Taking medicines: concordance is not compliance.
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Choice Behavior↗
Biomedical subjects
M Harris
Publications and source records attributed to M Harris.
Constitutive activation of sonic hedgehog signaling in the chicken mutant talpid(2): Shh-independent outgrowth and polarizing activity.
We have examined the developmental properties of the polydactylous chicken mutant, talpid(2). Ptc, Gli1, Bmp2, Hoxd13, and Fgf4 are expressed throughout the anteroposterior axis of the mutant limb bud, despite normal Shh expression. The expression of Gli3, Ihh, and Dhh appears to be normal, suggesting that the Shh signaling pathway is constitutively active in talpid(2) mutants. We show that preaxial talpid(2) limb bud mesoderm has polarizing activity in the absence of detectable Shh mRNA. When the postaxial talpid(2) limb bud (including all Shh-expressing cells) is removed, the preaxial cells reform a normal-shaped talpid(2) limb bud (regulate). However, a Shh-expressing region (zone of polarizing activity) does not reform; nevertheless Fgf4 expression in the apical ectodermal ridge is maintained. Such reformed talpid(2) limb buds develop complete talpid(2) limbs. After similar treatment, normal limb buds downregulate Fgf4, the preaxial cells do not regulate, and a truncated anteroposterior deficient limb forms. In talpid(2) limbs, distal outgrowth is independent of Shh and correlates with Fgf4, but not Fgf8, expression by the apical ectodermal ridge. We propose a model for talpid(2) in which leaky activation of the Shh signaling pathway occurs in the absence of Shh ligand.
Animals↗
The effect of tranexamic acid (cyclokapron) on blood loss after third molar extraction under a day case general anaesthetic.
OBJECTIVE: To evaluate the effect of pre-operative administration of tranexamic acid in preventing prolonged post-operative bleeding in day-case patients. Day-case admission is highly appropriate for dentoalveolar surgery but one of the problems is prolonged post-operative haemorrhage which at times may delay discharge or necessitate readmission to hospital. Tranexamic acid has traditionally been used to treat post-operative bleeding. DESIGN: A prospective double-blind randomised study. SETTING: Eastman Dental Hospital, London. SUBJECTS AND METHODS: Fifty-six patients were consecutively selected from healthy adult volunteers who were having third molar extraction in the day case unit of the Eastman Dental Hospital over a period of 22 weeks. Tranexamic acid (25 mg/kg) or normal saline was administered intravenously at induction by the anaesthetist and blood loss was measured intra- and post-operatively. RESULTS: A significant reduction (P = 0.023) in the post-operative blood loss was found in the tranexamic acid group. However, there was no significant difference in the intra-operative (P = 0.4) and the overall total blood loss (P = 0.21). No patient receiving tranexamic acid required readmission to control prolonged bleeding, or suffered any side effects from the drug. CONCLUSION: This study has shown that one intravenous pre-operative dose of tranexamic acid is effective in preventing excessive post-operative bleeding in patients undergoing third molar extraction under a day case general anaesthetic and therefore facilitates safe discharge from hospital.
Adolescent↗
HIV: a new role for Nef in the spread of HIV.
The HIV Nef protein downregulates the cell-surface expression of the HIV receptor glycoprotein CD4, but the significance of this event has remained obscure. Recent data suggest that Nef reduces cell-surface CD4 to promote the efficient spread of the virus.
CD4 Antigens↗
A randomized clinical trial of supported employment for inner-city patients with severe mental disorders.
