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Biomedical subjects

D Stokes

Publications and source records attributed to D Stokes.

At least 19 recordsLinked to original sources

Dealing with lead in Broken Hill--trends in blood lead levels in young children 1991-2003.

The objective of the study was to investigate trends in blood lead concentrations in preschool children between 1991 and 2003, as part of the evaluation strategy of a public health lead management program in Broken Hill, Australia. Since 1991, all Broken Hill children aged 1-4 years have been offered at least annual blood lead screening as part of a community-wide lead management program. Recruitment of children was promoted throughout the period using local media and distribution of promotional material from health care centres and preschool, childcare, and educational facilities around the city. Venous blood samples were collected using standard procedures and analyses were subjected to internal and external quality control programs. Because the frequency distribution of blood lead levels are skewed, geometric rather than arithmetic means were used for comparative purposes. Trend analysis was based on age and sex standardised mean blood lead levels. The number of 1- to 4-year-old children screened ranged between 496 and 948 in any one year and response rates varied between 39% and 73%. The age-sex standardised mean blood lead level decreased from 16.3 microg/dL to 7.1 microg/dL between 1991 and 2003. Overall, blood lead levels declined by 56% over 13 years. These reductions were consistently observed irrespective of age or where a child lived in the town. The rate of decline has slowed since 1997. We conclude that substantial progress has been made in dealing with the lead problem in Broken Hill children, although the rate of decline of blood lead levels has slowed. Continued public health action is still needed to bring the proportion of young children with significantly elevated blood lead levels (>15 microg/dL) down from the 2003 figure of 12% to the NHMRC community-based target for lead in young Australians of 5%.

Child, Preschool↗

Use of lacticin 481 to facilitate delivery of the bacteriophage resistance plasmid, pCBG104 to cheese starters.

AIMS: Use of lacticin 481 to facilitate the conjugal transfer of the bacteriophage resistance plasmid pCBG104 to various starter cultures. METHODS AND RESULTS: A raw milk isolate of Lactococcus was found to harbour determinants for lacticin 481 production and immunity and phage resistance on a plasmid designated pCBG104. The lacticin 481 was successfully used to mobilize the phage resistance determinant to a variety of cheese starters enabling the formation of highly phage resistant starters. In addition, it facilitated the stacking of a number of phage resistance genes, namely a type I restriction modification system, a phage abortive infection system and a phage adsorption blocking system in a single Lactococcus strain without the use of recombinant techniques. The transconjugants were all shown to produce lacticin 481 and to contain the entire 481 operon. Subsequently one transconjugant was selected and successfully used for large-scale cheddar cheese manufacture. CONCLUSIONS: Lacticin 481 could be used as a food-grade selectable marker to facilitate the introduction of advantageous traits to starter cultures for industrial food fermentations. SIGNIFICANCE AND IMPACT OF THE STUDY: Food-grade selectable markers greatly facilitate the introduction of various advantageous traits to starter cultures for industrial food fermentation. Indeed self-cloning which is becoming increasingly important for strain improvement has a requirement for the identification and demonstration of the utility of tools such as lacticin 481.

Bacterial Proteins↗

Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate.

Marrow stromal cells (MSCs) were isolated from bone marrow obtained by aspirates of the iliac crest of normal volunteers. The cells were isolated by their adherence to plastic and then passed in culture. Some of the samples expanded through over 15 cell doublings from the time frozen stocks were prepared. Others ceased replicating after about four cell doublings. The replicative potential of the cells in culture was best predicted by a simple colony-forming assay in which samples from early passages were plated at low densities of about 10 cells per cm2. Samples with high colony-forming efficiency exhibited the greatest replicative potential. The colonies obtained by plating early passage cells at low density varied in size and morphology. The large colonies readily differentiated into osteoblasts and adipocytes when incubated in the appropriate medium. As samples were expanded in culture and approached senescence, they retained their ability to differentiate into osteoblasts. However, the cells failed to differentiate into adipocytes. The loss of multipotentiality following serial passage in culture may have important implications for the use of expanded MSCs for cell and gene therapy.

Bone Marrow Cells↗

Impact of microbiology practice on cumulative prevalence of respiratory tract bacteria in patients with cystic fibrosis.

