoral head reminiscent of a 'chef's hat'. In order to confirm the consistency of this sign, we have reviewed the radiographs of 28 patients with CCD. All except three had this appearance. The sign was also seen in patients with coxa vara associated with a variety of other conditions. The chef's hat sign may occur secondary to the particular mechanical environment created by coxa vara as well as abnormal cellular function in patients with CCD. Although coxa vara has some influence on the shape of the femoral head, it is not entirely responsible for its morphology since it was present in only six of the 28 patients with CCD.

Adolescent↗

Recognized globe perforation during strabismus surgery: incidence, risk factors, and sequelae.

BACKGROUND: Inadvertent perforation of the globe is a well-recognized complication of extraocular muscle surgery. We evaluated the incidence, risk factors, and sequelae of this complication at our institution. METHODS: Medical records of patients who underwent extraocular muscle surgery at King Khaled Eye Specialist Hospital, Saudi Arabia, between September 1983 and April 1997, were reviewed for the occurrence of globe perforation. We documented preoperative visual acuity and refraction, surgical procedure, how the perforation occurred, and immediate management, as well as the sequelae of the perforation, its management, and final outcome. RESULTS: Recognized perforations occurred in 15 of 4886 procedures, for an overall incidence rate of 3/1000. Perforations were 3 times more common in myopic eyes (>-6.00 D, P =.05) and 2 times more common in eyes with previous extraocular muscle surgery. Perforations occurred during muscle reattachment (5 cases), placement of traction sutures at the limbus (4 cases with transient hyphema), muscle disinsertion (3 cases), and placement of sutures at the muscle insertion before disinsertion (3 cases). One patient had a large scleral laceration with uveal prolapse, necessitating scleral patch graft at the time of surgery, and later had retinal detachment surgery with loss of 2 lines of visual acuity. Endophthalmitis, cataract, glaucoma, and phthisis bulbi were not encountered in our review. CONCLUSION: The current incidence of globe perforation is low and only rarely associated with serious sequelae.

Adolescent↗

Detection of vancomycin resistant genes vanA and vanB by cycling probe technology.

Cycling Probe Technology (CPT) has been used to develop gene-based assays for detection of vancomycin resistance genes vanA and vanB in enterococci (VRE). Cycling Probe Technology utilizes a chimeric DNA-RNA-DNA probe that is cleaved by the enzyme RNase H when hybridized to its complementary DNA target. Conversion of full-length probe into the cleaved probe fragments is the basis for detection and quantification of the CPT reaction. Two gene-specific probes, each one unique to either the vanA or vanB gene, were utilized for development of vanA and vanB CPT assays, respectively. Both vanA and vanB CPT assays were used to determine the presence or absence of the corresponding gene in 440 clinical enterococcal isolates. The presence of vanA and vanB gene sequences was detected in 154 and 131 isolates, respectively. Phenotypic characterization of all isolates was determined through interpretation of conventional susceptibility data obtained with the disk diffusion method. Comparison between disk diffusion characterization and CPT assays revealed 11 discrepant isolates. The identity of these isolates was resolved by polymerase chain reaction (PCR) which confirmed the vanA and vanB CPT assay data. Therefore, compared to conventional phenotyping, both the vanA and vanB CPT assays appeared superior for accurate identification of VanA and VanB isolates.

Bacterial Proteins↗

Atypical vitellins in ponerine ants (Formicidae: Hymenoptera).

Higher hymenopteran vitellogenin/vitellins have been characterized as containing one large apoprotein. We show that in the ant subfamily Ponerinae, species in the tribes Odontomachini, Platythyrini, and Amblyoponini, also have a vitellin with this simple structure, containing a single apoprotein of 180-190kDa. Species in tribes Ponerini and Ectatommini, however, have vitellins containing multiple subunits. The size and number of the subunits varies, with differences even among species within the same genus. This is the first report of diversity in vitellogenin structure in the higher Hymenoptera. Vitellin and vitellogenin in Harpegnathos saltator (Ponerini) contain two large subunits of about 165kDa and two small subunits of about 45 and 43kDa. N-terminal sequence analysis suggests that provitellogenin is cleaved at two different sites, producing two large and two small subunits differing slightly in size. Diversity of vitellin types in Ponerini and Ectatommini is similar to that found in the more primitive tenthredinoid sawflies (Hymenoptera, Symphyta), and may indicate polyphyly in the Ponerinae. Insect vitellogenins and yolk proteins show considerably more diversity than originally believed, and the possibility of the functional significance of these differences should be considered.

Journal Article↗

Peak expiratory flow rate control chart in asthma care: chart construction and use in asthma care.