BACKGROUND: This experiment evaluated the effectiveness of 2 approaches to vocational services for persons with severe mental disorders: (1) individual placement and support (IPS), in which employment specialists within the mental health center help patients to obtain competitive jobs and provide ongoing support, and (2) enhanced vocational rehabilitation (EVR), in which stepwise vocational services are delivered by rehabilitation agencies. METHODS: One hundred fifty-two unemployed, inner-city patients with severe mental disorders who expressed interest in competitive employment were randomly assigned to IPS or EVR and followed up for 18 months. Following diagnostic assessment, participants were assessed with standardized measures of work, income, self-esteem, quality of life, symptoms, and hospitalization at baseline and at 6-, 12-, and 18-month follow-up evaluations. Employment was tracked monthly and job satisfaction every 2 months. RESULTS: During the 18-month study, participants in the IPS program were more likely to become competitively employed (60.8% vs 9.2%) and to work at least 20 hours per week in a competitive job (45.9% vs 5.3%), whereas EVR participants had a higher rate of participation in sheltered employment (71.1% vs 10.8%). Total earnings, job satisfaction, and nonvocational outcomes were similarly improved for both groups. CONCLUSION: The IPS model of supported employment is more effective than standard, stepwise EVR approaches for achieving competitive employment, even for inner-city patients with poor work histories and multiple problems.
Adult↗
Effect of ultrasound on the production of IL-8, basic FGF and VEGF.
Therapeutic angiogenesis is the controlled induction or stimulation of new blood vessel formation to reduce unfavourable tissue effects caused by local hypoxia and to enhance tissue repair. The effects of ultrasound on wound healing, chronic ulcers, fracture healing and osteoradionecrosis may be explained by the enhancement of angiogenesis. The aim of this study was to identify which cytokines and angiogenesis factors are induced by ultrasound in vitro. Two ultrasound machines were evaluated, a "traditional" (1 MHz, pulsed 1:4, tested at four intensities), and a "long wave" machine (45 kHz, continuous, also tested at four intensities). The ultrasound was applied to human mandibular osteoblasts, gingival fibroblasts and peripheral blood mononuclear cells (monocytes). The following cytokines and angiogenesis factors were assayed by ELISA techniques: interleukin-1beta(IL-1beta), IL-6, tumour necrosis factor alpha (TNF-alpha), IL-8, fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF).A slight stimulation of IL-1beta was noted in all cell types. There was no difference in the IL-6 and TNF-alpha levels. The angiogenesis-related cytokines, IL-8 and bFGF, were significantly stimulated in osteoblasts, and VEGF was significantly stimulated in all cell types. Both ultrasound machines produced similar results, and the optimum intensities were 0.1 and 0. 4 W/cm2 (SATA) with 1 MHz ultrasound, and 15 and 30 mW/cm2 (SATA) with 45 kHz ultrasound.The results show that therapeutic ultrasound stimulates the production of angiogenic factors such as IL-8, bFGF and VEGF. This may be one of the mechanisms through which therapeutic ultrasound induces angiogenesis and healing.
Angiogenesis Inducing Agents↗
In vitro effects of therapeutic ultrasound on cell proliferation, protein synthesis, and cytokine production by human fibroblasts, osteoblasts, and monocytes.
PURPOSE: The aim of this study was to evaluate several in vitro effects of ultrasound that could revert or prevent the hypoxia, hypovascularity, and hypocellularity observed in osteoradionecrosis. MATERIALS AND METHODS: Two different ultrasound machines were evaluated, a "traditional" (1 MHz, pulsed 1:4) and a "long wave" (45 kHz, continuous) machine, tested at various intensities. Ultrasound was applied to human gingival fibroblasts, mandibular osteoblasts, and monocytes. The assays performed were cell proliferation (DNA synthesis), collagen and noncollagenous protein (NCP) synthesis, and cytokine production (ELISA) involving interleukin (IL) 1 beta, IL-6, and IL-8, tumor necrosis factor alpha (TNF alpha), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF). RESULTS: Both ultrasound machines induced increased cell proliferation in fibroblasts and osteoblasts, between 35% and 52%. The collagen and NCP synthesis were also significantly enhanced to levels up to 112%, the best results being with the 45-kHz machine. The ELISA results showed a slight stimulation of IL-1 beta by all cell types; there was no difference in IL-6 and TNF alpha levels. The angiogenesis-related cytokines evaluated were significantly stimulated: IL-8 and bFGF production was enhanced in osteoblasts, and VEGF production was stimulated in all three cell types. Both ultrasound machines produced the same results, with the recommended intensities being 15 and 30 mW/cm2(SA) for the 45-kHz ultrasound, and 0.1 and 0.4 W/cm2(SAPA) for the 1 MHz ultrasound. CONCLUSIONS: Therapeutic ultrasound induces in vitro cell proliferation, collagen/NCP production, bone formation, and angiogenesis. These findings support its use in prospective clinical trials for the prevention and treatment of osteoradionecrosis.