Investigators participating in the Epidemiologic Study of Cystic Fibrosis project began to collect microbiological, pulmonary, and nutritional data on cystic fibrosis (CF) patients at 180 North American sites in 1994. Part of this study was a survey undertaken in August 1995 to determine microbiology laboratory practices with regard to pulmonary specimens from CF patients. The survey included a section on test ordering, completed by a site clinician, and a section on test performance and reporting, completed by each site's clinical microbiology laboratory staff. Seventy-nine percent of the surveys were returned. There was intersite consistency of microbiology laboratory practices in most cases. The majority of sites follow most of the CF Foundation consensus conference recommendations. There were differences in the frequency at which specimens for culture were obtained, in the use of selective media for Staphylococcus aureus and Haemophilus influenzae, and in the use of a prolonged incubation for Burkholderia cepacia. These variations in practice contribute to prevalence differences among sites and may result in differences in clinical care.

Adolescent↗

Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats--similarities to astrocyte grafts.

Neurotransplantation has been used to explore the development of the central nervous system and for repair of diseased tissue in conditions such as Parkinson's disease. Here, we examine the effects of direct injection into rat brain of human marrow stromal cells (MSCs), a subset of cells from bone marrow that include stem-like precursors for nonhematopoietic tissues. Human MSCs isolated by their adherence to plastic were infused into the corpus striatum. Five to 72 days later, brain sections were examined for the presence of the donor cells. About 20% of the infused cells had engrafted. There was no evidence of an inflammatory response or rejection. The cells had migrated from the injection site along known pathways for migration of neural stem cells to successive layers of the brain. After infusion into the brain, the human MSCs lost their immunoreactivity to antibodies for collagen I. Initially, the human cells continued to stain with antibodies to fibronectin but the region of staining with fibronectin was significantly decreased at 30 and 72 days. The results suggest that MSCs may be useful vehicles for autotransplantation in both cell and gene therapy for a variety of diseases of the central nervous system.

Adult↗

Energy absorption during running by leg muscles in a cockroach

Biologists have traditionally focused on a muscle's ability to generate power. By determining muscle length, strain and activation pattern in the cockroach Blaberus discoidalis, we discovered leg extensor muscles that operate as active dampers that only absorb energy during running. Data from running animals were compared with measurements of force and power production of isolated muscles studied over a range of stimulus conditions and muscle length changes.We studied the trochanter-femoral extensor muscles 137 and 179, homologous leg muscles of the mesothoracic and metathoracic legs, respectively. Because each of these muscles is innervated by a single excitatory motor axon, the activation pattern of the muscle could be defined precisely. Work loop studies using sinusoidal strains at 8 Hz showed these trochanter-femoral extensor muscles to be quite capable actuators, able to generate a maximum of 19-25 W kg-1 (at 25 degreesC). The optimal conditions for power output were four stimuli per cycle (interstimulus interval 11 ms), a strain of approximately 4 %, and a stimulation phase such that the onset of the stimulus burst came approximately half-way through the lengthening phase of the cycle. High-speed video analysis indicated that the actual muscle strain during running was 12 % in the mesothoracic muscles and 16 % in the metathoracic ones. Myographic recordings during running showed on average 3-4 muscle action potentials per cycle, with the timing of the action potentials such that the burst usually began shortly after the onset of shortening. Imposing upon the muscle in vitro the strain, stimulus number and stimulus phase characteristic of running generated work loops in which energy was absorbed (-25 W kg-1) rather than produced. Simulations exploring a wide parameter space revealed that the dominant parameter that determines function during running is the magnitude of strain. Strains required for the maximum power output by the trochanter-femoral extensor muscles simply do not occur during constant, average-speed running. Joint angle ranges of the coxa-trochanter-femur joint during running were 3-4 times greater than the changes necessary to produce maximum power output. None of the simulated patterns of stimulation or phase resulted in power production when strain magnitude was greater than 5 %. The trochanter-femoral extensor muscles 137/179 of a cockroach running at its preferred speed of 20 cm s-1 do not operate under conditions which maximize either power output or efficiency. In vitro measurements, however, demonstrate that these muscles absorb energy, probably to provide control of leg flexion and to aid in its reversal.