BACKGROUND: The home monitoring of peak expiratory flow rate (PEFR), although recommended in current asthma guidelines, remains seriously underutilized by both patients and physicians. Our assessment is that this is more a statement regarding the inability of current charting methods to fulfill the promises made for PEFR monitoring, rather than a commentary regarding the usefulness of peak expiratory flow rate monitoring per se. We have adapted the theory and charting tool of the discipline of statistical process control to the daily monitoring of PEFR in the care of patients with asthma. Statistical process control charts integrate the actual PEFR values and their day-to-day variation in a manner that permits more informed decision-making. This article introduces our adaptation of statistical process control theory and charts via three case presentations. OBJECTIVE: Report our experience in the use of statistical process control theory and charting to the monitoring of peak expiratory flow in the care of patients with asthma. METHODS: Discussion of methodology and case reports. CONCLUSION: This is the first report of the application of statistical process control (SPC) theory and charting to the home monitoring of peak expiratory flow rate and the clinical decision-making processes involved in the day-to-day care of patients with asthma. SPC charts integrate knowledge of actual serial PEFR measurements with knowledge of their associated serial variation. Our adaptation of this theory and its charting methodology results in a tool that loses nothing provided by the charting methods suggested in current guidelines and, at the same time, provides patient specific, statistically driven signals of significant change; facilitates identification of the reason(s) for the change in PEFR; predicts the range in which future function will occur; permits decision-making and care to be provided in an anticipatory manner; and, importantly, permits the early identification of the functionally at-risk patient. This report demonstrates that home monitoring of peak expiratory flow is a robust tool whose usefulness in the care of patients with asthma has been limited more by the paradigm in which we have required it be used than by any of the limitations of the measurement per se.

Adult↗

Secondary posterior chamber intraocular lens implantation in children.

BACKGROUND: Primary intraocular lens (IOL) implantation after cataract aspiration is a widely accepted means of correcting pediatric aphakia. However, little is available in the literature on secondary IOL implantation in children. We present our experience over the past 6 years. METHODS: The charts of 57 aphakic children (61 eyes) who underwent secondary posterior chamber IOL implantation between January 1989 and April 1996 were reviewed. In general, these children were either intolerant of or noncompliant with their contact lenses. An attempt was made to correlate visual outcome with patient variables. Evaluation of the ciliary sulcus structure was made in selected patients by ultrasonographic biomicroscopy to reveal any changes resulting from the presence of the IOL haptic in the sulcus. RESULTS: The age range at the time of surgery was 2 to 16 years (mean 8 y). Mean follow-up was 14 months (range 6 to 48 months). Forty-two percent of the patients had a best-corrected visual acuity of 20/40 or better and 78% saw better than 20/80. Posterior capsular opacification occurred in 10 eyes, 8 of which required neodymium:yttrium-aluminum-garnet laser capsulotomy. No major complications occurred. Ciliary sulcus evaluation by biomicroscopy did not reveal any significant ciliary body or scleral erosion. No changes were noted when the implanted sulcus was compared with the normal contralateral side. CONCLUSION: Although follow-up was short, this review suggests that secondary posterior chamber IOL implantation is a safe alternative when other methods of correcting pediatric aphakia fail.

Adolescent↗

BRCA1 and BRCA2 in breast cancer families from Wales: moderate mutation frequency and two recurrent mutations in BRCA1.

Mutations in the BRCA1/BRCA2 genes account for varying proportions of breast cancer families studied, and demonstrate considerable variation in mutational spectra coincident with ethnic and geographical diversity. We have screened for mutations in 17 families from Wales with two or more cases of breast cancer under age 50 and/or ovarian cancer. Eight out of 17 (47%) families had demonstrable mutations. Six out of 17 (35%) carried BRCA1 mutations and 2 out of 17 (12%) carried BRCA2 mutations. Two recurrent mutations in BRCA1 were identified, which appear to represent founder mutations in this population. These data support the existence of additional breast and ovarian cancer susceptibility genes.

Adult↗

The Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)-L-homoserine lactone has immunomodulatory activity.