Analysis of Variance↗
The effect of posture and anesthesia on the occlusal relationship in orthognathic surgery.
PURPOSE: This study investigated the differences in centric occlusion (intercuspal-CO) and centric relation contact position (CR) in patients in an upright and supine posture when conscious and when supine under general anesthesia to rationalize planning for complex bimaxillary osteotomies. PATIENTS AND METHODS: Twenty-four men and 37 women, with a mean age of 24.7 +/- 4.5 years were included in this study. Occlusal records on each patient included 1 in CO and 3 in CR in each of the following postures: conscious upright, conscious supine, and anesthetized supine. Casts were mounted in the Denar Mark II articulator and transferred to the Denar Vericheck (Denar Corp, Anaheim, CA) recording tool for measurements. The centric relation displacement vectors (CO-CR) were projected in various axes by 3D graphics. RESULTS: The upright conscious CO-CR (mm) vectors were significantly different from both the supine conscious and anesthetized positions in the anteroposterior plane. The difference in the vertical plane was only significant in Class II division 1 patients. CONCLUSION: The posterior change in centric relation explains the apparent occlusal discrepancies created by rigid fixation of the mandible applied in the supine anesthetized position. By taking the CR records in the supine conscious position, the "loss" of maxillary advancement can be avoided.
Adult↗
Low-grade endometrial stromal sarcoma with intracardiac extension. Evolution of extensive smooth muscle differentiation and usefulness of immunohistochemistry for its recognition and distinction from intravenous leiomyomatosis.
This case, a rare example of low-grade endometrial stroma sarcoma with extensive smooth muscle differentiation which extended to the inferior vena cava and cardiac chambers closely resembling intravenous leiomyomatosis grossly and microscopically, illustrates the importance of extensive sectioning and the usefulness of immunohistochemistry. Although spindle cell components arranged in interlacing bundles consistent with smooth muscle differentiation were recognizable in the primary tumor (on retrospective review), extensive smooth muscle differentiation in the recurrent tumors masked prototypical morphologic features of stromal sarcoma and only small neoplastic stromal components were preserved in limited areas, leading to initial failure to distinguish the lesion from intravenous leiomyomatosis. The immunophenotyping disclosed two distinct cell populations in the tumor: i.e. vimentin-positive and smooth muscle marker negative stromal cells, and vimentin-negative spindle-shaped desmin-positive smooth muscle cells. Our observation suggests that the predominance of a smooth muscle component in such a tumor can be misleading and does not always warrant a diagnosis of intravenous leiomyomatosis, nor does it predict a benign clinical course. This case also provides an insight into the relationship of the endometrial stroma and myometrium, and their cell of origin and the histogenesis of endometrial stromal sarcoma.
Actins↗
Developments in early lexical comprehension: a comparison of parental report and controlled testing.
Six children were studied from the age of 0;6 to 1;6 in order to chart their developing comprehension vocabularies from the first to the 100th word. Observational data were used in the first instance to identify newly comprehended words and then controlled testing was carried out for each word to confirm and expand the observational data. Comprehension of words was divided into four categories--object names, context-bound object words, action words and personal names. The relative frequency of the different categories of word was found to change with the size of the comprehension vocabulary as personal names decreased in importance and both object names and action words became increasingly more common. There was considerable variation among the six children especially in the proportion of object names and action words that they understood but vocabulary composition became highly stable between 60 and 100 words.