Journal Article↗

Managed care and the cystic fibrosis patient.

Since the first published report of mortality in cystic fibrosis in 1969, the median survival among cystic fibrosis patients has risen from 14 to 31 years. The reasons for this improved survival are complex and include earlier diagnosis; improved control of pulmonary infection; aggressive nutritional intervention; and enhanced monitoring of patients in peer-reviewed, accredited centers for cystic fibrosis care, teaching, and research. Emphasis on the importance of research on changing and improved treatment has been effectively communicated to patients and families. As a result, a group of highly educated medical consumers has been created. During the last decade, another focus of rapid change has appeared, that of cost containment in the medical profession, creating the field of managed care. Practicing medical professionals perceive the need for reduction in excessive spending in medicine and have taken a variety of approaches to balance better the value and cost of medical care while maintaining superb quality. Physicians and consumers continue to have concerns about the potential negative impact of managed care on a relatively rare, specialized, and chronic illness such as cystic fibrosis if managed care concepts are applied without proper understanding of the disease. A great concern is that managed care in cystic fibrosis may cause reversal of trends in improved quality and length of survival. The increased length of survival places an increasing demand on the already stressed system of health care financing. Understanding the changing area of managed care is therefore of paramount importance to clinicians involved in cystic fibrosis care. The Cystic Fibrosis Foundation has presented symposia on managed care at each of the last three annual meetings, including the North American Cystic Fibrosis Meeting, October 1996. The following issues were addressed by speakers and panel discussants, with portions excerpted for this review: trends in managed care, measures and guidelines useful in managed care, Medicaid managed care and cystic fibrosis, and practical aspects of using pathways in caring for patients with cystic fibrosis.

Critical Pathways↗

CONTRACTILE PROPERTIES OF A HIGH-FREQUENCY MUSCLE FROM A CRUSTACEAN - ACTIVATION PATTERNS IN VIVO

1. The flagella of crustaceans are small appendages, borne on the maxillipeds, which beat repetitively when active. Flagellar movement is brought about by contraction of a single muscle, the flagellum abductor (FA). 2. The stroke frequency of the flagella of the green crab, Carcinus maenas, was about 11 Hz at 15 °C and was relatively independent of animal size [frequency is proportional to (animal mass)-0.07], even though scaling considerations suggest that, for constant muscle stress, frequency should be proportional to mass-0.33. The coefficient of variation for intervals between successive strokes of a flagellum was about 4 %. 3. The FA is innervated by two excitatory motoneurones. Each of the neurones fired 0­5 times during a stroke. The interspike interval when a neurone fired more than once during a stroke was 3­4 ms.

Journal Article↗

CONTRACTILE PROPERTIES OF A HIGH-FREQUENCY MUSCLE FROM A CRUSTACEAN - CONTRACTION KINETICS

1. The flagella (small appendages on the maxillipeds) of the crab Carcinus maenas beat regularly when active at about 10 Hz (15 °C). The beat of a flagellum is due to contraction of a single small muscle, the flagellum abductor (FA). The optimal stimulus frequency for tetanic contraction of the FA was about 200 Hz. When the muscle was stimulated at 10 Hz with paired stimuli per cycle, the interstimulus interval that maximized peak force was 2­4 ms, which corresponded well to the interspike intervals within bursts recorded from motor axons during normal beating. 2. Contraction of the isolated FA showed pronounced neuromuscular facilitation and many stimuli were needed to activate the muscle fully. The dependence on facilitation in isolated muscles appeared to be greater than that in vivo. It is suggested that neuromodulators in the blood of the crab enhance neuromuscular transmission and reduce the dependency on facilitation in intact animals. 3. The FA had a narrow length­tension curve. Tetanic tension became vanishingly small at muscle lengths less than about 90 % of the maximum in vivo length. The maximum length change of the muscle during in vivo contraction was about 5 %. 4. The maximum isometric force of the FA was low (about 6 N cm-2) but its shortening velocity was high. Vm, the maximum shortening velocity determined from isotonic shortening, was 4.0 muscle lengths s-1; V0, the maximum shortening velocity from slack test measurements, was about 8 lengths s-1. 5. The structure and physiology of the FA are compared with those of locust flight muscle, chosen because it too is a muscle capable of long-duration, high-frequency performance.

