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Biomedical subjects

D Hawkins

Publications and source records attributed to D Hawkins.

At least 19 recordsLinked to original sources
PubMed2006

Burden of community-onset bloodstream infection: a population-based assessment.

Although community-onset bloodstream infection (BSI) is recognized to be a major cause of morbidity and mortality, there is a paucity of population-based studies defining its overall burden. We conducted population-based laboratory surveillance for all community-onset BSI in the Calgary Health Region during 2000-2004. A total of 4467 episodes of community-onset BSI were identified for an overall annual incidence of 81.6/100,000. The three species, Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae were responsible for the majority of community-onset BSI; they occurred at annual rates of 25.8, 13.5, and 10.1/100,000, respectively. Overall 3445/4467 (77%) episodes resulted in hospital admission representing 0.7% of all admissions to major acute care hospitals. The subsequent hospital length of stay was a median of 9 (interquartile range, 5-15) days; the total days of acute hospitalization attributable to community-onset BSI was 51,146 days or 934 days/100,000 annually. Four hundred and sixty patients died in hospital for a case-fatality rate of 13%. Community-onset BSI is common and has a major patient and societal impact. These data support further efforts to reduce the burden of community-onset BSI.

Adolescent↗
PubMed2006

Interactions between metabolic status, pre-breeding protein supplementation, uterine pH, and embrionic mortality in ewes: preliminary observations.

The effect of prebreeding short-term protein supplementation level (PL) and body condition (BC) on fertility rate (FERT,%), uterine pH and embryonic mortality (EMORT,%) in sheep, was evaluated. Multiparous Rambouillet ewes at low BC (LC; n = 6, 62.7+/-1.7 kg) or high BC (HC; n = 6, 71.9 +/-1.7 kg), received, within BC, one of two levels of ruminally undegradable protein: low (LP, 14 g/ewe per day) and high (HP, 30 g/ewe per day). Once the animals were euthanized, corpus luteum number (CLN), as an indicator of ovulation rate, was registered and uterine horns were irrigated to recover embryonic tissue plus associated membranes as well as to measure uterine pH (UpH). While EMORT- 1 considered a nonadjusted relationship between the number of embryos and CLN, EMORT-2 considered an analysis of covariance using CLN as the covariate. The HP-supplemented ewes had the lowest FERT (p = 0.06; 100% vs 50%) and the highest EMORT (EMORT-1, 16.6% vs 53.8%, p = 0.08; EMORT-2, 52.0% vs 14.5%, p = 0.07) when compared to the LP-supplemented ewes. Neither BC nor PL affected CLN, CL weight or P4 release (p > 0.10). While the lowest UpH (p = 0.04) was observed in the HP-supplemented ewes, this group also showed the lowest fertility and the highest embryonic mortality.

Animals↗
PubMed2005

Biological effects of helium-neon laser irradiation on normal and wounded human skin fibroblasts.

OBJECTIVE: This study aimed to investigate a number of structural, cellular, and molecular responses to heliumneon (632.8 nm) laser irradiation following a single dose of 0.5, 2.5, 5, or 10 J/cm2 on normal and wounded human skin fibroblasts. BACKGROUND DATA: Low-level laser therapy (LLLT) is a form of phototherapy, involving the application of low-power monochromatic and coherent light to injuries and lesions to stimulate healing. 1 This therapy has been successfully used for pain attenuation and to induce wound healing in nonhealing defects. 2 METHODS: Changes in normal and wounded fibroblast cell morphology were evaluated by light microscopy. Cellular parameters evaluated cell proliferation, cell viability, and cytotoxicity while molecular parameters assessed the extent of DNA damage. RESULTS: The results clearly demonstrate that LLLT has an effect on normal and wounded(3) human skin fibroblasts. The parameters showed that doses of 0.5, 2.5, 5, and 10 J/cm2 were sufficient to produce measurable changes in fibroblast cells. CONCLUSION: A dose of 10 J/cm2 appeared to produce a significant amount of cellular and molecular damage, which could be an important consideration for other therapies, such as photodynamic therapy.

Cell Proliferation↗
PubMed2005

Low level laser therapy (LLLT) as an effective therapeutic modality for delayed wound healing.

Low level laser therapy (LLLT) is a form of phototherapy that involves the application of low power monochromatic and coherent light to injuries and lesions. It has been used successfully to induce wound healing in nonhealing defects. Other wounds treated with lasers include burns, amputation injuries, skin grafts, infected wounds, and trapping injuries. The unique properties of lasers create an enormous potential for specific therapy of skin diseases. As with any new device, the most efficacious and appropriate use requires an understanding of the mechanisms of light interaction with tissue as well as the properties of the laser itself.

Diabetes Complications↗
PubMed2004

Age is a risk factor for chemotherapy-induced hepatopathy with vincristine, dactinomycin, and cyclophosphamide.