Age Factors↗
Further investigation of the role of HLA-DPB1 in adult Hodgkin's disease (HD) suggests an influence on susceptibility to different HD subtypes.
It has been suggested in a number of studies that susceptibility to adult Hodgkin's disease (HD) is influenced by the HLA class II region, and specifically by alleles at the HLA-DPB1 locus. Since HD is diagnostically complex, it is not clear whether different HLA-DPB1 alleles confer susceptibility to different HD subtypes. To clarify this we have extended a previous study to type DPB1 alleles in 147 adult HD patients from a single centre. We have analysed patients with nodular sclerosing (NS), mixed cellularity (MC) or lymphocyte predominant (LP) HD, and gender in relation to HLA-DPB1 type, in comparison with 183 adult controls. The results confirmed previously reported associations of DPB1*0301 with HD susceptibility (relative risk (RR) = 1.42; 95% confidence interval (CI) 0.86-2.36) and DPB1*0201 with resistance to HD (RR = 0.49; CI 0.27-0.90). However, analysis by HD subtype and gender showed that *0301-associated susceptibility was confined to females with HD (RR = 2.46; CI 1.02-5.92), and *0201-associated resistance to females with NS-HD (RR = 0.28; CI 0.10-0.79). Susceptibility to NS-HD was also associated in females with *1001 (RR = 11.73; CI 1.32-104.36), and resistance with *1101 (RR = 0.08; CI 0.01-0.65). In contrast, susceptibility to LP-HD was associated in males with *2001 (RR = 32.14; CI 3.17-326.17), and to MC-HD with *3401 (RR = 16.78; CI 2.84-99.17). Comparison of DPB1-encoded polymorphic amino-acid frequencies in patients and controls showed that susceptibility to MC-HD was associated with Leucine at position 35 of DPB1 (RR = 8.85; CI 3.04-25.77), Alanine-55 (RR = 15.17; CI 2.00-115.20) and Valine-84 (RR = 15.94; CI 3.55-71.49). In contrast, Glutamic acid 69 was significantly associated with resistance to MC-HD (RR = 0.14; CI 0.03-0.60). Certain DPB1 alleles and individual DPbeta1 polymorphic amino acid residues may thus affect susceptibility and resistance to specific HD subtypes. This may be through their influence on the binding of peptides derived from an HD-associated infectious agent, and the consequent effect on immune responses to the agent.
Adolescent↗
Management of an unstable lumbar fracture with a laminar split.
This is a case report describing the injury sustained by a 36-year-old man injured in a motorcycle crash who sustained a fracture dislocation of L2 upon L3, associated with a split in the lamina of L3. His neurologic lesion was T12 ASIA B: with a motor score of 52 but with preservation of sensory function (sensory score 96) in most parts of his lower extremities. He also suffered a lower extremity fracture. Imaging of the spine is presented showing a multiplanar fracture associated with translation and with a defect in the lamina that may be seen in certain AO type B or type C fractures, that may entrap the lumbar spinal nerve roots. Discussants of this case comment on the classification and clinical significance of this fracture pattern. and present their operative approaches, both for management of this particular fracture pattern and for any associated dural tear. The issues of steroid use and the place of rehabilitation are also discussed.
Accidents, Traffic↗
Extra-medullary myeloid tumour (granulocytic sarcoma) is often misdiagnosed: a study of 26 cases.