Journal Article↗

CONTRACTILE PROPERTIES OF A HIGH-FREQUENCY MUSCLE FROM A CRUSTACEAN - MECHANICAL POWER OUTPUT

The mechanical power output during oscillatory contraction was determined for the flagellum abductor muscle of the crab Carcinus maenas using the work loop technique. Measurements were made at 10 Hz, which is the normal operating frequency of the muscle. The temperature was 15 °C. Increasing the number of stimuli per cycle (given at an interstimulus interval of 3.3 ms) decreased the number of cycles required to reach a work plateau and increased the work per cycle at the plateau to a maximum at 4­5 stimuli per cycle. The maximum mechanical power output was 9.7 W kg-1 muscle (about 26 W kg-1 myofibril). The optimum strain for work output (5.7 %) was close to the estimated muscle strain in vivo (5.2 %).

Journal Article↗

Chest tube stripping in pediatric oncology patients: an experimental study.

BACKGROUND: Stripping of chest tubes to promote drainage of the thorax of postthoracotomy patients has been routine practice, based on tradition. Recent published findings indicate that significant negative pressures are generated in the tube during stripping that could cause pain, bleeding and possible damage to the patient's lung tissue. OBJECTIVE: To determine whether pediatric oncology patients whose chest tubes were not stripped would differ in frequency of pain, fever or lung complications from patients who underwent routine tube stripping. METHODS: Data were collected at multiple points during the first 72-hour postoperative period from 16 patients assigned to the stripped or unstripped groups. Pain was measured by the Faces Pain Scale and the Visual Analogue Scale; temperature, by electronic thermometer; and lung complications, by stethoscope and radiographs. Both groups, which were comparable for age, primary diagnosis and prior history of lung problems, received identical supportive nursing and medical care, with the physicians blind to group assignment. RESULTS: The two groups did not differ significantly in frequency of pain, incidence of fever, breath sounds or radiographic findings across measurement points. A strong correlation was found between the pain scores using the two instruments. DISCUSSION: Patients whose tubes were not stripped did not have an increased risk of infection or lung complications. Study findings indicated that stripping did not increase the frequency of pain. CONCLUSIONS: Stripping of chest tubes as a routine postoperative measure is questioned.

Adolescent↗

Mosaic structure of globular domains in the human type VI collagen alpha 3 chain: similarity to von Willebrand factor, fibronectin, actin, salivary proteins and aprotinin type protease inhibitors.

Human collagen alpha 3(VI) chain mRNA (approximately 10 kb) was cloned and shown by sequence analysis to encode a 25 residue signal peptide, a large N-terminal globule (1804 residues), a central triple helical segment (336 residues) and a C-terminal globule (803 residues). Some of the sequence was confirmed by Edman degradation of peptides. The N-terminal globular segment consists of nine consecutive 200 residue repeats (N1 to N9) showing internal homology and also significant identity (17-25%) to the A domains of von Willebrand Factor and similar domains present in some other proteins. Deletions were found in the N3 and N9 domains of several cDNA clones suggesting variation of these structures by alternative splicing. The C-terminal globule starts immediately after the triple helical segment with two domains C1 (184 residues) and C2 (248 residues) being similar to the N domains. They are followed by a proline rich, repetitive segment C3 of 122 residues, with similarity to some salivary proteins, and domain C4 (89 residues), which is similar to the type III repeats present in fibronectin and tenascin. The most C-terminal domain C5 (70 residues) shows 40-50% identity to a variety of serine protease inhibitors of the Kunitz type. The whole sequence contains 29 cysteines which are mainly clustered in short segments connecting domains N1, C1, C2 and the triple helix, and in the inhibitor domain. Five putative Arg-Gly-Asp cell-binding sequences are exclusively localized in the triple helical segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Severe obstructive sleep apnea in a child with osteopetrosis.

The clinical features of a 5-year-old patient with osteopetrosis and severe obstructive sleep apnea are presented. The patient responded to tonsillectomy, adenoidectomy, uvulectomy, and tracheostomy. The tracheostomy was later removed. Osteopetrosis, while rare, may be added to the list of causes of obstructive sleep apnea.

Blood Gas Analysis↗