Diverse gram-negative bacterial cells communicate with each other by using diffusible N-acyl homoserine lactone (AHL) signal molecules to coordinate gene expression with cell population density. Accumulation of AHLs above a threshold concentration renders the population "quorate," and the appropriate target gene is activated. In pathogenic bacteria, such as Pseudomonas aeruginosa, AHL-mediated quorum sensing is involved in the regulation of multiple virulence determinants. We therefore sought to determine whether the immune system is capable of responding to these bacterial signal molecules. Consequently the immunomodulatory properties of the AHLs N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) were evaluated in murine and human leukocyte immunoassays in vitro. OdDHL, but not OHHL, inhibited lymphocyte proliferation and tumor necrosis factor alpha production by lipopolysaccharide-stimulated macrophages. Furthermore, OdDHL simultaneously and potently down-regulated the production of IL-12, a Th-1-supportive cytokine. At high concentrations (>7 x 10(-5) M) OdDHL inhibited antibody production by keyhole limpet hemocyanin-stimulated spleen cells, but at lower concentrations (<7 x 10(-5) M), antibody production was stimulated, apparently by increasing the proportion of the immunoglobulin G1 (IgG1) isotype. OdDHL also promoted IgE production by interleukin-4-stimulated human peripheral blood mononuclear cells. These data indicate that OdDHL may influence the Th-1-Th-2 balance in the infected host and suggest that, in addition to regulating the expression of virulence determinants, OdDHL may contribute to the pathogenesis of P. aeruginosa infections by functioning as a virulence determinant per se.

4-Butyrolactone↗

The effects of femoral intramedullary reaming on pulmonary function in a sheep lung model.

Two methods of intramedullary fixation of fractures of the middle of the femoral shaft were evaluated in a sheep model to determine the effect of femoral reaming on pulmonary function. The effect of a modified reamer was also studied. A second experiment with the same model was performed to evaluate the relationship between embolization and pulmonary dysfunction. This experiment involved two groups of sheep--those with normal lungs and those with contused lungs--divided into subgroups--those that had nailing with reaming and those that had nailing without reaming. Intracardiac ultrasound was used to measure the magnitude and duration of transvenous particulate embolization during the operations. Both experiments involved hemodynamic monitoring during and after the nailing. The pulmonary tissue was examined histologically after the animals were killed. The hemodynamic monitoring revealed only a transient increase in pulmonary vascular resistance in the animals that had femoral nailing with reaming in both experiments. The modified reamer had no effect on the pulmonary response. Histological analysis of pulmonary tissue demonstrated a significant increase in the number of fat emboli in both the animals that had nailing with reaming and the animals that had nailing without reaming compared with the control animals. Intravascular ultrasound revealed that the operative maneuver associated with the greatest number of emboli was opening of the intramedullary canal with the awl. The first two passes of the reamer produced more emboli and embolism of longer duration than did the later passes. Pulmonary confusion did not increase the risk of pulmonary dysfunction due to intramedullary nailing in this model.

Animals↗

Management and outcome of pneumothoraces in patients infected with human immunodeficiency virus.

To better understand the natural history, management, and outcome of pneumothoraces in HIV-infected patients, we reviewed hospital charts and chest radiographs of HIV-infected adults discharged from the University of Maryland Medical Center over a 6-year period. Sixty pneumothoraces occurred in 39 patients. Twenty-three pneumothoraces resulted from trauma and 37 were spontaneous. Thirty-two (86%) of the spontaneous pneumothoraces occurred in patients with Pneumocystis carinii pneumonia (PCP). Eight percent of the traumatic pneumothoraces in patients who did not have PCP resolved. Patients who had pneumothorax as well as PCP were more difficult to manage and had a poorer outcome (50% mortality) than those who did not have PCP (25% mortality).

Adult↗

First trimester aneuploidy screening using nuchal translucency, free beta human chorionic gonadotrophin and maternal age.

Screening for aneuploidy using maternal age has a low detection rate and high false positive rate. Second trimester maternal serum screening increases trisomy 21 detection and decreases the false positive rate. First trimester screening would enable definitive diagnosis with chorionic villus sampling, and simple surgical termination of affected pregnancies would still be an option. Nuchal translucency (NT), free beta human chorionic gonadotrophin (f beta HCG) and maternal age were assessed in 302 patients before chorionic villus sampling. NT positively and f beta HCG negatively correlated with gestation, but neither correlated with maternal age nor with each other. Both NT and f beta HCG were increased in trisomy 21. NT was increased and f beta HCG was decreased in trisomy 18. Multivariate discriminant analysis enabled 87.5% detection of trisomy 21 in this high-risk population, for a 14% false positive rate. In a simulated normal population, using a risk cut-off of 1 in 250, 71% detection was achieved for a 7% false positive rate. The combination of NT, f beta HCG and maternal age is a simple, readily available and viable first trimester screening strategy.

Adult↗

The role of nourishment in oogenesis.