PURPOSE: To evaluate the spectrum of and determine the risk factors for the development of liver toxicity (hepatopathy) after therapy with vincristine, dactinomycin, and cyclophosphamide (VAC) for rhabdomyosarcoma in children and adolescents. PATIENTS AND METHODS: We prospectively captured all events of hepatopathy occurring on the ongoing Children's Oncology Group intermediate risk protocol, D9803, for children with rhabdomyosarcoma. Patients enrolled onto this trial were randomly assigned to receive either VAC alone or VAC alternating with vincristine, topotecan, and cyclophosphamide. In addition, we reviewed the toxicity database and requested additional information for all patients with elevated bilirubin or transaminase levels. Risk factors were analyzed. RESULTS: Of 339 patients enrolled through August 2002, 18 developed hepatopathy. All events were captured by mandated toxicity reporting and filing of MedWatch forms, with no additional cases found after the additional search of the database. Four children died after developing this toxicity. All cases occurred after cycles of VAC (n = 16) or vincristine and cyclophosphamide with concomitant abdominal radiotherapy (n = 2). The onset of hepatopathy was 5 to 16 days from the start of a treatment cycle. For the 89 patients under 36 months of age, the risk of hepatopathy was 15%, with two deaths. For the 239 children 3 years of age or older, the risk for hepatopathy was 4%, with two deaths. CONCLUSION: The greatest risk factor for development of hepatopathy after VAC therapy was age. Dose modifications for younger children receiving VAC therapy are recommended.

Age Factors↗
PubMed2003

Is increased surveillance for asymptomatic syphilis in an HIV outpatient department worthwhile?

OBJECTIVES: Syphilis outbreaks have recently been reported in the United Kingdom, some of which have included cohorts of HIV positive individuals. As a result we commenced 3 monthly screening of syphilis serology (STS) for HIV positive patients having routine follow up blood tests. We assessed if there was an increased number of individuals being screened and also whether the screening programme was diagnosing early cases of syphilis. METHODS: Data from a 1 year period following introduction of screening (May 2001) were analysed and compared with data from the same period last year. The case notes of patients with a positive VDRL were reviewed to establish, firstly, whether these represented new diagnoses and, secondly, whether patients were asymptomatic at the time of screening. RESULTS: 2670 patients had at least one CD4 count measured in the period (surrogate for patients having routine bloods). Of these, 2266 patients had STS performed (85%). 38 patients had a positive VDRL. Of these, 20 were confirmed as having early syphilis which was asymptomatic at the time of screening. Six asymptomatic cases were also confirmed with newly positive TPPAs and a negative VDRL. These 26 asymptomatic cases represent 29% of all cases of early syphilis diagnosed in our department and 50% of cases in the HIV positive cohort. CONCLUSION: With intensive surveillance significant numbers of cases of asymptomatic early syphilis are being identified in a group of HIV individuals under routine follow up, at an earlier stage than would otherwise have been the case. This presents an opportunity to intervene not only to prevent clinical illness but also to institute infection control measures.

AIDS-Related Opportunistic Infections↗
PubMed2002

Orofacial rhabdomyosarcoma in neonates and young children: a review of literature and management of four cases.

Rhabdomyosarcoma (RMS) is an aggressive malignant skeletal muscle neoplasm arising from embryonal mesenchyme. It accounts for over 50% of all pediatric soft tissue sarcomas. The head and neck region is the most common site for this tumor in children. Neonatal presentation of this tumor is rare. We present the management of one neonatal case and three additional cases of orofacial RMS in children under the age of 7 years. All four patients were seen in the department of oral and maxillofacial surgery at Children's Hospital and Regional Medical Center (CHRMC) in Seattle between 1992-2000. Three of the four cases were alveolar RMS and one was botryoid sub-type of embryonal RMS. Three patients were treated with a combination of surgery, chemotherapy and radiation, while the patient with botryoid RMS was treated with surgery and chemotherapy only. The patient with congenital RMS died at 2.5 years of age due to recurrent metastatic disease. The other three patients are alive without evidence of recurrent with a mean follow up was 5.5 years (range 2.5-8.5 years). We discuss the current management, diagnosis, biological behavior, histopathology, prognosis and survival of head and neck RMS in neonates and young children.

Child↗
PubMed2002

Penile intraepithelial neoplasia: clinical spectrum and treatment of 35 cases.

BACKGROUND: Penile intraepithelial neoplasia (PIN) is the term used to describe erythroplasia of Queyrat (EQ), Bowen's disease (BD) and bowenoid papulosis (BP). These conditions are distinct clinical entities and have different epidemiological and aetiological associations and prognostic implications. OBJECTIVES: To describe the presentation and treatment of patients with PIN. METHODS: Thirty-five patients presenting with PIN over a 7-year period are described. RESULTS: Our observations include: (i) patients with BP are younger than those with EQ or BD and sometimes have a history of immunosuppression; (ii) patients with BP usually have a history or clinical evidence of previous genital human papillomavirus infection; (iii) patients with EQ often have a concurrent penile dermatosis (lichen sclerosus or lichen planus); (iv) patients with PIN are usually uncircumcised; and (v) response to treatment of BP depends on the integrity of the immune system. CONCLUSIONS: We recommend vigorous treatment of all patients with PIN, including circumcision. Smoking should be actively discouraged. Patients should have life-long follow-up and partners of patients with BP should be screened for other forms of intraepithelial neoplasia (cervical and anal).