AIMS: To describe the clinicopathological and immunophenotypic features of 26 cases of extra-medullary myeloid tumour (EMMT)/granulocytic sarcoma, which remains poorly recognized and is frequently confused with malignant lymphoma, and to discuss the main diagnostic problems experienced by the referring pathologist. METHODS AND RESULTS: Haematoxylin and eosin (H & E) sections of 26 cases of EMMT were re-examined. Immunostains for myeloperoxidase, lysozyme, neutrophil elastase, LCA, CD79a, CD20, CD43, CD45RO, CD3, CD30, CD15, CD68, MAC387, VS38C, MIC2, and the Leder stain for naphthol-ASD-chloroacetate esterase were performed on all cases. Clinical and follow-up data were obtained through a questionnaire to the referring pathologist or from the notes of the patients where available. In the 10 cases with known myeloproliferative disease, the initial diagnosis was correct in 10 whereas all cases presenting with EMMT without a previous history of myeloproliferative disorder had an initial incorrect diagnosis. The most common suggested diagnosis was that of a non-Hodgkin's lymphoma. The morphology of the tumours varied from well differentiated which included all stages of myeloid differentiation to poorly differentiated or blastic showing little or no evidence of myeloid differentiation. The proportion of positive cells for each stain varied. Chloroacetate esterase, myeloperoxidase and CD15 stained a large proportion of cells of the majority of the well differentiated tumours and a smaller proportion of the poorly differentiated/blastic tumours with very focal staining of some of the cases. Lysozyme and CD43 were the most sensitive of the markers staining a large proportion of cells of the majority of the tumours in both groups. Neutrophil elastase was the least sensitive of the markers of myeloid differentiation. CD79a, CD20, CD3 and CD30 were negative in all cases. CD43 was positive in all cases. CD68 stained a substantial number of cells in the majority of tumours. A smaller proportion of the tumours stained with MAC387. Four of the tumours showed positivity for MIC2. One tumour was positive for VS38C. CONCLUSION: This series documents continuing difficulties in the diagnosis of EMMT. Even well differentiated tumours are frequently mistakenly diagnosed as malignant lymphomas when they present without any history of antecedent myeloproliferative disorder. Careful evaluation of morphology for evidence of myeloid differentiation and a high index of suspicion when confronted with a less differentiated neoplasm are required to avoid this important diagnostic error. We suggest that a panel which includes chloroacetate-esterase, myeloperoxidase, lysozyme and CD43, together with other B- and T-lineage markers, in particular CD79a and CD3 should be used to confirm the diagnosis.
Adolescent↗
Evaluation of a self-paced education package on violence against women for rural community-based health workers.
There are no reported education programs specifically focusing on the needs of rural health workers in the area of violence against women. The most commonly reported contact sought by women experiencing injuries and health problems associated with violence and abuse is with health workers. Women report a failure by health workers to make direct enquires, which may be due to their lack of education and confidence in responding to these issues. A convenience sample of 60 community-based rural health workers from a range of occupations and settings within the Wide Bay Health Region, Queensland, participated in the evaluation of a self-paced, distance education package on violence against women. The package contained seven modules. These included written and audio tape material, and activities that together formed a community development approach to addressing the needs in the participants' local community. Participants were given a mentor and teleconference support during the 8 weeks allocated to complete the package. A pre- and post-course evaluation, containing quantitative and qualitative data, was completed. Analysis of the quantitative data identified significant changes in participants' knowledge, and the qualitative data highlighted an increased sense of confidence in assisting women, forming support networks and using resources more effectively. Participants reported the most useful aspects of the package were: (i) modular- and user-friendly format; (ii) flexible, practical, health-focused content; and (iii) real world examples.
Adult↗
Cerebral responses to pain in patients suffering acute post-dental extraction pain measured by positron emission tomography (PET).
Previous studies with normal volunteers have demonstrated distributed cortical responses to experimental heat pain within a network of structures. The network includes the insula, anterior cingulate, prefrontal, inferior parietal and somatosensory cortices. Patients suffering from chronic nociceptive pain following rheumatoid arthritis (RA) have shown damped central responses to experimental heat pain applied to the back of the right hand. In this study of patients with acute, left-sided, post-molar-extraction (surgical) pain, we assessed the cortical responses to experimental heat pain, applied to the back of the right hand, using positron emission tomography (PET), and compared the responses with a previously reported control group and the RA group. In response to the experimental heat pain, the surgical group indicated significantly increased regional cerebral blood flow in the prefrontal cortex [Brodman's area (BA) 44] ipsilateral to the heat stimulus. Contralateral increases were detected in the putamen and transverse temporal gyrus (BA 40/41/42) with bilateral increases in the insular cortex. Compared to the control and RA group, there were significantly reduced responses in the anterior cingulate (BA 24), pre-frontal medial, and orbito-frontal (BA 9/10/32/47) cortices. These results suggest that relatively discrete regions of the cerebral cortex are responsible for acute nociceptive processing during an acute inflammatory episode. The reduced frontal and anterior cingulate responses to the experimental heat pain (applied to the right hand) during acute inflammatory pain (left jaw) illustrates cortical modulation of nociceptive processing that may be related to non-somatotopic, bilateral, nociceptive inputs to these areas. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.