Oogenesis in insects is typically a nutrient-limited process, triggered only if sufficient nourishment is available. This nourishment can be acquired during the larval or adult stage, depending on the insect. Timing of food intake will have major effects on mechanisms of hormonal control. When nourishment for eggs is taken primarily by adults, insufficient nutrition inhibits egg development through mechanisms such as inhibition of corpora allata, as seen in Orthoptera and Blattaria. In adult Diptera, lack of protein inhibits release of brain factors that produce reproductive competency or ovarian stimulation. Lepidoptera have been characterized as lacking substantial regulation of oogenesis because egg development is underway at emergence. Many species for which ecological data are available do not mobilize reserves carried over from the larval stage until they feed as adults. The endocrine mechanisms underlying these systems are poorly understood. In many insects, mating and activity can affect nutritional state and therefore oogenesis. Mating can stimulate oogenesis through mobilization of reserves or through nutritional contributions by males to females. Activity, especially flight, and oogenesis can compete for energy. The flight apparatus, especially the muscle, can also compete with oogenesis for protein. Social insects exhibit extreme specializations in oogenesis; females range in fertility from completely sterile to hyperfecund. Food flow within colonies is a major factor regulating fecundity. Finally, maternal nourishment is not needed for oogenesis in parasitoids and pseudoplacental viviparous insects, which produce eggs with little or no yolk. Virtually nothing is known about the endocrine regulation of oogenesis on these insects.

Journal Article↗

Excursion and strain of the median nerve.

Five fresh-frozen transthoracic cadaver specimens (ten upper extremities) were dissected in order to measure excursion and strain of the median nerve at the wrist and the elbow in association with different positions of the shoulder, elbow, wrist, and fingers. The relationships between motions of the joints and excursion and strain at the wrist and the elbow as well as between excursion and strain were also determined. When the wrist was moved from 60 degrees of extension to 65 degrees of flexion, the median nerve at the wrist underwent a mean total excursion of 19.6 millimeters (9.2 +/- 1.38 millimeters [mean and standard deviation] in extension and 10.4 +/- 1.50 millimeters in flexion). The change in strain was not measurable secondary to nerve-wrinkling. Motion of the fingers from hyperextension to full flexion caused a mean total excursion of 9.7 millimeters (6.3 +/- 1.31 millimeters in hyperextension and 3.4 +/- 1.04 millimeters in flexion) and a change in strain of 19.0 per cent. This change in strain became more pronounced when the wrist and the fingers moved in synergy. Such strain, if constant, has been shown to decrease microvascular perfusion and nerve conduction in rabbits. With motion of the shoulder, the mean total excursion of the median nerve at the elbow was 9.1 millimeters (4.4 +/- 1.64 millimeters in abduction and 4.7 +/- 1.81 millimeters in adduction) and the change in strain was 13.3 per cent. With motion of the elbow, the mean total excursion was 12.3 millimeters (12.3 +/- 4.20 millimeters in flexion and zero millimeters in the resting position) and the change in strain was not measurable because of the wrinkle effect in flexion. With motion of the wrist, the mean total excursion was 5.6 millimeters (4.3 +/- 1.95 millimeters in extension and 1.25 +/- 0.81 millimeters in flexion) and the change in strain was 14.8 per cent. With motion of the fingers, the mean total, excursion was 3.4 millimeters (2.6 +/- 1.13 millimeters in hyperextension and 0.80 +/- 0.92 millimeter in flexion) and the change in strain was 10.3 per cent. Motion of the wrist and the fingers induced profound excursion of the median nerve at the wrist, whereas motion of the shoulder and the elbow induced marked excursion of the median nerve at the elbow. These excursions were much more pronounced when a number of joints were moved in a composite manner. Any factor that might limit normal excursion, such as scarring, could induce strains that could adversely affect the function of the median nerve. The finding that the position and movement of the limb had a profound effect on excursion and strain of the median nerve at the wrist and the elbow may aid in the understanding of the pathophysiology of median-nerve neuropathy.

Cadaver↗

The role of N-methyl-D-aspartate receptors in the regulation of physiologically released dopamine.

In vivo voltammetry was used to measure changes in ascorbate, which are an index of changes in the release of glutamate, and microdialysis was used to measure changes in dopamine in the striatum of freely moving rats. A 5 min tail pinch produced a rapid rise in striatal ascorbate paralleled by an increase in motor activity and a slower, more prolonged rise in dopamine. Systemic administration of ketamine or dizocilpine maleate, non-competitive antagonists of the N-methyl-D-aspartate glutamate receptor, produced an increase in the basal level of ascorbate but not dopamine; however, the tail pinch-evoked rise in both ascorbate and dopamine was completely abolished by these drugs. The rise in dopamine was also abolished by local infusion of dizocilpine maleate into the striatum. Local application of N-methyl-D-aspartate produced a dose-dependent increase in dopamine, which was partially reduced in the presence of tetrodotoxin. The results show that the tail pinch-evoked increase in motor activity involves an increase in the release of striatal dopamine which requires the activation of N-methyl-D-aspartate receptors in the striatum. This suggests that phasic increases in striatal dopamine release are triggered by the action of glutamate on dopaminergic nerve terminals.

Animals↗