Adult↗
PubMed2002

A biomechanical review of factors affecting rowing performance.

This review analyses rowing by linking the biological and mechanical systems that comprise the rowing system. Blade force was found to be the only propulsive force to counter the drag forces, consisting of both air drag and hydrodynamic drag, acting on the system. Vertical oscillations of the shell are shown to have minimal impact on system dynamics. The oar acts as the link between the force generated by the rower and the blade force and transmits this force to the rowing shell through the oarlock. Blade dynamics consist of both lift and drag mechanisms. The force on the oar handle is the result of a phased muscular activation of the rower. Oar handle force and movement are affected by the joint strength and torque-velocity characteristics of the rower. Maximising sustainable power requires a matching of the rigging setup and blade design to the rower's joint torque-velocity characteristics. Coordination and synchrony between rowers in a multiple rower shell affects overall system velocity. Force-time profiles should be better understood to identify specific components of a rower's biomechanics that can be modified to achieve greater force generation.

Biomechanical Phenomena↗
PubMed2001

Regulation of type-II collagen gene expression during human chondrocyte de-differentiation and recovery of chondrocyte-specific phenotype in culture involves Sry-type high-mobility-group box (SOX) transcription factors.

During ex vivo growth as monolayer cultures, chondrocytes proliferate and undergo a process of de-differentiation. This process involves a change in morphology and a change from expression of chondrocyte-specific genes to that of genes that are normally expressed in fibroblasts. Transfer of the monolayer chondrocyte culture to three-dimensional culture systems induces the cells to re-acquire a chondrocyte-specific phenotype and produce a cartilaginous-like tissue in vitro. We investigated mechanisms involved in the control of the de-differentiation and re-differentiation process in vitro. De-differentiated chondrocytes re-acquired their chondrocyte-specific phenotype when cultured on poly-(2-hydroxyethyl methacrylate) (polyHEMA) as assayed by morphology, reverse transcriptase PCR of chondrocyte-specific mRNA, Western-blot analysis and chondrocyte-specific promoter activity. Essentially, full recovery of the chondrocyte-specific phenotype was observed when cells that had been cultured for 4 weeks on plastic were transferred to culture on polyHEMA. However, after subsequent passages on plastic, the phenotype recovery was incomplete or did not occur. The activity of a gene reporter construct containing the promoter and enhancer from the human type-II collagen gene (COL2A1) was modulated by the culture conditions, so that its transcriptional activity was repressed in monolayer cultures and rescued to some extent when the cells were switched to polyHEMA cultures. The binding of Sry-type high-mobility-group box (SOX) transcription factors to the enhancer region was modulated by the culture conditions, as were the mRNA levels for SOX9. A transfected human type-II collagen reporter construct was activated in de-differentiated cells by ectopic expression of SOX transcription factors. These results underscore the overt change in phenotype that occurs when chondrocytes are cultured as monolayers on tissue-culture plastic substrata.

Animals↗
PubMed2001

Structure-activity relationships in flexible protein domains: regulation of rho GTPases by RhoGDI and D4 GDI.

The guanine dissociation inhibitors RhoGDI and D4GDI inhibit guanosine 5'-diphosphate dissociation from Rho GTPases, keeping these small GTPases in an inactive state. The GDIs are made up of two domains: a flexible N-terminal domain of about 70 amino acid residues and a folded 134-residue C-terminal domain. Here, we characterize the conformation of the N-terminal regions of both RhoGDI and D4GDI using a series of NMR experiments which include (15)N relaxation and amide solvent accessibility measurements. In each protein, two regions with tendencies to form helices are identified: residues 36 to 58 and 9 to 20 in RhoGDI, and residues 36 to 57 and 20 to 25 in D4GDI. To examine the functional roles of the N-terminal domain of RhoGDI, in vitro and in vivo functional assays have been carried out with N-terminally truncated proteins. These studies show that the first 30 amino acid residues are not required for inhibition of GDP dissociation but appear to be important for GTP hydrolysis, whilst removal of the first 41 residues completely abolish the ability of RhoGDI to inhibit GDP dissociation. The combination of structural and functional studies allows us to explain why RhoGDI and D4GDI are able to interact in similar ways with the guanosine 5'-diphosphate-bound GTPase, but differ in their ability to regulate GTP-bound forms; these functional differences are attributed to the conformational differences of the N-terminal domains of the guanosine 5'-diphosphate dissociation inhibitors. Therefore, the two transient helices, appear to be associated with different biological effects of RhoGDI, providing a clear example of structure-activity relationships in a flexible protein domain.

Amides↗