Journal Article↗
Use of intra-articular morphine for postoperative analgesia following TMJ arthroscopy.
Recent studies have suggested that giving opioids locally into inflamed tissue may cause analgesia. This antinociceptive effect has been attributed to the interaction of the drug with opioid receptors upregulated by inflammation in the peripheral tissues. We have compared the analgesic effect of intra-articular morphine with that of normal saline and a combination of morphine and its antagonist naloxone after arthroscopy of the temporomandibular joint (TMJ). Twenty-one patients took part in a randomized controlled double-blind trial and received one of these three solutions at the end of operation. The pain scores, time to the first request for analgesia, and the analgesic consumption of the patients in the three groups did not differ significantly at any time during the study period.
Adult↗
A prospective study of computer-aided design and manufacture of titanium plate for cranioplasty and its clinical outcome.
The use of computerized three dimensional imaging and automated milling of models to produce accurate titanium plates for the reconstruction of craniofacial defects is described. A total of 148 patients have had extensive calvarial defects repaired using this (computer aided design and manufacture) technique developed in our unit. Of these, 141 were repaired secondarily (delayed cranioplasty), whilst seven were repaired immediately following craniectomy (single stage cranioplasty). All cases were assessed for accuracy of fit, restoration of natural skull contour and aesthetics. Seventy-two patients were reviewed after 1 year to determine the effect on adverse preoperative symptoms. Of the plates 97% had an excellent or good intraoperative fit. The modal insertion time was only 15 minutes. Postoperatively 98% resulted in the restoration of natural skull shape and symmetry. After 1 year, 82% of patients had complete resolution or diminution in severity of the adverse symptoms. A staphylococcus infection necessitated the temporary removal of one plate.
Adolescent↗
Epidemiology and predictors of post-concussive syndrome after minor head injury in an emergency population.
OBJECTIVE: To determine if clinical variables or neurobehavioural test (NBT) scores obtained in the ED within 24 hours of minor head injury (MHI) predict the development of postconcussive syndrome (PCS). METHODS: Prospective, observational study of 71 MHI patients and 60 orthopaedic controls. MHI defined as loss of consciousness < 10 minutes or amnesia, GCS 15, no skull fracture or new neurologic focality on PE, and no brain injury on CT (if done). All patients received a seven part NBT battery in the ED. Telephone follow-up was done at 1, 3 and 6 months to determine if patients met the DSM IV definition of PCS. ANALYSIS: Stepwise, multivariate, logistic regression. RESULTS: Predictors of PCS at 1 month were female gender (OR = 7.8; 95% CI = 41.6, 1.98), presence of both retrograde and anterograde amnesia (OR = 0.055; CI = 0.002, 0.47), Digit Span Forward Scores (OR = 0.748; CI = 0.52, 1.03) and Hopkins Verbal Learning A scores (OR = 0.786; CI = 0.65, 0.91); at 3 months, presence of both retrograde and anterograde amnesia (OR = 0.13; CI = 0.0, 0.93), Digit Span Forward Scores (OR = 0.744; CI = 0.58, 0.94). No variables fit the model at 6 months. 92% of males scoring > 25 on Hopkins Verbal Learning A did not have PCS at 1 month, and 89% of females scoring < 9 on Digit Span Forward did have PCS at 1 month. CONCLUSIONS: Gender and two NBTs can help predict PCS after MHI.
Adult↗